Sample records for venom-induced tissue damage

  1. Protective effects of the antioxidant Ginkgo biloba extract and the protease inhibitor aprotinin against Leiurus quinquestriatus venom-induced tissue damage in rats

    Directory of Open Access Journals (Sweden)

    A. J. Fatani


    Full Text Available Oxidative stress and proteases have been implicated in several diseases and extensive evidence indicates that antioxidants and protease inhibitors help prevent organ functional damage. Leiurus quinquestriatus (LQQ scorpion venom causes cellular injuries that may lead to multiple organ failure. Thus, the capability of the antioxidant "natural standardized extract of Gingko biloba leaves (Gin, EGb 761" and the non-selective protease inhibitor, aprotinin, in ameliorating venom-induced biochemical alterations indicative of cellular injury and oxidative stress was studied to determine their effectiveness in protecting rats from venom-evoked cellular damages. Thus, in this study, rats were treated with LQQ venom (, subcutaneously alone or after Gin (, orally, daily for 2 weeks before venom and/or aprotinin (Apr, 46000, intraperitoneally, 30 min before venom. Control groups were injected with saline or treatment modalities. Lungs and hearts were excised after decapitating rats (n=8/group 60 min after venom injection and the following activities were measured: reduced glutathione (GSH, malondialdehyde (MDA - an index of lipid peroxidation, glutathione peroxidase (GPx, glucose-6-phosphate dehydrogenase (G6PD, and lactate dehydrogenase (LDH. Our findings demonstrate that LQQ venomsignificantly elevated GSH (p<0.05 vs. control, MDA (p<0.05, G6PD (p<0.05, and LDH activities (p<0.001 in hearts of envenomed rats. The venom also elevated MDA (p<0.05 vs. control and reduced GSH and GPx (p<0.05 in the lungs of envenomed rats. In general, pretreatment with EGb761 attenuated LQQ venom-evoked increases in GSH (p<0.05 vs. venom, MDA in rat hearts and lungs (p<0.05 vs. venom, plus LDH in the heart (p<0.01. Aprotinin alone significantly reduced the venom-elicited increase in G6PD and LDH activities and the decrease in GPx levels (p<0.05. In general, these protective effects of EGb761 on GSH, MDA (p<0.01 vs. venom and LDH (p<0.001 in the

  2. Bypassing damaged nervous tissue

    CERN Document Server

    Shneider, M N


    We show the principal ability of bypassing damaged demyelinated portions of nervous tissue, thereby restoring its normal function for the passage of action potentials. We carry out a theoretical analysis on the basis of the synchronization mechanism of action potential propagation along a bundle of neurons, proposed recently in [1]. And we discuss the feasibility of implement a bypass to restore damaged nervous tissue and creating an artificial neuron network.

  3. Investigation of skin permeation, ex vivo inhibition of venom-induced tissue destruction, and wound healing of African plants used against snakebites

    DEFF Research Database (Denmark)

    Schmidt, Marianne Molander; Stærk, Dan; Nielsen, Hanne Mørck


    . Materials and methods Extracts which had previously shown in vitro inhibitory activity against necrosis enzymes, were tested in an ex vivo air–liquid-interface model, and a wound healing scratch assay as well as for their ability to permeate the skin barrier and inhibit venom induced cell death. Results...... Of the 14 water extracts and 16 ethanol extracts tested at a concentration of 10 μg/mL, only the ethanol extracts of Tamarindus indica and Paullinia pinnata resulted in a small but significant increase in cell migration of around 10% compared to treatment with buffer after 24 h treatment. The remaining...... extracts showed no effect, or they even delayed the cell migration compared to the treatment with buffer. After 48 h treatment, 10 of the tested extracts showed a decreased cell migration compared to no treatment. At a 100 μg/mL concentration all the extracts inhibited cell migration and five extracts...

  4. Tissue localization and extracellular matrix degradation by PI, PII and PIII snake venom metalloproteinases: clues on the mechanisms of venom-induced hemorrhage.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera


    Full Text Available Snake venom hemorrhagic metalloproteinases (SVMPs of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.

  5. Damage Models for Soft Tissues: A Survey. (United States)

    Li, Wenguang

    Damage to soft tissues in the human body has been investigated for applications in healthcare, sports, and biomedical engineering. This paper reviews and classifies damage models for soft tissues to summarize achievements, identify new directions, and facilitate finite element analysis. The main ideas of damage modeling methods are illustrated and interpreted. A few key issues related to damage models, such as experimental data curve-fitting, computational effort, connection between damage and fractures/cracks, damage model applications, and fracture/crack extension simulation, are discussed. Several new challenges in the field are identified and outlined. This review can be useful for developing more advanced damage models and extending damage modeling methods to a variety of soft tissues.

  6. Vipera russelli venom-induced oxidative stress and hematological alterations: amelioration by crocin a dietary colorant. (United States)

    Sebastin Santhosh, M; Hemshekhar, M; Thushara, R M; Devaraja, S; Kemparaju, K; Girish, K S


    Snakebite is a serious medical and socio-economic problem affecting the healthy individuals and agricultural and farming populations worldwide. In India, Vipera russelli snakebite is common, ensuing high morbidity and mortality. The venom components persuade multifactorial stress phenomenon and alter the physiological setting by causing disruption of the blood cells and vital organs. The present study demonstrates the anti-ophidian property of Crocin (Crocus sativus), a potent antioxidant against viper venom-induced oxidative stress. The in vivo oxidative damage induced by venom was clearly evidenced by the increased oxidative stress markers and antioxidant enzymes/molecules along with the proinflammatory cytokines including IL-1β, TNF-α and IL-6. Furthermore, venom depleted the hemoglobin, hematocrit, mean corpuscular volume and platelet count in experimental animals. Crocin ameliorated the venom-induced oxidative stress, hematological alteration and proinflammatory cytokine levels. At present, administration of antivenom is an effective therapy against systemic toxicity, but it offers no protection against the rapidly spreading oxidative damage and infiltration of pro-inflammatory mediators. These pathologies will continue even after antivenom administration. Hence, a long-term auxiliary therapy is required to treat secondary as well as neglected complications of snakebite. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Tissue damage thresholds during therapeutic electrical stimulation (United States)

    Cogan, Stuart F.; Ludwig, Kip A.; Welle, Cristin G.; Takmakov, Pavel


    Objective. Recent initiatives in bioelectronic modulation of the nervous system by the NIH (SPARC), DARPA (ElectRx, SUBNETS) and the GlaxoSmithKline Bioelectronic Medicines effort are ushering in a new era of therapeutic electrical stimulation. These novel therapies are prompting a re-evaluation of established electrical thresholds for stimulation-induced tissue damage. Approach. In this review, we explore what is known and unknown in published literature regarding tissue damage from electrical stimulation. Main results. For macroelectrodes, the potential for tissue damage is often assessed by comparing the intensity of stimulation, characterized by the charge density and charge per phase of a stimulus pulse, with a damage threshold identified through histological evidence from in vivo experiments as described by the Shannon equation. While the Shannon equation has proved useful in assessing the likely occurrence of tissue damage, the analysis is limited by the experimental parameters of the original studies. Tissue damage is influenced by factors not explicitly incorporated into the Shannon equation, including pulse frequency, duty cycle, current density, and electrode size. Microelectrodes in particular do not follow the charge per phase and charge density co-dependence reflected in the Shannon equation. The relevance of these factors to tissue damage is framed in the context of available reports from modeling and in vivo studies. Significance. It is apparent that emerging applications, especially with microelectrodes, will require clinical charge densities that exceed traditional damage thresholds. Experimental data show that stimulation at higher charge densities can be achieved without causing tissue damage, suggesting that safety parameters for microelectrodes might be distinct from those defined for macroelectrodes. However, these increased charge densities may need to be justified by bench, non-clinical or clinical testing to provide evidence of device

  8. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization. (United States)

    Tan, Kae Yi; Tan, Choo Hock; Sim, Si Mui; Fung, Shin Yee; Tan, Nget Hong


    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera


    Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  10. Visceral adipose tissue is associated with microstructural brain tissue damage. (United States)

    Widya, Ralph L; Kroft, Lucia J M; Altmann-Schneider, Irmhild; van den Berg-Huysmans, Annette A; van der Bijl, Noortje; de Roos, Albert; Lamb, Hildo J; van Buchem, Mark A; Slagboom, P Eline; van Heemst, Diana; van der Grond, Jeroen


    Obesity has been associated with microstructural brain tissue damage. Different fat compartments demonstrate different metabolic and endocrine behaviors. The aim was to investigate the individual associations between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and microstructural integrity in the brain. This study comprised 243 subjects aged 65.4 ± 6.7 years. The associations between abdominal VAT and SAT, assessed by CT, and magnetization transfer imaging markers of brain microstructure for gray and white matter were analyzed and adjusted for confounding factors. VAT was associated with normalized MTR peak height in gray (β -0.216) and white matter (β -0.240) (both P  0.05). Stepwise linear regression analysis showed that only VAT was associated with normalized MTR peak height in gray and white matter (both P VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals. © 2015 The Obesity Society.

  11. Soft tissue damage after minimally invasive THA

    NARCIS (Netherlands)

    van Oldenrijk, Jakob; Hoogland, Piet V. J. M.; Tuijthof, Gabriëlle J. M.; Corveleijn, Ruby; Noordenbos, Tom W. H.; Schafroth, Matthias U.


    Methods 5 surgeons each performed a total hip arthroplasty on 5 fresh frozen cadaver hips, using either a MIS anterior, MIS anterolateral, MIS 2-incision, MIS posterior, or lateral transgluteal approach. Postoperatively, the hips were dissected and muscle damage color-stained. We measured

  12. DNA damage in plant herbarium tissue.

    NARCIS (Netherlands)

    Staats, M.; Cuenca, A.; Richardson, J.E.; Ginkel, R.V.; Petersen, G.; Seberg, O.; Bakker, F.T.


    Dried plant herbarium specimens are potentially a valuable source of DNA. Efforts to obtain genetic information from this source are often hindered by an inability to obtain amplifiable DNA as herbarium DNA is typically highly degraded. DNA post-mortem damage may not only reduce the number of

  13. Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering. (United States)

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


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

  14. Prevention of tissue damage by water jet during cavitation (United States)

    Palanker, Daniel; Vankov, Alexander; Miller, Jason; Friedman, Menahem; Strauss, Moshe


    Cavitation bubbles accompany explosive vaporization of water following pulsed energy deposition in liquid media. Bubbles collapsing at the tip of a surgical endoprobe produce a powerful and damaging water jet propagating forward in the axial direction of the probe. We studied interaction of such jet with tissue using fast flash photography and modeled the flow dynamics using a two-dimensional Rayleigh-type hydrodynamic simulation. Maximal velocity of the jet generated at pulse energies of up to 1 mJ was about 80 m/s. The jet can produce tissue damage at a distance exceeding the radius of the cavitation bubble by a factor of 4. We demonstrate that formation of this flow and associated tissue damage can be prevented by application of the concave endoprobes that slow down the propagation of the back boundary of the bubble. Similar effect can be achieved by positioning an obstacle to the flow, such as a ring behind the tip.

  15. [Scanning electron microscopy of heat-damaged bone tissue]. (United States)

    Harsanyl, L


    Parts of diaphyses of bones were exposed to high temperature of 200-1300 degrees C. Damage to the bone tissue caused by the heat was investigated. The scanning electron microscopic picture seems to be characteristic of the temperature applied. When the bones heated to the high temperature of 700 degrees C characteristic changes appear on the periostal surface, higher temperatura on the other hand causes damage to the compact bone tissue and can be observed on the fracture-surface. Author stresses the importance of this technique in the legal medicine and anthropology.

  16. Zebrafish fin regeneration after cryoinjury-induced tissue damage

    Directory of Open Access Journals (Sweden)

    Bérénice Chassot


    Full Text Available Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump.

  17. Tissue Damage Characterization Using Non-invasive Optical Modalities (United States)

    Diaz, David

    The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p measurements correlated with the extent of tissue injury observed in histological stains. After proof of concept in animals, a human study was conducted and optical data was collected from 20 healthy subjects and 8 patients at risk of developing pressure ulcers. Blood flow index (BFI

  18. Tissue damage disrupts developmental progression and ecdysteroid biosynthesis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jennifer F Hackney

    Full Text Available In humans, chronic inflammation, severe injury, infection and disease can result in changes in steroid hormone titers and delayed onset of puberty; however the pathway by which this occurs remains largely unknown. Similarly, in insects injury to specific tissues can result in a global developmental delay (e.g. prolonged larval/pupal stages often associated with decreased levels of ecdysone - a steroid hormone that regulates developmental transitions in insects. We use Drosophila melanogaster as a model to examine the pathway by which tissue injury disrupts developmental progression. Imaginal disc damage inflicted early in larval development triggers developmental delays while the effects are minimized in older larvae. We find that the switch in injury response (e.g. delay/no delay is coincident with the mid-3rd instar transition - a developmental time-point that is characterized by widespread changes in gene expression and marks the initial steps of metamorphosis. Finally, we show that developmental delays induced by tissue damage are associated with decreased expression of genes involved in ecdysteroid synthesis and signaling.

  19. Assessing laser-tissue damage with bioluminescent imaging. (United States)

    Wilmink, Gerald J; Opalenik, Susan R; Beckham, Joshua T; Davidson, Jeffrey M; Jansen, E Duco


    Effective medical laser procedures are achieved by selecting laser parameters that minimize undesirable tissue damage. Traditionally, human subjects, animal models, and monolayer cell cultures have been used to study wound healing, tissue damage, and cellular effects of laser radiation. Each of these models has significant limitations, and consequently, a novel skin model is needed. To this end, a highly reproducible human skin model that enables noninvasive and longitudinal studies of gene expression was sought. In this study, we present an organotypic raft model (engineered skin) used in combination with bioluminescent imaging (BLI) techniques. The efficacy of the raft model was validated and characterized by investigating the role of heat shock protein 70 (hsp70) as a sensitive marker of thermal damage. The raft model consists of human cells incorporated into an extracellular matrix. The raft cultures were transfected with an adenovirus containing a murine hsp70 promoter driving transcription of luciferase. The model enables quantitative analysis of spatiotemporal expression of proteins using BLI. Thermal stress was induced on the raft cultures by means of a constant temperature water bath or with a carbon dioxide (CO2) laser (lambda=10.6 microm, 0.679 to 2.262 Wcm2, cw, unfocused Gaussian beam, omegaL=4.5 mm, 1 min exposure). The bioluminescence was monitored noninvasively with an IVIS 100 Bioluminescent Imaging System. BLI indicated that peak hsp70 expression occurs 4 to 12 h after exposure to thermal stress. A minimum irradiance of 0.679 Wcm2 activated the hsp70 response, and a higher irradiance of 2.262 Wcm2 was associated with a severe reduction in hsp70 response due to tissue ablation. Reverse transcription polymerase chain reaction demonstrated that hsp70 mRNA levels increased with prolonged heating exposures. Enzyme-linked immunosorbent protein assays confirmed that luciferase was an accurate surrogate for hsp70 intracellular protein levels. Hematoxylin

  20. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  1. Do Quiescence and Wasp Venom-Induced Lethargy Share Common Neuronal Mechanisms in Cockroaches?

    Directory of Open Access Journals (Sweden)

    Stav Emanuel

    Full Text Available The escape behavior of a cockroach may not occur when it is either in a quiescent state or after being stung by the jewel wasp (Ampulex compressa. In the present paper, we show that quiescence is an innate lethargic state during which the cockroach is less responsive to external stimuli. The neuronal mechanism of such a state is poorly understood. In contrast to quiescence, the venom-induced lethargic state is not an innate state in cockroaches. The Jewel Wasp disables the escape behavior of cockroaches by injecting its venom directly in the head ganglia, inside a neuropile called the central complex a 'higher center' known to regulate motor behaviors. In this paper we show that the coxal slow motoneuron ongoing activity, known to be involved in posture, is reduced in quiescent animals, as compared to awake animals, and it is further reduced in stung animals. Moreover, the regular tonic firing of the slow motoneuron present in both awake and quiescent cockroaches is lost in stung cockroaches. Injection of procaine to prevent neuronal activity into the central complex to mimic the wasp venom injection produces a similar effect on the activity of the slow motoneuron. In conclusion, we speculate that the neuronal modulation during the quiescence and venom-induced lethargic states may occur in the central complex and that both states could share a common neuronal mechanism.

  2. Temporal effects of mechanical loading on deformation-induced damage in skeletal muscle tissue

    NARCIS (Netherlands)

    Loerakker, S.; Stekelenburg, A.; Strijkers, G. J.; Rijpkema, J. J. M.; Baaijens, F. P. T.; Bader, D. L.; Nicolay, K.; Oomens, C. W. J.


    Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury. Recently, by means of an experimental-numerical approach, it was shown that local tissue deformations cause tissue damage once a

  3. A radiation damage repair model for normal tissues (United States)

    Partridge, Mike


    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  4. A radiation damage repair model for normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Partridge, Mike [Institute of Cancer Research, Downs Road, Sutton, SM2 5PT (United Kingdom)


    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions ({approx}2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 {mu}m h{sup -1} for large lesions (>15 000 cells)

  5. Intraoperative arrhythmias and tissue damage during transmyocardial laser revascularization. (United States)

    Kadipaşaoglu, K A; Sartori, M; Masai, T; Cihan, H B; Clubb, F J; Conger, J L; Frazier, O H


    Transmyocardial laser revascularization creates transmural channels to improve myocardial perfusion. Different laser sources and ablation modalities have been proposed for transmyocardial laser revascularization. We investigated the incidence of cardiac arrhythmias and laser-tissue interactions during transmyocardial laser revascularization of normal porcine myocardium with three different lasers. We used a continuous-wave, chopped CO2 laser (20 J/pulse, 15 ms/pulse) synchronized with the R wave; a holmium:yttrium aluminum garnet (Ho:YAG) laser (2 J/pulse, 250 micros/pulse, 5 Hz); and a xenon-chloride (excimer, Xe:Cl) laser (35 mJ/pulse, 20 ns/pulse, 30 Hz). Each laser was used 30 times as the sole modality in four consecutive pigs, yielding 120 channels. The average number of pulses needed to create a channel was 1, 11 +/- 4, and 37 +/- 8 for the CO2, Ho:YAG, and Xe:Cl lasers, respectively. All Ho:YAG and Xe:Cl channels had premature ventricular contractions. Ventricular tachycardia occurred in 70% of the Xe:Cl and 60% of the Ho:YAG channels. Only 36% of the CO2 channels had premature ventricular contractions, and only 3% of the CO2 channels had ventricular tachycardia (p CO2 channels were straight and well demarcated. The zone of structural and thermal damage extended over half the channel's diameter, measuring 0.52 +/- 0.25 mm. During transmyocardial laser revascularization, the CO2 laser synchronized with the R wave is significantly less arrhythmogenic than the Ho:YAG and Xe:Cl lasers not synchronized with the R wave. In addition, the interaction of the CO2 laser with porcine cardiac tissue is significantly less traumatic than that of the Ho:YAG and the Xe:Cl lasers.

  6. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    Directory of Open Access Journals (Sweden)

    Wajdy Al-Awaida


    Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

  7. Nd : YAG surgical laser effects in canine prostate tissue: temperature and damage distribution

    NARCIS (Netherlands)

    van Nimwegen, S. A.; L'Eplattenier, H. F.; Rem, A. I.; van der Lugt, J. J.; Kirpensteijn, J.


    An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact

  8. Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation. (United States)

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


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

  9. Modeling electrical power absorption and thermally-induced biological tissue damage. (United States)

    Zohdi, T I


    This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

  10. Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage. (United States)

    Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric


    To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

  11. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  12. Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

    Directory of Open Access Journals (Sweden)

    Rui V Lucato

    Full Text Available BACKGROUND: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI. There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In order to test Loxosceles gaucho venom (LV nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control. LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. CONCLUSIONS/SIGNIFICANCE: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

  13. Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.V.


    Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

  14. Suturing intraabdominal organs : When do we cause tissue damage?

    NARCIS (Netherlands)

    Rodrigues, S.P.; Horeman, T.; Dankelman, J.; Van den Dobbelsteen, J.J.; Jansen, F.W.


    It is generally assumed that safety of tissue manipulations during (laparoscopic) surgery is related to the magnitude of force that is exerted on the tissue. To provide trainees with performance feedback about tissuehandling skills, it is essential to define objective criteria for judging the safety

  15. Mechanisms of cell damage in agitated microcarrier tissue culture reactors (United States)

    Cherry, Robert S.; Papoutsakis, E. Terry


    Cells growing on microcarriers may be damaged by collisions of the microcarrier against another microcarrier or the reactor agitator. Bead-bead collisions are caused by small-scale turbulence, which can also cause high local shear stress on the cells. The cells are also exposed to 10-20 Hz cyclic shear stress by bead rotation.

  16. An Alternative Method of Evaluating 1540NM Exposure Laser Damage using an Optical Tissue Phantom

    National Research Council Canada - National Science Library

    Jindra, Nichole M; Figueroa, Manuel A; Rockwell, Benjamin A; Chavey, Lucas J; Zohner, Justin J


    An optical phantom was designed to physically and optically resemble human tissue, in an effort to provide an alternative for detecting visual damage resulting from inadvertent exposure to infrared lasers...

  17. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; van der Linden, JC


    In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Fi...

  18. Disease related tissue damage and subsequent changes in fillet structure

    DEFF Research Database (Denmark)

    (Oncorhynchus mykiss). Needle disrupted muscle tissue was sampled at different time points and subject to real-time RT-PCR for measuring the expression of the genes IL-1β, IL-8, IL-10, TGF-β, Myostatin-1ab, MMP-2, CTGF, Collagen-1α, VEGF, iNOS, Arg-2 and FGF. The results showed an initial phase with up...

  19. Application of immunohistochemical staining to detect antigen destruction as a measure of tissue damage. (United States)

    Onul, Abdullah; Colvard, Michael D; Paradise, William A; Elseth, Kim M; Vesper, Benjamin J; Gouvas, Eftychia; Deliu, Zane; Garcia, Kelly D; Pestle, William J; Radosevich, James A


    Electrocautery and directed energy devices (DEDs) such as lasers, which are used in surgery, result in tissue damage that cannot be readily detected by traditional histological methods, such as hematoxylin and eosin staining. Alternative staining methods, including 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to stain live tissue, have been reported. Despite providing superior detection of damaged tissue relative to the hematoxylin and eosin (H&E) method, the MTT method possesses a number of drawbacks, most notably that it must be carried out on live tissue samples. Herein, we report the development of a novel staining method, "antigen destruction immunohistochemistry" (ADI), which can be carried out on paraffin-embedded tissue. The ADI method takes advantage of epitope loss to define the area of tissue damage and provides many of the benefits of live tissue MTT staining without the drawbacks inherent to that method. In addition, the authors provide data to support the use of antibodies directed at a number of gene products for use in animal tissue for which there are no species-specific antibodies commercially available, as well as an example of a species-specific direct antibody. Data are provided that support the use of this method in many tissue models, as well as evidence that ADI is comparable to the live tissue MTT method.

  20. Portuguese Man-of-war (Physalia physalis) venom induces calcium influx into cells by permeabilizing plasma membranes. (United States)

    Edwards, L; Hessinger, D A


    Portuguese Man-of-war (Physalia physalis) nematocyst venom dose-dependently stimulates calcium (45Ca(2+)) influx into L-929, GH(4)C(1), FRL, and embryonic chick heart cells. Venom-induced calcium influx is not blocked by ouabain, vanadate, nor organic calcium channel blockers, but is blocked by transition metal cations, such as lanthanum and zinc. Venom-induced calcium influx is accompanied in a dose-dependent manner by the release of intracellular lactate dehydrogenase, indicating a loss in plasma membrane integrity and cytolysis. Concentrations of zinc that block 45Ca(2+) influx also block lactate dehydrogenase release. Lanthanum, which also blocks 45Ca(2+) uptake, does not neutralize the cytolytic activity of the venom, but rather inhibits the venom's cytolytic action at the level of the target cell plasma membrane. Our findings indicate that Man-of-war venom causes an influx of calcium into several different cells types, not just those of the cardiovascular system, and this influx likely occurs by permeabilizing the plasma membranes of cells.

  1. Neutralization of Naja naja venom induced lethality, edema and myonecrosis by ethanolic root extract of Coix lacryma-jobi. (United States)

    Rajesh, K S; Bharath, B R; Rao, C V; Bhat, K I; Bhat, K S Chandrashekhar; Bhat, Pritesh


    Coix lacryma-jobi, commonly known as job's tear, is a tall grain-bearing tropical plant of the family Poaceae. The ethanolic root extract (ERE) of the plant was investigated for the first time for anti-venom activity against Indian cobra Naja naja venom. In-vitro studies were conducted to determine neutralization of phospholipase A2 (PLA2) activity of the Naja naja venom by the ERE. ERE showed significant inhibition of PLA2 activity, which was further confirmed from effective neutralization of human red blood cells (HRBC) lysis induced by the venom. In addition, venom-induced proteolysis, fibrinogenolysis, DNase activity were also neutralized by the ERE, which contained carbohydrates, glycolides, resins and tannins. Oral administration of ERE at doses levels 100, 200 and 400 mg/kg effectively inhibited Naja naja venom-induced lethality in mice. Myotoxicity induced by Naja naja venom, measured by creatine kinase activity in rats was significantly neutralized by the ERE at a dose of 200 mg/kg. Stigmasterol, as one of the component isolated from the ERE, was found to have venom phospholipase A2 inhibition potential, which was confirmed by molecular docking studies with PLA2. In summary, these studies indicate the ability of ERE of Coix lacryma-jobi to effectively neutralize the toxic effects of the venom is, in part, contributed by the inhibition of PLA2 activity among other venom-derived factors.

  2. Current treatment for venom-induced consumption coagulopathy resulting from snakebite.

    Directory of Open Access Journals (Sweden)

    Kalana Maduwage


    Full Text Available Venomous snakebite is considered the single most important cause of human injury from venomous animals worldwide. Coagulopathy is one of the commonest important systemic clinical syndromes and can be complicated by serious and life-threatening haemorrhage. Venom-induced consumption coagulopathy (VICC is the commonest coagulopathy resulting from snakebite and occurs in envenoming by Viperid snakes, certain elapids, including Australian elapids, and a few Colubrid (rear fang snakes. Procoagulant toxins activate the clotting pathway, causing a broad range of factor deficiencies depending on the particular procoagulant toxin in the snake venom. Diagnosis and monitoring of coagulopathy is problematic, particularly in resource-poor countries where further research is required to develop more reliable, cheap clotting tests. MEDLINE and EMBASE up to September 2013 were searched to identify clinical studies of snake envenoming with VICC. The UniPort database was searched for coagulant snake toxins. Despite preclinical studies demonstrating antivenom binding toxins (efficacy, there was less evidence to support clinical effectiveness of antivenom for VICC. There were no placebo-controlled trials of antivenom for VICC. There were 25 randomised comparative trials of antivenom for VICC, which compared two different antivenoms (ten studies, three different antivenoms (four, two or three different doses or repeat doses of antivenom (five, heparin treatment and antivenom (five, and intravenous immunoglobulin treatment and antivenom (one. There were 13 studies that compared two groups in which there was no randomisation, including studies with historical controls. There have been numerous observational studies of antivenom in VICC but with no comparison group. Most of the controlled trials were small, did not use the same method for assessing coagulopathy, varied the dose of antivenom, and did not provide complete details of the study design (primary outcomes

  3. External ventricular drain causes brain tissue damage: an imaging study. (United States)

    Ortolano, Fabrizio; Carbonara, Marco; Stanco, Antonella; Civelli, Vittorio; Carrabba, Giorgio; Zoerle, Tommaso; Stocchetti, Nino


    An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions. Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes. In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time. EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema.

  4. Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage. (United States)

    Stephenson, Makeda K; Farris, Ashley L; Grayson, Warren L


    While the clinical potential of tissue engineering for treating joint damage has yet to be realized, research and commercialization efforts in the field are geared towards overcoming major obstacles to clinical translation, as well as towards achieving engineered grafts that recapitulate the unique structures, function, and physiology of the joint. In this review, we describe recent advances in technologies aimed at obtaining biomaterials, stem cells, and bioreactors that will enable the development of effective tissue-engineered treatments for repairing joint damage. 3D printing of scaffolds is aimed at improving the mechanical structure and microenvironment necessary for bone regeneration within a damaged joint. Advances in our understanding of stem cell biology and cell manufacturing processes are informing translational strategies for the therapeutic use of allogeneic and autologous cells. Finally, bioreactors used in combination with cells and biomaterials are promising strategies for generating large tissue grafts for repairing damaged tissues in pre-clinical models. Together, these advances along with ongoing research directions are making tissue engineering increasingly viable for the treatment of joint damage.

  5. Tissue damage in organic rainbow trout muscle investigated by proteomics and bioinformatics. (United States)

    Wulff, Tune; Silva, Tomé; Nielsen, Michael Engelbrecht


    The response to tissue damage is a complex process, which involves the coordinated regulation of multiple proteins to ensure tissue repair. In order to investigate the effect of tissue damage in a lower vertebrate, samples were taken from rainbow trout (Oncorhynchus mykiss) at day 7 after damage and proteins were separated using 2DE. The experimental design included two groups of rainbow trout, which were fed organic feed either with or without astaxanthin. In total, 96 proteins were found to be affected by tissue damage, clearly demonstrating in this lower vertebrate the complexity and magnitude of the cellular response, in the context of a regenerative process. Using a bioinformatics approach, the main biological function of these proteins were assigned, showing the regulation of proteins involved in processes such as apoptosis, iron homeostasis, and regulation of muscular structure. Interestingly, it was established that exclusively within the astaxanthin feed group, three members of the annexin protein family (annexin IV, V, and VI) were regulated in response to tissue damage. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Tissue damage modeling in gene electrotransfer: the role of pH. (United States)

    Olaiz, N; Signori, E; Maglietti, F; Soba, A; Suárez, C; Turjanski, P; Michinski, S; Marshall, G


    Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson-Nernst-Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase+GET protocol. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Inflammatory and regenerative responses in salmonids following mechanical tissue damage and natural infection

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Lunder, Tor; Nielsen, Michael Engelbrecht


    injured cells as well as PAMPs from the surface of pathogens are immunogenic. To examine this in salmonid fishes, Atlantic salmon (Salmo salar) were infected with Moritella viscosus, the causative agent of winter ulcer. Muscle tissue was sampled from infected fish at 4, 7 and 14 days post infection...... and TLR-22 following damage. Further, in both studies the regenerative genes TGF-β, MMP-2, CTGF, myostatin-1αβ were induced, but showed different kinetics. Collagen-1α was only induced in infected fish, probably due to heavier tissue damage in these....

  8. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  9. The Sensitization Model to Explain How Chronic Pain Exists Without Tissue Damage

    NARCIS (Netherlands)

    van Wilgen, C. Paul; Keizer, Doeke

    The interaction of nurses with chronic pain patients is often difficult. One of the reasons is that chronic pain is difficult to explain, because no obvious anatomic defect or tissue damage is present. There is now enough evidence available indicating that chronic pain syndromes such as low back

  10. Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy (United States)

    Vandersee, Staffan; Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Lange-Asschenfeldt, Bernhard


    Tissue tolerable plasma (TTP) represents a novel therapeutic method with promising capabilities in the field of dermatological interventions, in particular disinfection but also wound antisepsis and regeneration. The energy transfer by plasma into living tissue is not easily educible, as a variety of features such as the medium’s actual molecule-stream, the ions, electrons and free radicals involved, as well as the emission of ultraviolet, visible and infrared light contribute to its increasingly well characterized effects. Thus, relating possible adversary effects, especially of prolonged exposure to a single component of the plasma’s mode of action, is difficult. Until now, severe adverse events connected to plasma exposure have not been reported when conducted according to existing therapeutic protocols. In this study, we have compared the tissue damage-potential of CO2 and dye lasers with TTP in a porcine model. After exposure of pig ear skin to the three treatment modalities, all specimens were examined histologically and by means of laser scan microscopy (LSM). Light microscopical tissue damage could only be shown in the case of the CO2 laser, whereas dye laser and plasma treatment resulted in no detectable impairment of the specimens. In the case of TTP, LSM examination revealed only an impairment of the uppermost corneal layers of the skin, thus stressing its safety when used in vivo.

  11. Neutralization of Naja naja venom induced lethality, edema and myonecrosis by ethanolic root extract of Coix lacryma-jobi

    Directory of Open Access Journals (Sweden)

    K.S. Rajesh

    Full Text Available Coix lacryma-jobi, commonly known as job’s tear, is a tall grain-bearing tropical plant of the family Poaceae. The ethanolic root extract (ERE of the plant was investigated for the first time for anti-venom activity against Indian cobra Naja naja venom.In-vitro studies were conducted to determine neutralization of phospholipase A2 (PLA2 activity of the Naja naja venom by the ERE. ERE showed significant inhibition of PLA2 activity, which was further confirmed from effective neutralization of human red blood cells (HRBC lysis induced by the venom. In addition, venom-induced proteolysis, fibrinogenolysis, DNase activity were also neutralized by the ERE, which contained carbohydrates, glycolides, resins and tannins.Oral administration of ERE at doses levels 100, 200 and 400 mg/kg effectively inhibited Naja naja venom-induced lethality in mice. Myotoxicity induced by Naja naja venom, measured by creatine kinase activity in rats was significantly neutralized by the ERE at a dose of 200 mg/kg.Stigmasterol, as one of the component isolated from the ERE, was found to have venom phospholipase A2 inhibition potential, which was confirmed by molecular docking studies with PLA2. In summary, these studies indicate the ability of ERE of Coix lacryma-jobi to effectively neutralize the toxic effects of the venom is, in part, contributed by the inhibition of PLA2 activity among other venom-derived factors. Keywords: Naja naja, Phospholipase A2 inhibition, Myotoxicity, Stigmasterol, Molecular docking, Ethanolic root extract

  12. Mechanisms of tissue damage during ArF excimer endolaser microsurgery (United States)

    Palanker, Daniel V.; Turovets, Igor; Lewis, Aaron


    The novel fiberoptic delivery system for the 193 nm excimer laser has been developed for vitreoretinal microsurgery. During the application of this laser in a liquid environment both the short-living cavitation bubbles and hydrogen gas-containing insoluble bubbles are produced. In present work we study the influence of these bubbles generated in free liquid on membranous tissue. Damage zones resulting from application of pulse trains at various repetition rates were investigated using vital stains which indicate the increase of cell membrane permeability. Cavitation bubbles were created by laser above the tissue in a highly absorbing liquid--Hartmann's solution with an addition of 7% albumin. These conditions simulate a situation in which a thin membrane separated from the underlying retina by layer of liquid is cut. After application of 50 pulses at 20 Hz at energy levels varying from 14 to 68 (mu) J per pulse we have detected cell damage at corresponding distances varying from 100 to 1200 microns. In Hartmann's solution (physiological medium), where the cavitation bubbles could not be formed at the same applied energies, the laser damage has been detected only at the distances varying from 150 to 200 microns. Penetration depth of the laser radiation in this solution is about 50 microns. The cells damage in this case probably has a photochemical nature. The difference in damage distance obtained at 1 and 20 Hz repetition rates can be explained by the influence of insoluble gas bubbles that grow at the tip exit and play a role of a transparent medium for the laser radiation. This effect probably determines the minimal distance at which the surgeon can apply the laser in standard physiological medium without being concerned with underlying cells damage. On the other hand, this phenomenon enable to destroy the upper level of cells in tissue without the deep penetrating mechanical influence associated with cavitation bubble-based tissue removal.

  13. Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling. (United States)

    Sung, Pei-Hsun; Lee, Fan-Yen; Lin, Ling-Chun; Chen, Kuan-Hung; Lin, Hung-Sheng; Shao, Pei-Lin; Li, Yi-Chen; Chen, Yi-Ling; Lin, Kun-Chen; Yuen, Chun-Man; Chang, Hsueh-Wen; Lee, Mel S; Yip, Hon-Kan


    We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P DAMP inflammatory axis.

  14. Carcinoma cells misuse the host tissue damage response to invade the brain (United States)

    Chuang, Han-Ning; van Rossum, Denise; Sieger, Dirk; Siam, Laila; Klemm, Florian; Bleckmann, Annalen; Bayerlová, Michaela; Farhat, Katja; Scheffel, Jörg; Schulz, Matthias; Dehghani, Faramarz; Stadelmann, Christine; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias


    The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. PMID:23832647

  15. The role of tissue damage in whiplash associated disorders: Discussion paper 1 (United States)

    Bogduk, Nikolai; Ivancic, Paul C.; McLean, Samuel A.; Siegmund, Gunter P.; Winkelstein, Beth


    STUDY DESIGN Non-systematic review of cervical spine lesions in whiplash-associated disorders (WAD). OBJECTIVE To describe whiplash injury models in terms of basic and clinical science, to summarize what can and cannot be explained by injury models, and to highlight future research areas to better understand the role of tissue damage in WAD. SUMMARY OF BACKGROUND DATA The frequent lack of detectable tissue damage has raised questions about whether tissue damage is necessary for WAD and what role it plays in the clinical context of WAD. METHODS Non-systematic review. RESULTS Lesions of various tissues have been documented by numerous investigations conducted in animals, cadavers, healthy volunteers and patients. Most lesions are undetected by imaging techniques. For zygapophysial (facet) joints, lesions have been predicted by bioengineering studies and validated through animal studies; for zygapophysial joint pain, a valid diagnostic test and a proven treatment are available. Lesions of dorsal root ganglia, discs, ligaments, muscles and vertebral artery have been documented in biomechanical and autopsy studies, but no valid diagnostic test is available to assess their clinical relevance. The proportion of WAD patients in whom a persistent lesion is the major determinant of ongoing symptoms is unknown. Psychosocial factors, stress reactions and generalized hyperalgesia have also been shown to predict WAD outcomes. CONCLUSION There is evidence supporting a lesion-based model in WAD. Lack of macroscopically identifiable tissue damage does not rule out the presence of painful lesions. The best available evidence concerns zygapophysial joint pain. The clinical relevance of other lesions needs to be addressed by future research. PMID:22020601

  16. Non-damaging laser therapy of the macula: Titration algorithm and tissue response (United States)

    Palanker, Daniel; Lavinsky, Daniel; Dalal, Roopa; Huie, Philip


    Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

  17. Hydrogen peroxide as a damage signal in tissue injury and inflammation: Murderer, mediator, or messenger? (United States)

    van der Vliet, Albert; Janssen-Heininger, Yvonne M. W.


    Tissue injury and inflammation are associated with increased production of reactive oxygen species (ROS), which have the ability to induce oxidative injury to various biomolecules resulting in e.g. protein dysfunction or cell death. However, recent observations indicate that formation of hydrogen peroxide (H2O2) during tissue injury is also an essential feature of the ensuing wound healing response, and functions as an early damage signal to control several critical aspects of the wound healing process. Because innate oxidative wound responses must be tightly coordinated to avoid chronic inflammation or tissue injury, a more complete understanding is needed regarding the origins and dynamics of ROS production, and their critical biological targets. This Prospect highlights the current experimental evidence implicating H2O2 in early epithelial wound responses, and summarizes technical advances and approaches that may help distinguish its beneficial actions from its more deleterious actions in conditions of chronic tissue injury or inflammation. PMID:24122865

  18. Laser treatment of female stress urinary incontinence: optical, thermal, and tissue damage simulations (United States)

    Hardy, Luke A.; Chang, Chun-Hung; Myers, Erinn M.; Kennelly, Michael J.; Fried, Nathaniel M.


    Treatment of female stress urinary incontinence (SUI) by laser thermal remodeling of subsurface tissues is studied. Light transport, heat transfer, and thermal damage simulations were performed for transvaginal and transurethral methods. Monte Carlo (MC) provided absorbed photon distributions in tissue layers (vaginal wall, endopelvic fascia, urethral wall). Optical properties (n,μa,μs,g) were assigned to each tissue at λ=1064 nm. A 5-mm-diameter laser beam and power of 5 W for 15 s was used, based on previous experiments. MC output was converted into absorbed energy, serving as input for ANSYS finite element heat transfer simulations of tissue temperatures over time. Convective heat transfer was simulated with contact cooling probe set at 0 °C. Thermal properties (κ,c,ρ) were assigned to each tissue layer. MATLAB code was used for Arrhenius integral thermal damage calculations. A temperature matrix was constructed from ANSYS output, and finite sum was incorporated to approximate Arrhenius integral calculations. Tissue damage properties (Ea,A) were used to compute Arrhenius sums. For the transvaginal approach, 37% of energy was absorbed in endopelvic fascia layer with 0.8% deposited beyond it. Peak temperature was 71°C, treatment zone was 0.8-mm-diameter, and almost all of 2.7-mm-thick vaginal wall was preserved. For transurethral approach, 18% energy was absorbed in endopelvic fascia with 0.3% deposited beyond it. Peak temperature was 80°C, treatment zone was 2.0-mm-diameter, and only 0.6 mm of 2.4-mm-thick urethral wall was preserved. A transvaginal approach is more feasible than transurethral approach for laser treatment of SUI.

  19. Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak


    Full Text Available Mesenchymal stem cells (MSCs are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs, along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  20. Thermal Damage Analysis in Biological Tissues Under Optical Irradiation: Application to the Skin (United States)

    Fanjul-Vélez, Félix; Ortega-Quijano, Noé; Solana-Quirós, José Ramón; Arce-Diego, José Luis


    The use of optical sources in medical praxis is increasing nowadays. In this study, different approaches using thermo-optical principles that allow us to predict thermal damage in irradiated tissues are analyzed. Optical propagation is studied by means of the radiation transport theory (RTT) equation, solved via a Monte Carlo analysis. Data obtained are included in a bio-heat equation, solved via a numerical finite difference approach. Optothermal properties are considered for the model to be accurate and reliable. Thermal distribution is calculated as a function of optical source parameters, mainly optical irradiance, wavelength and exposition time. Two thermal damage models, the cumulative equivalent minutes (CEM) 43 °C approach and the Arrhenius analysis, are used. The former is appropriate when dealing with dosimetry considerations at constant temperature. The latter is adequate to predict thermal damage with arbitrary temperature time dependence. Both models are applied and compared for the particular application of skin thermotherapy irradiation.

  1. Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

    Directory of Open Access Journals (Sweden)

    Samanta Portão de Carlos


    Full Text Available OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively] in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group: a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice, the greatest differences (increases in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

  2. Antivenom activity of triterpenoid (C34H68O2) from Leucas aspera Linn. against Naja naja naja venom induced toxicity: antioxidant and histological study in mice. (United States)

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Thomas, John; Balachander, V; Babu, V Sarath; Bilal, S Mohammed Yusuf; Majeed, S Abdul; Madan, N; Raj, N Sundar; Vimal, S; Nambi, K S N; Hameed, A S Sahul


    The isolated and identified triterpenoid, 1-hydroxytetratriacontane-4-one (C34H68O2), obtained from the methanolic leaf extract of Leucas aspera Linn. was explored for the first time for antisnake venom activity. The plant (L. aspera Linn.) extract significantly antagonized the spectacled cobra (Naja naja naja) venom induced lethal activity in a mouse model. It was compared with commercial antiserum obtained from King Institute of Preventive Medicine (Chennai, Tamil Nadu, India). N. naja naja venom induced a significant decrease in antioxidant superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH and glutathione-S-transferase activities and increased lipid peroxidase (LPO) activity in different organs such as heart, liver, kidney and lungs. The histological changes following the antivenom treatment were also evaluated in all these organs. There were significant alterations in the histology. Triterpenoid from methanol extract of L. aspera Linn. at a dose level of 75 mg per mouse significantly attenuated (neutralized) the venom-induced antioxidant status and also the LPO activity in different organs.

  3. Damage to fetal bovine ovarian tissue caused by cryoprotectant exposure and vitrification is mitigated during tissue culture. (United States)

    Mouttham, Lara; Fortune, Joanne E; Comizzoli, Pierre


    The objective of this study is to characterize the impact of exposure to cryoprotectants followed by vitrification on primordial follicle survival and activation using a fetal bovine model. In the first study, fetal bovine cortical pieces were exposed to cryoprotectants with or without sucrose and cultured up to 7 days in the presence or absence of insulin. In the second study, cortical pieces were exposed to cryoprotectants with or without sucrose, vitrified, and cultured up to 7 days after warming in the presence or absence of insulin. Viability and morphology of follicles, as well as proliferation and/or DNA repair in ovarian tissue were analyzed. When compared to non-exposed controls, normal follicular morphology was affected in groups exposed to cryoprotectants only immediately post-exposure and after 1 day of culture, but improved by day 3 and did not significantly differ by day 7. Similarly, normal follicular morphology was compromised in vitrified groups after warming and on day 1 compared to controls, but improved by days 3 and 7. Proliferation and/or DNA repair in ovarian tissue was not affected by vitrification in this model. Cryoprotectant exposure and vitrification of ovarian tissue did not impair the activation of primordial follicles in response to insulin, although activation was delayed relative to non-exposed controls. Interestingly, sucrose had no noticeable protective effect. Vitrified fetal bovine ovarian tissue has the intrinsic capacity to mitigate the immediate damage to primordial follicles' morphology and retains the capacity to activate. These findings provide a basis for a successful cryopreservation protocol for ovarian cortical tissue in other species including humans.

  4. Missing in action-The meaning of cell death in tissue damage and inflammation. (United States)

    Muñoz, Luis E; Leppkes, Moritz; Fuchs, Tobias A; Hoffmann, Markus; Herrmann, Martin


    Billions of cells die every day in higher organisms as part of the normal process of tissue homeostasis. During special conditions like in development, acute infections, mechanical injuries, and immunity, cell death is a common denominator and it exerts profound effects in the outcome of these scenarios. To prevent the accumulation of aged, superfluous, infected, damaged and dead cells, professional phagocytes act in a rapid and efficient manner to clear the battle field and avoid spread of the destruction. Neutrophils are the most abundant effector immune cells that extravasate into tissues and can turn injured tissues into gory battle fields. In peace times, neutrophils tend to patrol tissues without provoking inflammatory reactions. We discuss in this review actual and forgotten knowledge about the meaning of cell death during homeostatic processes and drive the attention to the importance of the action of neutrophils during patrolling and for the maintenance or recovery of the homeostatic state once the organism gets attacked or injured, respectively. In this fashion, we disclose several disease conditions that arise as collateral damage of physiological responses to death. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues (United States)

    Griko, Y. V.; Yan, Xiaoli


    Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

  6. Predictive analysis of thermal distribution and damage in thermotherapy on biological tissue (United States)

    Fanjul-Vélez, Félix; Arce-Diego, José Luis


    The use of optical techniques is increasing the possibilities and success of medical praxis in certain cases, either in tissue characterization or treatment. Photodynamic therapy (PDT) or low intensity laser treatment (LILT) are two examples of the latter. Another very interesting implementation is thermotherapy, which consists of controlling temperature increase in a pathological biological tissue. With this method it is possible to provoke an improvement on specific diseases, but a previous analysis of treatment is needed in order for the patient not to suffer any collateral damage, an essential point due to security margins in medical procedures. In this work, a predictive analysis of thermal distribution in a biological tissue irradiated by an optical source is presented. Optical propagation is based on a RTT (Radiation Transport Theory) model solved via a numerical Monte Carlo method, in a multi-layered tissue. Data obtained are included in a bio-heat equation that models heat transference, taking into account conduction, convection, radiation, blood perfusion and vaporization depending on the specific problem. Spatial-temporal differential bio-heat equation is solved via a numerical finite difference approach. Experimental temperature distributions on animal tissue irradiated by laser radiation are shown. From thermal distribution in tissue, thermal damage is studied, based on an Arrhenius analysis, as a way of predicting harmful effects. The complete model can be used for concrete treatment proposals, as a way of predicting treatment effects and consequently decide which optical source parameters are appropriate for the specific disease, mainly wavelength and optical power, with reasonable security margins in the process.

  7. Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury. (United States)

    Diaz-Ruiz, Araceli; Salgado-Ceballos, Hermelinda; Montes, Sergio; Guizar-Sahagún, Gabriel; Gelista-Herrera, Noemi; Mendez-Armenta, Marisela; Diaz-Cintra, Sofia; Ríos, Camilo


    After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI. Copyright © 2011 Wiley-Liss, Inc.

  8. Relative binding affinity of carboxylate-, phosphonate-, and bisphosphonate-functionalized gold nanoparticles targeted to damaged bone tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Ryan D. [Rush University Medical Center, Department of Anatomy and Cell Biology (United States); Cole, Lisa E.; Roeder, Ryan K., E-mail: [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)


    Functionalized Au NPs have received considerable recent interest for targeting and labeling cells and tissues. Damaged bone tissue can be targeted by functionalizing Au NPs with molecules exhibiting affinity for calcium. Therefore, the relative binding affinity of Au NPs surface functionalized with either carboxylate (l-glutamic acid), phosphonate (2-aminoethylphosphonic acid), or bisphosphonate (alendronate) was investigated for targeted labeling of damaged bone tissue in vitro. Targeted labeling of damaged bone tissue was qualitatively verified by visual observation and backscattered electron microscopy, and quantitatively measured by the surface density of Au NPs using field-emission scanning electron microscopy. The surface density of functionalized Au NPs was significantly greater within damaged tissue compared to undamaged tissue for each functional group. Bisphosphonate-functionalized Au NPs exhibited a greater surface density labeling damaged tissue compared to glutamic acid- and phosphonic acid-functionalized Au NPs, which was consistent with the results of previous work comparing the binding affinity of the same functionalized Au NPs to synthetic hydroxyapatite crystals. Targeted labeling was enabled not only by the functional groups but also by the colloidal stability in solution. Functionalized Au NPs were stabilized by the presence of the functional groups, and were shown to remain well dispersed in ionic (phosphate buffered saline) and serum (fetal bovine serum) solutions for up to 1 week. Therefore, the results of this study suggest that bisphosphonate-functionalized Au NPs have potential for targeted delivery to damaged bone tissue in vitro and provide motivation for in vivo investigation.

  9. Gastric Tissue Damage Analysis Generated by Ischemia: Bioimpedance, Confocal Endomicroscopy, and Light Microscopy

    Directory of Open Access Journals (Sweden)

    Nohra E. Beltran


    Full Text Available The gastric mucosa ischemic tissular damage plays an important role in critical care patients’ outcome, because it is the first damaged tissue by compensatory mechanism during shock. The aim of the study is to relate bioimpedance changes with tissular damage level generated by ischemia by means of confocal endomicroscopy and light microscopy. Bioimpedance of the gastric mucosa and confocal images were obtained from Wistar male rats during basal and ischemia conditions. They were anesthetized, and stain was applied (fluorescein and/or acriflavine. The impedance spectroscopy catheter was inserted and then confocal endomicroscopy probe. After basal measurements and biopsy, hepatic and gastric arteries clamping induced ischemia. Finally, pyloric antrum tissue was preserved in buffered formaldehyde (10% for histology processing using light microscopy. Confocal images were equalized, binarized, and boundary defined, and infiltrations were quantified. Impedance and infiltrations increased with ischemia showing significant changes between basal and ischemia conditions (. Light microscopy analysis allows detection of general alterations in cellular and tissular integrity, confirming gastric reactance and confocal images quantification increments obtained during ischemia.

  10. Gastric Tissue Damage Analysis Generated by Ischemia: Bioimpedance, Confocal Endomicroscopy, and Light Microscopy (United States)

    Beltran, Nohra E.; Garcia, Laura E.; Garcia-Lorenzana, Mario


    The gastric mucosa ischemic tissular damage plays an important role in critical care patients' outcome, because it is the first damaged tissue by compensatory mechanism during shock. The aim of the study is to relate bioimpedance changes with tissular damage level generated by ischemia by means of confocal endomicroscopy and light microscopy. Bioimpedance of the gastric mucosa and confocal images were obtained from Wistar male rats during basal and ischemia conditions. They were anesthetized, and stain was applied (fluorescein and/or acriflavine). The impedance spectroscopy catheter was inserted and then confocal endomicroscopy probe. After basal measurements and biopsy, hepatic and gastric arteries clamping induced ischemia. Finally, pyloric antrum tissue was preserved in buffered formaldehyde (10%) for histology processing using light microscopy. Confocal images were equalized, binarized, and boundary defined, and infiltrations were quantified. Impedance and infiltrations increased with ischemia showing significant changes between basal and ischemia conditions (P < 0.01). Light microscopy analysis allows detection of general alterations in cellular and tissular integrity, confirming gastric reactance and confocal images quantification increments obtained during ischemia. PMID:23841094

  11. Effect of propolis feeding on rat tissues damaged by X-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hoon; Seo, Eul Won [Andong National Univ., Andong (Korea, Republic of); Ji, Tae Jeong [Kaya Univ., Goryeong (Korea, Republic of)


    Present study aimed to investigate the radioprotective effects of propolis feeding on rat tissues damaged by X-ray irradiation. It was shown that the number of white blood cell in X-ray irradiated group supplemented with propolis increased as much to those of the control group and also the GOT activities among the blood components were decreased after propolis feeding. The mineral contents such as Mg, Fe, Ca, Mn, Cu, Mo, Ni, As in liver were increased as compared with those of the control group but maintained lower level than those of only irradiated groups, implying that the propolis feeding elevated the recovery capability of white blood cell effectively and propolis have a potential resistance to cell damage by X-ray. According to histological observations of the testis, intestine and liver tissues which are irradiated after feeding propolis, the numbers of damaged undifferentiated cells were decreased in testis and the shape of the goblet cells and inner and outer muscular layers in intestine were restored to the original state and the hepatocytes and interlobular veins were shown intact in liver, suggesting that propolis has a potential capacity to restore cell shapes or resist deformation of cell.

  12. Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Peter H Lapchak

    Full Text Available Several innate and adaptive immune cell types participate in ischemia/reperfusion induced tissue injury. Amongst them, platelets have received little attention as contributors in the process of tissue damage after ischemia reperfusion (I/R injury. It is currently unknown whether platelets participate through the immunologically important molecules including, CD40 and when activated, CD154 (CD40L, in the pathogenesis of I/R injury. We hypothesized that constitutive expression of CD40 and activation-induced expression of CD154 on platelets mediate local mesenteric and remote lung tissue damage after I/R injury. Wild type (WT; C57BL/6J, CD40 and CD154 deficient mice underwent mesenteric ischemia for 30 minutes followed by reperfusion for 3 hours. WT mice subjected to mesenteric I/R injury displayed both local intestinal and remote lung damage. In contrast, there was significantly less intestinal damage and no remote lung injury in CD40 and CD154 deficient mice when compared to WT mice. Platelet-depleted WT mice transfused with platelets from CD40 or CD154 deficient mice failed to reconstitute remote lung damage. In contrast, when CD40 or CD154 deficient mice were transfused with WT platelets lung tissue damage was re-established. Together, these findings suggest that multiple mechanisms are involved in local and remote tissue injury and also identify platelet-expressed CD40 and/or CD154 as mediators of remote tissue damage.

  13. DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos (United States)

    Montero, Juan A.; Sanchez-Fernandez, Cristina; Lorda-Diez, Carlos I.; Garcia-Porrero, Juan A.; Hurle, Juan M.


    DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells γH2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of γH2AX-only cells increases after caspase inhibition while the relative number of TUNEL-only cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration. PMID:27752097

  14. Bisphenol A induces oxidative stress and DNA damage in hepatic tissue of female rat offspring

    Directory of Open Access Journals (Sweden)

    Jehane I. Eid


    Full Text Available Bisphenol A (BPA is an endocrine disrupting compound widely spread in our living environment. It is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to the limited information concerning the effect of BPA on the liver, the present study was designed to assess hepatic tissue injury induced by early life exposure to BPA in female rat offspring. Rat dams (n = 9 were gavaged with 0.5 and 50 mg of BPA/kg b.w./day throughout lactation until weaning. The sham group received olive oil for the same duration while the control group did not receive any injection. The liver tissue was collected from female pups at different pubertal periods (PND50, 90 and 110 to evaluate oxidative stress biomarkers, extent of DNA damage and histopathological changes. Our results indicated that early life exposure to BPA significantly increased oxidative/nitrosative stress, decreased antioxidant enzyme activities, induced DNA damage and chronic severe inflammation in the hepatic tissue in a time dependent manner. These data suggested that BPA causes long-term adverse effects on the liver, which leads to deleterious effects in the liver of female rat offspring.

  15. DNA damage in preserved specimens and tissue samples: a molecular assessment

    Directory of Open Access Journals (Sweden)

    Cantin Elizabeth


    Full Text Available Abstract The extraction of genetic information from preserved tissue samples or museum specimens is a fundamental component of many fields of research, including the Barcode of Life initiative, forensic investigations, biological studies using scat sample analysis, and cancer research utilizing formaldehyde-fixed, paraffin-embedded tissue. Efforts to obtain genetic information from these sources are often hampered by an inability to amplify the desired DNA as a consequence of DNA damage. Previous studies have described techniques for improved DNA extraction from such samples or focused on the effect of damaging agents – such as light, oxygen or formaldehyde – on free nucleotides. We present ongoing work to characterize lesions in DNA samples extracted from preserved specimens. The extracted DNA is digested to single nucleosides with a combination of DNase I, Snake Venom Phosphodiesterase, and Antarctic Phosphatase and then analyzed by HPLC-ESI-TOF-MS. We present data for moth specimens that were preserved dried and pinned with no additional preservative and for frog tissue samples that were preserved in either ethanol, or formaldehyde, or fixed in formaldehyde and then preserved in ethanol. These preservation methods represent the most common methods of preserving animal specimens in museum collections. We observe changes in the nucleoside content of these samples over time, especially a loss of deoxyguanosine. We characterize the fragmentation state of the DNA and aim to identify abundant nucleoside lesions. Finally, simple models are introduced to describe the DNA fragmentation based on nicks and double-strand breaks.

  16. A Study of the Therapeutic Effects of Vitamin E on Testicular Tissue Damage Caused by Fluoxetine

    Directory of Open Access Journals (Sweden)

    Jalili Tohid


    Full Text Available Objective: Fluoxetine is widely used in the treatment of neurological disorders. Hence, considering the adverse effects of this drug on the endocrine axes of the body is very important. Fluoxetine has been shown to cause significant changes in testicular tissue structure and sex hormones in rats. It seems that antioxidant compounds such as vitamin E can reduce free radicals and inhibit these changes. Therefore, the aim of this study is to investigate the therapeutic effects of vitamin E on testicular tissue damage caused by fluoxetine use. Materials and Methods: In the present study, 40 Wistar rats (weight = 250 ± 10 gr were randomly divided into 4 groups; control group that received normal saline (with intraperitoneal (IP method, fluoxetine group (n = 10 that received 10 mg/kg of fluoxetine (IP, vitamin E group (n = 10 that received 100 mg/kg of vitamin E (IP, and the treatment group that received both vitamin E (100 mg/kg and fluoxetine (10 mg/kg for 28 days. On the 28th day of the study testis tissue was removed and sent to the pathology lab and blood samples were taken for analyzing of testosterone and total antioxidant capacity. Results: The highest testosterone levels are related to the control group and the lowest levels are related to the fluoxetine receiving group. Significant differences were observed between sperm density in the seminiferous tubes, spermatogonia cells, and primary spermatocyte, and leydig and sertoli cells in the experimental groups compared to the control group after a 28-day period. Conclusion: Fluoxetine can damage the leydig cells and decrease activity of testis and production of testosterone, but vitamin E can repair the leydig cells and reduce damages caused by fluoxetine.

  17. SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Ai, H [IU School of Medicine, Indianapolis, IN (United States); Zhang, H [Northwestern Memorial Hospital, Chicago, IL (United States)


    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.

  18. Linking ontogeny and tissue regeneration: a study on tissue damage and wound healing in carp in connection to the developmental stage

    DEFF Research Database (Denmark)

    Nielsen, Michael Engelbrecht; Schmidt, Jacob; Ingerslev, Hans-Christian

    healing and tissue regeneration, the developmental stage of the individual may influence the immune reaction initiated following damage and thus the proliferative responses, which usually cross-talk with the immune system. Common carp (Cyprinus carpio) is an excellent fish specie to study tissue...

  19. Pulsed and Tissue Doppler Echocardiographic Changes in Hypertensive Crisis with and without End Organ Damage. (United States)

    Garadah, Taysir; Kassab, Salah; Gabani, Saleh; Abu-Taleb, Ahmed; Abdelatif, Ahmed; Asef, Aysha; Shoroqi, Issa; Jamsheer, Anwer


    Hypertensive crisis (HC) is a common medical emergency associated with acute rise in arterial blood pressure that leads to end-organ damage (EOD). Therefore, it is imperative to find markers that may help in the prediction of EOD in acute hypertensive crisis. To assess the clinical presentations on admission; echocardiographic changes of pulsed and tissue Doppler changes in EOD patients compared with no EOD; and the risk of developing end organ damage for clinical and biochemical variables in hypertension crisis. The data of 241 patients with hypertensive crisis with systolic blood pressure (SBP) of >180 mmHg or diastolic blood pressure (DBP) >120 mmHg were extracted from patients files. Patients divided into hypertensive emergency (HE) with EOD, n = 62 and hypertensive urgency (HU) without EOD, n = 179. LV hypertrophy on ECG, echo parameters for wall thickness, left Ventricular mass index (LVMI), Body mass index (BMI), pulse Doppler ratio of early filling velocity E wave to late A wave (E/A) and ratio of E wave velocity to tissue Doppler Em to E wave (E/Em) were evaluated. Serum creatinine, hemoglobin, age, gender, body mass Index (BMI), history of diabetes mellitus, smoking, hypertension, stroke and hyperlipidemia were recorded. Multiple logistic regression analysis was applied for risk prediction of end organ damage of clinical variables. Patients with HE compared with HU were significantly older, with a significantly higher SBP on admission, high BMI and LVMI. Further there were significantly higher E/A ratio on Doppler echo and higher E/Em ratio on tissue Doppler echocardiogram. Multiple regression analysis with adjustment for age and sex shows positive predictive value with odds ratio of SBP on admission >220 mmHg of 1.98, serum creatinine > 120 µg/L of 1.43, older age > 60 year of 1.304, obesity (BMI ≥ 30) of 1.9, male gender of 2.26 and left ventricle hypertrophy on ECG of 1.92. The hemoglobin level, history of smoking, hyperlipidemia and DM were with no

  20. Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity. (United States)

    M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra


    The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

  1. Fibroblasts Express Immune Relevant Genes and Are Important Sentinel Cells during Tissue Damage in Rainbow Trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Ossum, Carlo Gunnar; Lindenstrom, Thomas


    from E. coli, supernatant and debris from sonicated RTHDF cells. LPS was overall the strongest inducer of IL-1 beta, IL-8, IL-10, TLR-3 and TLR-9. IL-1 beta and IL-8 were already highly up regulated after 1 hour of LPS stimulation. Supernatant stimuli significantly increased the expression of IL-1 beta......, TLR-3 and TLR-9, whereas the debris stimuli only increased expression of IL-1 beta. Consequently, an in vivo experiment was further set up. By mechanically damaging the muscle tissue of rainbow trout, it was shown that fibroblasts in the muscle tissue of rainbow trout contribute to electing a highly...... local inflammatory response following tissue injury. The damaged muscle tissue showed a strong increase in the expression of the immune genes IL-1 beta, IL-8 and TGF-beta already 4 hours post injury at the site of injury while the expression in non-damaged muscle tissue was not influenced. A weaker...

  2. Role of the immune system in cardiac tissue damage and repair following myocardial infarction. (United States)

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya


    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  3. Tissue damage caused by the intramuscular injection of long-acting penicillin. (United States)

    Schanzer, H; Jacobson, J H


    In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

  4. Vitamin E prevents neutrophil accumulation and attenuates tissue damage in ischemic-reperfused human skeletal muscle. (United States)

    Formigli, L; Ibba Manneschi, L; Tani, A; Gandini, E; Adembri, C; Pratesi, C; Novelli, G P; Zecchi Orlandini, S


    Neutrophil accumulation and the consequent production of oxygen-derived free radicals are involved in the pathogenesis of Ischemia-Reperfusion syndrome. In this study we investigated whether a treatment with Vitamin E, which has antioxidant properties, could attenuate the tissue damage by interfering with the influx of neutrophils within the ischemic and reperfused human skeletal muscle. To this purpose, patients undergoing aortic cross-clamping during the surgical repair of aortic abdominal aneurysm were studied as a model of ischemia-reperfusion of the lower limb muscles. Muscle biopsies from the right femoral quadriceps of patients not receiving and receiving Vitamin E pretreatment before surgery were taken: a) after the induction of anaesthesia, as control samples, and b) after a period of ischemia followed by 30 min of reperfusion. The tissue samples were either routinely processed for morphological study and immunohistochemical analysis to detect an altered expression of specific endothelial adhesion proteins, such as E-selectin and ICAM-1. The results obtained showed that Vitamin E administration was able to prevent the accumulation of neutrophils within the ischemic and reperfused muscle. This beneficial effect of Vitamin E was due to its ability to hinder the expression of E-selectin and ICAM-1, molecules known to increase the adhesiveness of endothelium to circulating neutrophils. After treatment with Vitamin E a marked attenuation of the reperfusion injury was also evident. In conclusion, Vitamin E treatment may be considered a valuable tool for protection against the ischemia-reperfusion damage of human skeletal muscle.

  5. Freezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue. (United States)

    Poornejad, Nafiseh; Frost, Timothy S; Scott, Daniel R; Elton, Brinden B; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D


    Whole organ decellularization of porcine renal tissue and recellularization with a patient's own cells would potentially overcome immunorejection, which is one of the most significant problems with allogeneic kidney transplantation. However, there are obstacles to achieving this goal, including preservation of the decellularized extracellular matrix (ECM), identifying the proper cell types, and repopulating the ECM before transplantation. Freezing biological tissue is the best option to avoid spoilage; however, it may damage the structure of the tissue or disrupt cellular membranes through ice crystal formation. Cryoprotectants have been used to repress ice formation during freezing, although cell toxicity can still occur. The effect of freezing/thawing on native (n = 10) and decellularized (n = 10) whole porcine kidneys was studied without using cryoprotectants. Results showed that the elastic modulus of native kidneys was reduced by a factor of 22 (P freezing/thawing or decellularization, while the elastic modulus for decellularized ECM was essentially unchanged by the freezing/thawing process (p = 0.0636). Arterial pressure, representative of structural integrity, was also reduced by a factor of 52 (P freezing/thawing for native kidneys, compared to a factor of 43 (P freezing/thawing decellularized structures. Both freezing/thawing and decellularization reduced stiffness, but the reductions were not additive. Investigation of the microstructure of frozen/thawed native and decellularized renal tissues showed increased porosity due to cell removal and ice crystal formation. Orcein and Sirius staining showed partial damage to elastic and collagen fibers after freezing/thawing. It was concluded that cellular damage and removal was more responsible for reducing stiffness than fibril destruction. Cell viability and growth were demonstrated on decellularized frozen/thawed and non-frozen samples using human renal cortical tubular epithelial (RCTE) cells over 12 d. No

  6. [Unreamed tibial nail in tibial shaft fractures with severe soft tissue damage. Initial clinical experiences]. (United States)

    Krettek, C; Haas, N; Schandelmaier, P; Frigg, R; Tscherne, H


    In a prospective study, since March 1989, 55 tibial shaft fractures have been treated with a new, unreamed solid tibial nail (UTN). This nail was initially designed as a temporary implant. The first 33 cases with second or third degree soft tissue damage were reviewed 6 months or more after the operation. Fractures were classified according to Müller: 6 type A (18.2%), 15 type B (45.5%), and 12 type C (36.7%). In 9 cases (27.3%), there was GII (n = 4) or GIII (n = 5) closed soft tissue damage according to Tscherne's classification. The 24 open fractures (72.7%) comprised 11 OII, 3 OIIIA and 10 OIIIB fractures (Gustilo classification). 24 patients (72.7%) were polytraumatized, the mean PTS (Hannover Polytrauma Score) was 18 points (range: 8-65 points). All fractures were stabilized without reaming. The implant diameter was 8mm (n = 14) or 9 mm (n = 19). Static locking was performed in 31 cases. Dermatofasciotomy was necessary because of compartment syndrome in 14 cases. In 1 grade IIIB open fracture soft tissue coverage was performed with a latissimus dorsi myocutaneous free flap 4 days after nailing. In 32 of the 33 cases the use of an additional cast or brace was not necessary during the follow-up treatment; 1 patient had a cast for 8 weeks for the treatment of accompanying injuries. Full weight-bearing was achieved in 5 cases within 3 weeks, in 16 cases within 12 weeks, and in 30 cases within 26 weeks. In 16 cases (48.5%) the interlocking screws were removed after 5-26 weeks (mean: 10 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Disease related tissue damage in rainbow trout versus infection of Atlantic salmon by Moritella viscosus – a comparative study

    DEFF Research Database (Denmark)

    phenomenon occurs in salmonid fishes, Atlantic salmon (Salmo salar) were infected with the gram-negative bacterium Moritella viscosus, the causative agent of winter ulcer. The clinical signs showing visible, punctual lesions in the skin make this pathogen unique in order to study local inflammation. Muscle......Physical damage of tissue and multiple kinds of infections are found to cause inflammatory reactions in mammals. Regardless of the difference between non-pathogenic induced tissue damage and a bacterial infection, many of the same pathways and genes are triggered. To determine if the same...... tissue was sampled from infected fish at 4, 7 and 14 days post infection. Samples were obtained from site of lesions and from locations without clinical signs of disease and lesions. To compare the inflammatory reactions from infected fish relative to sterile, mechanical tissue damage, rainbow trout...

  8. Ascorbate ameliorates Echis coloratus venom-induced oxidative stress in human fibroblasts (United States)

    Al-Sheikh, Yazeed A.; Ghneim, Hazem K.; Aljaser, Feda S.; Aboul-Soud, Mourad A.M.


    Reports related to the effects of Echis coloratus venom (EcV) on the antioxidant capacity of human tissues is very scarce. The present study was undertaken to investigate the activities and gene expression levels of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), as well as the levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and the generation rates of superoxide anions (SOA), hydrogen peroxide (H2O2) and lipid peroxides (LPO) in cultured human fibroblasts incubated with EcV, ascorbate (Asc) and EcV plus Asc at concentrations and incubation periods that maintained cell viability. Results indicated that the activities of all antioxidant enzymes and their corresponding transcripts underwent highly significant decreases and downregulation in EcV-treated cultures (0.5 µg/ml medium for 4 h) compared to venom-free controls (PEcV-treated cultures with Asc (400 µM for 12 h) restored the activities and levels of all investigated parameters including the expression levels of the antioxidant genes to control venom-free values. It is concluded that Asc acted to neutralize the increased reactive oxygen species generation, thus ameliorating the EcV-induced oxidative stress and alleviating the downregulation of antioxidant genes. PMID:28672988

  9. Assessment of tissue damage due to percutaneous nephrolithotomy using serum concentrations of inflammatory mediators. (United States)

    Pérez-Fentes, D; Gude, F; Blanco-Parra, M; Morón, E; Ulloa, B; García, C


    To determine the percutaneous nephrolithotomy (PCNL) effects on the tissues using the quantification of inflammatory mediators, and to assess their impact on the development of postoperative complications. Prospective observational non-randomized study on 40 patients underwent to PCNL. 50 patients with kidney stone who were treated by extracorporeal shock wave lithotripsy (ESWL) were used as control group. Interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were determined at baseline (T0: before treatment), and at 2, 6 and 24hours after (T1, T2 and T3). No relevant changes on IL-1β and TNF-α were found. IL-6 showed two peaks at 2 and 6hours post-PCNL (median 17.8 and 15.8 pg/mL, respectively). At 24hours CRP had reached its peak value (3.4mg/L). The group treated with ESWL no showed significant changes in any of the markers. The serum concentration of IL-6 and CRP at 24hours post-NLP is different depending on the occurrence of complications (P=.001 and P=.039, respectively). IL-6 showed a good predictive power for the development of complications (AUC .801). Tissue damage caused by the PCNL is low. This damage increases significantly in those cases showing postoperative complications. IL-6 at 24hours has been shown to be a good predictive tool for the development of complications. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Susceptibility to glaucoma damage related to age and connective tissue mutations in mice. (United States)

    Steinhart, Matthew R; Cone-Kimball, Elizabeth; Nguyen, Cathy; Nguyen, Thao D; Pease, Mary E; Chakravarti, Shukti; Oglesby, Ericka N; Quigley, Harry A


    The purpose of this research was to study the effects of age and genetic alterations in key connective tissue proteins on susceptibility to experimental glaucoma in mice. We used mice haploinsufficient in the elastin gene (EH) and mice without both alleles of the fibromodulin gene (FM KO) and their wild type (WT) littermates of B6 and CD1 strains, respectively. FM KO mice were tested at two ages: 2 months and 12 months. Intraocular pressure (IOP) was measured by Tonolab tonometer, axial lengths and widths measured by digital caliper post-enucleation, and chronic glaucoma damage was measured using a bead injection model and optic nerve axon counts. IOP in EH mice was not significantly different from WT, but FM KO were slightly lower than their controls (p = 0.04). Loss of retinal ganglion cell (RGC) axons was somewhat, but not significantly greater in young EH and younger or older FM KO strains than in age-matched controls (p = 0.48, 0.34, 0.20, respectively, multivariable regression adjusting for IOP exposure). Older CD1 mice lost significantly more RGC axons than younger CD1 (p = 0.01, multivariable regression). The CD1 mouse strain showed age-dependence of experimental glaucoma damage to RGC in the opposite, and more expected, direction than in B6 mice in which older mice are more resistant to damage. Genetic alteration in two genes that are constituents of sclera, fibromodulin and elastin do not significantly affect RGC loss. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Honey bee (Apis mellifera) venom induces AIM2 inflammasome activation in human keratinocytes. (United States)

    Dombrowski, Y; Peric, M; Koglin, S; Kaymakanov, N; Schmezer, V; Reinholz, M; Ruzicka, T; Schauber, J


    Following allergen exposure, cytokines and other pro-inflammatory signals play an important role in the immunological cascade leading to allergic sensitization. Inflammasomes sense exogenous and endogenous danger signals and trigger IL-1β and IL-18 activation which in turn shape Th2 responses. Honey bee venom (BV) allergies are very common; however, the local inflammatory cascade leading to the initiation of allergic sensitization is poorly understood. In this study, the local inflammatory cascades in skin after exposure to BV were investigated. The mechanisms of inflammasome activation in human skin and in cultured keratinocytes upon BV exposure were analyzed by ELISA, Western blot, flow cytometry, siRNA techniques, and immunofluorescence. In an ex vivo bee sting model, BV induced IL-1β release suggesting the activation of inflammasomes. Indeed, in cultured keratinocytes, the BV component melittin triggered IL-1β and IL-18 release via the AIM2 inflammasome. AIM2 is a cytosolic DNA receptor, and mitochondrial as well as genomic DNA was detected in the cytosol of melittin-treated keratinocytes as triggers of inflammasome activation. As a mechanism, melittin mediated destruction of mitochondrial membranes leading to the leakage of mitochondrial DNA into the cytosolic compartment. These data suggest that upon BV exposure, keratinocytes are involved in an innate immune response by the activation of the AIM2 inflammasome and subsequent IL-1β and IL-18 release triggered by endogenous DNA. As IL-1β and IL-18 are involved in Th2- and IgE-mediated immune reactions, these results could add to the understanding of the role of the tissue microenvironment to subsequent allergic responses. © 2012 John Wiley & Sons A/S.

  12. Tissue damage in kidney, adrenal glands and diaphragm following extracorporeal shock wave lithotripsy. (United States)

    Gecit, Ilhan; Kavak, Servet; Oguz, Elif Kaval; Pirincci, Necip; Günes, Mustafa; Kara, Mikail; Ceylan, Kadir; Kaba, Mehmet; Tanık, Serhat


    This study was designed to investigate whether exposure to short-term extracorporeal shock wave lithotripsy (ESWL) produces histologic changes or induces apoptosis in the kidney, adrenal glands or diaphragm muscle in rats. The effect of shock waves on the kidney of male Wistar rats (n = 12) was investigated in an experimental setting using a special ESWL device. Animals were killed at 72 h after the last ESWL, and the tissues were stained with an in situ Cell Death Detection Kit, Fluorescein. Microscopic examination was performed by fluorescent microscopy. Apoptotic cell deaths in the renal tissue were not observed in the control group under fluorescent microscopy. In the ESWL group, local apoptotic changes were observed in the kidney in the area where the shock wave was focused. The apoptotic cell deaths observed in the adrenal gland of the control group were similar to those observed in the ESWL groups, and apoptosis was occasionally observed around the capsular structure. Apoptotic cell deaths in the diaphragm muscle were infrequently observed in the control group. Apoptosis in the ESWL group was limited to the mesothelial cells. This study demonstrated that serious kidney, adrenal gland and diaphragm muscles damage occurred following ESWL, which necessitated the removal of the organ in the rat model. It is recognized that the ESWL complications related to the kidney, adrenal gland and diaphragm muscles are rare and may be managed conservatively. © The Author(s) 2012.

  13. Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

    Directory of Open Access Journals (Sweden)

    Marina Burgos-Silva

    Full Text Available Acute and chronic kidney injuries (AKI and CKI constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs in an experimental model of nephrotoxicity induced by folic acid (FA in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

  14. Synchrotron X-ray CT of rose peduncles. Evaluation of tissue damage by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Herppich, Werner B. [Leibniz-Institut fuer Agrartechnik Potsdam-Bornim e.V., Potsdam (Germany). Abt. Technik im Gartenbau; Matsushima, Uzuki [Iwate Univ., Morioka (Japan). Faculty of Agriculture; Graf, Wolfgang [Association for Technology and Structures in Agriculture (KTBL), Darmstadt (Germany); Zabler, Simon [Fraunhofer-Institut fuer Integrierte Schaltungen (IIS), Wuerzburg (Germany). Project group NanoCT Systems (NCTS); Dawson, Martin [Salford Univ., Greater Manchester (United Kingdom); Choinka, Gerard; Manke, Ingo [Helmholtz Center Berlin for Materials and Energy (HZB), Berlin (Germany)


    ''Bent-neck'' syndrome, an important postharvest problem of cut roses, is probably caused by water supply limitations and/or the structural weakness of vascular bundles of the peduncle tissue. For this reason, advanced knowledge about the microstructures of rose peduncles and their cultivar specific variations may lead to a better understanding of the underlying mechanisms. Synchrotron X-ray computed tomography (SXCT), especially phase-based CT, is a highly suitable technique to nondestructively investigate plants' micro anatomy. SXCT with monochromatic X-ray beams of 30, 40 and 50 keV photon energy was used to evaluate the three-dimensional inner structures of the peduncles of 3 rose cultivars that differ greatly in their bent-neck susceptibility. Results indicated that this technique achieves sufficiently high spatial resolution to investigate complex tissues. However, further investigations with chlorophyll fluorescence analysis (CFA) and optical microscope imagery reveal different kinds of heavy damage of the irradiated regions induced by synchrotron X-rays; in a cultivar-specific manner, partial destruction of cell walls occurred a few hours after X-ray irradiation. Furthermore, a delayed inhibition of photosynthesis accompanied by the degradation of chlorophyll was obvious from CFA within hours and days after the end of CT measurements. Although SXCT is certainly well suited for three-dimensional anatomical analysis of rose peduncles, the applied technique is not nondestructive.

  15. Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

    LENUS (Irish Health Repository)

    Biniecka, Monika


    OBJECTIVES: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers. METHODS: Oxygen levels in synovial tissue were assessed using an oxygen\\/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry. 8-Oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) levels were also measured by ELISA. RESULTS: The median oxygen tension in synovial tissue was profoundly hypoxic at 19.35 mm Hg (2.5%). Nuclear 8-oxo-dG levels were significantly higher than nuclear 4-HNE levels in the lining and sublining layers (all p<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG levels in both cell layers (all p<0.001). Reduced in vivo oxygen tension correlated with high lipid peroxidation in synovial fluid (p=0.027; r=0.54) and tissue (p=0.004; r=0.58). Serum VEGF levels were positively correlated with cytoplasmic 4-HNE expression (p=0.05; r=0.43) and intensity (p=0.006; r=0.59) in the lining layer. Serum Ang2 levels were positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p < or = 0.05). DAS28-C-reactive protein was correlated with nuclear 4-HNE expression in the sublining layer (p=0.02; r=0.48) and DAS28-erythrocyte sedimentation rate was correlated with nuclear 4-HNE expression in both cell layers (p < or = 0.03). CONCLUSIONS: Lipid peroxidation is associated with low oxygen tension in vivo, disease activity and angiogenic marker expression in inflammatory arthritis.

  16. Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis.

    Directory of Open Access Journals (Sweden)

    Arundhati Ray

    Full Text Available Inclusion body myositis (IBM belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG. These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens.

  17. Investigations of the damage mechanisms during ultrashort pulse laser ablation of dental tissue (United States)

    Domke, Matthias; Wick, Sebastian; Laible, Maike; Rapp, Stephan; Kuznetsova, Julia; Homann, Christian; Huber, Heinz P.; Sroka, Ronald


    Several investigations of dental tissue ablation with ultrashort pulsed lasers suggest that these lasers enable precise and selective material removal and reduce the formation of micro cracks and thermal effects, when compared to ns-pulses. In this study, two damage mechanisms are presented occurring during ablation of dentin using a laser emitting pulses of a duration of 380 fs at a wavelength of 1040 nm. First, it was found that nano cracks appear around the craters after single fs-pulse ablation. These cracks are directed to the crater and cross the dentinal tubules. Transient investigation of the single fs-pulse ablation process by pump-probe microscopy suggest that the driving mechanism could be a pressure wave that is released after stress confinement. Second, squared ablation holes were created by moving the laser focus at scan speeds between 0.5 mm/s and 2.0 m/s and fluences up to 14 J/cm2. It was found that deep cracks appear at the edges of the squared holes, if the scan speed is about 0.5 m/s. The fluence has only a minor impact on the crack formation. The crack propagation was investigated in the depth using x-ray micro tomography and optical coherence tomography. It was found that these cracks appear in the depth down to the dental pulp. These findings suggest that fast scanning of the laser beam is the key for damage free processing using ultrashort pulse lasers. Then, ablation rates of about 2.5 - 3.5 mm3/min/W can be achieved in dentine with pulse durations of 380 fs.

  18. Influence of estrogen on markers of muscle tissue damage following eccentric exercise. (United States)

    Carter, A; Dobridge, J; Hackney, A C


    This study tested the hypothesis that estrogen levels of women influences the development of a muscle-tissue damage (creatine kinase, CK) marker and delayed onset muscle soreness (DOMS) following eccentric exercise. Seventeen oral contraceptive (OC) users and ten eumenorrheic (EU) subjects completed a 30-min downhill running bout at approximately 60% VO2max. The OC completed the exercise during the mid-luteal phase (day 22.9 +/- 1.5; high estrogen) while the EU did their exercise in the mid-follicular phase (day 9.6 +/- 4.4; low estrogen) of the menstrual cycle, respectively. The CK activity and DOMS were assessed pre-exercise, immediately post-, 24, 48 and 72 h post-exercise. ANOVA results indicated that there was a significant increase in CK activity in response to the downhill run (p < 0.001), and the interaction of group x time was significantly different (p < 0.01). The OC group had lower CK at 72 h post-exercise than did the EU group. Pre-exercise estrogen levels correlated with the overall mean CK (r = -0.43, p < 0.05) and 72 h (r = -0.38, p < 0.05) responses, respectively. Exercise caused an increase in DOMS in both groups (p < 0.001); but, no significant interaction was observed. These findings suggest that elevated estrogen levels have a protective effect on muscle tissue following eccentric exercise. The mechanism of this protective effect is unclear but may be related to the anti-oxidant characteristics and membrane stability properties associated with estrogen and its derivatives.

  19. Tissue Damage Markers after a Spinal Manipulation in Healthy Subjects: A Preliminary Report of a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    A. Achalandabaso


    Full Text Available Spinal manipulation (SM is a manual therapy technique frequently applied to treat musculoskeletal disorders because of its analgesic effects. It is defined by a manual procedure involving a directed impulse to move a joint past its physiologic range of movement (ROM. In this sense, to exceed the physiologic ROM of a joint could trigger tissue damage, which might represent an adverse effect associated with spinal manipulation. The present work tries to explore the presence of tissue damage associated with SM through the damage markers analysis. Thirty healthy subjects recruited at the University of Jaén were submitted to a placebo SM (control group; n=10, a single lower cervical manipulation (cervical group; n=10, and a thoracic manipulation (n=10. Before the intervention, blood samples were extracted and centrifuged to obtain plasma and serum. The procedure was repeated right after the intervention and two hours after the intervention. Tissue damage markers creatine phosphokinase (CPK, lactate dehydrogenase (LDH, C-reactive protein (CRP, troponin-I, myoglobin, neuron-specific enolase (NSE, and aldolase were determined in samples. Statistical analysis was performed through a 3×3 mixed-model ANOVA. Neither cervical manipulation nor thoracic manipulation did produce significant changes in the CPK, LDH, CRP, troponin-I, myoglobin, NSE, or aldolase blood levels. Our data suggest that the mechanical strain produced by SM seems to be innocuous to the joints and surrounding tissues in healthy subjects.

  20. DNA damage and metal accumulation in four tissues of feral Octopus vulgaris from two coastal areas in Portugal. (United States)

    Raimundo, Joana; Costa, Pedro M; Vale, Carlos; Costa, Maria Helena; Moura, Isabel


    The alkaline comet assay has been employed for the first time to estimate the basal DNA damage in the digestive gland, gills, kidney and gonads of Octopus vulgaris. Octopuses were captured in two coastal areas adjacent to the cities of Matosinhos (N) and Olhão (S), Portugal. The area of Matosinhos is influenced by discharges of the Douro River, city of Porto, industries and intensive agriculture, while Olhão is an important fisheries port. Previous works point to contrasting metal availability in the two coastal areas. Among the analysed tissues digestive gland presented the highest levels of Zn, Cu, Cd and Pb. Tissues of specimens from Matosinhos exhibited high levels of Cd and from Olhão enhanced Pb concentrations. The DNA damages in digestive gland, gills and kidney were more accentuated in specimens from Matosinhos than from Olhão, suggesting a stronger effect of contaminants. Elevated strand breakages were registered in digestive gland, recognised for its ability to store and detoxify accumulated metals. The DNA damages in kidney, gills and gonads were lower, reflecting reduced metal accumulation or efficient detoxification. The broad variability of damages in the three tissues may also mirror tissue function, specific defences to genotoxicants and cell-cycle turnover. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Metformin ameliorates podocyte damage by restoring renal tissue nephrin expression in type 2 diabetic rats. (United States)

    Zhai, Limin; Gu, Junfei; Yang, Di; Hu, Wen; Wang, Wei; Ye, Shandong


    Previous studies found that metformin provided some renoprotection for diabetic renal damage. In the present study, we evaluated the effects of different doses of metformin on the expression of renal tissue nephrin in type 2 diabetes mellitus (T2DM) model rats and the possible mechanism underlying its protective effect in kidney podocytes. A high-fat diet combined with a low dose of streptozotocin was used to induce T2DM model rats. Diabetic rats were treated with 150, 300, or 500 mg/kg metformin for 8 weeks. At the end of the study, urine and blood samples were collected for measurement of different indices. Light microscopy and transmission electron microscopy were used to identify morphological changes. Renal expression of nephrin protein was assayed by immunohistochemical staining, whereas real-time polymerase chain reaction was used to detect renal nephrin (Nphs1) mRNA expression. Metformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment. Metformin protects kidney podocytes in T2DM model rats by dose-dependently adjusting renal nephrin expression. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  2. Skin and soft tissue artifacts due to postmortem damage caused by rodents. (United States)

    Tsokos, M; Matschke, J; Gehl, A; Koops, E; Püschel, K


    Five cases of postmortem bite-injuries inflicted by rodents are presented (five males between 41 and 89 years; three cases caused by mice, one case by rats, one case of possible mixed rodent activity by rats and mice). The study presents a spectrum of phenomenological aspects of postmortem artifacts due to rodent activity to fresh skin and soft tissue: the majority of the injuries have a circular appearance. The wound margins are finely serrated with irregular edges and circumscribed 1-2 mm intervals within, partly showing protruding indentations up to 5 mm. Distinct parallel cutaneous lacerations deriving from the biting action of the upper and lower pairs of the rodents incisors are diagnostic for tooth marks of rodent origin but cannot always be found. No claw-induced damage can be found in the skin beyond the wound margins. Areas involved in the present study were: exposed and unprotected parts of the body, such as eyelids, nose and mouth (representing moist parts of the face); and the back of the hands. Postmortem rodent activity may occasionally be expected on clothed and therefore protected parts of the body. The phenomenon of postmortem rodent activity to human bodies can be found indoors especially under circumstances of low socioeconomic settings; outdoors this finding is particularly observed among fatalities among homeless people.

  3. Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction (United States)

    Marks, Edward D.

    The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell

  4. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.


    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

  5. Damage of rat liver tissue caused by repeated and sustained +Gz exposure and the mechanism thereof

    Directory of Open Access Journals (Sweden)

    Wen-bing LI


    Full Text Available Objective  To explore the mechanisms of positive acceleration (+Gz on the damage of rat liver tissue and the effect of +Gz on the expression of JNK/c-Jun in liver cells. Methods  Twenty four male Wistar rats were randomly divided into 4 groups (n=6: control, +2Gz, +6Gz and +10Gz group. With prone position, the rats in control group were fixed to the turning arm of centrifuge with head towards the axis for 5 minutes. The fixation method in +2Gz, +6Gz and +10Gz group was the same as in the control group. The increase rate of acceleration was 1G/s with a peak-time of 3 minutes, and each +Gz exposure repeated 5 times with an interval of 30 minutes. HE staining was used to observe the morphological changes of liver tissue, fluorescence real-time quantitative PCR to detect the expression of hepatic c-Jun mRNA, and Western blotting to detect the hepatic protein expression of p-c-Jun, c-Jun, p-JNK and JNK. Plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT were determined. Results  The levels of serum ALT and AST increased significantly in +6Gz and, especially, the +10Gz group than in control group and +2Gz group (P<0.05. The same situation also existed in the increase of c-Jun mRNA expression (P<0.05. Hepatic c-jun and p-c-Jun (c-Jun activated form protein expression increased with the increase of G value. Compared with control group, no change was found in JNK protein expression in the other three groups, but the expression of p-JNK (activated form of JNK increased in +6Gz and +10Gz groups (P<0.05. HE staining showed the disorganized liver cells with irregular shapes, the unclear cell gap and the vacuolar changes in +6Gz and +10Gz groups. Conclusions  Repeated and sustained +Gz may cause enhanced expression of c-Jun/ p-c-Jun and p-JNK in hepatic cells. JNK/c-Jun signaling pathway may play an important role in the process of hepatic stress injury. DOI: 10.11855/j.issn.0577-7402.2014.03.15

  6. Correlation of renal complications with extent and progression of tissue damage in electrical burns

    Directory of Open Access Journals (Sweden)

    Chauhan D


    Full Text Available Electrical injuries due to high-tension voltage (>1000 volts cause destruction at the point of contact with massive necrosis of deeper structures such as muscles, vessels and nerves. Rhabdomyolysis due to massive breakdown of skeletal muscles may lead to acute renal failure secondary to myoglobinuria. The study was undertaken to observe the correlation of renal complications with extent and progression of tissue damage in high-tension voltage electrical burns. Renal biochemical parameters as predictors of acute renal failure were also studied. Thirty two patients of high tension voltage electrical burn injuries presenting during one year period 1-1-2001 to 31-12-2001 were studied. Low-tension voltage electrical injuries (< 1000 volts mimic thermal burns were excluded from the study. The electrical wound assessment and the renal biochemical parameters were done daily for the first seven days and then on alternate days for another seven days. Assessment of progression of wounds and correlation with the renal biochemical parameters was done. Patients who died following electrical burns were subjected to autopsy and histopathological examination of both kidneys. Out of the thirty-two patients, six (18.75% went into acute renal failure. Five out of these six patients died because of renal failure (mortality rate 83.33%. There was definite progression of electric burn wounds. There was no correlation between progression of electrical burn wounds and acute renal failure. Serum creatinine was found to be the most important biochemical parameter as a prognostic indicator of acute renal failure.

  7. Fractal-based analysis of optical coherence tomography data to quantify retinal tissue damage. (United States)

    Somfai, Gábor Márk; Tátrai, Erika; Laurik, Lenke; Varga, Boglárka E; Ölvedy, Vera; Smiddy, William E; Tchitnga, Robert; Somogyi, Anikó; DeBuc, Delia Cabrera


    The sensitivity of Optical Coherence Tomography (OCT) images to identify retinal tissue morphology characterized by early neural loss from normal healthy eyes is tested by calculating structural information and fractal dimension. OCT data from 74 healthy eyes and 43 eyes with type 1 diabetes mellitus with mild diabetic retinopathy (MDR) on biomicroscopy was analyzed using a custom-built algorithm (OCTRIMA) to measure locally the intraretinal layer thickness. A power spectrum method was used to calculate the fractal dimension in intraretinal regions of interest identified in the images. ANOVA followed by Newman-Keuls post-hoc analyses were used to test for differences between pathological and normal groups. A modified p value of Fractal dimension was higher for all the layers (except the GCL + IPL and INL) in MDR eyes compared to normal healthy eyes. When comparing MDR with normal healthy eyes, the highest AUROC values estimated for the fractal dimension were observed for GCL + IPL and INL. The maximum discrimination value for fractal dimension of 0.96 (standard error =0.025) for the GCL + IPL complex was obtained at a FD ≤ 1.66 (cut off point, asymptotic 95% Confidence Interval: lower-upper bound = 0.905-1.002). Moreover, the highest AUROC values estimated for the thickness measurements were observed for the OPL, GCL + IPL and OS. Particularly, when comparing MDR eyes with control healthy eyes, we found that the fractal dimension of the GCL + IPL complex was significantly better at diagnosing early DR, compared to the standard thickness measurement. Our results suggest that the GCL + IPL complex, OPL and OS are more susceptible to initial damage when comparing MDR with control healthy eyes. Fractal analysis provided a better sensitivity, offering a potential diagnostic predictor for detecting early neurodegeneration in the retina.

  8. The role of the cerebral ganglia in the venom-induced behavioral manipulation of cockroaches stung by the parasitoid jewel wasp. (United States)

    Kaiser, Maayan; Libersat, Frederic


    The jewel wasp stings cockroaches and injects venom into their cerebral ganglia, namely the subesophageal ganglion (SOG) and supraesophageal ganglion (SupOG). The venom induces a long-term hypokinetic state, during which the stung cockroach shows little or no spontaneous walking. It was shown that venom injection to the SOG reduces neuronal activity, thereby suggesting a similar effect of venom injection in the SupOG. Paradoxically, SupOG-ablated cockroaches show increased spontaneous walking in comparison with control. Yet most of the venom in the SupOG of cockroaches is primarily concentrated in and around the central complex (CX). Thus the venom could chiefly decrease activity in the CX to contribute to the hypokinetic state. Our first aim was to resolve this discrepancy by using a combination of behavioral and neuropharmacological tools. Our results show that the CX is necessary for the initiation of spontaneous walking, and that focal injection of procaine to the CX is sufficient to induce the decrease in spontaneous walking. Furthermore, it was shown that artificial venom injection to the SOG decreases walking. Hence our second aim was to test the interactions between the SupOG and SOG in the venom-induced behavioral manipulation. We show that, in the absence of the inhibitory control of the SupOG on walking initiation, injection of venom in the SOG alone by the wasp is sufficient to induce the hypokinetic state. To summarize, we show that venom injection to either the SOG or the CX of the SupOG is, by itself, sufficient to decrease walking. © 2015. Published by The Company of Biologists Ltd.

  9. Design of endoscopic micro-robotic end effectors: safety and performance evaluation based on physical intestinal tissue damage characteristics. (United States)

    Kim, Young-Tae; Kim, Dae-Eun; Yang, Sungwook; Yoon, Eui-Sung


    During the last several years, legged locomotive mechanism has been considered as one of the main self-propelling mechanisms for future endoscopic microrobots due to its superior propulsion efficiency of an endoscopic microrobot inside the intestinal track. Nevertheless, its clinical application has been largely limited since the legged locomotive mechanism utilizes an end effector which has a sharp tip to generate sufficient traction by physically penetrating and interlocking with the intestinal tissue. This can cause excessive physical tissue damage or even complete perforation of the intestinal wall that can lead to abdominal inflammation. Hence, in this work two types of new end effectors, penetration-limited end effector (PLEE) and bi-material structured end effector (BMEE) were specially designed to acquire high medical safety as well as effective traction generation performance. The microscopic end effector specimens were fabricated with micro-wire electric discharge machining process. Traction generation performance of the end effectors was evaluated by direct measurement of resistance forces during contact-sliding tests using a custom-built contact-sliding tester. The safety of the end effector design was evaluated by examination of microscopic intestinal tissue damage using a scanning electron microscope (SEM). Physical damage characteristics of the intestinal tissue and related contact physics of the end effectors were discussed. From the results, the end effectors were evaluated with respect to their prospects in future medical applications as safe end effectors as well as micro-surgical tools.

  10. Effect of exercise-induced muscle damage on muscle hardness evaluated by ultrasound real-time tissue elastography


    Yanagisawa, Osamu; Sakuma, Jun; Kawakami, Yasuo; Suzuki, Katsuhiko; Fukubayashi, Toru


    Purpose To assess the effect of exercise-induced muscle damage on muscle hardness and evaluate the relationship between muscle hardness and muscle damage indicators. Methods Seven men (mean 25.3?years; 172.7?cm; 66.8?kg) performed the single-leg ankle plantar flexion exercise involving both concentric and eccentric contractions (10 sets of 40 repetitions). The hardness of the medial gastrocnemius (MG) was evaluated using ultrasound real-time tissue elastography before, from day 1 to 4, and da...

  11. Clozapine linked to nanocapsules minimizes tissue and oxidative damage to biomolecules lipids, proteins and DNA in brain of rats Wistar. (United States)

    da Costa Güllich, Angélica Aparecida; Coelho, Ritiéle Pinto; Pilar, Bruna Cocco; Ströher, Deise Jaqueline; Galarça, Leandro Alex Sander Leal; Vieira, Simone Machado; da Costa Escobar Piccoli, Jacqueline; Haas, Sandra Elisa; Manfredini, Vanusa


    Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (n = 6): saline (SAL), free clozapine (CZP) (25 mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25 mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25 mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25 mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (p < 0.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.

  12. The impact of impaired DNA damage responses on cells, tissues and organisms

    NARCIS (Netherlands)

    Yi, Xia


    Current cancer therapies rely mainly on DNA damaging insults (irradiation, DNA alkylating agents, DNA synthesis inhibitors etc.). The rationale behind these treatments is that rapidly growing cancer cells suffer more from DNA damaging insults. Unfortunately, the majority of current therapies fail to

  13. Oxidative damage parameters in renal tissues of aged and young rats based on gender

    Directory of Open Access Journals (Sweden)

    Uzun D


    young control group for both genders. Conclusion: With respect to PCO and AOPP, impaired redox homeostasis is substantially more prominent in males than females. The decrease of G-SH levels in male groups could be attributed to stabilizing the redox status of protein thiol groups by the depletion of the GSH groups. Considering the results, the renal tissue proteins and lipids in different genders may have different susceptibilities to oxidative damage. Keywords: lipid peroxidation, protein oxidation, radicals, renal aging

  14. Acceleration of normal-tissue damage expression by early stimulation of cell proliferation in rat spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C.; Andratschke, N. [Technical Univ., Munich (Germany). Dept. of Radiation Oncology, Klinikum rechts der Isar; Price, R.E. [The Univ. of Texas, M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Veterinary Medicine and Surgery; Kian-Ang, K. [The Univ. of Texas, M.D. Anderson Cancer Center, Houston, TX (United States). Dept. of Radiation Oncology


    Purpose: To examine experimental strategies for prevention of radiation-induced late spinal cord damage. Material and Methods: The effects of treatment with high, proliferation-stimulating doses of platelet-derived growth factor (PDGF) administered at various times after radiotherapy of rat spinal cord, and aiming at increased tissue regeneration, were studied in an established model. Animals were followed and monitored for expression of radiation myelopathy (RM), which was confirmed by histopathologic diagnosis. Results: High doses of PDGF given 8 weeks after radiotherapy significantly accelerated the development of RM compared to control animals (Figure 1). Such effects were observed also for concomitant treatment, but not for PDGF administration after 12 or 15 weeks (Figure 2). On the microscopic level, the spinal cord showed more pronounced vascular damage with vessel necroses and hemorrhages (Figure 3). Conclusion: These data suggest that the vascular system plays an important role during development of RM and that early stimulation of cell proliferation negatively influences the time course of spinal cord damage. Further experiments should address different concepts of tissue regeneration or damage prevention. (orig.)

  15. The Extent of Tissue Damage in the Epidural Space by Ho / YAG Laser During Epiduroscopic Laser Neural Decompression. (United States)

    Jo, Daehyun; Lee, Dong Joo


    Lasers have recently become very useful for epiduroscopy. As the use of lasers increases, the potential for unwanted complications with direct application of laser energy to nerve tissue has also increased. Even using the lowest laser power to test for nerve stimulation, there are still risks of laser ablation. However, there are no studies investigating tissue damage from laser procedures in the epidural space. This is a study on the risks of Ho/YAG laser usage during epiduroscopy. Observatory cadaver study. Department of anatomy and clinical research institute at the University Hospital. We used 5 cadavers for this study. After removing the dura and nerve root from the spinal column, laser energy from a Ho/YAG laser was applied directly to the dura and nerve root as well as in the virtual epidural space, which mimicked the conditions of epiduroscopy with the dura folded. Tissue destruction at all laser ablation sites was observed with the naked eye as well as with a microscope. Specimens were collected from each site of laser exposure, fixed in 10% neutral formalin, and dyed with H/E staining. Tissue destruction was observed in all laser ablation sites, regardless of the length of exposure and the power of the laser beam. A cadaver is not exactly the same as a living human because dura characteristics change and tissue damage can be influenced by dura thickness according to the spinal level. Even with low power and short duration, a laser can destroy tissue if the laser beam makes direct contact with the tissue.

  16. Fibroblasts express immune relevant genes and are important sentinel cells during tissue damage in rainbow trout (Oncorhynchus mykiss.

    Directory of Open Access Journals (Sweden)

    Hans-Christian Ingerslev

    Full Text Available Fibroblasts have shown to be an immune competent cell type in mammals. However, little is known about the immunological functions of this cell-type in lower vertebrates. A rainbow trout hypodermal fibroblast cell-line (RTHDF was shown to be responsive to PAMPs and DAMPs after stimulation with LPS from E. coli, supernatant and debris from sonicated RTHDF cells. LPS was overall the strongest inducer of IL-1beta, IL-8, IL-10, TLR-3 and TLR-9. IL-1beta and IL-8 were already highly up regulated after 1 hour of LPS stimulation. Supernatant stimuli significantly increased the expression of IL-1beta, TLR-3 and TLR-9, whereas the debris stimuli only increased expression of IL-1beta. Consequently, an in vivo experiment was further set up. By mechanically damaging the muscle tissue of rainbow trout, it was shown that fibroblasts in the muscle tissue of rainbow trout contribute to electing a highly local inflammatory response following tissue injury. The damaged muscle tissue showed a strong increase in the expression of the immune genes IL-1beta, IL-8 and TGF-beta already 4 hours post injury at the site of injury while the expression in non-damaged muscle tissue was not influenced. A weaker, but significant response was also seen for TLR-9 and TLR-22. Rainbow trout fibroblasts were found to be highly immune competent with a significant ability to express cytokines and immune receptors. Thus fish fibroblasts are believed to contribute significantly to local inflammatory reactions in concert with the traditional immune cells.

  17. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L., protects rat tissues against oxidative damage after acute ethanol administration

    Directory of Open Access Journals (Sweden)

    Carmen Pinto


    Full Text Available Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol bingeing also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of xanthohumol (XN on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w. of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S-transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.

  18. Pancreatic-derived pathfinder cells enable regeneration of critically damaged adult pancreatic tissue and completely reverse streptozotocin-induced diabetes. (United States)

    Stevenson, Karen; Chen, Daxin; MacIntyre, Alan; McGlynn, Liane M; Montague, Paul; Charif, Rawiya; Subramaniam, Murali; George, W D; Payne, Anthony P; Davies, R Wayne; Dorling, Anthony; Shiels, Paul G


    We demonstrate that intravenous delivery of human, or rat, pancreas-derived pathfinder (PDP) cells can totally regenerate critically damaged adult tissue and restore normal function across a species barrier. We have used a mouse model of streptozotocin (STZ)-induced diabetes to demonstrate this. Normoglycemia was restored and maintained for up to 89 days following the induction of diabetes and subsequent intravenous delivery of PDP cells. Normal pancreatic histology also appeared to be restored, and treated diabetic animals gained body weight. Regenerated tissue was primarily of host origin, with few rat or human cells detectable by fluorescent in situ hybridization (FISH). Crucially, the insulin produced by these animals was overwhelmingly murine in origin and was both types I and II, indicative of a process of developmental recapitulation. These results demonstrate the feasibility of using intravenous administration of adult cells to regenerate damaged tissue. Critically, they enhance our understanding of the mechanisms relating to such repair and suggest a means for novel therapeutic intervention in loss of tissue and organ function with age.

  19. Residual late radiation damage in mouse stromal tissue assessed by the tumor bed effect

    NARCIS (Netherlands)

    Haveman, Jaap; Rodermond, Hans; van Bree, Chris; Wondergem, Jan; Franken, Nicolaas A. P.


    Irradiation of murine subcutaneous stroma before implantation of tumor cells leads to retarded tumor growth. This effect is called Tumor Bed Effect (TBE) and can be used to assess the sensitivity of stromal tissue to radiation. We tested the ability of stromal tissue to recover from X-ray-induced

  20. Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

    Directory of Open Access Journals (Sweden)

    Paolo Durigutto


    Full Text Available Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI. As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

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

    Directory of Open Access Journals (Sweden)

    Francisco Javier Guzmán-de la Garza


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

  2. Manifestations of oxidative stress and molecular damages in ovarian cancer tissue

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska


    Full Text Available Indices of oxidative stress are recognized molecular markers and prognostic criteria for malignant transformation of tissue, but their value depends on the type of tumor and the stage of its development. The goal of this study was to clarify the relationship between the characteristics of the oxidative stress system including­ metal-associated ones and the cytotoxicity manifestations in neoplastically transformed human ovarian tissue. The highest level of Mn-superoxide dismutase activity (by 630% and metallothionein protein (MT, 100% has been estimated for the first time in malignant ovarian tissue compared to normal ovarian tissue. The researchers have also found a much higher level of oxy-radical formation (by 332%, a lower activity of catalase (by 49% and a lower level of reduced glutathione (by 46% and its redox index (0.84 versus 0.89 in the control in tumor tissue. Under the relatively stable content of zinc, copper and cadmium in MTs, the content of zinc and especially copper in a form non-binding with MTs was significantly lower in the malignant tissue compared to normal one while the content of cadmium was higher. A discriminant analysis of all definable parameters revealed that the higher content of the products of oxidative destruction of proteins, lipids, fragmented DNA and the activity of cathepsin D, especially in its free form (by 235%, are the main characteristic signs of malignant ovarian tissue.

  3. Protective effect of annexin-A1 against irreversible damage to cavernous tissue after cavernous nerve injury in the rat. (United States)

    Facio, Fernando N; Burnett, Arthur L


    Study Type - Aetiology (case control) Level of Evidence 3b. What's known on the subject? and What does the study add? Penile rehabilitation is still controversial regarding good results. Our study shows a non-invasive treatment option to recovery after cavernous nervous damage. The assessment of changes in the intracavernous pressure and karyometry demonstrates the protective effect of annexin-A1 in an animal model of cavernous nerve injury. We found that annexin-A1 effectively preserved erectile function, evidently through significantly protecting the corpus cavernosum tissue against fibrosis. • To evaluate the protective effect of annexin-A1 against irreversible damage to cavernous tissue after cavernous nerve injury. • Thirty Sprague-Dawley male rats were divided into 3 groups; sham-operated rats (n= 10), bilateral cavernous nerve injury treated intravenously with 100 µg/kg annexin-A1 (n= 10), and a crush group of rats submitted to bilateral cavernous nerve injury and vehicle (n= 10). Groups were compared in respect to intracavernous pressure and karyometric parameters. • After annexin-A1 treatment, the maximum changes in intracavernous pressure responses were significantly higher in the annexin-A1 group compared to the vehicle-only group on the 7(th) postoperative day (p-value cavernous nerve injury. We found that annexin-A1 effectively preserved erectile function, evidently through significantly protecting the corpus cavernosum tissue against fibrosis. © 2012 BJU INTERNATIONAL.

  4. A comparison of the thermal-dose equation and the intensity-time product, Itm, for predicting tissue damage thresholds. (United States)

    Harris, Gerald R; Herman, Bruce A; Myers, Matthew R


    Thermal dose is the most generally accepted concept for estimating temperature-related tissue damage thresholds in high-intensity focused ultrasound (HIFU) procedures. However, another approach based on the intensity-time product I t(m) =D has been used, where D is a tissue-dependent damage threshold, I is the spatial-peak, temporal-average intensity and t is time. In this study, these two approaches were compared analytically by substituting a well-known soft-tissue solution for temperature vs. time into the thermal dose equation. From power law fits of I vs. t, m was found to fall between about 0.3 and 0.8. In terms of the intensity required for cell death for a given exposure time, the standard deviation of the error between the full thermal-dose formulation and the I t(m) =D prediction based upon the power-law fit was less than 5% for focal beam diameters up to 3 mm. Thus, for the practical range of HIFU parameters examined, the intensity-time product relationship is equivalent to the thermal dose formulation. Published by Elsevier Inc.

  5. Pathological research on acute hepatic and renal tissue damage in Wistar rats induced by cocoa

    Directory of Open Access Journals (Sweden)

    Chiedozie Onyejiaka Ibegbulem


    Conclusions: The pattern of alanine aminotransferase activity being more active than aspartate aminotransferase one in serum appeared to correlate with the extent of disarrangement of hepatic tissue architecture. The experimental rat groups exhibited no hyperbilirubinemia. Also, diets containing processed cocoa bean and raw cocoa bean products did not substantially interfere with the capacity of the hepatocytes to biosynthesize plasma proteins and the functionality of renal tissues.

  6. Th e eff ects of Nigella Sativa extract on renal tissue oxidative damage during neonatal and juvenile growth in propylthiouracil-induced hypothyroid rats

    Directory of Open Access Journals (Sweden)

    Mohebbati R.


    Full Text Available Objective. We investigated the effects of hydroalcoholic extract of Nigella sativa (NS on renal tissue oxidative damage associated with propylthiouracil (PTU-induced hypothyroidism during neonatal and juvenile growth in rats.

  7. Quantitative MRI analysis of the brain after twenty-two years of neuromyelitis optica indicates focal tissue damage

    DEFF Research Database (Denmark)

    Aradi, Mihaly; Koszegi, Edit; Orsi, Gergely


    BACKGROUND: The long-term effect of neuromyelitis optica (NMO) on the brain is not well established. METHODS: After 22 years of NMO, a patient's brain was examined by quantitative T1- and T2-weighted mono- and biexponential diffusion and proton spectroscopy. It was compared to 3 cases with short......, and they were also not quantitatively different from the controls. CONCLUSION: After NMO of 22-year duration, metabolic changes, altered diffusivity and magnetic resonance relaxation features of patchy brain areas may suggest tissue damage in NAWM that persist for at least 6 months....

  8. Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat. (United States)

    Nalbantsoy, Ayse; Erel, Sura Baykan; Köksal, Cinel; Göçmen, Bayram; Yıldız, Mehmet Zülfü; Karabay Yavaşoğlu, Nefise Ülkü


    The present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti-snake venom activities of Artemisia absinthium L. in comparison with carrageenan-induced acute inflammation model in rats. The LD50 value was estimated as 8.78 mg/kg within 24 h by different venom doses administrated intraperitoneally in mice. The IC50 value was 0.43 ± 0.18 μg/ml after 48 h treatment while the calculated value was 0.73 ± 0.10 μg/ml for the culture media totally refreshed after 2 h treatment with venom. Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw. Intraperitoneal administration of 25 and 50 mg/kg extract was inhibited venom induced paw swelling at 0.5, 1, 2 and 3 h (p absinthium was described. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography

    NARCIS (Netherlands)

    Jansen, H M; Pruim, J; vd Vliet, A M; Paans, A M; Hew, J M; Franssen, E J; de Jong, B M; Kosterink, J G; Haaxma, R; Korf, J

    UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+

  10. C60 exposure induced tissue damage and gene expression alterations in the earthworm Lumbricus rubellus

    NARCIS (Netherlands)

    Ploeg, van der M.J.C.; Handy, R.D.; Heckmann, L.H.; Hout, van der A.; Brink, van den N.W.


    Effects of C60 exposure (0, 15 or 154 mg/kg soil) on the earthworm Lumbricus rubellus were assessed at the tissue and molecular level, in two experiments. In the first experiment, earthworms were exposed for four weeks, and in the second lifelong. In both experiments, gene expression of heat shock

  11. Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia in Alloxan-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Amanda Alves da Rocha


    Full Text Available Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage.

  12. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.


    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  13. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study. (United States)

    Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride


    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia in Alloxan-Induced Diabetic Mice (United States)

    da Rocha, Amanda Alves; Araújo, Tiago Ferreira da Silva; da Fonseca, Caíque Silveira Martins; da Mota, Diógenes Luís; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso; Correia, Maria Tereza dos Santos; Lima, Vera Lúcia de Menezes


    Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage. PMID:24324521

  15. Beneficial Effects of Teucrium polium and Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats

    Directory of Open Access Journals (Sweden)

    S. Mojtaba Mousavi


    Full Text Available Objective. The effects of hydroalcoholic extract of Teucrium polium and metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated. Methods. The rats were divided into: (1 Control, (2 Diabetic, (3 Diabetic-Extract 100 (Dia-Ext 100, (4 Diabetic-Extract 200 (Dia-Ext 200, (5 Diabetic-Extract 400 (Dia-Ext 400, and (6 Diabetic-Metformin (Dia-Met. Groups 3–6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally. Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P<0.01. In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P<0.01. Lipid peroxides levels (reported as malondialdehyde, MDA, concentration in the brain of Diabetic group were higher than Control (P<0.001. Treatment by all doses of the extract and metformin decreased the MDA concentration (P<0.01. Conclusions. The results of present study showed that metformin and the hydroalcoholic extract of Teucrium polium prevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.

  16. Effect of exercise-induced muscle damage on muscle hardness evaluated by ultrasound real-time tissue elastography. (United States)

    Yanagisawa, Osamu; Sakuma, Jun; Kawakami, Yasuo; Suzuki, Katsuhiko; Fukubayashi, Toru


    To assess the effect of exercise-induced muscle damage on muscle hardness and evaluate the relationship between muscle hardness and muscle damage indicators. Seven men (mean 25.3 years; 172.7 cm; 66.8 kg) performed the single-leg ankle plantar flexion exercise involving both concentric and eccentric contractions (10 sets of 40 repetitions). The hardness of the medial gastrocnemius (MG) was evaluated using ultrasound real-time tissue elastography before, from day 1 to 4, and day 7 after exercise. The strain ratio between the MG and a reference material was calculated. Simultaneously, we evaluated the magnetic resonance T2 value (an index of edema) of the triceps surae, the ankle dorsiflexion range of motion (ROM), and calf muscle soreness. Serum creatine kinase activity was assessed before, 2 and 4 h, and from day 1 to 4 after exercise. The MG showed lower strain ratio, indicating increased muscle hardness, on day 4 post-exercise (P muscle soreness among the post-exercise time points was similar. The decreased strain ratio did not correlate with the increased T2, the decreased joint ROM or muscle soreness. Muscle hardness increased after strenuous resistance exercise, but the change was not related with muscle edema, decreased joint ROM, or muscle soreness resulting from muscle damage.

  17. Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Rα-independent alternative differentiation of macrophages.

    Directory of Open Access Journals (Sweden)

    Julia Esser-von Bieren

    Full Text Available Approximately one-third of the world's population suffers from chronic helminth infections with no effective vaccines currently available. Antibodies and alternatively activated macrophages (AAM form crucial components of protective immunity against challenge infections with intestinal helminths. However, the mechanisms by which antibodies target these large multi-cellular parasites remain obscure. Alternative activation of macrophages during helminth infection has been linked to signaling through the IL-4 receptor alpha chain (IL-4Rα, but the potential effects of antibodies on macrophage differentiation have not been explored. We demonstrate that helminth-specific antibodies induce the rapid trapping of tissue migrating helminth larvae and prevent tissue necrosis following challenge infection with the natural murine parasite Heligmosomoides polygyrus bakeri (Hp. Mice lacking antibodies (JH (-/- or activating Fc receptors (FcRγ(-/- harbored highly motile larvae, developed extensive tissue damage and accumulated less Arginase-1 expressing macrophages around the larvae. Moreover, Hp-specific antibodies induced FcRγ- and complement-dependent adherence of macrophages to larvae in vitro, resulting in complete larval immobilization. Antibodies together with helminth larvae reprogrammed macrophages to express wound-healing associated genes, including Arginase-1, and the Arginase-1 product L-ornithine directly impaired larval motility. Antibody-induced expression of Arginase-1 in vitro and in vivo occurred independently of IL-4Rα signaling. In summary, we present a novel IL-4Rα-independent mechanism of alternative macrophage activation that is antibody-dependent and which both mediates anti-helminth immunity and prevents tissue disruption caused by migrating larvae.

  18. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail:


    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  19. Effects of cryotherapy combined with therapeutic ultrasound on oxidative stress and tissue damage after musculoskeletal contusion in rats. (United States)

    Martins, C N; Moraes, M B; Hauck, M; Guerreiro, L F; Rossato, D D; Varela, A S; da Rosa, C E; Signori, L U


    To investigate the combined effects of cryotherapy and pulsed ultrasound therapy (PUT) on oxidative stress parameters, tissue damage markers and systemic inflammation after musculoskeletal injury. Experimental animal study. Research laboratory. Seventy male Wistar rats were divided into five groups: control, lesion, cryotherapy, PUT, and cryotherapy+PUT. The gastrocnemius muscle was injured by mechanical crushing. Cryotherapy was applied immediately after injury (immersion in water at 10°C for 20minutes). PUT was commenced 24hours after injury (1MHz, 0.4W/cm2SPTA, 20% duty cycle, 5minutes). All animals were treated every 8hours for 3 days. Oxidative stress in muscle was evaluated by concentration of reactive oxygen species (ROS), lipid peroxidation (LPO), anti-oxidant capacity against peroxyl radicals (ACAP) and catalase. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were assessed. When applied individually, cryotherapy and PUT reduced CK, LDH, CRP and LPO caused by muscle damage. Cryotherapy+PUT in combination maintained the previous results, caused a reduction in ROS [P=0.005, mean difference -0.9×10-8 relative area, 95% confidence interval (CI) -0.2 to -1.9], and increased ACAP {P=0.007, mean difference 0.34 1/[relative area with/without 2,2-azobis(2-methylpropionamidine)dihydrochloride], 95% CI 0.07 to 0.61} and catalase (P=0.002, mean difference 0.41units/mg protein, 95% CI 0.09 to 0.73) compared with the lesion group. Cryotherapy+PUT in combination reduced oxidative stress in muscle, contributing to a reduction in adjacent damage and tissue repair. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  20. Inorganic arsenic in drinking water accelerates N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder tissue damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Paul-Yann [Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Chang Gung University, Chiayi, Taiwan (China); Lin, Yung-Lun; Huang, Chin-Chin; Chen, Sin-Syu [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China); Liu, Yi-Wen, E-mail: [Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi, Taiwan (China)


    Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycan layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in

  1. Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil [and others


    Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay.

  2. Quercetin, a Flavonoid Antioxidant, Ameliorated Procarbazine-Induced Oxidative Damage to Murine Tissues

    Directory of Open Access Journals (Sweden)

    Ebenezer Tunde Olayinka


    Full Text Available Procarbazine (PCZ (indicated in Hodgkin’s disease, is an alkylating agent known to generate free radicals in vivo, while Quercetin (QCT is a flavonoid antioxidant with proven free radical scavenging capacity. This study investigated the protective effects of QCT on PCZ-induced oxidative damage in the rat. Male Wistar rats (160–180 g were randomized into five groups (n = 5/group: I (control, II PCZ-treated (2 mg/kg body weight (bw for seven days; III pre-treated with QCT (20 mg/kg bw for seven days, followed by PCZ for seven days; IV co-treated with PCZ and QCT for seven days and V administered QCT alone for seven days. PCZ caused a significant increase in plasma total bilirubin, urea, and creatinine when compared with control (P < 0.05. Similarly, plasma activities of alkaline phosphatase (ALP, aspartate aminotransferase (AST, alanine aminotransferase (ALT, and γ-glutamyl transferase (γ-GT were significantly increased in the PCZ-treated group relative to control. Furthermore, PCZ caused a significant decrease in the activities of hepatic superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST as well as levels of ascorbic acid (AA and glutathione (GSH. This was followed by a significant increase in hepatic malondialdehyde (MDA content. However, QCT pre-treatment and co-treatment ameliorated the PCZ-induced changes in plasma levels of urea, creatinine, and bilirubin as well as the activities of ALP, AST, ALT, and GGT. QCT also ameliorated hepatic AA and GSH levels and the activities of SOD, CAT, and GST. This all suggests that QCT protected against PCZ-induced oxidative damage in rats.

  3. Photodynamic damage to cartilage and synovial tissue grafted on a chick's chorioallantoic membrane (United States)

    Fisher, M.; Nahir, A. M.; Kimel, Sol


    Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints causing pain deformities and disability. The highly vascular inflamed synovium has aggressive and destructive characteristics, it invades, erodes and gradually destroys cartilage and underlying bone. Photodynamic therapy (PDT) was performed using the chick chorioallantoic membrane (CAM) model to investigate the vitality of synovium and cartilage implanted on the CAM. Synovium, obtained from human patients, was grafted onto the CAM; gross microscopy and histology proved its vitality 7 days post grafting. Cartilage obtained from rabbit knee joint was also maintained on the CAM for 7 days. Its vitality was demonstrated by histology and by measuring metabolic and enzymatic activity of cartilage cells (chondrocytes) as well as the collagen and proteoglycans content. Selective PDT was performed using aluminum phthalocyanine tetrasulfonate (AlPcS4), a hydrophilic compound, soluble in biological solutions, as a photosensitizer. After irradiation with a diode laser (lambda equals 670 nm, 10 mW) damage was observed in vascularized synovium grafts, whereas avascular cartilage remained intact.

  4. Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats. (United States)

    Yanardag, Refiye; Tunali, Sevim


    Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of vanadyl sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg vanadyl sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given vanadyl sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased. The present study showed that vanadyl sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.

  5. Ameliorating effects of CAPE on oxidative damage caused by pneumoperitoneum in rat lung tissue (United States)

    Davarci, Isil; Alp, Harun; Ozgur, Tumay; Karcioglu, Murat; Tuzcu, Kasim; Evliyaoglu, Osman; Motor, Sedat; Durgun Yetim, Tulin


    We investigated the biochemical and histopathological effects of caffeic acid phenethyl ester (CAPE) against oxidative stress causing lung injury induced by pneumoperitoneum. Twenty-eight rats were selected at random and seven rats were assigned to each of the following groups. The control group (S) was subjected to a sham operation without pneumoperitoneum. The other groups were subjected to CO2 pneumoperitoneum 15 mmHg for 60 min. The laparoscopy group (L) had no additional drugs administered, the laparoscopy + alcohol (LA) group had 1 ml of 70% ethyl alcohol administered 1 h before the desufflation period, and the laparoscopy + CAPE (LC) group had CAPE administered at 10 μmol/kg 1 h before the desufflation period. The total oxidative status levels of lung and plasma were significantly increased in the LA group as compared with the LC and S group. When the LC group was compared with the L group, there was a decrease in the level of total oxidant status and increase in the levels of total antioxidant status and paraoxonase in lung tissue. The level of total antioxidative status in the S group was increased compared with the L group in lung tissue and bronchoalveolar lavage fluid. TNF-α and IL-6 were found significantly elevated in the L group compared with the LC and S groups in bronchoalveolar lavage fluid. There was a similar increase in plasma levels of IL-6. These results were supported by histopathological examination. CAPE was found to considerably reduce oxidative stress and inflammation induced by pneumoperitoneum. PMID:25126167

  6. [Interference of vitamin E on the brain tissue damage by electromagnetic radiation of cell phone in pregnant and fetal rats]. (United States)

    Gao, Xian; Luo, Rui; Ma, Bin; Wang, Hui; Liu, Tian; Zhang, Jing; Lian, Zhishun; Cui, Xi


    To investigate the interlerence ot vitamin E on brain tissue damage by electromagnetic radiation of cell phone in pregnant and fetal rats. 40 pregnant rats were randomly divided into five groups (positive control, negative control, low, middle and high dosage of vitamin E groups). The low, middle and high dosage of vitamin E groups were supplemented with 5, 15 and 30 mg/ml vitamin E respectively since the first day of pregnancy. And the negative control group and the positive control group were given peanut oil without vitamin E. All groups except for the negative control group were exposed to 900MHz intensity of cell phone radiation for one hour each time, three times per day for 21 days. After accouchement, the right hippocampus tissue of fetal rats in each group was taken and observed under electron microscope. The vitality of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of malondialdehyde (MDA) in pregnant and fetal rats' brain tissue were tested. Compared with the negative control group, the chondriosomes in neuron and neuroglia of brain tissues was swelling, mild edema was found around the capillary, chromatin was concentrated and collected, and bubbles were formed in vascular endothelial cells (VEC) in the positive fetal rat control group, whereas the above phenomenon was un-conspicuous in the middle and high dosage of vitamin E groups. We can see uniform chromatin, abundant mitochondrion, rough endoplasmic reticulum and free ribosomes in the high dosage group. The apoptosis has not fond in all groups'sections. In the antioxidase activity analysis, compared with the negative control group, the vitality of SOD and GSH-Px significantly decreased and the content of MDA significantly increased both in the pregnant and fetal rats positive control group (P electromagnetic radiation of cell phone in pregnant rats and fetal rats.

  7. Mercuric dichloride induces DNA damage in human salivary gland tissue cells and lymphocytes. (United States)

    Schmid, Katharina; Sassen, Andrea; Staudenmaier, Rainer; Kroemer, Susanne; Reichl, Franz-Xaver; Harréus, Ulrich; Hagen, Rudolf; Kleinsasser, Norbert


    Amalgam is still one of the most frequently used dental filling materials. However, the possible adverse effects especially that of the mercuric component have led to continued controversy. Considering that mercury may be released from amalgam fillings into the oral cavity and also reach the circulating blood after absorption and resorption, it eventually may contribute to tumorigenesis in a variety of target cells. The present investigation focuses on genotoxic effects below a cytotoxic dose level of mercuric dichloride (HgCl(2)) in human samples of salivary glands and lymphocytes to elucidate a possible role in tumor initiation. DNA migration due to single strand breaks, alkali labile sites and incomplete excision repair was quantified with the aid of the single cell microgel electrophoresis (Comet) assay. The concepts of Olive Tail Moment, percentage of DNA in the Tail and Tail Length were used as measures of DNA damage. To control for cytotoxic effects, the trypan blue exclusion test was applied. Human samples of the parotid salivary gland and lymphocytes of ten donors were exposed to HgCl(2)concentrations from 1 to 50 microM. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) served as controls. Increasing dose-dependent DNA migration could be demonstrated after exposure to HgCl(2) in cells of the salivary glands and lymphocytes. In both cell types a significant increase in DNA migration could be shown starting from HgCl(2)concentrations of 5 microM in comparison to the negative control. The viability of the cell systems was not affected except at the highest concentration (50 microM) tested. These data indicate genotoxic effects of mercuric dichloride in human salivary glands and lymphocytes at concentrations not leading to cytotoxic effects or cell death. Consequently, a contributory role in oral salivary gland tumor initiation warrants further investigation.

  8. The influence of water/air cooling on collateral tissue damage using a diode laser with an innovative pulse design (micropulsed mode)-an in vitro study. (United States)

    Beer, F; Körpert, W; Buchmair, A G; Passow, H; Meinl, A; Heimel, P; Moritz, A


    Since the diode laser is a good compromise for the daily use in dental offices, finding usage in numerous dental indications (e.g., surgery, periodontics, and endodontics), the minimization of the collateral damage in laser surgery is important to improve the therapeutical outcome. The aim of this study was to investigate the effect of water/air cooling on the collateral thermal soft tissue damage of 980-nm diode laser incisions. A total of 36 mechanically executed laser cuts in pork liver were made with a 980-nm diode laser in micropulsed mode with three different settings of water/air cooling and examined by histological assessment to determine the area and size of carbonization, necrosis, and reversible tissue damage as well as incision depth and width. In our study, clearly the incision depth increased significantly under water/air cooling (270.9 versus 502.3 μm-test group 3) without significant changes of incision width. In test group 2, the total area of damage was significantly smaller than in the control group (in this group, the incision depth increases by 65 %). In test group 3, the total area of damage was significantly higher (incision depth increased by 85 %), but the bigger part of it represented a reversible tissue alteration leaving the amount of irreversible damage almost the same as in the control group. This first pilot study clearly shows that water/air cooling in vitro has an effect on collateral tissue damage. Further studies will have to verify, if the reduced collateral damage we have proved in this study can lead to accelerated wound healing. Reduction of collateral thermal damage after diode laser incisions is clinically relevant for promoted wound healing.

  9. A reduction in DNA damage in neural tissue and peripheral blood of old mice treated with caffeine. (United States)

    Damiani, Adriani Paganini; Garcez, Michelle Lima; Letieli de Abreu, Larissa; Tavares, Taís Helena; Rodrigues Boeck, Carina; Moraes de Andrade, Vanessa


    Studies on caffeine consumption have shown a negative correlation with development of some diseases with subsequent beneficial manifestations. Our aim was to assess the effects of caffeine on peripheral blood and neural tissue DNA in young adult and aged mice. Male Swiss mice (age 2-3 or 16-18 months, respectively) were treated with a caffeine solution (0.3 g/l) for 4 weeks, while controls received water. After the treatments, blood and hippocampal cells (for a comet assay) and femurs (for a micronucleus [MN] test) were collected. The comet assay of peripheral blood and hippocampal cells demonstrated no significant differences between caffeine-treated and control young adult mice in terms of DNA damage index (DI) and frequency. In contrast, when comparing young adult with aged animals, significant differences were observed in DNA damage in blood and hippocampal cells. The differences between aged animals (with or without caffeine) consisted of a significant decrease in DNA DI in the group that received caffeine. In the MN test, an increase in frequency of micronucleated polychromatic (PCE) erythrocytes was noted in aged animals that received water compared to young adult mice. In addition, comparing treated with control aged murine groups, a decrease in frequency of MN was found in PCE erythrocytes of caffeine-treated mice. Chronic caffeine consumption was neither genotoxic nor mutagenic at the dose tested; however, it appears that caffeine actually protected mice from genotoxicity and mutagenicity, consequences attributed to aging.

  10. Innate lymphoid cells: the role in respiratory infections and lung tissue damage. (United States)

    Głobińska, Anna; Kowalski, Marek L


    Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

  11. HLA-DRB1*15 influences the development of brain tissue damage in early PPMS. (United States)

    Tur, Carmen; Ramagopalan, Sreeram; Altmann, Daniel R; Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Thompson, Alan J; Ciccarelli, Olga


    To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared with HLA-DRB1*15-negative patients. HLA-DRB1*15 typing was performed in 41 patients with primary progressive multiple sclerosis (PPMS) who were recruited within 5 years of symptom onset. All patients and 18 healthy controls were studied clinically and with MRI at baseline, and every 6 months for 3 years, and then at 5 years. Magnetization transfer ratio parameters and volumes for brain gray matter and normal-appearing white matter, brain T2 lesion load, and spinal cord cross-sectional area were obtained. Patient disability was assessed at each visit using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite subscores. There were no significant differences between HLA-DRB1*15-positive and -negative patients at baseline. HLA-DRB1*15-positive patients showed a greater decline in brain magnetization transfer ratio for gray matter and normal-appearing white matter (both p = 0.005) than HLA-DRB1*15-negative patients over 5 years, while the same parameters did not change over time in healthy controls. HLA-DRB1*15-positive patients also showed a trend toward a faster increase in brain T2 lesion load than HLA-DRB1*15-negative patients (0.29 [95% confidence interval 0.20-0.38] vs 0.21 [0.13-0.30] mL/mo, p = 0.085) and higher T2 lesion volumes at all time points (average difference [95% confidence interval]: 10.58 mL [7.09-14.07], p < 0.001) during the follow-up, after adjusting for disease duration. These findings suggest that HLA-DRB1*15 influences the progression of brain pathology in PPMS. © 2014 American Academy of Neurology.

  12. Proteome profiling in murine models of multiple sclerosis: identification of stage specific markers and culprits for tissue damage.

    Directory of Open Access Journals (Sweden)

    Ralf A Linker

    Full Text Available The identification of new biomarkers is of high interest for the prediction of the disease course and also for the identification of pathomechanisms in multiple sclerosis (MS. To specify markers of the chronic disease phase, we performed proteome profiling during the later phase of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE, day 35 after immunization as a model disease mimicking many aspects of secondary progressive MS. In comparison to healthy controls, high resolution 2 dimensional gel electrophoresis revealed a number of regulated proteins, among them glial fibrilary acidic protein (GFAP. Phase specific up-regulation of GFAP in chronic EAE was confirmed by western blotting and immunohistochemistry. Protein levels of GFAP were also increased in the cerebrospinal fluid of MS patients with specificity for the secondary progressive disease phase. In a next step, proteome profiling of an EAE model with enhanced degenerative mechanisms revealed regulation of alpha-internexin, syntaxin binding protein 1, annexin V and glutamate decarboxylase in the ciliary neurotrophic factor (CNTF knockout mouse. The identification of these proteins implicate an increased apoptosis and enhanced axonal disintegration and correlate well the described pattern of tissue injury in CNTF -/- mice which involve oligodendrocyte (OL apoptosis and axonal injury.In summary, our findings underscore the value of proteome analyses as screening method for stage specific biomarkers and for the identification of new culprits for tissue damage in chronic autoimmune demyelination.

  13. YAP and TAZ in epithelial stem cells: A sensor for cell polarity, mechanical forces and tissue damage. (United States)

    Elbediwy, Ahmed; Vincent-Mistiaen, Zoé I; Thompson, Barry J


    The YAP/TAZ family of transcriptional co-activators drives cell proliferation in epithelial tissues and cancers. Yet, how YAP and TAZ are physiologically regulated remains unclear. Here we review recent reports that YAP and TAZ act primarily as sensors of epithelial cell polarity, being inhibited when cells differentiate an apical membrane domain, and being activated when cells contact the extracellular matrix via their basal membrane domain. Apical signalling occurs via the canonical Crumbs/CRB-Hippo/MST-Warts/LATS kinase cascade to phosphorylate and inhibit YAP/TAZ. Basal signalling occurs via Integrins and Src family kinases to phosphorylate and activate YAP/TAZ. Thus, YAP/TAZ is localised to the nucleus in basal stem/progenitor cells and cytoplasm in differentiated squamous cells or columnar cells. In addition, other signals such as mechanical forces, tissue damage and possibly receptor tyrosine kinases (RTKs) can influence MST-LATS or Src family kinase activity to modulate YAP/TAZ activity. © 2016 The Authors BioEssays Published by WILEY Periodicals, Inc.

  14. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats

    Directory of Open Access Journals (Sweden)

    Akbar Anaeigoudari


    Full Text Available Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum, on pentylenetetrazole (PTZ-induced seizures and brain tissues oxidative damage were investigated in rats. Materials and Methods: The rats were divided into the following groups: (1 vehicle, (2 PTZ (90 mg/kg, (3 water fraction (WF of C. sativum (25 and 100 mg/kg, (4 n-butanol fraction (NBF of C. sativum (25 and 100 mg/kg, and (5 ethyl acetate fraction (EAF of C. sativum (25 and 100 mg/kg. Results: The first generalized tonic-clonic seizures (GTCS latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p< 0.01. In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS latency. Malondialdehyde (MDA levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p< 0.001. Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (pConclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

  15. Safety and effectiveness of a polyvinyl alcohol barrier in reducing risks of vascular tissue damage during anterior spinal revision surgery. (United States)

    Jeffords, Paul; Li, Jinsheng; Panchal, Deepal; Denoziere, Guilhem; Fetterolf, Donald


    This study was conducted as a controlled, prospective investigation to show the safety and efficacy of a polyvinyl alcohol (PVA) device in a sheep model. To evaluate the ability of a permanent PVA hydrogel barrier to reduce the risk of potential vessel damage during anterior vertebral revision surgery, to provide a nonadhesive barrier at the surgical site, and to create a surgical revision plane of dissection. The development of scar tissue and adhesions presents a significant postoperative problem in spine surgery, where adhesion involvement of overlying structures can cause pain, neurovascular complications, and present a difficult surgical environment during revisions. The devices were implanted onto the ventral surface of exposed lumbar intervertebral discs using an anterolateral approach. One disc separated from the study site was also exposed to serve as a control. Three sheep each were then evaluated with an explant procedure at 30 and 90 days. Extensive sampling was undertaken to evaluate gross anatomic, micropathologic, and biochemical environments and properties of the device. The structural properties and appearance of the device remained intact at both 30 and 90 days. The material remained flexible, hydrophilic, and soft, without visible resorption or decomposition. The material was well tolerated by the animal, with minimal histologic signs of inflammation or rejection. Tissue planes were easily able to be localized by the surgeon attempting to locate the prior surgical site at the time of resection. The PVA vessel shield effectively protected the structures overlying the sheep spine during revision, providing a clear dissection plane for resection at repeat surgery. The overlying structures separated from the previous surgical site with no adhesion, and allowed safe separation of adjacent tissues without the use of sharp dissection.

  16. Differences in supratentorial white matter diffusion after radiotherapy - New biomarker of normal brain tissue damage?

    Energy Technology Data Exchange (ETDEWEB)

    Ravn, Soeren; Jens Broendum Froekaer, Jens [Dept. of Radiology, Aalborg Univ. Hospital, Aalborg (Denmark)], e-mail:; Holmberg, Mats [Dept. of Oncology, Aalborg Univ. Hospital, Aalborg (Denmark); Soerensen, Preben [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark); Carl, Jesper [Dept. of Neurosurgery, Aalborg Univ. Hospital, Aalborg (Denmark)


    Introduction: Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods: DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35-71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0-7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on iso curves from Eclipse. Data was analysed by t-test. Estimates are given with 95 % CI. Results: A mean ADC difference of 4.6(0.3;8.9) X 10{sup -5} mm{sup 2}/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60) X 10{sup -5} mm{sup 2}/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(-1.76;5.58) X 10{sup -5} mm{sup 2}/s, p = 0.29; 15 Gy; 5.81(1.53;10.11) X 10{sup -5} mm{sup 2}/s, p = 0.01; 25 Gy; 5.80(2.43;9.18) X 10{sup -5} mm{sup 2}/s, p = 0.002; 35 Gy; 5.93(2.89;8.97) X 10

  17. Renal deterioration caused by carcinogens as a consequence of free radical mediated tissue damage: a review of the protective action of melatonin

    Energy Technology Data Exchange (ETDEWEB)

    Gultekin, Fatih; Hicyilmaz, Hicran [Suleyman Demirel University, School of Medicine, Department of Biochemistry, Isparta (Turkey)


    This brief review summarizes some of the publications that document the preventive role of melatonin in kidney damage caused by carcinogens such as 2-nitropropane, arsenic, carbon tetrachloride, nitrilotriacetic acid and potassium bromate. Numerous chemicals generate excessive free radicals that eventually induce renal worsening. Melatonin partially or totally prevents free radical mediated tissue damages induced by many carcinogens. Protective actions of melatonin against the harmful effects of carcinogens are believed to stem from its direct free radical scavenging and indirect antioxidant activities. Dietary or pharmacologically given melatonin may attenuate the oxidative stress, thereby mitigating the subsequent renal damage. (orig.)

  18. The Role of Platelet Factor 4 in Local and Remote Tissue Damage in a Mouse Model of Mesenteric Ischemia/Reperfusion Injury (United States)

    Lapchak, Peter H.; Ioannou, Antonis; Rani, Poonam; Lieberman, Linda A.; Yoshiya, Kazuhisa; Kannan, Lakshmi; Lucca, Jurandir J. Dalle; Kowalska, M. Anna; Tsokos, George C.


    The robust inflammatory response that occurs during ischemia reperfusion (IR) injury recruits factors from both the innate and adaptive immune systems. However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4), during the pathogenesis of IR injury has not been thoroughly investigated. We show that a deficiency in PF4 protects mice from local and remote tissue damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-/- mice compared to control B6 mice. This protection was independent from Ig or complement deposition in the tissues. However, neutrophil and monocyte infiltration were decreased in the lungs of PF4-/- mice compared with B6 control mice. Platelet-depleted B6 mice transfused with platelets from PF4-/- mice displayed reduced tissue damage compared with controls. In contrast, transfusion of B6 platelets into platelet depleted PF4-/- mice reconstituted damage in both intestine and lung tissues. We also show that PF4 may modulate the release of IgA. Interestingly, we show that PF4 expression on intestinal epithelial cells is increased after IR at both the mRNA and protein levels. In conclusion, these findings demonstrate that may PF4 represent an important mediator of local and remote tissue damage. PMID:22792197

  19. The role of platelet factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Peter H Lapchak

    Full Text Available The robust inflammatory response that occurs during ischemia reperfusion (IR injury recruits factors from both the innate and adaptive immune systems. However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4, during the pathogenesis of IR injury has not been thoroughly investigated. We show that a deficiency in PF4 protects mice from local and remote tissue damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-/- mice compared to control B6 mice. This protection was independent from Ig or complement deposition in the tissues. However, neutrophil and monocyte infiltration were decreased in the lungs of PF4-/- mice compared with B6 control mice. Platelet-depleted B6 mice transfused with platelets from PF4-/- mice displayed reduced tissue damage compared with controls. In contrast, transfusion of B6 platelets into platelet depleted PF4-/- mice reconstituted damage in both intestine and lung tissues. We also show that PF4 may modulate the release of IgA. Interestingly, we show that PF4 expression on intestinal epithelial cells is increased after IR at both the mRNA and protein levels. In conclusion, these findings demonstrate that may PF4 represent an important mediator of local and remote tissue damage.

  20. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum

    Directory of Open Access Journals (Sweden)

    Zargar Bilal


    Full Text Available Abstract Background The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl4 is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals. Methods 36 albino rats were divided into six groups of 6 animals each, all animals were allowed food and water ad libitum. Group I (control was given olive oil, while the rest groups were injected intraperitoneally with a single dose of CCl4 (1 ml/kg as a 50% (v/v solution in olive oil. Group II received CCl4 only. Group III animals received vitamin E at a concentration of 50 mg/kg body weight and animals of groups IV, V and VI were given extract of Podophyllum hexandrum at concentration dose of 20, 30 and 50 mg/kg body weight. Antioxidant status in both kidney and lung tissues were estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR, glutathione peroxidase (GPX, glutathione-S-transferase (GST and superoxide dismutase (SOD; as well as by determining the levels of reduced glutathione (GSH and thiobarbituric acid reactive substances (TBARS. In addition, superoxide and hydrogen peroxide radical scavenging activity of the extract was also determined. Results Results showed that the extract possessed strong superoxide and hydrogen peroxide radical scavenging activity comparable to that of known antioxidant butylated hydroxy toluene (BHT. Our results also showed that CCl4 caused a marked increase in TBARS levels whereas GSH, SOD, GR, GPX and GST levels were decreased in kidney and lung tissue homogenates of CCl4 treated rats. Aqueous extract of Podophyllum hexandrum successfully prevented the alterations

  1. Reactive tissue proliferation and damage of elastic lamina caused by hydrogel coated coils in experimental rat aneurysms. (United States)

    Zhang, Chao; Chaudhary, Neeraj; Gemmete, Joseph J; Thompson, B Gregory; Xi, Guohua; Pandey, Aditya S


    The HydroCoil Endovascular Aneurysm Occlusion and Packing Study clinical trial, comparing HydroCoil with platinum coils, reported an 8.6% reduction in significant recurrence following cerebral aneurysm coil embolization. We sought to better understand the mechanism of aneurysmal healing following HydroCoil implantation using the rat external carotid artery (ECA) sidewall aneurysm model. We ligated the proximal ECA, creating a blind pouch in our rat model. HydroCoil or bare platinum coil segments (5 mm) were inserted into aneurysms. Sham operated rats underwent identical procedures without coil insertion. 14 days after coil embolization, animals were sacrificed and the common carotid artery/internal carotid artery/ECA complex removed. Sac and surrounding vasculature underwent microscopic and histopathologic evaluation. Cellular and fibrotic components within the sac were defined as the organized area. Percentage of organized area and residual length of internal elastic lamina were calculated. Organized tissue area in ECA sac 2 weeks following coil embolization was significantly greater in the HydroCoil group than the bare coil (60.42±22.58% vs 15.62±19.24%; p=0.01) and sham (60.42±22.58% vs 4.61±3.86%; p=0.002) groups. Elastic lamina was significantly reduced in the HydroCoil group compared with the sham and bare coil groups (21.67±16.50% vs 100% and 96.06±8.78%; both pgroups for organized tissue formation or reduction in elastic lamina. Greater numbers of B cells, T cells, and neutrophils were present within HydroCoil induced organized tissue compared with the platinum group; this difference was not statistically significant. In the rat ECA sidewall aneurysm model, hydrogel coated coils cause more tissue reaction and organization compared with bare platinum coils, possibly attributed to observed elastic lamina damage and vascular smooth muscle cell proliferation. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  2. Cutaneous tissue damage induces long-lasting nociceptive sensitization and regulation of cellular stress- and nerve injury-associated genes in sensory neurons. (United States)

    Rau, Kristofer K; Hill, Caitlin E; Harrison, Benjamin J; Venkat, Gayathri; Koenig, Heidi M; Cook, Sarah B; Rabchevsky, Alexander G; Taylor, Bradley K; Hai, Tsonwin; Petruska, Jeffrey C


    Tissue damage is one of the major etiological factors in the emergence of chronic/persistent pain, although mechanisms remain enigmatic. Using incision of the back skin of adult rats as a model for tissue damage, we observed sensitization in a nociceptive reflex enduring to 28days post-incision (DPI). To determine if the enduring behavioral changes corresponded with a long-term impact of tissue damage on sensory neurons, we examined the temporal expression profile of injury-regulated genes and the electrophysiological properties of traced dorsal root ganglion (DRG) sensory neurons. The mRNA for the injury/stress-hub gene Activating Transcription Factor 3 (ATF3) was upregulated and peaked within 4 DPI, after which levels declined but remained significantly elevated out to 28 DPI, a time when the initial incision appears healed and tissue-inflammation largely resolved. Accordingly, stereological image analysis indicated that some neurons expressed ATF3 only transiently (mostly medium-large neurons), while in others it was sustained (mostly small neurons), suggesting cell-type-specific responses. In retrogradely-traced ATF3-expressing neurons, Calcium/calmodulin-dependent protein kinase type IV (CAMK4) protein levels and isolectin-B4 (IB4)-binding were suppressed whereas Growth Associated Protein-43 (GAP-43) and Neuropeptide Y (NPY) protein levels were enhanced. Electrophysiological recordings from DiI-traced sensory neurons 28 DPI showed a significant sensitization limited to ATF3-expressing neurons. Thus, ATF3 expression is revealed as a strong predictor of single cells displaying enduring pain-related electrophysiological properties. The cellular injury/stress response induced in sensory neurons by tissue damage and indicated by ATF3 expression is positioned to contribute to pain which can occur after tissue damage. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. A quantitative and non-contact technique to characterise microstructural variations of skin tissues during photo-damaging process based on Mueller matrix polarimetry. (United States)

    Dong, Yang; He, Honghui; Sheng, Wei; Wu, Jian; Ma, Hui


    Skin tissue consists of collagen and elastic fibres, which are highly susceptible to damage when exposed to ultraviolet radiation (UVR), leading to skin aging and cancer. However, a lack of non-invasive detection methods makes determining the degree of UVR damage to skin in real time difficult. As one of the fundamental features of light, polarization can be used to develop imaging techniques capable of providing structural information about tissues. In particular, Mueller matrix polarimetry is suitable for detecting changes in collagen and elastic fibres. Here, we demonstrate a novel, quantitative, non-contact and in situ technique based on Mueller matrix polarimetry for monitoring the microstructural changes of skin tissues during UVR-induced photo-damaging. We measured the Mueller matrices of nude mouse skin samples, then analysed the transformed parameters to characterise microstructural changes during the skin photo-damaging and self-repairing processes. Comparisons between samples with and without the application of a sunscreen showed that the Mueller matrix-derived parameters are potential indicators for fibrous microstructure in skin tissues. Histological examination and Monte Carlo simulations confirmed the relationship between the Mueller matrix parameters and changes to fibrous structures. This technique paves the way for non-contact evaluation of skin structure in cosmetics and dermatological health.

  4. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes. (United States)

    Jones, D A; Prior, S L; Barry, J D; Caplin, S; Baxter, J N; Stephens, J W


    In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (Pstress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue

    Directory of Open Access Journals (Sweden)

    Abolhasan Rezaeyan


    Full Text Available This study was carried out to evaluate radioprotective effects of hesperidin (HES administration before the irradiation on the cardiac oxidative stress and histopathological changes in an experimental rat model. The cardiovascular complications of radiation exposure cause morbidity and mortality in patients who received radiotherapy. HES, an antioxidant flavonoid found in citrus fruits, suggests the protection against the tissue damage. Fifty-eight rats were divided into four groups: Group 1 received phosphate buffered saline (PBS and sham radiation; Group 2, HES and sham radiation; Group 3, PBS and radiation; and Group 4, HES and radiation. The rats were exposed to single dose of 18 Gy of 6 MV X-ray. One hundred milligrams per kilogram doses of HES was administered for 7 days before irradiation. The estimation of superoxide dismutase (SOD, malondialdehyde (MDA, and histopathological analyses was performed at 24 h and 8 weeks after radiation exposure. The irradiation of chest area resulted in an elevated MDA level and decreased SOD activity. Moreover, long-term pathological lesions of radiation were inflammation, fibrosis, the increased number of mast cells and macrophages, and development of plaque, vascular leakage, myocardial degeneration, and myocyte necrosis. Although the administration of HES decreases inflammation, fibrosis, mast cell and macrophage numbers, and myocyte necrosis, it did not result in reduced thrombus, myocardium degeneration, and vascular leakage. In conclusion, these results suggest that HES can perform a radioprotection action. The protective effect of HES may be attributable to its immunomodulatory effects and free radical-scavenging properties.

  6. Green tea (Camellia sinensis) alleviates arsenic-induced damages to DNA and intestinal tissues in rat and in situ intestinal loop by reinforcing antioxidant system. (United States)

    Acharyya, Nirmallya; Sajed Ali, Sk; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit


    This study elucidates the protective role of Green tea (Camellia sinensis or CS) against arsenic-induced mutagenic DNA-breakage/intestinal (small) damages in female rats. Intestinal epithelial cells receive ingested arsenic initially. Though, the possibility of damages in this tissue is immense and the therapeutic strategies against this damage are of great concern, reports on either issue are scanty. Our earlier study on arsenic-exposed human unveils a link between carcinogenesis and mutagenic DNA damage. Here, we demonstrate that supplementation of CS-extract (10 mg/mL water) with NaAsO2 (0.6 ppm)/100 g b.w. for 28 days to rats offered a significant protection against arsenic-induced oxidative damages to DNA and intestinal (small) tissues by buttressing antioxidant systems. Necrotic and apoptotic damages and their CS-protection are shown in DNA-fragmentation, comet-assay, and histoarchitecture (hematoxylin and eosin and periodic acid-schiff staining) results. Only arsenic exposure significantly decreased intestinal superoxide dismutase, catalase activities, and level of soluble thiol with a concomitant increase in malondialdehyde/conjugated dienes. Alteration of serum necrotic marker lactate dehydrogenase and the metabolic inflammatory marker c-reactive protein also indicate the impairment may be occurring at transcription and/or cellular signal transduction level. In addition, in situ incubation in rat intestinal loop filled for 24 h with NaAsO2 alone (250 µM) or with aqueous CS-extract (250 mg/mL) suggests that small intestinal epithelial cells are significantly protected by CS against arsenic-associated necrotic/mutagenic damages, which is observed in DNA-breakage studies. In conclusion, besides intensifying endogenous antioxidant system, CS polyphenols also offer a direct role on free radical scavenging activity that is associated to the protection from mutagenic DNA-breakages and prevention of tissue necrosis/carcinogenesis generated by arsenic. © 2014

  7. The effects of vitamin E on brain derived neurotrophic factor, tissues oxidative damage and learning and memory of juvenile hypothyroid rats. (United States)

    Baghcheghi, Yousef; Beheshti, Farimah; Shafei, Mohammad Naser; Salmani, Hossein; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Anaeigoudari, Akbar; Hosseini, Mahmoud


    The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P E (P E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.

  8. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12. (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit


    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  9. Epicardial Adipose Tissue (EAT Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Anna Ludovica Fracanzani

    Full Text Available Epicardial adipose tissue (EAT has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD. Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1 the association between EAT, the other metabolic parameters and the severity of steatosis 2 the relationship between cardiovascular (cIMT, cplaques, E/A, liver (presence of NASH and significant fibrosis damage and metabolic risk factors including EAT 3 the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100. EAT, severity of steatosis, carotid intima-media thickness (cIMT and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm were female gender (p = 0.003, age (p = 0.001, BMI (p = 0.01, diastolic blood pressure (p = 0.009, steatosis grade 2 (p = 0.01 and 3 (p = 0.04, fatty liver index (p = 0.001 and statin use (p = 0.03. Variables independently associated with carotid IMT were age (p = 0.0001, hypertension (p = 0.009, diabetes (p = 0.04, smoking habits (p = 0.04 and fatty liver index (p = 0.02, with carotid plaques age (p = 0.0001, BMI (p = 0.03, EAT (p = 0.02, and hypertension (p = 0.02, and with E/A age (p = 0.0001, diabetes (p = 0.005, hypertension (p = 0.04 and fatty liver index (p = 0.004. In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH was independently associated with EAT (p = 0.04 and diabetes (p = 0.054 while significant fibrosis with EAT (p = 0.02, diabetes (p = 0.01 and waist circumference (p = 0.05. No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

  10. Stimulated release of tissue plasminogen activator from artery wall sympathetic nerves: implications for stress-associated wall damage. (United States)

    Hao, Zhifang; Jiang, Xi; Sharafeih, Roshanak; Shen, Shujing; Hand, Arthur R; Cone, Robert E; O'Rourke, James


    Recurrent stress is clinically associated with early onset hypertension and coronary artery disease. A mechanism linking emotion to pathogenic remodeling of the artery wall has not been identified. Stress stimulates acute regulated release of tissue plasminogen activator (t-PA) into the circulation, which is presently attributed to the vascular endothelium. Sympathetic neurons also synthesize t-PA and axonally transport it to the arterial smooth muscle. Unlike release by the endothelium, a stress-stimulated sympathetic discharge would potentially accelerate degradation of the wall matrix by plasmin. To assess whether sympathetic axons are the principal source of acute stress-induced arterial release of t-PA, we compared the output from small densely innervated and large sparsely innervated isolated artery segments before and after sympathetic stimulation, and after ablations. Following phenylephrine infusion densely-innervated microvessels in uveal eyecups were released over 60-fold greater amounts of active t-PA per milligram than the sparsely innervated aorta; and ten-fold more than carotid artery segments. Mesenteric artery release was 4.8-fold greater than release by the carotid artery. In vivo, uveal release of t-PA increased more than three-fold within one minute following superior cervical sympathetic ganglion electrical stimulation, and after phenylephrine, or nicotine infusions of the anterior chamber. Circulating levels of t-PA fell 70% following chemical sympathectomy. We propose that sympathetic nerves are the primary source of stress-induced release of t-PA into and from the densely innervated resistance arteries and arterioles, where dysregulated plasmin-induced proteolysis could damage the wall matrix.

  11. Effect of vitamin C on tissue damage and oxidative stress following tunica vaginalis flap coverage after testicular torsion. (United States)

    Moghimian, Maryam; Soltani, Malihe; Abtahi, Hossein; Shokoohi, Majid


    The aim was to investigate the protective effect of vitamin C on tissue damage and oxidative stress following tunica albuginea incision with tunica vaginalis flap coverage for testicular torsion. Adult male Wistar rats were randomly divided into two experimental groups. The first group experienced 5h of testicular torsion followed by treatment with vitamin C alone, with tunica vaginalis flap coverage alone, and with both vitamin C and tunica vaginalis flap coverage along with a control group subjected to a sham procedure. The second group experienced 9h of testicular torsion followed by the same treatment options as described for the 5h group. The oxidative stress and testosterone levels were measured 24h posttreatment. The Johnsen score, diameter of the seminiferous tubules, and thickness of the seminiferous tubule epithelium were recorded 30days following the treatment. The Johnsen score, diameter of the seminiferous tubules, and thickness of the seminiferous tubule epithelium significantly increased in the 5h testicular torsion group receiving treatment with vitamin C and tunica vaginalis flap coverage compared with the group receiving tunica vaginalis flap alone. The level of testosterone decreased significantly in all groups except for the 5h testicular torsion group receiving treatment with vitamin C and tunica vaginalis flap coverage. The MDA level also decreased in the group receiving treatment with vitamin C and tunica vaginalis flap coverage compared with the group receiving tunica vaginalis flap coverage alone. The results showed that the histological parameters and testosterone levels improved with the administration of vitamin C before tunica vaginalis flap coverage in the group experiencing 5h of torsion. This may be a result of the antioxidant effect of vitamin C. No advantage was observed for the 9h group, possibly because the dosage of vitamin C was inadequate. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model. (United States)

    Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue


    Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations

  13. Can pulsed ultrasound increase tissue damage during ischemia? A study of the effects of ultrasound on infarcted and non-infarcted myocardium in anesthetized pigs

    Directory of Open Access Journals (Sweden)

    Grins Edgars


    Full Text Available Abstract Background The same mechanisms by which ultrasound enhances thrombolysis are described in connection with non-beneficial effects of ultrasound. The present safety study was therefore designed to explore effects of beneficial ultrasound characteristics on the infarcted and non-infarcted myocardium. Methods In an open chest porcine model (n = 17, myocardial infarction was induced by ligating a coronary diagonal branch. Pulsed ultrasound of frequency 1 MHz and intensity 0.1 W/cm2 (ISATA was applied during one hour to both infarcted and non-infarcted myocardial tissue. These ultrasound characteristics are similar to those used in studies of ultrasound enhanced thrombolysis. Using blinded assessment technique, myocardial damage was rated according to histopathological criteria. Results Infarcted myocardium exhibited a significant increase in damage score compared to non-infarcted myocardium: 6.2 ± 2.0 vs. 4.3 ± 1.5 (mean ± standard deviation, (p = 0.004. In the infarcted myocardium, ultrasound exposure yielded a further significant increase of damage scores: 8.1 ± 1.7 vs. 6.2 ± 2.0 (p = 0.027. Conclusion Our results suggest an instantaneous additive effect on the ischemic damage in myocardial tissue when exposed to ultrasound of stated characteristics. The ultimate damage degree remains to be clarified.

  14. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo


    tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity...... of topoisomerase II alpha and thereby prevents access of anthracycline to the enzyme and thus cytotoxicity, and also acts as a strong iron chelator following opening of its two bisdioxopiperazine rings. Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation...


    NARCIS (Netherlands)


    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

  16. High sCD40L levels Early After Trauma are Associated with Enhanced Shock, Sympathoadrenal Activation, Tissue and Endothelial Damage, Coagulopathy and Mortality

    DEFF Research Database (Denmark)

    Johansson, P I; Sørensen, A M; Perner, A


    the association between the sCD40L level and tissue injury, shock, coagulopathy and mortality in trauma patients. Methods: Prospective, observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry, Injury Severity Score (ISS) and 30-day mortality were recorded...... was associated with enhanced tissue and endothelial damage (ISS, hcDNA, Annexin V, syndecan-1, sTM), shock (pH, SBE), sympathoadrenal activation (adrenaline) and coagulopathy evidenced by reduced thrombin generation (PF1.2), hyperfibrinolysis (D-dimer), increased APTT and inflammation (IL-6) (all p...

  17. An inverse problem in estimating the laser irradiance and thermal damage in laser-irradiated biological tissue with a dual-phase-lag model. (United States)

    Yang, Yu-Ching; Lee, Haw-Long; Chang, Win-Jin; Chen, Wen-Lih


    The aim of this study is to solve an inverse heat conduction problem to estimate the unknown time-dependent laser irradiance and thermal damage in laser-irradiated biological tissue from the temperature measurements taken within the tissue. The dual-phase-lag model is considered in the formulation of heat conduction equation. The inverse algorithm used in the study is based on the conjugate gradient method and the discrepancy principle. The effect of measurement errors and measurement locations on the estimation accuracy is also investigated. Two different examples of laser irradiance are discussed. Results show that the unknown laser irradiance and thermal damage can be predicted precisely by using the present approach for the test cases considered in this study.

  18. In vivo phenytoin-initiated oxidative damage to proteins and lipids in murine maternal hepatic and embryonic tissue organelles: potential molecular targets of chemical teratogenesis. (United States)

    Liu, L; Wells, P G


    The widely used anticonvulsant drug phenytoin may be bioactivated by peroxidases such as prostaglandin H synthase (PHS) to a reactive free radical intermediate that initiates teratogenesis. This in vivo study evaluated the potential molecular targets mediating phenytoin teratogenicity. In vivo phenytoin-induced oxidative tissue damage following bioactivation was quantified in both maternal hepatic and embryonic tissues from pregnant CD-1 mice using lipid peroxidation and protein oxidation and degradation as indices. Pregnant mice were injected with a teratogenic dose of phenytoin, 65 mg/kg ip, during organogenesis on Gestational Day 12. alpha-Phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent, 41.5 mg/kg, or acetylsalicylic acid (ASA), an inhibitor of the cyclooxygenase component of PHS, 10 mg/kg, were injected ip 2 hr before phenytoin treatment, and maternal hepatic and embryonic tissues were obtained at 0, 3, 6, 8, and 24 hr. Phenytoin enhanced lipid peroxidation in maternal plasma, hepatic microsomes, cytosol, mitochondria, and nuclei and in embryonic microsomes, cytosol, and mitochondria (p teratogenicity by PBN and ASA, suggest that peroxidase-catalyzed bioactivation of phenytoin may initiate oxidative damage to lipids and proteins in embryonic tissues, with teratological consequences.

  19. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F


    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  20. Protective efficacy of antioxidants on cisplatin-induced tissue damage caused in Leishmania donovani infected BALB/c mice against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Meenakshi Sharma


    Full Text Available Objective: Therapeutic interventions against visceral leishmaniasis (VL are limited and facing serious concerns of toxicity, high cost and emerging resistance, there is a greater interest in new drug developments which are cost effective, efficient and easily available to people suffering from leishmaniasis. Cisplatin (cis-diamminedichloroplatinum II; CDDP has been found to have antileishmanial activity in vitro and in vivo which lead towards an apoptosis like cell death of both promastigotes and amastigotes and a significant reduction in parasite load and enhanced DTH responses which suggested the generation of protective cell-mediated immune responses. But, at higher doses it causes nephrotoxicity-a major side effect. The present study was designed to evaluate the protective efficacy of antioxidants on cisplatin induced tissue damage in Leishmania donovani infected BALB/c mice. Materials and methods: L. donovani infected and uninfected animals were treated with higher doses (5 and 2.5 mg/kg body weight of cisplatin alone and in combination with antioxidants (vitamin C, vitamin E and silibinin for 5 days. Mice were examined for the protective effects of antioxidants on cisplatin indiced tissue damage by DNA fragmentation and histological studies of kidneys, liver and spleen. Results: The damage caused by cisplatin was ameliorated after the supplementation of antioxidants showing a marked reduction in the extent of tubular damage, the focal reaction changes in liver were reversed and no signs of toxicity in the spleen were reported. Moreover, no DNA damage was observed in animals treated with cisplatin along with various antioxidants. Conclusion: The present results showed that antioxidants helped in the amelioration of drug induced toxic effects against murine visceral leishmaniasis, making the combination a potential anti-leishmanial therapy. [J Interdiscipl Histopathol 2013; 1(3.000: 121-136

  1. Hair cell counts in a rat model of sound damage: Effects of tissue preparation & identification of regions of hair cell loss. (United States)

    Neal, Christopher; Kennon-McGill, Stefanie; Freemyer, Andrea; Shum, Axel; Staecker, Hinrich; Durham, Dianne


    Exposure to intense sound can damage or kill cochlear hair cells (HC). This loss of input typically manifests as noise induced hearing loss, but it can also be involved in the initiation of other auditory disorders such as tinnitus or hyperacusis. In this study we quantify changes in HC number following exposure to one of four sound damage paradigms. We exposed adult, anesthetized Long-Evans rats to a unilateral 16 kHz pure tone that varied in intensity (114 dB or 118 dB) and duration (1, 2, or 4 h) and sacrificed animals 2-4 weeks later. We compared two different methods of tissue preparation, plastic embedding/sectioning and whole mount dissection, for quantifying hair cell loss as a function of frequency. We found that the two methods of tissue preparation produced largely comparable cochleograms, with whole mount dissections allowing a more rapid evaluation of hair cell number. Both inner and outer hair cell loss was observed throughout the length of the cochlea irrespective of sound damage paradigm. Inner HC loss was either equal to or greater than outer HC loss. Increasing the duration of sound exposures resulted in more severe HC loss, which included all HC lesions observed in an analogous shorter duration exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Real-time optical coherence tomography observation of retinal tissue damage during laser photocoagulation therapy on ex-vivo porcine samples (United States)

    Steiner, P.; Považay, B.; Stoller, M.; Morgenthaler, P.; Inniger, D.; Arnold, P.; Sznitman, R.; Meier, Ch.


    Retinal laser photocoagulation represents a widely used treatment for retinal pathologies such as diabetic chorioretinopathy or diabetic edema. For effective treatment, an appropriate choice of the treatment energy dose is crucial to prevent excessive tissue damage caused by over-irradiation of the retina. In this manuscript we investigate simultaneous and time-resolved optical coherence tomography for its applicability to provide feedback to the ophthalmologist about the introduced retinal damage during laser photocoagulation. Time-resolved and volumetric optical coherence tomography data of 96 lesions on ex-vivo porcine samples, set with a 577 nm laser prototype and irradiance of between 300 and 8800 W=cm2 were analyzed. Time-resolved scans were compared to volumetric scans of the lesion and correlated with ophthalmoscopic visibility. Lastly, image parameters extracted from optical coherence tomography Mscans, suitable for lesion classification were identified. Results presented in this work support the hypothesis that simultaneous optical coherence tomography provides valuable information about the extent of retinal tissue damage and may be used to guide retinal laser photocoagulation in the future.

  3. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan


    Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory an...

  4. Tissue structure damage in late-stage knee osteoarthritis: medication, markers, and disease modification before replacement surgery

    NARCIS (Netherlands)

    de Boer, T.N.


    The aim of this thesis is to gain more insight in the characteristics of end-stage osteoarthritic patients who are about to undergo total knee replacement surgery. Their use of medication, potential markers of actual characteristics of joint damage and inflammation, and effects of potential disease

  5. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis

    National Research Council Canada - National Science Library

    Herrera, Cristina; Macêdo, Jéssica Kele A; Feoli, Andrés; Escalante, Teresa; Rucavado, Alexandra; Gutiérrez, José María; Fox, Jay W


    The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected...

  6. Chilling-related cell damage of apple (Malus × domestica Borkh.) fruit cortical tissue impacts antioxidant, lipid and phenolic metabolism. (United States)

    Leisso, Rachel S; Buchanan, David A; Lee, Jinwook; Mattheis, James P; Sater, Chris; Hanrahan, Ines; Watkins, Christopher B; Gapper, Nigel; Johnston, Jason W; Schaffer, Robert J; Hertog, Maarten L A T M; Nicolaï, Bart M; Rudell, David R


    'Soggy breakdown' (SB) is an internal flesh disorder of 'Honeycrisp' apple (Malus × domestica Borkh.) fruit that occurs during low temperature storage. The disorder is a chilling injury (CI) in which visible symptoms typically appear after several weeks of storage, but information about the underlying metabolism associated with its induction and development is lacking. The metabolic profile of flesh tissue from wholly healthy fruit and brown and healthy tissues from fruit with SB was characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatograph-mass spectrometry (LC-MS). Partial least squares discriminant analysis (PLS-DA) and correlation networks revealed correlation among ester volatile compounds by composition and differences in phytosterol, phenolic and putative triacylglycerides (TAGs) metabolism among the tissues. anova-simultaneous component analysis (ASCA) was used to test the significance of metabolic changes linked with tissue health status. ASCA-significant components included antioxidant compounds, TAGs, and phytosterol conjugates. Relative to entirely healthy tissues, elevated metabolite levels in symptomatic tissue included γ-amino butyric acid, glycerol, sitosteryl (6'-O-palmitoyl) β-d-glucoside and sitosteryl (6'-O-stearate) β-d-glucoside, and TAGs containing combinations of 16:0, 18:3, 18:2 and 18:1 fatty acids. Reduced metabolite levels in SB tissue included 5-caffeoyl quinate, β-carotene, catechin, epicatechin, α-tocopherol, violaxanthin and sitosteryl β-d glucoside. Pathway analysis indicated aspects of primary metabolism differed according to tissue condition, although differences in metabolites involved were more subtle than those of some secondary metabolites. The results implicate oxidative stress and membrane disruption processes in SB development and constitute a diagnostic metabolic profile for the disorder. © 2014 Scandinavian Plant Physiology Society.

  7. The relationship between oxidative damage and vitamin E concentration in blood, milk, and liver tissue from vitamin E supplemented and nonsupplemented periparturient heifers. (United States)

    Bouwstra, R J; Goselink, R M A; Dobbelaar, P; Nielen, M; Newbold, J R; van Werven, T


    This study investigated the relationship between oxidative damage and the effect of vitamin E supplementation in blood, milk, and liver tissue in 16 periparturient heifers. The question is whether measurements of oxidative and vitamin E status in blood of a periparturient cow are representative of the total body, given that blood concentrations of both vitamin E and oxidative stress products change around this period. The daily vitamin E intake of the vitamin E-supplemented Holstein-Friesian heifers (n = 8) was 3,000 international units and was started 2 mo before calving; the control heifers (n = 8) were not supplemented. Oxidative damage was determined on the basis of malondialdehyde (MDA) concentrations. Blood was sampled 9 times before calving, on calving day, and twice after calving. Liver biopsies were taken at wk -5, -1, and 2 relative to calving day. Milk was obtained from all heifers immediately after calving, the first 2 milkings and on d 3, 7, and 14 at 0600 h. Serum and liver tissue were analyzed for vitamin E, cholesterol, and MDA; and milk samples were analyzed for vitamin E, MDA, fat, protein, and somatic cell count. The results showed that vitamin E supplements increased both absolute vitamin E concentrations and the ratio of vitamin E to cholesterol in blood and liver tissue. Absolute vitamin E concentration in milk tended to be greater in supplemented cows. Based on the increased MDA blood concentrations at calving, it seems that dairy heifers experience oxidative stress. The effect of vitamin E on MDA differs between the blood, liver, and mammary gland. Vitamin E supplementation could not prevent the increase in blood MDA at calving, but the significantly lower MDA blood concentrations of supplemented cows in the 2 wk after calving suggest that vitamin E has a role in recovery from parturition-related oxidative stress. Vitamin E supplementation reduced oxidative damage in liver, whereas no obvious effect was found on milk MDA concentrations. A

  8. Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria

    Directory of Open Access Journals (Sweden)

    Bruno Coelho Rocha


    Full Text Available Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. However, the role of these polymorphonuclear cells in mediating either the resistance or the pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, enhanced release of reactive oxygen species and myeloperoxidase, and a high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed intense recruitment of neutrophils to liver sinusoids. Neutrophil migration and IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggest that type I interferon signaling has a central role in neutrophil activation and malaria pathogenesis.

  9. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  10. Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice


    Cyrus Jalili; Mohammad Reza Salahshoor; Ali Naseri


    Background: Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. Objective: The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. Materials and Methods: In thi...

  11. Brain Tissues Oxidative Damage as a Possible Mechanism of Deleterious Effects of Propylthiouracil- Induced Hypothyroidism on Learning and Memory in Neonatal and Juvenile Growth in Rats

    Directory of Open Access Journals (Sweden)

    Esmeil Farrokhi


    randomly selected and tested in the Morris water maze (MWM. Then, samples of blood were collected to measure thyroxine. Finally, the brains were removed and total thiol groups and molondialdehyde (MDA concentrations were determined. Results: Compared to the control group’s offspring, serum thyroxine levels in the PTU group’s off spring were significantly low (P<0.001. In MWM, the escape latency and traveled path in the PTU group were significantly higher than that in the control group (P<0.01- P<0.001. In PTU group, the total thiol concentrations in both cortical and hippocampal tissues were significantly lower and MDA concentrations were higher than control group (P<0.001. Discussion: It seems that deleterious effect of hypothyroidism during neonatal and juvenile growth on learning and memory is at least in part due to brain tissues oxidative damage.

  12. Cell kinetics during regeneration in the sponge Halisarca caerulea: how local is the response to tissue damage?

    Directory of Open Access Journals (Sweden)

    Brittany E. Alexander


    Full Text Available Sponges have a remarkable capacity to rapidly regenerate in response to wound infliction. In addition, sponges rapidly renew their filter systems (choanocytes to maintain a healthy population of cells. This study describes the cell kinetics of choanocytes in the encrusting reef sponge Halisarca caerulea during early regeneration (0–8 h following experimental wound infliction. Subsequently, we investigated the spatial relationship between regeneration and cell proliferation over a six-day period directly adjacent to the wound, 1 cm, and 3 cm from the wound. Cell proliferation was determined by the incorporation of 5-bromo-2′-deoxyuridine (BrdU. We demonstrate that during early regeneration, the growth fraction of the choanocytes (i.e., the percentage of proliferative cells adjacent to the wound is reduced (7.0 ± 2.5% compared to steady-state, undamaged tissue (46.6 ± 2.6%, while the length of the cell cycle remained short (5.6 ± 3.4 h. The percentage of proliferative choanocytes increased over time in all areas and after six days of regeneration choanocyte proliferation rates were comparable to steady-state tissue. Tissue areas farther from the wound had higher rates of choanocyte proliferation than areas closer to the wound, indicating that more resources are demanded from tissue in the immediate vicinity of the wound. There was no difference in the number of proliferative mesohyl cells in regenerative sponges compared to steady-state sponges. Our data suggest that the production of collagen-rich wound tissue is a key process in tissue regeneration for H. caerulea, and helps to rapidly occupy the bare substratum exposed by the wound. Regeneration and choanocyte renewal are competing and negatively correlated life-history traits, both essential to the survival of sponges. The efficient allocation of limited resources to these life-history traits has enabled the ecological success and diversification of sponges.

  13. 4-Aminobiphenyl (4-ABP) - DNA Damage in Breast Tissue and Relationship to p53 Mutations and Polymorphisms of Metabolizing Genes

    National Research Council Canada - National Science Library

    Niguidula, Nancy


    .... The analysis of the CYP1A2 gene is currently in progress. Due to the difficulty in obtaining large fragments of DNA from the tumor tissue sections required for PCR-RFLP, a new method is under development for genotyping NAT2...

  14. Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence (United States)

    Félix-Silva, Juliana; Silva-Junior, Arnóbio Antônio; Zucolotto, Silvana Maria


    Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage. PMID:28904556

  15. Histopathology of Incontinence-Associated Skin Lesions: Inner Tissue Damage Due to Invasion of Proteolytic Enzymes and Bacteria in Macerated Rat Skin (United States)

    Mugita, Yuko; Minematsu, Takeo; Huang, Lijuan; Nakagami, Gojiro; Kishi, Chihiro; Ichikawa, Yoshie; Nagase, Takashi; Oe, Makoto; Noguchi, Hiroshi; Mori, Taketoshi; Abe, Masatoshi; Sugama, Junko; Sanada, Hiromi


    A common complication in patients with incontinence is perineal skin lesions, which are recognized as a form of dermatitis. In these patients, perineal skin is exposed to digestive enzymes and intestinal bacterial flora, as well as excessive water. The relative contributions of digestive enzymes and intestinal bacterial flora to skin lesion formation have not been fully shown. This study was conducted to reveal the process of histopathological changes caused by proteases and bacterial inoculation in skin maceration. For skin maceration, agarose gel containing proteases was applied to the dorsal skin of male Sprague-Dawley rats for 4 h, followed by Pseudomonas aeruginosa inoculation for 30 min. Macroscopic changes, histological changes, bacterial distribution, inflammatory response, and keratinocyte proliferation and differentiation were examined. Proteases induced digestion in the prickle cell layer of the epidermis, and slight bleeding in the papillary dermis and around hair follicles in the macerated skin without macroscopic evidence of erosion. Bacterial inoculation of the skin macerated by proteolytic solution resulted in the formation of bacteria-rich clusters comprising numerous microorganisms and inflammatory cells within the papillary dermis, with remarkable tissue damage around the clusters. Tissue damage expanded by day 2. On day 3, the proliferative keratinocyte layer was elongated from the bulge region of the hair follicles. Application of proteases and P. aeruginosa induced skin lesion formation internally without macroscopic erosion of the overhydrated area, suggesting that the histopathology might be different from regular dermatitis. The healing process of this lesion is similar to transepidermal elimination. PMID:26407180

  16. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Cucinotta, Francis A [Univ. of Nevada, Las Vegas, NV (United States)


    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  17. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Peter [University of Oxford; Anderson, Jennifer [University of Oxford


    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  18. Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines. (United States)

    Boaventura, Viviane S; Santos, Claire S; Cardoso, Cristina R; de Andrade, José; Dos Santos, Washington L C; Clarêncio, Jorge; Silva, João S; Borges, Valeria M; Barral-Netto, Manoel; Brodskyn, Claudia I; Barral, Aldina


    Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein, we evaluated the involvement of the IL-17-type response in the inflammatory infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing cytokines (IL-1β, IL-23, IL-6 and TGF-β) were detected by immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were regularly detected in necrotic and perinecrotic areas and stained positive for neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these observations demonstrate the existence of Th17 cells in ML lesions associated with neutrophils in areas of tissue injury and suggest that IL-17 is involved in ML pathogenesis.

  19. Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis.

    Directory of Open Access Journals (Sweden)

    Pramod K Mishra


    Full Text Available Neurocysticercosis (NCC is one of the most common helminth parasitic diseases of the central nervous system (CNS and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT and eosinophil-deficient mice (ΔdblGATA using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte

  20. DNA damage in the kidney tissue cells of the fish Rhamdia quelen after trophic contamination with aluminum sulfate. (United States)

    Klingelfus, Tatiane; Costa, Paula Moiana da; Scherer, Marcos; Cestari, Marta Margarete


    Even though aluminum is the third most common element present in the earth's crust, information regarding its toxicity remains scarce. It is known that in certain cases, aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of the fish Rhamdia quelen after trophic contamination for 60 days. Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50 mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The three types of chromosomal abnormalities (CA) found were categorized as chromatid breaks, decondensation of telomeric region, and early separation of sister chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum sulfate had genotoxic potential. Under these treatments, early separation of the sister chromatids was observed more frequently and decondensation of the telomeric region tended to increase in frequency. We suggest that structural changes in the proteins involved in DNA compaction may have led to the decondensation of the telomeric region, making the DNA susceptible to breaks. Moreover, early separation of the sister chromatids may have occurred due to changes in the mobility of chromosomes or proteins that keep the sister chromatids together. The comet assay confirmed the genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia quelen at the three doses of exposure.

  1. Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.

    Directory of Open Access Journals (Sweden)

    Jae-Yol Lim

    Full Text Available OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged salivary gland (SG tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 × 10(6 were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs was observed in vitro using a co-culture system. RESULTS: The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18% were observed to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

  2. Crataegus songarica methanolic extract accelerates enzymatic status in kidney and heart tissue damage in albino rats and its in vitro cytotoxic activity. (United States)

    Ganie, Showkat Ahmad; Ali Dar, Tanveer; Zargar, Sabuhi; Bhat, Aashiq Hussain; Dar, Khalid Bashir; Masood, Akbar; Zargar, Mohammad Afzal


    Crataegus songarica K. Koch (Rosaceae) has been used in folk medicine to treat various diseases. This study evaluates the effect of C. songarica methanol extract on the kidney and heart tissue damage of albino rats, and to determine cytotoxic activity of various extracts of songarica on various human cancer cell lines. Rats were divided into six groups, Group I received water only; Group II received CCl4 (1 mL/kg b wt) intraperitoneal; C. songarica extract (at doses of 100, 200 and 300 mg/kg b wt) orally for 15 days. Cytotoxic activity was determined by SRB method using MCF-7, HeLa, HepG2, SF-295, SW480 and IMR-32 cell lines. Compared with CCl4 group, administration of C. songarica extract at the dose of 300 mg/kg b wt, significantly decreases serum creatinine (59.74%), urea (40.23%) and cholesterol (54 mg/dL), MDA (0.007 nmol/mg protein) in kidney and (0.025 nmol/mg protein) in heart tissue, along with evaluation of GSH (209.79 ± 54.6), GR (111.45 ± 2.84), GPx (94.01 ± 14.80), GST (201.71) in kidney tissue and GSH (51.47 ± 1.47), GR (45.42 ± 6.69), GPx (77.19 ± 10.94), GST (49.89) in heart tissue. In addition, methanol, ethanol and ethyl acetate extracts exhibited potent anticancer activity on six cancer cell lines with IC50 values ranging from 28.57 to 85.106 µg/mL. Crataegus songarica methanol extract has a potential antioxidant effect as it protects the kidney and heart tissue against CCl4-induced toxicity, prevents DNA damage and showed strong anticancer activity.

  3. DNA damage in the kidney tissue cells of the fish Rhamdia quelen after trophic contamination with aluminum sulfate

    Directory of Open Access Journals (Sweden)

    Tatiane Klingelfus


    Full Text Available Abstract Even though aluminum is the third most common element present in the earth's crust, information regarding its toxicity remains scarce. It is known that in certain cases, aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of the fish Rhamdia quelen after trophic contamination for 60 days. Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50 mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The three types of chromosomal abnormalities (CA found were categorized as chromatid breaks, decondensation of telomeric region, and early separation of sister chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum sulfate had genotoxic potential. Under these treatments, early separation of the sister chromatids was observed more frequently and decondensation of the telomeric region tended to increase in frequency. We suggest that structural changes in the proteins involved in DNA compaction may have led to the decondensation of the telomeric region, making the DNA susceptible to breaks. Moreover, early separation of the sister chromatids may have occurred due to changes in the mobility of chromosomes or proteins that keep the sister chromatids together. The comet assay confirmed the genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia quelen at the three doses of exposure.

  4. Tissue damage and embryonic malformation induced by aqueous extract of Pteridium aquilinum on chorioallantoic membrane of chick embryo (CAM

    Directory of Open Access Journals (Sweden)

    Amanda Leitolis


    Full Text Available The aim of this study was evaluate the effects of Bracken fern (BF (Pteridium aquilinum (L. Kuhn. on biological systems. When consumed by animals can cause acute intoxication, hematuria, biochemistry alterations and cancer. To humans the toxicity is associated with its intake on contaminated ground water or milk and inhalation of its spores. In order to check the BF aqueous extract (AEB deleterious effects on animals blood vessels system, chick embryo chorioallantoic membrane (CAM was used. It were applying on CAM 0.1, 0.5, 1, 5, 10 e 15 µg/mL of AEB and saline as control. The angiogenesis was analyzed and the vascular density index (VDI calculated. The CAM samples were prepared and stained with H&E to evaluation of microvessels, Masson’s trichrome to characterize collagen and fibrin deposition and Picro-sirius used to evaluate collagen using polarized light. Also the morphological aspects of embryos were analysed. We observe on the results of neovascularization that AEB did not change significantly the number of vessels/mm², however, membranes treated with AEB (5 or 10 µg/mL exhibit opacity and tissue fibrosis, both signs of inflammation. Histological analysis with Masson's trichrome and picro-sirius on tissues exposed to AEB respectively has shown increased collagen fibers and presence of fibrilar collagen. The embryos exposed to concentrations of 5 or 10 µg/mL AEB, showed changes as poor face formation and poor closing of abdominal wall. The highest concentration of AEB (15 µg/mL was lethal to embryos. Although significant effects on the CAM’s vasculature has not observed, tissue aggression was detected, a desmoplasia (an extensive inflammatory signal triggered by tissue injury, changes caused on embryos as well as the presence of toxic substances in the AEB show us an important and deleterious pathway of this bracken fern extract on its intoxicants effects on humans and animals, and even cancer or the death of animals.

  5. Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Darawan Rinchai


    Full Text Available Background: Members of the ADAM (a disintegrin and metalloprotease domain family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1 The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2 changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs. 3 Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes.

  6. Effect of Kombucha, a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats. (United States)

    Bhattacharya, Semantee; Gachhui, Ratan; Sil, Parames C


    Diabetic complications associated with increased oxidative stress can be suppressed by antioxidants. In the present study we investigated the antidiabetic and antioxidant effects of Kombucha (KT), a fermented black tea, in comparison to that of unfermented black tea (BT), in ALX-induced diabetic rats. ALX exposure lowered the body weight and plasma insulin by about 28.12% and 61.34% respectively and elevated blood glucose level and glycated Hb by about 3.79 and 3.73 folds respectively. The oxidative stress related parameters like lipid peroxidation end products (increased by 3.38, 1.7, 1.65, 1.94 folds respectively), protein carbonyl content (increased by 2.5, 2.35, 1.8, 3.26 folds respectively), glutathione content (decreased by 59.8%, 47.27%, 53.69%, 74.03% respectively), antioxidant enzyme activities were also altered in the pancreatic, hepatic, renal and cardiac tissues of diabetic animals. Results showed significant antidiabetic potential of the fermented beverage (150 mg lyophilized extract/kg bw for 14 days) as it effectively restored ALX-induced pathophysiological changes. Moreover, it could ameliorate DNA fragmentation and caspase-3 activation in the pancreatic tissue of diabetic rats. Although unfermented black tea is effective in the above pathophysiology, KT was found to be more efficient. This might be due to the formation of some antioxidant molecules during fermentation period. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Promising anti-oxidative therapeutic potentials of edible freshwater snail Bellamya bengalensis extract against arsenic-induced rat hepatic tissue and DNA damage

    Directory of Open Access Journals (Sweden)

    Sk Sajed Ali


    Full Text Available Epidemiological data suggest that arsenic ultimately results in cancer in different parts of the body. Several synthetic therapeutic agents manifest inadequate potency with severe side effects against arsenic toxicity. The flesh of B. bengalensis, has long been used as an ethno-medicine in case of arthritis, blood-impurities, impaired immune system, conjunctivitis and liver anomalies. This potent organism might be a natural choice against arsenic and several other toxicities. Our earlier studies on arsenic-exposed human can correlate carcinogenesis with DNA-damage. In an attempt to investigate the possible protective and therapeutic effect against arsenic induced hepatotoxicity, the extract of B. bengalensis was tested in arsenic intoxicated rat model. The time- and dose-dependent effect of arsenic toxicity was also tested in B. bengalensis. Sodium-meta-arsenite NaAsO2 (0.6 ppm/100g bw/day for 28 days, as earlier reported was treated alone or in combination with the B. bengalensis water extract (BBE, 100 mg/100g bw to rat and compared with vehicle treated control. In a separate experiment, the B. bengalensis was exposed to high concentration of NaAsO2 contaminated water (5 to 20 ppm for 1 to 9 days in laboratory condition and their DNA quality was evaluated in relation to its possible oxidative threat. Any concentration of arsenic was incapable to initiate a significant DNA damage in B. bengalensis. Lipid peroxidation was increased in arsenic exposed B. bengalensis after longer duration of its exposure. Increase in reduced antioxidant like non-protein-soluble thiol (NPSH is concordant with the decrease in lipid peroxidation and DNA stability in this organism. In rat experiment, the BBE supplementation strongly prevented arsenic-induced oxidative, necrotic and apoptotic damages to liver tissue/DNA by strengthening antioxidant systems, which has been shown in hepatic DNA-fragmentation, comet-assay, histo-architecture (hematoxylin/eosin, alkaline

  8. Effects of chronic alcohol consumption on DNA damage and immune regulation induced by the environmental pollutant dibenzo[a,l]pyrene in oral tissues of mice. (United States)

    Chen, Kun-Ming; Schell, Todd D; Richie, John P; Sun, Yuan-Wan; Zhang, Shang-Min; Calcagnotto, Ana; Aliaga, Cesar; Gowda, Krishne; Amin, Shantu; El-Bayoumy, Karam


    Previously, we showed that oral application of the environmental pollutant dibenzo[a,l]pyrene (DB[a,l]P) induces oral tumors in mice. Thus, in the present investigation we examined the effect of alcohol on DB[a,l]P-induced DNA damage and immune regulation; we showed that alcohol (6.4% v/v in the diet, 35% of Calories) significantly enhanced the levels of (-)-anti-trans-DB[a,l]P-dA while decreased the levels of GSH in the mouse oral tissues. Analysis of RNA expression revealed that DB[a,l]P alone upregulates inflammatory genes while alcohol suppresses several markers of immune surveillance. Collectively, these results suggest that alcohol may enhance oral carcinogenesis induced by DB[a,l]P.

  9. Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma. (United States)

    Zaghloul, Randa A; El-Shishtawy, Mamdouh M; El Galil, Khaled H Abd; Ebrahim, Mohamed A; Metwaly, AbdelHamid A; Al-Gayyar, Mohammed M


    In Egypt, hepatocellular carcinoma (HCC) was predicted to continue to rise over the next few decades causing a national problem. Meanwhile, glypican-3 (GPC3), a highly expressed glypican, has emerged as a potential target for HCC immunotherapy. Therefore, we aimed to identify the impact of blocking GPC3 on liver damage in HCC as well as a possible mechanism. Fifty four HCC patients, 20 cirrhotic patients and 10 healthy subjects were recruited. Serum levels of GPC3, sulfatase-2 (SULF-2), heparan sulfate proteoglycan (HSPG), insulin-like growth factor-II (IGF-II) were measured by ELISA. In parallel, HCC was induced in 40 male Sprague-Dawley rats in presence/absence of antiGPC-3. Liver impairment was detected by investigating liver sections stained with hematoxylin/eosin and serum α-fetoprotein (AFP). Liver homogenates of GPC3, SULF-2, and HSPG were measured by ELISA. Gene expression of caspase-3 and IGF-II were assayed by RT-PCR. HCC patients showed significant elevated serum levels of GPC3, IGF-II and SULF-2 accompanied by decreased HSPG. However, treatment of HCC rats with antiGPC-3 significantly reduced serum AFP and showed nearly normal hepatocytes. In addition, antiGPC-3 significantly reduced elevated liver homogenates protein levels of GPC3 and SULF-2 and gene expression of IGF-II and caspase-3. antiGPC-3 restored the reduced hepatic HSPG. antiGPC-3 showed anti-tumor activity as well as hepatoprotective effects. antiGPC-3-chemoprotective effect can be explained by forced reduction of IGF-II expression, restoration of HSPGs, deactivation of SULF-2 and reduction of gene expression of caspase-3. Targeting GPC3 is a promising therapeutic approach for HCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice. (United States)

    Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali


    Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters.

  11. Serum concentrations of two biochemical markers of brain tissue damage S‐100B and neurone specific enolase are increased in elite female soccer players after a competitive game (United States)

    Stålnacke, B‐M; Ohlsson, A; Tegner, Y; Sojka, P


    Background It is a matter of debate whether or not ordinary heading of the ball in soccer causes injury to brain tissue. Objective To analyse concentrations of the biochemical markers of brain tissue damage S‐100B and neurone specific enolase (NSE) in serum of female elite soccer players in association with a competitive game. Methods Venous blood samples were obtained from 44 female soccer players before and after a competitive game for analysis. The number of headers and trauma events (falls, collisions, etc) was assessed from videotape recordings for each player. Results Concentrations of both brain damage markers were increased after the game (S‐100B, 0.18 (0.11) v 0.11 (0.05) μg/l (p  =  0.000); NSE, 10.14 (1.74) v 9.05 (1.59) μg/l (p  =  0.001)). There was a significant correlation between changes in S‐100B concentrations and both the number of headers (r  =  0.430, p  =  0.004) and the number of other trauma events (r  =  0.517, p<0.001). Conclusion The concentrations of both S‐100B and NSE were increased by game associated activities and events. The increases in S‐100B concentration were significantly related to the number of headers and other trauma events, which indicates that both these factors may have contributed to these increases. PMID:16556784

  12. The effects of tamoxifen on learning, memory and brain tissues oxidative damage in ovariectomized and naïve female rats

    Directory of Open Access Journals (Sweden)

    Hoda Zabihi


    Full Text Available Background: Regarding the modulatory effects of tamoxifen (TAM on the actions of estrogen in the present study, the effects of TAM on learning, memory and brain tissues oxidative damage in ovariectomized (OVX and naοve female rats was investigated. Materials and Methods: The animals were divided into: (1 Sham, (2 OVX, (3 Sham-tamoxifen (Sham-TAM and (4 ovariectomized-tamoxifen (OVX-TAM. The animals of the Sham-TAM and OVX-TAM groups were treated by TAM (1 mg/kg; 4 weeks. Results : In Morris water maze, the escape latency in the OVX group was higher than in the Sham group (P < 0.01. The time latency in the animals of OVX-TAM group was lower than that of OVX group (P < 0.01; however, there were no significant differences between the Sham-TAM and Sham groups. In the probe trial, the time spent in target quadrant (Q 1 by the animals of OVX group was lower than that of Sham group (P < 0.01. Interestingly, the animals of OVX-TAM group spent more times in target quadrant (Q 1 compared with OVX group (P < 0.01. In passive avoidance test, the animals of OVX group had lower latencies to enter the dark compartment compared with the Sham group (P < 0.05. The time latency to enter the dark compartment by animals of OVX-TAM group was higher than in OVX group (P < 0.01. In OVX-TAM group, the total thiol concentration was significantly higher (P < 0.05 and malondialdehyde concentration was lower (P < 0.01 than OVX group. Conclusions: These results allow us to propose that TAM enhances learning and memory of OVX rats. The possible mechanism may be due to the protective effects against brain tissues oxidative damage.

  13. [Role of orexin-A-mediated communication system between brain and peripheral tissues on the development of post-ischemic glucose intolerance-induced neuronal damage]. (United States)

    Harada, Shinichi


    I recently found that cerebral ischemic stress per se causes hyperglycemia (i.e., post-ischemic glucose intolerance) and suppression of post-ischemic glucose intolerance might be important to improve prognosis. Here, I analyzed the efficacy of suppression of post-ischemic glucose intolerance using orexin-A (OXA) endogenous neuropeptide as a novel therapeutic strategy against cerebral ischemic neuronal damage. OXA in hypothalamus plays a role in many physiological functions including regulation of glucose metabolism. I previously found that the development of post-ischemic glucose intolerance is suppressed by OXA. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic OXA-mediated suppression of post-ischemic glucose intolerance and neuronal damage. Intrahypothalamic administration of OXA significantly suppressed the development of post-ischemic glucose intolerance on day 1 and of neuronal damage on day 3 after middle cerebral artery occlusion (MCAO). In the liver, MCAO-induced decrease in insulin receptors and increase in gluconeogenic enzymes on day 1 was recovered to control levels by OXA; these effects were reversed by hepatic vagotomy. In the medulla oblongata, OXA induced co-localization of the cholinergic neuronal marker choline acetyltransferase with orexin-1 receptor and c-Fos. These results suggest that the vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates neuroprotection by hypothalamic OXA.

  14. Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E. (United States)

    Ma, Ping; Wu, Yang; Zeng, Qiang; Gan, Yaping; Chen, Jiaoe; Ye, Xin; Yang, Xu


    Chlorpyrifos is a broad-spectrum, chlorinated organophosphate pesticide employed for pest control in various agricultural and animal husbandries. Acute and chronic exposure to CPF can elicit several adverse effects, including oxidative stress. We investigated neurotoxicity of CPF-treated mice, and evaluated the antioxidant effect of vitamin E against oxidative stress and histological changes in the livers and kidneys of CPF-treated mice. Kunming mice were divided randomly into five exposure groups of six: (A) peanut oil; (B) 3mg/kg CPF; (C) 6 mg/kg CPF; (D) 12 mg/kg CPF; (E) vitamin E (100 mg/kg), 3h after administration of CPF (12 mg/kg) and used as a post-treatment group. Oral administration of high-dose groups (12 mg/kg) CPF led to a significant increase in levels of reactive oxygen species, DNA-protein crosslinks, 8-hydroxy-2-deoxyguanosine and malondialdehyde, decreases in acetylcholinesterase activity and glutathione level, as well as causing hepatic and renal histopathological change. Except for AChE activity levels, administration of vitamin E to CPF-treated mice restored these biochemical parameters to within normal levels, and resulted in overall improvement in damage to livers and kidneys. These data suggest that oxidative stress is involved in CPF-induced toxicity and that vitamin E can protect against the tissue damage induced by CPF. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Comparison of laser-assisted damage in soft tissue using bi-directional and forward-firing optical fiber (United States)

    Kim, Changhwan; Sohn, Ik-Bu; Park, Hoyong; Lee, Yong Joong; Lee, Ho


    Laser-assisted endoscopic surgery is made possible by employing optical devices such as fiber optics and hollow wave-guides. In some applications of laser-assisted endoscopic surgery, it is necessary to change the direction of the light emission. Our group reported a new fabrication method for bi-directional firing fibers. The conical surface of the fiber tip made the bi-directional emission of the laser light at the distal end of the fiber. In this study, we employed the bi-directional firing fiber for laser-assisted coagulation of soft tissue. The developed fiber and the normal forward-firing fiber are used for the endoscopic delivery system of a continuous IR laser into an in vitro porcine liver. The ablation and coagulation pattern were compared for two distinctive fiber systems. Regardless of the laser's parameters, the bi-directional firing fiber produced a cavity and coagulation zone with more or less a circular shape, while the forward fiber produced an elongated cavity and coagulation region. The bi-directional firing fiber produced wider and shorter coagulation and cavity zones compared to that of the forward-firing fiber. We expect the bi-directional firing fiber to be an excellent optical delivery system for endoscopic laser-hyperthermia when used against various tumors in the liver, breast and thyroid.

  16. Proteomic analysis of the honey bee worker venom gland focusing on the mechanisms of protection against tissue damage. (United States)

    Peiren, Nico; de Graaf, Dirk C; Vanrobaeys, Frank; Danneels, Ellen L; Devreese, Bart; Van Beeumen, Jozef; Jacobs, Frans J


    Honey bee workers use venom for the defence of the colony and themselves when they are exposed to dangers and predators. It is produced by a long thin, convoluted, and bifurcated gland, and consists of several toxic proteins and peptides. The present study was undertaken in order to identify the mechanisms that protect the venom gland secretory cells against these harmful components. Samples of whole venom glands, including the interconnected reservoirs, were separated by two-dimensional gel electrophoresis and the most abundant protein spots were subjected to mass spectrometric identification using MALDI TOF/TOF-MS and LC MS/MS. This proteomic study revealed four antioxidant enzymes: CuZn superoxide dismutase (SOD1), glutathione-S-transferase sigma 1 isoform A (GSTS1), peroxiredoxin 2540 (PXR2540) and thioredoxin peroxidase 1 isoform A (TPX1). Although glutathione-S-transferase (GST) has also been associated with xenobiotic detoxification, the protein we found belongs to the GST Sigma class which is known to protect against oxidative stress only. Moreover, we could demonstrate that the GST and SOD activity of the venom gland was low and moderate, respectively, when compared to other tissues from the adult honey bee. Several proteins involved in other forms of stress were likewise found but it remains uncertain what their function is in the venom gland. In addition to major royal jelly protein 9 (MRJP9), already found in a previous proteomic study, we identified MRJP8 as second member of the MRJP protein family to be associated with the venom gland. Transcripts of both MRJPs were amplified and sequenced. Two endocuticular structural proteins were abundantly present in the 2D-gel and most probably represent a structural component of the epicuticular lining that protects the secretory cells from the toxins they produce.

  17. Spinal cord injury after blunt cervical spine trauma: correlation of soft-tissue damage and extension of lesion. (United States)

    Martínez-Pérez, R; Paredes, I; Cepeda, S; Ramos, A; Castaño-León, A M; García-Fuentes, C; Lobato, R D; Gómez, P A; Lagares, A


    In patients with spinal cord injury after blunt trauma, several studies have observed a correlation between neurologic impairment and radiologic findings. Few studies have been performed to correlate spinal cord injury with ligamentous injury. The purpose of this study was to retrospectively evaluate whether ligamentous injury or disk disruption after spinal cord injury correlates with lesion length. We retrospectively reviewed 108 patients diagnosed with traumatic spinal cord injury after cervical trauma between 1990-2011. Plain films, CT, and MR imaging were performed on patients and then reviewed for this study. MR imaging was performed within 96 hours after cervical trauma for all patients. Data regarding ligamentous injury, disk injury, and the extent of the spinal cord injury were collected from an adequate number of MR images. We evaluated anterior longitudinal ligaments, posterior longitudinal ligaments, and the ligamentum flavum. Length of lesion, disk disruption, and ligamentous injury association, as well as the extent of the spinal cord injury were statistically assessed by means of univariate analysis, with the use of nonparametric tests and multivariate analysis along with linear regression. There were significant differences in lesion length on T2-weighted images for anterior longitudinal ligaments, posterior longitudinal ligaments, and ligamentum flavum in the univariate analysis; however, when this was adjusted by age, level of injury, sex, and disruption of the soft tissue evaluated (disk, anterior longitudinal ligaments, posterior longitudinal ligaments, and ligamentum flavum) in a multivariable analysis, only ligamentum flavum showed a statistically significant association with lesion length. Furthermore, the number of ligaments affected had a positive correlation with the extension of the lesion. In cervical spine trauma, a specific pattern of ligamentous injury correlates with the length of the spinal cord lesion in MR imaging studies

  18. Protective Effect of Tulbaghia violacea Harv. on Aortic Pathology, Tissue Antioxidant Enzymes and Liver Damage in Diet-Induced Atherosclerotic Rats

    Directory of Open Access Journals (Sweden)

    Anthony J. Afolayan


    Full Text Available The protective effect Tulbaghia violacea rhizomes (TVR against derangements in serum lipid profile, tissue antioxidant enzyme depletion, endothelium dysfunction and histopathological changes in the aorta and liver of rats fed with an atherosclerogenic (Ath diet (4% cholesterol, 1% cholic acid and 0.5% thiouracil was investigated in this study. Co-treatment with the TVR extracts (250 and 500 mg/kg body weight for two weeks significantly (p < 0.05 protected against elevated serum triglyceride (TG, total cholesterol (TC, LDL-cholesterol, VLDL-cholesterol and decreased HDL-cholesterol in a dose-dependent manner when compared with the atherogenic control. The extracts also reduced (p < 0.05 elevated thiobabutric reacting substance (TBARS and reversed endothelial dysfunction parameters (fibrinogen and total NO levels and tissue antioxidant enzyme activities to near normal. The protective ability of the extract was confirmed by the significant (p < 0.05 reduction in the activities of serum markers of liver (LDH, AST, ALT, ALP, bilirubin and kidney damage (creatinine and bilirubin in extract-treated groups compared with the atherogenic control group. Also, histopathology evaluations of aorta sections revealed that the extracts protected against the development of fatty streak plaques (aorta and fatty changes in hepatocytes. The observed activities of the extracts compared favorably with standard drug atorvastatin. Our study thus showed that the methanolic extract of TVR could protect against the early onset of atherosclerosis.

  19. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo


    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

  20. Clinical and histological comparison of tissue damage and healing following incisions with the CO2-laser and stainless steel surgical blade in dogs. (United States)

    Durante, E J; Kriek, N P


    The tissue damage and subsequent healing of skin, linea alba and intestinal wall incisions made with a CO2-laser and a stainless steel surgical blade were evaluated clinically and histologically in dogs (n = 10). The amount of blood lost in each type of skin incision was measured by taking the pre- and postoperative mass of surgical swabs. The tissues were sutured and the skin incisions examined every day. The animals were subsequently euthanased (Day 12) and all incisions examined histologically. A delay in the healing process was observed in the laser incisions of the skin during the first 4 d, but there was no difference in the healing rate of the intestinal wounds or of the linea alba. The blood loss due to the laser incisions was significantly less than that caused by the surgical blade. It was concluded that the CO2-laser can be used with confidence when incising the skin and intestine and that, due to its precision, the surgical blade is by far a more accurate method to incise the linea alba.

  1. DNA damage induced in mouse tissues by organic wood preserving waste extracts as assayed by {sup 32}P-postlabeling

    Energy Technology Data Exchange (ETDEWEB)

    Randerath, E. [Division of Toxicology, Department of Pharmacology, Baylor College of Medicine, Houston, TX (United States); Zhou, G.D. [Division of Toxicology, Department of Pharmacology, Baylor College of Medicine, Houston, TX (United States); Donnelly, K.C. [Department of Veterinary Anatomy and Public Health, Texas A and M University, College Station, TX (United States); Safe, S.H. [Department of Veterinary Physiology/Pharmacology, Texas A and M University, College Station, TX (United States); Randerath, K. [Division of Toxicology, Department of Pharmacology, Baylor College of Medicine, Houston, TX (United States)


    In the present study, a mouse bioassay was used in combination with {sup 32}P-postlabeling to determine DNA adduct formation induced by hexane/acetone extracts of two samples from a WPW site. Female ICR mice were treated dermally with extract corresponding to 3 mg residue or vehicle control once per day for 2 days and killed 24 h later. Skin, lung, liver, kidney, and heart DNA preparations were assayed by nuclease P1-enhanced postlabeling. Adduct profiles were tissue-specific and displayed a multitude of non-polar DNA adducts with levels amounting to one adduct in 1.6 x 10{sup 6} DNA nucleotides in skin (both extracts) and one adduct in 3.2 x 10{sup 7} or 1.2 x 10{sup 7} DNA nucleotides in liver (extract 1 or extract 2). Based on their chromatographic properties, these adducts appeared largely derived from polycyclic aromatic hydrocarbons (PAHs) present in the extracts. One of the major adducts was identified as the {sup 32}P-labeled derivative of the reaction product of 7{beta}, 8{alpha}-dihydroxy-9{alpha}, 10{alpha}-epoxy-7, 8, 9, 10-tetrahydrobenzo[a]pyrene (BPDE I) with N{sup 2} of deoxyguanosine. Total non-polar DNA adduct levels were highest in skin and lung, amounting to 17.4 and 24.0% of the skin values for extracts 1 and 2, respectively, in lung while the corresponding levels in liver were 5.0 and 12.6%. These results were in accord with the carcinogenic potencies of PAHs in these organs. Extract 2 induced higher adduct levels in internal organs, although its PAH concentrations were lower than those of extract 1, i.e. lung, liver, kidney, and heart had 1.4, 2.5, 1.9, and 1.7 times higher total adduct levels and 1.6, 3.3, 1.6, and 1.9 times higher benzo[a]pyrene adduct levels. With the exception of total adducts in lung, the differences between the two extracts were all significant, suggestive of compound interactions. (orig.) (orig.). With 5 figs., 6 tabs.

  2. [The possibility of using the synthetic compound for the purpose of modeling of the human soft tissues in connection with the evaluation of gunshot damages]. (United States)

    Latyshov, I V; Vasil'ev, V A; Zaporotskova, I V; Ermakova, T A


    The necessity of using a simulator of human soft tissues for the purpose of criminalistic and forensic medical expertises is dictated by the requirements put forward by the expert practice. The objective of the present study was to develop a synthetic simulator of the human soft tissues (compound) to ensure reliability of comparative criminalistics and forensic medical studies for the evaluation of gunshot injuries. The synthetic compound was prepared by mixing up the petroleum and/or synthetic oil with a polymeric thickening agent. This procedure was followed by heating the mixture at 90 degrees Celsius during 5 hours. Thereafter, petrolatum and/or ceresin and/or paraffin were added to the mixture. At the final stage, ionol was introduced, and the mixture was poured into a mold measuring 70×70×210 mm with its subsequent cooling down to 40 degrees Celsius during 10-12 hours. The experimental shooting was effected from the Kalashnikov AKS-74U assault rifle using the 5.45×39 mm (7H6) cartridges, Makarov pistol using the 9×18 mm cartridges and Nagant pistol using the CHELP-1000 cartridges. Five shots were fired from each of the three models. The experimental gunshot damages were evaluated visually by examining the inlet and exit openings and the bullet channel. In addition, criminalistic analysis of the grooves in cartridges was carried out. The technology for the fabrication of synthetic compounds based on ethylene, propylene, and butadiene co-polymers in the combination with such low molecular weight compounds as paraffins and ceresins having a homogeneous structure makes it possible to vary the rheological and mechanical properties of the simulators of human soft tissues for the solution of diagnostic and identification problems in the framework of criminalistics and forensic medical expertises.

  3. Assessment of penetrating thermal tissue damage/spread associated with PhotonBlade™, Valleylab™ Pencil, Valleylab™ EDGE™ Coated Pencil, PlasmaBlade® 3.0S and PlasmaBlade® 4.0 for intraoperative tissue dissection using the fresh extirpated porcine muscle model (United States)

    Bennett, Haydon E.; Taylor, Scott D.; Fugett, James H.; Shrout, Joshua L.; Davison, Paul O.; Ryan, S. Eric; Coad, James E.


    Penetrating thermal tissue damage/spread is an important aspect of many electrosurgical devices and correlates with effective tissue cutting, hemostasis, preservation of adjacent critical structures and tissue healing. This study compared the thermal damage/spread associated with the PhotonBlade, Valleylab Pencil, Valleylab EDGE Coated Pencil, PlasmaBlade 3.0S and PlasmaBlade 4.0, when performing a single pass dynamic tissue cut in fresh extirpated porcine longissimus muscle. These devices were used in a fashion that emulated their use in the clinical setting. Each device's thermal damage/spread, at Minimum, Median and Maximum power input settings, was assessed with nitroblue tetrazolium viability staining in the WVU Pathology Laboratory for Translational Medicine. The thermal damage/spread associated with the PhotonBlade was compared with the other devices tested based on the individual treatment results (n=179 cuts combined). In summary, the PhotonBlade overall demonstrated the least penetrating thermal tissue damage/spread, followed by the PlasmaBlade 4.0, then Valleylab Pencil and PlasmaBlade 3.0S and then Valleylab EDGE Coated Pencil in order of increasing thermal damage/spread depths.

  4. Di-D-fructose dianhydride-enriched caramels: effect on colon microbiota, inflammation, and tissue damage in trinitrobenzenesulfonic acid-induced colitic rats. (United States)

    Arribas, Belén; Suárez-Pereira, Elena; Ortiz Mellet, Carmen; García Fernández, José M; Buttersack, Christoph; Rodríguez-Cabezas, Maria Elena; Garrido-Mesa, Natividad; Bailon, Elvira; Guerra-Hernández, Eduardo; Zarzuelo, Antonio; Gálvez, Julio


    In the present study we describe the preparation and chemical characterization of a caramel with a high (70%) content of difructose dianhydrides (DFAs) and glycosylated derivatives (DFAs). This product was obtained by thermal activation (90 degrees C) of highly concentrated (90% w/v) aqueous D-fructose solutions using the sulfonic acid ion-exchange resin Lewatit S2328 as caramelization catalyst. DFAs represent a unique family of cyclic fructans with prebiotic properties already present in low proportions (caramel. We report the antiinflammatory activity of the new DFA-enriched caramel in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis, an experimental model that resembles human inflammatory bowel disease (IBD), and compare its effects with those obtained with a commercial sucrose caramel and with linear fructooligosaccharides (FOS). For this purpose, the effects on colon tissue damage, gut microbiota, short-chain fatty acid (SCFAs) production, and different inflammatory markers were evaluated. The administration of DFA-enriched caramel to colitic rats showed intestinal antiinflammatory effect, as evidenced macroscopically by a significant reduction in the extent of the colonic damage induced by TNBS. This effect was similar to that obtained with FOS in the same experimental settings, whereas commercial caramel was devoid of any significant antiinflammatory effect. The beneficial effect was associated with the inhibition of the colonic levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha) and interleukin 1beta (IL-1beta), and the reduction in colonic myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) expression. The DFA-enriched caramel also promoted a more favorable intestinal microbiota, increasing lactobacilli and bifidobacteria counts as well as inducing higher concentrations of SCFAs in the luminal colonic contents. These results reinforce the concept of DFAs and glycosyl-DFAs as dietary beneficial

  5. Assessment of DNA Binding and Oxidative DNA Damage by Acrylonitrile in Two Rat Target Tissues of Carcinogenicity: Implications for the Mechanism of Action. (United States)

    Williams, Gary M; Kobets, Tetyana; Duan, Jian-Dong; Iatropoulos, Michael J


    Exposure to acrylonitrile induces formation of tumors at multiple sites in rats, with females being more sensitive. The present study assessed possible mechanisms of acrylonitrile tumorigenicity, covalent DNA binding, DNA breakage, and oxidative DNA damage, in two target tissues, the brain and Zymbal's glands, of sensitive female Fischer (F344) and Sprague-Dawley (SD) rats. One group received acrylonitrile in drinking water at 100 ppm for 28 days. Two other groups were administered either acrylonitrile in drinking water at 100 ppm or drinking water alone for 27 days, followed by a single oral gavage dose of 11 mg/kg bw (14)C-acrylonitrile on day 28. A positive control group received a single dose of 5 mg/kg bw of 7-(14)C-benzo[a]pyrene, on day 27 following the administration of drinking water for 26 days. Using liquid scintillation counting, no association of radiolabeled acrylonitrile with brain DNA was found. In accelerator mass spectrometry analysis, the association of (14)C of acrylonitrile with DNA in brains was detected and was similar in both strains, which may reflect acrylonitrile binding to protein as well as to DNA. Nucleotide (32)P-postlabeling assay analysis of brain samples from rats of both strains yielded no evidence of acrylonitrile DNA adducts. Negative conventional comet assay results indicate the absence of direct DNA strand breaks in the brain and Zymbal's gland in both strains of rats dosed with acrylonitrile. In both rat strains, positive results in an enhanced comet assay were found only in brain samples digested with formamidopyrimidine-DNA glycosylase but not with human 8-hydroxyguanine-DNA glycosylase, indicating possible oxidative DNA damage, other than 8-oxodG formation. In conclusion, definitive evidence of DNA binding of acrylonitrile in the brain and Zymbal's gland was not obtained under the test conditions. A role for oxidative stress in tumorigenesis in the brain but not Zymbal's gland may exist.

  6. High-speed scanning ablation of dental hard tissues with a λ=9.3-μm CO2 laser: heat accumulation and peripheral thermal damage (United States)

    Nguyen, Daniel; Staninec, Michal; Lee, Chulsung; Fried, Daniel


    A mechanically scanned CO2 laser operated at high laser pulse repetition rates can be used to rapidly and precisely remove dental decay. This study aims to determine whether these laser systems can safely ablate enamel and dentin without excessive heat accumulation and peripheral thermal damage. Peripheral thermal damage can adversely impact the mechanical strength of the irradiated tissue, particularly for dentin, and reduce the adhesion characteristics of the modified surfaces. Samples were derived from noncarious extracted molars. Pulpal temperatures were recorded using microthermocouples situated at the pulp chamber roof of samples (n=12), which were occlusally ablated using a rapid-scanning, water-cooled 300 Hz CO2 laser over a two minute time course. The mechanical strength of facially ablated dentin (n=10) was determined via four-point bend test and compared to control samples (n=10) prepared with 320 grit wet sand paper to simulate conventional preparations. Composite-to-enamel bond strength was measured via single-plane shear test for ablated/non-etched (n=10) and ablated/acid-etched (n=8) samples and compared to control samples (n=9) prepared by 320 grit wet sanding. Thermocouple measurements indicated that the temperature remained below ambient temperature at 19.0°C (s.d.=0.9) if water-cooling was used. There was no discoloration of either dentin and enamel, the treated surfaces were uniformly ablated and there were no cracks observable on the laser treated surfaces. Fourpoint bend tests yielded mean mechanical strengths of 18.2 N (s.d.=4.6) for ablated dentin and 18.1 N (s.d.=2.7) for control (p>0.05). Shear tests yielded mean bond strengths of 31.2 MPa (s.d.=2.5, p<0.01) for ablated/acid-etched samples, 5.2 MPa (s.d.=2.4, p<0.001) for ablated/non-etched samples, and 37.0 MPa (s.d.=3.6) for control. The results indicate that a rapid-scanning 300 Hz CO2 laser can effectively ablate dentin and enamel without excessive heat accumulation and with minimal

  7. Intestinal titres of anti-tissue transglutaminase 2 antibodies correlate positively with mucosal damage degree and inversely with gluten-free diet duration in coeliac disease. (United States)

    Tosco, A; Auricchio, R; Aitoro, R; Ponticelli, D; Primario, M; Miele, E; Rotondi Aufiero, V; Discepolo, V; Greco, L; Troncone, R; Maglio, M


    It has always been known that anti-tissue transglutaminase 2 (anti-TG2) antibodies are produced in the small intestine. Their serum titres correlate with mucosal damage degree and decrease on a gluten-free diet (GFD). We aimed to correlate intestinal anti-TG2 antibodies levels with degree of mucosal damage and GFD duration. Thirty-four active, 71 potential and 24 CD patients on GFD for at least 2 years were enrolled. Anti-TG2 deposits were detected in intestinal biopsies by double immunofluorescence. Biopsies were cultured for 24 h with medium, and with gliadin peptic tryptic digest (PTG) or A-gliadin peptide 31-43 (P31-43). Anti-TG2 antibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay (ELISA). All active CD patients secreted high titres of anti-TG2 antibodies into culture medium that increased with the worsening of mucosal injury (Spearman's r = 0·71; P < 0·0001). Seventy of 71 potential CD patients and 15 of 24 treated CD patients secreted low titres of anti-TG2 antibodies into supernatants, eight of nine negative treated patients being on GFD for more than 10 years. An inverse correlation between antibody titres and duration of GFD was found, (Spearman's r = -0·52; P < 0·01). All active, 53 of 71 potential and six of 24 treated, CD patients showed anti-TG2 mucosal deposits. Five of six positive treated CD patients had been on GFD for fewer than 6 years and were also positive for secreted anti-TG2. In treated patients, PTG/P31-43 was not able to induce secretion of anti-TG2 antibodies into culture medium. Measurement of anti-TG2 antibodies in biopsy supernatants proved to be more sensitive than detection by immunofluorescence to reveal their intestinal production. Intestinal antiTG2 antibodies titres correlated positively with the degree of mucosal damage and inversely with the duration of GFD. © 2014 British Society for Immunology.

  8. Evaluation of photodynamically induced damage to healthy eye tissues of rabbits using the second-generation photosensitizers bacteriochlorin a and mTHPC (United States)

    Schuitmaker, Hans J.; Barthen, Ed; Keunen, Jan E.; Ms Wolff-Rouendaal, Didi


    Immediate illumination after sensitizer administration is currently often applied in PDT-trials in ophthalmology. The extent of possible damage to healthy ocular tissue after i.v. administration of the photosensitizers bacteriochlorin a (BCA) or mesa (tetrahydroxyphenyl) chlorin (mTHPC) and subsequent illumination with light of the appropriate wavelength and dose was assessed in rabbit eyes. Both hydrophobic drugs were formulated in 30% polyethylene glycol, 20% ethanol and 50% water to obtain an iv injectable suspension. Rabbits destined for BCA-PDT received a single dose of 10 mg/ Rabbits destined for mTHPC-PDT received a dose of 0.3 mg/ BCA- treated animals were illuminated immediately and 1, 2 and three hours after administration of the dye with an experimental Philips laser diode (760 nm, c.w., 100 mW/cm2, 100 J). To illuminate the eyes of the mTHPC- treated animals a Krypton laser was used (648 nm, c.w., 100 mW/cm2, 20 J). Illumination of these animals was performed immediately, 24, 48 and 72 hours after administration of the dye. BCA or mTHPC without illumination or illumination without administration of a sensitizing dye did not affect normal ocular tissues as judged by histology. Illumination of the entire eye of BCA-treated animals, immediately after administration of the dye caused a lesion in the macula area with a diameter of 3 mm. At the lesion side the photoreceptors were destroyed, ganglion cells were swollen and the sclera was affected. No skin photosensitivity was observed at anytime. Skin photosensitivity was observed in animals treated with mTHPC. Illumination caused swollen eyelids in all animals except when performed immediately after dye administration.

  9. Amebic cysteine proteinase 2 (EhCP2) plays either a minor or no role in tissue damage in acute experimental amebic liver abscess in hamsters. (United States)

    Olivos-García, Alfonso; González-Canto, Augusto; López-Vancell, Rosario; García de León, Maria del Carmen; Tello, Eusebio; Nequiz-Avendaño, Mario; Montfort, Irmgard; Pérez-Tamayo, Ruy


    Amebic cysteine protease 2 (EhCP2) was purified from ethyl ether extracts of axenically grown trophozoites of Entamoeba histolytica strain HM1-IMSS. The purification procedure involved molecular filtration and electroelution. Sequence analysis of the purified product revealed EhCP2 and ubiquitin(s). Electrophoretic migration patterns, isoelectric point determination and Western blot studies failed to reveal other EhCP molecules. Polyclonal antibodies against the purified EhCP2 prepared in rabbits either stabilized or enhanced the enzyme activity in a dose-response manner. Purified EhCP2 was enclosed within inert resin microspheres (22-44 microm in diameter) and injected into the portal vein of normal hamsters. In the liver, the microspheres caused mild acute inflammation and occasional minimal necrosis of short duration. Sections of the liver were immunohistochemically stained with the anti-EhCP2 antibody and the microspheres were positive for only a very short period (1 h) after injection. Sections of experimental acute (1 day, 5 days) amebic liver abscess produced in hamsters were also stained with the anti-EhCP2 antibody; and amebas were intensely positive but no staining was observed at any time in the surrounding necrotic structures. It is suggested that EhCP2 plays either a minor or no role in the causation of tissue damage in experimental acute liver amebiasis.

  10. Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snake Bothrops asper

    Directory of Open Access Journals (Sweden)

    Alexandra Rucavado


    Full Text Available Envenomations by the snake Bothrops asper are characterized by prominent local tissue damage (i.e. myonecrosis, blistering, hemorrhage and edema. Various phospholipases A2 and metalloproteinases that induce local pathological alterations have been purified from this venom. Since these toxins induce a conspicuous inflammatory response, it has been hypothesized that inflammatory mediators may contribute to the local pathological alterations described. This study evaluated the local production of cytokines and matrix metalloproteinases (MMPs as a consequence of intramuscular injections of an Asp-49 myotoxic phospholipase A2 (myotoxin III (MT-III and a P-I type hemorrhagic metalloproteinase (BaP1 isolated from B. asper venom. Both enzymes induced prominent tissue alterations and conspicuous increments in interleukin (IL-1β, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after injection. In contrast, no increments in tumor necrosis factor-α (TNF-α and interferon-γ were detected. In agreement, MT-III and BaP1 did not induce the synthesis of TNF-α by resident peritoneal macrophages in vitro. Despite the conspicuous expression of latent forms of MMPs in muscle, evidenced by zymography, there were no increments in activated MMP-2 and only a small increase in activated MMP-9, as detected by a functional enzymatic assay. This suggests that MMP activity was regulated by a highly controlled activation of latent forms and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage nor dermonecrosis were observed after injection of MT-III, despite a prominent increase in MMP expression, and since inflammatory exudate did not enhance hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the tissue are not responsible for the dermonecrosis and hemorrhage characteristic of B. asper envenomation. Moreover, pretreatment of mice with the peptidomimetic MMP inhibitor batimastat did not reduce myotoxic nor

  11. Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model. (United States)

    Lögters, Tim T; Altrichter, Jens; Paunel-Görgülü, Adnana; Sager, Martin; Witte, Ingo; Ott, Annina; Sadek, Sarah; Baltes, Jessica; Bitu-Moreno, José; Schek, Alberto; Müller, Wolfram; Jeri, Teresa; Windolf, Joachim; Scholz, Martin


    Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation. In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 +/- 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 +/- 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer' solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation and apoptosis were specifically determined in lung, bowel, and liver. In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment. Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage.

  12. Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis. (United States)

    Audoin, Bertrand; Au Duong, My Van; Ranjeva, Jean-Philippe; Ibarrola, Danielle; Malikova, Irina; Confort-Gouny, Sylviane; Soulier, Elisabeth; Viout, Patrick; Ali-Chérif, André; Pelletier, Jean; Cozzone, Patrick J


    We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT. Copyright 2004 Wiley-Liss, Inc.

  13. Lymphoid tissue damage in HIV-1 infection depletes naïve T cells and limits T cell reconstitution after antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Ming Zeng


    Full Text Available Highly active antiretroviral therapy (HAART can suppress HIV-1 replication and normalize the chronic immune activation associated with infection, but restoration of naïve CD4+ T cell populations is slow and usually incomplete for reasons that have yet to be determined. We tested the hypothesis that damage to the lymphoid tissue (LT fibroblastic reticular cell (FRC network contributes to naïve T cell loss in HIV-1 infection by restricting access to critical factors required for T cell survival. We show that collagen deposition and progressive loss of the FRC network in LTs prior to treatment restrict both access to and a major source of the survival factor interleukin-7 (IL-7. As a consequence, apoptosis within naïve T cell populations increases significantly, resulting in progressive depletion of both naïve CD4+ and CD8+ T cell populations. We further show that the extent of loss of the FRC network and collagen deposition predict the extent of restoration of the naïve T cell population after 6 month of HAART, and that restoration of FRC networks correlates with the stage of disease at which the therapy is initiated. Because restoration of the FRC network and reconstitution of naïve T cell populations are only optimal when therapy is initiated in the early/acute stage of infection, our findings strongly suggest that HAART should be initiated as soon as possible. Moreover, our findings also point to the potential use of adjunctive anti-fibrotic therapies to avert or moderate the pathological consequences of LT fibrosis, thereby improving immune reconstitution.

  14. 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. (United States)

    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


    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.

  15. Depth of tissue ablation and residual thermal damage caused by a pixilated 2,940 nm laser in a swine skin model. (United States)

    Regan, Thomas D; Uebelhoer, Nathan S; Satter, Elizabeth; Ross, E Victor


    The purpose of this study was to assess the effects of fluence, pulse stacking, and multiple passes on the depth of injury caused by a fractionated Er:YAG laser in an in vivo farm pig model. DESIGN/MATERIAL/METHODS: A fractionated 2,940 nm Er:YAG laser (Pixel, Alma Lasers, Caesarea, Israel) was applied to the flank skin of a Yorkshire cross pig. The 11 mmx11 mm handpiece was comprised of either 49 or 81 microbeams (200 microm diameter), depending on the tip configuration. There were six different parameter sets divided according to total energy per pulse (150, 285, and 500 mJ) and tip type (81 or 49 microbeams per 11 mmx11 mm macrospot). Each of these six groups was subdivided according to number of stacked pulses (1, 3, and 6) and number of passes (1, 3, and 6). This resulted in a total of 36 treatment parameters. With the 49 microbeam configuration, a single pulse resulted in partial epidermal ablation at 150 mJ, complete epidermal ablation at 285 mJ and partial dermal ablation at 500 mJ to a depth of 90 microm. Stacking the pulses resulted in a significant increase in ablation with each fluence with the maximal depth of ablation measured at 140 microm after six stacked pulses at 500 mJ. Increasing the number of passes did not result in a significant increase in ablative depth, but did create a larger surface area of ablation. Residual thermal damage (RTD) was minimal and remained between 10 and 20 microm. The fractionated Er:YAG laser exhibited some of the same tissue interactions as its fully ablative counterparts. An increase in fluence resulted in an increase in ablative depth with minimal RTD. Additionally, RTD was unaffected by pulse stacking or by additional passes. Differences were that pulse stacking appeared to yield a more rapid decrease in ablation efficiency and additional passes did not seem to increase the depth of ablation.

  16. Tissue responses to low protracted doses of high let radiations or photons: Early and late damage relevant to radio-protective countermeasures

    Energy Technology Data Exchange (ETDEWEB)

    Ainsworth, E.J.; Afzal, S.M.J.; Crouse, D.A.; Hanson, W.R.; Fry, R.J.M.


    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for ..gamma..-radiation. When total doses of 96 or 247 cGy of neutrons or ..gamma.. rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and ..gamma..-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. 63 refs., 6 figs., 7 tabs.

  17. Raman spectral markers of collagen denaturation and hydration in human cortical bone tissue are affected by radiation sterilization and high cycle fatigue damage. (United States)

    Flanagan, Christopher D; Unal, Mustafa; Akkus, Ozan; Rimnac, Clare M


    Thermal denaturation and monotonic mechanical damage alter the organic and water-related compartments of cortical bone. These changes can be detected using Raman spectroscopy. However, less is known regarding Raman sensitivity to detect the effects of cyclic fatigue damage and allograft sterilization doses of gamma radiation. To determine if Raman spectroscopic biomarkers of collagen denaturation and hydration are sensitive to the effects of (a) high cycle fatigue damage and (b) 25kGy irradiation. Unirradiated and gamma-radiation sterilized human cortical bone specimens previously tested in vitro under high-cycle (> 100,000 cycles) fatigue conditions at 15MPa, 25MPa, 35MPa, 45MPa, and 55MPa cyclic stress levels were studied. Cortical bone Raman spectral profiles from wavenumber ranges of 800-1750cm-1 and 2700-3800cm-1 were obtained and compared from: a) non-fatigue vs fatigue fracture sites and b) radiated vs. unirradiated states. Raman biomarker ratios 1670/1640 and 3220/2949, which reflect collagen denaturation and organic matrix (mainly collagen)-bound water, respectively, were assessed. One- and two-way ANOVA analyses were utilized to identify differences between groups along with interaction effects between cyclic fatigue and radiation-induced damage. Cyclic fatigue damage resulted in increases in collagen denaturation (1670/1640: 1.517 ± 0.043 vs 1.579 ± 0.021, p denaturation (r = 0.514, p denaturation was sensitive to cyclic fatigue damage but not 25kGy irradiation. Collagen denaturation was correlated with organic matrix-bound water, suggesting that denaturation of collagen to gelatinous form may expose more binding sites to water by unwinding the triple alpha chains. This research may eventually be useful to help identify allograft quality and more appropriately match donors to recipients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Cytosolic Double-Stranded DNA as a Damage-Associated Molecular Pattern Induces the Inflammatory Response in Rat Pancreatic Stellate Cells: A Plausible Mechanism for Tissue Injury-Associated Pancreatitis

    Directory of Open Access Journals (Sweden)

    Taichi Nakamura


    Full Text Available Pancreatitis is an inflammatory disease of unknown causes. There are many triggers causing pancreatitis, such as alcohol, common bile duct stone, virus and congenital or acquired stenosis of main pancreatic duct, which often involve tissue injuries. Pancreatitis often occurs in sterile condition, where the dead/dying pancreatic parenchymal cells and the necrotic tissues derived from self-digested-pancreas were observed. However, the causal relationship between tissue injury and pancreatitis and how tissue injury could induce the inflammation of the pancreas were not elucidated fully until now. This study demonstrates that cytosolic double-stranded DNA increases the expression of several inflammatory genes (cytokines, chemokines, type I interferon, and major histocompatibility complex in rat pancreatic stellate cells. Furthermore, these increase accompanied the multiple signal molecules genes, such as interferon regulatory factors, nuclear factor-kappa B, low-molecular-weight protein 2, and transporter associated with antigen processing 1. We suggest that this phenomenon is a plausible mechanism that might explain how cell damage of the pancreas or tissue injury triggers acute, chronic, and autoimmune pancreatitis; it is potentially relevant to host immune responses induced during alcohol consumption or other causes.

  19. Lactation Affects Isolated Mitochondria and Its Fatty Acid Composition but Has No Effect on Tissue Protein Oxidation, Lipid Peroxidation or DNA-Damage in Laboratory Mice

    Directory of Open Access Journals (Sweden)

    Teresa G. Valencak


    Full Text Available Linking peak energy metabolism to lifespan and aging remains a major question especially when focusing on lactation in females. We studied, if and how lactation affects in vitro mitochondrial oxygen consumption and mitochondrial fatty acid composition. In addition, we assessed DNA damage, lipid peroxidation and protein carbonyls to extrapolate on oxidative stress in mothers. As model system we used C57BL/6NCrl mice and exposed lactating females to two ambient temperatures (15 °C and 22 °C while they nursed their offspring until weaning. We found that state II and state IV respiration rates of liver mitochondria were significantly higher in the lactating animals than in non-lactating mice. Fatty acid composition of isolated liver and heart mitochondria differed between lactating and non-lactating mice with higher n-6, and lower n-3 polyunsaturated fatty acids in the lactating females. Surprisingly, lactation did not affect protein carbonyls, lipid peroxidation and DNA damage, nor did moderate cold exposure of 15 °C. We conclude that lactation increases rates of mitochondrial uncoupling and alters mitochondrial fatty acid composition thus supporting the “uncoupling to survive” hypothesis. Regarding oxidative stress, we found no impact of lactation and lower ambient temperature and contribute to growing evidence that there is no linear relationship between oxidative damage and lactation.

  20. Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid. (United States)

    Ghasemi, Simagol; Hosseini, Mahmoud; Feizpour, Azadeh; Alipour, Fatemeh; Sadeghi, Akram; Vafaee, Farzaneh; Mohammadpour, Toktam; Soukhtanloo, Mohammad; Ebrahimzadeh Bideskan, Alireza; Beheshti, Farimah


    The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated. The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar). In Morris water maze (MWM), the escape latency and traveled path in the Lead group were significantly higher while, the time spent in the target quadrant (Q1) was lower than Control. Both Lead-Gar and Lead-AA groups spent more times in Q1than to lead group. There were no significant differences in swimming speed between the groups. In passive avoidance (PA) test, the time latency for entering the dark compartment by Lead group was lower than Control. Treatment of the animals by AA and garlic significantly increased the time latency. In Lead group, the total thiol concentration in brain tissues was significantly lower while, MDA was higher than Control. Treatment by both garlic and AA increased total thiol concentrations and decreased MDA. Both garlic and AA decreased the lead content of brain tissues. It is suggested that treatment with garlic attenuates the learning and memory impairments due to lead exposure during juvenile rat growth which is comparable to AA. The possible mechanism may be due to its protective effects against brain tissues oxidative damage as well the lowering effects of brain lead content.

  1. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo


    to be similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing...

  2. Tissue damage after single high-dose intraoperative irradiation of the canine liver : Evaluation in time by means of radionuclide imaging and light microscopy

    NARCIS (Netherlands)

    Cromheecke, M; Piers, BA; Beekhuis, H; ter Veen, H; Sluiter, WJ; Hoekstra, HJ


    To establish the tolerance of liver tissue to single high-dose intraoperative irradiation, the histopathological changes in the canine liver after single high-dose intraoperative irradiation were investigated by means of radionuclide imaging and light microscopy, Intraoperative irradiation at doses

  3. Residual tissue post splenectomy detected by splenic scintillography with erythrocytes damaged by heat; Tejido residual postesplenectomia detectado por centellografia esplenica con eritrocitos danados por calor

    Energy Technology Data Exchange (ETDEWEB)

    Rivera B, B.; Garcia C, E.S.; Garcia O, J.R. [Centro Medico ABC, Departamento de Medicina Nuclear, Mexico, D.F. (Mexico)


    Feminine of 26 years old with diagnostic of purple thrombocytopenic idiopathic to those 4 years of age, tried with steroids and splenectomy at 11 years old. Pathway practically asymptomatic until 4 months ago she had presented asthenia, adynamia and general uneasiness, with platelet figures of 40,000 plat/microliter. It was carried out scintillographic study with damaged erythrocytes for post surgical remainder search. Its were took two-dimensional images and tomography by single photon emission (SPECT), being knitted splenic residual in area of anatomical projection of the spleen. (Author)

  4. Chemo Protective role of Moringa oleifera and its isolated Saponin against DMBA induced Tissue Damage in male mice: A Histopathological analysis


    Veena Sharma; Ritu Paliwal


    Moringa oleifera, a well known traditional medicinal plant from Moringaceae family has a remarkable reputation among the indigenous medical practitioners. The chemo protective role of hydroethanolic extract of Moringa oleifera and its isolated saponin against 7, 12- dimethyl-benz[a]anthracene (DMBA) intoxicated mice was investigated in the present study with the help of histopathological analysis of soft tissues (liver and kidney). The PAH 7, 12-dimethyl-benz[a]anthracene (DMBA) acts as a pot...

  5. M-CSF deficiency leads to reduced metallothioneins I and II expression and increased tissue damage in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, Milena; Poulsen, Christian; Carrasco, Javier


    6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray-matter astrocytes followed by a vigorous inflammatory response. Macrophage colony stimulating factor (M-CSF) is important during inflammation, and in order to further clarify the roles for M-CSF in neurodegener......6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray-matter astrocytes followed by a vigorous inflammatory response. Macrophage colony stimulating factor (M-CSF) is important during inflammation, and in order to further clarify the roles for M......-CSF is an important growth factor for coping with 6-AN-induced central nervous system damage and suggest that MT-I+II are likely to have a significant role....

  6. Correlation of hemorrhage, axonal damage and blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria

    Directory of Open Access Journals (Sweden)

    Jesse eGreiner


    Full Text Available Background: The retinal and brain histopathological findings in children who died from cerebral malaria (CM have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM.Methods: The features systematically compared in the same patient were: 1 clinical, gross and microscopic retinal hemorrhages with microscopic cerebral hemorrhages, 2 retinal and cerebral hemorrhage-associated and -unassociated axonal damage, and fibrinogen leakage, and 3 differences in the above features between the pathological categories of CM without microvascular pathology (CM1 and CM with microvascular pathology (CM2 in retina and brain. Results: Forty-seven patients were included: 7 CM1, 28 CM2 and 12 controls. In the 35 malaria cases retinal and cerebral pathology correlated in all features except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2 cases, the only differences were in the proportion of patients with hemorrhage-associated cerebral pathology, and this was expected, based on the definitions of CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated pathology was similar for the two groups. Comment: As postulated, histopathological features of hemorrhages, axonal damage and non-hemorrhage associated fibrinogen leakage correlated in the retina and brain of individual patients, although the difference in hemorrhages between the CM1 and CM2 groups was not consistently observed in the retina. These results help to underpin the utility of ophthalmoscopic examination and fundus findings to help in diagnosis and assessment of cerebral malaria patients, but may not help in distinguishing between CM1 and CM2 patients during life.

  7. Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array.

    Directory of Open Access Journals (Sweden)

    Songliu Hu

    Full Text Available To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, Ku heterodimeric regulatory complex 70-KD subunit (Ku70 and ataxia-telangiectasia mutated (ATM.The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC.The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009 and lymph node status (P = 0.004. The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012 and DNA-PKcs (P = 0.02. Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001 and Ku70 expression (P<0.001.Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.

  8. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage. (United States)

    Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa


    Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

  9. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.


    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  10. DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration. (United States)

    Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A


    Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

  11. Coenzyme Q10 for the Protection of Lacrimal Gland against High-Dose Radioiodine Therapy-Associated Oxidative Damage: Histopathologic and Tissue Cytokine Level Assessments in an Animal Model. (United States)

    Yakin, Mehmet; Eksioglu, Umit; Sadic, Murat; Koca, Gokhan; Ozkan-Uney, Guner; Yumusak, Nihat; Husniye Telek, Hande; Demir, Ayten; Yazihan, Nuray; Ornek, Firdevs; Korkmaz, Meliha


    To evaluate protective effect of coenzyme Q10 (CoQ10) in lacrimal glands against high-dose radioactive iodine (RAI)-associated oxidative damage. Thirty Wistar albino rats were randomly divided into three groups. Group 1 was the control group. Group 2 received 3 mCi/kg RAI via gastric gavage but no medication. Group 3 received 3 mCi/kg RAI via gastric gavage and 30 mg/kg/day CoQ10 intraperitoneally. CoQ10 was started at day one just before RAI administration and continued for five days. Seven days after RAI therapy, the animals were anesthetized and decapitated. Intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were removed bilaterally for histopathological and tissue cytokine level assessments. Abnormal lobular pattern, acinar fibrosis, lipofuscin-like accumulations, perivascular infiltration, cell size variation, abnormal cell outlines, irregular nucleus shapes in all lacrimal gland types (p < 0.05 for each), periductal fibrosis, periductal and periacinar fibrosis in EG (p = 0.01, 0.044, respectively) and in HG (p = 0.036, 0.044, respectively), periductal infiltration in HG (p = 0.039) and IG (p = 0.029), acinar atrophy in EG (p = 0.044), and cell shape variation in IG (p = 0.036) were observed more frequently in group 2 than in other groups. RAI caused significant increase in TNF-α, IL-6, nuclear factor kappa B, and total oxidant status, and decrease in IL-2, IL-10, and total antioxidant status levels (p < 0.05 for each). Addition of CoQ10 decreased all cytokine levels, increased nuclear factor kappa B levels more, and increased total antioxidant status levels significantly (p < 0.05 for each). RAI administration causes prominent inflammatory response in lacrimal glands. Addition of CoQ10 ameliorates the oxidative damage and protects lacrimal glands both in histopathological and tissue cytokine level assessments. Protection of lacrimal glands against oxidative damage may become a new era of CoQ10 use in the future.

  12. Study of damages induced by fungicide propiconazole on testicular tissue and process of spermatogenesis and protective effects of selenium in male Sprague Dawley rat

    Directory of Open Access Journals (Sweden)

    H Mohsenikouchesfehani


    Full Text Available Background & aim: Propiconazole is an herbal fungicide which is used as a tropical and systematic drug for fungal infection and also as an agricultural chemical for protection and preservation of fruits, vegetables and grains. The aim of this study was to assess the efficacy of fungicides propiconazol and possible protective effects of selenium on testes tissue. Methods: The present expremental trail study was conducted on forty rats which were divided into ten groups of four including control , sham (solvent of propiconazole, distilled water, solvent of selenium (normal saline and seven experimental groups : group 1 received 0.5 mg/kg/day of selenium, groups 2,3,4 received three doses of 10,50,75 mg/kg/day of Propiconazole, and groups 5,6,7 received three doses of 10, 50, 75 mg/kg/day of propiconazole with 0.5 mg/kg/day of selenium toevaluate. The administration was done intrapritoneal for two weeks in an alternatively fashion. After determining the level of LH, FSH, Testosterone, sperm was counted by hemocitometer. Data were analyzed by the SPSS software using ANOVA test. Results: No significant differences was observed in the level of hormones in the experimental groups2-7 compared with the control group, but the number of sertoli cells, spermatogonia , primary spermatocyte , spermatid and sperm decreased significantly in comparison with the control group (p<0.05. Conclusion: The decrease in numbers of counted sperm indicates that propiconazole has disrupted the production process of these cells and selenium was unable to improve that.

  13. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)


    Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

  14. Protection against brain tissues oxidative damage as a possible mechanism for the beneficial effects of Rosa damascena hydroalcoholic extract on scopolamine induced memory impairment in rats. (United States)

    Mohammadpour, Toktam; Hosseini, Mahmoud; Naderi, Asieh; Karami, Reza; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Vafaee, Farzaneh


    Hypnotic, analgesic, anticonvulsant, and antioxidant effects of Rosa damascena have been reported. This study, investigated the effect of R. damascena hydroalcoholic extract on memory performance in a scopolamine-induced memory impairment model. The rats were divided into control group received just saline; scopolamine group was treated by saline for 2 weeks, but was injected by scopolamine 30 minutes before each trial in Morris water maze test; treatment groups (scopolamine + extract 50; Sco + Ext 50) and (scopolamine + extract 250; Sco + Ext 250) were daily treated by 50 and 250 mg/kg of R. damascena extract (2 weeks) and were finally injected by scopolamine before each trial in Morris water maze. The brains were removed for biochemical measurements. Time latency and path length in the scopolamine group were higher than control (P < 0.01 to <0.001). Both treatment groups showed shorter traveled distance and time latency compared with scopolamine group (P < 0.05 to <0.001). Time spent in target quadrant by scopolamine group was lower than control (P < 0.05), while Sco + Ext 250 group spent longer time in target quadrant than scopolamine group (P < 0.05). Malondialdehyde concentrations in hippocampal and cortical tissues of scopolamine group were higher, while thiol concentrations were lower than control ones (P < 0.001). Treatment by both doses of the extract decreased the malondialdehyde concentration, while increased the thiol concentration (P < 0.05 to <0.001). The results of this study showed that the hydroalcoholic extract of R. damascena prevents scopolamine-induced memory deficits. This finding suggests that memory improvement may be in part due to the antioxidant effects.

  15. Skeletal muscle tissue engineering

    National Research Council Canada - National Science Library

    Bach, A. D; Beier, J. P; Stern‐Staeter, J; Horch, R. E


    The reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution...

  16. TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-α blockade

    Directory of Open Access Journals (Sweden)

    Karina Kroll-Palhares


    Full Text Available In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-α is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-α levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-α, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-α+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-α treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-α-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-α treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.

  17. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios (United States)

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.


    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  18. High-speed scanning ablation of dental hard tissues with a λ = 9.3 μm CO2 laser: adhesion, mechanical strength, heat accumulation, and peripheral thermal damage (United States)

    Nguyen, Daniel; Chang, Kwang; Hedayatollahnajafi, Saba; Staninec, Michal; Chan, Kenneth; Lee, Robert; Fried, Daniel


    CO2 lasers can be operated at high laser pulse repetition rates for the rapid and precise removal of dental decay. Excessive heat accumulation and peripheral thermal damage is a concern when using high pulse repetition rates. Peripheral thermal damage can adversely impact the mechanical strength of the irradiated tissue, particularly for dentin, and reduce the adhesion characteristics of the modified surfaces. The interpulpal temperature rise was recorded using microthermocouples situated at the roof of the pulp chamber on teeth that were occlusally ablated using a rapidly-scanned CO2 laser operating at 9.3 μm with a pulse duration of 10 to 15 μs and repetition rate of 300 Hz over a 2 min time course. The adhesion strength of laser treated enamel and dentin surfaces was measured for various laser scanning parameters with and without post-ablation acid etching using the single-plane shear test. The mechanical strength of laser-ablated dentin surfaces were determined via the four-point bend test and compared to control samples prepared with 320 grit wet sand paper to simulate conventional preparations. Thermocouple measurements indicated that the temperature remained below ambient temperature if water-cooling was used. There was no discoloration of either dentin or enamel laser treated surfaces, the surfaces were uniformly ablated, and there were no cracks visible. Four-point bend tests yielded mean mechanical strengths of 18.2 N (s.d. = 4.6) for ablated dentin and 18.1 N (s.d. = 2.7) for control (p > 0.05). Shear tests yielded mean bond strengths approaching 30 MPa for both enamel and dentin under certain irradiation conditions. These values were slightly lower than nonirradiated acid-etched control samples. Additional studies are needed to determine if the slightly lower bond strength than the acid-etched control samples is clinically significant. These measurements demonstrate that enamel and dentin surfaces can be rapidly ablated by CO2 lasers with minimal

  19. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva


    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  20. Laser/tissue interaction. (United States)

    Dederich, D N


    When laser light impinges on tissue, it can reflect, scatter, be absorbed, or transmit to the surrounding tissue. Absorption controls to a great degree the extent to which reflection, scattering and transmission occur, and wavelength is the primary determinant of absorption. The CO2 laser is consistently absorbed by most materials and tissues and the Nd-YAG laser wavelength is preferentially absorbed in pigmented tissues. The factors which determine the initial tissue effect include the laser wavelength, laser power, laser waveform, tissue optical properties, and tissue thermal properties. There are almost an infinite number of combinations of these factors possible, many of which would result in unacceptable damage to the tissues. This underscores the need to thoroughly test any particular combination of these factors on the conceptual, in-vitro, and in-vivo level before a treatment is offered.

  1. Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats. (United States)

    Abdel Moneim, Ahmed E; Ortiz, Francisco; Leonardo-Mendonça, Roberto C; Vergano-Villodres, Roberto; Guerrero-Martínez, Jose Antonio; López, Luis C; Acuña-Castroviejo, Darío; Escames, Germaine


    Naja haje envenomation is one of the leading causes of death due to snakebite. Antiserum therapy sometimes fails to provide enough protection against venom toxicity. In this study, we investigated the protective effects of melatonin against N. haje venom in rats. The animals were injected with venom (0.25mg/kg) and/or melatonin (10mg/kg) and compared with vehicle-treated rats. There was oxidative/nitrosative damage and apoptosis in the liver, heart, and kidneys of venom-injected rats. Melatonin counteracted the increased lipoperoxidation and nitric oxide, prevented decreased glutathione peroxidase and reductase activity, reduced the glutathione disulfide/glutathione (GSSG/GSH) ratio, and maintained the GSH pool. Furthermore, melatonin administration was associated with a reduction of apoptosis, which was increased in venom-injected rats. Overall, these results suggest that melatonin mitigates oxidative/nitrosative stress in venom-induced cardio-hepato-renal injury in rats. Our results suggest that melatonin treatment may ameliorate some of the effects of N. haje envenomation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Regulating Damage from Sterile Inflammation: A Tale of Two Tolerances. (United States)

    Wu, Shin-Rong; Reddy, Pavan


    The severity of immunopathology from non-infectious inflammation is mainly understood and is managed by targeting immune cells. However, the role of target tissues in determining damage severity has been largely overlooked. Here, we discuss the concept of 'tissue tolerance' for tissue-intrinsic programs that ameliorate organ damage in the setting of sterile immunopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Irradiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Howe, L.M


    There is considerable interest in irradiation effects in intermetallic compounds from both the applied and fundamental aspects. Initially, this interest was associated mainly with nuclear reactor programs but it now extends to the fields of ion-beam modification of metals, behaviour of amorphous materials, ion-beam processing of electronic materials, and ion-beam simulations of various kinds. The field of irradiation damage in intermetallic compounds is rapidly expanding, and no attempt will be made in this chapter to cover all of the various aspects. Instead, attention will be focused on some specific areas and, hopefully, through these, some insight will be given into the physical processes involved, the present state of our knowledge, and the challenge of obtaining more comprehensive understanding in the future. The specific areas that will be covered are: point defects in intermetallic compounds; irradiation-enhanced ordering and irradiation-induced disordering of ordered alloys; irradiation-induced amorphization.

  4. Collateral Damage (United States)


    Revised, October 1971. 3.13 Cockayne , Z.E., and E.V. Lofgren, "Tactical Implictions of Air B6a=1 ,ariations from Nuclear Weapon Tests," SAIReport SAI...radiation lethality is characterized by three syndromes depending upon dose (Ref. 5.34): * Hematopoietic syndrome - whole-body doses of less than 500 rads...Gastrointestinal syndrome - whole-body doses between about 500 and 2000 rads 5-16 ,ew.tologic oep.$$ion 14:5 Ot~er/ .BD so(%.CRP) Tissue Kermin (free

  5. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail:; Migliore, Lucia, E-mail:


    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  6. Sensing damage by the NLRP3 inflammasome

    NARCIS (Netherlands)

    Leemans, Jaklien C.; Cassel, Suzanne L.; Sutterwala, Fayyaz S.


    The NLRP3 inflammasome is activated in response to a variety of signals that are indicative of damage to the host including tissue damage, metabolic stress, and infection. Upon activation, the NLRP3 inflammasome serves as a platform for activation of the cysteine protease caspase-1, which leads to

  7. DNA from keratinous tissue

    DEFF Research Database (Denmark)

    Bengtsson, Camilla F.; Olsen, Maja E.; Brandt, Luise Ørsted


    Keratinous tissues such as nail, hair, horn, scales and feather have been used as a source of DNA for over 20 years. Particular benefits of such tissues include the ease with which they can be sampled, the relative stability of DNA in such tissues once sampled, and, in the context of ancient...... genetic analyses, the fact that sampling generally causes minimal visual damage to valuable specimens. Even when freshly sampled, however, the DNA quantity and quality in the fully keratinized parts of such tissues is extremely poor in comparison to other tissues such as blood and muscle – although little...... systematic research has been undertaken to characterize how such degradation may relate to sample source. In this review paper we present the current understanding of the quality and limitations of DNA in two key keratinous tissues, nail and hair. The findings indicate that although some fragments of nuclear...

  8. Photothermal damage prediction of laser interstitial thermotherapy (United States)

    Li, Xiaoxia; Fan, Shifu; Zhao, Youquan


    An improved scattering optical model was developed under cylindrical coordinate to simulate the thermal effect of diffusing applicator in laser interstitial thermotherapy (LITT). The thermal damage was calculated by finite element method (FEM) using Pennes bio-heat transfer equation and Arrhenius injury integral formula. The numerical results showed that the scattering can considerably influence the evaluation of the lesion area, and the relationship between application powers or time and resulting tissue thermal damage was nonlinear. Although usually applying relatively low power can avoid tissue charring, rather higher power is recommended because it is indispensable to achieve necessary damage threshold and the therapy time can be shortened.

  9. Radiation damage in electron cryomicroscopy. (United States)

    Baker, Lindsay A; Rubinstein, John L


    In an electron microscope, the electron beam used to determine the structures of biological tissues, cells, and molecules destroys the specimen as the image is acquired. This destruction occurs before a statistically well-defined image can be obtained and is consequently the fundamental limit to resolution in biological electron cryomicroscopy (cryo-EM). Damage from the destructive interaction of electrons with frozen-hydrated specimens occurs in three stages: primary damage, as electrons ionize the sample, break bonds, and produce secondary electrons and free radicals; secondary damage, as the secondary electrons and free radicals migrate through the specimen and cause further chemical reactions; and tertiary damage, as hydrogen gas is evolved within the sample, causing gross morphological changes to the specimen. The deleterious effects of radiation are minimized in cryo-EM by limiting the exposure of the specimen to incident electrons and cooling the sample to reduce secondary damage. This review emphasizes practical considerations for minimizing radiation damage, including measurement of electron exposure, estimation of absorbed doses of energy, selection of microscope voltage and specimen temperature, and selection of electron exposure to optimize images. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Impact damage development in damaged composite materials (United States)

    Duke, J. C., Jr.; Kiernan, M. T.


    A procedure for predicting the nature of impact damage development based on the measured acousto-ultrasonic (AU) response of fiber reinforced crossply laminates with or without damage is described. Results of AU evaluation as well as penetrant enhanced radiographs of damaged laminates are presented.

  11. Studies on the strategies of minimizing radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hee Yong; Sohn, Young Sook


    We studied on the strategies of minimizing radiation damage in animal system. To this end we studied following areas of research (1) mechanisms involved in bone marrow damage after total body irradiation, (2) extraction of components that are useful in protecting hematopoietic system from radiation damage, (3) cell therapy approach in restoring the damaged tissue, (4) development of radioprotective chemical reagent, and (5) epidemiological study on the population that had been exposed to radiation.

  12. Avaliação da expressão tecidual do gene de reparo MLH1 e dos níveis de dano oxidativo ao DNA em doentes com câncer colorretal Evaluation of expression of mismatch repair gene MLH1 and levels of oxidative DNA damage in normal and neoplastic tissues of patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Carlos Augusto Real Martinez


    form the DNA, allowing mutations in controlling genes of the cell cycle. The cells have a defense system represented by the DNA mismatch repair genes that correct the errors of matching prevent the development of DNA mutations. Few studies have evaluated the relationship between oxidative DNA damage and the tissue expression of mismatch repair genes. AIM: The aim of the present study was evaluate the levels of oxidative DNA and the tissue expression of MLH1 mismatch repair gene in the cells of normal and neoplastic colonic mucosa of patients with colorectal cancer. MATERIAL AND METHODS: Were studied 44 patients with diagnosis of colorectal adenocarcinoma. Were excluded patients with hereditary colorectal cancer, with colorectal cancer associate with inflammatory bowel diseases and those undergoing neoadjuvant radioquimiotherapy. To evaluate the levels of oxidative DNA damage was used the single cell gel electrophoresis (comet assay evaluating 100 cells obtained from normal and neoplastic tissues. For the evaluation of the tissue expression of MLH1 gene was employed the technique of polymerase chain reaction in real time (RT-PCR with primer specifically designed for MLH1 gene. The comparison among the levels of DNA oxidative stress and expression of MLH1 mismatch repair gene in normal and neoplastic tissues was done by Student t test adopting a significance level of 5% (p< 0.05. RESULTS: The levels of oxidative DNA damage in tumor tissue were significantly higher when compared to the level of the normal tissue (p = 0.0001. The tissue expression of MLH1 mismatch repair gene in tumor tissue was significantly lower when compared to normal tissue (p=0.02. CONCLUSION: The mismatch repair gene MLH1 are less expressed in tumor tissue and inversely related to levels of oxidative DNA damage.

  13. Impact of static cold storage VS hypothermic machine preservation on ischemic kidney graft: inflammatory cytokines and adhesion molecules as markers of ischemia/reperfusion tissue damage. Our preliminary results. (United States)

    Tozzi, Matteo; Franchin, Marco; Soldini, Gabriele; Ietto, Giuseppe; Chiappa, Corrado; Maritan, Emanuele; Villa, Francesca; Carcano, Giulio; Dionigi, Renzo


    At the present time, deceased heart-beating donor kidney allografts are usually stored cold. Extended-criteria donor (ECD) grafts show higher sensitivity to ischemia-reperfusion damage than standard kidneys. The increasing use of marginal organs in clinical transplantation urgently requires a more effective preservation system. Pulsatile hypothermic machine perfusion has shown major advantages over static cold storage in terms of reduced organ injury during preservation and improved early graft function. This preliminary study aims to compare pulsatile hypothermic machine perfusion and static cold storage of kidney allografts, outlining differences in the levels of early inflammatory cytokines (TNF-α, IL-2 and IL-1β) and soluble intracellular adhesion molecule (sICAM-1) in perfusion and preservation liquid. Copyright © 2013 Elsevier Ltd and Surgical Associates Ltd. All rights reserved.

  14. , 1584), increase in lean body mass (ID 1579, 1582, 1583), increase in muscle strength (ID 1578, 1583, 1587), increase in endurance performance (ID 1580, 1581), skeletal muscle tissue repair (ID 1586) and faster recovery from muscle fatigue after exercise (ID 1576, 1585) pursuant to Article 13, EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to β-hydroxy β-methylbutyrate monohydrate (HMB) alone or in combination with α-ketoisocaproic acid (KIC) and reduction of muscle tissue damage during exercise (ID 1577

    DEFF Research Database (Denmark)

    Tetens, Inge

    and faster recovery from muscle fatigue after exercise. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food constituent...... claims in relation to β-hydroxy β-methylbutyrate monohydrate (HMB) alone or in combination with α-ketoisocaproic acid (KIC) and reduction of muscle tissue damage during exercise, increase in lean body mass, increase in muscle strength, increase in endurance performance, skeletal muscle tissue repair...

  15. Tissue tests

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.


    Tissue tests are widely used in horticulture practice and have in comparison with soil or substrate testing advantages as well disadvantages in comparison with soil testing. One of the main advantages of tissue tests is the certainty that analysed nutrients in plant tissues are really present in the

  16. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.


    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  17. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis. (United States)

    Honarpisheh, Mohsen; Desai, Jyaysi; Marschner, Julian A; Weidenbusch, Marc; Lech, Maciej; Vielhauer, Volker; Anders, Hans-Joachim; Mulay, Shrikant R


    The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively. © 2016 The Author(s).

  18. Combat damage control surgery. (United States)

    Blackbourne, Lorne H


    Although the use of damage control surgery for blunt and penetrating injury has been widely reported and defined, the use of damage control surgery on the battlefield (combat damage control surgery) has not been well detailed. Damage control surgery is now well established as the standard of care for severely injured civilian patients requiring emergent laparotomy in the United States. The civilian damage control paradigm is based on a "damage control trilogy." This trilogy comprises an abbreviated operation, intensive care unit resuscitation, and a return to the operating room for the definitive operation. The goal of damage control surgery and the triology is avoidance of irreversible physiological insult termed the lethal triad. The lethal triad comprises the vicious cycle of hypothermia, acidosis, and coagulopathy. Although the damage control model involves the damage control trilogy, abbreviated operation, intensive care unit resuscitation, and definitive operation, all in the same surgical facility, the combat damage control paradigm must incorporate global evacuation through several military surgical facilities and involves up to ten stages to allow for battlefield evacuation, surgical operations, multiple resuscitations, and transcontinental transport. Combat damage control surgery represents many unique challenges for those who care for the severely injured patients in a combat zone.

  19. Caracterização de seqüelas subseqüentes à punção folicular em bovinos Characterization of tissue damages after ovum pick-up in bovine

    Directory of Open Access Journals (Sweden)

    João Henrique M. Viana


    oocyte yield (r=0.53; P<0.05. Histopathologic evaluation revealed scar tissue, inflammatory cell infiltration and presence of luteal tissue dispersed within the ovarian stroma.

  20. Tissue types (image) (United States)

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  1. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans


    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an

  2. Gradient polymers for tissue engineering

    NARCIS (Netherlands)

    Klein Gunnewiek, Michel


    With increasing life expectancy, there is an constant demand for finding solutions to restore damaged or diseased tissues and organs. Regenerative medicine holds the promise to create continuous body-part replacements through the combination of cells, biological factors, and synthetic scaffolds.

  3. Damage signals in the insect immune response

    Directory of Open Access Journals (Sweden)

    Robert eKrautz


    Full Text Available Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (nonself patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have afflicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes.

  4. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula


    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  5. Animal damage management handbook. (United States)

    Hugh C. Black


    This handbook treats animal damage management (ADM) in the West in relation to forest, range, and recreation resources; predator management is not addressed. It provides a comprehensive reference of safe, effective, and practical methods for managing animal damage on National Forest System lands. Supporting information is included in references after each chapter and...

  6. Animal damage to birch (United States)

    James S. Jordan; Francis M. Rushmore


    A relatively few animal species are responsible for most of the reported damage to the birches. White-tailed deer, yellow-bellied sapsuckers, porcupines, moose, and hares are the major animals involved. We will review reports of damage, discuss the underlying causes, and describe possible methods of control. For example, heavy deer browsing that eliminates birch...

  7. DNA damage response

    NARCIS (Netherlands)

    G. Giglia-Mari (Giuseppina); A. Zotter (Angelika); W. Vermeulen (Wim)


    textabstractStructural changes to DNA severely affect its functions, such as replication and transcription, and play a major role in age-related diseases and cancer. A complicated and entangled network ofDNA damage response (DDR) mechanisms, including multiple DNA repair pathways, damage tolerance

  8. Tree damage and mycotrophy

    Energy Technology Data Exchange (ETDEWEB)

    Heyser, W.; Iken, J.; Meyer, F.H.


    Tree species that are particularly endangered in our forests are characterized by the fact that they live in an obligatory symbiosis with ectomycorrhiza fungii. In verifying which tree species appear to be more damaged or less severely damaged, a conspicuous phenomenon noted was that the tree species exhibiting slight symptoms of damage or none at all included such ones as form mycorrhizas facultatively or dispense with mycorrhizas, e.g. Acer, Aesculus, Fraxinus, Populus, Salix. Given that trees in municipal gardens reflect the development and extent of damage in a way similar to forests, and given also that much greater numbers of tree species are often cultured in parks of this type, the latter were considered particularly suited to examine the question of whether a relationship exists between mycotrophy and the severity of damage.

  9. Hydrostatic Pressure in Articular Cartilage Tissue Engineering: From Chondrocytes to Tissue Regeneration


    Elder, Benjamin D.; Athanasiou, Kyriacos A.


    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) ...

  10. Coronal tissue loss in endodontically treated teeth. (United States)

    Sulaiman, A O; Shaba, O P; Dosumu, O O; Ajayi, D M


    To categorize the endodontically treated teeth according to the extent of coronal tissue loss in order to determine the appropriate restoration required. A two year descriptive study was done at the Conservative Clinic of the Department of Restorative Dentistry, Dental Centre, University College Hospital, Ibadan. Successful endodontically treated teeth were assessed and categorized according to the extent of tissue loss based on standard criteria proposed by Smith and Schuman. Two hundred and ninety endodontically treated teeth were assessed for success both clinically and radiographically. Eighty (27.6%) were anterior teeth, 78 (26.9%) were premolars while 132 (45.5%) were molars. Dental caries was found to be the most common (61.4%) indication for endodontic treatment and caused more coronal tissue damage (moderate and significant) when compared with other indications for endodontic treatment. Two hundred and twenty seven (78.3%) endodontically treated teeth had moderate coronal tissue loss, 41 (14.1%) had minimal damage while 22 (7.6%) had significant tissue damage. Dental caries was the most common indication for endodontic treatment of the posterior teeth while trauma was the most common indication for the anterior teeth. Majority of the endodontically treated teeth that were evaluated for tissue loss had moderate coronal tissue damage. It is therefore recommended that proper and prompt evaluation of the remaining coronal tooth tissue following successful endodontic treatment be carried out in order to determine the appropriate definitive restoration required that will be easy for the clinician and less expensive to the patients.

  11. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

    Directory of Open Access Journals (Sweden)

    Cinthya Kimori Okamoto


    Full Text Available Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP. Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.

  12. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,


    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  13. Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability via a DAMPs/TLR-4 Mediated Pathway (United States)

    Rucavado, Alexandra; Nicolau, Carolina A.; Escalante, Teresa; Kim, Junho; Herrera, Cristina; Gutiérrez, José María; Fox, Jay W.


    Viperid snakebite envenomation is characterized by inflammatory events including increase in vascular permeability. A copious exudate is generated in tissue injected with venom, whose proteomics analysis has provided insights into the mechanisms of venom-induced tissue damage. Hereby it is reported that wound exudate itself has the ability to induce increase in vascular permeability in the skin of mice. Proteomics analysis of exudate revealed the presence of cytokines and chemokines, together with abundant damage associated molecular pattern molecules (DAMPs) resulting from both proteolysis of extracellular matrix and cellular lysis. Moreover, significant differences in the amounts of cytokines/chemokines and DAMPs were detected between exudates collected 1 h and 24 h after envenomation, thus highlighting a complex temporal dynamic in the composition of exudate. Pretreatment of mice with Eritoran, an antagonist of Toll-like receptor 4 (TLR4), significantly reduced the exudate-induced increase in vascular permeability, thus suggesting that DAMPs might be acting through this receptor. It is hypothesized that an “Envenomation-induced DAMPs cycle of tissue damage” may be operating in viperid snakebite envenomation through which venom-induced tissue damage generates a variety of DAMPs which may further expand tissue alterations. PMID:27886127

  14. Tissue Classification

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, David Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    The project began as a e ort to support InLight and Lumidigm. With the sale of the companies to a non-New Mexico entity, the project then focused on supporting a new company Medici Technologies. The Small Business (SB) is attempting to quantify glucose in tissue using a series of short interferometer scans of the nger. Each scan is produced from a novel presentation of the nger to the device. The intent of the project is to identify and, if possible, implement improved methods for classi cation, feature selection, and training to improve the performance of predictive algorithms used for tissue classi cation.

  15. Diabetes and nerve damage (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  16. LSD and Genetic Damage (United States)

    Dishotsky, Norman I.; And Others


    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  17. Levels of oxidative damage and lipid peroxidation in thyroid neoplasia.

    LENUS (Irish Health Repository)

    Young, Orla


    BACKGROUND: This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia. METHODS: Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue. RESULTS: Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status. CONCLUSION: High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

  18. Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik


    Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here........ When biochemical signs of cerebral ischemia progressed, i.v. infusion of prostacyclin was started....

  19. Regeneration of damaged osteoporotic bone tissue with synthetic biomaterials

    Directory of Open Access Journals (Sweden)

    Petrović Nenad D.


    Full Text Available In some cases in oral and maxillofacial surgery, bone regeneration is required in large quantities. One of these cases is osteoporosis. This paper aims to show the new approach to solving this problem of impaired healing of bone defects in the jaw, as well as in other bones, with the use of synthetic biomaterials whose properties resemble the natural bone. Latest development in this area present an effort to create local drug-delivery systems for BMPs and growth factors, direct delivery of MSCs, as well as scaffolds for osteoconduction and also to utilize nanotechnology to synthesize composite biomaterials, predominantly based on HAp and polymers, that would mimic the natural bone nanocomposite architecture. There is also a tendency to create injectable biomaterials for simplified application.

  20. Platelets Orchestrate Remote Tissue Damage After Mesenteric Ischemia-Reperfusion (United States)


    J Trans- plant 5: 1186–1193, 2005. 9. Chen J, Crispin JC, Dalle LJ, Tsokos GC. A novel inhibitor of the alternative pathway of complement attenuates...and protec- tion against Listeria monocytogenes challenge. Blood 111: 3684–3691. 2008. 25. Elzey BD, Tian J, Jensen RJ, Swanson AK, Lees JR, Lentz SR

  1. Assessing Tropical Cyclone Damage (United States)

    Done, J.; Czajkowski, J.


    Landfalling tropical cyclones impact large coastal and inland areas causing direct damage due to winds, storm-surge flooding, tornadoes, and precipitation; as well as causing substantial indirect damage such as electrical outages and business interruption. The likely climate change impact of increased tropical cyclone intensity, combined with increases in exposure, bring the possibility of increased damage in the future. A considerable amount of research has focused on modeling economic damage due to tropical cyclones, and a series of indices have been developed to assess damages under climate change. We highlight a number of ways this research can be improved through a series of case study analyses. First, historical loss estimates are revisited to properly account for; time, impacted regions, the source of damage by type, and whether the damage was direct/indirect and insured/uninsured. Second, the drivers of loss from both the socio-economic and physical side are examined. A case is made to move beyond the use of maximum wind speed to more stable metrics and the use of other characteristics of the wind field such as direction, degree of gustiness, and duration is explored. A novel approach presented here is the potential to model losses directly as a function of climate variables such as sea surface temperature, greenhouse gases, and aerosols. This work is the first stage in the development of a tropical cyclone loss model to enable projections of losses under scenarios of both socio-economic change (such as population migration or altered policy) and physical change (such as shifts in tropical cyclone activity one from basin to another or within the same basin).

  2. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C


    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  3. Indirect identification of damage functions from damage records

    CERN Document Server

    Steinhäuser, J Micha; Kropp, Jürgen P


    In order to assess future damage caused by natural disasters, it is desirable to estimate the damage caused by single events. So called damage functions provide -- for a natural disaster of certain magnitude -- a specific damage value. However, in general, the functional form of such damage functions is unknown. We study the distributions of recorded flood damages on extended scales and deduce which damage functions lead to such distributions when the floods obey Generalized Extreme Value statistics and follow Generalized Pareto distributions. Based on the finding of broad damage distributions we investigate two possible functional forms to characterize the data. In the case of Gumbel distributed extreme events, (i) a power-law distribution density with an exponent close to 2 (Zipf's law) implies an exponential damage function; (ii) stretched exponential distribution densities imply power-law damage functions. In the case of Weibull (Frechet) distributed extreme events we find correspondingly steeper (less st...

  4. Identification of inclusions in lung tissue with a Raman microprobe

    NARCIS (Netherlands)

    Buiteveld, H.; de Mul, F.F.M.; Mud, J.; Greve, Jan


    Inhaled particles smaller than 4 μm can cause damage to lung tissue, a disease called silicosis. We present an investigation on the use of a Raman microspectrometer for the identification of inclusions in lung tissue. We measured Raman spectra of such inclusions in lung tissue of a patient whose

  5. mapDamage

    DEFF Research Database (Denmark)

    Ginolhac, Aurélien; Rasmussen, Morten; Gilbert, Tom


    Ancient DNA extracts consist of a mixture of contaminant DNA molecules, most often originating from environmental microbes, and endogenous fragments exhibiting substantial levels of DNA damage. The latter introduce specific nucleotide misincorporations and DNA fragmentation signatures in sequencing...... in embedded R script in order to detect typical patterns of genuine ancient DNA sequences. Availability and implementation: The Perl script mapDamage is freely available with documentation and example files at The script requires prior installation...

  6. The influence of freezing and tissue porosity on the material properties of vegetable tissues

    CERN Document Server

    Ralfs, J D


    Tissue porosity and fluid flow have been shown to be important parameters affecting the mechanical and sensorial behaviour of edible plant tissues. The quantity of fluid and the manner with which it was released on compression of the plant tissue were also important regarding the sensory perception and a good indication of any structural damage resulting from freezing, for example. Potato, carrot and Chinese water chestnut were used to study the effects freezing has on model plant tissues. Mechanical and structural measurements of the plant tissue were correlated with sensory analysis. Conventional freezing was shown to cause severe structural damage predominantly in the form of cavities between or through cells, resulting in decreases in mechanical strength and stiffness, and samples that were perceived in the mouth as 'soft' and 'wet'. The location and size of the cavities formed from ice crystals, depended on the particular plant tissue being frozen, the processing it was subjected to prior to freezing, th...

  7. Cancer risk and oxidative DNA damage in man

    DEFF Research Database (Denmark)

    Loft, Steffen; Poulsen, H E


    of ROS. These include oxidative damage to DNA, which experimental studies in animals and in vitro have suggested are an important factor in carcinogenesis. Despite extensive repair oxidatively modified DNA is abundant in human tissues, in particular in tumors, i.e., in terms of 1-200 modified nucleosides...... per 10(5) intact nucleosides. The damaged nucleosides accumulate with age in both nuclear and mitochondrial DNA. The products of repair of these lesions are excreted into the urine in amounts corresponding to a damage rate of up to 10(4) modifications in each cell every day. The most abundant...... and their biological significance less apparent. The biomarkers for study of oxidative DNA damage in humans include urinary excretion of oxidized nucleosides and bases as repair products and modifications in DNA isolated from target tissue or surrogate cells, such as lymphocytes. These biomarkers reflect the rate...

  8. Cartilage tissue engineering: its potential and uses. (United States)

    Kuo, Catherine K; Li, Wan-Ju; Mauck, Robert L; Tuan, Rocky S


    The prevalent nature of osteoarthritis, a cartilage degenerative disease that results in the erosion of joint surfaces and loss of mobility, underscores the importance of developing functional articular cartilage replacement. Recent research efforts have focused on tissue engineering as a promising approach for cartilage regeneration and repair. Tissue engineering is a multidisciplinary research area that incorporates both biological and engineering principles for the purpose of generating new, living tissues to replace the diseased/damaged tissue and restore tissue/organ function. This review surveys and highlights the current concepts and recent progress in cartilage tissue engineering, and discusses the challenges and potential of this rapidly advancing field of biomedical research. Cartilage tissue engineering is critically dependent on selection of appropriate cells (differentiated or progenitor cells); fabrication and utilization of biocompatible and mechanically suitable scaffolds for cell delivery; stimulation with chondrogenically bioactive molecules introduced in the form of recombinant proteins or via gene transfer; and application of dynamic, mechanical loading regimens for conditioning of the engineered tissue constructs, including the design of specialized biomechanically active bioreactors. Cell selection, scaffold design and biological stimulation remain the challenges of function tissue engineering. Successful regeneration or replacement of damaged or diseased cartilage will depend on future advances in our understanding of the biology of cartilage and stem cells and technological development in engineering.

  9. Ghrelin against alendronate-induced gastric damage in rats. (United States)

    Işeri, S O; Sener, G; Yüksel, M; Contuk, G; Cetinel, S; Gedik, N; Yegen, B C


    Alendronate sodium, a primary amino bisphosphonate, is widely used in the treatment of various diseases that are associated with bone resorption, such as postmenopausal osteoporosis and Paget's disease of bone. Although the adverse effects of biphosphonates on the gastrointestinal system have been demonstrated in experimental and clinical studies, the exact mechanisms underlying this damage are not clear yet. Ghrelin, a 28 amino acid peptide produced predominantly by the stomach, was shown to exert a potent protective action on the stomach of rats exposed to ethanol or stress. Our objective was to evaluate the possible anti-oxidant and anti-inflammatory effects of ghrelin against alendronate-induced gastric damage. Wistar albino rats were administered alendronate (20 mg/kg) by gavage for 4 days, along with either ghrelin (10 ng/kg per day) or saline given i.p. After decapitation, stomach tissues were removed for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and tissue collagen content, while the extent of tissue damage was analyzed microscopically. Formation of reactive oxygen species was determined by chemiluminesence using a luminol probe in fresh gastric tissues. Serum tumor necrosis factor (TNF-alpha) and lactate dehydrogenase levels were assessed in trunk blood. Oral administration of alendronate-induced significant gastric damage, accompanied by increased MPO activity, collagen content, MDA and luminol levels (P ghrelin treatment reversed these alterations (P ghrelin ameliorates this damage by its possible antioxidant and anti-inflammatory properties.

  10. Nowcasting Disaster Damage


    Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel


    Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and intensity of natural disasters due to climate change. And during such events, citizens are turning to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. Additionally, spatiotemporal distri...

  11. Heart Regeneration with Engineered Myocardial Tissue (United States)

    Bajpai, Vivek K.; Andreadis, Stelios T.; Murry, Charles E.


    Heart disease is the leading cause of morbidity and mortality worldwide, and regenerative therapies that replace damaged myocardium could benefit millions of patients annually. The many cell types in the heart, including cardiomyocytes, endothelial cells, vascular smooth muscle cells, pericytes, and cardiac fibroblasts, communicate via intercellular signaling and modulate each other’s function. Although much progress has been made in generating cells of the cardiovascular lineage from human pluripotent stem cells, a major challenge now is creating the tissue architecture to integrate a microvascular circulation and afferent arterioles into such an engineered tissue. Recent advances in cardiac and vascular tissue engineering will move us closer to the goal of generating functionally mature tissue. Using the biology of the myocardium as the foundation for designing engineered tissue and addressing the challenges to implantation and integration, we can bridge the gap from bench to bedside for a clinically tractable engineered cardiac tissue. PMID:24819474

  12. [Vital pulp therapy of damaged dental pulp]. (United States)

    Xuedong, Zhou; Dingming, Huang; Jianguo, Liu; Zhengwei, Huang; Xin, Wei; Deqin, Yang; Jin, Zhao; Liming, Chen; Lin, Zhu; Yanhong, Li; Jiyao, Li


    The development of an expert consensus on vital pulp therapy can provide practical guidance for the improvement of pulp damage care in China. Dental pulp disease is a major type of illness that adversely affects human oral health. Pulp capping and pulpotomy are currently the main methods for vital pulp therapy. Along with the development of minimal invasion cosmetic dentistry, using different treatment technologies and materials reasonably, preserving healthy tooth tissue, and extending tooth save time have become urgent problems that call for immediate solution in dental clinics. This paper summarizes the experiences and knowledge of endodontic experts. We develop a clinical path of vital pulp therapy for clinical work by utilizing the nature, approach, and degree of pulp damage as references, defense and self-repairing ability of pulp as guidance, and modern technologies of diagnosis and treatment as means.

  13. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D


    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  14. Grounding Damage to Conventional Vessels

    DEFF Research Database (Denmark)

    Lützen, Marie; Simonsen, Bo Cerup


    regulations for design of bottom compartment layout with regard to grounding damages are largely based on statistical damage data. New and updated damage statistics holding 930 grounding accident records has been investigated. The bottom damage statistics is compared to current regulations for the bottom......The present paper is concerned with rational design of conventional vessels with regard to bottom damage generated in grounding accidents. The aim of the work described here is to improve the design basis, primarily through analysis of new statistical data for grounding damage. The current...... for the relation between the amount of deformed structure and the energy absorption. Finally, the paper shows how damage statistics for existing, conventional vessels can be used together with theoretical prediction methods for determining grounding damage distributions for new vessel types not included...

  15. Cell damage after shock. (United States)

    Barber, A E; Shires, G T


    Hypoperfusion of tissue results in cell membrane dysfunction. Normally, the cell membrane serves to preserve the milieu interior through the maintenance of a negative charge or membrane potential. Maintenance of a negative membrane potential across the cell membrane serves as a semipermeable barrier, preserving the balance of intra- and extracellular electrolytes and water.

  16. DNA damage checkpoint recovery and cancer development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiyong [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Zhang, Xiaoshan [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States); Teng, Lisong, E-mail: [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Legerski, Randy J., E-mail: [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States)


    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  17. Network Using Damage Progression Trends

    Directory of Open Access Journals (Sweden)

    C. J. Keulen


    damage (RAPID technique. Two damage metrics are used with the algorithm and a comparison is made to the more commonly used signal difference coefficient (SDC metric. Best case results show that damage is detected within 12 mm. The algorithm is also run on a more sparse network with no damage detection, therefore indicating that the selected arrangement is the most sparse arrangement with this configuration.

  18. DNA damage and mutation. Types of DNA damage


    Chakarov, Stoyan; Petkova, Rumena; Russev,George Ch; Zhelev, Nikolai


    This review outlines the basic types of DNA damage caused by exogenous and endogenous factors, analyses the possible consequences of each type of damage and discusses the need for different types of DNA repair. The mechanisms by which a minor damaging event to DNA may eventually result in the introduction of heritable mutation/s are reviewed. The major features of the role of DNA damage in ageing and carcinogenesis are outlined and the role of iatrogenic DNA damage in human health and dis...

  19. DNA damage and mutation. Types of DNA damage (United States)

    Chakarov, Stoyan; Petkova, Rumena; Russev, George Ch; Zhelev, Nikolai


    This review outlines the basic types of DNA damage caused by exogenous and endogenous factors, analyses the possible consequences of each type of damage and discusses the need for different types of DNA repair. The mechanisms by which a minor damaging event to DNA may eventually result in the introduction of heritable mutation/s are reviewed. The major features of the role of DNA damage in ageing and carcinogenesis are outlined and the role of iatrogenic DNA damage in human health and disease (with curative intent as well as a long-term adverse effect of genotoxic therapies) are discussed in detail.

  20. Morphological studies of laser-induced photoacoustic damage (United States)

    Flotte, Thomas J.; Yashima, Yutaka; Watanabe, Shinichi; McAuliffe, Daniel J., Sr.; Jacques, Steven L.


    Argon-fluoride excimer laser ablation of stratum comeum causes deeper tissue damage than expected for thermal or photochemical mechanisms, suggesting thatphotoacoustic waves have arole in tissue damage. Laserirradiation (193 nm, 14 ns pulses, 1-2 Hz) attworadiantexposures, 60 and 160 mJ/cm2perpulse was usedto ablate the stratumcomeumofskin. Light and electron microscopy ofimmediate biopsies demonstrated damage to fibroblasts as deep as 88 and 220 jun, respectively, below the ablation site. Ablation throughwaterwas usedtoinertially confine the ablation zone. Partial ablationofs.c. through airproducedno damage, whereas partial ablation through water damaged skin to amean depth of 1 14.5 8.8( Full thickness ablation of s.c. through air and water produced damage zones measuring 192.2 16.2 and 293.0 71.6 rim, respectively (p mechanism ofdamage. The depths ofdamage for thelarge spot, line, and small spots were 43 1 164 urn, 269 96xni, andno damage. The spot size dependence ofthedepthofdamage is consistentwiththe geometric attenuation one would expect to be present from a pressure wave related phenomena. Sequential biopsies were taken over a 7 day period for light and transmission electron microscopy. At 24 hours, there was necrosis of the epidermis and papillary dermis subjacent to the ablation site, with neutrophils surrounding and demarcating the affected area. The necrotic zone sloughedby48 hours. Thereepithelializationwas completeby7 days. The sequenceofrepairis similartoknife wound healing which we have previously studied, and is analogous to other wound healing processes. We have used an experimental model of ArF excimer laser ablation of stratum corneum to investigate laser-induced photoacoustic damage. The evidence for the injury being due to pressure transients is indirectbutcompelling. Whether these pressuretransients are acoustic transients orshockwaves has notbeendetermined, although itis ourprejudicethatshockwaves are the predominant force under these

  1. Contextualizing aquired brain damage

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard


    Contextualizing aquired brain damage Traditional approaches study ’communicational problems’ often in a discourse of disabledness or deficitness. With an ontology of communcation as something unique and a presupposed uniqueness of each one of us, how could an integrational approach (Integrational...... for people with aquired brain injuries will be presented and comparatively discussed in a traditional versus an integrational perspective. Preliminary results and considerations on ”methods” and ”participation” from this study will be presented along with an overview of the project's empirical data....

  2. Fatigue Damage in Wood

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben


    An investigation of fatigue failure in wood subjected to load cycles in compression parallel to grain is presented. Fatigue failure is found to depend both on the total time under load and on the number of cycles.Recent accelerated fatigue research on wood is reviewed, and a discrepancy between...... to 10 Hz are used. The number of cycles to failure is found to be a poor measure of the fatigue performance of wood. Creep, maximum strain, stiffness and work are monitored throughout the fatigue tests. Accumulated creep is suggested identified with damage and a correlation between stiffness reduction...

  3. Use of apo j isoforms as tissue lesion biomarkers


    Badimón, Lina; Cubedo, Judit; Padró, Teresa


    [EN] The present invention relates to use of the glycosylated fonns of apolipoprotein J as markers of tissue damage and of the acute inflammation said damage entails, more particularly the product of acute myocardial infarction, together with a method of diagnosis of said damage and/or inflammation and a kit comprising the elements necessary to effect said diagnosis. In the present invention it is demonstrated that the diverse glycosylated fonns vary their expression should ...

  4. Stem Cells and Tissue Engineering

    CERN Document Server

    Pavlovic, Mirjana


    Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

  5. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo


    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001. No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001. Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001. Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo

  6. Changes in optical properties during heating of ex vivo liver tissues (United States)

    Nagarajan, Vivek Krishna; Gogineni, Venkateshwara R.; White, Sarah B.; Yu, Bing


    Thermal ablation is the use of heat to induce cell death through coagulative necrosis. Ideally, complete ablation of tumor cells with no damage to surrounding critical structures such as blood vessels, nerves or even organs is desired. Ablation monitoring techniques are often employed to ensure optimal tumor ablation. In thermal tissue ablation, tissue damage is known to be dependent on the temperature and time of exposure. Aptly, current methods for monitoring ablation rely profoundly on local tissue temperature and duration of heating to predict the degree of tissue damage. However, such methods do not take into account the microstructural and physiological changes in tissues as a result of thermocoagulation. Light propagation within biological tissues is known to be dependent on the tissue microstructure and physiology. During tissue denaturation, changes in tissue structure alter light propagations in tissue which could be used to directly assess the extent of thermal tissue damage. We report the use of a spectroscopic system for monitoring the tissue optical properties during heating of ex vivo liver tissues. We observed that during tissue denaturation, continuous changes in wavelength-averaged μa(λ) and μ's(λ) followed a sigmoidal trend and are correlated with damage predicted by Arrhenius model.

  7. Thoracic damage control surgery. (United States)

    Gonçalves, Roberto; Saad, Roberto


    The damage control surgery came up with the philosophy of applying essential maneuvers to control bleeding and abdominal contamination in trauma patients who are within the limits of their physiological reserves. This concept was extended to thoracic injuries, where relatively simple maneuvers can shorten operative time of in extremis patients. This article aims to revise the various damage control techniques in thoracic organs that must be known to the surgeon engaged in emergency care. RESUMO A cirurgia de controle de danos surgiu com a filosofia de se aplicar manobras essenciais para controle de sangramento e contaminação abdominal, em doentes traumatizados, nos limites de suas reservas fisiológicas. Este conceito se estendeu para as lesões torácicas, onde manobras relativamente simples, podem abreviar o tempo operatório de doentes in extremis. Este artigo tem como objetivo, revisar as diversas técnicas de controle de dano em órgãos torácicos, que devem ser de conhecimento do cirurgião que atua na emergência.


    Dietary exposures have been implicated as risk factors in colorectal cancer. Such agents may act by causing DNA damage or may be protective against DNA damage. The effects of dietary exposures in causing or preventing damage have not been assessed directly in colon tissues. In th...

  9. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury

    NARCIS (Netherlands)

    Fischer, Julius C.; Bscheider, Michael; Eisenkolb, Gabriel; Lin, Chia Ching; Wintges, Alexander; Otten, Vera; Lindemans, Caroline A.; Heidegger, Simon; Rudelius, Martina; Monette, Sébastien; Rodriguez, Kori A.Porosnicu; Calafiore, Marco; Liebermann, Sophie; Liu, Chen; Lienenklaus, Stefan; Weiss, Siegfried; Kalinke, Ulrich; Ruland, Jürgen; Peschel, Christian; Shono, Yusuke; Docampo, Melissa; Velardi, Enrico; Jenq, Robert R; Hanash, Alan M; Dudakov, Jarrod A; Haas, Tobias; van den Brink, Marcel R M; Poeck, Hendrik


    The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial

  10. Photo-oxidative damage in Cucumis leaves during chilling

    NARCIS (Netherlands)

    van Hasselt, Philip Robbert


    Low temperatures below the freezing point cause freezing injury to plants. The direct cause of freezing injury is the formation of ice in the plant tissue. Many thermophilic ("heat loving") plants, however, are already damaged at low temperatures above the freezing point. This is called chilling

  11. Oxidatively damaged DNA in animals exposed to particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Jantzen, Kim


    Exposure to combustion-derived particles, quartz and asbestos is associated with increased levels of oxidized and mutagenic DNA lesions. The aim of this survey was to critically assess the measurements of oxidatively damaged DNA as marker of particle-induced genotoxicity in animal tissues...

  12. Damage scenarios and an onboard support system for damaged ships

    Directory of Open Access Journals (Sweden)

    Choi Jin


    Full Text Available Although a safety assessment of damaged ships, which considers environmental conditions such as waves and wind, is important in both the design and operation phases of ships, in Korea, rules or guidelines to conduct such assessments are not yet developed. However, NATO and European maritime societies have developed guidelines for a safety assessment. Therefore, it is required to develop rules or guidelines for safety assessments such as the Naval Ship Code (NSC of NATO. Before the safety assessment of a damaged ship can be performed, the available damage scenarios must be developed and the safety assessment criteria must be established. In this paper, the parameters related to damage by accidents are identified and categorized when developing damage scenarios. The need for damage safety assessment criteria is discussed, and an example is presented. In addition, a concept and specifications for the DB-based supporting system, which is used in the operation phases, are proposed.

  13. Melatonin Has An Ergogenic Effect But Does Not Prevent Inflammation and Damage In Exhaustive Exercise (United States)

    Beck, Wladimir Rafael; Botezelli, José Diego; Pauli, José Rodrigo; Ropelle, Eduardo Rochete; Gobatto, Claudio Alexandre


    It is well documented that exhaustive physical exercise leads to inflammation and skeletal muscle tissue damage. With this in mind, melatonin has been acutely administered before physical exercise; nevertheless, the use of melatonin as an ergogenic agent to prevent tissue inflammation and damage remains uncertain. We evaluated the effects of melatonin on swimming performance, muscle inflammation and damage and several physiological parameters after exhaustive exercise at anaerobic threshold intensity (iLAn) performed during light or dark circadian periods. The iLAn was individually determined and two days later, the animals performed an exhaustive exercise bout at iLAn 30 minutes after melatonin administration. The exercise promoted muscle inflammation and damage, mainly during the dark period, and the exogenous melatonin promoted a high ergogenic effect. The expressive ergogenic effect of melatonin leads to longer periods of muscle contraction, which superimposes a possible melatonin protective effect on the tissue damage and inflammation. PMID:26669455

  14. Quantifying tissue heterogeneity using quadtree decomposition. (United States)

    Subramaniam, K; Hoffman, E A; Tawhai, M H


    Volumetric computed tomography (CT) imaging provides a three-dimensional map of image intensities from which lung soft tissue density distribution can be estimated. The information gained from analyzing these images can prove valuable in diagnosis of conditions where lung tissue is damaged or has degenerated, and it is also necessary for modeling lung tissue mechanics. This paper presents a new technique for quantifying heterogeneity based on individual CT images, and investigates the heterogeneity of lung tissue in a group of healthy young subjects. It is intended that development of this technique leads to a standard model of classifying heterogeneity in lung tissue, while taking into account variables such as different imaging platforms and resolutions, and the position of the patient during imaging.

  15. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan


    Full Text Available Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer.Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed.Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration.Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.

  16. Thulium fiber laser damage to the ureter (United States)

    Wilson, Christopher R.; Hardy, Luke A.; Irby, Pierce B.; Fried, Nathaniel M.


    Our laboratory is studying experimental thulium fiber laser (TFL) as a potential alternative lithotripter to the clinical gold standard Holmium:YAG laser. Safety studies characterizing undesirable Holmium laser-induced damage to ureter tissue have been previously reported. Similarly, this study characterizes TFL induced ureter and stone basket damage. A TFL beam with pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rates of 150-500 Hz was delivered through a 100-μm-core, low-OH, silica optical fiber to the porcine ureter wall, in vitro. Ureter perforation times were measured and gross, histological, and optical coherence tomography images of the ablation zone were acquired. TFL operation at 150, 300, and 500 Hz produced mean ureter perforation times of 7.9, 3.8, and 1.8 s, respectively. Collateral damage averaged 510, 370, and 310 μm. TFL mean perforation time exceeded 1 s at each setting, which is a greater safety margin than previously reported during Holmium laser ureter perforation studies.

  17. Investigation of retinal damage during refractive eye surgery (United States)

    Schumacher, S.; Sander, M.; Dopke, C.; Grone, A.; Ertmer, W.; Lubatschowski, H.


    Ultrashort laser pulses are increasingly used in refractive eye surgery to cut inside transparent corneal tissue. This is exploited by the fs-LASIK procedure which affords the opportunity to correct ametropia without any mechanical effects. The cutting process is caused by the optical breakdown occurring in the laser focus. During this process only a certain amount of the pulse energy is deposited into the tissue. The remaining pulse energy propagates further through the eye and interacts with the retina and the strong absorbing tissue layers behind. Therefore this investigation shall clarify if the intensity of the remaining laser pulse and the resulting temperature field can damage the retina and the surrounding tissue. Threshold values of the retinal tissue and theoretical calculations of the temperature field will be presented.

  18. Biomaterials in myocardial tissue engineering. (United States)

    Reis, Lewis A; Chiu, Loraine L Y; Feric, Nicole; Fu, Lara; Radisic, Milica


    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternative sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augmenting injured or impaired myocardium, with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds - composed of natural or synthetic biomaterials or decellularized extracellular matrix - that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue; and finally, injectable biomaterials (hydrogels) designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Biomaterials in myocardial tissue engineering (United States)

    Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica


    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

  20. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine (United States)

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.


    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  1. DNA damage markers in dermal fibroblasts in vitro reflect chronological donor age

    DEFF Research Database (Denmark)

    Waaijer, Mariëtte E C; Croco, Eleonora; Westendorp, Rudi G J


    The aging process is accompanied by an accumulation of cellular damage, which compromises the viability and function of cells and tissues. We aim to further explore the association between in vitro DNA damage markers and the chronological age of the donor, as well as long-lived family membership...

  2. Estimating willingness to pay for protection of eastern black walnut from deer damage (United States)

    Larry D. Godsey; John P. Dwyer


    For many landowners willing to plant trees, one of the biggest establishment and maintenance costs is protecting those young trees from deer browse damage. In some cases, the method of protection used can cost two to three times as much as the cost of planting. Deer damage such as nipping off terminal buds and buck rub penetrating the bark and cambial tissue can kill...

  3. The comparison of thermal tissue injuries caused by ultrasonic scalpel and electrocautery use in rabbit tongue tissue

    Directory of Open Access Journals (Sweden)

    Guclu Kaan Beriat


    Full Text Available The aim of this study compares to the increase in tissue temperature and the thermal histological effects of ultrasonic scalpel, bipolar and unipolar electrosurgery incisions in the tongue tissue of rabbits. This study evaluates the histopathological changes related to thermal change and the maximum temperature values in the peripheral tissue brought about by the incisions carried out by the three methods in a comparative way. To assess thermal tissue damage induced by the three instruments, maximum tissue temperatures were measured during the surgical procedure and tongue tissue samples were examined histopathologically following the surgery. The mean maximum temperature values of the groups were 93.93±2.76 C° for the unipolar electrocautery group, whereas 85.07±5.95 C° for the bipolar electrocautery group, and 108.23±7.64 C° for the ultrasonic scalpel group.There was a statistically significant relationship between the increase in maximum temperature values and the separation among tissue layers, edema, congestion, necrosis, hemorrhage, destruction in blood vessel walls and fibrin accumulation, and between the existence of fibrin thrombus and tissue damage depth (p<0.05.It was concluded that the bipolar electrocautery use gives way to less temperature increase in the tissues and less thermal tissue damage in comparison to the other methods.

  4. Preparing the ground for tissue regeneration: from mechanism to therapy. (United States)

    Forbes, Stuart J; Rosenthal, Nadia


    Chronic diseases confer tissue and organ damage that reduce quality of life and are largely refractory to therapy. Although stem cells hold promise for treating degenerative diseases by 'seeding' injured tissues, the regenerative capacity of stem cells is influenced by regulatory networks orchestrated by local immune responses to tissue damage, with macrophages being a central component of the injury response and coordinator of tissue repair. Recent research has turned to how cellular and signaling components of the local stromal microenvironment (the 'soil' to the stem cells' seed), such as local inflammatory reactions, contribute to successful tissue regeneration. This Review discusses the basic principles of tissue regeneration and the central role locally acting components may play in the process. Application of seed-and-soil concepts to regenerative medicine strengthens prospects for developing cell-based therapies or for promotion of endogenous repair.

  5. Multiscale mechanical modeling of soft biological tissues (United States)

    Stylianopoulos, Triantafyllos


    Soft biological tissues include both native and artificial tissues. In the human body, tissues like the articular cartilage, arterial wall, and heart valve leaflets are examples of structures composed of an underlying network of collagen fibers, cells, proteins and molecules. Artificial tissues are less complex than native tissues and mainly consist of a fiber polymer network with the intent of replacing lost or damaged tissue. Understanding of the mechanical function of these materials is essential for many clinical treatments (e.g. arterial clamping, angioplasty), diseases (e.g. arteriosclerosis) and tissue engineering applications (e.g. engineered blood vessels or heart valves). This thesis presents the derivation and application of a multiscale methodology to describe the macroscopic mechanical function of soft biological tissues incorporating directly their structural architecture. The model, which is based on volume averaging theory, accounts for structural parameters such as the network volume fraction and orientation, the realignment of the fibers in response to strain, the interactions among the fibers and the interactions between the fibers and the interstitial fluid in order to predict the overall tissue behavior. Therefore, instead of using a constitutive equation to relate strain to stress, the tissue microstructure is modeled within a representative volume element (RVE) and the macroscopic response at any point in the tissue is determined by solving a micromechanics problem in the RVE. The model was applied successfully to acellular collagen gels, native blood vessels, and electrospun polyurethane scaffolds and provided accurate predictions for permeability calculations in isotropic and oriented fiber networks. The agreement of model predictions with experimentally determined mechanical properties provided insights into the mechanics of tissues and tissue constructs, while discrepancies revealed limitations of the model framework.

  6. Overload road damage model

    CSIR Research Space (South Africa)

    Roux, MP


    Full Text Available .02 1.07 1.02 1.07 1.05 Current Condition: Provincial 1.07 1.17 1.03 1.08 1.05 1.12 1.05 1.12 1.09 Deteriorated Condition 1.14 1.27 1.06 1.14 1.10 1.18 1.10 1.20 1.15 TR 2005/26 - TBP51: Overload Road Damage Model Report – March 2005 CSIR... million Ave. O/L E80s/vehicle (n=4) Low High Average 1996 50,595 14,220 16% 1.28 19.7 40.4 30.1 1997 45,657 13,691 15% 1.31 18.8 38.9 28.9 1998 33,235 14,291 15% 1.22 17.6 36.2 26.9 1999 72,546 25,788 15% 1.13 16.3 33.4 24.9 2000 135...

  7. Treatment of anisotropic damage development within a scalar damage formulation (United States)

    Chan, K. S.; Bodner, S. R.; Munson, D. E.

    This paper is concerned with describing a damage mechanics formulation which provides for non-isotropic effects using a scalar damage variable. An investigation has been in progress for establishing the constitutive behavior of rock salt at long times and low to moderate confining pressures in relation to the possible use of excavated rooms in rock salt formations as repositories for nuclear waste. An important consideration is the effect of damage manifested principally by the formation of shear induced wing cracks which have a stress dependent orientation. The analytical formulation utilizes a scalar damage parameter, but is capable of indicating the non-isotropic dependence of inelastic straining on the stress state and the confining pressure. Also, the equations indicate the possibility of volumetric expansions leading to the onset of tertiary creep and eventually rupture if the damage variable reaches a critical value.

  8. Ribonucleotide triggered DNA damage and RNA-DNA damage responses. (United States)

    Wallace, Bret D; Williams, R Scott


    Research indicates that the transient contamination of DNA with ribonucleotides exceeds all other known types of DNA damage combined. The consequences of ribose incorporation into DNA, and the identity of protein factors operating in this RNA-DNA realm to protect genomic integrity from RNA-triggered events are emerging. Left unrepaired, the presence of ribonucleotides in genomic DNA impacts cellular proliferation and is associated with chromosome instability, gross chromosomal rearrangements, mutagenesis, and production of previously unrecognized forms of ribonucleotide-triggered DNA damage. Here, we highlight recent findings on the nature and structure of DNA damage arising from ribonucleotides in DNA, and the identification of cellular factors acting in an RNA-DNA damage response (RDDR) to counter RNA-triggered DNA damage.

  9. Shock Initiation of Damaged Explosives

    Energy Technology Data Exchange (ETDEWEB)

    Chidester, S K; Vandersall, K S; Tarver, C M


    Explosive and propellant charges are subjected to various mechanical and thermal insults that can increase their sensitivity over the course of their lifetimes. To quantify this effect, shock initiation experiments were performed on mechanically and thermally damaged LX-04 (85% HMX, 15% Viton by weight) and PBX 9502 (95% TATB, 5% Kel-F by weight) to obtain in-situ manganin pressure gauge data and run distances to detonation at various shock pressures. We report the behavior of the HMX-based explosive LX-04 that was damaged mechanically by applying a compressive load of 600 psi for 20,000 cycles, thus creating many small narrow cracks, or by cutting wedge shaped parts that were then loosely reassembled, thus creating a few large cracks. The thermally damaged LX-04 charges were heated to 190 C for long enough for the beta to delta solid - solid phase transition to occur, and then cooled to ambient temperature. Mechanically damaged LX-04 exhibited only slightly increased shock sensitivity, while thermally damaged LX-04 was much more shock sensitive. Similarly, the insensitive explosive PBX 9502 was mechanically damaged using the same two techniques. Since PBX 9502 does not undergo a solid - solid phase transition but does undergo irreversible or 'rachet' growth when thermally cycled, thermal damage to PBX 9502 was induced by this procedure. As for LX-04, the thermally damaged PBX 9502 demonstrated a greater shock sensitivity than mechanically damaged PBX 9502. The Ignition and Growth reactive flow model calculated the increased sensitivities by igniting more damaged LX-04 and PBX 9502 near the shock front based on the measured densities (porosities) of the damaged charges.

  10. Plasmalogen phospholipids protect internodal myelin from oxidative damage. (United States)

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A


    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The masonry damage diagnostic system

    NARCIS (Netherlands)

    Hees, R.P.J. van; Naldini, S.


    The MDDS (Masonry Damage Diagnostic Systetn) is an expert system for the evaluation of the deterioration of ancient brick masonry structures. A demo version was developed in an EC-Environment project. The system is centered on damage related to the interaction between materials (brick masonry,

  12. Myocardial damage after continuous aerobic and anaerobic exercise in rats

    Directory of Open Access Journals (Sweden)

    Rostika Flora


    Full Text Available Background: Regular physical activity is highly recommended in preventive, curative, and rehabilitative programs in order to promote health, especially cardiovascular health. However, physical activity can also cause sudden death. In athletes, sudden death may occur during sport competitions, with myocardial infarction as the most common etiology. It is suspected that continuous training without any rest-day play a role in cardiac muscle damage and sudden death during competition. Our study was aimed to learn about cardiac muscle adaptation on continuous aerobic and anaerobic physical activity without any rest-day. Methods: The specimens in our study were cardiac muscle tissue obtained from rats that had performed aerobic and anaerobic physical activity on treadmill for 1, 3, 7, and 10 days without any rest-day. Blood gas analysis and hematological assessment were used as parameters of systemic adaptation to hypoxia during physical activity. Moreover, histopathology of cardiac muscle tissue was performed as parameter for cardiac muscle damage.Results: The results showed that aerobic and anaerobic physical activity caused a systemic hypoxic condition and triggered adaptation responses. Cardiac muscle damage occurred on the 10th day in both treatment groups, with more severe damage observed in the group with anaerobic physical activity. The tissue protein level in the anaerobic group increased progressively on the 10th day.Conclusion: Physical activity may result in hypoxia and systemic adaptation. Aerobic and anaerobic physical activities performed for 10 days without any rest-day may cause cardiac muscle damage. (Med J Indones. 2013;22:209-14. doi: 10.13181/mji.v22i4.601Keywords: Cardiac muscle, cardiac muscle damage, histopathology, physical activity

  13. Damage growth in aerospace composites

    CERN Document Server


    This book presents novel methods for the simulation of damage evolution in aerospace composites that will assist in predicting damage onset and growth and thus foster less conservative designs which realize the promised economic benefits of composite materials. The presented integrated numerical/experimental methodologies are capable of taking into account the presence of damage and its evolution in composite structures from the early phases of the design (conceptual design) through to the detailed finite element method analysis and verification phase. The book is based on the GARTEUR Research Project AG-32, which ran from 2007 to 2012, and documents the main results of that project. In addition, the state of the art in European projects on damage evolution in composites is reviewed. While the high specific strength and stiffness of composite materials make them suitable for aerospace structures, their sensitivity to damage means that designing with composites is a challenging task. The new approaches describ...

  14. Tissue bionics: examples in biomimetic tissue engineering. (United States)

    Green, David W


    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  15. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail:


    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  16. American Association of Tissue Banks (United States)


  17. Envenomations by Bothrops and Crotalus Snakes Induce the Release of Mitochondrial Alarmins (United States)

    Zornetta, Irene; Caccin, Paola; Fernandez, Julián; Lomonte, Bruno; Gutierrez, José María; Montecucco, Cesare


    Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as ‘danger’ signals. These are known as ‘alarmins’, and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial ‘alarmins’ might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations. PMID:22363828

  18. Envenomations by Bothrops and Crotalus snakes induce the release of mitochondrial alarmins.

    Directory of Open Access Journals (Sweden)

    Irene Zornetta

    Full Text Available Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as 'danger' signals. These are known as 'alarmins', and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix and cytochrome c (Cyt c from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial 'alarmins' might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations.

  19. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)


    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  20. Multiphoton nanosurgery in cells and tissues (United States)

    Riemann, Iris; Stracke, Frank; Sauer, Daniel; Martin, Sven; König, Karsten


    Near infrared (NIR) femtosecond laser microscopes enable the user to perform highly precise nanosurgery. Tissue components, cells and single organelles of cells inside tumor-sphaeroids and tissues can be precisely manipulated and optically knocked out without collateral damage. In addition, the monitoring effects of nanosurgery in situ using two photon excitation of auto fluorescence of endogenous fluorophores can be performed quite easily with a sub-cellular resolution. This method may become a useful instrument for nano manipulation and nano-surgery in several fields of life sciences.

  1. Fast Detection of Seeds and Freeze Damage of Mandarines Using Magnetic Resonance Imaging (United States)

    Kim, Seong Min; Milczarek, Rebecca; McCarthy, Michael

    Fast detection of seeds and freeze damage in mandarine citrus fruit was performed using magnetic resonance imaging. A 1 T industrial grade permanent magnet was used to acquire the image data. The spatial resolution of the image was 550 μm. A fast spin echo pulse sequence was used to detect freeze damage and seeds. The signal intensity of seeds and freeze damaged regions was weaker than normal tissue. Threshold based image analysis has proven successful in detecting seeds and quantifying freeze damage.

  2. The effect of ascorbic acid on Bitis arietans venom induced toxicity in rats

    Directory of Open Access Journals (Sweden)

    Abdulrahman K. Al-Asmari


    Full Text Available Ascorbic acid (AsAc was tested to evaluate its ability to reverse the oxidative stress induced by envenoming. Test groups of rats were envenomed with sub-lethal doses (4.0 mg/kg s.c. of Bitis arietans venom (BaV whilst, single doses (500 mg/kg, orally of AsAc were pre-administered in half of them. Blood samples were collected within three periods and levels of lipid peroxidation (LPO and total-SH increased significantly, whilst, the ‘Venom + AsAc’ groups were significantly less than both, the respective ‘Venom’ groups and controls, at different periods. The antioxidant, superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx enzyme level changes were trivial at the three periods, whilst, there were no changes in the ‘Venom + AsAc’ groups, compared with controls, except SOD which, became significant after 24 h. SCr and BUN levels were significantly higher than the controls within the three periods with variable degrees, whilst, the ‘Venom + AsAc’ group level changes were insignificant compared with controls and their respective ‘Venom’ groups at all periods. Blood urea Nitrogen (BUN, became significantly lower after 24 h. After 6 and 24 h AST levels were significantly higher than controls, whilst, ALT was not. Level changes of both AST and ALT ‘Venom + AsAc’ groups were insignificant, compared with controls at all periods. It is concluded that oxidative stress due to envenoming by BaV induced variable levels of significant changes in levels of nephrotoxic, hepatotoxic markers and antioxidant enzyme parameters. Administration of AsAc relatively adjusted these changes with different degrees, at variable periods of time that demands further deeper research in beneficiary mechanisms of antioxidants.

  3. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. (United States)

    Zargan, Jamil; Sajad, Mir; Umar, Sadiq; Naime, M; Ali, Shakir; Khan, Haider A


    Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200 μg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24 h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100 μg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20 μg/ml. Two concentrations viz. 50 and 100 μ/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentration-dependent manner, only 50 μg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100 μg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentration-dependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties make scorpion venom a valuable therapeutic agent in cancer research.

  4. Ohanin, a novel protein from king cobra venom, induces hypolocomotion and hyperalgesia in mice. (United States)

    Pung, Yuh Fen; Wong, Peter T H; Kumar, Prakash P; Hodgson, Wayne C; Kini, R Manjunatha


    We have identified, purified, and determined the complete amino acid sequence of a novel protein, ohanin from Ophiophagus hannah (king cobra) venom. It is a small protein containing 107 amino acid residues with a molecular mass of 11951.47 +/- 0.67 Da as assessed by electrospray ionization-mass spectrometry. It does not show similarity to any known families of snake venom proteins and hence is the first member of a new family of snake venom proteins. It shows similarity to PRY and SPRY domain proteins. It is nontoxic up to 10 mg/kg when injected intraperitoneally in mice. Ohanin produced statistically significant and dose-dependent hypolocomotion in mice. In a pain threshold assay, it showed dose-dependent hyperalgesic effect. The ability of the protein to elicit a response at greatly reduced doses when injected intracerebroventricularly as compared with intraperitoneal administration in both the locomotion and hot plate experiments strongly suggests that ohanin acts on the central nervous system. Since the natural abundance of the protein in the venom is low (approximately 1 mg/g), a synthetic gene was constructed and expressed. The recombinant protein, which was obtained in the insoluble fraction in Escherichia coli, was purified under denaturing condition and was refolded. Recombinant ohanin is structurally and functionally similar to native protein as determined by circular dichroism and hot plate assay, suggesting that it will be useful in future structure-function relationship studies.

  5. Testicular Damage following Testicular Sperm Retrieval

    DEFF Research Database (Denmark)

    Fedder, Jens; Marcussen, Niels; Fedder, Maja D.K.


    The aim of this study was to evaluate the possible development of histological abnormalities such as fibrosis and microcalcifications after sperm retrieval in a ram model. Fourteen testicles in nine rams were exposed to open biopsy, multiple TESAs, or TESE, and the remaining four testicles were...... left unoperated on as controls. Three months after sperm retrieval, the testicles were removed, fixed, and cut into 1/2 cm thick slices and systematically put onto a glass plate exposing macroscopic abnormalities. Tissue from abnormal areas was cut into 3 μm sections and stained for histological...... evaluation. Pathological abnormalities were observed in testicles exposed to sperm retrieval (≥11 of 14) compared to 0 of 4 control testicles. Testicular damage was found independently of the kind of intervention used. Therefore, cryopreservation of excess sperm should be considered while retrieving sperm....

  6. Oxidative Damage in Parkinson's Disease

    National Research Council Canada - National Science Library

    Beal, M


    The objective of the present research is to determine whether there is a coherent body of evidence implicating oxidative damage in the pathogenesis of Parkinson's Disease and the MPTP model of Parkinsonism...

  7. Civil Liability for Environmental Damages

    Directory of Open Access Journals (Sweden)

    Daniela Ciochină


    Full Text Available We debated in this article the civil liability for environmental damages as stipulated in ourlegislation with reference to Community law. The theory of legal liability in environmental law is basedon the duty of all citizens to respect and protect the environment. Considering the importance ofenvironment in which we live, the liability for environmental damages is treated by the Constitution as aprinciple and a fundamental obligation. Many human activities cause environmental damages and, in linewith the principle of sustainable development, they should be avoided. However, when this is notpossible, they must be regulated (by criminal or administrative law in order to limit their adverse effectsand, according to the polluter pays principle, to internalize in advance their externalities (through taxes,insurances or other forms of financial security products. Communication aims to analyze these issues andlegal regulations dealing with the issue of liability for environmental damage.

  8. Loss and damage post Paris (United States)

    Petherick, Anna


    The Paris Agreement gave the Warsaw International Mechanism for Loss and Damage a permanent and potentially prominent place in climate negotiations, but beyond that its impact remains wide open for interpretation.

  9. Pain Medicines and Kidney Damage (United States)

    ... Damage Related Topics Section Navigation Kidney Disease Acquired Cystic Kidney Disease Amyloidosis & Kidney Disease Chronic Kidney Disease (CKD) What ... Eating, Diet, & Nutrition for PKD Race, Ethnicity, & Kidney Disease Renal Artery ... Kidney Cysts Solitary Kidney Your Kidneys & How They Work Pain ...

  10. Radiolytic Damage to Genetic Material. (United States)

    Ward, John F.


    Describes some basic findings in the radiation chemistry of genetic material derived from studies of model systems. Uses these findings to extrapolate the consequences of radiation damage to DNA within cells. (CS)

  11. Structural significance of mechanical damage. (United States)


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

  12. Probabilistic Fatigue Damage Program (FATIG) (United States)

    Michalopoulos, Constantine


    FATIG computes fatigue damage/fatigue life using the stress rms (root mean square) value, the total number of cycles, and S-N curve parameters. The damage is computed by the following methods: (a) traditional method using Miner s rule with stress cycles determined from a Rayleigh distribution up to 3*sigma; and (b) classical fatigue damage formula involving the Gamma function, which is derived from the integral version of Miner's rule. The integration is carried out over all stress amplitudes. This software solves the problem of probabilistic fatigue damage using the integral form of the Palmgren-Miner rule. The software computes fatigue life using an approach involving all stress amplitudes, up to N*sigma, as specified by the user. It can be used in the design of structural components subjected to random dynamic loading, or by any stress analyst with minimal training for fatigue life estimates of structural components.

  13. Excitation optimization for damage detection

    Energy Technology Data Exchange (ETDEWEB)

    Bement, Matthew T [Los Alamos National Laboratory; Bewley, Thomas R [UCSD


    A technique is developed to answer the important question: 'Given limited system response measurements and ever-present physical limits on the level of excitation, what excitation should be provided to a system to make damage most detectable?' Specifically, a method is presented for optimizing excitations that maximize the sensitivity of output measurements to perturbations in damage-related parameters estimated with an extended Kalman filter. This optimization is carried out in a computationally efficient manner using adjoint-based optimization and causes the innovations term in the extended Kalman filter to be larger in the presence of estimation errors, which leads to a better estimate of the damage-related parameters in question. The technique is demonstrated numerically on a nonlinear 2 DOF system, where a significant improvement in the damage-related parameter estimation is observed.

  14. Spall Damage of Concrete Structures (United States)


    C1 APPENDIX D DATA ON DAMAGE OF REINFORCED CONCRETE STRUCTURES CAUSED BY’ NEARBY BOMB DETONATIONS ..................... D1 LIST OF...27.6799 grams/centimeters 3 xiii SPALL DAMAGE TO CONCRETE STRUCTURES PART I: INTRODUCTION Backaround Spall is defined as the ejection of fragments of a...of the walls. Additional data from other tests with detonations of bombs near concrete structures were also collected in a literature search. The data

  15. Damage Atlas for Photographic materials

    Directory of Open Access Journals (Sweden)

    Kristel Van Camp


    Full Text Available La conservation des documents photographiques peut nécessiter des interventions préventives ou curatives. Ce choix est guidé par leur état de conservation. Une meilleure connaissance des détériorations est donc cruciale. Le répertoire présenté ici essaie de les classifier selon des caractéristiques spécifiques et leur niveau de gravité. Les différents types de dégradation sont illustrés et décrits avec une terminologie précise. L’auteur propose en regard de ceux-ci l’intervention qui semble la plus appropriée. Ce répertoire s’adresse à toutes les personnes concernées par la photographie, qu’ils soient dans le milieu de la conservation ou dans le domaine artistique, dans les musées ou dans les archives. In order to rescue a damaged photographic object, preventive or conservative actions are needed. Knowing the specific characteristics of different types of damage is crucial. A damage atlas can provide these characteristics. With this atlas the damage can be recognised and appropriate actions can be taken. This damage atlas offers a first attempt to such a characterisation in the field of photography. The damage atlas contains images and the necessary information about damage on photographic material. The atlas with special annotations about the terminology and the grade of the damage is meant for everybody who works with photographic material, as well in museums as in archives.

  16. Radiation Damage of Quartz Fibers


    Hagopian, V


    Quartz fibers are used in high energy physics experiments as the active medium in high radiation area calorimetry. Quartz fibers are also used in the transmission of optical signals. Even though quartz does not damage by moderate amounts of irradiation, the clad of the fibers and the protective coating ( buffer) do damage reducing light transmission. Various types of quartz fibers have been irradiated and measured for light transmission. The most radiation hard quartz fibers are those with qu...

  17. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics


    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.


    Directory of Open Access Journals (Sweden)

    I. B. Kolina


    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  19. Mechanism of DNA damage tolerance (United States)

    Bi, Xin


    DNA damage may compromise genome integrity and lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including damage repair and tolerance mechanisms, as well as damage checkpoints. The DNA damage tolerance (DDT) pathway promotes the bypass of single-stranded DNA lesions encountered by DNA polymerases during DNA replication. This prevents the stalling of DNA replication. Two mechanistically distinct DDT branches have been characterized. One is translesion synthesis (TLS) in which a replicative DNA polymerase is temporarily replaced by a specialized TLS polymerase that has the ability to replicate across DNA lesions. TLS is mechanistically simple and straightforward, but it is intrinsically error-prone. The other is the error-free template switching (TS) mechanism in which the stalled nascent strand switches from the damaged template to the undamaged newly synthesized sister strand for extension past the lesion. Error-free TS is a complex but preferable process for bypassing DNA lesions. However, our current understanding of this pathway is sketchy. An increasing number of factors are being found to participate or regulate this important mechanism, which is the focus of this editorial. PMID:26322163

  20. Time-dependent damage in predictions of fatigue behaviour of normal and healing ligaments (United States)

    Thornton, Gail M.; Bailey, Soraya J.; Schwab, Timothy D.


    Ligaments are dense fibrous tissues that connect bones across a joint and are exposed daily to creep and fatigue loading. Ligaments are tensile load-bearing tissues; therefore, fatigue loading will have a component of time-dependent damage from the non-zero mean stress and cycle-dependent damage from the oscillating stress. If time-dependent damage is not sufficient to completely predict the fatigue response, then cycle-dependent damage could be an important contributor. Using data from normal ligaments (current study and Thornton et al., Clin. Biomech. 22:932-940, 2007a) and healing ligaments (Thornton and Bailey, J. Biomech. Eng. 135:091004-1-091004-6, 2013), creep data was used to predict the fatigue response considering time-dependent damage. Relationships between creep lifetime and test stress or initial strain were modelled using exponential or power-law regression. In order to predict fatigue lifetimes, constant rates of damage were assumed and time-varying stresses were introduced into the expressions for time-dependent damage from creep. Then, the predictions of fatigue lifetime were compared with curvefits to the fatigue data where exponential or power-law regressions were used to determine the relationship between fatigue lifetime and test stress or initial strain. The fatigue prediction based on time-dependent damage alone greatly overestimated fatigue lifetime suggesting that time-dependent damage alone cannot account for all of the damage accumulated during fatigue and that cycle-dependent damage has an important role. At lower stress and strain, time-dependent damage was a greater relative contributor for normal ligaments than healing ligaments; however, cycle-dependent damage was a greater relative contributor with incremental increases in stress or strain for normal ligaments than healing ligaments.

  1. Combining Electrolysis and Electroporation for Tissue Ablation. (United States)

    Phillips, Mary; Rubinsky, Liel; Meir, Arie; Raju, Narayan; Rubinsky, Boris


    Electrolytic ablation is a method that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. This study was designed to explore the hypothesis stating that electrolytic ablation can be made more effective when the electrolysis-producing electric charges are delivered using electric pulses with field strength typical in reversible electroporation protocols. (For brevity we will refer to tissue ablation protocols that combine electroporation and electrolysis as E(2).) The mechanistic explanation of this hypothesis is related to the idea that products of electrolysis generated by E(2) protocols can gain access to the interior of the cell through the electroporation permeabilized cell membrane and therefore cause more effective cell death than from the exterior of an intact cell. The goal of this study is to provide a first-order examination of this hypothesis by comparing the charge dosage required to cause a comparable level of damage to a rat liver, in vivo, when using either conventional electrolysis or E(2) approaches. Our results show that E(2) protocols produce tissue damage that is consistent with electrolytic ablation. Furthermore, E(2) protocols cause damage comparable to that produced by conventional electrolytic protocols while delivering orders of magnitude less charge to the target tissue over much shorter periods of time. © The Author(s) 2014.

  2. Heat-damaged RBC scan: a case of intrahepatic splenosis. (United States)

    Tamm, Alexander; Decker, Martha; Hoskinson, Michael; Abele, Jonathan; Patel, Vimal


    Intrahepatic splenosis results from autotransplantation of splenic tissue within the liver, usually after splenic trauma or splenectomy. We present a case of a 43-year-old male patient with an incidental liver lesion discovered on abdominal ultrasound. The diagnosis of intrahepatic splenosis was considered after CT and MRI before being definitively made with Tc-labeled heat-damaged RBC scintigraphy. The case report illustrates the imaging characteristics of this rare location of abdominal splenosis.

  3. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

    Directory of Open Access Journals (Sweden)

    Sana Chakroun


    Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

  4. Heart tissue grown in NASA Bioreactor (United States)


    Lisa Freed and Gordana Vunjak-Novakovic, both of the Massachusetts Institute of Technology (MIT), have taken the first steps toward engineering heart muscle tissue that could one day be used to patch damaged human hearts. Cells isolated from very young animals are attached to a three-dimensional polymer scaffold, then placed in a NASA bioreactor. The cells do not divide, but after about a week start to cornect to form a functional piece of tissue. Here, a transmission electron micrograph of engineered tissue shows a number of important landmarks present in functional heart tissue: (A) well-organized myofilaments (Mfl), z-lines (Z), and abundant glycogen granules (Gly); and (D) intercalcated disc (ID) and desmosomes (DES). The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). Credit: MIT

  5. Multiplexed lasing in tissues (United States)

    Chen, Yu-Cheng; Chen, Qiushu; Fan, Xudong


    Biolasers are an emerging technology for next generation biochemical detection and clinical applications. Progress has recently been made to achieve lasing from biomolecules and single living cells. Tissues, which consist of cells embedded in extracellular matrix, mimic more closely the actual complex biological environment in a living body and therefore are of more practical significance. Here, we developed a highly versatile tissue laser platform, in which tissues stained with fluorophores are sandwiched in a high-Q Fabry-Pérot microcavity. Distinct lasing emissions from muscle and adipose tissues stained respectively with fluorescein isothiocyanate (FITC) and boron-dipyrromethene (BODIPY), and hybrid muscle/adipose tissue with dual-staining were achieved with a threshold of only 10 μJ/mm2. Additionally, we investigated how tissue structure/geometry, tissue thickness, and staining dye concentration affect the tissue laser. It is further found that, despite large fluorescence spectral overlap between FITC and BODIPY in tissues, their lasing emissions could be clearly distinguished and controlled due to their narrow lasing bands and different lasing thresholds, thus enabling highly multiplexed detection. Our tissue laser platform can be broadly applicable to various types of tissues/diseases. It provides a new tool for a wide range of biological and biomedical applications, such as diagnostics/screening of tissues and identification/monitoring of biological transformations in tissue engineering.

  6. Recognition memory and DNA damage in undernourished young rats

    Directory of Open Access Journals (Sweden)



    Full Text Available ABSTRACT This study evaluated the recognition memory and the levels of DNA damage (blood and hippocampus in undernourished young Wistar rats. The experiment was conducted along 14-week with rodents divided in control group (CG, n=8 and undernourished group (UG, n=12 which was submitted to caloric restriction. Nutritional status for undernutrition was defined by Body Mass Index (BMI ≤0.45g/cm2 and by weighting the organs/tissue (liver, spleen, intestine, peritoneal fat, kidney and encephalon. The Novel Object Recognition Test assessed recognition memory and the Comet Assay evaluated the levels of DNA damage. Student t test, 2-way ANOVA and Pearson's correlation analysis were used and the significance level was of p<0.05. The UG showed lower BMI and organ/tissue weights than CG (p<0.001. In short-term memory, the recognition rate was higher in the UG (p<0.05, only after 4 weeks. In the long-term memory, again recognition rate was higher in the UG than the CG, after 4 weeks (p<0.001 and 14 weeks (p<0.01. The UG showed decreased levels of DNA damage in the blood (p<0.01 and increased levels in the hippocampus (p<0.01. We concluded in this study that the undernutrition by caloric restriction did not cause impairment in recognition memory, however induced DNA damage in the hippocampus.

  7. Interplay between mechanisms of damage and repair in multiple sclerosis. (United States)

    Stadelmann, Christine; Brück, Wolfgang


    The neuropathology of multiple sclerosis is characterised by focal damage to white matter. However, tissue damage is also present in the cortical grey matter, with a particularly high prevalence of cortical demyelination being observed in secondary progressive and primary progressive forms of the disease. The presence of meningeal B-cell follicle-like structures, which frequently appear during the secondary progressive phase of disease, may be involved in the formation of these subpial cortical lesions. Diffuse white matter inflammation accompanied by axonal damage can also be observed in normal appearing white matter and, again, this is more prominent in chronic progressive forms of multiple sclerosis than in acute stages of disease. Axonal damage is a particularly important component of the pathology of multiple sclerosis and appears to be a critical determinant of clinical outcome. Axons appear to become vulnerable to injury as a result of loss of their myelin sheaths. Remyelination represents an important mechanism of tissue repair in multiple sclerosis and already occurs at an early stage of lesion development and in both white and grey matter lesions. The extent of remyelination appears to be greater in cortical lesions and in lesions further from the ventricles. There is important heterogeneity between patients in terms of the extent of remyelination, which may reflect underlying differences in pathogenetic mechanisms between patients.

  8. Metformin Treatment Prevents Sedentariness Related Damages in Mice

    Directory of Open Access Journals (Sweden)

    Pamela Senesi


    Full Text Available Metformin (METF, historical antihyperglycemic drug, is a likely candidate for lifespan extension, treatment and prevention of sedentariness damages, insulin resistance, and obesity. Skeletal muscle is a highly adaptable tissue, capable of hypertrophy response to resistance training and of regeneration after damage. Aims of this work were to investigate METF ability to prevent sedentariness damage and to enhance skeletal muscle function. Sedentary 12-week-old C57BL/6 mice were treated with METF (250 mg/kg per day, in drinking water for 60 days. METF role on skeletal muscle differentiation was studied in vitro using murine C2C12 myoblasts. Muscular performance evaluation revealed that METF enhanced mice physical performance (Estimated VO2max. Biochemical analyses of hepatic and muscular tissues indicated that in liver METF increased AMPK and CAMKII signaling. In contrast, METF inactivated ERKs, the principal kinases involved in hepatic stress. In skeletal muscle, METF activated AKT, key kinase in skeletal muscle mass maintenance. In in vitro studies, METF did not modify the C2C12 proliferation capacity, while it positively influenced the differentiation process and myotube maturation. In conclusion, our novel results suggest that METF has a positive action not only on the promotion of healthy aging but also on the prevention of sedentariness damages.

  9. Epithelial-mesenchymal transition: An emerging target in tissue fibrosis (United States)

    Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong


    Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

  10. Clinical translation of controlled protein delivery systems for tissue engineering. (United States)

    Spiller, Kara L; Vunjak-Novakovic, Gordana


    Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed.

  11. Road Damage Externalities and Road User Charges.


    Newbery, David M


    Vehicles damage roads and, thus, increase road repair costs and create a road damage externality by raising the operating costs of subsequent vehicles. The main result is that if periodic road maintenance is condition responsive and if all road damage is attributable to traffic, then, in steady state with zero traffic growth, the average road damage externality is zero a nd the appropriate road damage charge is the average maintenance cost. Where weather accounts for some road damage, the roa...

  12. Glaucomatous damage of the macula. (United States)

    Hood, Donald C; Raza, Ali S; de Moraes, Carlos Gustavo V; Liebmann, Jeffrey M; Ritch, Robert


    There is a growing body of evidence that early glaucomatous damage involves the macula. The anatomical basis of this damage can be studied using frequency domain optical coherence tomography (fdOCT), by which the local thickness of the retinal nerve fiber layer (RNFL) and local retinal ganglion cell plus inner plexiform (RGC+) layer can be measured. Based upon averaged fdOCT results from healthy controls and patients, we show that: 1. For healthy controls, the average RGC+ layer thickness closely matches human histological data; 2. For glaucoma patients and suspects, the average RGC+ layer shows greater glaucomatous thinning in the inferior retina (superior visual field (VF)); and 3. The central test points of the 6° VF grid (24-2 test pattern) miss the region of greatest RGC+ thinning. Based upon fdOCT results from individual patients, we have learned that: 1. Local RGC+ loss is associated with local VF sensitivity loss as long as the displacement of RGCs from the foveal center is taken into consideration; and 2. Macular damage is typically arcuate in nature and often associated with local RNFL thinning in a narrow region of the disc, which we call the macular vulnerability zone (MVZ). According to our schematic model of macular damage, most of the inferior region of the macula projects to the MVZ, which is located largely in the inferior quadrant of the disc, a region that is particularly susceptible to glaucomatous damage. A small (cecocentral) region of the inferior macula, and all of the superior macula (inferior VF), project to the temporal quadrant, a region that is less susceptible to damage. The overall message is clear; clinicians need to be aware that glaucomatous damage to the macula is common, can occur early in the disease, and can be missed and/or underestimated with standard VF tests that use a 6° grid, such as the 24-2 VF test. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Plant tissue culture techniques

    Directory of Open Access Journals (Sweden)

    Rolf Dieter Illg


    Full Text Available Plant cell and tissue culture in a simple fashion refers to techniques which utilize either single plant cells, groups of unorganized cells (callus or organized tissues or organs put in culture, under controlled sterile conditions.

  14. FRD tissue archive (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The fishery genetics tissue collection has over 80,000 tissues stored in 95% ethanol representing fishes and invertebrates collected globally but with a focus on the...

  15. Nonorgan specific autoantibodies and heart damage. (United States)

    Tincani, A; Biasini-Rebaioli, C; Cattaneo, R; Riboldi, P


    Heart damage, mediated by different autoantibodies can involve several anatomical heart structures: valves, arteries, conduction tissue. Verrucous endocarditis is frequently reported in patients with antiphospholipid syndrome (APS) with or without systemic lupus erythematosus (SLE), particularly if they suffer from central nervous system involvement. Antiphospholipid antibodies (aPL) were shown deposited at subendothelial level of the affected valves. According to several in vitro and in vivo experimental models, aPL, anti-oxidized LDL (oxLDL), anti-heat shock protein 65 (HSP65) and anti-endothelial cells antibodies (AECA) seem to be involved in the pathogenesis of the atherosclerosis phenomena described in systemic autoimmune disease and vasculitis. However, the observation of the association of the same antibodies with clinical and subclinical atherosclerosis in patients is still controversial. The children of anti-Ro/SSA positive mothers can be affected by the congenital heart block. Anti Ro/SS-A antibodies play a major pathogenic role in affecting the heart conduction tissue in this rare condition.

  16. Adipose tissue fibrosis


    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina


    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. The...

  17. Bioreactors for tissue engineering. (United States)

    Chen, Huang-Chi; Hu, Yu-Chen


    Bioreactors are essential in tissue engineering, not only because they provide an in vitro environment mimicking in vivo conditions for the growth of tissue substitutes, but also because they enable systematic studies of the responses of living tissues to various mechanical and biochemical cues. The basic principles of bioreactor design are reviewed, the bioreactors commonly used for the tissue engineering of cartilage, bone and cardiovascular systems are assessed in terms of their performance and usefulness. Several novel bioreactor types are also reviewed.

  18. Rapid screening and diagnosis of various cancers from human voice using Bi-Digital O-Ring Test resonance phenomenon between 2 identical substances i.e. between microscope slide of specific cancer tissue & cancer information in the sound of human voice, and detection of myocardial damage & infection from human voice. (United States)

    Omura, Yoshiaki


    Since 1982, the author has been successfully using Bi-Digital O-Ring Test (BDORT) electro-magnetic resonance phenomenon between 2 identical substances; i.e. between specific cancer (in vivo) of a patient and a microscope slide of identical cancer tissue to detect cancers at a very early stage. Since 2000, the author has found that when BDORT is performed while an individual with a malignant tumor is talking, BDORT became (-1 approximately -10) in 94% of 200 cases and the number of openings (-) is approximately proportional to the degree of abnormality up to -10. Thus, cancer can be screened from voice within 1 min., without any instruments. Also, when cancer-free persons hold slides of cancer tissue or 10ng or higher Oncogene C-fos Ab2 or Integrin alpha5beta1 while talking over a short or long distance, BDORT always opens. To identify the type of the patient's malignancy, if BDORT is performed by an examiner holding a microscope slide of cancer tissue identical to the patient's cancer, characteristic strong BDORT resonance phenomenon appears with opening of all O-Rings formed between thumb and other fingers. When patients with myocardial infarct or various infections speak, no O-Rings open without holding identical pathological substances. Thus, it is possible to detect any type of malignancy from the voice, as long as a set of about 35 different tumor tissue slides is available. Based on these new findings, the author concluded that the voice of an individual with a malignancy carries information about the amount and structure of molecules present in malignant tissue.

  19. Vascularization Tissue Engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen; Rivron, N.C.; van Blitterswijk, Clemens


    Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial

  20. Tertiary lymphoid tissue (United States)

    Di Caro, Giuseppe; Marchesi, Federica


    Tumor-infiltrating lymphocytes influence colorectal cancer progression. We have recently documented that tertiary lymphoid tissue in the colorectal cancer microenvironment orchestrates lymphocyte infiltration and that tertiary lymphoid tissue and lymphocytes cooperate in a coordinated antitumor immune response to improve patient outcome. Thus, tertiary lymphoid tissue represents a potential target in the design of tailored immune-based therapeutic approaches. PMID:25083321

  1. Development of tissue bank

    Directory of Open Access Journals (Sweden)

    R P Narayan


    Full Text Available The history of tissue banking is as old as the use of skin grafting for resurfacing of burn wounds. Beneficial effects of tissue grafts led to wide spread use of auto and allograft for management of varied clinical conditions like skin wounds, bone defects following trauma or tumor ablation. Availability of adequate amount of tissues at the time of requirement was the biggest challenge that forced clinicians to find out techniques to preserve the living tissue for prolonged period of time for later use and thus the foundation of tissue banking was started in early twentieth century. Harvesting, processing, storage and transportation of human tissues for clinical use is the major activity of tissue banks. Low temperature storage of processed tissue is the best preservation technique at present. Tissue banking organization is a very complex system and needs high technical expertise and skilled personnel for proper functioning in a dedicated facility. A small lapse/deviation from the established protocol leads to loss of precious tissues and or harm to recipients as well as the risk of transmission of deadly diseases and tumors. Strict tissue transplant acts and stringent regulations help to streamline the whole process of tissue banking safe for recipients and to community as whole.

  2. Comet assay comparison of different Corbicula fluminea (Mollusca tissues for the detection of genotoxicity

    Directory of Open Access Journals (Sweden)

    Janaina Rigonato


    Full Text Available The comet assay was used to study the sensitivity of the widely distributed freshwater bivalve mollusk Corbicula fluminea to the DNA-damaging alkylating-agent methylmethane sulfonate (MMS. This study was undertaken to ascertain if C. fluminea is a good bioindicator of pollutants in aquatic environments and identify which C. fluminea tissue is most effective and practical for genotoxicity studies. The mollusks were exposed to 0.6, 1.2 or 2.4 X 10-4 M MMS for 40 min and their hemolymph, gill tissue and digestive gland tissue assessed for the level of DNA damage and the time needed for the tissues to recovery. Regression analysis showed a direct linear dose-response relationship between MMS concentration and the number of damaged cells for hemolymph and digestive gland tissue but a quadratic relationship for gill tissue, which made the interpretation the gill tissue results difficult. The basal level of DNA damage to gill tissue was very high, possibly because gill is the organs most directly exposed to environmental toxins and mutagenic agents. Although all three types of tissue produced useful results, hemolymph and digestive gland tissue produced more reproducible and reliable results. Hemolymph was the best sample type in that it was easy to obtain and handle, while gill tissue required more manipulation to obtain cell suspensions. Our results indicate that C. fluminea is an optimal bioindicator for the determination genotoxic contaminants in aquatic environments.

  3. Cancer risk and oxidative DNA damage in man. (United States)

    Loft, S; Poulsen, H E


    In living cells reactive oxygen species (ROS) are formed continuously as a consequence of metabolic and other biochemical reactions as well as external factors. Some ROS have important physiological functions. Thus, antioxidant defense systems cannot provide complete protection from noxious effects of ROS. These include oxidative damage to DNA, which experimental studies in animals and in vitro have suggested are an important factor in carcinogenesis. Despite extensive repair oxidatively modified DNA is abundant in human tissues, in particular in tumors, i.e., in terms of 1-200 modified nucleosides per 10(5) intact nucleosides. The damaged nucleosides accumulate with age in both nuclear and mitochondrial DNA. The products of repair of these lesions are excreted into the urine in amounts corresponding to a damage rate of up to 10(4) modifications in each cell every day. The most abundant of these lesions, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), is also the most mutagenic, resulting in GT transversions which are frequently found in tumor relevant genes. A series of other oxidative modifications of base and sugar residues occur frequently in DNA, but they are less well studied and their biological significance less apparent. The biomarkers for study of oxidative DNA damage in humans include urinary excretion of oxidized nucleosides and bases as repair products and modifications in DNA isolated from target tissue or surrogate cells, such as lymphocytes. These biomarkers reflect the rate of damage and the balance between the damage and repair rate, respectively. By means of biomarkers a number of important factors have been studied in humans. Ionizing radiation, a carcinogenic and pure source of ROS, induced both urinary and leukocyte biomarkers of oxidative DNA damage. Tobacco smoking, another carcinogenic source of ROS, increased the oxidative DNA damage rate by 35-50% estimated from the urinary excretion of 8-oxodG, and the level of 8-oxodG in leukocytes by 20

  4. Rapid Recovery of Damaged Ecosystems (United States)

    Jones, Holly P.; Schmitz, Oswald J.


    Background Recent reports on the state of the global environment provide evidence that humankind is inflicting great damage to the very ecosystems that support human livelihoods. The reports further predict that ecosystems will take centuries to recover from damages if they recover at all. Accordingly, there is despair that we are passing on a legacy of irreparable damage to future generations which is entirely inconsistent with principles of sustainability. Methodology/Principal Findings We tested the prediction of irreparable harm using a synthesis of recovery times compiled from 240 independent studies reported in the scientific literature. We provide startling evidence that most ecosystems globally can, given human will, recover from very major perturbations on timescales of decades to half-centuries. Significance/Conclusions Accordingly, we find much hope that humankind can transition to more sustainable use of ecosystems. PMID:19471645

  5. System for estimating fatigue damage (United States)

    LeMonds, Jeffrey; Guzzo, Judith Ann; Liu, Shaopeng; Dani, Uttara Ashwin


    In one aspect, a system for estimating fatigue damage in a riser string is provided. The system includes a plurality of accelerometers which can be deployed along a riser string and a communications link to transmit accelerometer data from the plurality of accelerometers to one or more data processors in real time. With data from a limited number of accelerometers located at sensor locations, the system estimates an optimized current profile along the entire length of the riser including riser locations where no accelerometer is present. The optimized current profile is then used to estimate damage rates to individual riser components and to update a total accumulated damage to individual riser components. The number of sensor locations is small relative to the length of a deepwater riser string, and a riser string several miles long can be reliably monitored along its entire length by fewer than twenty sensor locations.

  6. Measurement of small intestinal damage. (United States)

    Takeuchi, Koji; Satoh, Hiroshi


    Many animal models have been devised for investigating the pathogenesis of intestinal lesions and for screening drugs for the treatment of intestinal ulcers in humans. Recently, particular attention has been focused on NSAID-induced intestinal lesions as a result of the development of the capsule endoscope and double-balloon endoscope. Ischemic enteritis, one of the most dramatic abdominal emergencies, is known to cause severe damage to the small intestine by a significant decrease of arterial blood flow in the small intestine. In this unit, two animal models for small intestinal damage induced by NSAIDs or intestinal ischemia are described. Also included are methods for lesion induction and evaluation of the damage as well as the measurement of pathogenic functional and biochemical changes.

  7. [Damage control surgery: an update]. (United States)

    Edelmuth, Rodrigo Camargo Leão; Buscariolli, Yuri dos Santos; Ribeiro, Marcelo Augusto Fontenelle


    The damage control surgery is a widely accepted concept today among abdominal trauma specialists when it comes to the severely traumatized. In these patients, the death is due, in most cases, to the installation of the lethal triad (hypothermia, coagulopathy and acidosis) and not the inability to repair the serious initial damage. In this review, the authors address the lethal triad in its three phases and emphasize the measures taken to prevent them, as well as discussing the indication and employment of damage control surgery in its various stages. Restoring the physiological status of the patient in the ICU, so that he/she can be submitted to final operation and closure of the abdominal cavity, another challenge in severe trauma patients, is also discussed.

  8. The CATDAT damaging earthquakes database

    Directory of Open Access Journals (Sweden)

    J. E. Daniell


    Full Text Available The global CATDAT damaging earthquakes and secondary effects (tsunami, fire, landslides, liquefaction and fault rupture database was developed to validate, remove discrepancies, and expand greatly upon existing global databases; and to better understand the trends in vulnerability, exposure, and possible future impacts of such historic earthquakes.

    Lack of consistency and errors in other earthquake loss databases frequently cited and used in analyses was a major shortcoming in the view of the authors which needed to be improved upon.

    Over 17 000 sources of information have been utilised, primarily in the last few years, to present data from over 12 200 damaging earthquakes historically, with over 7000 earthquakes since 1900 examined and validated before insertion into the database. Each validated earthquake includes seismological information, building damage, ranges of social losses to account for varying sources (deaths, injuries, homeless, and affected, and economic losses (direct, indirect, aid, and insured.

    Globally, a slightly increasing trend in economic damage due to earthquakes is not consistent with the greatly increasing exposure. The 1923 Great Kanto ($214 billion USD damage; 2011 HNDECI-adjusted dollars compared to the 2011 Tohoku (>$300 billion USD at time of writing, 2008 Sichuan and 1995 Kobe earthquakes show the increasing concern for economic loss in urban areas as the trend should be expected to increase. Many economic and social loss values not reported in existing databases have been collected. Historical GDP (Gross Domestic Product, exchange rate, wage information, population, HDI (Human Development Index, and insurance information have been collected globally to form comparisons.

    This catalogue is the largest known cross-checked global historic damaging earthquake database and should have far-reaching consequences for earthquake loss estimation, socio-economic analysis, and the global

  9. Damage control surgery in the era of damage control resuscitation. (United States)

    Lamb, C M; MacGoey, P; Navarro, A P; Brooks, A J


    Damage control surgery (DCS) is a concept of abbreviated laparotomy, designed to prioritize short-term physiological recovery over anatomical reconstruction in the seriously injured and compromised patient. Over the last 10 yr, a new addition to the damage control paradigm has emerged, referred to as damage control resuscitation (DCR). This focuses on initial hypotensive resuscitation and early use of blood products to prevent the lethal triad of acidosis, coagulopathy, and hypothermia. This review aims to present the evidence behind DCR and its current application, and also to present a strategy of overall damage control to include DCR and DCS in conjunction. The use of DCR and DCS have been associated with improved outcomes for the severely injured and wider adoption of these principles where appropriate may allow this trend of improved survival to continue. In particular, DCR may allow borderline patients, who would previously have required DCS, to undergo early definitive surgery as their physiological derangement is corrected earlier. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email:

  10. Adipose tissue fibrosis. (United States)

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina


    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases.

  11. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. (United States)

    Elder, Benjamin D; Athanasiou, Kyriacos A


    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction.

  12. Cell and Tissue Engineering

    CERN Document Server


    “Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of ...

  13. Ocular tissue engineering: current and future directions. (United States)

    Karamichos, D


    Tissue engineering (TE) is a concept that was first emerged in the early 1990s to provide solutions to severe injured tissues and/or organs [1]. The dream was to be able to restore and replace the damaged tissue with an engineered version which would ultimately help overcome problems such as donor shortages, graft rejections, and inflammatory responses following transplantation. While an incredible amount of progress has been made, suggesting that TE concept is viable, we are still not able to overcome major obstacles. In TE, there are two main strategies that researchers have adopted: (1) cell-based, where cells are been manipulated to create their own environment before transplanted to the host, and (2) scaffold-based, where an extracellular matrix is created to mimic in vivo structures. TE approaches for ocular tissues are available and have indeed come a long way, over the last decades; however more clinically relevant ocular tissue substitutes are needed. Figure 1 highlights the importance of TE in ocular applications and indicates the avenues available based on each tissue.[...].

  14. Increased oxidative DNA damage, 8-hydroxydeoxy- guanosine, in human pterygium. (United States)

    Kau, H-C; Tsai, C-C; Lee, C-F; Kao, S-C; Hsu, W-M; Liu, J-H; Wei, Y-H


    Chronic exposure to ultraviolet (UV) light is a widely accepted aetiological factor in the development of pterygium. UV radiation may induce production of reactive oxygen species via photosensitized oxidation, thus causing oxidative damage. This study was conducted to test the hypothesis that oxidative damage to DNA is increased in pterygium. Immunohistochemical analysis employing a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a ubiquitous maker of oxidative stress, was performed in three patients with primary pterygium. The levels of 8-OHdG in DNA isolated from the other 29 pterygium specimens and their adjacent normal conjunctival tissues were determined using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry of 8-OHdG showed a distinct pattern of more extensive and intense staining in the nuclei of pterygium tissue compared with that in their adjacent normal conjunctiva. ELISA also revealed that the average level of 8-OHdG in the pterygium tissues was 4.7-fold higher than that of the corresponding normal conjunctiva (P<0.001). The increased levels of 8-OHdG in the pterygium tissues indicate that oxidative stress could play a role in the development of pterygium. These findings provide new information to better understand the pathogenesis of pterygium and are useful in the prevention and treatment of this disease.

  15. Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion


    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-guo


    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary ...

  16. Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach. (United States)

    Harrison, Noel M; McDonnell, Pat; Mullins, Liam; Wilson, Niall; O'Mahoney, Denis; McHugh, Peter E


    Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage -1.16 %, tension damage 0.69 %, compression fracture -2.91 % and tension fracture 1.98 %. Ultimate strength and post-ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile-brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post-ultimate strength softening.

  17. Pre-damage biomass allocation and not invasiveness predicts tolerance to damage in seedlings of woody species in Hawaii. (United States)

    Lurie, Matthew H; Barton, Kasey E; Daehler, Curtis C


    Plant-herbivore interactions have been predicted to play a fundamental role in plant invasions, although support for this assertion from previous research is mixed. While plants may escape from specialist herbivores in their introduced ranges, herbivory from generalists is common. Tolerance traits may allow non-native plants to mitigate the negative consequences of generalist herbivory that they cannot avoid in their introduced range. Here we address whether tolerance to herbivory, quantified as survival and compensatory growth, is associated with plant invasion success in Hawaii and investigate traits that may enhance tolerance in seedlings, the life stage most susceptible to herbivory. In a greenhouse experiment, we measured seedling tolerance to simulated herbivory through mechanical damage (50% leaf removal) of 16 non-native woody plant species differing in invasion status (invasive vs. non-invasive). Seedlings were grown for 2 weeks following damage and analyzed for biomass to determine whether damaged plants could fully compensate for the lost leaf tissue. Over 99% of all seedlings survived defoliation. Although species varied significantly in their levels of compensation, there was no consistent difference between invasive and non-invasive species. Seedlings of 11 species undercompensated and remained substantially smaller than control seedlings 2 weeks after damage; four species were close to compensating, while one species overcompensated. Across species, compensation was positively associated with an increased investment in potential storage reserves, specifically cotyledons and roots, suggesting that these organs provide resources that help seedlings re-grow following damage. Our results add to a growing consensus that pre-damage growth patterns determine tolerance to damage, even in young seedlings which have relatively low biomass. The lack of higher tolerance in highly invasive species may suggest that invaders overcome herbivory barriers to invasion

  18. Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo. (United States)

    Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J


    Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL

  19. Non-contact hematoma damage and healing assessment using reflectance photoplethysmographic imaging (United States)

    Amelard, Robert; Pfisterer, Kaylen J.; Clausi, David A.; Wong, Alexander


    Impact trauma may cause a hematoma, which is the leakage of venous blood into surrounding tissues. Large hematomas can be dangerous as they may inhibit local blood ow. Hematomas are often diagnosed visually, which may be problematic if the hematoma leaks deeper than the visible penetration depth. Furthermore, vascular wound healing is often monitored at home without the aid of a clinician. We therefore investigated the use of near infrared (NIR) re ectance photoplethysmographic imaging (PPGI) to assess vascular damage resulting from a hematoma, and monitor the healing process. In this case study, the participant experienced internal vascular damage in the form of a hematoma. Using a PPGI system with dual-mode temporally coded illumination for ambient-agnostic data acquisition and mounted optical elements, the tissue was illuminated with a spatially uniform irradiance pattern of 850 nm wavelength light for increased tissue penetration and high oxy-to-deoxyhemoglobin absorption ratio. Initial and follow-up PPGI data collection was performed to assess vascular damage and healing. The tissue PPGI sequences were spectrally analyzed, producing spectral maps of the tissue area. Experimental results show that spatial differences in spectral information can be observed around the damaged area. In particular, the damaged site exhibited lower pulsatility than the surrounding healthy tissue. This pulsatility was largely restored in the follow-up data, suggesting that the tissue had undergone vascular healing. These results indicate that hematomas can be assessed and monitored in a non-contact visual manner, and suggests that PPGI can be used for tissue health assessment, with potential extensions to peripheral vascular disease.



    Iviglia, Giorgio


    Periodontium is a complex system of different tissues, such as connective tissue, cartilage and bone, which work together to sustain the tooth. Gingivitis and periodontitis are devastating diseases that could affect the structure and function of the periodontal tissue. When the gingivitis are not treated and controlled with a correct oral hygiene, they could evolve in periodontitis, which could seriously damage the tissue surrounding the tooth and lead tooth loss. The main objective of period...

  1. Regeneration of the skin and muscle tissue in rainbow trout (Oncorhynchus mykiss) following mechanical injury

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Nielsen, Michael Engelbrecht

    Mechanical injury induced by needles penetrating the skin and underlying muscle tissue in rainbow trout (Oncorhynchus mykiss) was used as a model to study the initial phase(s) of tissue regeneration. Tissue regeneration in humans is characterised by four phases; hemostatis, inflammation......, proliferation and remodelling. We investigated the expression of genes traditionally being important in these processes untill 7 days after the tissue damage in order to find inducible genetic markers following mechanical injury....

  2. Stress, depression and hippocampal damage

    Indian Academy of Sciences (India)

    Amongst the prime targets of stress in the brain is the hippocampus, which has high receptor levels for corticoster- oids that are released during stress (McEwen 1999). Over the years evidence has built up that stress leads to damage of the hippocampus. Initial reports from Uno et al (1989) indicated that primates exposed to ...

  3. LX-10 Explosive Damage Studies (United States)


    3  Experiment ...damaged spherical samples were returned to LLNL for further study at that facility. EXPERIMENT SHOTGUN A schematic of the Naval Air...regression rate based on thermochemistry , as determined from a thermochemical equilibrium code (BLAKE in this study) (Reference 7). The mass burning

  4. Heavy snowfall damage Virginia pine (United States)

    Richard H. Fenton


    In the Coastal Plain from Virginia to Pennsylvania, snowstorms heavy enough to damage trees are unusual. Weather Bureau records for the general area show that heavy snowfall - 8 to 25 inches in a single storm - occurs at an average frequency of about once in 7 years.

  5. (UVB)-induced DNA damage

    African Journals Online (AJOL)



    Aug 17, 2011 ... effects of extract from P. ordoratissimus flowers on ultraviolet B (UVB)-induced DNA damage have not yet been reported. ... POE significantly decreased tail DNA (TD%), tail length (TL) and micronucleus frequencies (MNFs) .... UVB radiation used in this experiment was EUV at three levels, namely, 5.70 ...

  6. Muscle damage and inflammation during recovery from exercise. (United States)

    Peake, Jonathan M; Neubauer, Oliver; Della Gatta, Paul A; Nosaka, Kazunori


    Unaccustomed exercise consisting of eccentric (i.e., lengthening) muscle contractions often results in muscle damage characterized by ultrastructural alterations in muscle tissue, clinical signs, and symptoms (e.g., reduced muscle strength and range of motion, increased muscle soreness and swelling, efflux of myocellular proteins). The time course of recovery following exercise-induced muscle damage depends on the extent of initial muscle damage, which in turn is influenced by the intensity and duration of exercise, joint angle/muscle length, and muscle groups used during exercise. The effects of these factors on muscle strength, soreness, and swelling are well characterized. By contrast, much less is known about how they affect intramuscular inflammation and molecular aspects of muscle adaptation/remodeling. Although inflammation has historically been viewed as detrimental for recovery from exercise, it is now generally accepted that inflammatory responses, if tightly regulated, are integral to muscle repair and regeneration. Animal studies have revealed that various cell types, including neutrophils, macrophages, mast cells, eosinophils, CD8 and T-regulatory lymphocytes, fibro-adipogenic progenitors, and pericytes help to facilitate muscle tissue regeneration. However, more research is required to determine whether these cells respond to exercise-induced muscle damage. A large body of research has investigated the efficacy of physicotherapeutic, pharmacological, and nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage, with mixed results. More research is needed to examine if/how these treatments influence inflammation and muscle remodeling during recovery from exercise. Copyright © 2017 the American Physiological Society.

  7. Regeneration of periodontal tissues: guided tissue regeneration. (United States)

    Villar, Cristina C; Cochran, David L


    The concept that only fibroblasts from the periodontal ligament or undifferentiated mesenchymal cells have the potential to re-create the original periodontal attachment has been long recognized. Based on this concept, guided tissue regeneration has been applied with variable success to regenerate periodontal defects. Quantitative analysis of clinical outcomes after guided tissue regeneration suggests that this therapy is a successful and predictable procedure to treat narrow intrabony defects and class II mandibular furcations, but offers limited benefits in the treatment of other types of periodontal defects.

  8. Mechanisms of Sensorineural Cell Damage, Death and Survival in the Cochlea

    Directory of Open Access Journals (Sweden)

    Allen Frederic Ryan


    Full Text Available The majority of acquired hearing loss, including presbycusis, is caused by irreversible damage to the sensorineural tissues of the cochlea. This article reviews the intracellular mechanisms that contribute to sensorineural damage in the cochlea, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. These data have primarily been generated in hearing loss not directly related to age. However, there is evidence that similar mechanisms operate in presbycusis. Moreover, accumulation of damage from other causes can contribute to age-related hearing loss. Potential therapeutic interventions to balance opposing but interconnected cell damage and survival pathways, such as antioxidants, anti-apoptotics, and pro-inflammatory cytokine inhibitors, are also discussed.

  9. Comparison of soft and hard tissue ablation with sub-ps and ns pulse lasers

    Energy Technology Data Exchange (ETDEWEB)

    Da Silva, L.B.; Stuart, B.C.; Celliers, P.M.; Feit, M.D.; Glinsky, M.E.; Heredia, N.J.; Herman, S.; Lane, S.M.; London, R.A.; Matthews, D.L.; Perry, M.D.; Rubenchik, A.M. [Lawrence Livermore National Lab., CA (United States); Chang, T.D. [Veterans Administration Hospital, Martinez, CA (United States); Neev, J. [Beckman Laser Inst. and Medical Clinic, Irvine, CA (United States)


    Tissue ablation with ultrashort laser pulses offers several unique advantages. The nonlinear energy deposition is insensitive to tissue type, allowing this tool to be used for soft and hard tissue ablation. The localized energy deposition lead to precise ablation depth and minimal collateral damage. This paper reports on efforts to study and demonstrate tissue ablation using an ultrashort pulse laser. Ablation efficiency and extent of collateral damage for 0.3 ps and 1000 ps duration laser pulses are compared. Temperature measurements of the rear surface of a tooth section is also presented.

  10. Plate tectonics, damage and inheritance. (United States)

    Bercovici, David; Ricard, Yanick


    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  11. Injectable hydrogels for cartilage and bone tissue engineering (United States)

    Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue


    Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

  12. Fiber-reinforced scaffolds in soft tissue engineering (United States)

    Wang, Wei; Fan, Yubo; Wang, Xiumei; Watari, Fumio


    Abstract Soft tissue engineering has been developed as a new strategy for repairing damaged or diseased soft tissues and organs to overcome the limitations of current therapies. Since most of soft tissues in the human body are usually supported by collagen fibers to form a three-dimensional microstructure, fiber-reinforced scaffolds have the advantage to mimic the structure, mechanical and biological environment of natural soft tissues, which benefits for their regeneration and remodeling. This article reviews and discusses the latest research advances on design and manufacture of novel fiber-reinforced scaffolds for soft tissue repair and how fiber addition affects their structural characteristics, mechanical strength and biological activities in vitro and in vivo. In general, the concept of fiber-reinforced scaffolds with adjustable microstructures, mechanical properties and degradation rates can provide an effective platform and promising method for developing satisfactory biomechanically functional implantations for soft tissue engineering or regenerative medicine. PMID:28798872

  13. Hyperthermia-induced vascular injury in normal and neoplastic tissue. (United States)

    Badylak, S F; Babbs, C F; Skojac, T M; Voorhees, W D; Richardson, R C


    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 degrees C and 45 degrees C for 20 minutes), were studied by histologic and ultrastructural examination. Normal muscle and Walker 256 tumors showed edema, congestion, and hemorrhage at 5 minutes post-heating (PH), followed by suppuration, macrophage infiltration, and thrombosis at 6 and 48 hours PH, and finally by regeneration and repair by 7 days PH. Vascular endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive injury occurred for at least 48 hours PH. Two hyperthermia treatments separated by a 30- or 60-min cooling interval, were applied to Walker 256 tumors in a subsequent study. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral steady state temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results suggest that vascular damage contributes to the immediate and latent cytotoxic effects of hyperthermia in normal tissue and some types of neoplastic tissue, and that selective heating of neoplastic tissue occurs in tumor tissue with disrupted microvasculature.

  14. Towards high throughput tissue engineering: development of chitosan-calcium phosphate scaffolds for engineering bone tissue from embryonic stem cells


    Ko, Junghyuk; Kolehmainen, Kathleen; Ahmed, Farid; Jun, Martin BG; Willerth, Stephanie M.


    Tissue engineering strategies have shown promise for the repair of damaged organs, including bone. One of the major challenges associated with tissue engineering is how to scale up such processes for high throughput manufacturing of biomaterial scaffolds used to support stem cell culture. Generation of certain types of 3D biomaterial scaffolds, including chitosan-calcium phosphate blends, involves a slow fabrication process followed by a lengthy required freeze drying step. This work investig...

  15. Cartilage Tissue Engineering: the effect of different biomaterials, cell types and culture methods

    NARCIS (Netherlands)

    W.J.C.M. Marijnissen (Willem)


    textabstractChapter 1 outlines the normal structure and composition of articular cartilage and the inefficient spontaneous healing response after focal damage. Current surgical treatment options are briefly discussed and tissue engineering techniques for the repair of articular cartilage defects

  16. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    NARCIS (Netherlands)

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.


    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for

  17. Common Laundry Detergent Ingredient May Help Preserve Muscle Tissue After Severe Injury (United States)

    ... has not previously been tested for treating skeletal muscle injuries. The compound was modified so that it could be injected directly into damaged muscle tissue. Initial laboratory studies compared SPO-treated and ...

  18. Montelukast prevents ischaemia/reperfusion-induced ovarian damage in rats. (United States)

    Akdemir, A; Erbaş, O; Ergenoğlu, M; Ozgür Yeniel, A; Oltulu, F; Yavaşoğlu, A; Taskiran, D


    To investigate the efficacy of montelukast for prevention of ischaemia/reperfusion (I/R) injury in rat ovary. Twenty-four female adult rats were included in the study. I/R injury was induced by CO2 pneumoperitoneum in a laparoscopic rat model. The rats were divided at random into three groups: the sham group was subjected to catheter insertion but was not subjected to pneumoperitoneum; the saline group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 1 mg/kg physiological saline administered 10 min before pneumoperitoneum; and the montelukast group was subjected to 60 min of pneumoperitoneum and 30 min of reperfusion, with 20mg/kg montelukast administered 10 min before pneumoperitoneum. Damage to ovarian tissue was scored by histopathological evaluation. Caspase-3 expression was determined immunohistochemically. Ovarian tissue levels of malondialdehyde and glutathione, and plasma total antioxidant capacity were measured biochemically. In comparison with the sham group, ovarian sections in the montelukast group had higher scores for follicular degeneration and oedema (pMontelukast treatment prevented tissue damage in ovaries, and this result was significant. Caspase-3 expression was only observed in ovarian surface epithelium in the saline and montelukast groups. However, the mean caspase-3 expression score was higher in the saline group than the montelukast group (pmontelukast group than the sham group, but plasma total antioxidant capacity and tissue levels of glutathione were significantly lower. Pretreatment with montelukast reduced lipid peroxidation (pMontelukast is effective for the prevention of I/R-induced damage in rat ovary. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Tissue engineering in dentistry. (United States)

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C


    of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the

  20. Anisotropic Materials for Skeletal-Muscle-Tissue Engineering. (United States)

    Jana, Soumen; Levengood, Sheeny K Lan; Zhang, Miqin


    Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of large volumetric skeletal-muscle loss. As an alternative, tissue engineering represents a promising approach for the functional restoration of damaged muscle tissue. A typical tissue-engineering process involves the design and fabrication of a scaffold that closely mimics the native skeletal-muscle extracellular matrix (ECM), allowing organization of cells into a physiologically relevant 3D architecture. In particular, anisotropic materials that mimic the morphology of the native skeletal-muscle ECM, can be fabricated using various biocompatible materials to guide cell alignment, elongation, proliferation, and differentiation into myotubes. Here, an overview of fundamental concepts associated with muscle-tissue engineering and the current status of muscle-tissue-engineering approaches is provided. Recent advances in the development of anisotropic scaffolds with micro- or nanoscale features are reviewed, and how scaffold topographical, mechanical, and biochemical cues correlate to observed cellular function and phenotype development is examined. Finally, some recent developments in both the design and utility of anisotropic materials in skeletal-muscle-tissue engineering are highlighted, along with their potential impact on future research and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Direct plasma interaction with living tissue (United States)

    Fridman, Gregory

    For some time, plasma has been used in medicine to cauterize or cut tissue using heat and mechanical energy. In the recent decade, some researchers around the world have started to investigate how gas jets that pass through thermal plasma can be employed in medicine. This thesis presents the first investigation of biomedical uses of non-thermal plasma discharge which comes in direct contact with living tissue. It is demonstrated that the direct application of non-thermal plasma in air can cause rapid deactivation of bacteria on surfaces of tissues without causing any visible tissue damage. Medical need for such a device is discussed. Construction and operation of various types of non-thermal plasma power supplies and many types of treatment electrodes are presented as well. Application of this plasma to living organisms is shown to be safe from both the electrical perspective and from the biological perspective. Biological safety is revealed through a series of differential skin toxicity trials on human cadaver tissue, live hairless mouse skin tissue, live pig skin tissue, and finally in an open wound model on pigs. Direct non-thermal plasma in air is shown to deactivate bacteria about 100 times faster than indirect application using jets. A series of experiments reveal that this effectiveness is due to the ability of direct discharge to bring charges to tissue surfaces. It is demonstrated that neither ultraviolet (UV) radiation nor neutral active species such as hydroxyl radicals or ozone produced in plasma are responsible for the main effect on bacteria. Although much additional work remains on establishing detailed mechanism by which charges from plasma achieve this effect, the work carried out in this thesis clearly demonstrates that direct application of non-thermal plasma in air can be a very useful tool in medicine.

  2. X-ray phase contrast imaging of calcified tissue and biomaterial structure in bioreactor engineered tissues. (United States)

    Appel, Alyssa A; Larson, Jeffery C; Garson, Alfred B; Guan, Huifeng; Zhong, Zhong; Nguyen, Bao-Ngoc B; Fisher, John P; Anastasio, Mark A; Brey, Eric M


    Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. Techniques that allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. These results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors. © 2014 Wiley Periodicals, Inc.

  3. X-ray Phase Contrast Imaging of Calcified Tissue and Biomaterial Structure in Bioreactor Engineered Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Appel, Alyssa A. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States); Larson, Jeffery C. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States); Garson, III, Alfred B. [George Washington Univ., Washington, DC (United States); Guan, Huifeng [George Washington Univ., Washington, DC (United States); Zhong, Zhong [Brookhaven National Lab. (BNL), Upton, NY (United States); Nguyen, Bao-Ngoc [Univ. of Maryland, College Park, MD (United States); Fisher, John P. [Univ. of Maryland, College Park, MD (United States); Anastasio, Mark A. [George Washington Univ., Washington, DC (United States); Brey, Eric M. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States)


    Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. These techniques allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems and will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. Furthermore, these results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.

  4. Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. (United States)

    Schrauwen, Patrick; Hesselink, Matthijs K C


    Recent evidence points toward decreased oxidative capacity and mitochondrial aberrations as a major contributor to the development of insulin resistance and type 2 diabetes. In this article we will provide an integrative view on the interrelation between decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations in type 2 diabetes. Type 2 diabetes is characterized by disturbances in fatty acid metabolism and is accompanied by accumulation of fatty acids in nonadipose tissues. In metabolically active tissues, such as skeletal muscle, fatty acids are prone to so-called oxidative damage. In addition to producing energy, mitochondria are also a major source of reactive oxygen species, which can lead to lipid peroxidation. In particular, the mitochondrial matrix, which contains DNA, RNA, and numerous enzymes necessary for substrate oxidation, is sensitive to peroxide-induced oxidative damage and needs to be protected against the formation and accumulation of lipids and lipid peroxides. Recent evidence reports that mitochondrial uncoupling is involved in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Disturbances in this protection mechanism can contribute to the development of type 2 diabetes.

  5. Impact of Hot Environment on Fluid and Electrolyte Imbalance, Renal Damage, Hemolysis, and Immune Activation Postmarathon

    Directory of Open Access Journals (Sweden)

    Rodrigo Assunção Oliveira


    Full Text Available Previous studies have demonstrated the physiological changes induced by exercise exposure in hot environments. We investigated the hematological and oxidative changes and tissue damage induced by marathon race in different thermal conditions. Twenty-six male runners completed the São Paulo International Marathon both in hot environment (HE and in temperate environment (TE. Blood and urine samples were collected 1 day before, immediately after, 1 day after, and 3 days after the marathon to analyze the hematological parameters, electrolytes, markers of tissue damage, and oxidative status. In both environments, the marathon race promotes fluid and electrolyte imbalance, hemolysis, oxidative stress, immune activation, and tissue damage. The marathon runner’s performance was approximately 13.5% lower in HE compared to TE; however, in HE, our results demonstrated more pronounced fluid and electrolyte imbalance, renal damage, hemolysis, and immune activation. Moreover, oxidative stress induced by marathon in HE is presumed to be related to protein/purine oxidation instead of other oxidative sources. Fluid and electrolyte imbalance and protein/purine oxidation may be important factors responsible for hemolysis, renal damage, immune activation, and impaired performance after long-term exercise in HE. Nonetheless, we suggested that the impairment on performance in HE was not associated to the muscle damage and lipoperoxidation.

  6. Ablation of skin tissue by holmium:YAG laser (United States)

    Chen, Wei R.; Holt, Andrew; Nordquist, Robert E.


    Surface epithelial damage by Ho:YAG laser and recovery were studied using histology and electron microscopy. Rabbit skin was irradiated with fluence varying from 55 J/cm2 to 680 J/cm2. Laser damage was determined by histological measurement of three major injury indicators: surface lesion width, depth of photocoagulation, and depth of thermal damage. When the fluence increased, the surface lesion widened and the photocoagulation zone extended deeper into the dermis. The thermally damaged zone (60 degree(s)C muscle and nerve tissues appeared to remain intact under most of our irradiance except at 500 J/cm2 and greater. Thermally injured tissues began recovery within a short period and eventually returned to normal; electron microscopic findings indicated that severe swelling occurred in the individual collagen fibrils, but they were not disrupted and usually recovered to appear normal. A layer of new epithelium started growing underneath the photocoagulated zone around day 3. After 7 days, most photocoagulated tissue was partially, in some cases completely, separated from the skin by the new epithelium. The damage and recovery parameters established should aid in the clinical use of Holmium laser in treating lesions, benign or malignant, in hollow tubular organs and on surface epithelia.

  7. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)


    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  8. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’Dea, R. D.


    In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

  9. Monitoring of tissue optical properties during thermal coagulation of ex vivo tissues. (United States)

    Nagarajan, Vivek Krishna; Yu, Bing


    Real-time monitoring of tissue status during thermal ablation of tumors is critical to ensure complete destruction of tumor mass, while avoiding tissue charring and excessive damage to normal tissues. Currently, magnetic resonance thermometry (MRT), along with magnetic resonance imaging (MRI), is the most commonly used technique for monitoring and assessing thermal ablation process in soft tissues. MRT/MRI is very expensive, bulky, and often subject to motion artifacts. On the other hand, light propagation within tissue is sensitive to changes in tissue microstructure and physiology which could be used to directly quantify the extent of tissue damage. Furthermore, optical monitoring can be a portable, and cost-effective alternative for monitoring a thermal ablation process. The main objective of this study, is to establish a correlation between changes in tissue optical properties and the status of tissue coagulation/damage during heating of ex vivo tissues. A portable diffuse reflectance spectroscopy system and a side-firing fiber-optic probe were developed to study the absorption (μa (λ)), and reduced scattering coefficients (μ's (λ)) of native and coagulated ex vivo porcine, and chicken breast tissues. In the first experiment, both porcine and chicken breast tissues were heated at discrete temperature points between 24 and 140°C for 2 minutes. Diffuse reflectance spectra (430-630 nm) of native and coagulated tissues were recorded prior to, and post heating. In a second experiment, porcine tissue samples were heated at 70°C and diffuse reflectance spectra were recorded continuously during heating. The μa (λ) and μ's (λ) of the tissues were extracted from the measured diffuse reflectance spectra using an inverse Monte-Carlo model of diffuse reflectance. Tissue heating was stopped when the wavelength-averaged scattering plateaued. The wavelength-averaged optical properties, and , for native porcine tissues (n = 66) at room temperature, were 5.4

  10. Ionic liquids in embalming and tissue preservation. Can traditional formalin-fixation be replaced safely? (United States)

    Majewski, Przemysław; Pernak, Agnieszka; Grzymisławski, Marian; Iwanik, Katarzyna; Pernak, Juliusz


    Ionic liquids (ILs) can be used for embalming and tissue preservation. ILs does not cause tissue damage and the tissue colour remains unaltered after treatment. Microscopical morphology of tissues fixed in ILs is of better quality than that of tissues fixed in formalin. Tissue preservation depends on the type of ILs. Best results were obtained with 1-methyl-3-octyloxymethylimidazolium tetrafluoroborate, the density of which resembles that of water. The salt is nonvaporous and when used as a formalin substitute, it eliminates health hazards in the pathological laboratory.

  11. Garlic and vitamin E provides antioxidant defence in tissues of ...

    African Journals Online (AJOL)

    Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats ...

  12. Cell-derived vesicles exposing coagulant tissue factor in saliva

    NARCIS (Netherlands)

    Berckmans, René J.; Sturk, Auguste; van Tienen, Laurens M.; Schaap, Marianne C. L.; Nieuwland, Rienk


    On vascular damage, coagulation is initiated by extravascular tissue factor (TF). Intravascular TF, which is present on circulating cell-derived vesicles, is non-coagulant under physiologic conditions but prothrombotic under pathologic conditions. Human saliva triggers coagulation, but the mechanism

  13. Corrosion damage of rivet joints

    Directory of Open Access Journals (Sweden)

    Michal Černý


    Full Text Available The work describes the effect of the atmospheric corrosion upon the mechanical properties of blind rivets. The subject of given research is: corrosion of metal materials, system resistance, design modification and others means of prevention against the corrosion attack. The problem of blind rivets, blind rivet setting, setting equipment, terminology and definitions, characteristic, and special blind rivet setting is also analysed. The experiment itself, the experimental method and the evaluation of the test are described. Mechanism of riveted joint damage produced by galvanic corrosion is proposed. Considerable corrosion damage occurred at combination of the joint members and connected materials with different electrochemical potentials. Exposition to the corroding environment produces release of rivet clam, together with decrease of rivet stiffness. The proof of these mechanisms is documented by functional dependence F – ∆L and metallographic tests.

  14. Radiation damage in biomolecular systems

    CERN Document Server

    Fuss, Martina Christina


    Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

  15. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke


    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  16. Undifferentiated Connective Tissue Disease (United States)

    ... Examples of connective tissue diseases include lupus , scleroderma , rheumatoid arthritis , Sjögren's syndrome , myositis and vasculitis . There are many people who have features of connective tissue disease, however, they do not fulfill the diagnostic criteria established for any one disease. In such ...

  17. Engineering Vascularized Adipose Tissue

    NARCIS (Netherlands)

    F. Verseijden (Femke)


    textabstractA large portion of the plastic and reconstructive surgical procedures performed each year is aimed at repairing soft tissue defects, which result for example from traumatic injury or tumor resections. Large soft tissue defects, lead to a change in function and ‘normal’ body contour,

  18. Tissue engineered aortic valve


    Dohmen, P M


    Several prostheses are available to replace degenerative diseased aortic valves with unique advantages and disadvantages. Bioprotheses show excellent hemodynamic behavior and low risk of thromboembolic complications, but are limited by tissue deterioration. Mechanical heart valves have extended durability, but permanent anticoagulation is mandatory. Tissue engineering created a new generation heart valve, which overcome limitations of biological and mechanical heart valves due to remodelling,...

  19. Loss and damage livelihood resilience


    Geest, Kees van der; Kreft, Sönke; Zommers, Zinta; Huq, Saleemul; Quandt, Amy; Preato, Alberto; Chandra, Alvin; Mulla, Ava; Chaffin, Brian; Koto, Camari; Barthelt, Christian; Carter, Christopher J.; Corendea, Cosmin; Wrathall, David; Opondo, Denis Opiyo


    Climate change Loss and Damage has emerged as a key challenge of the 21st century. This Policy Brief first frames the challenge and then introduces the Resilience Academy, highlighting 5 key insights that both feed the debate and inform action. Finally, it provides 5 recommendations to the Executive Committee of the Warsaw International Mechanism (WIM ExCom) for its 5-year work plan.

  20. Myoglobin-induced oxidative damage

    DEFF Research Database (Denmark)

    Irwin, J A; Ostdal, H; Davies, Michael Jonathan


    -to-protein radical transfer and hence chain-oxidation occurs, and the factors that control these reactions. Three amino acids show significant reactivity: Tyr, Trp, and Cys, with Cys the least efficient. Evidence has also been obtained for (inefficient) hydrogen abstraction at peptide alpha-carbon sites; this may...... that protein-to-protein damage transfer and protein chain-oxidation may occur readily in biological systems....

  1. Composite heat damage spectroscopic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Janke, C.J.; Muhs, J.D.; Wachter, E.A.; Ziegler, R.E. (Oak Ridge National Lab., TN (USA)); Powell, G.L.; Smyrl, N.R. (Oak Ridge Y-12 Plant, TN (USA)); Philpot, H.E. (Oak Ridge Gaseous Diffusion Plant, TN (USA))


    The Oak Ridge National Laboratory/Applied Technology Division (ORNL/ATD) has successfully demonstrated the unique applicability of two spectroscopic techniques that possess the capability of detecting heat damage in IM6/3501-6 laminates and correlation of this damage with the residual mechanical-strength properties. The results on the diffuse reflectance infrared fourier transform (DRIFT) and laser-pumped fluorescence (LPF) spectroscopic techniques, which are capable of rapid, in-service, non-destructive detection and quantitation of heat damage in IM6/3501-6 laminates, is presented. Both of these techniques have been shown to be quite effective at probing the elusive and complex molecular changes that take place in IM6/3501-6 laminates subjected to varying degrees of thermal degradation. Using LPF or DRIFT techniques, it has been shown that laminates having different thermal histories can be readily differentiated from one another due to their characteristic fingerprint'' spectral features. The effects of short-term, elevated temperature heating on the room- temperature compressive interlaminar-shear, and flexural strengths and room-temperature shore-D hardness properties of dry'' and wet'' preconditioned IM6/3501-6 laminates are discussed. Additionally, the geometrical changes and percent-weight-loss measurements of IM6/3501-6 laminates that accompany heat damage are also examined. It was found that below a certain temperature/time exposure threshold, these laminates visually and microscopically appeared to be undamaged but, in fact, may have lost a significant percentage of their original strength. In addition, laminates that were exposed above the temperature/time exposure threshold suffered dramatic geometrical changes and large amounts of weight loss. 32 refs., 39 figs., 10 tabs.

  2. Smart accelerometer. [vibration damage detection (United States)

    Bozeman, Richard J., Jr. (Inventor)


    The invention discloses methods and apparatus for detecting vibrations from machines which indicate an impending malfunction for the purpose of preventing additional damage and allowing for an orderly shutdown or a change in mode of operation. The method and apparatus is especially suited for reliable operation in providing thruster control data concerning unstable vibration in an electrical environment which is typically noisy and in which unrecognized ground loops may exist.

  3. DNA-Damage-Induced Type I Interferon Promotes Senescence and Inhibits Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Qiujing Yu


    Full Text Available Expression of type I interferons (IFNs can be induced by DNA-damaging agents, but the mechanisms and significance of this regulation are not completely understood. We found that the transcription factor IRF3, activated in an ATM-IKKα/β-dependent manner, stimulates cell-autonomous IFN-β expression in response to double-stranded DNA breaks. Cells and tissues with accumulating DNA damage produce endogenous IFN-β and stimulate IFN signaling in vitro and in vivo. In turn, IFN acts to amplify DNA-damage responses, activate the p53 pathway, promote senescence, and inhibit stem cell function in response to telomere shortening. Inactivation of the IFN pathway abrogates the development of diverse progeric phenotypes and extends the lifespan of Terc knockout mice. These data identify DNA-damage-response-induced IFN signaling as a critical mechanism that links accumulating DNA damage with senescence and premature aging.

  4. Continuum damage and fracture mechanics

    CERN Document Server

    Öchsner, Andreas


    This textbook offers readers an introduction to damage and fracture mechanics, equipping them to grasp the basic ideas of the presented approaches to modeling in applied mechanics. In the first part, the book reviews and expands on the classical theory of elastic and elasto-plastic material behavior. A solid understanding of these two topics is the essential prerequisite to advancing to damage and fracture mechanics. Thus, the second part of this course provides an introduction to the treatment of damage and fractures in the context of applied mechanics. Wherever possible, the one-dimensional case is first introduced and then generalized in a following step. This departs somewhat from the more classical approach, where first the most general case is derived and then simplified to special cases. In general, the required mathematics background is kept to a minimum.   Tutorials are included at the end of each chapter, presenting the major steps for the solution and offering valuable tips and tricks. The supplem...

  5. Economic measurement of environment damages

    Energy Technology Data Exchange (ETDEWEB)

    Krawiec, F.


    The densities, energy consumption, and economic development of the increasing population exacerbate environmental degradation. Air and water pollution is a major environmental problem affecting life and health, outdoor recreation, household soiling, vegetation, materials, and production. The literature review indicated that numerous studies have assessed the physical and monetary damage to populations at risk from excessive concentrations of major air and water pollutants-sulfur dioxide, total suspended particulate matter, oxidants, and carbon monoxide in air; and nutrients, oil, pesticides, and toxic metals and others in water. The measurement of the damages was one of the most controversial issues in pollution abatement. The methods that have been used to estimate the societal value of pollution abatement are: (1) chain of effects, (2) market approaches, and (3) surveys. National gross damages of air pollution of $20.2 billion and of water pollution of $11.1 billion for 1973 are substantial. These best estimates, updated for the economic and demographic conditions, could provide acceptable control totals for estimating and predicting benefits and costs of abating air and water pollution emissions. The major issues to be resolved are: (1) lack of available noneconomic data, (2) theoretical and empirical difficulties of placing a value on human life and health and on benefits such as aesthetics, and (3) lack of available demographic and economic data.

  6. Tissue engineering and ureter regeneration: is it possible? (United States)

    Kloskowski, Tomasz; Kowalczyk, Tomasz; Nowacki, Maciej; Drewa, Tomasz


    Large ureter damages are difficult to reconstruct. Current techniques are complicated, difficult to perform, and often associated with failures. The ureter has never been regenerated thus far. Therefore the use of tissue engineering techniques for ureter reconstruction and regeneration seems to be a promising way to resolve these problems. For proper ureter regeneration the following problems must be considered: the physiological aspects of the tissue, the type and shape of the scaffold, the type of cells, and the specific environment (urine). 
This review presents tissue engineering achievements in the field of ureter regeneration focusing on the scaffold, the cells, and ureter healing.

  7. Messages from the Other Side: Parasites Receive Damage Cues from their Host Plants. (United States)

    Tjiurutue, Muvari Connie; Stevenson, Philip C; Adler, Lynn S


    As sessile organisms, plants rely on their environment for cues indicating imminent herbivory. These cues can originate from tissues on the same plant or from different individuals. Since parasitic plants form vascular connections with their host, parasites have the potential to receive cues from hosts that allow them to adjust defenses against future herbivory. However, the role of plant communication between hosts and parasites for herbivore defense remains poorly investigated. Here, we examined the effects of damage to lupine hosts (Lupinus texensis) on responses of the attached hemiparasite (Castilleja indivisa), and indirectly, on a specialist herbivore of the parasite, buckeyes (Junonia coenia). Lupines produce alkaloids that act as defenses against herbivores that can be taken up by the parasite. We found that damage to lupine host plants by beet armyworm (Spodoptera exigua) significantly increased jasmonic acid (JA) levels in both the lupine host and parasite, suggesting uptake of phytohormones or priming of parasite defenses by using host cues. However, lupine host damage did not induce changes in alkaloid levels in the hosts or parasites. Interestingly, the parasite had substantially higher concentrations of JA and alkaloids compared to lupine host plants. Buckeye herbivores consumed more parasite tissue when attached to damaged compared to undamaged hosts. We hypothesize that increased JA due to lupine host damage induced higher iridoid glycosides in the parasite, which are feeding stimulants for this specialist herbivore. Our results demonstrate that damage to hosts may affect both parasites and associated herbivores, indicating cascading effects of host damage on multiple trophic levels.

  8. Mechanisms of Retinal Damage after Ocular Alkali Burns. (United States)

    Paschalis, Eleftherios I; Zhou, Chengxin; Lei, Fengyang; Scott, Nathan; Kapoulea, Vassiliki; Robert, Marie-Claude; Vavvas, Demetrios; Dana, Reza; Chodosh, James; Dohlman, Claes H


    Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  9. Cancer risk and oxidative DNA damage in man

    DEFF Research Database (Denmark)

    Loft, S; Poulsen, H E


    In living cells reactive oxygen species (ROS) are formed continuously as a consequence of metabolic and other biochemical reactions as well as external factors. Some ROS have important physiological functions. Thus, antioxidant defense systems cannot provide complete protection from noxious effec...... of biobank material using a nested case control design. In addition, oxidative damage may be important for the aging process, particularly with respect to mitochondrial DNA and the pathogenesis of inflammatory diseases....... of ROS. These include oxidative damage to DNA, which experimental studies in animals and in vitro have suggested are an important factor in carcinogenesis. Despite extensive repair oxidatively modified DNA is abundant in human tissues, in particular in tumors, i.e., in terms of 1-200 modified nucleosides...... per 10(5) intact nucleosides. The damaged nucleosides accumulate with age in both nuclear and mitochondrial DNA. The products of repair of these lesions are excreted into the urine in amounts corresponding to a damage rate of up to 10(4) modifications in each cell every day. The most abundant...

  10. Biomechanics Analysis of Pressure Ulcer Using Damaged Interface Model between Bone and Muscle in the Human Buttock (United States)

    Slamet, Samuel Susanto; Takano, Naoki; Tanabe, Yoshiyuki; Hatano, Asako; Nagasao, Tomohisa

    This paper aims at building up a computational procedure to study the bio-mechanism of pressure ulcer using the finite element method. Pressure ulcer is a disease that occurs in the human body after 2 hours of continuous external force. In the very early stage of pressure ulcer, it is found that the tissues inside the body are damaged, even though skin surface looks normal. This study assumes that tension and/or shear strain will cause damage to loose fibril tissue between the bone and muscle and that propagation of damaged area will lead to fatal stage. Analysis was performed using the finite element method by modeling the damaged fibril tissue as a cutout. By varying the loading directions and watching both tensile and shear strains, the risk of fibril tissue damage and propagation of the damaged area is discussed, which may give new insight for the careful nursing for patients, particularly after surgical treatment. It was found that the pressure ulcer could reoccur for a surgical flap treatment. The bone cut and surgical flap surgery is not perfect to prevent the bone-muscle interfacial damage.

  11. A new in vitro model to study cellular responses after thermomechanical damage in monolayer cultures. (United States)

    Hettler, Alice; Werner, Simon; Eick, Stefan; Laufer, Stefan; Weise, Frank


    Although electrosurgical instruments are widely used in surgery to cut tissue layers or to achieve hemostasis by coagulation (electrocautery), only little information is available concerning the inflammatory or immune response towards the debris generated. Given the elevated local temperatures required for successful electrocautery, the remaining debris is likely to contain a plethora of compounds entirely novel to the intracorporal setting. A very common in vitro method to study cell migration after mechanical damage is the scratch assay, however, there is no established model for thermomechanical damage to characterise cellular reactions. In this study, we established a new in vitro model to investigate exposure to high temperature in a carefully controlled cell culture system. Heatable thermostat-controlled aluminium stamps were developed to induce local damage in primary human umbilical vein endothelial cells (HUVEC). The thermomechanical damage invoked is reproducibly locally confined, therefore allowing studies, under the same experimental conditions, of cells affected to various degrees as well as of unaffected cells. We show that the unaffected cells surrounding the thermomechanical damage zone are able to migrate into the damaged area, resulting in a complete closure of the 'wound' within 48 h. Initial studies have shown that there are significant morphological and biological differences in endothelial cells after thermomechanical damage compared to the mechanical damage inflicted by using the unheated stamp as a control. Accordingly, after thermomechanical damage, cell death as well as cell protection programs were activated. Mononuclear cells adhered in the area adjacent to thermomechanical damage, but not to the zone of mechanical damage. Therefore, our model can help to understand the differences in wound healing during the early phase of regeneration after thermomechanical vs. mechanical damage. Furthermore, this model lends itself to study the

  12. A new in vitro model to study cellular responses after thermomechanical damage in monolayer cultures.

    Directory of Open Access Journals (Sweden)

    Alice Hettler

    Full Text Available Although electrosurgical instruments are widely used in surgery to cut tissue layers or to achieve hemostasis by coagulation (electrocautery, only little information is available concerning the inflammatory or immune response towards the debris generated. Given the elevated local temperatures required for successful electrocautery, the remaining debris is likely to contain a plethora of compounds entirely novel to the intracorporal setting. A very common in vitro method to study cell migration after mechanical damage is the scratch assay, however, there is no established model for thermomechanical damage to characterise cellular reactions. In this study, we established a new in vitro model to investigate exposure to high temperature in a carefully controlled cell culture system. Heatable thermostat-controlled aluminium stamps were developed to induce local damage in primary human umbilical vein endothelial cells (HUVEC. The thermomechanical damage invoked is reproducibly locally confined, therefore allowing studies, under the same experimental conditions, of cells affected to various degrees as well as of unaffected cells. We show that the unaffected cells surrounding the thermomechanical damage zone are able to migrate into the damaged area, resulting in a complete closure of the 'wound' within 48 h. Initial studies have shown that there are significant morphological and biological differences in endothelial cells after thermomechanical damage compared to the mechanical damage inflicted by using the unheated stamp as a control. Accordingly, after thermomechanical damage, cell death as well as cell protection programs were activated. Mononuclear cells adhered in the area adjacent to thermomechanical damage, but not to the zone of mechanical damage. Therefore, our model can help to understand the differences in wound healing during the early phase of regeneration after thermomechanical vs. mechanical damage. Furthermore, this model lends itself

  13. Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

    Directory of Open Access Journals (Sweden)

    Bipin Gaihre


    Full Text Available Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies.

  14. Recent advances in hydrogels for cartilage tissue engineering. (United States)

    Vega, S L; Kwon, M Y; Burdick, J A


    Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.


    Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE


    Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

  16. Comparative assessment of the effects on lung tissue of three coal mine dusts. Determination of various biomarkers for inflammation, oxidative DNS damage and mutagenicity; Vergleich der Lungenwirksamkeit von drei untertaegigen Staeuben aus dem Steinkohlebergbau. Bestimmung verschiedener Biomarker fuer Entzuendung, oxidative DNS-Schaedigung und Mutagenitaet

    Energy Technology Data Exchange (ETDEWEB)

    Rehn, B.; Seiler, F.; Rehn, S.; Bruch, J. [Universitaetsklinikum Essen-Gesamthochschule (Germany). Inst. fuer Hygiene und Arbeitsmedizin


    Exposure to certain types of quartz (e.g. type DQ12) can lead to the development of lung tumors in the rat. The initial mechanisms involved in particle-induced tumor formation are the inflammation associated production of reactive oxygen species (ROS) and DNA-damage. ROS induce 8-oxoguanine and various other DNA oxidation products. In proliferating cells such DNA lesions can lead to various types of mutations, which is critical for cancer-related genes with respect to tumor formation. All these processes are connected with thresholds, which are dependent on the type of dust and the dose. Therefore we investigated the dose dependent effects of quartz DQ12 and three coalmine dusts on proliferation, various pulmonar inflammation and toxicity markers in the bronchoalveolar lavage fluid (BALF), on the induction of 8-oxoguanine in the DNA of rat lung cells and p53 mutant protein synthesis. Rats were exposed by intratracheal instillation to 0.6, 1.2 and 7.5 mg of the dust/lung and examined 90 after the exposures. Significant changes in the BALF were detected after all quartz doses. 8-oxoguanine was significantly increased only after 1.2 mg and 7.5 mg/animal. The amount of cells that expressed p53 mutant protein was slightly increased at 1.2 and 7.5 mg dust/lung. In contrast after exposure to the coalmine dusts signs of inflammation and increased levels of 8-oxoguanine could observed at 7.5 mg/lung. These investigations clearly show that for Quartz DQ12 and coalmine dusts exists different threshold for inflammation and 8-oxoguanine formation in the rat. (orig.)

  17. Damage Tolerance of Large Shell Structures (United States)

    Minnetyan, L.; Chamis, C. C.


    Progressive damage and fracture of large shell structures is investigated. A computer model is used for the assessment of structural response, progressive fracture resistance, and defect/damage tolerance characteristics. Critical locations of a stiffened conical shell segment are identified. Defective and defect-free computer models are simulated to evaluate structural damage/defect tolerance. Safe pressurization levels are assessed for the retention of structural integrity at the presence of damage/ defects. Damage initiation, growth, accumulation, and propagation to fracture are included in the simulations. Damage propagation and burst pressures for defective and defect-free shells are compared to evaluate damage tolerance. Design implications with regard to defect and damage tolerance of a large steel pressure vessel are examined.

  18. How to Stop Damaging Your Hair (United States)

    ... damage your hair Washing your hair by rubbing shampoo into the length of your hair Changes that can help prevent hair damage: Gently massage shampoo into your scalp. When you rinse the shampoo ...

  19. Rapporteur report: other tissues. (United States)

    Sienkiewicz, Z


    This report covers the session devoted to 'other tissues'. It considers the effects of internal electric fields such as those induced by exposure to weak, extremely low frequency (ELF) electromagnetic fields, on cardiac physiology, neuroendocrine (pineal) function and on the processes of tissue repair and embryonic development. Summaries are provided for each of the papers presented, and the major aspects of the plenary session are discussed. Overall, these tissues and processes were not considered to be sensitive to the direct effects of weak ELF fields, although indirect effects may occur via field induced changes to the central nervous system.

  20. Rapporteur report: Other tissues

    Energy Technology Data Exchange (ETDEWEB)

    Sienkiewicz, Z


    This report covers the session devoted to other tissues. It considers the effects of internal electric fields such as those induced by exposure to weak, extremely low frequency (ELF) electromagnetic fields, on cardiac physiology, neuroendocrine (pineal) function and on the processes of tissue repair and embryonic development. Summaries are provided for each of the papers presented, and the major aspects of the plenary session are discussed. Overall, these tissues and processes were not considered to be sensitive to the direct effects of weak ELF fields, although indirect effects may occur via field induced changes to the central nervous system. (author)

  1. Avionics Box Cold Plate Damage Prevention (United States)

    Stambolian, Damon; Larcher, Steven; Henderson, Gena; Tran, Donald


    Over the years there have been several occurrences of damage to Space Shuttle Orbiter cold plates during removal and replacement of avionics boxes. Thus a process improvement team was put together to determine ways to prevent these kinds of damage. From this effort there were many solutions including, protective covers, training, and improved operations instructions. The focus of this paper is to explain the cold plate damage problem and the corrective actions for preventing future damage to aerospace avionics cold plate designs.

  2. Multilayer Thin Film Sensors for Damage Diagnostics (United States)

    Protasov, A. G.; Gordienko, Y. G.; Zasimchuk, E. E.


    The new innovative approach to damage diagnostics within the production and maintenance/servicing procedures in industry is proposed. It is based on the real-time multiscale monitoring of the smart-designed multilayer thin film sensors of fatigue damage with the standard electrical input/output interfaces which can be connected to the embedded and on-board computers. The multilayer thin film sensors supply information about the actual unpredictable deformation damage, actual fatigue life, strain localization places, damage spreading, etc.

  3. An in vitro scratch tendon tissue injury model: effects of high frequency low magnitude loading. (United States)

    Adekanmbi, Isaiah; Zargar, Nasim; Hulley, Philippa


    The healing process of ruptured tendons is suboptimal, taking months to achieve tissue with inferior properties to healthy tendon. Mechanical loading has been shown to positively influence tendon healing. However, high frequency low magnitude (HFLM) loads, which have shown promise in maintaining healthy tendon properties, have not been studied with in vitro injury models. Here, we present and validate an in vitro scratch tendon tissue injury model to investigate effects of HFLM loading on the properties of injured rat tail tendon fascicles (RTTFs). A longitudinal tendon tear was simulated using a needle aseptically to scratch a defined length along individual RTTFs. Tissue viability, biomechanical, and biochemical parameters were investigated before and 7 days after culture . The effects of static, HFLM (20 Hz), and low frequency (1 Hz) cyclic loading or no load were also investigated. Tendon viability was confirmed in damaged RTTFs after 7 days of culture, and the effects of a 0.77 ± 0.06 cm scratch on the mechanical property (tangent modulus) and tissue metabolism in damaged tendons were consistent, showing significant damage severity compared with intact tendons. Damaged tendon fascicles receiving HFLM (20 Hz) loads displayed significantly higher mean tangent modulus than unloaded damaged tendons (212.7 ± 14.94 v 92.7 ± 15.59 MPa), and damaged tendons receiving static loading (117.9 ± 10.65 MPa). HFLM stimulation maintained metabolic activity in 7-day cultured damaged tendons at similar levels to fresh tendons immediately following damage. Only damaged tendons receiving HFLM loads showed significantly higher metabolism than unloaded damaged tendons (relative fluorescence units -7021 ± 635.9 v 3745.1 ± 641.7). These validation data support the use of the custom-made in vitro injury model for investigating the potential of HFLM loading interventions in treating damaged tendons.

  4. Transgenic Mouse Model for Reducing Oxidative Damage in Bone (United States)

    Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.


    Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the

  5. The Role of Cardiac Tissue Macrophages in Homeostasis and Disease. (United States)

    Ilinykh, Alexei; Pinto, Alexander R


    Macrophages are principally recognized as an important cell type for removal of tissue debris and as sentinels for tissue damage and foreign antigens. However, macrophages also participate in a diverse range of biological processes including angiogenesis, fibrosis, immune modulation, cell survival, and stem cell mobilization. Cardiac tissue macrophages (cTMs) are a heterogeneous population of phagocytic cells with distinct ontogenetic, phenotypic, and functional characteristics. While our understanding of cTMs has increased substantially over the last 5 years, large gaps in our knowledge regarding the cell biology of cTMs exist, in particular, the development of their unique phenotype and their roles in cardiac homeostasis and tissue stress. This review aims to discuss the current knowledge regarding cTMs and identify key questions that must be addressed to gain a better understanding of the role of cTMs in tissue development, homeostasis, and disease.

  6. Corticosteroids for treating nerve damage in leprosy

    NARCIS (Netherlands)

    N.H.J. van Veen (Natasja); P.G. Nicholls (Peter); W.C.S. Smith (Cairns); J.H. Richardus (Jan Hendrik)


    textabstractBackground: Leprosy causes nerve damage which can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although the long-term effect is uncertain. Objectives: To assess the effects of corticosteroids on nerve damage in leprosy.

  7. UV Photography Shows Hidden Sun Damage (United States)

    ... var c = 0; c UV photography shows hidden sun damage A UV photograph gives us a safe way to see how the sun damages our skin. In the UV photos that ... on the right, you can see what hidden sun damage looks like. Compare these UV photos with ...

  8. Damage control: Concept and implementation. (United States)

    Malgras, B; Prunet, B; Lesaffre, X; Boddaert, G; Travers, S; Cungi, P-J; Hornez, E; Barbier, O; Lefort, H; Beaume, S; Bignand, M; Cotte, J; Esnault, P; Daban, J-L; Bordes, J; Meaudre, E; Tourtier, J-P; Gaujoux, S; Bonnet, S


    The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied

  9. Damage control resuscitation: lessons learned. (United States)

    Giannoudi, M; Harwood, P


    Damage control resuscitation describes an approach to the early care of very seriously injured patients. The aim is to keep the patient alive whilst avoiding interventions and situations that risk worsening their situation by driving the lethal triad of hypothermia, coagulopathy and acidosis or excessively stimulating the immune-inflammatory system. It is critical that the concepts and practicalities of this approach are understood by all those involved in the early management of trauma patients. This review aims to summarise this and discusses current knowledge on the subject. Damage control resuscitation forms part of an overall approach to patient care rather than a specific intervention and has evolved from damage control surgery. It is characterised by early blood product administration, haemorrhage arrest and restoration of blood volume aiming to rapidly restore physiologic stability. The infusion of large volumes of crystalloid is no longer appropriate, instead the aim is to replace lost blood and avoid dilution and coagulopathy. In specific situations, permissive hypotension may also be of benefit, particularly in patients with severe haemorrhage from an arterial source. As rapid arrest of haemorrhage is so important, team-based protocols that del