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Sample records for tissue damage chronic

  1. 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

  2. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    Science.gov (United States)

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  3. Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-08-30

    Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  4. Periodontal tissue damage in smokers

    Directory of Open Access Journals (Sweden)

    Hutojo Djajakusuma

    2006-09-01

    Full Text Available Dental plaque is the primary etiological factor in periodontal diseases. However, there are many factors that can modify how an individual periodontal tissue will respond to the accumulation of dental plaque. Among such risk factors, there is increasing evidence that smoking tobacco products alters the expression and rate of progression of periodontal diseases. The aim of this study was to find out the loss of periodontal tissue adhesion in smokers by measuring pocket depth using probe, and by measuring alveolar bone damage using Bone Loss Score (BLS radiographic methods on teeth 12, 11, 21, 22, 32, 31, 41, 42. Based on T Test statistical analysis, there were significant differences in pocket depth damage of alveolar bone in smokers and non smokers. In conclusion there were increasing pocket depth and alveolar bone damage in smokers.

  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

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo

    2013-05-01

    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.

  6. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    Xu Feng; Wen Ting; Lu Tianjian; Seffen Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great problem for burn patients. Thus, it is of great importance to quantify the thermal damage in skin tissue. In this paper, the available models and experimental methods for quantification of thermal damage in skin tissue are discussed.

  7. Quantification of thermal damage in skin tissue

    Institute of Scientific and Technical Information of China (English)

    徐峰; 文婷; 卢天健; Seffen; Keith

    2008-01-01

    Skin thermal damage or skin burns are the most commonly encountered type of trauma in civilian and military communities. Besides, advances in laser, microwave and similar technologies have led to recent developments of thermal treatments for disease and damage involving skin tissue, where the objective is to induce thermal damage precisely within targeted tissue structures but without affecting the surrounding, healthy tissue. Further, extended pain sensation induced by thermal damage has also brought great...

  8. Damage Models for Soft Tissues: A Survey.

    Science.gov (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.

  9. Chronic inflammatory cells and damaged limbal cells in pterygium

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells were ..... Jiang Y, Goldberg ID, Shi YE. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 2002; 21: 2245-2252. 6. Kato S, Aoshima H, Saitoh Y, Miwa N. Fullerene-.

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

    Science.gov (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

    2003-01-01

    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. Protective Effect of HSP25 on Radiation Induced Tissue Damage

    International Nuclear Information System (INIS)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Bae, Sang-Woo; Lee, Yun-Sil; Kim, Sung Ho

    2007-01-01

    Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage

  12. An experimental study on tissue damage following subcutaneous injection of water soluble contrast media

    International Nuclear Information System (INIS)

    Kim, Seung Hyup; Park, Jae Hyung; Kang, Heung Sik; Kim, Chu Wan; Han, Man Chung; Kim, Yong Il

    1989-01-01

    The water soluble contrast media cause tissue necrosis infrequently by extravasation during intravenous injection in various radiological examinations. However, it has not been well documented that what kind and what concentration of contrast media can cause tissue necrosis. And also, the mechanism of tissue necrosis by extravasated contrast media has not been well known. The purpose of this experimental study was to evaluate the frequency and severity of tissue damage following subcutaneous injection of various water soluble contrast media to investigate the characteristics of the contrast media acting on the tissue damage, and to provide the basic data for the clinical application. Meglumine ioxithalamate,sodium and meglumine ioxithalamate, iopromide, iopamidol, ioxaglate,meglumine diatrizoate and sodium diatrizoate of various iodine content and osmolality were injected into subcutaneous tissue of the dorsum of 970 feet of 485 rats. The tissue reaction of injection sites were grossly examined with period from 1 day to 8 weeks after the injection. Representative gross changes were correlated with histologic findings. The results were as follows; 1. The basic tissue damage by extravasated contrast media was acute and chronic inflammatory reaction of the soft tissue with subsequent progress into the hemorrhagic and necrotizing lesion. 2. Lager volume of contrast media caused more severe tissue damage. 3. Contrast media of higher osmolality caused more severe tissue damage. 4. At same osmolality, contrast media of higher iodine content caused more severe tissue damage

  13. Electrocautery causes more ischemic peritoneal tissue damage than ultrasonic dissection.

    NARCIS (Netherlands)

    Broek, R.P.G ten; Wilbers, J.; Goor, H. van

    2011-01-01

    BACKGROUND: Minimizing peritoneal tissue injury during abdominal surgery has the benefit of reducing postoperative inflammatory response, pain, and adhesion formation. Ultrasonic dissection seems to reduce tissue damage. This study aimed to compare electrocautery and ultrasonic dissection in terms

  14. Chronic inflammatory cells and damaged limbal cells in pterygium ...

    African Journals Online (AJOL)

    Background: Chronic inflammation in pterygium occurrence has not been explained. Whether damaged limbal basal epithelial cells are associated with pterygium occurrence in black Africans is not clear. Objective: To explain chronic inflammation in pterygium, and to clarify whether damaged limbal basal epithelial cells ...

  15. Radiation damages in solids and tissues

    International Nuclear Information System (INIS)

    Cevc, P.; Kogovsek, F.; Kanduser, A.; Peternelj, M.; Skaleric, U.; Funduk, N.

    1977-01-01

    In submitted research work we have studied radiation damages in ferroelectric crystals and application of ferroelectric crystals. Studying the radiation damages we have introduced new technique of EPR measurements under high hydrostatic pressure, that will enable us to obtain additional data on crystal lattice dynamics. A change of piroelectric coefficient with high radiation doses in dopped TGS has been measured also

  16. The ultrastructure and etiology of chronic radiotherapy damage in human skin

    International Nuclear Information System (INIS)

    Rudolph, R.; Arganese, T.; Woodward, M.

    1982-01-01

    Ulcerated and nonulcerated skin from 5 patients with chronic radiation skin damage was examined using electron microscopy. Noticeable fibroblast disorganization was seen, with swollen and degenerating mitochondria, multiple vacuoles, and dilated irregular rough endoplasmic reticulum. Unusual crystalline inclusions were seen in some fibroblasts. In the ulcerated skin, contractile fibroblasts (myofibroblasts) were seen in 2 of 4 specimens. Stroma showed dense collagen and prominent elastosis. The microvasculature in the radiation-damaged tissue showed occasional lumen occlusion and vacuolization of endothelial cells, without consistent abnormality. These data suggest that permanent damage to fibroblasts or fibroblast stem cells may play an important role in chronic radiation skin ulceration

  17. DNA damage in plant herbarium tissue.

    Science.gov (United States)

    Staats, Martijn; Cuenca, Argelia; Richardson, James E; Vrielink-van Ginkel, Ria; Petersen, Gitte; Seberg, Ole; Bakker, Freek T

    2011-01-01

    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 amplifiable template molecules, but may also lead to the generation of erroneous sequence information. A qualitative and quantitative assessment of DNA post-mortem damage is essential to determine the accuracy of molecular data from herbarium specimens. In this study we present an assessment of DNA damage as miscoding lesions in herbarium specimens using 454-sequencing of amplicons derived from plastid, mitochondrial, and nuclear DNA. In addition, we assess DNA degradation as a result of strand breaks and other types of polymerase non-bypassable damage by quantitative real-time PCR. Comparing four pairs of fresh and herbarium specimens of the same individuals we quantitatively assess post-mortem DNA damage, directly after specimen preparation, as well as after long-term herbarium storage. After specimen preparation we estimate the proportion of gene copy numbers of plastid, mitochondrial, and nuclear DNA to be 2.4-3.8% of fresh control DNA and 1.0-1.3% after long-term herbarium storage, indicating that nearly all DNA damage occurs on specimen preparation. In addition, there is no evidence of preferential degradation of organelle versus nuclear genomes. Increased levels of C→T/G→A transitions were observed in old herbarium plastid DNA, representing 21.8% of observed miscoding lesions. We interpret this type of post-mortem DNA damage-derived modification to have arisen from the hydrolytic deamination of cytosine during long-term herbarium storage. Our results suggest that reliable sequence data can be obtained from herbarium specimens.

  18. Damage of hippocampal neurons in rats with chronic alcoholism

    OpenAIRE

    Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

    2014-01-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons i...

  19. 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.

    2011-01-01

    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

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

    Science.gov (United States)

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

    2016-02-06

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

  1. Damage of hippocampal neurons in rats with chronic alcoholism.

    Science.gov (United States)

    Du, Ailin; Jiang, Hongbo; Xu, Lei; An, Na; Liu, Hui; Li, Yinsheng; Zhang, Ruiling

    2014-09-01

    Chronic alcoholism can damage the cytoskeleton and aggravate neurological deficits. However, the effect of chronic alcoholism on hippocampal neurons remains unclear. In this study, a model of chronic alcoholism was established in rats that were fed with 6% alcohol for 42 days. Endogenous hydrogen sulfide content and cystathionine-beta-synthase activity in the hippocampus of rats with chronic alcoholism were significantly increased, while F-actin expression was decreased. Hippocampal neurons in rats with chronic alcoholism appeared to have a fuzzy nuclear membrane, mitochondrial edema, and ruptured mitochondrial crista. These findings suggest that chronic alcoholism can cause learning and memory decline in rats, which may be associated with the hydrogen sulfide/cystathionine-beta-synthase system, mitochondrial damage and reduced expression of F-actin.

  2. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

  3. Trefoil factors in saliva and gingival tissues of patients with chronic periodontitis

    DEFF Research Database (Denmark)

    Chaiyarit, Ponlatham; Chayasadom, Anek; Wara-Aswapati, Nawarat

    2012-01-01

    BACKGROUND: Trefoil factors (TFFs) are secreted molecules that are involved in cytoprotection against tissue damage and the immune response. TFFs have been detected in saliva and oral tissues, but their clinical significance has never been investigated in patients with chronic periodontitis....... The objective of this study is to determine whether TFF expression in saliva and gingival tissues is associated with periodontal pathology. METHODS: Saliva and gingival tissue samples were collected from 25 non-periodontitis individuals and 25 patients with chronic periodontitis (CP). Enzyme...... observed in patients with CP (P = 0.003 and P periodontal pathology and number of Porphyromonas gingivalis...

  4. Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Menno Pruijm

    2013-01-01

    Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

  5. [Scanning electron microscopy of heat-damaged bone tissue].

    Science.gov (United States)

    Harsanyl, L

    1977-02-01

    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.

  6. DNA-repair, cell killing and normal tissue damage

    International Nuclear Information System (INIS)

    Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

    1998-01-01

    Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

  7. Radiation-induced normal tissue damage: implications for radiotherapy

    International Nuclear Information System (INIS)

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

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

    Science.gov (United States)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    of the fish and subsequent a reduction in price. Despite this, the impact of infectious diseases on the meat quality and the mechanisms behind are poorly investigated. Wound repair is a dynamic, interactive response to tissue injury that involves a complex interaction and cross talk of various cell types......, extracellular matrix molecules, soluble mediators and cytokines. In order to describe the molecular mechanisms and processes of wound repair, a panel of genes covering immunological factors and tissue regeneration were used to measure changes at the mRNA level following mechanical tissue damage in rainbow trout...... (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...

  10. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  11. Tissue Damage Characterization Using Non-invasive Optical Modalities

    Science.gov (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 differences detected in optical properties and hemoglobin content by optical 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

  12. Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

    Science.gov (United States)

    Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

    2004-07-01

    Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

  13. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    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)

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

    Science.gov (United States)

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

    2009-04-30

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

  15. Renal tissue damage induced by focused shock waves

    Science.gov (United States)

    Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

    1990-07-01

    Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

  16. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  17. 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.

  18. Preliminary evidence of hippocampal damage in chronic users of ecstasy.

    Science.gov (United States)

    den Hollander, Bjørnar; Schouw, Marieke; Groot, Paul; Huisman, Henk; Caan, Matthan; Barkhof, Frederik; Reneman, Liesbeth

    2012-01-01

    Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.

  19. Contribution to the microchemistry of smoke damage by fluoride. The migration of fluorides in plant tissue. 2. The visible damage

    Energy Technology Data Exchange (ETDEWEB)

    Reckendorfer, P

    1953-01-01

    In continuation of former investigations, a theory of damage caused by fluorine compounds on green plants was developed. It is possible to differentiate between acute and chronic damages by use of microanalytical estimation of total fluorine and inorganic and organic fluorine compounds in the plants.

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

    Directory of Open Access Journals (Sweden)

    Jehane I. Eid

    2015-08-01

    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.

  1. Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

    Directory of Open Access Journals (Sweden)

    Nayeem Bilal

    2017-06-01

    Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

  2. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... were compared with preoperative endoscopic retrograde cholangiopancreatography (ERCP) morphology. The preoperatively elevated pressure decreased in all patients but one, to normal or slightly elevated values. The median pressure decrease was 50% (range, 0-90%; p = 0.01). The drainage anastomosis (a...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  3. On radiation damage to normal tissues and its treatment. Pt. 2

    International Nuclear Information System (INIS)

    Michalowski, A.S.

    1994-01-01

    In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A 2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.)

  4. LYCOPENE EFFICIENCY IN THE MODULATION OF OXIDATIVE DAMAGE IN DIFFERENT TISSUES OF GAMMA IRRADIATED RATS

    International Nuclear Information System (INIS)

    EL-TAHAWY, N.A.; NADA, A.S.; REZK, R.G.

    2008-01-01

    Exposure to ionizing radiation induces oxidative stress that has been recognized as an important etiological factor in the causation of several chronic diseases. Lycopene, a carotenoid almost exclusively present in tomatoes and tomatoes products, is a lipid soluble antioxidant claimed to possess cardio protective and anticancer properties. The present study was designed to determine the possible modulator effects of lycopene on radiation-induced oxidative damage to liver, spleen and lung tissues. Animals were supplemented with lycopene (5 mg/kg body weight/ day) by gavages for two weeks before whole body exposure to gamma rays and within the period of irradiation (3 successive doses, each of 3 Gy at 72 hours intervals). Animals were sacrificed on the 3 r d day post the last irradiation session.The results obtained in the present study showed that whole body gamma irradiation produced oxidative stress manifested by significant elevation in lipid peroxides levels measured as thiobarbituric acid reactive substances (TBARS) associated with significant decrease of nitric oxide (NO) content. Non-significant change in total cupper (Cu) in the three tissues was recorded while significant increase of total iron (Fe) was observed in liver and spleen tissues only. Liver tissue of irradiated rats showed significant decrease in the activities of the antioxidant enzymes as superoxide dismutase (SOD) and catalase (CAT). In spleen tissues, there was a significant increase of SOD and significant decrease of CAT activities while in lung tissues, both SOD and CAT activities showed significant increase.Histological observations of photomicrograph of liver sections showed that radiation-induced sever damage obvious by dilated portal vein, ruptured hepatocytes, necrotic, pyknotic, karyolitic nuclei and vacuolated cytoplasm. In spleen tissue, radiation was induced degeneration of lymphatic nodules, dilation follicular artery and marked hemorrhage. In lung tissue, radiation- induces ill

  5. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

  6. Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

    Science.gov (United States)

    Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

    2015-11-01

    The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

  7. Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

    Science.gov (United States)

    Schomacker, K T; Walsh, J T; Flotte, T J; Deutsch, T F

    1990-01-01

    Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

  8. 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.

    2009-01-01

    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

  9. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.

    1994-01-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  10. Regulation of annexins following infection like tissue damage – investigated by 2-dimensional gel electrophoresis

    DEFF Research Database (Denmark)

    Wulff, Tune; Nielsen, Michael Engelbrecht

    are regulated after tissue damaged on the protein level. These proteins have been assign to functions like regulation of coagulation, apoptosis, and exocytosis, indicating their importance following infection and subsequent repair in fish. In addition the regulation observed in this study are supported...... an established model. In the model infection is mimicked by a well-defined tissue damage allowing each fish to be equally affected. Samples were taken 7 days after tissue damage and included samples from the damaged tissue, internal control and an external control. Changes in protein expression between the wound...... by previous findings on the mRNA level, where both proteins are regulated following infection. In conclusion this study show regulation on the protein level of two members of the annexin protein family after infection like tissue damage....

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

    Science.gov (United States)

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

    2017-01-02

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

  12. Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

    Science.gov (United States)

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

    2017-10-01

    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.

  13. Thermal damage control of dye-assisted laser tissue welding: effect of dye concentration

    Science.gov (United States)

    Xie, Hua; Buckley, Lisa A.; Prahl, Scott A.; Shaffer, Brian S.; Gregory, Kenton W.

    2001-05-01

    Successful laser-assisted tissue welding was implemented to provide proper weld strength with minimized tissue thermal injury. We investigated and compared the weld strengths and morphologic changes in porcine small intestinal submucose (SIS) and porcine ureteral tissues with various concentration of indocyanine green (ICG) and with a solid albumin sheet. The study showed that the tissues were welded at lower ICG concentration (0.05 mM) with minimized tissue thermal damage using an 800-nm wavelength diode laser.

  14. Experimental investigations on chronic irradiation damage of the heart

    International Nuclear Information System (INIS)

    Lauk, S.

    1984-02-01

    Irradiation of rat hearts induced the following clinical phenomena: increasingly severe dyspnea, associated flank respiration and deterioration of the general condition bordering on a prefinal syndrome. Dissection of the sick animals and thoracal x-rays taken regularly revealed extensive pesicardial and pleural effusions. The tissue of the pericardium was thickened and edematous. The most striking histological finding consisted in a focal degeneration and destruction of the myocardium without an increase in collagenous fibres. This damage to the heart muscle was quite severe and seen in all dose groups from 15 to 40 Gy. At the same time there was a reduction of the capillary density as a function of the radiation dose. Clinical symptoms were also observed in animals irradiated with 10 Gy only. All animals irradiated with at least 20 Gy, attained a state where death was imminent. Consequently, the LD-50 must be lower than 20 Gy. The latency period was over a year at 15 Gy but decreased considerably as the dose increased. (orig.) [de

  15. Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

    Science.gov (United States)

    Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

    2011-01-01

    Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

  16. Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

    2015-12-01

    Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.V.

    1976-10-01

    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.

  18. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

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

    2011-01-01

    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.

  19. Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis.

    Science.gov (United States)

    Hu, Shenlin; Shang, Wei; Yue, Haitao; Chen, Ruini; Dong, Zheng; Hu, Jinhua; Mao, Zhao; Yang, Jian

    2015-04-01

    To evaluate the DEC1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. 20 non-smoking patients with chronic periodontitis and 20 healthy individuals were enrolled. Periodontal ligament tissue and gingival tissue samples from healthy subjects were collected during teeth extraction for orthodontic reason or the third molar extraction. The parallel samples from patients with chronic periodontitis were obtained during periodontal flap operations or teeth extraction as part of periodontal treatment. The DEC1 expression and the alkaline phosphatase (ALP) activity of both the periodontal ligament tissue and gingival tissue were determined by Western blot, Immunohistochemistry and ALP Detection Kit. The DEC1 expression of periodontal ligament tissue in the patients with chronic periodontitis decreased significantly along with the decreased ALP activity. On the contrary, the DEC1 expression of gingival tissue in the patients with chronic periodontitis increased significantly. Further study found that the DEC1 expression of gingival tissue increased mainly in the suprabasal layer of gingival epithelial cells but decreased in the gingival connective tissue of the patients with chronic periodontitis. The DEC1 expression decreases in the periodontal ligament tissue which is related to the osteogenic capacity, whereas the DEC1 expression increases in the suprabasal layer of gingival epithelial cells which are involved in immune inflammatory response in the patients with chronic periodontitis. The findings provide a new target to explore the pathology and the therapy of periodontitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Automated Tissue Classification Framework for Reproducible Chronic Wound Assessment

    Directory of Open Access Journals (Sweden)

    Rashmi Mukherjee

    2014-01-01

    Full Text Available The aim of this paper was to develop a computer assisted tissue classification (granulation, necrotic, and slough scheme for chronic wound (CW evaluation using medical image processing and statistical machine learning techniques. The red-green-blue (RGB wound images grabbed by normal digital camera were first transformed into HSI (hue, saturation, and intensity color space and subsequently the “S” component of HSI color channels was selected as it provided higher contrast. Wound areas from 6 different types of CW were segmented from whole images using fuzzy divergence based thresholding by minimizing edge ambiguity. A set of color and textural features describing granulation, necrotic, and slough tissues in the segmented wound area were extracted using various mathematical techniques. Finally, statistical learning algorithms, namely, Bayesian classification and support vector machine (SVM, were trained and tested for wound tissue classification in different CW images. The performance of the wound area segmentation protocol was further validated by ground truth images labeled by clinical experts. It was observed that SVM with 3rd order polynomial kernel provided the highest accuracies, that is, 86.94%, 90.47%, and 75.53%, for classifying granulation, slough, and necrotic tissues, respectively. The proposed automated tissue classification technique achieved the highest overall accuracy, that is, 87.61%, with highest kappa statistic value (0.793.

  1. Pitfalls in soft tissue sarcoma imaging: chronic expanding hematomas.

    Science.gov (United States)

    Jahed, Kiarash; Khazai, Behnaz; Umpierrez, Monica; Subhawong, Ty K; Singer, Adam D

    2018-01-01

    Solid or nodular enhancement is typical of soft tissue sarcomas although high grade soft tissue sarcomas and those with internal hemorrhage often appear heterogeneous with areas of nonenhancement and solid or nodular enhancement. These MRI findings often prompt an orthopedic oncology referral, a biopsy or surgery. However, not all masses with these imaging findings are malignant. We report the multimodality imaging findings of two surgically proven chronic expanding hematomas (CEH) with imaging features that mimicked sarcomas. A third case of nonenhancing CEH of the lower extremity is also presented as a comparison. It is important that in the correct clinical scenario with typical imaging findings, the differential diagnosis of a chronic expanding hematoma be included in the workup of these patients. An image-guided biopsy of nodular tissue within such masses that proves to be negative for malignancy should not necessarily be considered discordant. A correct diagnosis may prevent a morbid unnecessary surgery and may indicate the need for a conservative noninvasive follow-up with imaging.

  2. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    International Nuclear Information System (INIS)

    Balaha, Mohamed; Kandeel, Samah; Barakat, Waleed

    2016-01-01

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL 4 in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL 4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis in chronic

  3. Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats

    Energy Technology Data Exchange (ETDEWEB)

    Balaha, Mohamed, E-mail: Mohamed.Balaha@Med.Tanta.Edu.Eg [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Kandeel, Samah [Histology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt); Barakat, Waleed [Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527 Tanta (Egypt)

    2016-11-15

    Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1 ml/kg 10% CCL{sub 4} in olive oil three times/week (every other day) for 12 weeks to induce hepatic cirrhosis. Carvedilol (10 mg/kg/day suspended in 0.5% CMC orally), silymarin (50 mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL{sub 4} induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries. - Highlights: • Chronic liver damage ends into hepatocellular carcinoma in 5% of patients. • Persistent elevation of IL-6 induces hepatocarcinogenesis

  4. 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

    2006-01-01

    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...

  5. Acrolein: An Effective Biomarker for Tissue Damage Produced from Polyamines.

    Science.gov (United States)

    Igarashi, Kazuei; Uemura, Takeshi; Kashiwagi, Keiko

    2018-01-01

    It is thought that the major factor responsible for cell damage is reactive oxygen species (ROS), but our recent studies have shown that acrolein (CH 2 =CH-CHO) produced from spermine and spermidine is more toxic than ROS. Thus, (1) the mechanism of acrolein production during brain stroke, (2) one of the mechanisms of acrolein toxicity, and (3) the role of glutathione in acrolein detoxification are described in this chapter.

  6. 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

    2001-01-01

    determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected...

  7. Using electrolyte leakage tests to determine lifting windows and detect tissue damage

    Science.gov (United States)

    Richard W. Tinus

    2002-01-01

    Physiological testing is rapidly coming into use as a means to determine the condition of nursery stock and predict how it will respond to treatment or use. One such test, the electrolyte leakage test, can be used to measure cold hardiness and detect tissue damage. The principle of this test is that when cell membranes are damaged, electrolytes leak out into the water...

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

    Science.gov (United States)

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

    2016-11-01

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

  9. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Science.gov (United States)

    Calvo, Jennifer A; Moroski-Erkul, Catherine A; Lake, Annabelle; Eichinger, Lindsey W; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T; Christiani, David C; Meira, Lisiane B; Samson, Leona D

    2013-04-01

    Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  10. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Directory of Open Access Journals (Sweden)

    Jennifer A Calvo

    2013-04-01

    Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  11. Effect of mechanical tissue properties on thermal damage in skin after IR-laser ablation

    Energy Technology Data Exchange (ETDEWEB)

    Frenz, M.; Romano, V.; Forrer, M.; Weber, H.P. (Inst. of Applied Physics, Bern Univ. (Switzerland)); Mischler, C.; Mueller, O.M. (Anatomical Inst., Bern Univ. (Switzerland))

    1991-04-01

    The damage created instantaneously in dorsal skin and in the subjacent skeletal muscle layer after CO{sub 2} and Er{sup 3+} laser incisions is histologically and ultrastructurally investigated. Light microscopical examinations show an up to three times larger damage zone in the subcutaneous layer of skeletal muscle than in the connective tissue above. The extent of thermally altered muscle tissue is classified by different zones and characterized by comparison to long time heating injuries. The unexpectedly large damage is a result of the change of elastic properties occurring abruptly at the transition between different materials. This leads to a discontinuity of the cutting dynamics that reduces the ejection of tissue material. We show that the degree of thermal damage originates from the amount of hot material that is not ejected out of the crater acting as a secondary heat source. (orig.).

  12. Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

    Directory of Open Access Journals (Sweden)

    Viktor M Pastukh

    2011-03-01

    Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

  13. [Damage effects of chronic hypoxia on medulla oblongata associated with oxidative stress and cell apoptosis].

    Science.gov (United States)

    Hou, Xuefei; Ding, Yan; Nie, Zheng; Li, Hui; Tang, Yuhong; Zhou, Hua; Chen, Li; Zheng, Yu

    2012-08-01

    The aim of this study is to study the damage effects of chronic hypoxia on medulla oblongata and to explore whether the damage is associated with oxidative stress and cell apoptosis. Adult male SD rats were randomly divided into two groups: control group and chronic hypoxia group. Medulla oblongata was obtained for the following methods of analyses. Nissl's staining was used to examine the Niss bodies of neurons in medullary respiratory related nuclei, biochemistry methods were utilized to examine oxidant stress damage induced by chronic hypoxia on medulla oblongata through measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and RT-PCR technique was used to study the influence of apoptosis induced by chronic hypoxia on medulla oblongata through analyzing the levels of Bax mRNA and Bcl-2 mRNA. The results showed the optical densities of Nissl's staining in pre-BötC, NA, NTS, FN, and 12N were significantly decreased in chronic hypoxia group in comparison with that in control group (P 0.05). Bax mRNA expression had no obvious change and Bcl-2 mRNA expression significantly decreased in chronic hypoxia group in comparison with that in control group (P < 0.05). The results suggest that chronic hypoxia could bring about serious damage to medullary respiratory centers through aggravating oxidative stress and increasing cell apoptosis.

  14. The neuroimaging evidence for chronic brain damage due to boxing

    Energy Technology Data Exchange (ETDEWEB)

    Moseley, I.F. [Lysholm Radiological Department, National Hospital for Neurology and Neurosurgery, London (United Kingdom)

    2000-01-01

    A number of imaging techniques have been used to investigate changes produced in the brain by boxing. Most morphological studies have failed to show significant correlations between putative abnormalities on imaging and clinical evidence of brain damage. Fenestration of the septum pellucidum, with formation of a cavum, one of the most frequent observations, does not appear to correlate with neurological or physiological evidence of brain damage. Serial studies on large groups may be more informative. Magnetic resonance spectroscopy and cerebral blood flow studies have been reported in only small numbers of boxers; serial studies are not available to date. (orig.)

  15. A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage.

    Science.gov (United States)

    Shaban, Lamyaa; Chen, Ying; Fasciano, Alyssa C; Lin, Yinan; Kaplan, David L; Kumamoto, Carol A; Mecsas, Joan

    2018-04-01

    Endospore-forming Clostridioides difficile is a causative agent of antibiotic-induced diarrhea, a major nosocomial infection. Studies of its interactions with mammalian tissues have been hampered by the fact that C. difficile requires anaerobic conditions to survive after spore germination. We recently developed a bioengineered 3D human intestinal tissue model and found that low O 2 conditions are produced in the lumen of these tissues. Here, we compared the ability of C. difficile spores to germinate, produce toxin and cause tissue damage in our bioengineered 3D tissue model versus in a 2D transwell model in which human cells form a polarized monolayer. 3D tissue models or 2D polarized monolayers on transwell filters were challenged with the non-toxin producing C. difficile CCUG 37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in the presence of the germinant, taurocholate. Spores germinated in both the 3D tissue model as well as the 2D transwell system, however toxin activity was significantly higher in the 3D tissue models compared to the 2D transwells. Moreover, the epithelium damage in the 3D tissue model was significantly more severe than in 2D transwells and damage correlated significantly with the level of toxin activity detected but not with the amount of germinated spores. Combined, these results show that the bioengineered 3D tissue model provides a powerful system with which to study early events leading to toxin production and tissue damage of C. difficile with mammalian cells under anaerobic conditions. Furthermore, these systems may be useful for examining the effects of microbiota, novel drugs and other potential therapeutics directed towards C. difficile infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. 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

    2013-05-01

    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

  17. Arterial spin labelling shows functional depression of non-lesion tissue in chronic Wernicke's aphasia.

    Science.gov (United States)

    Robson, Holly; Specht, Karsten; Beaumont, Helen; Parkes, Laura M; Sage, Karen; Lambon Ralph, Matthew A; Zahn, Roland

    2017-07-01

    Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow (CBF) is rarely investigated in chronic stroke. This study investigated CBF in individuals with chronic Wernicke's aphasia (WA) and examined the relationship between lesion, CBF and neuropsychological impairment. Arterial spin labelling CBF imaging and structural MRIs were collected in 12 individuals with chronic WA and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures. Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures. This study found that core language impairments in chronic WA are associated with a combination of structural lesion and abnormal perfusion in non-lesioned tissue. This indicates that post-stroke impairments are due to a wider disruption of neural function than observable on structural T1w MRI. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

    Directory of Open Access Journals (Sweden)

    Mi Ran Choi

    2017-10-01

    Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

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

    Directory of Open Access Journals (Sweden)

    Paolo Durigutto

    2017-09-01

    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.

  20. Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

    Science.gov (United States)

    Funes, Lorena; Carrera-Quintanar, Lucrecia; Cerdán-Calero, Manuela; Ferrer, Miguel D; Drobnic, Franchek; Pons, Antoni; Roche, Enrique; Micol, Vicente

    2011-04-01

    Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.

  1. A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

    Science.gov (United States)

    Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

    2010-12-01

    Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  2. Effect of laminaria japonica polysaccharides (LJP) on radiation damage of testis tissue in male rats

    International Nuclear Information System (INIS)

    Ren Shicheng; Luo Qiong; Yang Mingliang; Yang Jiajuan; Yan Jun; Li Zhuoneng; Wang Lihong; Cui Xiaoyan

    2007-01-01

    Objective: To observe the effect of laminaria japonica polysaccharides (LJP) on local radiation damage of testis tissue in male rats. Methods: The Wistar rats were randomly divided into 4 groups: the normal group, the model group, positive control group and LJP treatment group (50 mg·kg -1 ·d -1 ). LJP was applied to the treatment group for 10 d before local irradiation with γ-ray (6.0 Gy). The morphological change of the testis, organ index of testis and epididymides, sperm count, motility rate, superoxide dismutase (SOD) activity and malonic aldehyde (MDA) contents were measured. Results: LJP could make the damaged testis recover to near normal, elevate the organ index of testis and epididymides, promote the sperm count and motility rate, increase the activity of SOD and decrease the contents of MDA in testis tissue. Conclusions: LJP could inhibit testis tissue damage induced by local radiation, hence enhance the significant radioprotective effect to testis tissue. LJP has the conspicuous protective effect on radiation damage of testis tissue. (authors)

  3. Infrared laser damage thresholds in corneal tissue phantoms using femtosecond laser pulses

    Science.gov (United States)

    Boretsky, Adam R.; Clary, Joseph E.; Noojin, Gary D.; Rockwell, Benjamin A.

    2018-02-01

    Ultrafast lasers have become a fixture in many biomedical, industrial, telecommunications, and defense applications in recent years. These sources are capable of generating extremely high peak power that can cause laser-induced tissue breakdown through the formation of a plasma upon exposure. Despite the increasing prevalence of such lasers, current safety standards (ANSI Z136.1-2014) do not include maximum permissible exposure (MPE) values for the cornea with pulse durations less than one nanosecond. This study was designed to measure damage thresholds in corneal tissue phantoms in the near-infrared and mid-infrared to identify the wavelength dependence of laser damage thresholds from 1200-2500 nm. A high-energy regenerative amplifier and optical parametric amplifier outputting 100 femtosecond pulses with pulse energies up to 2 mJ were used to perform exposures and determine damage thresholds in transparent collagen gel tissue phantoms. Three-dimensional imaging, primarily optical coherence tomography, was used to evaluate tissue phantoms following exposure to determine ablation characteristics at the surface and within the bulk material. The determination of laser damage thresholds in the near-IR and mid-IR for ultrafast lasers will help to guide safety standards and establish the appropriate MPE levels for exposure sensitive ocular tissue such as the cornea. These data will help promote the safe use of ultrafast lasers for a wide range of applications.

  4. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-09-01

    The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 μg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 μg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

  5. Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

    International Nuclear Information System (INIS)

    Plevova, P.

    2002-01-01

    Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

  6. Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage.

    Science.gov (United States)

    Vassallo, Christopher N; Wall, Daniel

    2016-04-01

    Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. © 2016 WILEY Periodicals, Inc.

  7. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

    Science.gov (United States)

    Mastropasqua, Rodolfo; Agnifili, Luca; Fasanella, Vincenzo; Nubile, Mario; Gnama, Agbeanda A; Falconio, Gennaro; Perri, Paolo; Di Staso, Silvio; Mariotti, Cesare

    2017-08-01

    Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

  8. Comparison of tissue damage caused by various laser systems with tissue tolerable plasma by light and laser scan microscopy

    International Nuclear Information System (INIS)

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

    2013-01-01

    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 CO 2 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 CO 2 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. (letter)

  9. 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

  10. Stem cell therapy for the treatment of radiation-induced normal tissue damage

    International Nuclear Information System (INIS)

    Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

    2013-01-01

    Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

  11. Chronic Broca's Aphasia Is Caused by Damage to Broca's and Wernicke's Areas.

    Science.gov (United States)

    Fridriksson, Julius; Fillmore, Paul; Guo, Dazhou; Rorden, Chris

    2015-12-01

    Despite being perhaps the most studied form of aphasia, the critical lesion location for Broca's aphasia has long been debated, and in chronic patients, cortical damage often extends far beyond Broca's area. In a group of 70 patients, we examined brain damage associated with Broca's aphasia using voxel-wise lesion-symptom mapping (VLSM). We found that damage to the posterior portion of Broca's area, the pars opercularis, is associated with Broca's aphasia. However, several individuals with other aphasic patterns had considerable damage to pars opercularis, suggesting that involvement of this region is not sufficient to cause Broca's aphasia. When examining only individuals with pars opercularis damage, we found that patients with Broca's aphasia had greater damage in the left superior temporal gyrus (STG; roughly Wernicke's area) than those with other aphasia types. Using discriminant function analysis and logistic regression, based on proportional damage to the pars opercularis and Wernicke's area, to predict whether individuals had Broca's or another types of aphasia, over 95% were classified correctly. Our findings suggest that persons with Broca's aphasia have damage to both Broca's and Wernicke's areas, a conclusion that is incongruent with classical neuropsychology, which has rarely considered the effects of damage to both areas. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    Science.gov (United States)

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  13. The role of tissue damage in whiplash associated disorders: Discussion paper 1

    Science.gov (United States)

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

    2011-01-01

    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

  14. Non-damaging laser therapy of the macula: Titration algorithm and tissue response

    Science.gov (United States)

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

    2014-02-01

    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.

  15. Laser treatment of female stress urinary incontinence: optical, thermal, and tissue damage simulations

    Science.gov (United States)

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

    2016-02-01

    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.

  16. 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.

  17. 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

    regeneration since its genome is well-described and it is easy visually to follow the wound healing. In this study, carps were physically damaged in the musculature using sterile needles at day 10, 16, 24, 47 and 94 post hatch. Muscle tissue samples were subsequently taken at day 1, 3 and 7 post damage...... 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...

  18. A chronic increase of corticosterone age-dependently reduces systemic DNA damage from oxidation in rats

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Kalliokoski, Otto; Forsberg, Kristin

    2017-01-01

    Stress and depression are associated with an acceleration of brain and bodily aging; effects which have been attributed to chronic elevations of glucocorticoids. We tested the hypothesis that a three week administration of stress-associated levels of corticosterone (CORT, the principal rodent...... glucocorticoid) would increase systemic and CNS DNA and RNA damage from oxidation; a phenomenon known to be centrally involved in the aging process. We also hypothesized that older individuals would be more sensitive to this effect and that the chronic CORT administration would exacerbate age-related memory...

  19. Contribution Of Brain Tissue Oxidative Damage In Hypothyroidism-associated Learning and Memory Impairments

    Directory of Open Access Journals (Sweden)

    Yousef Baghcheghi

    2017-01-01

    Full Text Available The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.

  20. The influence of parotid gland sparing on radiation damages of dental hard tissues.

    Science.gov (United States)

    Hey, Jeremias; Seidel, Johannes; Schweyen, Ramona; Paelecke-Habermann, Yvonne; Vordermark, Dirk; Gernhardt, Christian; Kuhnt, Thomas

    2013-07-01

    The aim of the present study was to evaluate whether radiation damage on dental hard tissue depends on the mean irradiation dose the spared parotid gland is subjected to or on stimulated whole salivary flow rate. Between June 2002 and October 2008, 70 patients with neck and cancer curatively irradiated were included in this study. All patients underwent dental treatment referring to the guidelines and recommendations of the German Society of Dental, Oral and Craniomandibular Sciences prior, during, and after radiotherapy (RT). During the follow-up period of 24 months, damages on dental hard tissues were classified according to the RTOG/EORTC guidelines. The mean doses (D(mean)) during spared parotid gland RT were determined. Stimulated whole saliva secretion flow rates (SFR) were measured before RT and 1, 6, 12, 24 months after RT. Thirty patients showed no carious lesions (group A), 18 patients developed sporadic carious lesions (group B), and 22 patients developed general carious lesions (group C). Group A patients received a D mean of 21.2 ± 11.04 Gy. Group B patients received a D(mean) of 26.5 ± 11.59 Gy and group C patients received a D(mean) of 33.9 ± 9.93 Gy, respectively. The D(mean) of group A was significantly lower than the D(mean) of group C (p dental hard tissue correlates with increased mean irradiation doses as well as decreased salivary flow rates. Parotid gland sparing resulting in a dose below 20 Gy reduces radiation damage on dental hard tissues, and therefore, the dose may act as a predictor for the damage to be expected.

  1. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  2. Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

    Science.gov (United States)

    Sakakura, Kenichi; Ladich, Elena; Fuimaono, Kristine; Grunewald, Debby; O'Fallon, Patrick; Spognardi, Anna-Maria; Markham, Peter; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Shen, Kai; Kolodgie, Frank D; Joner, Michael; Virmani, Renu

    2015-01-01

    The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (Pradiofrequency group (Pradiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (Pradiofrequency ablation, and there is a trend toward less nerve damage. © 2014 American Heart Association, Inc.

  3. The Cell Nucleus Serves as a Mechanotransducer of Tissue Damage-Induced Inflammation.

    Science.gov (United States)

    Enyedi, Balázs; Jelcic, Mark; Niethammer, Philipp

    2016-05-19

    Tissue damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidized to proinflammatory eicosanoids by 5-lipoxygenase (5-LOX) on the nuclear envelope. How tissue damage is sensed to activate cPLA2 is unknown. We investigated this by live imaging in wounded zebrafish larvae, where damage of the fin tissue causes osmotic cell swelling at the wound margin and the generation of a chemotactic eicosanoid signal. Osmotic swelling of cells and their nuclei activates cPla2 by translocating it from the nucleoplasm to the nuclear envelope. Elevated cytosolic Ca(2+) was necessary but not sufficient for cPla2 translocation, and nuclear swelling was required in parallel. cPla2 translocation upon nuclear swelling was reconstituted in isolated nuclei and appears to be a simple physical process mediated by tension in the nuclear envelope. Our data suggest that the nucleus plays a mechanosensory role in inflammation by transducing cell swelling and lysis into proinflammatory eicosanoid signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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

    2014-08-01

    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.

  5. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  6. Is there a similarity between DNA damage in adults with chronic alcoholism and community-dwelling healthy older adults?

    Science.gov (United States)

    Retana-Ugalde, Raquel; Altamirano-Lozano, Mario; Mendoza-Núñez, Víctor Manuel

    2007-01-01

    Daily alcohol consumption and ageing have been linked with DNA damage, leading to the hypothesis that chronic alcoholism causes DNA damage similar to that which occurs with ageing. Likewise, it has been suggested that chronic alcoholism is the cause of accelerated or premature ageing. The objective of this study was to evaluate the frequency and magnitude of DNA damage among adults with chronic alcoholism and healthy older adults residing in Mexico City. A cross-sectional and comparative study was carried out in a sample of 53 chronic alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days) without additional diseases, 26 healthy subjects >or=60 years of age, and 25 healthy adults of 25-44 years of age without alcohol addiction, all residents of Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel electrophoresis technique (Comet assay). Our results showed a similar percentage of DNA damage between healthy elderly subjects and chronic alcoholics (62 vs 55%, P >0.05), although average DNA migration was greater in alcoholics than in the elderly (78.1 +/- 33.2 vs 58.6 +/- 26.2, P = 0.09). However, the percentage of subjects with more than six damaged cells was higher in the older adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16). Data suggest that DNA damage is not similar in young subjects with chronic alcoholism that which occurs with ageing.

  7. Comparison of regional pancreatic tissue fluid pressure and endoscopic retrograde pancreatographic morphology in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation. The predrain......The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation...

  8. Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Oohara, Hiroshi.

    1989-01-01

    Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

  9. Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

    Science.gov (United States)

    Griko, Y. V.; Yan, Xiaoli

    2016-01-01

    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

  10. Hypersensitivity to DNA-damaging agents in primary degenerations of excitable tissue

    International Nuclear Information System (INIS)

    Robbins, J.H.

    1983-01-01

    Defects in DNA-repair mechanisms render xeroderma pigmentosum cells hypersensitive to killing by the uv-type of DNA-damaging agent. Some xeroderma pigmentosum patients develop a primary neuronal degeneration, and cell lines from patients with the earliest onset of neurodegeneration are the most sensitive to killing by uv radiation. These findings led to the neuronal DNA integrity theory which holds that when the integrity of neuronal DNA is destroyed by the accumulation of unrepaired DNA damaged spontaneously or by endogenous metabolites, the neurons will undergo a primary degeneration. Cells from patients with Cockayne syndrome, a demyelinating disorder with a primary retinal degeneration, are also hypersensitive to the uv-type of DNA-damaging agent. Cells from patients with the primary neuronal degeneration of ataxia telangiectasia are hypersensitive to the x-ray-type of DNA-damaging agent. Cells from other patients with primary degeneration of excitable tissue also have hypersensitivity to the x-ray-type of DNA-damaging agent. These disorders include (1) primary neuronal degenerations which are either genetic (e.g., Huntington disease, familial dysautonomia, Friedreich ataxia) or sporadic (e.g., Alzheimer disease, Parkinson disease), (2) primary muscle degenerations (e.g., Duchenne muscular dystrophy), and (3) a primary retinal degeneration (Usher syndrome). Death of excitable tissue in vivo in these radiosensitive diseases may result from unrepaired DNA. This hypersensitivity provides the basis for developing suitable presymptomatic and prenatal tests for these diseases, for elucidating their pathogenesis, and for developing future therapies. 119 references, 3 figures, 3 tables

  11. 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: rroeder@nd.edu [University of Notre Dame, Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program (United States)

    2012-10-15

    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.

  12. Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid

    International Nuclear Information System (INIS)

    Wnek, S.M.; Medeiros, M.K.; Eblin, K.E.; Gandolfi, A.J.

    2009-01-01

    Malignant transformation was demonstrated in UROtsa cells following 52-weeks of exposure to 50 nM monomethylarsonous acid (MMA III ); the result was the malignantly transformed cell line, URO-MSC. URO-MSC cells were used to study the induction of DNA damage and the alteration of DNA repair enzymes in both the presence of MMA III [URO-MSC(+)] and after subsequent removal of MMA III [URO-MSC(-)] following chronic, low-level exposure. In the presence of MMA III , URO-MSC(+) cells demonstrated a sustained increase in DNA damage following 12-weeks of exposure; in particular, a significant increase in DNA single-strand breaks at 12-weeks of exposure consistently elevated through 52 weeks. The persistence of DNA damage in URO-MSC cells was assessed after a 2-week removal of MMA III . URO-MSC(-) cells demonstrated a decrease in DNA damage compared to URO-MSC(+); however, DNA damage in URO-MSC(-) remained significantly elevated when compared to untreated UROtsa and increased in a time-dependent manner. Reactive oxygen species (ROS) were demonstrated to be a critical component in the generation of DNA damage determined through the incubation of ROS scavengers with URO-MSC cells. Poly (ADP-ribose) polymerase (PARP) is a key repair enzyme in DNA single-strand break repair. URO-MSC(+) resulted in a slight increase in PARP activity after 36-weeks of MMA III exposure, suggesting the presence of MMA III is inhibiting the increase in PARP activity. In support, PARP activity in URO-MSC(-) increased significantly, coinciding with a subsequent decrease in DNA damage demonstrated in URO-MSC(-) compared to URO-MSC(+). These data demonstrate that chronic, low-level exposure of UROtsa cells to 50 nM MMA III results in: the induction of DNA damage that remains elevated upon removal of MMA III ; increased levels of ROS that play a role in MMA III induced-DNA damage; and decreased PARP activity in the presence of MMA III .

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

    Directory of Open Access Journals (Sweden)

    Nohra E. Beltran

    2013-01-01

    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.

  14. 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)

    2007-06-15

    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.

  15. Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection.

    Science.gov (United States)

    Hofer, Ursula; Speck, Roberto F

    2009-07-01

    Why and how HIV makes people sick is highly debated. Recent evidence implicates heightened immune activation due to breakdown of the gastrointestinal barrier as a determining factor of lentiviral pathogenesis. HIV-mediated loss of Th17 cells from the gut-associated lymphoid tissue (GALT) impairs mucosal integrity and innate defense mechanisms against gut microbes. Translocation of microbial products from the gut, in turn, correlates with increased immune activation in chronic HIV infection and may further damage the immune system by increasing viral and activation-induced T cell death, by reducing T cell reconstitution due to tissue scarring, and by impairing the function of other cell types, such as gammadelta T cells and epithelial cells. Maintaining a healthy GALT may be the key to reducing the pathogenic potential of HIV.

  16. Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing

    Science.gov (United States)

    Feng, Yi; Sanders, Andrew J.; Ruge, Fiona; Morris, Ceri-Ann; Harding, Keith G.; Jiang, Wen G.

    2016-01-01

    Cytokines play important roles in the wound healing process through various signalling pathways. The JAK-STAT pathway is utilised by most cytokines for signal transduction and is regulated by a variety of molecules, including suppressor of cytokine signalling (SOCS) proteins. SOCS are associated with inflammatory diseases and have an impact on cytokines, growth factors and key cell types involved in the wound-healing process. SOCS, a negative regulator of cytokine signalling, may hold the potential to regulate cytokine-induced signalling in the chronic wound-healing process. Wound edge tissues were collected from chronic venous leg ulcer patients and classified as non-healing and healing wounds. The expression pattern of seven SOCSs members, at the transcript and protein level, were examined in these tissues using qPCR and immunohistochemistry. Significantly higher levels of SOCS3 (P=0.0284) and SOCS4 (P=0.0376) in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level. Relocalisation of SOCS3 protein in the non-healing wound environment was evident in the investigated chronic biopsies. Thus, the results show that the expression of SOCS transcript indicated that SOCS members may act as a prognostic biomarker of chronic wounds. PMID:27635428

  17. Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue.

    Science.gov (United States)

    Sundararaj, Sharath; Slusarewicz, Paul; Brown, Matt; Hedman, Thomas

    2017-11-01

    The most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid-release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid-release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull-out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199-2205, 2017. © 2016 Wiley Periodicals, Inc.

  18. The number of bleaching sessions influences pulp tissue damage in rat teeth.

    Science.gov (United States)

    Cintra, Luciano Tavares Angelo; Benetti, Francine; da Silva Facundo, Aguinaldo Cândido; Ferreira, Luciana Louzada; Gomes-Filho, João Eduardo; Ervolino, Edilson; Rahal, Vanessa; Briso, André Luiz Fraga

    2013-12-01

    Hydrogen peroxide tooth bleaching is claimed to cause alterations in dental tissue structures. This study investigated the influence of the number of bleaching sessions on pulp tissue in rats. Male Wistar rats were studied in 5 groups (groups 1S-5S) of 10 each, which differed by the number (1-5) of bleaching sessions. In each session, the animals were anesthetized, and 35% hydrogen peroxide gel was applied to 3 upper right molars. Two days after the experimental period, the animals were killed, and their jaws were processed for light microscope evaluation. Pulp tissue reactions were scored as follows: 1, no or few inflammatory cells and no reaction; 2, session, necrotic tissue in the pulp horns and underlying inflammatory changes were observed. The extent and intensity of these changes increased with the number of bleaching sessions. After 5 sessions, the changes included necrotic areas in the pulp tissue involving the second third of the radicular pulp and intense inflammation in the apical third. The number of bleaching sessions directly influenced the extent of pulp damage. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Cantin Elizabeth

    2008-10-01

    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.

  20. Effects of heavy ions on rabbit tissues: damage to the forebrain

    International Nuclear Information System (INIS)

    Cox, A.B.; Keng, P.C.; Lee, A.C.; Lett, J.T.

    1982-01-01

    As part of a study of progressive radiation effects in normal tissues, the forebrains of New Zealand white rabbits (Oryctolagus cuniculus) (about 6 weeks old) were irradiated locally with single acute doses of 60 Co γ-photons (LETsub(infinity)=0.3 keV/μm), Ne ions (LETsub(infinity)=35+-3 keV/μm) or Ar ions (LETsub(infinity)=90+-5 keV/μm). Other rabbits received fractionated doses of 60 Co γ-photons according to a standard radiotherapeutic protocol. Irradiated rabbits and appropriately aged controls were sacrificed at selected intervals, and whole sagittal sections of their brains were examined for pathological changes. Forebrain damage was scored with subjective indices based on histological differences between the anterior (irradiated) and posterior (unirradiated) regions of the brain. Those indices ranged from zero (no apparent damage) to five (severe infarctions, etc.). At intermediate levels of forebrain damage, the relative biological effectiveness (r.b.e.) of each heavy ion was similar to that found for alopecia and cataractogenesis, and the early expression of the damage was also accelerated as the LETsub(infinity) increased. Late deterioration of the forebrain appeared also to be accelerated by increasing LETsub(infinity), although its accurate quantification was not possible because other priorities in the overall experimental design limited systematic sacrifice of the animals. (author)

  1. Leaf hairs of Olea europaea protect underlying tissues against ultraviolet-B radiation damage

    International Nuclear Information System (INIS)

    Karabourniotis, G.; Kyparissis, A.; Manetas, Y.

    1993-01-01

    The photochemical efficiency of photosystem II, as measured by chlorophyll fluorescence induction, was not affected in de-haired olive leaves kept in the dark or intact leaves irradiated with a moderate (3.75 W m-2) ultraviolet-B (UV-B) intensity. In de-haired, UV-B-irradiated leaves, however, the ratio of variable to maximum (F(v)/F(m)) chlorophyll fluorescence declined significantly and irreversibly. Reduction in F(v)/V(m) was associated with an increase in instantaneous and a decrease in maximum (F(m)) fluorescence, indicating perturbation by the UV-B exposure of more than one photosynthetic site. Extensive epidermal browning in de-haired, UV-B irradiated leaves was also observed, indicating possible damage to cell membranes. The results strengthen the hypothesis that leaf hairs protect the underlying tissues against UV-B radiation damage

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

    International Nuclear Information System (INIS)

    Ai, H; Zhang, H

    2014-01-01

    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

  3. Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats.

    Directory of Open Access Journals (Sweden)

    Matilde Otero-Losada

    Full Text Available This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats.Forty-eight Wistar rats were randomly assigned to 4 groups depending on a beverage consumption ad libitum, water (W or cola beverage (C, and b physical activity, sedentary (S or treadmill running (R. Accordingly, 4 groups were studied: WS (water sedentary, WR (water runner, CS (cola sedentary and CR (cola runner. Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry, and systolic blood pressure (plethysmography were measured. After 6 months, euthanasia was performed (overdose sodium thiopental. Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations.The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001 rather than simple summation. Cola drinking (CS vs WS reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001 and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001, and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001. In water drinking rats (WR vs WS, running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001 and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001. Differently, in cola drinking rats (CR vs CS, running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05, increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001 and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05.This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and

  4. Pain and Tissue Damage in Response to Orthodontic Tooth Movement: Are They Correlated?

    Science.gov (United States)

    Cuoghi, Osmar A; Topolski, Francielle; de Faria, Lorraine P; de Mendonça, Marcos R

    2016-09-01

    To evaluate the correlation between pain and tissue damage in response to orthodontic tooth movement (OTM), such as hyalinization and external apical root resorption (EARR). The literature review was used as a methodological strategy, following the knowledge development process - constructivist (ProKnow-C). Study axes were defined and keywords that best represented each axis were selected. The terms were submitted to an adherence test and validation, resulting in 12 keyword combinations. Searches were carried out in the most representative databases for the selected terms, without restriction as for language or publication dates. Retrieved studies were filtered using the EndNote X6 program and classified according to analysis of title, abstract, and keywords. The final portfolio of articles was submitted to bibliometric and systematic analysis. A total of 1,091 studies were retrieved, out of which 719 were repeated and 335 were removed in the classification stage. A total of 37 articles remained in the final portfolio. Only one article was in line with the purpose of this study, indicating absence of correlation between pain and EARR in response to OTM. Further studies are necessary to confirm whether orthodontic pain might serve as a criterion for the use of appropriate mechanical forces, contributing to minimize tissue damage following OTM. This article presents a systematic literature review, in which scientific evidence of the correlation between pain and tissue damage during orthodontic movement was studied, providing a scientific answer for the following question: Is pain reported by patients associated with application of inappropriate orthodontic force? Thus, it aims at aiding the orthodontist in the definition of clinical parameters for the use of optimal orthodontic force.

  5. Effect of dexmedetomidine combined with propofol on brain tissue damage in brain glioma resection

    Institute of Scientific and Technical Information of China (English)

    2017-01-01

    Objective:To study the effect of dexmedetomidine combined with propofol on brain tissue damage in brain glioma resection.Methods: A total of 74 patients who received brain glioma resection in our hospital between May 2014 and December 2016 were selected and randomly divided into Dex group and control group who received dexmedetomidine intervention and saline intervention before induction respectively. Serum brain tissue damage marker, PI3K/AKT/iNOS and oxidation reaction molecule contents as well as cerebral oxygen metabolism index levels were determined before anesthesia (T0), at dura mater incision (T1), immediately after recovery (T2) and 24 h after operation (T3).Results: Serum NSE, S100B, MBP, GFAP, PI3K, AKT, iNOS and MDA contents as well as AVDO2 and CERO2 levels of both groups at T2 and T3 were significantly higher than those at T0 and T1 while serum SOD and CAT contents as well as SjvO2levels were significantly lower than those at T0 and T1, and serum NSE, S100B, MBP, GFAP, PI3K, AKT, iNOS and MDA contents as well as AVDO2 and CERO2 levels of Dex group at T2 and T3 were significantly lower than those of control group while serum SOD and CAT contents as well as SjvO2 levels were significantly higher than those of control group.Conclusions: Dexmedetomidine combined with propofol can reduce the brain tissue damage in brain glioma resection.

  6. Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and Combats Hyperglycaemia in Diabetic Rats.

    Science.gov (United States)

    Suresh, Sithara; Waly, Mostafa Ibrahim; Rahman, Mohammad Shafiur; Guizani, Nejib; Al-Kindi, Mohamed Abdullah Badar; Al-Issaei, Halima Khalfan Ahmed; Al-Maskari, Sultan Nasser Mohd; Al-Ruqaishi, Bader Rashid Said; Al-Salami, Ahmed

    2017-12-01

    Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli ( Brassica oleracea ) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics ( P <0.05). The treatment of diabetic rats with BE significantly reduced DNA damage and conserved GSH and TAC values ( P <0.01). BE attenuated pancreatic histopathological changes in diabetic rats. The results of this study indicated that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as an anti-diabetic herbal medicine and provided insights into the capacity of BE to be used for phytoremediation purposes for human type 2 diabetes.

  7. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.......e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously...

  8. Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

    Science.gov (United States)

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

    2017-10-01

    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.

  9. Fracture mechanics model of stone comminution in ESWL and implications for tissue damage

    Science.gov (United States)

    Lokhandwalla, Murtuza; Sturtevant, Bradford

    2000-07-01

    Focused shock waves administered during extracorporeal shock-wave lithotripsy (ESWL) cause stone fragmentation. The process of stone fragmentation is described in terms of a dynamic fracture process. As is characteristic of all brittle materials, fragmentation requires nucleation, growth and coalescence of flaws, caused by a tensile or shear stress. The mechanisms, operative in the stone, inducing these stresses have been identified as spall and compression-induced tensile microcracks, nucleating at pre-existing flaws. These mechanisms are driven by the lithotripter-generated shock wave and possibly also by cavitation effects in the surrounding fluid. In this paper, the spall mechanism has been analysed, using a cohesive-zone model for the material. The influence of shock wave parameters, and physical properties of stone, on stone comminution is described. The analysis suggests a potential means to exploit the difference between the stone and tissue physical properties, so as to make stone comminution more effective, without increasing tissue damage.

  10. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    Science.gov (United States)

    Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

    2014-01-01

    Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  11. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

    International Nuclear Information System (INIS)

    Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

    2009-01-01

    Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

  12. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    Science.gov (United States)

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

    2017-09-01

    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.

  13. The causes of skin damage and leg ulceration in chronic venous disease.

    Science.gov (United States)

    Smith, Philip Coleridge

    2006-09-01

    Chronic venous disease with skin changes of the leg is a common condition affecting up to 1 in 20 people in westernized countries. The causes of this problem are not fully understood, although research in recent years has revealed a number of important mechanisms that contribute to the disease process. Patients with chronic venous disease suffer persistently raised pressures in their deep and superficial veins in the lower limb. Leucocytes become "trapped" in the circulation of the leg during periods of venous hyper-tension produced by sitting or standing. Studies of the plasma levels of neutrophil granule enzymes shows that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligands CD11b and CD62L shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the endothelial adhesion molecules VCAM, ICAM, and ELAM show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 minutes of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. Chronic injury to the endothelium leads to a chronic inflammatory condition of the skin that we know clinically as lipodermatosclerosis. This is mediated by perivascular inflammatory cells, principally macrophages, in the skin microcirculation. These stimulate fibroblasts in the skin leading to tissue remodeling and laying down of fibrous tissue. Vascular endothelial growth factor stimulates proliferation of capillaries within the skin. Skin in this state has the potential to ulcerate in response to minor injury.

  14. Damage to apparel layers and underlying tissue due to hand-gun bullets.

    Science.gov (United States)

    Carr, Debra; Kieser, Jules; Mabbott, Alexander; Mott, Charlotte; Champion, Stephen; Girvan, Elizabeth

    2014-01-01

    Ballistic damage to the clothing of victims of gunshot wounds to the chest can provide useful forensic evidence. Anyone shot in the torso will usually be wearing clothing which will be damaged by the penetrating impact event and can reportedly be the source of some of the debris in the wound. Minimal research has previously been reported regarding the effect of bullets on apparel fabrics and underlying tissue. This paper examines the effect of ammunition (9 mm full metal jacket [FMJ] DM11 A1B2, 8.0 g; and soft point flat nose Remington R357M3, 10.2 g) on clothing layers that cover the torso (T-shirt, T-shirt plus hoodie, T-shirt plus denim jacket) and underlying structures represented by porcine thoracic wall (skin, underlying tissue, ribs). Impacts were recorded using a Phantom V12 high speed camera. Ejected bone debris was collected before wound tracts were dissected and measured; any debris found was recovered for further analysis. Size and mass of bony debris was recorded; fibre debris recovered from the wound and impact damage to fabrics were imaged using scanning electron microscopy (SEM). Remington R357M3 ammunition was characteristically associated with stellate fabric damage; individual fibres were less likely to show mushrooming. In contrast, 9 mm FMJ ammunition resulted in punch-out damage to fabric layers, with mushrooming of individual fibres being more common. Entry wound sizes were similar for both types of ammunition and smaller than the diameter of the bullet that caused them. In this work, the Remington R357M3 ammunition resulted in larger exit wounds due to the bullet construction which mushroomed. That fabric coverings did not affect the amount of bony debris produced is interesting, particularly given there was some evidence that apparel layers affected the size of the wound. Recent work has suggested that denim (representative of jeans) can exacerbate wounding caused by high-velocity bullet impacts to the thigh when the bullet does not

  15. Chronic irradiation of gonad tissue of the male rat

    International Nuclear Information System (INIS)

    Lemaire, G.; Maas, J.

    1982-01-01

    The effects of chronically irradiating rats' testes with daily gamma radiation doses of (1.4 - 8.6) x 10 -2 Gy for 71-140 days were studied. After about 30 days irradiation, the testes weights decrease and level off at about 75 days. Irradiation also caused the germ cells in the seminiferous tubules to disappear progressively, completely when the dose exceeded 6 x 10 -2 Gy/day and partially with the lower doses. At doses below 6 x 10 -2 Gy/day, there was also a delay in the spermatogenesis cycle with the spermatogonia and spermatocytes appearing to reach a new equilibrium, the level of which depended on the dose. (U.K.)

  16. Class I and II histone deacetylase expression in human chronic periodontitis gingival tissue.

    Science.gov (United States)

    Cantley, M D; Dharmapatni, A A S S K; Algate, K; Crotti, T N; Bartold, P M; Haynes, D R

    2016-04-01

    Histone deacetylase inhibitors (HDACi) are being considered to treat chronic inflammatory diseases at low doses. Currently HDACi that are more specific are being developed to target particular HDACs; therefore, this study aimed to determine levels and distribution of class I and II HDAC in human gingival samples obtained from patients with chronic periodontitis. Gingival biopsies were obtained from patients with and without (mild inflammation, no bone loss) periodontitis. Total RNA was isolated for real-time quantitative polymerase chain reaction to determine expression of HDACs 1-10. Immunohistochemistry was used to determine protein distribution of HDACs 1, 5, 8 and 9. Factor VIII, CD3 and tartrate resistant acid phosphatase (TRAP) were detected in serial sections to identify blood vessels, lymphocytes, pre-osteoclasts and osteoclasts cells respectively. Tumour necrosis factor α (TNF-α) expression was also assessed. mRNA for HDAC 1, 5, 8 and 9 were significantly upregulated in chronic periodontitis gingival tissues compared to non-periodontitis samples (p chronic periodontitis samples (p chronic periodontitis gingival tissues. HDAC 1, 5, 8 and 9 expression was higher in gingival tissues from patients with chronic periodontitis compared to non-periodontitis samples. Results suggest that these HDACs could therefore be targeted with specific acting HDACi. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Role of free tissue transfer in management of chronic venous ulcer

    Directory of Open Access Journals (Sweden)

    Reddy K

    2004-01-01

    Full Text Available Most of the venous ulcers will heal with the treatment of primary venous problem. But a few patients will have refractory, recurrent chronic venous ulcers causing inconvenience to the patients in terms of loss of productive working hours. There is no standard method available for treatment of this chronic problem. Our modality of treatment includes wide excision of ulcer, ligation of incompetent perforators and coverage of defect with well vascularized tissue by free tissue transfer. We have analyzed this form of treatment in five patients with satisfactory result.

  18. Electrolysed reduced water decreases reactive oxygen species-induced oxidative damage to skeletal muscle and improves performance in broiler chickens exposed to medium-term chronic heat stress.

    Science.gov (United States)

    Azad, M A K; Kikusato, M; Zulkifli, I; Toyomizu, M

    2013-01-01

    1. The present study was designed to achieve a reduction of reactive oxygen species (ROS)-induced oxidative damage to skeletal muscle and to improve the performance of broiler chickens exposed to chronic heat stress. 2. Chickens were given a control diet with normal drinking water, or diets supplemented with cashew nut shell liquid (CNSL) or grape seed extract (GSE), or a control diet with electrolysed reduced water (ERW) for 19 d after hatch. Thereafter, chickens were exposed to a temperature of either 34°C continuously for a period of 5 d, or maintained at 24°C, on the same diets. 3. The control broilers exposed to 34°C showed decreased weight gain and feed consumption and slightly increased ROS production and malondialdehyde (MDA) concentrations in skeletal muscle. The chickens exposed to 34°C and supplemented with ERW showed significantly improved growth performance and lower ROS production and MDA contents in tissues than control broilers exposed to 34°C. Following heat exposure, CNSL chickens performed better with respect to weight gain and feed consumption, but still showed elevated ROS production and skeletal muscle oxidative damage. GSE chickens did not exhibit improved performance or reduced skeletal muscle oxidative damage. 4. In conclusion, this study suggests that ERW could partially inhibit ROS-induced oxidative damage to skeletal muscle and improve growth performance in broiler chickens under medium-term chronic heat treatment.

  19. MRI in diagnostic of soft tissue damages by fractures of lateral tibial plate

    International Nuclear Information System (INIS)

    Dimitrova, D.; Proichev, V.; Popov, I.

    2015-01-01

    Full text: The knee is one of the most often injured joint. Fractures of tibial condyles are the most common articular damages. Koton and Berg call them „bumper“ fractures the tibia plateau is vulnerable to both high- and low-energy injury mechanisms due to its vulnerable position in the lower extremity. It must bear significant weight and sustain significant impact and deceleration forces with little skeletal constraint, and has scant surrounding soft tissue and a tethered medial and lateral integument. Furthermore, the tibial plateau has relatively forgiving ligamentous attachments that must allow for a large range of motion in a single plane. Not surprisingly, given the diversity of injury, management of these fractures has come to include a wide variety of treatment strategies. traditionally, ligament injury associated with plateau fractures has been diagnosed indirectly with stress radiographs and physical examination. With increasing use of more sensitive MRI and arthroscopy, associated ligament and meniscus injuries have been found in significant percentages of plateau fractures. these soft tissue injuries consist primarily of MCL lesions, meniscal injuries, and ACL disruptions. However, studies addressing associated soft tissue injuries all agree that neither the type of plateau fracture nor the presence or absence of ligament injury correlates with the incidence of meniscal tears

  20. QRS slopes for assessment of myocardial damage in chronic chagasic patients

    International Nuclear Information System (INIS)

    Pueyo, E; Laciar, E; Anzuola, E; Laguna, P; Jane, R

    2007-01-01

    In this study the slopes of the QRS complex are evaluated for determination of the degree of myocardial damage in chronic chagasic patients. Previous studies have demonstrated the ability of the slope indices to reflect alterations in the conduction velocity of the cardiac impulse. Results obtained in the present study show that chronic chagasic patients have significantly flatter QRS slopes as compared to healthy subjects. Not only that but the extent of slope lessening turns out to be proportional to the degree of myocardial damage caused by the disease. Additionally, when incorporating the slope indices into a classification analysis together with other indices indicative of the presence of ventricular late potentials obtained from high resolution electrocardiography, results show that the percentages of correct classification increase up to 62.5%, which means eight points above the percentages obtained prior to incorporation of the slope indices. It can be concluded that QRS slopes have great potential for assessing the degree of severity associated with Chagas' disease

  1. Medial tibial “spackling” to lessen chronic medial tibial soft tissue irritation

    Directory of Open Access Journals (Sweden)

    J. Ryan Martin, MD

    2016-09-01

    Full Text Available We describe a unique, utilitarian reconstructive treatment option known as tibial “spackling” for chronic, localized medial joint line pain corresponding with progressive radiographic peripheral medial tibial bone loss beneath a well-fixed revision total knee arthroplasty tibial baseplate. It is believed that this localized pain is due to chronic irritation of the medial capsule and collateral ligament from the prominent medial edge of the tibial component. In the setting of failed nonoperative treatment, our experience with utilizing bone cement to reconstruct the medial tibial bone defect and create a smooth medial tibial surface has been successful in eliminating chronic medial soft tissue irritation.

  2. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

    Directory of Open Access Journals (Sweden)

    Godwin Sokpor

    2012-05-01

    Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

  3. Select tissue mineralconcentrations and chronic wasting disease status in mule deer from north-central Colorado

    OpenAIRE

    Wolfe, Lisa L.; Conner, Mary M.; Bedwell, Cathy L.; Lukacs, Paul M.; Miller, Michael W.

    2010-01-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (≥2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populati...

  4. Modulation of radiation induced DNA damage by natural products in hemopoietic tissue of mice

    International Nuclear Information System (INIS)

    Jayakumar, S.; Bhilwade, H.N.; Chaubey, R.C.

    2014-01-01

    Ionizing radiation is known to induce oxidative stress through generation of ROS leading to a variety of DNA lesions. However, the most dangerous DNA lesions which are responsible for the origin of lethal effects, mutagenesis, genomic instability and carcinogenesis are the DSBs. During recent years efforts are being made to identify phytochemicals, antioxidants or neutraxeuticals which can reduce harmful effect of radiation during accidental exposure or prevent normal tissue injury during radiotherapy. In the present study, we have investigated the radioprotective role of curcumin, a dietary antioxidant, taurine, malabaricone-C, and umbelliferone, for their radioprotective properties in hemopoietic cells of mice. Groups of mice-were fed 1% of curcumin in diet for three weeks. Similarly other groups of mice were injected i.p. with 50 mg/kg body weight of taurine for five consecutive days. After the completion of the treatment mice pre-treated with curcumin and taurine were exposed to 3 Gy of gamma rays. Malabaricone-C was tested for its radiomodulation potential in vitro, in spleenocytes of mouse. Spleenocytes were isolated and treated with different concentrations (0.5-25 ìM) of malabaricone-C. Immediately after irradiation, alkaline comet assay were performed using standard procedures. Twenty four post radiation exposure mice were sacrificed for micronucleus test. Results of these studies showed significant reduction in DNA damage by curcumin. The micronucleus data showed marginal increase in the frequency of micronucleated erythrocytes in curcumin fed group as compared to the controls. Mice receiving curcumin for 3 weeks in diet followed by gamma radiation (3 Gy), showed approximately 50% reduction in the frequency of micro nucleated polychromatic erythrocytes. Pre-treatment of mice with taurine significantly (p < 0.01) reduced the frequency of gamma rays induced mn-PCEs in bone marrow tissue. Malabaricone-C at 1.5 ìM concentration showed very good protection

  5. Tissue viral load variability in chronic hepatitis C.

    LENUS (Irish Health Repository)

    Fanning, L

    2012-02-03

    OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

  6. Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Ping; Xu, Tiantian; Wu, Siyu; Lei, Lili; He, Defu

    2017-10-01

    Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l -1 GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S.

    2000-01-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant > for processing and temporary storage of

  8. Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

    Directory of Open Access Journals (Sweden)

    Miao Long

    2016-10-01

    Full Text Available Lead is harmful for human health and animals. Proanthocyanidins (PCs, a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER stress-related genes and protein (GRP78 and CHOP. Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress

  9. Effect of dental restoration with epoxy and bioceramic paste on periodontal tissue damage

    Institute of Scientific and Technical Information of China (English)

    Nan-Lin Meng

    2017-01-01

    Objective:To study the effect of dental restoration with epoxy and bioceramic paste on periodontal tissue damage.Methods: Patients with pulpal and periapical diseases who received root canal therapy in our hospital between May 2013 and October 2016 were retrospectively analyzed, and according to the different root canal filling materials they used, they were divided into epoxy group and bioceramic group who used epoxy paste and bioceramic paste as root canal filling materials respectively. Before and after treatment, gingival crevicular fluid was collected respectively to determine the levels of inflammatory factors, oxidative stress products, cell apoptosis molecules and protease-related molecules.Results: 2 weeks after treatment, IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bcl-2, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1, MMP-2, TIMP-1 and TIMP-2 levels in gingival crevicular fluid of epoxy group were not significantly different from those before treatment; IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1 and MMP-2 levels in gingival crevicular fluid of bioceramic group were significantly higher than those before treatment while Bcl-2, TIMP-1 and TIMP-2 levels were significantly lower than those before treatment; IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bcl-2, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1, MMP-2, TIMP-1 and TIMP-2 levels in gingival crevicular fluid were significantly different between two groups of patients after treatment.Conclusion:Epoxy paste for dental restoration causes less damage to periodontal tissue than bioceramic paste.

  10. Effect of dental restoration with epoxy and bioceramic paste on periodontal tissue damage

    Directory of Open Access Journals (Sweden)

    Nan-Lin Meng

    2017-05-01

    Full Text Available Objective: To study the effect of dental restoration with epoxy and bioceramic paste on periodontal tissue damage. Methods: Patients with pulpal and periapical diseases who received root canal therapy in our hospital between May 2013 and October 2016 were retrospectively analyzed, and according to the different root canal filling materials they used, they were divided into epoxy group and bioceramic group who used epoxy paste and bioceramic paste as root canal filling materials respectively. Before and after treatment, gingival crevicular fluid was collected respectively to determine the levels of inflammatory factors, oxidative stress products, cell apoptosis molecules and protease-related molecules. Results: 2 weeks after treatment, IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bcl-2, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1, MMP-2, TIMP-1 and TIMP-2 levels in gingival crevicular fluid of epoxy group were not significantly different from those before treatment; IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1 and MMP-2 levels in gingival crevicular fluid of bioceramic group were significantly higher than those before treatment while Bcl-2, TIMP-1 and TIMP-2 levels were significantly lower than those before treatment; IL-1β, IL-6, CRP, ROS, MDA, AOPP, Bcl-2, Bax, Cyt-C, caspase-3, Smac, EMMPRIN, MMP-1, MMP-2, TIMP-1 and TIMP-2 levels in gingival crevicular fluid were significantly different between two groups of patients after treatment. Conclusion: Epoxy paste for dental restoration causes less damage to periodontal tissue than bioceramic paste.

  11. Is chronic fatigue syndrome a connective tissue disorder? A cross-sectional study in adolescents

    NARCIS (Netherlands)

    van de Putte, E. M.; Uiterwaal, C. S. P. M.; Bots, M. L.; Kuis, W.; Kimpen, J. L. L.; Engelbert, R. H. H.

    2005-01-01

    To investigate whether constitutional laxity of the connective tissues is more frequently present in adolescents with chronic fatigue syndrome (CFS) than in healthy controls. Increased joint hypermobility in patients with CFS has been previously described, as has lower blood pressure in fatigued

  12. Ultrasonic energy vs monopolar electrosurgery in laparoscopic cholecystectomy: a comparison of tissue damage

    Directory of Open Access Journals (Sweden)

    Mehdi Asgari

    2016-04-01

    Full Text Available Background: Laparoscopic cholecystectomy is a minimally invasive procedure whereby the gallbladder is removed using laparoscopic techniques. Monopolar electerosurgical energy is the method of dissection of gallbladder from liver bed. Ultrasonic energy causes less thermal damage and suggests an alternative to monopolar elevterocautery. Leptin is a tissue factor and C-reactive protein (CRP is an acute phase protein that builds up in surgical damages. In laparoscopy, pneumoperitoneum and thermal damage cause this increase. In this study, after completion of surgery with both methods, plasma leptin and CPR were measured. Next, the complications and benefits of the two methods were compared. Methods: This single blind randomized clinical trial was conducted on 78 patients who were candidate for laparoscopic cholecystectomy in surgery clinic of Razi Teaching Hospital in Ahvaz Jundishapur University of Medical Sciences from March 2013 to March 2015. Patients were divided randomly into two groups of ultrasonic and electerocautery. Then, leptin’s level and CRP’s level were measured at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in the two groups. Results: This study shows that the average rate of leptin at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in ultrasonic group had less increase than electerocautery group and the difference was statistically significant (P= 0.0001. The average rate of CRP at completion of surgery, 30 minutes after completion, 6 and 24 hours after completion of surgery in ultrasonic group had less increase than electerocautery group and the difference was statistically significant (P= 0.0001. Conclusion: The level of leptin and CRP shows that surgery with ultrasonic method will provoke the immune system less than electerocautery method.

  13. Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease.

    Science.gov (United States)

    Cosola, Carmela; Rocchetti, Maria Teresa; Cupisti, Adamasco; Gesualdo, Loreto

    2018-04-01

    In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design

  14. Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

    DEFF Research Database (Denmark)

    O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas

    2007-01-01

    be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus...... in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain......Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could...

  15. Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.

    Science.gov (United States)

    Calo, Eliezer; Gu, Bo; Bowen, Margot E; Aryan, Fardin; Zalc, Antoine; Liang, Jialiang; Flynn, Ryan A; Swigut, Tomek; Chang, Howard Y; Attardi, Laura D; Wysocka, Joanna

    2018-02-01

    Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and

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

    International Nuclear Information System (INIS)

    Herppich, Werner B.; Zabler, Simon; Dawson, Martin; Choinka, Gerard; Manke, Ingo

    2015-01-01

    ''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.

  17. 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)

    2015-02-01

    ''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.

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

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2012-02-01

    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.

  19. Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

    NARCIS (Netherlands)

    Seiffge, David J.; Lapina, Natalia E.; Tsagogiorgas, Charalambos; Theisinger, Bastian; Henning, Robert H.; Schilling, Lothar

    Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane

  20. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    Science.gov (United States)

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.

  1. The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

    Science.gov (United States)

    Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

    2012-01-01

    The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

  2. Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM.

    Science.gov (United States)

    Paoletti, Ernesto; Bellino, Diego; Amidone, Marco; Rolla, Davide; Cannella, Giuseppe

    2006-01-01

    To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist. We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods. According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p nighttime SBP > 24-hour PP > daytime PP > daytime SBP > 24-hour SBP. In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).

  3. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

    Science.gov (United States)

    Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

    2016-12-01

    Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort.

    Science.gov (United States)

    Conti, F; Ceccarelli, F; Perricone, C; Leccese, I; Massaro, L; Pacucci, V A; Truglia, S; Miranda, F; Spinelli, F R; Alessandri, C; Valesini, G

    2016-06-01

    Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). In the present study chronic damage was identified in about one third of SLE patients. The

  5. Photodynamic damage to cartilage and synovial tissue grafted on a chick's chorioallantoic membrane

    Science.gov (United States)

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

    1997-09-01

    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.

  6. Chronic exposure to microcystin-LR affected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice

    International Nuclear Information System (INIS)

    Li, Xinxiu; Xu, Lizhi; Zhou, Wei; Zhao, Qingya; Wang, Yaping

    2016-01-01

    Microcystin-LR (MC-LR), an important variant of cyanotoxin family, was frequently encountered in the contaminated aquatic environment and taken as a potent hepatotoxin. However, a little was known on the association between the long-term MC-LR exposure and lung damage. In this study, we investigated the changes of the pulmonary histopathology, mitochondrial DNA (mtDNA) integrity and the expression of mtDNA encoded genes in the mice with chronic exposed to MC-LR at different concentrations (1, 5, 10, 20 and 40 μg/L) for 12 months. Our results showed that the long-term and persistent exposure to MC-LR disturbed the balance of redox system, influenced mtDNA stability, changed the expression of mitochondrial genes in the lung cells. Notably, MC-LR exposure influenced the level of inflammatory cytokines and resulted in thickening of the alveolar septa. In conclusion, chronic exposure to MC-LR affected mtDNA maintenance, and caused lung impairment in mice. - Highlights: • A simulated natural exposure to MC-LR caused the lung pathological changes. • The chronic exposure disturbed the redox system balance of lung tissue cells. • The chronic exposure impaired the mtDNA stability and mitochondria function. • The lung was one of the vulnerable organs to MC-LR exposure in mice. - Long-term exposure to MC-LR in drinking water disturbed the balance of redox system, affected mitochondrial DNA maintenance and caused lung impairment in mice.

  7. Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

    OpenAIRE

    Mustafa Talip Sener; Hamit Hakan Alp; Beyzagul Polat; Bunyamin Borekci; Yakup Kumtepe; Nesrin Gursan; Serkan Kumbasar; Suleyman Salman; Halis Suleyman

    2011-01-01

    Background In this study, we investigated the effects of treatment with chronic antihypertensive drugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine) on oxidant-antioxidant parameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examined histopathologically. Materials and Methods A total of 36 albino Wistar rats were divided into the following six groups: 0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg...

  8. Microbeam Radiation-Induced Tissue Damage Depends on the Stage of Vascular Maturation

    International Nuclear Information System (INIS)

    Sabatasso, Sara; Laissue, Jean Albert; Hlushchuk, Ruslan; Graber, Werner; Bravin, Alberto; Braeuer-Krisch, Elke; Corde, Stephanie; Blattmann, Hans; Gruber, Guenther; Djonov, Valentin

    2011-01-01

    Purpose: To explore the effects of microbeam radiation (MR) on vascular biology, we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular system with immature vessels (lacking periendothelial coverage) at Day 8 and mature vessels (with coverage) at Day 12 of development. Methods and Materials: CAMs were irradiated with microplanar beams (width, ∼25 μm; interbeam spacing, ∼200 μm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy. Results: In vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near total destruction of the immature capillary plexus. Conversely, 200 Gy MR barely affected Day-12 CAM mature microvasculature. Morphological evaluation of Day-12 CAMs after the dose was increased to 300 Gy revealed opened interendothelial junctions, which could explain the transient mesenchymal edema immediately after irradiation. Electron micrographs revealed cytoplasmic vacuolization of endothelial cells in the beam path, with disrupted luminal surfaces; often the lumen was engorged with erythrocytes and leukocytes. After 30 min, the capillary plexus adopted a striated metronomic pattern, with alternating destroyed and intact zones, corresponding to the beam and the interbeam paths within the array. SLR at a dose of 10 Gy caused growth retardation, resulting in a remarkable reduction in the vascular endpoint density 24 h postirradiation. A dose of 40 Gy damaged the entire CAM vasculature. Conclusions: The effects of MR are mediated by capillary damage, with tissue injury caused by insufficient blood supply. Vascular toxicity and physiological effects of MR depend on the stage of capillary maturation and appear in the first 15 to 60 min after irradiation. Conversely, the effects of SLR, due to the arrest of cell proliferation, persist for a longer time.

  9. Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

    Science.gov (United States)

    Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

    2013-01-01

    Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

  10. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Bouffard Nicole A

    2009-12-01

    Full Text Available Abstract Background Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP, there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. Methods In each of 107 human subjects (60 with LBP and 47 without LBP, parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. Results There were no significant differences in age, sex, body mass index (BMI or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p Conclusion This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  11. The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet.

    Science.gov (United States)

    Wang, Hui; Tian, Jian-li; Feng, Shu-zhi; Sun, Ning; Chen, Bao-yuan; Zhang, Yun

    2013-09-01

    It is known today that sleep apnea hypopnea syndrome and its characteristic chronic intermittent hypoxia can cause damages to multiple organs, including the cardiovascular system, urinary system, and liver. It is still unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and the severity of the damage are organ-specific. This research observed the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta, myocardium, liver, and kidney, under the condition of lipid metabolism disturbance, through establishing the rat model of chronic intermittent hypoxia with high-fat diet by imitating the features of human sleep apnea hypopnea syndrome. In this model, 24 male Wistar rats were randomly divided into three groups: a control group fed by regular diet, a high-fat group fed by high-fat diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the pathological changes of rat's organs, including the thoracic aorta, myocardium, liver, and kidney are observed (under both optical microscopy and transmission electron microscopy). As the result of the experiment shows, while there was no abnormal effect observed on any organs of the control group, slight pathological changes were found in the organs of the high-fat group. For the high-fat plus intermittent hypoxia group, however, remarkably severer damages were found on all the organs. It also showed that the severity of the damage varies by organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta being the worst, followed by the liver and myocardium, and the kidney being the slightest. Chronic intermittent hypoxia can lead to multiple-organ damage to rat with high-fat diet. Different organs appear to have different sensitivity to chronic intermittent hypoxia.

  12. Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

    Science.gov (United States)

    Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

    2018-02-17

    The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

  13. Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

    Science.gov (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

  14. ALK1 heterozygosity delays development of late normal tissue damage in the irradiated mouse kidney

    International Nuclear Information System (INIS)

    Scharpfenecker, Marion; Floot, Ben; Korlaar, Regina; Russell, Nicola S.; Stewart, Fiona A.

    2011-01-01

    Background and Purpose: Activin receptor-like kinase 1 (ALK1) is a transforming growth factor β (TGF-β) receptor, which is mainly expressed in endothelial cells regulating proliferation and migration in vitro and angiogenesis in vivo. Endothelial cells also express the co-receptor endoglin, which modulates ALK1 effects on endothelial cells. Our previous studies showed that mice with reduced endoglin levels develop less irradiation-induced vascular damage and fibrosis, caused by an impaired inflammatory response. This study was aimed at investigating the role of ALK1 in late radiation toxicity. Material and Methods: Kidneys of ALK +/+ and ALK1 +/- mice were irradiated with 14 Gy. Mice were sacrificed at 10, 20, and 30 weeks after irradiation and gene expression and protein levels were analyzed. Results: Compared to wild type littermates, ALK1 +/- mice developed less inflammation and fibrosis at 20 weeks after irradiation, but displayed an increase in pro-inflammatory and pro-fibrotic gene expression at 30 weeks. In addition, ALK1 +/- mice showed superior vascular integrity at 10 and 20 weeks after irradiation which deteriorated at 30 weeks coinciding with changes in the VEGF pathway. Conclusions: ALK1 +/- mice develop a delayed normal tissue response by modulating the inflammatory response and growth factor expression after irradiation.

  15. Relationship between X-ray irradiation and chromosomal damage in bone marrow tissue of mice

    International Nuclear Information System (INIS)

    Chaubey, R.C.; George, K.P.; Sundaram, K.

    1976-01-01

    X-ray induced chromosomal damage in bone-marrow tissue of male mice was studied using micronucleus technique. Dose response relationship was evaluated. Male Swiss mice received whole body x-ray irradiation at different doses from 25-1000 rads. Animals were sacrificed at the end of 24 hours, bone-marrow smears were made and stained in May-Grunwald-Giemsa. The preparatians were scored for the following types of aberrations: micronuclei in young erythocytes-polychromatic cells and in the mature erythrocytes-normechromatic cells. A dose dependent increase in the frequency of micronuclei in polychromatic cells up to a dose of 100 rads was observed. In addition the effect of post-irradiation duration on the frequency of micronuclei in polychromatic and normochromatic cells were studied. Male Swiss mice were exposed to 200 rads x-rays and were then sacrificed at different time intervals after irradiation and bone-marrow preparations were made and scored. Maximum polychromatic cells with micronuclei were observed in 24 hours post-irradiated animals, thereafter a decrease in the frequency of polychromatic cells with micronuclei was observed in 40 hours post irradiated animals. (author

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  17. Influence of chronic internal and acute external irradiations on the critical tissues of plants

    International Nuclear Information System (INIS)

    Kostyuk, O.P.; Ryasnenko, N.A.; Grodzins'kij, D.M.

    1998-01-01

    Peculiarities of chronic internal and acute external irradiations of the critical (as for irradiation influence) plants part, meristem, are studied. In particular, the investigation has aimed to evaluate the level of doses, accumulated by plant tissues, of the chronic internal irradiation from radiocaesium incorporated by them, and to compare its possible effect to one caused by the acute external irradiation. It is shown that the effects of both chronic and acute irradiations have similar features, and it is assumed that they have the very same mechanisms. We think that such a parameter of the plant ability to accumulate radiocaesium as the ratio of its content in a root tip and in the whole root system is a very sensible and useful criterion to estimate the irradiation influence on plants

  18. Amniotic Tissues for the Treatment of Chronic Plantar Fasciosis and Achilles Tendinosis

    Directory of Open Access Journals (Sweden)

    Bruce Werber

    2015-01-01

    Full Text Available Introduction. Allogeneic amniotic tissue and fluid may be used to treat chronic plantar fasciosis and Achilles tendinosis. This innovative approach involves delivering a unique allograft of live human cells in a nonimmunogenic structural tissue matrix to treat chronic tendon injury. These tissues convey very positive regenerative attributes; procurement is performed with maternal consent during elective caesarian birth. Materials and Methods. In the present investigation all patients were unresponsive to multiple standard therapies for a minimum of 6 months and were treated with one implantation of PalinGen SportFLOW around the plantar fascia and/or around the Achilles paratenon. The patients were given a standard protocol for postimplant active rehabilitation. Results. The analogue pretreatment pain score (VAS of 8. By the fourth week after treatment, all patients had significantly reduced self-reported pain. Twelve weeks following the procedure the average pain level had reduced to only 2. No adverse reactions were reported in any of the patients. Conclusion. All patients in this study experienced heel or Achilles pain, unresponsive to standard therapy protocols. After treatment all patients noted significant pain reduction, indicating that granulized amniotic membrane and amniotic fluid can be successfully used to treat both chronic plantar fasciosis and Achilles tendinosis.

  19. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE

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    M. Y. Shagidulin

    2013-01-01

    Full Text Available Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80 with a model of fibrotic toxic liver damage (FLD it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells. The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue. Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr., but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism. 

  20. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells

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    R. Heru Prasetyo

    2017-06-01

    Full Text Available Aim: This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Materials and Methods: Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1 expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. Results: There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Conclusion: Honey can improve the liver tissue based on: (1 Mobilization of endogenous stem cells (CD34 and CD45; (2 Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3 regeneration histologically of liver tissue.

  1. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

    Science.gov (United States)

    Prasetyo, R Heru; Hestianah, Eka Pramyrtha

    2017-06-01

    This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

  2. 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

    2014-03-01

    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

  3. Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

    Directory of Open Access Journals (Sweden)

    Xu Li

    Full Text Available BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL. The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2S has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2S synthetase cystathionine-γ-lyase (CSE in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP, NaHS or DL-propargylglycine (PPG were locally administered. Local sodium hydrosulfide (NaHS significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR, cochlear scanning electron microscope (SEM and outer hair cell (OHC count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

  4. Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

    Science.gov (United States)

    Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

    2016-02-01

    Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

  5. Pulmonary perfusion scintigraphy in children with chronic pulmonary damage: Preliminary results from application of the SPECT technique

    International Nuclear Information System (INIS)

    Lobo S, Gabriel; Ladron de Guevara H, David; Munoz G, Maria Angelica; Araya A, Fernando; Coll C, Claudia; Donoso R, Gilda; Jimenez J, Cesar; Perez R; Andres

    2003-01-01

    The aim was to describe lung perfusion SPECT (LPS) findings in children with chronic pulmonary damage. Material and Method: We revised 106 LPS of children (age:3.9 ± 3.3 yr) with chronic pulmonary damage, performed with a two headed gamma camera. The most common clinical diagnosis were adenovirus bronchopneumonia sequelae (ADV)(29%), unknown origin chronic pulmonary damage (UOPD) (21%), bronchopulmonary dysplasia (BPD)(15%), and chronic obstructed bronchitis (COB)(14%). Severity of pulmonary alterations were evaluated using a Score, which considered extent and type of lung involvement and differential pulmonary perfusion. Pattern of involvement and Score were correlated with diagnosis and gender. Results: Ninety one percent (96/106) of LPS were abnormal (62% boys). Fifty two (54%) showed bilateral alterations, being this finding (p:0.019) more frequent in boys. ADV group showed mainly a mixed bilateral pattern (35%), UOPD a focal unilateral pattern (32%), COB a diffuse unilateral pattern (33%), and BPD a normal pattern (25%). Miscellaneous and UOPD showed the highest score values, and BPD and COB the lowest ones. Conclusion: In this population, LPS is abnormal in high proportion, with some differential characteristics according gender and original diagnosis (au)

  6. In vitro prediction of in vivo skin damage associated with the wiping of dry tissue against skin.

    Science.gov (United States)

    Koenig, David W; Dvoracek, Barb; Vongsa, Rebecca

    2013-02-01

    The ideal gentle cleansing product is one that effectively removes soils while minimizing damage to the skin. Thus, measuring physical abrasion caused by cleansing tissues is critical to the continued development of gentle cleansing products. Current analysis of cleansing materials for skin gentleness is time consuming and requires expensive human subject testing. This report describes the development of a rapid and inexpensive bench assay for the assessment of skin abrasion caused by wiping. Coefficient of friction (COF) evaluations using bench methods were compared with results from clinical studies of repeated wiping and with confocal visualizations of excised skin. A Monitor/Slip and Friction instrument (model 32-06; TMI, Amityville, NY, USA) was used to measure tissue friction on simulated skin (Vitro-Skin, N19-5X; IMS, Milford, CT, USA). Clinical data from a 4-day repetitive forearm wiping study measuring transepidermal water loss (TEWL) in 30 subjects was compared with results from the bench top assay. In addition, excised skin samples were also treated using the COF bench assay and examined using confocal microscopy to visualize stratum corneum damage caused by wiping. Using the bench COF assay, we were able to distinguish between bath tissue codes by comparing average static friction value (ASFV) for the test codes, where lower ASFV indicated less abrasive tissue. The ASFV followed the same gentleness trend observed in the clinical study. Confocal microscopy of excised skin wiped with the same materials indicated stratum corneum damage consistent with the bench COF and clinical TEWL observations. We observed significant correlation between bench and clinical methods for measuring skin damage caused by wiping of skin with tissue. The bench method will facilitate rapid and inexpensive skin gentleness assessment of cleansing materials. © 2012 John Wiley & Sons A/S.

  7. The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

    Directory of Open Access Journals (Sweden)

    Arpita Chatterjee

    2018-01-01

    Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

  8. Effect of the Plasmid-DNA Vaccination on Macroscopic and Microscopic Damage Caused by the Experimental Chronic Trypanosoma cruzi Infection in the Canine Model

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    Olivia Rodríguez-Morales

    2013-01-01

    Full Text Available The dog is considered the main domestic reservoir for Trypanosoma cruzi infection and a suitable experimental animal model to study the pathological changes during the course of Chagas disease (CD. Vaccine development is one of CD prevention methods to protect people at risk. Two plasmids containing genes encoding a trans-sialidase protein (TcSP and an amastigote-specific glycoprotein (TcSSP4 were used as DNA vaccines in a canine model. Splenomegaly was not found in either of the recombinant plasmid-immunized groups; however, cardiomegaly was absent in animals immunized only with the plasmid containing the TcSSP4 gene. The inflammation of subendocardial and myocardial tissues was prevented only with the immunization with TcSSP4 gene. In conclusion, the vaccination with these genes has a partial protective effect on the enlargement of splenic and cardiac tissues during the chronic CD and on microscopic hearth damage, since both plasmids prevented splenomegaly but only one avoided cardiomegaly, and the lesions in heart tissue of dog immunized with plasmid containing the TcSSP4 gene covered only subepicardial tissue.

  9. Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

    Science.gov (United States)

    Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

    2017-11-01

    The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Repair of accurate radiation damage and development and consequence of chronic radiation damage of the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Oehlert, W; Brendlein, F [Freiburg Univ. (Germany, F.R.). Abt. Experimentelle Pathologie

    1976-01-01

    The first part of the essay deals with structural, proliferation kinetic, and functional considerations important for the understanding of the pathogenesis of radiolesions and their repair. Then acute radiolesions of the vesophagus, the gastric mucosa and the mucosa of the small intestine and the colon as well as its repair are discussed with reference to experiments on rats. Another chapter deals with the histo- and pathogenesis of chronic radiolesions and the development of radiolesions in the capillary system. Late radiolesions in the vesophagus and phrenic ampulla, in the glandular stomach, duodenum and jejunum, colon and capillary and vessel system in the gastro-intestinal tract of rats are discussed in detail. Finally the importance of chronic radiolesions in the gastro-intestinal tract for civil protection is shown. It is required to protect persons with primary radiolesions from infections during the following time and to assure cell regeneration by suitable nutrition.

  11. Can cell survival parameters be deduced from non-clonogenic assays of radiation damage to normal tissue

    International Nuclear Information System (INIS)

    Michalowski, A.; Wheldon, T.E.; Kirk, J.

    1984-01-01

    The relationship between dose-response curves for large scale radiation injury to tissues and survival curves for clonogenic cells is not necessarily simple. Sterilization of clonogenic cells occurs near-instantaneously compared with the protracted lag period for gross injury to tissues. Moreover, with some types of macroscopic damage, the shapes of the dose-response curves may depend on time of assay. Changes in the area or volume of irradiated tissue may also influence the shapes of these curves. The temporal pattern of expression of large scale injury also varies between tissues, and two distinct groups can be recognized. In rapidly proliferating tissues, lag period is almost independent of dose, whilst in slowly proliferating tissues, it is inversely proportional to dose. This might be explained by invoking differences in corresponding proliferative structures of the tissues. (Three compartmental Type H versus one compartmental Type F proliferative organization). For the second group of tissues particularly, mathematical modelling suggests a systematic dissociation of the dose-response curves for clonogenic cell survival and large scale injury. In particular, it may be difficult to disentangle the contributions made to inter-fraction sparing by cellular repair processes and by proliferation-related factors. (U.K.)

  12. Chronic Expanding Hematoma in the Extremities: A Clinical Problem of Adhesion to the Surrounding Tissues

    Science.gov (United States)

    Okamoto, Takeshi; Matsuda, Shuichi

    2017-01-01

    Chronic expanding hematoma is characterized by continuous growth of a blood collection. We analyzed the clinical features of 7 patients with chronic expanding hematomas in the extremities, with an average age of 65.6 years. All lesions occurred in the lower extremities, with 4 seen in the thigh and 3 in the knee region. Six patients had subcutaneous hematomas, while 1 was deep-seated in the thigh. The magnetic resonance features of the lesion were compatible with those of a standard hematoma. A low signal intensity on T1- and T2-weighted imaging at the pseudocapsule was also characteristic. Cystic features were seen in 5 of 7 patients. All lesions were resected together with their pseudocapsule. In the subcutaneous lesions, it was necessary to resect adherent fascia, with or without involved skin. In the deep-seated thigh lesion, the common peroneal nerve was completely adherent to the pseudocapsule, a phenomenon from absence of the common peroneal nerve which appeared after resection. Chronic expanding hematomas of the extremities are predominantly located in the subcutaneous tissue of the lower extremity. The surrounding pseudocapsule is adherent to the adjacent tissues, and clinicians must be aware of this, especially when resecting a deep-seated lesion. PMID:28642872

  13. Chronic Expanding Hematoma in the Extremities: A Clinical Problem of Adhesion to the Surrounding Tissues

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    Akio Sakamoto

    2017-01-01

    Full Text Available Chronic expanding hematoma is characterized by continuous growth of a blood collection. We analyzed the clinical features of 7 patients with chronic expanding hematomas in the extremities, with an average age of 65.6 years. All lesions occurred in the lower extremities, with 4 seen in the thigh and 3 in the knee region. Six patients had subcutaneous hematomas, while 1 was deep-seated in the thigh. The magnetic resonance features of the lesion were compatible with those of a standard hematoma. A low signal intensity on T1- and T2-weighted imaging at the pseudocapsule was also characteristic. Cystic features were seen in 5 of 7 patients. All lesions were resected together with their pseudocapsule. In the subcutaneous lesions, it was necessary to resect adherent fascia, with or without involved skin. In the deep-seated thigh lesion, the common peroneal nerve was completely adherent to the pseudocapsule, a phenomenon from absence of the common peroneal nerve which appeared after resection. Chronic expanding hematomas of the extremities are predominantly located in the subcutaneous tissue of the lower extremity. The surrounding pseudocapsule is adherent to the adjacent tissues, and clinicians must be aware of this, especially when resecting a deep-seated lesion.

  14. Lipid metabolism in rat tissues exposed to the chronic effects of γ-irradiation and ubiquinone Q9

    International Nuclear Information System (INIS)

    Novoselova, E.G.

    1992-01-01

    Chronic γ-irradiation of rats with the daily dose of 0.129 Gy activates the synthesis of various classes of lipids in the thymus, spleen and bone marrow cells and induces lipid accumulation in these tissues. Feeding of rats with the antioxidant, ubiquinone Q-9, under conditions of chronic irradiation causes a considerable normalization of lipogenesis and levels of the lipid concentration in the tissues of animals irradiated with the dose of 20 Gy

  15. Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

    International Nuclear Information System (INIS)

    Zhang, H.; Wheeler, K.T.

    1994-01-01

    Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

  16. Tissue Damage, Temperature, and pH Induced by Different Electrode Arrays on Potato Pieces (Solanum tuberosum L.

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    Maraelys Morales González

    2018-04-01

    Full Text Available One of the most challenging problems of electrochemical therapy is the design and selection of suitable electrode array for cancer. The aim is to determine how two-dimensional spatial patterns of tissue damage, temperature, and pH induced in pieces of potato (Solanum tuberosum L., var. Mondial depend on electrode array with circular, elliptical, parabolic, and hyperbolic shape. The results show the similarity between the shapes of spatial patterns of tissue damage and electric field intensity, which, like temperature and pH take the same shape of electrode array. The adequate selection of suitable electrodes array requires an integrated analysis that involves, in a unified way, relevant information about the electrochemical process, which is essential to perform more efficiently way the therapeutic planning and the personalized therapy for patients with a cancerous tumor.

  17. Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice.

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    Masashi Fujihara

    2008-09-01

    Full Text Available The purpose of this study was to determine whether mice exposed to chronic cigarette smoke develop features of early age-related macular degeneration (AMD. Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in 2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes by transmission electron microscopy. The contralateral eye was fixed in 2% paraformaldehyde and examined for oxidative injury to the retinal pigmented epithelium (RPE by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG immunolabeling and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had immunolabeling for 8-OHdG in 85+/-3.7% of RPE cells counted compared to 9.5+/-3.9% in controls (p<0.00001. Bruch membrane was thicker in mice exposed to smoke (1086+/-332 nm than those raised in air (543+/-132 nm; p = 0.0069. The two most pronounced ultrastructural changes (severity grading scale from 0-3 seen were a loss of basal infoldings (mean difference in grade = 1.98; p<0.0001, and an increase in intracellular vacuoles (mean difference in grade = 1.7; p<0.0001. Ultrastructural changes to Bruch membrane in cigarette-smoke exposed mice were smaller in magnitude but consistently demonstrated significantly higher grade injury in cigarette-exposed mice, including basal laminar deposits (mean difference in grade = 0.54; p<0.0001, increased outer collagenous layer deposits (mean difference in grade = 0.59; p = 0.002, and increased basal laminar deposit continuity (mean difference in grade = 0.4; p<0.0001. TUNEL assay showed a higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 8.0+/-1.1% than room air (average 0+/-0%; p = 0.043. Mice exposed to chronic cigarette smoke develop evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model could be useful for studying the

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

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    Cristina Herrera

    2016-04-01

    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.

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

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    Uzun D

    2013-06-01

    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

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

    Science.gov (United States)

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

    2018-02-01

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

  1. Effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis

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    Ying Feng

    2017-02-01

    Full Text Available Objective: To study the effect of smoking on EA and NOS expression as well as NO and ET-1 content in gingival tissue of patients with chronic periodontitis. Methods: Patients diagnosed with periodontitis in our hospital between May 2013 and March 2016 were selected to screen 72 cases of smokers and 80 cases of non-smokers who were enrolled in smoking group and non-smoking group respectively, periodontal tissue was collected to detect the expression of EA, NOS and NLRP3 inflammasome, and gingival crevicular fluid was collected to detect the content of ET-1, NO, inflammatory factors and MMPs. Results: EA expression and ET-1 content in gingival tissue of smoking group were significantly higher than those of nonsmoking group while NOS expression and NO content in gingival tissue were significantly lower than those of non-smoking group; NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression in gingival tissue of smoking group were significantly higher than those of nonsmoking group, and IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content in gingival crevicular fluid were significantly higher than those of non-smoking group; NLRP3, ASC, Caspase-1, IL-1β and IL-18 expression as well as IL-1β, IL-18, TNF-α, IFN-γ, MMP1, MMP8 and MMP13 content were positively correlated with EA and ET-1, and negatively correlated with NOS and NO. Conclusion: Smoking can cause increased EA and ET-1 as well as decreased NOS and NO in gingival tissue of patients with chronic periodontitis, thus adjusting the expression of NLRP3 inflammasome and MMPs to periodontal tissue inflammation and structure damage.

  2. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    Science.gov (United States)

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Quantitatively characterizing microstructural variations of skin tissues during ultraviolet radiation damaging process based on Mueller matrix polarimetry

    Science.gov (United States)

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

    2018-02-01

    As one of the most fundamental features of light, polarization can be used to develop imaging techniques which can provide insight into the optical and structural properties of tissues. Especially, the Mueller matrix polarimetry is suitable to detect the changes in collagen and elastic fibres, which are the main compositions of skin tissue. Here we demonstrate a novel quantitative, non-contact and in situ technique to monitor the microstructural variations of skin tissue during ultraviolet radiation (UVR) induced photoaging based on Mueller matrix polarimetry. Specifically, we measure the twodimensional (2D) backscattering Mueller matrices of nude mouse skin samples, then calculate and analyze the Mueller matrix derived parameters during the skin photoaging and self-repairing processes. To induce three-day skin photoaging, the back skin of each mouse is irradiated with UVR (0.05J/cm2) for five minutes per day. After UVR, the microstructures of the nude mouse skin are damaged. During the process of UV damage, we measure the backscattering Mueller matrices of the mouse skin samples and examine the relationship between the Mueller matrix parameters and the microstructural variations of skin tissue quantitatively. The comparisons between the UVR damaged groups with and without sunscreens show that the Mueller matrix derived parameters are potential indicators for fibrous microstructure variation in skin tissue. The pathological examinations and Monte Carlo simulations confirm the relationship between the values of Mueller matrix parameters and the changes of fibrous structures. Combined with smart phones or wearable devices, this technique may have a good application prospect in the fields of cosmetics and dermatological health.

  4. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  5. Distribution of orally administered and chronically fed sup(95m)Tc in Japanese quail tissues and eggs

    International Nuclear Information System (INIS)

    Thomas, J.M.; Cadwell, L.L.; Cataldo, D.A.; Garland, T.R.

    1986-01-01

    In the present study, male and female Japanese quail were chronically fed alfalfa grown on solutions containing TcO 4 which was mixed into a commercial turkey starter. The objective was to estimate concentration ratios and transfer coefficients from Tc incorporated into alfalfa tissue to quail eggs, edible tissues and other organs. (author)

  6. Selective modulation of Wnt ligands and their receptors in adipose tissue by chronic hyperadiponectinemia.

    Directory of Open Access Journals (Sweden)

    Nobuhiko Wada

    Full Text Available BACKGROUND: Adiponectin-transgenic mice had many small adipocytes in both subcutaneous and visceral adipose tissues, and showed higher sensitivity to insulin, longer life span, and reduced chronic inflammation. We hypothesized that adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte proliferation and chronic inflammation in adipose tissue. MATERIALS AND METHODS: We examined the expression of all Wnt ligands and their receptors and the activity of Wnt signaling pathways in visceral adipose tissue from wild-type mice and two lines of adiponectin-transgenic mice. The effects of adiponectin were also investigated in cultured 3T3-L1 cells. RESULTS: The Wnt5b, Wnt6, Frizzled 6 (Fzd6, and Fzd9 genes were up-regulated in both lines of transgenic mice, whereas Wnt1, Wnt2, Wnt5a, Wnt9b, Wnt10b, Wnt11, Fzd1, Fzd2, Fzd4, Fzd7, and the Fzd coreceptor low-density-lipoprotein receptor-related protein 6 (Lrp6 were reduced. There was no difference in total β-catenin levels in whole-cell extracts, non-phospho-β-catenin levels in nuclear extracts, or mRNA levels of β-catenin target genes, indicating that hyperadiponectinemia did not affect canonical Wnt signaling. In contrast, phosphorylated calcium/calmodulin-dependent kinase II (p-CaMKII and phosphorylated Jun N-terminal kinase (p-JNK were markedly reduced in adipose tissue from the transgenic mice. The adipose tissue of the transgenic mice consisted of many small cells and had increased expression of adiponectin, whereas cyclooxygenase-2 expression was reduced. Wnt5b expression was elevated in preadipocytes of the transgenic mice and decreased in diet-induced obese mice, suggesting a role in adipocyte differentiation. Some Wnt genes, Fzd genes, and p-CaMKII protein were down-regulated in 3T3-L1 cells cultured with a high concentration of adiponectin. CONCLUSION: Chronic hyperadiponectinemia selectively modulated the expression of Wnt ligands, Fzd receptors and LRP coreceptors

  7. Extensive tissue damage of bovine ovaries after bipolar ovarian drilling compared to monopolar electrocoagulation or carbon dioxide laser.

    Science.gov (United States)

    Hendriks, Marja-Liisa; van der Valk, Paul; Lambalk, Cornelis B; Broeckaert, Mark A M; Homburg, Roy; Hompes, Peter G A

    2010-02-01

    To evaluate the size of ovarian damage caused by ovarian drilling in polycystic ovary syndrome, the amount of inflicted damage was assessed for the most frequently used ovarian drilling techniques. Experimental prospective design. University clinic. Six fresh bovine ovaries per technique. Carbon dioxide (CO(2)) laser, monopolar electrocoagulation, and bipolar electrocoagulation were used for in vitro ovarian drilling. Amount of inflicted ovarian damage per procedure. Bipolar electrocoagulation resulted in significantly more destruction per burn than the CO(2) laser and monopolar electrocoagulation (287.6 versus 24.0 and 70.0 mm(3), respectively). The damage found per lesion was multiplied by the regularly applied number of punctures per procedure in daily practice (based on the literature). Again, the bipolar electrocoagulation resulted in significantly more tissue damage than the CO(2) laser and monopolar coagulation (2,876 versus 599 and 700 mm(3), respectively). Ovarian drilling, especially bipolar electrocoagulation, causes extensive destruction of the ovary. Given the same clinical effectiveness of the various procedures, it is essential to use the lowest possible dose that works; thus, the first choice should be CO(2) laser or monopolar electrocoagulation. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. High throughput DNA damage quantification of human tissue with home-based collection device

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V.; Tang, Jonathan; Yannone, Steven M.

    2018-04-03

    Kits, methods and systems for providing a service to provide a subject with information regarding the state of a subject's DNA damage. Collection, processing and analysis of samples are also described.

  9. High throughput DNA damage quantification of human tissue with home-based collection device

    Science.gov (United States)

    Costes, Sylvain V.; Tang, Jonathan; Yannone, Steven M.

    2018-04-03

    Kits, methods and systems for providing a service to provide a subject with information regarding the state of a subject's DNA damage. Collection, processing and analysis of samples are also described.

  10. Modification by cystamine of radiation-induced free radical damages to biomolecules in tissues of mouse organs

    International Nuclear Information System (INIS)

    Svistunenko, D.A.; Gudtsova, K.V.

    1989-01-01

    The method of low-temperature ESR-spectroscopy was used to study a modifying effect of cystamine on the yield of radiation-induced free radicals in different biomolecules of liver and spleen tissues of mice. Intraperitoneal administration of cystamine (150 mg/kg) 15 min before isolation and freezing of the tissues was shown to reduce by 11 per cent the yield of radicals of H-adducts of thymine DNA bases, to decrease by 23 per cent the yield of radicals of triacyglycerol and phospholipid radiolysis, and to increase by 24 per cent the yield of radicals of lipid fatty acid residues in splenic tissues. According to the criterion used, cystamine has no modyfying action on the yield of free-radical damages to liver biomolecules

  11. The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

    2018-01-09

    Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

  12. Laser-induced damage in biological tissue: Role of complex and dynamic optical properties of the medium

    Science.gov (United States)

    Ahmed, Elharith M.

    Since its invention in the early 1960's, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser-tissue interaction model was developed to predict the spatial and temporal temperature and pressure rise during laser exposure to biological tissues. Our new model also takes into account the dynamic nature of tissue optical properties and their impact on the induced temperature and pressure profiles. The laser-induced retinal damage is attributed to the formation of microbubbles formed around melanosomes in the retinal pigment epithelium (RPE) and the damage mechanism is assumed to be photo-thermal. Selective absorption by melanin creates these bubbles that expand and collapse around melanosomes, destroying cell membranes and killing cells. The Finite Element (FE) approach taken provides suitable ground for modeling localized pigment absorption which leads to a non-uniform temperature distribution within pigmented cells following laser pulse exposure. These hot-spots are sources for localized thermo-elastic stresses which lead to rapid localized expansions that manifest themselves as microbubbles and lead to microcavitations. Model predictions for the interaction of lasers at wavelengths of 193, 694, 532, 590, 1314, 1540, 2000, and 2940 nm with biological tissues were generated and comparisons were made with available experimental data for the retina

  13. Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation

    International Nuclear Information System (INIS)

    Matsushita, Satoru; Ando, Koichi; Koike, Sachiko

    1994-01-01

    To evaluate the protective effect of WR-151327 on late radiation-induced damaged to normal tissues in mice, the right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137 Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. Latae damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. WR-151327 has the potential to protect against radiation-induced late normal tissue damage. 17 refs., 6 figs., 2 tabs

  14. A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development

    NARCIS (Netherlands)

    Breuls, R.G.M.; Bouten, C.V.C.; Oomens, C.W.J.; Bader, D.L.; Baaijens, F.P.T.

    2003-01-01

    Soft tissues are sensitive to prolonged compressive loading, eventually leading to tissue necrosis in the form of pressure ulcers [1]. Pressure ulcers can occur in situations where people are subjected to sustained mechanical loads, such as when bedridden, sitting in a wheelchair or from wearing

  15. Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis.

    Science.gov (United States)

    Takebayashi, Koichi; Koboziev, Iurii; Ostanin, Dmitry V; Gray, Laura; Karlsson, Fridrik; Robinson-Jackson, Sherry A; Kosloski-Davidson, Melissa; Dooley, Angela Burrows; Zhang, Songlin; Grisham, Matthew B

    2011-01-01

    It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice. Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinβ-deficient (LTβ(-/-) ) mice with RAG(-/-) animals to generate LTβ(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis. We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTβ(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTβ(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTβ(-/-) x RAG(-/-) mice or their littermate controls (LTβ(+/+) x RAG

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

    International Nuclear Information System (INIS)

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-01-01

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

  17. Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

    1985-01-01

    The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

  18. Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

    2016-03-01

    Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

  19. DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry.

    Science.gov (United States)

    Savina, Natalya V; Smal, Marharyta P; Kuzhir, Tatyana D; Ershova-Pavlova, Alla A; Goncharova, Roza I

    2012-10-09

    The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored. © 2012 Elsevier B.V. All rights reserved.

  20. Protective effect of hydroalcoholic extract of tribulus terrestris on cisplatin induced renal tissue damage in male mice

    Directory of Open Access Journals (Sweden)

    Amir Raoofi

    2015-01-01

    Full Text Available Background: According beneficial effects of Tribulus terrestris (TT extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS (EBEWE Pharma, Unterach, Austria induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6. The first group (control was treated with normal saline (0.9% NaCl and experimental groups with CIS (E1, CIS + 100 mg/kg extract of TT (E2, CIS + 300 mg/kg extract of TT (E3, CIS + 500 mg/kg extract of TT (E4 intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey′s post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman′s capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  1. Protective Effect of Hydroalcoholic Extract of Tribulus Terrestris on Cisplatin Induced Renal Tissue Damage in Male Mice

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    Background: According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Methods: Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. Results: The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. Conclusions: The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice. PMID:25789143

  2. Protective effect of hydroalcoholic extract of tribulus terrestris on Cisplatin induced renal tissue damage in male mice.

    Science.gov (United States)

    Raoofi, Amir; Khazaei, Mozafar; Ghanbari, Ali

    2015-01-01

    According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice. Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed. The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal-Wallis and Mann-Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days. The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

  3. Evaluation of an In Vitro of Human Immune Activation Induced by Freeze-Thaw Tissue Damage

    National Research Council Canada - National Science Library

    DuBose, D

    2002-01-01

    In training and in combat, soldiers are under the constant threat of injury. Injury that results in tissue necrosis can activate the immune system and ultimately enhance disturbances in organ function...

  4. Factors Associated with Decreased Lean Tissue Index in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yi-Wen Wang

    2017-04-01

    Full Text Available Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD. However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM, a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height2. An LTI of less than 10% of the normal value (low LTI indicates muscle wasting. Patients with low LTI (n = 40 tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.

  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

    2016-01-01

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

    2012-06-15

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

  7. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis.

    Science.gov (United States)

    Ali, Mohammad Javed; Mulay, Kaustubh; Pujari, Aditi; Naik, Milind N

    2013-12-01

    To study the changes in the lacrimal drainage-associated lymphoid tissue of the lacrimal sac in human chronic dacryocystitis and its possible implications in understanding the immune defense mechanisms and etiopathogenesis of primary acquired nasolacrimal duct obstruction. Retrospective interventional study involving 200 lacrimal sacs of 164 consecutive patients seen between July 2009 and July 2012. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, diagnostic irrigation, indications for a dacyrocystectomy, pattern and severity of lymphoid infiltrate, types of lymphoid follicles and their locations, plasma cells, and other cellular infiltrates. The associated epithelial, stromal, and luminal changes with an emphasis on acini, mucosal glands, blood vessels, lymphatics, and goblet cells were also noted. Immunohistochemistry using CD3, CD20, CD138, and immunoglobulin A were used to substantiate the lymphoid tissues of the lacrimal sac. A total of 200 lacrimal sacs were obtained from dacryocystectomy of 164 patients. The patients included 60.5% (99/164) females and 39.6% (65/164) males, with a mean age of 58.4 years at presentation. Laterality showed a predominance of left lacrimal sacs (55%, 110/200) as compared to the right lacrimal sacs (45%, 90/200). Symptoms of epiphora and discharge of more than 6 months duration were considered to be chronic. Lymphoid infiltrate pattern was diffuse in majority of the sacs (81%, 162/200), with subepithelial and intraepithelial together being the commonest location (46.5%, 93/200). Distinct lymphoid follicles were seen in 28% (56/200). Most of the sacs showed mild plasma cell infiltration (66.5%, 133/200). IgA-rich secretions were noted in the lumen and the lining epithelium in 34.5% (69/200). Other common changes noted include increase in the goblet cells (82%, 164/200), dilated lymphatics (94%, 188/200), proliferating blood vessels (99%, 198/200), thickened

  8. Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue.

    Science.gov (United States)

    Häke, Ines; Schönenberger, Silvia; Neumann, Jens; Franke, Katrin; Paulsen-Merker, Katrin; Reymann, Klaus; Ismail, Ghazally; Bin Din, Laily; Said, Ikram M; Latiff, A; Wessjohann, Ludger; Zipp, Frauke; Ullrich, Oliver

    2009-01-03

    Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 microg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.

  9. Case report: transpalatal arch resulting in soft tissue damage of the tongue 3 years post-orthodontic treatment.

    Science.gov (United States)

    Noar, Joe; Woods, Eva; Hodgson, Tim

    2015-03-01

    Whilst transient effects of orthodontic appliances on the oral mucosa are well recognized, chronic lesions, persisting post therapy are unusual. We describe a persistent lingual mucosal defect related to a transpalatal arch (TPA) in a healthy 19-year-old female. The asymptomatic lesion is presently being monitored, however, surgical revision in the future may be requested by the patient if the area fails to remodel. Clinical Relevance: Soft tissue trauma to the tongue by anchorage reinforcing appliances may result in long-term effects that could require surgical management.

  10. Effect of chronic irradiation combined with other damaging factors on some morphological systems of mice

    International Nuclear Information System (INIS)

    Ponomareva, T.V.; Merkushev, G.N.; Pil'shchuk, E.M.; Bikkulov, R.I.

    1978-01-01

    A model experiment on mice is carried out to study morphofunctional changes that occur in mammals chronically exposed to radiation in doses close to those in occupational exposures of a man. Mice have been exposed to gamma-radiation at dose rates of 6, 16, 40, 120, and 300 mr/day from the time of birth onward throughout lifetime. It is concluded that, where a chronic purulent infection is present, chronic irradiation at the above dose rates, with the exception of 6 mr/day, accelerates the onset of irreversible pathologic changes, in particular of amyloidosis, in immunocompetent organs

  11. MR imaging of brain tissue changes in acute and chronic solvent intoxication

    International Nuclear Information System (INIS)

    Rinck, P.A.; Nilsen, G.; Kvaerness, J.

    1988-01-01

    Acute and chronic intoxication with solvents is found both as an occupational hazard and as self-inflicted in addicts to solvent. Objective demonstration of such brain tissue changes is difficult with conventional imaging methods, and in most cases findings are negative. In a preliminary study, the brains of eight patients (aged 28-62 years) exposed to aggressive solvents for 1-27 years were examined with magnetic resonance imaging. All of the patients showed brain atrophy of varying extent, and seven of eight patients (all except the youngest and least exposed) had brain lesions that somewhat resembled dymyelinating changes (focal and confluent periventricular and deep white matter lesions, brain stem and cerebellar lesions); one patient showed cloudy, poorly defined lesions

  12. Pancreatic tissue fluid pressure in chronic pancreatitis. Relation to pain, morphology, and function

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Bülow, J

    1990-01-01

    The relation between pancreatic tissue fluid pressure and pain, morphology, and function was studied in a cross-sectional investigation. Pressure measurements were performed by percutaneous fine-needle puncture. Thirty-nine patients with chronic pancreatitis were included, 25 with pain and 14...... without (p = 0.004 and p = 0.0003, respectively). The pressure was significantly related (inversely) to pancreatic duct diameter only in the group of 19 patients with earlier pancreatic surgery (R = -0.57, p = 0.02). The pressure was not related to functional factors or the presence of pancreatic...... without pain. The pressure was higher in patients with pain than in patients without pain (p = 0.000001), and this was significantly related to a pain score from a visual analogue scale (p less than 0.001). Patients with pancreatic pseudocysts had both higher pressure and higher pain score than patients...

  13. Analysis of DNA vulnerability to damage, repair and degradation in tissues of irradiated animals

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Ivannik, B.P.

    1982-01-01

    Single-strand and paired ruptures of DNA were found to result in appearance of locally denaturated areas in its secondary structure and to disordered protein-DNA interaction. It was shown with the use of the viscosimeter method of measuring the molecular mass of single stranded high-polymeric DNA that cells of various tissues by the intensity of DNA repair can be divided into two groups, rapid- and slow-repair ones. Tissue specificity of enzyme function of the repair systems and systems responsible for post-irradiation DNA degradation depends on the activity of endonucleases synthesized by the cells both in health and in their irradiation-induced synthesis

  14. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Directory of Open Access Journals (Sweden)

    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  15. Apoptosis modulation in the immune system reveals a role of neutrophils in tissue damage in a murine model of chlamydial genital infection.

    Science.gov (United States)

    Zortel, Tom; Schmitt-Graeff, Annette; Kirschnek, Susanne; Häcker, Georg

    2018-03-07

    Chlamydial infection frequently causes damage to the female genital tract. The precise mechanisms of chlamydial clearance and tissue damage are unknown but studies suggest immunopathology with a particular role of neutrophils. The goal of this study was to understand the contribution of the immune system, in particular neutrophils. Using Chlamydia muridarum, we infected mice with a prolonged immune response due to expression of Bcl-2 in haematopoietic cells (Bcl-2-mice), and mice where mature neutrophils are lacking due to the deletion of Mcl-1 in myeloid cells (LysM-cre-mcl-1-flox-mice; Mcl-1-mice). We monitored bacterial clearance, cellular infiltrate and long-term tissue damage. Both mutant strains showed slightly delayed clearance of the acute infection. Bcl-2-mice had a strongly increased inflammatory infiltrate concerning almost all cell lineages. The infection of Bcl-2-mice caused increased tissue damage. The loss of neutrophils in Mcl-1-mice was associated with substantial quantitative and qualitative alterations of the inflammatory infiltrate. Mcl-1-mice had higher chlamydial burden and reduced tissue damage, including lower incidence of hydrosalpinx and less uterine dilation. Inhibition of apoptosis in the haematopoietic system increases inflammation and tissue damage. Neutrophils have broad functions, including a role in chlamydial clearance and in tissue destruction.

  16. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

    Science.gov (United States)

    Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

    2011-08-01

    Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Toe Tissue Transfer for Reconstruction of Damaged Digits due to Electrical Burns

    Directory of Open Access Journals (Sweden)

    Hyung-Do Kim

    2012-03-01

    Full Text Available Background Electrical burns are one of the most devastating types of injuries, and can becharacterized by the conduction of electric current through the deeper soft tissue such asvessels, nerves, muscles, and bones. For that reason, the extent of an electric burn is veryfrequently underestimated on initial impression.Methods From July 1999 to June 2006, we performed 15 cases of toe tissue transfer for thereconstruction of finger defects caused by electrical burns. We performed preoperative rangeof motion exercise, early excision, and coverage of the digital defect with toe tissue transfer.Results We obtained satisfactory results in both functional and aesthetic aspects in all 15cases without specific complications. Static two-point discrimination results in the transferredtoe cases ranged from 8 to 11 mm, with an average of 9.5 mm. The mean range of motionof the transferred toe was 20° to 36° in the distal interphalangeal joint, 16° to 45° in theproximal interphalangeal joint, and 15° to 35° in the metacarpophalangeal joint. All of thepatients were relatively satisfied with the function and appearance of their new digits.Conclusions The strategic management of electrical injury to the hands can be both challengingand complex. Because the optimal surgical method is free tissue transfer, maintenance ofvascular integrity among various physiological changes works as a determining factor for thepostoperative outcome following the reconstruction.

  18. 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

    2010-01-01

    are coding for immunological factors and tissue regeneration. Locale, inflammatory responses were seen as strong up-regulation of IL-1β and IL-8 in both groups of fish, but it was more pronounced in infected fish. Expression of the toll-like receptors showed induction of TLR-5m following infection, but TLR-9...

  19. 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.

    2013-01-01

    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

  20. Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

    International Nuclear Information System (INIS)

    Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

    2001-01-01

    To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

  1. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

  2. TOF-SIMS analysis of adipose tissue from patients with chronic kidney disease

    Science.gov (United States)

    Sjövall, Peter; Johansson, Björn; Belazi, Dalila; Stenvinkel, Peter; Lindholm, Bengt; Lausmaa, Jukka; Schalling, Martin

    2008-12-01

    In this work, time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for detecting systematic variations in the spatial and compositional distributions of lipids in human tissue samples. Freeze-dried sections of subcutaneous adipose tissue from six chronic kidney disease (CKD) patients and six control subjects were analysed by TOF-SIMS using 25 keV Bi 3+ primary ions. Principal component analysis of signal intensities from different fatty acids, diacylglycerol and triacylglycerol ions showed evidence for systematic variations in the lipid distributions between different samples. The main observed difference in the spectra was a concerted variation in the signal intensities from the saturated lipids relative to the unsaturated lipids, while variations in the fatty acid chain lengths were considerably weaker. Furthermore, the three samples showing the lowest degree of saturation came from CKD patients, while three of the four samples with the highest degree of saturation were from control subjects, indicating that low saturation levels in the glycerol lipid distribution may be more frequent in patients with CKD. Systematic differences in the spatial distributions between saturated and unsaturated glycerol lipids were observed in several analysed areas.

  3. Chronic consumption of fructose rich soft drinks alters tissue lipids of rats

    Directory of Open Access Journals (Sweden)

    Botezelli Jose D

    2010-06-01

    Full Text Available Abstract Background Fructose-based diets are apparently related to the occurrence of several metabolic dysfunctions, but the effects of the consumption of high amounts of fructose on body tissues have not been well described. The aim of this study was to analyze the general characteristics and the lipid content of different tissues of rats after chronic ingestion of a fructose rich soft drink. Methods Forty-five Wistar rats were used. The rats were divided into three groups (n = 15 and allowed to consume water (C, light Coca Cola ® (L or regular Coca Cola® (R as the sole source of liquids for eight weeks. Results The R group presented significantly higher daily liquid intake and significantly lower food intake than the C and L groups. Moreover, relative to the C and L groups, the R group showed higher triglyceride concentrations in the serum and liver. However, the L group animals presented lower values of serum triglycerides and cholesterol than controls. Conclusions Based on the results, it can be concluded that daily ingestion of a large amount of fructose- rich soft drink resulted in unfavorable alterations to the lipid profile of the rats.

  4. Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

    Directory of Open Access Journals (Sweden)

    Mustafa Talip Sener

    2011-01-01

    Full Text Available Background: In this study, we investigated the effects of treatment with chronic antihypertensivedrugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine on oxidant-antioxidantparameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examinedhistopathologically.Materials and Methods: A total of 36 albino Wistar rats were divided into the following six groups:0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kgramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drugadministration for 30 days and at the end, biochemical and histopathological examinations wereperformed. All data were subjected to one-way ANOVA test.Results: We divided these drugs into the following three groups according to their effects on ratuteri: (I mild negative effects (clonidine, (II moderate negative effects (rilmenidine, methyldopaand (III drugs which had severe negative effects (amlodipine, ramipril.Conclusion: These data may help with selection of antihypertensive drugs, in order to determinewhich drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy women.

  5. Residual tissue post splenectomy detected by splenic scintillography with erythrocytes damaged by heat

    International Nuclear Information System (INIS)

    Rivera B, B.; Garcia C, E.S.; Garcia O, J.R.

    2005-01-01

    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)

  6. Effects of cryotherapy combined with therapeutic ultrasound on oxidative stress and tissue damage after musculoskeletal contusion in rats.

    Science.gov (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

    2016-12-01

    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/cm 2SPTA , 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.

  7. Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

    Directory of Open Access Journals (Sweden)

    Germana Zaccagnini

    Full Text Available Magnetic resonance imaging (MRI provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time, diffusion-tensor imaging (Fractional Anisotropy and perfusion by Dynamic Contrast-Enhanced MRI (K-trans were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1 T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2 Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3 K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

  8. Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

    Science.gov (United States)

    Zaccagnini, Germana; Palmisano, Anna; Canu, Tamara; Maimone, Biagina; Lo Russo, Francesco M; Ambrogi, Federico; Gaetano, Carlo; De Cobelli, Francesco; Del Maschio, Alessandro; Esposito, Antonio; Martelli, Fabio

    2015-01-01

    Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

  9. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  10. Cavitation Induced Structural and Neural Damage in Live Brain Tissue Slices: Relevance to TBI

    Science.gov (United States)

    2014-09-29

    objective of this project is to determine the conditions conducive for cavitation in cerebrospinal fluid (CSF) and corresponding tissue injury in 2-D brain...the radius of an isolated spherical bubble in an infinite, incompressible liquid is given by Where, R is the instantaneous bubble radius, which can...by the pressure transducer placed in the test chamber, and PR is the pressure in the liquid at the boundary of the bubble. The measurable bubble

  11. Clinical implications of oral candidiasis: host tissue damage and disseminated bacterial disease.

    Science.gov (United States)

    Kong, Eric F; Kucharíková, Sona; Van Dijck, Patrick; Peters, Brian M; Shirtliff, Mark E; Jabra-Rizk, Mary Ann

    2015-02-01

    The clinical significance of polymicrobial interactions, particularly those between commensal species with high pathogenic potential, remains largely understudied. Although the dimorphic fungal species Candida albicans and the bacterium Staphylococcus aureus are common cocolonizers of humans, they are considered leading opportunistic pathogens. Oral candidiasis specifically, characterized by hyphal invasion of oral mucosal tissue, is the most common opportunistic infection in HIV(+) and immunocompromised individuals. In this study, building on our previous findings, a mouse model was developed to investigate whether the onset of oral candidiasis predisposes the host to secondary staphylococcal infection. The findings demonstrated that in mice with oral candidiasis, subsequent exposure to S. aureus resulted in systemic bacterial infection with high morbidity and mortality. Histopathology and scanning electron microscopy of tongue tissue from moribund animals revealed massive C. albicans hyphal invasion coupled with S. aureus deep tissue infiltration. The crucial role of hyphae in the process was demonstrated using a non-hypha-producing and a noninvasive hypha-producing mutant strains of C. albicans. Further, in contrast to previous findings, S. aureus dissemination was aided but not contingent upon the presence of the Als3p hypha-specific adhesion. Importantly, impeding development of mucosal C. albicans infection by administering antifungal fluconazole therapy protected the animals from systemic bacterial disease. The combined findings from this study demonstrate that oral candidiasis may constitute a risk factor for disseminated bacterial disease warranting awareness in terms of therapeutic management of immunocompromised individuals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Stochastic Threshold Exponential (TE) Model for Hematopoietic Tissue Reconstitution Deficit after Radiation Damage.

    Science.gov (United States)

    Scott, B R; Potter, C A

    2014-07-01

    Whole-body exposure to large radiation doses can cause severe loss of hematopoietic tissue cells and threaten life if the lost cells are not replaced in a timely manner through natural repopulation (a homeostatic mechanism). Repopulation to the baseline level N 0 is called reconstitution and a reconstitution deficit (repopulation shortfall) can occur in a dose-related and organ-specific manner. Scott et al. (2013) previously introduced a deterministic version of a threshold exponential (TE) model of tissue-reconstitution deficit at a given follow-up time that was applied to bone marrow and spleen cellularity (number of constituent cells) data obtained 6 weeks after whole-body gamma-ray exposure of female C.B-17 mice. In this paper a more realistic, stochastic version of the TE model is provided that allows radiation response to vary between different individuals. The Stochastic TE model is applied to post gamma-ray-exposure cellularity data previously reported and also to more limited X-ray cellularity data for whole-body irradiated female C.B-17 mice. Results indicate that the population average threshold for a tissue reconstitution deficit appears to be similar for bone marrow and spleen and for 320-kV-spectrum X-rays and Cs-137 gamma rays. This means that 320-kV spectrum X-rays could successfully be used in conducting such studies.

  13. 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: claudia.ruebe@uks.eu

    2015-08-01

    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.

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

    International Nuclear Information System (INIS)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

    2015-01-01

    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

  15. Histological changes in lung tissues related with sub-chronic exposure to ambient urban levels of PM2.5 in Córdoba, Argentina

    Science.gov (United States)

    Tavera Busso, Iván; Vera, Anahí; Mateos, Ana Carolina; Amarillo, Ana Carolina; Carreras, Hebe

    2017-10-01

    Concentration of fine particulate matter (PM2.5) is one of the most important environmental parameters to estimate health impacts attributable to air pollution. Despite the fact there are many studies regarding PM2.5 effects on human health, most of them were performed under conditions that do not simulate the natural particles interaction with the organism. In the present paper, we studied the effects of mammals' sub-chronic exposure to PM2.5 on the lower respiratory tract, addressing realistic exposure conditions to normal urban air. Thus, we exposed Wistar rats under controlled settings to the same normal urban air, with and without particles. Next, we analyzed chemical composition of PM2.5 and lungs samples, performed a histologic examination and run the comet assay to assess genotoxic effects. We found a strong agreement between lung tissues and PM2.5 elemental composition suggesting that metals found in lungs came from the particles inhaled. Histological analysis showed a mild to moderate infiltration, with a reduction of alveoli lumen and increment of alveolar macrophages and periodic acid-Schiff (PAS) (+) cells in treated animals. We also observed an increase in the number of nuclei with comets, mostly comets type 3, with a high DNA fragmentation as well. These results provide strong evidence that sub-chronic exposure to low particle levels, even below the 24 h WHO standard, can cause injuries in lungs tissues and DNA damage, as well.

  16. Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers.

    Science.gov (United States)

    Zhang, Xu-Hui; Zhang, Xuan; Wang, Xu-Chu; Jin, Li-Fen; Yang, Zhang-Ping; Jiang, Cai-Xia; Chen, Qing; Ren, Xiao-Bin; Cao, Jian-Zhong; Wang, Qiang; Zhu, Yi-Min

    2011-04-12

    Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P electroplating workers. Low-level occupational chromium exposure induced DNA damage.

  17. A pilot study using Tissue Velocity Ultrasound Imaging (TVI to assess muscle activity pattern in patients with chronic trapezius myalgia

    Directory of Open Access Journals (Sweden)

    Brodin Lars-Åke

    2008-09-01

    Full Text Available Abstract Background Different research techniques indicate alterations in muscle tissue and in neuromuscular control of aching muscles in patients with chronic localized pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical practice. Aim This study introduces a new muscle tissue sensitive ultrasound technique in order to provide a new methodology for providing a description of local muscle changes. This method is applied to investigate trapezius muscle tissue response – especially with respect to specific regional deformation and deformation rates – during concentric shoulder elevation in patients with chronic trapezius myalgia and healthy controls before and after pain provocation. Methods Patients with trapezius myalgia and healthy controls were analyzed using an ultrasound system equipped with tissue velocity imaging (TVI. The patients performed a standardized 3-cm concentric shoulder elevation before and after pain provocation/exercise at a standardized elevation tempo (30 bpm. A standardized region of interest (ROI, an ellipsis with a size that captures the upper and lower fascia of the trapezius muscle (4 cm width at rest, was placed in the first frame of the loop registration of the elevation. The ROI was re-anchored frame by frame following the same anatomical landmark in the basal fascia during all frames of the concentric phase. In cardiac measurement, tissue velocities are measured in the axial projection towards and against the probe where red colour represents shortening and red lengthening. In the case of measuring the trapezius muscle, tissue deformation measurements are made orthogonally, thus, indirectly. Based on the assumption of muscle volume incompressibility, blue represents tissue contraction and red relaxation. Within the ROI, two variables were calculated as a function of time: deformation and deformation rate. Hereafter, max, mean, and quadratic mean values (RMS of each variable were

  18. Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mary C Vázquez

    Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a neurovisceral lipid storage disorder mainly characterized by unesterified cholesterol accumulation in lysosomal/late endosomal compartments, although there is also an important storage for several other kind of lipids. The main tissues affected by the disease are the liver and the cerebellum. Oxidative stress has been described in various NPC cells and tissues, such as liver and cerebellum. Although considerable alterations occur in the liver, the pathological mechanisms involved in hepatocyte damage and death have not been clearly defined. Here, we assessed hepatic tissue integrity, biochemical and oxidative stress parameters of wild-type control (Npc1(+/+; WT and homozygous-mutant (Npc1(-/-; NPC mice. In addition, the mRNA abundance of genes encoding proteins associated with oxidative stress, copper metabolism, fibrosis, inflammation and cholesterol metabolism were analyzed in livers and cerebella of WT and NPC mice. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed various oxidative stress parameters in the liver and hepatic and cerebellum gene expression in 7-week-old NPC1-deficient mice compared with control animals. We found signs of inflammation and fibrosis in NPC livers upon histological examination. These signs were correlated with increased levels of carbonylated proteins, diminished total glutathione content and significantly increased total copper levels in liver tissue. Finally, we analyzed liver and cerebellum gene expression patterns by qPCR and microarray assays. We found a correlation between fibrotic tissue and differential expression of hepatic as well as cerebellar genes associated with oxidative stress, fibrosis and inflammation in NPC mice. CONCLUSIONS/SIGNIFICANCE: In NPC mice, liver disease is characterized by an increase in fibrosis and in markers associated with oxidative stress. NPC is also correlated with altered gene expression, mainly of genes involved in oxidative stress

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

    International Nuclear Information System (INIS)

    Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil

    2000-04-01

    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

  20. 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

    2000-04-01

    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.

  1. Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

    Science.gov (United States)

    Baldo, Cristiani; Jamora, Colin; Yamanouye, Norma; Zorn, Telma M.; Moura-da-Silva, Ana M.

    2010-01-01

    Background Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs). The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. Methodology/Principal Findings In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP) and BnP1 (weakly hemorrhagic SVMP) using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition, BnP1 did not accumulate in the tissues. Conclusions/Significance These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the difference between

  2. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Kwangwon [Eulji Univ. Hospital, Daejeon (Korea, Republic of); Kwon, Jungkee [Chonbuk National Univ., Jeonju (Korea, Republic of); Kim, Taewoon [Jeonbuk Technopark, Jeonju (Korea, Republic of)

    2012-03-15

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage.

  3. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    International Nuclear Information System (INIS)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon; Lee, Kwangwon; Kwon, Jungkee; Kim, Taewoon

    2012-01-01

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage

  4. Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients

    NARCIS (Netherlands)

    Wassenaar, A.; Reinhardus, C.; Thepen, T.; Abraham-Inpijn, L.; Kievits, F.

    1995-01-01

    Chronic periodontitis is characterized by dense infiltrations of B and T lymphocytes within the gingival connective tissue. Distinct anaerobic gram-negative bacteria as well as autoimmunity to collagen have been reported to play a role in the etiology and the pathogenesis of this disease. Here we

  5. Reaction of the hemocoagulation system to tissue hypoxia in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Anna A. Bulanova

    2017-01-01

    Full Text Available Background. Nowadays little data related to the hemostatic system and fibrinolysis in patients with chronic obstructive pulmonary disease (COPD are available. This is due to the lack of standardized methods for studying the hemostasis system, as well as to the lack of a single functional test that allows the evaluation of the complete fibrinogenesis cycle in whole blood.Aim. The aim of our study was to develop a functional test capable of analyzing the blood gas composition in the “point-of-care test” method for the evaluation of the hemostatic potential in patients with COPD, based on a standardized test stimulus, which is tissue hypoxia. The current level of clinical and laboratory diagnostics requires personification and research of the hemo-coagulation system in real time (point-of-care test, which allows low-frequency piezotromboelastography(NVTEG to be performed.Materials and methods. NVTEG was chosen to estimate the state of the hemocoagulation system. Ten patients with COPD and 10 healthy volunteers were examined. Hypoxia was selected as a standardized test stimulus. Hypoxia conditions were caused by smoking one standard cigarette (composition: resin 10 mg/cig., nicotine 0,7 mg/cig., CO 10 mg/cig.. The degree of tissue hypoxia was assessed with the GASTAT-navi blood gas analyzer.Results. The study has shown that in response to the standard test stimulus, which is the tissue hypoxia caused by smoking of a standardized cigarette, two types of haemostatic potential reaction were detected both in patients with COPD and healthy volunteers. The first type of reaction – “hypercoagulation” – is characterized by the formation of chronometric and structural hypercoagulation at all stages of fibrinogenesis and increased coagulation activity by 25–30% compared with the response in healthy individuals. The second type of reaction – “hypocoagulation” – is characterized by the formation of chronometric and structural

  6. Impact of Chronic Neonatal Intermittent Hypoxia on Severity of Retinal Damage in a Rat Model of Oxygen-Induced Retinopathy.

    Science.gov (United States)

    Beharry, Kay D; Cai, Charles L; Ahmad, Taimur; Guzel, Sibel; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Neonatal intermittent hypoxia (IH) followed by re-oxygenation in normoxia or supplemental oxygen (IHR) increases the risk for severe retinopathy of prematurity (ROP). The exact timing for the onset of retinal damage which may guide strategic interventions during retinal development, is unknown. We tested the hypothesis that chronic exposure of the immature retina to neonatal IH induces early manifestations of retinal damage that can be utilized as key time points for strategic pharmacologic intervention. Newborn rats were exposed to IH within 2 hours of birth (P0) until P14, or allowed to recover in room air (RA) from P14 to P21 (IHR). Retinal integrity and angiogenesis biomarkers were progressively assessed before (P0), during IH, and post IH (recovery in RA), or IHR, and compared to normoxic age-matched controls. Retinal damage occurred as early as day 3 of neonatal IH, consistent with vascular abnormalities and disturbances in the astrocytic template. These abnormalities worsened during IHR. Pharmacologic and non-pharmacologic interventions to identify, prevent, or minimize neonatal IH should be implemented shortly after birth in high risk preterm newborns. This strategy may lead to a reduction in the outcome of severe ROP requiring later invasive treatments.

  7. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine.

    Science.gov (United States)

    Pagel, René; Bär, Florian; Schröder, Torsten; Sünderhauf, Annika; Künstner, Axel; Ibrahim, Saleh M; Autenrieth, Stella E; Kalies, Kathrin; König, Peter; Tsang, Anthony H; Bettenworth, Dominik; Divanovic, Senad; Lehnert, Hendrik; Fellermann, Klaus; Oster, Henrik; Derer, Stefanie; Sina, Christian

    2017-11-01

    Endogenous circadian clocks regulate 24-h rhythms of physiology and behavior. Circadian rhythm disruption (CRD) is suggested as a risk factor for inflammatory bowel disease. However, the underlying molecular mechanisms remain unknown. Intestinal biopsies from Per1/2 mutant and wild-type (WT) mice were investigated by electron microscopy, immunohistochemistry, and bromodeoxyuridine pulse-chase experiments. TNF-α was injected intraperitoneally, with or without necrostatin-1, into Per1/2 mice or rhythmic and externally desynchronized WT mice to study intestinal epithelial cell death. Experimental chronic colitis was induced by oral administration of dextran sodium sulfate. In vitro , caspase activity was assayed in Per1/2-specific small interfering RNA-transfected cells. Wee1 was overexpressed to study antiapoptosis and the cell cycle. Genetic ablation of circadian clock function or environmental CRD in mice increased susceptibility to severe intestinal inflammation and epithelial dysregulation, accompanied by excessive necroptotic cell death and a reduced number of secretory epithelial cells. Receptor-interacting serine/threonine-protein kinase (RIP)-3-mediated intestinal necroptosis was linked to increased mitotic cell cycle arrest via Per1/2-controlled Wee1, resulting in increased antiapoptosis via cellular inhibitor of apoptosis-2. Together, our data suggest that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. © FASEB.

  8. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Joanna Świdrowska

    2015-04-01

    Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

  9. Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Song, Jia; Wang, Hai; Zhang, Ya-Na; Cao, Ping-Ping; Liao, Bo; Wang, Zhe-Zheng; Shi, Li-Li; Yao, Yin; Zhai, Guan-Ting; Wang, Zhi-Chao; Liu, Li-Meng; Zeng, Ming; Lu, Xiang; Wang, Heng; Yang, Xiang-Ping; Yu, Di; Bachert, Claus; Liu, Zheng

    2018-03-01

    The contribution of ectopic lymphoid tissues (eLTs) to local immunoglobulin hyperproduction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. We sought to explore the cellular basis, formation mechanisms, and function of eLTs in patients with CRSwNP. We graded lymphoid aggregations in sinonasal mucosa and histologically studied their structures. The expression of lymphorganogenic factors and molecules required for immunoglobulin production was measured by using real-time PCR, and their localization was analyzed by means of immunohistochemistry and immunofluorescence. The phenotype of follicular helper T cells was analyzed by performing flow cytometry. Immunoglobulin levels were quantified by using the Bio-Plex assay or ImmunoCAP system. Nasal tissue explants were challenged ex vivo with Dermatophagoides pteronyssinus group 1 (Der p 1), and the expression of Iε-Cμ and Iε-Cγ circle transcripts was detected by using seminested PCR. Increased formation of eLTs with germinal center-like structures was discovered in patients with eosinophilic (20.69%) and noneosinophilic (17.31%) CRSwNP compared with that in patients with chronic rhinosinusitis without nasal polyps (5.66%) and control subjects (3.70%). The presence of eLTs was associated with increased expression of lymphorganogenic and inflammatory chemokines and cytokines, as well as their receptors. The expression of molecules required for immunoglobulin production, generation of follicular helper T cells, and production of IgE in eosinophilic polyps and IgG and IgA in both eosinophilic and noneosinophilic polyps were predominantly upregulated in patients with eLTs. After Der p 1 challenge ex vivo, Iε-Cμ transcript was detected only in eosinophilic polyps with eLTs but not in polyps without eLTs and noneosinophilic polyps. eLTs might support local immunoglobulin production and therefore significantly contribute to the development of CRSwNP. Copyright © 2017 American Academy of

  10. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    Science.gov (United States)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  11. [Interference of vitamin E on the brain tissue damage by electromagnetic radiation of cell phone in pregnant and fetal rats].

    Science.gov (United States)

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

    2013-07-01

    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.

  12. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L

    2017-01-01

    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  13. Biomarkers of cardio-renal damage in chronic kidney disease: one size cannot fit all.

    Science.gov (United States)

    Bolignano, Davide; Coppolino, Giuseppe

    2014-04-17

    Biomarkers are useful tools for diagnosis and risk assessment of acute kidney injury and acute heart failure, particularly in ICU patients. Most biomarkers are produced or cleared by the kidney, so the presence of chronic kidney disease may affect their clinical reliability, particularly if the putative diagnosis of acute kidney injury or acute heart failure is based on a single measurement/single threshold approach. Better alternatives, such as establishing different diagnostic cutoff values per different chronic kidney disease strata or evaluating the diagnostic performance of a delta value (change from baseline levels) instead of a single threshold, should be carefully considered in critically ill patients with renal impairment and other co-morbidities.

  14. Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

    Science.gov (United States)

    Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

    2015-06-01

    Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

    Directory of Open Access Journals (Sweden)

    Yan Qiang

    2012-01-01

    Full Text Available Abstract Objective To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Methods Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5 years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0 were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. Results The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. Conclusion There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. Virtual slides The virtual slide(s for this article can be found here: http

  16. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

    2017-05-04

    Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

  17. Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers

    Directory of Open Access Journals (Sweden)

    Ren Xiao-Bin

    2011-04-01

    Full Text Available Abstract Background Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI exposure can cause DNA damage in electroplating workers. Methods 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%. Urinary 8-OHdG levels were measured by ELISA. Results Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L than that in control subjects (1.54 μg/L, P P P P Conclusion The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage.

  18. 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.

    Science.gov (United States)

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

    2013-05-01

    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.

  19. Mercuric dichloride induces DNA damage in human salivary gland tissue cells and lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Katharina; Kroemer, Susanne [University of Regensburg, Regensburg (Germany); Sassen, Andrea [University of Regensburg, Department of Pathology, Regensburg (Germany); Staudenmaier, Rainer [Technical University of Munich, Department of Otorhinolaryngology, Head and Neck Surgery, Munich (Germany); Reichl, Franz-Xaver [University of Munich, Institute of Pharmacology and Toxicology, Munich (Germany); Harreus, Ulrich [University of Munich, Department of Otorhinolaryngology, Head and Neck Surgery, Munich (Germany); Hagen, Rudolf; Kleinsasser, Norbert [University of Wuerzburg, Department of Otorhinolaryngology, Head and Neck Surgery, Wuerzburg (Germany)

    2007-11-15

    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{sub 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{sub 2} concentrations from 1 to 50 {mu}M. 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{sub 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{sub 2} concentrations of 5 {mu}M in comparison to the negative control. The viability of the cell systems was not affected except at the highest concentration (50 {mu}M) 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. (orig.)

  20. Protective effect of pumpkin powder (Cucurbita pepo L. on fetal testicular tissue damage in alloxan- induced diabetic rats

    Directory of Open Access Journals (Sweden)

    2014-08-01

    Full Text Available The occurrence of abnormalities in different organs of the fetus and newborn of diabetic mothers has been proven today. Considering the irreversible damages of the disease in newborns’ reproductive system any action to reduce the abnormalities has an especial importance and necessity. In this experimental study, the protective effects of pumpkin powder on reducing testicular tissue damages of rats born from diabetic mothers has been studied. The pregnant rats were divided into 4 groups of 10 rats, as follows: 1 treatment group with pumpkin powder, 2 diabetic control group, 3 treatment group (diabetic animals treated with pumpkin powder and 4 healthy control group. Experimental diabetes was induced in pregnant rats by intraperitoneal injection of 120 mg/kg b.w. alloxan monohydrate. The first and third groups received 2 g/kg b.w. pumpkin powder for 4 weeks via gavage. The histological and morphometric changes such as weight, seminiferous tubules diameter, spermatogonia, leydig and sertoli cell numbers were compared. Data was analyzed using the ANOVA and Tukey multiple comparisons test and p

  1. Cadmium chronic administration to lactating ewes. Reproductive performance, cadmium tissue accumulation and placental transfer

    Energy Technology Data Exchange (ETDEWEB)

    Floris, B.; Bomboi, G.; Sechi, P.; Marongiu, M. L. [Sassari Univ., Sassari (Italy). Dipt. di Biologia Animale; Pirino, S. [Sassari Univ., Sassari (Italy). Ist. di Patologia Generale, Anatomia Patologica e Clinica Ostetrico-chirurgica Veterinaria

    2000-12-01

    20 lactating ewes were allotted to two groups: 10 subjects received orally 100 mg/day of CdCl{sub 2} for 108 consecutive days, and the remaining 10 acted as control. Reproductive performance in ewes and cadmium tissue accumulation, both in ewes and their lambs, were investigated. The results showed that in ewes: 1) the regular cadmium intestinal intake negatively influences all reproductive parameters; 2) cadmium is particularly accumulated in kidney and liver, bur also in mammary gland, although at distinctly lower level; 3) chronic administration does not increase cadmium placental transfer in lactating pregnant subjects. [Italian] 20 pecore in lattazione sono state suddivise in 2 gruppi: 10 soggetti ricevettero per os 100 mg/giorno di CdCl{sub 2} per 108 giorni consecutivi, e i restanti 10 funsero da controllo. Sono stati studiati i parametri riproduttivi delle pecore e l'accumulo di cadmio nei tessuti, sia delle pecore che dei loro agnelli. I risultati hanno mostrato che negli ovini: 1) il regolare assorbimento intestinale di cadmio influenza negativamente tutti i parametri riproduttivi; 2) il cadmio viene accumulato principalmente nei reni e nel fegato, ma anche dalla ghiandola mammaria, sebbene in misura nettamente inferiore; 3) la somministrazione cronica di cadmio nei soggetti gravidi non incrementa il suo passaggio transplacentare.

  2. Chronic intermittent hypoxia activates nuclear factor-κB in cardiovascular tissues in vivo

    International Nuclear Information System (INIS)

    Greenberg, Harly; Ye Xiaobing; Wilson, David; Htoo, Aung K.; Hendersen, Todd; Liu Shufang

    2006-01-01

    Obstructive sleep apnea (OSA) is an important risk factor for cardiovascular morbidity and mortality. The mechanisms through which OSA promotes the development of cardiovascular disease are poorly understood. In this study, we tested the hypotheses that chronic exposure to intermittent hypoxia and reoxygenation (CIH) is a major pathologic factor causing cardiovascular inflammation, and that CIH-induces cardiovascular inflammation and pathology by activating the NF-κB pathway. We demonstrated that exposure of mice to CIH activated NF-κB in cardiovascular tissues, and that OSA patients had markedly elevated monocyte NF-κB activity, which was significantly decreased when obstructive apneas and their resultant CIH were eliminated by nocturnal CPAP therapy. The elevated NF-κB activity induced by CIH is accompanied by and temporally correlated to the increased expression of iNOS protein, a putative and important NF-κB-dependent gene product. Thus, CIH-mediated NF-κB activation may be a molecular mechanism linking OSA and cardiovascular pathologies seen in OSA patients

  3. Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

    Science.gov (United States)

    Głobińska, Anna; Kowalski, Marek L

    2017-10-01

    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.

  4. Can Rotational Atherectomy Cause Thermal Tissue Damage? A Study of the Potential Heating and Thermal Tissue Effects of a Rotational Atherectomy Device

    International Nuclear Information System (INIS)

    Gehani, Abdurrazzak A.; Rees, Michael R.

    1998-01-01

    Purpose: Thermal tissue damage (TTD) is customarily associated with some lasers. The thermal potential of rotational atherectomy (RA) devices is unknown. We investigated the temperature profile and potential TTD as well as the value of fluid flushing of an RA device. Methods: We used a high-resolution infrared imaging system that can detect changes as small as 0.1 deg. C to measure the temperature changes at the tip of a fast RA device with and without fluid flushing. To assess TTD, segments of porcine aorta were subjected to the rotating tip under controlled conditions, stained by a special histochemical stain (picrisirius red) and examined under normal and polarized light microscopy. Results: There was significant heating of the rotating cam. The mean 'peak' temperature rise was 52.8 ± 16.9 deg. C. This was related to rotational speed; thus the 'peak' temperature rise was 88.3 ± 12.6 deg. C at 80,000 rpm and 17.3 ± 3.8 deg. C at 20,000 rpm (p < 0.001, t-test). Fluid flushing at 18 ml/min reduced, but did not abolish, heating of the device (11.8 ± 2.9 deg. C). A crater was observed in all segments exposed to the rotating tip. The following features were most notable: (i) A zone of 'thermal' tissue damage extended radially from the crater reaching adventitia in some sections, especially at high speeds. This zone showed markedly reduced or absent birefringence. (ii) Fluid flushing of the catheter reduced the above changes but increased the incidence and extent of dissections in the media, especially when combined with high atherectomy speeds. (iii) These changes were observed in five of six specimens exposed to RA without flushing, but in only one of six with flushing (p < 0.05). (iv) None of the above changes was seen in control segments. Conclusion: RA is capable of generating significant heat and potential TTD. Fluid flushing reduced heating and TTD. These findings warrant further studies in vivo, and may influence the design of atherectomy devices

  5. Expression of the stem cell factor in fibroblasts, endothelial cells, and macrophages in periapical tissues in human chronic periapical diseases.

    Science.gov (United States)

    Shen, S Q; Wang, R; Huang, S G

    2017-03-08

    Stem cell factor (SCF), an important stem cell cytokine, has multiple functions. Fibroblasts (FBs), mature mast cells, endothelial cells (ECs), and eosinophil granulocytes can produce SCF in the inflammatory process. Therefore, we aimed to observe SCF expression in FBs, ECs, and macrophages (MPs) in periapical tissues in human chronic periapical disease and investigate the effects of cells expressing SCF in pathogenesis of the disease. Healthy (N = 20), periapical cyst (N = 15), and periapical granuloma (N = 15) tissues were fixed in 10% formalin for 48 h, embedded in paraffin, and stained with hematoxylin and eosin to observe histological changes. SCF expression was observed in FBs, ECs, and MPs in periapical tissues by double immunofluorescence. CD334, CD31, and CD14 are specific markers of FBs, ECs, and MPs, respectively. Results showed that densities of CD334-SCF double-positive FBs, CD31-SCF double-positive ECs, and CD14-SCF double-positive MPs were significantly increased in periapical tissue groups (P periapical tissue groups (P > 0.05). CD14-SCF double-positive MP density was considerably higher in periapical granulomas than in cysts (P periapical tissues, suggesting that the cells might be related to occurrence, development, and pathogenesis of chronic periapical disease.

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

    Science.gov (United States)

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

    2014-07-01

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

  7. Effects of chronic exposure to waterborne copper and nickel in binary mixture on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Driessnack, Melissa K; Jamwal, Ankur; Niyogi, Som

    2017-10-01

    The current study evaluated the interactive effects of chronic waterborne copper (Cu) and nickel (Ni) exposure on tissue-specific metal accumulation and reproductive performance in fathead minnow (Pimephales promelas). Fish trios (1 male: 2 female; n = 5-6) were exposed for 21 days to: (i) control (no added Cu or Ni), (ii) waterborne Cu (45 μg/L), (iii) waterborne Ni (270 μg/L), and (iv) binary mixture of waterborne Cu and Ni (45 and 270 μg/L, respectively). Fish fecundity (cumulative egg production) was found to be the most sensitive reproductive endpoint, and the interaction of Cu and Ni elicited an additive effect on egg production. Tissue-specific accumulation of both metals was not influenced by the interaction of Cu and Ni, except an increased Cu and Ni burden in the carcass and ovary, respectively, were recorded. The expressions of hepatic estrogen receptor genes (ER-α and ER-β) and the circulating estradiol level in females were also not affected by the metal-mixture treatment. However, co-exposure to waterborne Cu and Ni resulted in a significant downregulation of the hepatic vitellogenin gene in females, which was associated with the maximum upregulation of the hepatic metallothionein gene. In addition, a significant alteration of ovarian histopathology (decreased abundance of post-vitellogenic follicles, and increased follicular atresia) was also observed only in females exposed to Cu and Ni in mixture. Collectively, these observations suggest that chronic waterborne exposure to Cu and Ni in binary mixture may impair fish reproductive capacity by inducing histopathological damage in ovarian tissue, and disrupting of energy homeostasis in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Mechanistic simulation of normal-tissue damage in radiotherapy-implications for dose-volume analyses

    International Nuclear Information System (INIS)

    Rutkowska, Eva; Baker, Colin; Nahum, Alan

    2010-01-01

    A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V 20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

  9. Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

    Directory of Open Access Journals (Sweden)

    Jiann-Hwa Chen

    2015-05-01

    Full Text Available Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM and the control rats were separated using two-dimensional gel electrophoresis (2-DE to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT and cathepsin D (CATD, which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2 protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia

  10. 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

    2016-03-01

    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.

  11. ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage

    Science.gov (United States)

    Jordan, Jennifer J; Chhim, Sophea; Margulies, Carrie M; Allocca, Mariacarmela; Bronson, Roderick T; Klungland, Arne; Samson, Leona D; Fu, Dragony

    2017-01-01

    Regulated necrosis has emerged as a major cell death mechanism in response to different forms of physiological and pharmacological stress. The AlkB homolog 7 (ALKBH7) protein is required for regulated cellular necrosis in response to chemotherapeutic alkylating agents but its role within a whole organism is unknown. Here, we show that ALKBH7 modulates alkylation-induced cellular death through a tissue and sex-specific mechanism. At the whole-animal level, we find that ALKBH7 deficiency confers increased resistance to MMS-induced toxicity in male but not female mice. Moreover, ALKBH7-deficient mice exhibit protection against alkylation-mediated cytotoxicity in retinal photoreceptor and cerebellar granule cells, two cell types that undergo necrotic death through the initiation of the base excision repair pathway and hyperactivation of the PARP1/ARTD1 enzyme. Notably, the protection against alkylation-induced cerebellar degeneration is specific to ALKBH7-deficient male but not female mice. Our results uncover an in vivo role for ALKBH7 in mediating a sexually dimorphic tissue response to alkylation damage that could influence individual responses to chemotherapies based upon alkylating agents. PMID:28726787

  12. The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

    Science.gov (United States)

    Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

    2017-08-01

    The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

  13. Effect of juice and fermented vinegar from Hovenia dulcis peduncles on chronically alcohol-induced liver damage in mice.

    Science.gov (United States)

    Xiang, Jinle; Zhu, Wenxue; Li, Zhixi; Ling, Shengbao

    2012-06-01

    The protective effects of juice and fermented vinegar from Hovenia dulcis peduncles on chronically ethanol-induced biochemical changes in male mice were investigated. Administration of ethanol (50%, v/v, 10 mL kg⁻¹) to mice for 6 weeks induced liver damage with a significant increase (P vinegar from Hovenia dulcis peduncles (10 mL kg⁻¹ bw) along with alcohol significantly (P vinegar from Hovenia dulcis peduncles showed better profiles of the antioxidant systems with relatively higher glutathione (GSH) content, total superoxide dismutase (T-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. All these results were accompanied by histological observations in liver. The results demonstrate that both of the juice and fermented vinegar from Hovenia dulcis peduncles have beneficial effects in reducing the adverse effect of alcohol.

  14. Safety and effectiveness of a polyvinyl alcohol barrier in reducing risks of vascular tissue damage during anterior spinal revision surgery.

    Science.gov (United States)

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

    2012-05-01

    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.

  15. Evidence of direct cardiac damage following high-intensity exercise in chronic energy restriction: A case report and literature review.

    Science.gov (United States)

    Baird, Marianne F; Grace, Fergal; Sculthorpe, Nicholas; Graham, Scott M; Fleming, Audrey; Baker, Julien S

    2017-07-01

    Following prolonged endurance events such as marathons, elevated levels of cardiospecific biomarkers are commonly reported. Although transiently raised levels are generally not considered to indicate clinical myocardial damage, comprehension of this phenomenon remains incomplete. The popularity of high-intensity interval training highlights a paucity of research measuring cardiac biomarker response to this type of exercise. This a posteriori case report discusses the elevation of cardiac troponins (cTn) associated with short interval, high-intensity exercise. In this case report, an apparently healthy 29-year-old recreationally active female presented clinically raised cardiac troponin I (cTnI) levels (>0.04 ng/mL), after performing high-intensity cycle ergometer sprints. As creatine kinase (CK) is expressed by multiple organs (e.g., skeletal muscle, brain, and myocardium), cTnI assays were performed to determine any changes in total serum CK levels not originating from skeletal muscle damage. A posteriori the individual's daily energy expenditure indicated chronically low-energy availability. Psychometric testing suggested that the individual scored positive for disordered eating, highly for fatigue levels, and low in mental health components. The current case report provides novel evidence of elevated cTnI occurring as a result of performing short duration, high intensity, cycle ergometer exercise in an individual with self-reported chronically depleted energy balance. A schematic to identify potentially "at risk" individuals is presented. Considering this as a case report, results cannot be generalized; however, the main findings suggest that individuals who habitually restrict their calorie intake below their bodies' daily energy requirements, may have elevated biomarkers of exercise induced myocardial stress from performing high-intensity exercise.

  16. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans

    2016-01-01

    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

  17. Treatment of chronic desquamative gingivitis using tissue-engineered human cultured gingival epithelial sheets: a case report.

    Science.gov (United States)

    Okuda, Kazuhiro; Momose, Manabu; Murata, Masashi; Saito, Yoshinori; lnoie, Masukazu; Shinohara, Chikara; Wolff, Larry F; Yoshie, Hiromasa

    2004-04-01

    Human cultured gingival epithelial sheets were used as an autologous grafting material for regenerating gingival tissue in the maxillary left and mandibular right quadrants of a patient with chronic desquamative gingivitis. Six months post-surgery in both treated areas, there were gains in keratinized gingiva and no signs of gingival inflammation compared to presurgery. In the maxillary left quadrant, preoperative histopathologic findings revealed the epithelium was separated from the connective tissue and inflammatory cells were extensive. After grafting with the gingival epithelial sheets, inflammatory cells were decreased and separation between epithelium and connective tissue was not observed. The human cultured gingival epithelial sheets fabricated using tissue engineering technology showed significant promise for gingival augmentation in periodontal therapy.

  18. Intradermal therapy (mesotherapy) with lymdiaral in chronic venous insufficiency and associated fibrosclerotic edema damage: a pilot study.

    Science.gov (United States)

    Maggiori, Enrica; Bartoletti, Emanuele; Mammucari, Massimo

    2013-09-01

    Chronic venous insufficiency (CVI) induces alterations that cause fibrosclerotic edema of the subcutaneous tissue. This study examined the effects of a complex naturopathic compound with vasoactive and antiedema activities (Lymdiaral®) administered intradermally. 40 patients with signs and symptoms of CVI and associated fibrosclerotic edema of the subcutaneous tissue. Efficacy was assessed by using clinical investigation, subjective and objective measures, and ultrasonography performed at baseline and after treatment. Thirty-four patients completed the study; 6 of the original 40 (15%) had stopped for reasons unrelated to study treatment. The treatment was well tolerated. Fifteen adverse reactions were reported among a total of 378 doses administered (3.97%). None of these reactions were severe or required discontinuation of treatment. Subjective symptoms and objective measures improved, and ultrasonography showed statistically significant changes in hypodermal thickness of the medial aspect of the knees. Its open-label design and small sample size notwithstanding, this study indicates that intradermal therapy, according to the recommendation of the Italian Society of Mesotherapy, may provide a valuable contribution to the treatment of CVI and related fibrosclerotic edema of the subcutaneous tissue by prolonging the local effect of the pharmacologically active compounds. Comparative studies are needed to identify the broader clinical and economic benefits of local therapy compared with other systemic therapies.

  19. 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: sorl@rn.dk; 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)

    2013-10-15

    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

  20. Normal tissue damage in radiotherapy development of a clinical audit tool

    International Nuclear Information System (INIS)

    Barrett, A.

    2001-01-01

    Radiotherapy treatments are evaluated by two main outcomes, rates of cure or local tumour control and normal tissue complication rates. Many excellent schemes have been devised for recording the late effects of radiotherapy treatments including the RTOG and LENT SOMA Scales. These have proved invaluable in documenting the outcome of clinical trials, but have proved too complex and time consuming for routine daily use in busy departments. A group in Eindhoven led by Professor Lybeert undertook a pilot study of a potential way of auditing late radiation complications. Using a simplified form derived from the LENT SOMA scales, they collected data on grade 3 and 4 complications in a total of 675 patients and were able to correlate a number of particular complications with specific protocols, ICD codes and physician practice. Further review of the case records made it possible to identify specific factors which may have led to toxicity and could be taken into account to modify treatment protocols. From September 1999 clinicians in participating centres undertaking normal follow-up procedures were asked to identify patients who showed evidence of grade 3 or 4 toxicity as defined in the pro-forma. Date of radiotherapy was recorded so that a temporal correlation of complication with treatment could be made, but this study did not attempt to assess the incidence of complications, but to provide a cross-sectional study of prevalence. Centres participating in the study have been Eindhoven, Koeln, Gent, Brussels, Glasgow, Mount Vernon, Madrid, Geneva and Lyon. In Eindhoven 651 reports were collected between January 1995 and December 1999. 89 reports had to be discarded because complications were not validated by the reviewing radiotherapists. Dr Lybeert noticed that individual radiotherapists appeared to have different thresholds for reporting specific complications. 13 patients deaths appeared to be related to radiation problems. An overall level of detection of morbidity was

  1. Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2017-11-01

    Full Text Available It is well-established that there is a crosstalk between the lung and the kidney, and several studies have reported association between chronic kidney disease (CKD and pulmonary pathophysiological changes. Experimentally, CKD can be caused in mice by dietary intake of adenine. Nevertheless, the consequence of such intervention on the lung received only scant attention. Here, we assessed the pulmonary effects of adenine (0.2% w/w in feed for 4 weeks-induced CKD in mice by assessing various physiological histological and biochemical endpoints. Adenine treatment induced a significant increase in urine output, urea and creatinine concentrations, and it decreased the body weight and creatinine clearance. It also increased proteinuria and the urinary levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Compared with control group, the histopathological evaluation of lungs from adenine-treated mice showed polymorphonuclear leukocytes infiltration in alveolar and bronchial walls, injury, and fibrosis. Moreover, adenine caused a significant increase in lung lipid peroxidation and reactive oxygen species and decreased the antioxidant catalase. Adenine also induced DNA damage assessed by COMET assay. Similarly, adenine caused apoptosis in the lung characterized by a significant increase of cleaved caspase-3. Moreover, adenine induced a significant increase in the expression of nuclear factor erythroid 2–related factor 2 (Nrf2 in the lung. We conclude that administration of adenine in mice induced CKD is accompanied by lung oxidative stress, DNA damage, apoptosis, and Nrf2 expression and fibrosis.

  2. Protective effect of topically applied polypeptide from Chlamys farreri against ultraviolet radiation-induced chronic skin damage in guinea pig

    Science.gov (United States)

    Chi, Mingliang; Cao, Pengli; Yu, Guoying; Zhu, Li; Wang, Yuejun; Wang, Chunbo

    2003-12-01

    Polypeptide from Chlamys farreri (PCF), a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed: (1) PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner. (2) PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px. (3) The differences among the PCF groups and UV model group were significant ( Psolar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

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

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    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.

  4. Influence of bushenhuoxue on primary visual cortex' BDNF damage in rat model of chronic elevated intraocular pressure

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2013-04-01

    Full Text Available AIM: To observe the effect of traditional Chinese medicine(TCMof bushenhuoxue on primary visual cortex(PVCbrain-derived neurotrophic factor(BDNFin rat model of chronic elevated intraocular pressure(EIOP, and explore the mechanism of it initially. METHODS: The rat model of chronic EIOP was established by unilaterally cauterizing 3 episcleral veins, then 30 rats were divided into 3 groups randomly: control group, model group, and treatment group. After given drugs or normal saline for 8 weeks, the rats were put to death. The effect of intraocular pressure(IOP, expression of BDNF and ultrastructure of neuron cell in the PVC was observed. RESULTS: Unilaterally cauterizing episcleral veins increased IOP of the rat model obviously, there was significant difference compared with pre-operation(P<0.01. Semi-quantitative pathological analysis on PVC showed that BDNF of total area in the model group was(82438±2597.39S/μm2,mean optical density was(1155.9±123.14, integrated optical density was(12915±673.28, compared with the control group {total area was(132370±7588.47S/μm2, mean optical density was(5365±379.65, integrated optical density was(35102±2648.5}, there were statistical differences(all P<0.05,there was statistical difference in BDNF of total area between model group and treatment group{(108980±9126.77S/μm2, P<0.05}, significant difference in mean optical density between the model group and treatment group(3220.4±413.67, P<0.05, statistical difference in integrated optical density between the model group and treatment group(23821±3431.68, P<0.05. CONCLUSION: TCM of bushenhuoxue can repair the PVC damage in the rat model of chronic EIOP by enhancing expression of BDNF, improving ultrastructure of neuron cell.

  5. Behavioral Impairment and Oxidative Damage Induced by Chronic Application of Nonylphenol

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    Zhen Mao

    2010-12-01

    Full Text Available Nonylphenol (NP is a degradation product of nonylphenol polyethoxylates, which are widely used in the production of industrial and consumer surfactants. The aim of the present study was to evaluate the effect of NP on the antioxidant capacity and cognitive ability of mice. NP was given orally by gavages at doses of 0, 50, 100, and 200 mg kg−1 d−1 for 90 days. The results showed that NP significantly decreased the activity of superoxide dismutases (SOD, catalase (CAT, glutathione peroxidase (GPx, and glutathione reductase (GR and at the same time increased malondialdehyde (MDA levels in mice brains. Exploration, memory function and ability to learn a novel task were significantly decreased in NP fed mice. These results indicate that chronic high dose of NP exposure has the potential to generate oxidative stress and induce the cognitive impairment in male mice.

  6. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

    Science.gov (United States)

    Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

    1986-01-01

    In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

  7. Cytogenetic Damages Induced by Chronic Exposure to Microwave Non-Ionizing Radiofrequency Fields

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    Boris Đinđić

    2013-12-01

    Full Text Available Non-ionizing radiation has a significant and positive impact on modern society through a number of uses. There is increasing public concern regarding the health risks of radio-frequency (RF radiation, particularly that produced by mobile phones. Concern regarding the potential risks of exposure to EMFs has led to many epidemiological investigations, but the effects of EMF exposure on human and other mammalian cells are still unclear. One of the most frequently asked questions about the effects of microwave radiation on biological systems is whether they produce genotoxic effects and could be there a possible link with oncogenic processes. It is most difficult to get accurate and reproducible results for the studies that tell us most about the effects of EMF on humans. Based on some “weak” evidence suggesting an association between exposure to radiofrequency fields (RF emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as ‘possibly carcinogenic to humans’ in group 2B. Literature results suggest that pulsed microwaves from working environment can be the cause of genetic and cell alterations. Taken together, the increased frequency of DNA damages, increased intensity of oxydative stress and production of reactive oxygen species as well as prolonged disruption in DNA repair mechanisms could be possible mechanisms for microwave induced cytogenetic damages even at low-level electromagnetic fields. Although there were contradictory results about harmful effects of electromagnetic fields we recommend that the mobile phone should be kept as far as possible from the body during conversations and also during usual daily activities to reduce the absorption of radiation by cells. In addition, the appropriate intake of antioxidant-rich food or drugs may be helpful for preventing the genotoxic effects that could be caused by mobile phone use.

  8. 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)

    2007-10-15

    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.)

  9. Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

    Directory of Open Access Journals (Sweden)

    S.Q. Cui

    2015-06-01

    Full Text Available We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each. The model group received 60% (v/v ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N and microglia (by Ib1 were conducted. Glutamic acid (Glu and gamma amino butyric acid (GABA in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC, and tumor necrosis factor (TNF-α and interleukin (IL-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05 by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01, and neurons were reduced only in the hippocampal dentate gyrus (P<0.01 in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05, and Glu/GABA, TNF-α, and IL-1β increased (P<0.01 with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

  10. Does a Better Perfusion of Deconditioned Muscle Tissue Release Chronic Low Back Pain?

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    Paola Valdivieso

    2018-03-01

    Full Text Available Non-specific chronic low back pain (nsCLBP is a multifactorial condition of unknown etiology and pathogenesis. Physical and genetic factors may influence the predisposition of individuals to CLBP, which in many instances share a musculoskeletal origin. A reduced pain level in low back pain patients that participate in exercise therapy highlights that disuse-related muscle deconditioning may predispose individuals to nsCLBP. In this context, musculoskeletal pain may be the consequence of capillary rarefaction in inactive muscle as this would lower local tissue drainage and washing out of toxic waste. Muscle activity is translated into an angio-adaptative process, which implicates angiogenic-gene expression and individual response differences due to heritable modifications of such genes (gene polymorphisms. The pathophysiologic mechanism underlying nsCLBP is still largely unaddressed. We hypothesize that capillary rarefaction due to a deconditioning of dorsal muscle groups exacerbates nsCLBP by increasing noxious sensation, reducing muscle strength and fatigue resistance by initiating a downward spiral of local deconditioning of back muscles which diminishes their load-bearing capacity. We address the idea that specific factors such as angiotensin-converting enzyme and Tenascin-C might play an important role in altering susceptibility to nsCLBP via their effects on microvascular perfusion and vascular remodeling of skeletal muscle, inflammation, and pain sensation. The genetic profile may help to explain the individual predisposition to nsCLBP, thus identifying subgroups of patients, which could benefit from ad hoc treatment types. Future therapeutic approaches aimed at relieving the pain associated with nsCLBP should be based on the verification of mechanistic processes of activity-induced angio-adaptation and muscle-perfusion.

  11. Percutaneous Soft Tissue Release for Treating Chronic Recurrent Myofascial Pain Associated with Lateral Epicondylitis: 6 Case Studies

    Science.gov (United States)

    Lin, Ming-Ta; Chou, Li-Wei; Chen, Hsin-Shui; Kao, Mu-Jung

    2012-01-01

    Objective. The purpose of this pilot study is to investigate the effectiveness of the percutaneous soft tissue release for the treatment of recurrent myofascial pain in the forearm due to recurrent lateral epicondylitis. Methods. Six patients with chronic recurrent pain in the forearm with myofascial trigger points (MTrPs) due to chronic lateral epicondylitis were treated with percutaneous soft tissue release of Lin's technique. Pain intensity (measured with a numerical pain rating scale), pressure pain threshold (measured with a pressure algometer), and grasping strength (measured with a hand dynamometer) were assessed before, immediately after, and 3 months and 12 months after the treatment. Results. For every individual case, the pain intensity was significantly reduced (P lateral epicondylitis to avoid recurrence, if other treatment, such as oral anti-inflammatory medicine, physical therapy, or local steroid injection, cannot control the recurrent pain. PMID:23243428

  12. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue.

    Directory of Open Access Journals (Sweden)

    Andrea S Bauer

    Full Text Available A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC curves and the corresponding area under the curve (AUC analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875. Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer.

  13. Percutaneous Soft Tissue Release for Treating Chronic Recurrent Myofascial Pain Associated with Lateral Epicondylitis: 6 Case Studies

    Directory of Open Access Journals (Sweden)

    Ming-Ta Lin

    2012-01-01

    Full Text Available Objective. The purpose of this pilot study is to investigate the effectiveness of the percutaneous soft tissue release for the treatment of recurrent myofascial pain in the forearm due to recurrent lateral epicondylitis. Methods. Six patients with chronic recurrent pain in the forearm with myofascial trigger points (MTrPs due to chronic lateral epicondylitis were treated with percutaneous soft tissue release of Lin’s technique. Pain intensity (measured with a numerical pain rating scale, pressure pain threshold (measured with a pressure algometer, and grasping strength (measured with a hand dynamometer were assessed before, immediately after, and 3 months and 12 months after the treatment. Results. For every individual case, the pain intensity was significantly reduced (P<0.01 and the pressure pain threshold and the grasping strength were significantly increased (P<0.01 immediately after the treatment. This significant effectiveness lasts for at least one year. Conclusions. It is suggested that percutaneous soft tissue release can be used for treating chronic recurrent lateral epicondylitis to avoid recurrence, if other treatment, such as oral anti-inflammatory medicine, physical therapy, or local steroid injection, cannot control the recurrent pain.

  14. Clinical studies of functional imaging of dynamic CT for chronic brain-damaged patients

    International Nuclear Information System (INIS)

    Inada, Haruo; Miyano, Satoshi

    1995-01-01

    The 311 brain-damaged patients, mostly of cerebrovascular disease (CVD) were examined by functional imaging to dynamic CT (FIDCT) at Tokyo Metropolitan Rehabilitation Hospital. The abnormal patterns of FIDCT were classified according to two categories, i.e. focal area where plain CT showed low density area (LDA), and extra-focal area where plain CT showed no abnormal findings. These patterns were diagnosed by using the two parameters, i.e. Corrected First Moment (CM) and Time to Peak (TP). Over 50% of the focal abnormal FIDCT revealed tha same area with LDA on plain CT. The extra-focal FIDCT showed various abnormal patterns, and only 11% of all the findings had no abnormalities. The correlation of the specific patterns of extra-focal FIDCT with the multiple CVD episodes was investigated, and the findings that had significant correlation were (a) delayed CM of bilateral white matter, (b) diffusely delayed TP of the affected hemisphere, and the patient group that showed no extra-focal abnormal FIDCT had significant low incidence of multiple CVD episodes. From these results, it is concluded that the high-risk group of stroke recurrence can be predicted by extra-focal findings of FIDCT. (author)

  15. Chronic brain damage in sickle cell disease and its relation with quality of life.

    Science.gov (United States)

    Cela, Elena; Vélez, Ana G; Aguado, Alejandra; Medín, Gabriela; Bellón, José M; Beléndez, Cristina

    2016-12-16

    Sickle cell anaemia causes progressive organ damage. The objective is to describe school performance of patients with sickle cell anaemia and their clinical parameters and quality of life that may have an influence. The hypothesis is that if school alterations occur without other objective data, additional factors must be present besides the disease itself. Transversal study performed in November 2015 considering analytical variables, complications and neuroradiological images of children with sickle cell anaemia, and family survey on school performance and quality of life. Median age was 6.8 years and 78% were diagnosed at birth. Sixty patients were included. School performance was altered in 51% of cases and was related to nocturnal hypoxemia. Acute stroke incidence was 6.7%. Transcranial ultrasound was abnormal in 4% of cases and magnetic resonance imaging in 16% of cases. Quality of life showed pathological findings in all areas and the low values increased proportionally in older ages. The stroke affected the physical and social sphere, and lung disease affected the physical and emotional spheres. Poor school performance affects half of the patients and it is related to nocturnal hypoxemia, although other socio-cultural factors may have an influence. Quality of life is affected in most of these cases independently of academic results. The absence of alterations in neuroimaging or the apparent lack of severe clinical parameters do not mean that quality of life and schooling are normal. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  16. Clinical studies of functional imaging of dynamic CT for chronic brain-damaged patients

    Energy Technology Data Exchange (ETDEWEB)

    Inada, Haruo; Miyano, Satoshi [Jikei Univ., Tokyo (Japan). School of Medicine

    1995-03-01

    The 311 brain-damaged patients, mostly of cerebrovascular disease (CVD) were examined by functional imaging to dynamic CT (FIDCT) at Tokyo Metropolitan Rehabilitation Hospital. The abnormal patterns of FIDCT were classified according to two categories, i.e. focal area where plain CT showed low density area (LDA), and extra-focal area where plain CT showed no abnormal findings. These patterns were diagnosed by using the two parameters, i.e. Corrected First Moment (CM) and Time to Peak (TP). Over 50% of the focal abnormal FIDCT revealed tha same area with LDA on plain CT. The extra-focal FIDCT showed various abnormal patterns, and only 11% of all the findings had no abnormalities. The correlation of the specific patterns of extra-focal FIDCT with the multiple CVD episodes was investigated, and the findings that had significant correlation were (a) delayed CM of bilateral white matter, (b) diffusely delayed TP of the affected hemisphere, and the patient group that showed no extra-focal abnormal FIDCT had significant low incidence of multiple CVD episodes. From these results, it is concluded that the high-risk group of stroke recurrence can be predicted by extra-focal findings of FIDCT. (author).

  17. Monomeric neutrophil gelatinase associated lipocalin is associated with tubulointerstitial damage in chronic kidney disease

    Science.gov (United States)

    Nickolas, Thomas L.; Forster, Catherine; Sise, Meghan E.; Barasch, Nicholas; Valle, David Solá-Del; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-01-01

    The rate of progression of chronic kidney disease (CKD) is difficult to predict using single measurements of serum creatinine or proteinuria. On the other hand, documented tubulointerstitial disease presages worsening CKD, but kidney biopsy is not practical for routine use and generally does not sample the tubulointerstitial compartment of the medulla. Perhaps a urine test that correlates with specific histological findings may serve as a surrogate for the kidney biopsy. Here we compared both immunoblot analysis (under non-reducing conditions) and a commercially available monomer immunoassays of Neutrophil Gelatinase Associated Lipocalin (NGAL) with pathological changes found in kidney biopsies, to determine whether specific histological characteristics associated with a specific NGAL species. We found that the urine of patients with advanced CKD contained NGAL monomers as well as higher molecular weight complexes containing NGAL, identified by MALDI-TOF/TOF mass spectroscopy. The NGAL monomer significantly correlated with glomerular filtration rate, interstitial fibrosis and tubular atrophy. Hence, specific assays of the NGAL monomer implicate histology associated with progressive, severe CKD. PMID:22695331

  18. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

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

    Science.gov (United States)

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

    2017-10-31

    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.

  20. Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

    Science.gov (United States)

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

    2014-12-01

    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.

  1. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    International Nuclear Information System (INIS)

    Gimpel, Charlotte; Pohl, Martin; Jung, Bernd A.; Jung, Sabine; Brado, Johannes; Odening, Katja E.; Schwendinger, Daniel; Burkhardt, Barbara; Geiger, Julia; Arnold, Raoul

    2017-01-01

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V E ), late diastolic (V A ) and peak systolic (V S ) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz base -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz mid -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz apex -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr base -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr mid -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr apex -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

  2. Magnetic resonance tissue phase mapping demonstrates altered left ventricular diastolic function in children with chronic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Gimpel, Charlotte; Pohl, Martin [Medical Center - University of Freiburg, Department of General Pediatrics, Adolescent Medicine and Neonatology, Center for Pediatrics, Freiburg (Germany); Jung, Bernd A. [Inselspital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Jung, Sabine [Medical Center - University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Brado, Johannes; Odening, Katja E. [University Heart Center Freiburg, Department of Cardiology and Angiology I, Freiburg (Germany); Schwendinger, Daniel [University Children' s Hospital Zurich, Zurich (Switzerland); Burkhardt, Barbara [University Children' s Hospital Zurich, Pediatric Heart Center, Zurich (Switzerland); Geiger, Julia [University Children' s Hospital Zurich, Department of Radiology, Zurich (Switzerland); Northwestern University, Department of Radiology, Chicago, IL (United States); Arnold, Raoul [University Hospital Heidelberg, Department of Pediatric and Congenital Cardiology, Heidelberg (Germany)

    2017-02-15

    Echocardiographic examinations have revealed functional cardiac abnormalities in children with chronic kidney disease. To assess the feasibility of MRI tissue phase mapping in children and to assess regional left ventricular wall movements in children with chronic kidney disease. Twenty pediatric patients with chronic kidney disease (before or after renal transplantation) and 12 healthy controls underwent tissue phase mapping (TPM) to quantify regional left ventricular function through myocardial long (Vz) and short-axis (Vr) velocities at all 3 levels of the left ventricle. Patients and controls (age: 8 years - 20 years) were matched for age, height, weight, gender and heart rate. Patients had higher systolic blood pressure. No patient had left ventricular hypertrophy on MRI or diastolic dysfunction on echocardiography. Fifteen patients underwent tissue Doppler echocardiography, with normal z-scores for mitral early diastolic (V{sub E}), late diastolic (V{sub A}) and peak systolic (V{sub S}) velocities. Throughout all left ventricular levels, peak diastolic Vz and Vr (cm/s) were reduced in patients: Vz{sub base} -10.6 ± 1.9 vs. -13.4 ± 2.0 (P < 0.0003), Vz{sub mid} -7.8 ± 1.6 vs. -11 ± 1.5 (P < 0.0001), Vz{sub apex} -3.8 ± 1.6 vs. -5.3 ± 1.6 (P = 0.01), Vr{sub base} -4.2 ± 0.8 vs. -4.9 ± 0.7 (P = 0.01), Vr{sub mid} -4.7 ± 0.7 vs. -5.4 ± 0.7 (P = 0.01), Vr{sub apex} -4.7 ± 1.4 vs. -5.6 ± 1.1 (P = 0.05). Tissue phase mapping is feasible in children and adolescents. Children with chronic kidney disease show significantly reduced peak diastolic long- and short-axis left ventricular wall velocities, reflecting impaired early diastolic filling. Thus, tissue phase mapping detects chronic kidney disease-related functional myocardial changes before overt left ventricular hypertrophy or echocardiographic diastolic dysfunction occurs. (orig.)

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

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    Abolhasan Rezaeyan

    2016-01-01

    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.

  4. Adjuvant therapy of chronic gastroduodenitis in children with dysplasia of connective tissue

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    О. М. Mukvich

    2018-04-01

    Full Text Available Chronic gastroduodenitis (CGD hold one of main places among leading diseases of gastro-intestinal tract (GIT in childhood. A special category is children who have CGD against the background of connective tissue (CT dysplasia (DCT. CGD in such children is characterized by early appearance, aggressive, gradient course with frequent acute conditions and recurrences with evident symptoms of nonspecific intoxication manifestations. Defect of collagen synthesis leads to pronounced morphological changes of proximal GIT mucous membrane (MM and decline in its cytoptotecive abilities. Challenges related to the qualitative and quantitative local ecosystem changes can aggravate immune and metabolic local processes and enhance the destruction of proximal GIT mucous membrane. Aforesaid defines the need to include multiprobiotics into the treatment schemes of patient with CGD, associated with congenital fibrogenesis disorders, as adjuvant therapy with complex therapeutic action; they positively influence the CT metabolism, improve reparative processes in MM, normalize immune processes and maintain composition and functions of physiological microbiota. Purposes – improvement of CGD treatment efficiency in children with DCT through inclusion of the multiprobiotic Symbiter® forte-M into the treatment schemes. Materials and methods. There were examined 33 children with CGD on the background of DCT and 32 healthy children (control from 11 to 17 years old. The state of the mucous barrier was estimated by certain mucin constituents (fucose, glycosaminoglycans, sialic acids assessing, antimicrobial peptides (ß2-defencins, non-specific humoral factors of the local immunity (immunoglobulins, lysozyme in mucous secretions (saliva, coprofiltrate (CF before and after probiotic therapy. Results. Increased concentrations of ß2-defencins (psaliva = 0.03, pCF = 0.03, sialic acids (P = 0.04 and lysozyme (P = 0.01 and decreased of fucose level (P = 0.03 in mucous secretions

  5. ACTIVATION MECHANISMS OF GUT-ASSOCIATED LYMPHOID TISSUE UNDER CHRONIC SOCIAL STRESS CONDITIONS

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    A. M. Kamyshnyi

    2015-01-01

    Full Text Available Stress-induced immune disregulation is a risk factor of autoimmune and inflammatory diseases, but, so far, the mechanisms for this effect are not fully known. Expression levels of specific mRNAs were assessed in gut-associated lymphoid tissue (GALT from Wistar rats subjected to chronic social stress (CSS. Gene expression was evaluated for NR3C1, Adrβ2, as well as IL-1β, IL-17α pro-inflammatory cytokines, and Nlrp, an inflammasome gene. Under the CSS conditions, we have shown altered distribution of RORγt +, FoxP3+, LMP2+, XBP1+ lymphocytes in GALT.The experiments were carried out with female Wistar rats aged 5–6 months. Specific mRNA expression for the target genes was determined by means of real-time PCR performed in a CFX96™ thermocycler («BioRadLaboratories, Inc»,USA. Relative levels of a target gene expression were quantified by the ΔΔCt method, being compared with rat GAPDH reference gene expression. Statistical analysis was performed with available «BioRad СFX Manager 3.1» software. Specific monoclonal rat antibodes were used for detection of immunopositive lymphocytes by means of indirect immunofluorescence technique.CSS development leads to decreased levels of mRNA expression for Nr3c1 and Adrβ2-genes in the GALT cells, being accompanied with unidirectional changes, i.e., increased transcription of pro-inflammatory cytokine mRNAs (IL-1β, IL-17α and Nlrp3-inflammasome genes. These changes are accompanied by decreased FoxP3+/RORγt + cell ratio and predominant Th17 differentiation accompanied by suppressor failure. In addition, CSS development was characterized by unidirectional tendency for increasing total number of LMP2+ lymphocytes and reduced ХВР1+ cell population density in lymphoid structures of rat ileum.The events observed in GALT cell populations under CSS conditions are opposing classical paradigm of the stress response. The CSS-associated effects do not promote immunosuppression, however, are able to cause

  6. Abnormal phenotype of cultured fibroblasts in human skin with chronic radiotherapy damage

    International Nuclear Information System (INIS)

    Delanian, S.; Martin, M.; Lefaix, J.-L.; Bravard, A.; Luccioni, C.

    1998-01-01

    Purpose: The pathophysiological aspects of radiation-induced fibrosis (RIF) have not been well characterized. We therefore cultured human fibroblasts from samples of skin with RIF to investigate the long-term effects of therapeutic irradiation. Materials and methods: Biopsies of normal and RIF skin were obtained from patients previously irradiated for cancer, without recurrence. Cells were extracted from dermis samples by the outgrowth technique, seeded as monolayers and cultured at confluence. Enzyme activities and proteins were assayed, RNA was isolated and Northern blot analysis was performed on surviving cells between passages 2 and 5. Results: RIF cell cultures displayed heterogeneous fibroblasts populations. The initial outgrowth consisted of one-third small cells that floated rapidly, one-third spindle-shaped cells migrating far from the explant to form islets and one-third large pleiomorphic cells. In subsequent subcultures, surviving cells exhibited either myofibroblastic characteristics with a normal proliferative capacity or senescent morphology with a reduced proliferative capacity. These RIF cells had a brief finite lifespan, with dramatically reduced growth rate during their initial outgrowth and the following passages. Study of the antioxidant metabolism showed that Mn superoxide dismutase and catalase activities were significantly weaker in surviving RIF cells than healthy fibroblasts. These exhausted RIF cells exhibited no overexpression of transforming growth factor β or tissue inhibitor of metalloproteinase. Conclusion: Irradiation may lead to apparently contradictory effects such as fibrosis and necrosis in clinical practice. In cell culture, we observed two main cellular phenotypes which may be related to both processes, i.e. myofibroblast-like cells and fibrocyte-like cells. These two phenotypes may represent two steps in the differentiation induced as a long-term effect of therapeutic irradiation of the skin. Cell culture probably

  7. Brain Damage and Motor Cortex Impairment in Chronic Obstructive Pulmonary Disease: Implication of Nonrapid Eye Movement Sleep Desaturation.

    Science.gov (United States)

    Alexandre, Francois; Heraud, Nelly; Sanchez, Anthony M J; Tremey, Emilie; Oliver, Nicolas; Guerin, Philippe; Varray, Alain

    2016-02-01

    Nonrapid eye movement (NREM) sleep desaturation may cause neuronal damage due to the withdrawal of cerebrovascular reactivity. The current study (1) assessed the prevalence of NREM sleep desaturation in nonhypoxemic patients with chronic obstructive pulmonary disease (COPD) and (2) compared a biological marker of cerebral lesion and neuromuscular function in patients with and without NREM sleep desaturation. One hundred fifteen patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 2 and 3), resting PaO2 of 60-80 mmHg, aged between 40 and 80 y, and without sleep apnea (apnea-hypopnea index sleep recordings. In addition, twenty-nine patients (substudy) were assessed i) for brain impairment by serum S100B (biological marker of cerebral lesion), and ii) for neuromuscular function via motor cortex activation and excitability and maximal voluntary quadriceps strength measurement. A total of 51.3% patients (n = 59) had NREM sleep desaturation (NREMDes). Serum S100B was higher in the NREMDes patients of the substudy (n = 14): 45.1 [Q1: 37.7, Q3: 62.8] versus 32.9 [Q1: 25.7, Q3: 39.5] pg.ml(-1) (P = 0.028). Motor cortex activation and excitability were lower in NREMDes patients (both P = 0.03), but muscle strength was comparable between groups (P = 0.58). Over half the nonhypoxemic COPD patients exhibited NREM sleep desaturation associated with higher values of the cerebral lesion biomarker and lower neural drive reaching the quadriceps during maximal voluntary contraction. The lack of muscle strength differences between groups suggests a compensatory mechanism(s). Altogether, the results are consistent with an involvement of NREM sleep desaturation in COPD brain impairment. The study was registered at www.clinicaltrials.gov as NCT01679782. © 2016 Associated Professional Sleep Societies, LLC.

  8. The effects of vitamin E on brain derived neurotrophic factor, tissues oxidative damage and learning and memory of juvenile hypothyroid rats.

    Science.gov (United States)

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

    2018-06-01

    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.

  9. Tissue

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    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  10. Effect of self-ligating bracket appliance on the periodontal tissues in patients with chronic periodontitis after orthodontic treatment

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    Liu-Qing Yang

    2017-04-01

    Full Text Available Objective: To explore the effect of self-ligating bracket appliance on the periodontal tissues in patients with chronic periodontitis after orthodontic treatment. Methods: A total of 56 patients with chronic periodontitis who were admitted in our hospital were included in the study and divided into the observation group and the control group according to different treatment protocols. The patients in the observation group were given self-ligating brackets, while the patients in the control group were given traditional brackets. The periodontal tissues and tooth motility (TM before and after treatment in the two groups were observed and recorded. IL-1 毬 and TNF-毩 levels in the gingival crervicular fluid (GCF before and after treatment in the two groups were detected. Results: PD, CAL, SBI, and PLI after treatment in the two groups were significantly reduced, while GR was significantly elevated when compared with the control group. PD, CAL, SBI, and PLI after treatment in the observation group were significantly lower than those in the control group, while GR was significantly higher than that in the control group. TM after treatment in the two groups was significantly improved, among which the number of 0° TM was significantly increased, while the number of Ⅰ°-Ⅲ°TM was significantly reduced. IL-1β and TNF-α levels in GCF after treatment in the two groups were significantly reduced when compared with before treatment. IL-1β and TNF-α levels in GCF after treatment in the observation group were significantly lower than those in the control group. Conclusions: The self-ligating brackets can effectively improve the periodontal tissues and TM in patients with chronic periodontitis, and reduce the levels of inflammatory cytokines in periodontal tissues, with an accurate efficacy.

  11. Estimation of tissue and crevicular fluid oxidative stress marker in premenopausal, perimenopausal and postmenopausal women with chronic periodontitis.

    Science.gov (United States)

    Chandra, Rampalli Viswa; Sailaja, Sistla; Reddy, Aileni Amarender

    2017-09-01

    The aim of this study was to estimate tissue and gingival crevicular fluid (GCF) levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in premenopausal, perimenopausal and postmenopausal women with chronic periodontitis. Oxidative stress has been implicated in the etiopathogenesis of periodontitis and menopause induces oxidative stress. According to Stages of Reproductive Aging Workshop (STRAW) criteria, women diagnosed with periodontitis were subdivided into three groups of 31 participants each 1. Premenopausal 2. Perimenopausal and 3. Postmenopausal. GCF and gingival tissue samples were collected from sites with maximum probing depth. Tissue DNA was extracted from the gingival sample and 8-OHdG in the extracted DNA, and GCF samples were measured using ELISA. There was a highly significant difference in the overall GCF 8-OHdG levels among the three groups with the pairwise difference being highly significant between the premenopausal-postmenopausal groups and perimenopausal-postmenopausal groups. However, no overall significant differences in tissue 8-OHdG levels were found among the three groups. Pairwise, highly significant differences were found between the premenopausal-postmenopausal groups and perimenopausal-postmenopausal groups for tissue 8-OHdG levels. No significant correlations were found between various measure of periodontal disease and GCF/tissue 8-OHdG levels among all the groups. Premenopausal-postmenopausal and perimenopausal-postmenopausal transition resulted in significant increase in tissue and GCF 8-OHdG levels. However, no association was found between stages of reproductive ageing and tissue levels of 8-OHdG. © 2017 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  12. Estimation of pentraxin-3 levels in the gingival tissues of chronic and aggressive periodontitis participants: an in vivo study.

    Science.gov (United States)

    Lakshmanan, Reema; Jayakumar, N D; Sankari, Malaiappan; Padmalatha, Ogoti; Varghese, Sheeja

    2014-02-01

    Pentraxins are acute-phase proteins that belong to a family of evolutionarily conserved proteins, and they are considered markers of inflammation. Pentraxin-3 (PTX3) is a prototype of the long pentraxin group. It is suggested to play an important role in innate resistance against pathogens, regulation of inflammation, and clearance of apoptotic cells. The aim of this study is to estimate the level of PTX3 in gingival tissues of individuals with chronic (CP) and aggressive (AgP) periodontitis and control participants and further correlate the level of PTX3 with clinical parameters. The study population consisted of 50 participants ranging in age from 20 to 55 years and attending the outpatient section of Department of Periodontics, Saveetha Dental College and Hospital, Chennai, India. The study groups included the following: 1) group A, patients with generalized CP (n = 20); 2) group B (n = 20), patients with generalized AgP (GAgP); and 3) group C (n = 10), healthy controls. Tissue samples from participants were assayed for PTX3 levels using enzyme-linked immunosorbent assay. Gingival tissues from patients with GAgP (8.349 ± 5.076 ng/mL) had a higher mean concentration of PTX3 than tissues from patients with generalized CP (5.068 ± 3.274 ng/mL) and controls (0.251 ± 0.277). The PTX3 levels in the gingival tissues correlated positively with clinical parameters in all the groups. Among the parameters, probing depth was the most significant predictor variable associated with PTX3 in cases with periodontitis. PTX3 concentration in gingival tissues of patients with GAgP was higher than in tissues from patients with CP, and the levels correlated positively with clinical parameters. Hence, tissue PTX3 level can be considered a marker of inflammation in periodontal disease.

  13. 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.

  14. Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus).

    Science.gov (United States)

    Lattin, Christine R; Romero, L Michael

    2014-07-15

    The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. © 2014. Published by The Company of Biologists Ltd.

  15. Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

    Science.gov (United States)

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

    2016-01-01

    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

  16. Combined antibacterial effects of tissue-tolerable plasma and a modern conventional liquid antiseptic on chronic wound treatment.

    Science.gov (United States)

    Klebes, Martin; Ulrich, Christin; Kluschke, Franziska; Patzelt, Alexa; Vandersee, Staffan; Richter, Heike; Bob, Adrienne; von Hutten, Johanna; Krediet, Jorien T; Kramer, Axel; Lademann, Jürgen; Lange-Asschenfeld, Bernhard

    2015-05-01

    Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Skin autofluorescence as a novel marker of vascular damage in children and adolescents with chronic kidney disease.

    Science.gov (United States)

    Makulska, Irena; Szczepańska, Maria; Drożdż, Dorota; Polak-Jonkisz, Dorota; Zwolińska, Danuta

    2015-05-01

    Skin autofluorescence (sAF) was examined as a marker of the accumulation of advanced glycation end products (AGEs) in tissues of children with chronic kidney disease (CKD) in relation to renal function, dialysis modality and markers of endothelial inflammation and dysfunction. A total of 76 children with CKD were enrolled in the study, of whom 20 children were on hemodialysis (HD), 20 were on peritoneal dialysis (PD) and 36 were treated conservatively. A control group of 26 healthy subjects was also included in the study. In all children, sAF intensity, carotid intima-media (cIMT) thickness and plasma concentrations of sE-selectin, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and plasminogen activator inhibitor type 1 (PAI-1) were measured. Compared to the controls, children with CKD had significantly elevated sAF levels. sAF in the children with CKD was positively correlated with sE-selectin, MMP-9, TIMP-1, ADMA, SDMA and PAI-1 levels. In the predialysis group (conservative treatment) sAF levels were positively correlated with sE-selectin and ADMA levels and negatively correlated with glomerular filtration rate. Multiple regression analysis showed a significant association of sAF with sE-selectin and MMP-9 in CKD children. The results reveal that AGEs were accumulated in the children with CKD. This accumulation was related to early vascular changes and a number of biochemical vascular risk markers. sAF measurement, as a noninvasive method, may be useful for identification of clinical risk factors of vascular disease in CKD children.

  18. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  19. Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Joanna Gertow

    2017-11-01

    Discussion: These findings demonstrate that adipose tissue of CKD patients shows signs of inflammation and disturbed functionality, thus potentially contributing to the unfavorable metabolic profile and increased risk of CVD in these patients.

  20. Far-Infrared Radiation Thermotherapy Improves Tissue Fibrosis in Chronic Extremity Lymphedema.

    Science.gov (United States)

    Li, Ke; Zhang, Zheng; Liu, Ning Fei; Sadigh, Parviz; Evans, Verity Joyce; Zhou, Huihong; Gao, Weiqing; Zhang, Yi Xin

    2017-09-29

    Fibrosis can enhance the exacerbation of lymphedema, which becomes obvious in late stage II-III lymphedema. However, whether far-infrared radiation thermotherapy (FIRT) can cure lymphedema fibrosis is still lack of research. This research was to investigate the therapeutic effect of FIRT on tissue fibrosis in the treatment of Late stage II-III lymphedema. Patients accepted only FIRT for a total of 20 sessions. The treatment session duration was 2 hours, and a stable machine temperature of 42°C was maintained throughout treatments. Clinical evaluation and laboratory evaluation were conducted before and after FIRT. Clinical outcome measures included circumference of affected extremity, skin elasticity, ultrasound, patients' subjective assessment, and quality of life (QOL). Laboratory outcome measures included serum and local lymphedema tissue fluid concentrations of fibrosis associated cytokines, tissue growth factor beta-1 (TGF-β1), interleukin (IL)-1β, IL-4, IL-18, and caspase-1. Between 2015 and 2016, clinical evaluation of 64 patients with late stage II-III lymphedema was conducted. From this group, 12 cases (18.75%) underwent simultaneous laboratory evaluation. Circumferences of affected extremities improved significantly following treatment (p pain, discomfort, and numbness (p effective treatment for lymphedema tissue fibrosis; it reduces the concentration of fibrosis cytokines in local lymphedema tissues. Consequently, this treatment can reduce the density of fibrosed tissue in the affected extremity, increase skin elasticity, significantly improve clinical symptoms, and improve QOL of patients.

  1. Extensive tissue damage of bovine ovaries after bipolar ovarian drilling compared to monopolar electrocoagulation or carbon dioxide laser

    NARCIS (Netherlands)

    Hendriks, M.L.; van der Valk, P.; Lambalk, C.B.; Broeckaert, M.A.M.; Homburg, R.R.; Hompes, P.G.A.

    2010-01-01

    Objective: To evaluate the size of ovarian damage caused by ovarian drilling in polycystic ovary syndrome, the amount of inflicted damage was assessed for the most frequently used ovarian drilling techniques. Design: Experimental prospective design. Setting: University clinic. Patient(s): Six fresh

  2. Role of Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease

    Science.gov (United States)

    OBJECTIVE: Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by ho...

  3. The influence of combined treatment of Cd, and γ-irradiation on DNA damage and repair in lymphoid tissues of mice

    International Nuclear Information System (INIS)

    Privezentsev, K.V.; Sirota, N.P.; Gaziev, A.I.

    1996-01-01

    The effect of combined treatment of Cd and γ-irradiation on DNA damage and repair was studied in lymphoid tissues of mice using single-cell gel assay. Single i.p. injection of CdCl 2 (1 mg Cd/kg body wt), 2 h prior to irradiation resulted in increasing of DNA lesions in peripheral blood lymphocytes (PBL) when compared to non-injected animals. However, the same treatment, 48 h prior to irradiation is shown to decrease DNA damage in PBL and splenocytes in comparison with untreated mice. In thymocytes maximal protective effect of Cd was determined when mice were irradiated in 24 h after injection. The protective effect observed is due to decreasing of initial level of DNA damage in thymocytes as well as acceleration of DNA repair in PBL and splenocytes. 28 refs.; 2 figs

  4. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    OpenAIRE

    Borini, Paulo; Guimarães, Romeu Cardoso

    1999-01-01

    Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehy...

  5. Tissue Damage Caused by Myeloablative, but Not Non-Myeloablative, Conditioning before Allogeneic Stem Cell Transplantation Results in Dermal Macrophage Recruitment without Active T-Cell Interaction

    Directory of Open Access Journals (Sweden)

    Peter van Balen

    2018-02-01

    Full Text Available IntroductionConditioning regimens preceding allogeneic stem cell transplantation (alloSCT can cause tissue damage and acceleration of the development of graft-versus-host disease (GVHD. T-cell-depleted alloSCT with postponed donor lymphocyte infusion (DLI may reduce GVHD, because tissue injury can be restored at the time of DLI. In this study, we investigated the presence of tissue injury and inflammation in skin during the period of hematologic recovery and immune reconstitution after alloSCT.MethodsSkin biopsies were immunohistochemically stained for HLA class II, CD1a, CD11c, CD40, CD54, CD68, CD86, CD206, CD3, and CD8. HLA class II-expressing cells were characterized as activated T-cells, antigen-presenting cells (APCs, or tissue repairing macrophages. In sex-mismatched patient and donor couples, origin of cells was determined by multiplex analysis combining XY-FISH and fluorescent immunohistochemistry.ResultsNo inflammatory environment due to pretransplant conditioning was detected at the time of alloSCT, irrespective of the conditioning regimen. An increase in HLA class II-positive macrophages and CD3 T-cells was observed 12–24 weeks after myeloablative alloSCT, but these macrophages did not show signs of interaction with the co-localized T-cells. In contrast, during GVHD, an increase in HLA class II-expressing cells coinciding with T-cell interaction was observed, resulting in an overt inflammatory reaction with the presence of activated APC, activated donor T-cells, and localized upregulation of HLA class II expression on epidermal cells. In the absence of GVHD, patient derived macrophages were gradually replaced by donor-derived macrophages although patient-derived macrophages were detectable even 24 weeks after alloSCT.ConclusionConditioning regimens cause tissue damage in the skin, but this does not result in a local increase of activated APC. In contrast to the inflamed situation in GVHD, when interaction takes place between

  6. A Chronic Autoimmune Dry Eye Rat Model with Increase in Effector Memory T Cells in Eyeball Tissue.

    Science.gov (United States)

    Hou, Aihua; Bose, Tanima; Chandy, K George; Tong, Louis

    2017-06-07

    Dry eye disease is a very common condition that causes morbidity and healthcare burden and decreases the quality of life. There is a need for a suitable dry eye animal model to test novel therapeutics to treat autoimmune dry eye conditions. This protocol describes a chronic autoimmune dry eye rat model. Lewis rats were immunized with an emulsion containing lacrimal gland extract, ovalbumin, and complete Freund's adjuvant. A second immunization with the same antigens in incomplete Freund's adjuvant was administered two weeks later. These immunizations were administered subcutaneously at the base of the tail. To boost the immune response at the ocular surface and lacrimal glands, lacrimal gland extract and ovalbumin were injected into the forniceal subconjunctiva and lacrimal glands 6 weeks after the first immunization. The rats developed dry eye features, including reduced tear production, decreased tear stability, and increased corneal damage. Immune profiling by flow cytometry showed a preponderance of CD3 + effector memory T cells in the eyeball.

  7. 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

    2007-05-15

    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)

  8. 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

    2007-05-15

    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)

  9. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.

    Science.gov (United States)

    Wu, Shan; Ren, Jun

    2006-02-13

    Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg, i.p.). Fourteen days later, control and diabetic (fasting blood glucose >13.9 mM) mice received benfotiamine (100 mg/kg/day, i.p.) for 14 days. Oxidative stress and protein damage were evaluated by glutathione/glutathione disulfide (GSH/GSSG) assay and protein carbonyl formation, respectively. Pro-oxidative or pro-inflammatory factors including advanced glycation end-product (AGE), tissue factor and tumor necrosis factor-alpha (TNF-alpha) were evaluated by immunoblot analysis. Four weeks STZ treatment led to hyperglycemia, enhanced cerebral oxidative stress (reduced GSH/GSSG ratio), elevated TNF-alpha and AGE levels without changes in protein carbonyl or tissue factor. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

  10. Subepidermal moisture (SEM) and bioimpedance: a literature review of a novel method for early detection of pressure-induced tissue damage (pressure ulcers).

    Science.gov (United States)

    Moore, Zena; Patton, Declan; Rhodes, Shannon L; O'Connor, Tom

    2017-04-01

    Current detection of pressure ulcers relies on visual and tactile changes at the skin surface, but physiological changes below the skin precede surface changes and have a significant impact on tissue health. Inflammatory and apoptotic/necrotic changes in the epidermal and dermal layers of the skin, such as changes in interstitial fluid (also known as subepidermal moisture (SEM)), may precede surface changes by 3-10 days. Those same epidermal and subepidermal changes result in changes in the electrical properties (bioimpedance) of the tissue, thereby presenting an objective, non-invasive method for assessing tissue damage. Clinical studies of bioimpedance for the detection of pressure ulcers have demonstrated that changes in bioimpedance correlate with increasing severity of pressure ulcer stages. Studies have also demonstrated that at anatomical locations with pressure ulcers, bioimpedance varies with distance from the centre of the pressure ulcers. The SEM Scanner, a handheld medical device, offers an objective and reliable method for the assessment of local bioimpedance, and therefore, assessment of tissue damage before signs become visible to the unaided eye. This literature review summarises pressure ulcer pathophysiology, principles of bioimpedance and clinical research using bioimpedance technology to assess pressure ulcers. © 2016 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  11. Pathomorphological features of the skin and muscle tissue of experimental animals in the case of lifetime and postmortem damage

    Directory of Open Access Journals (Sweden)

    A. V. Kis

    2013-04-01

    Full Text Available The problem of forensic medical diagnosis of tissue injury is currently the subject of numerous investigations. Pathomorphological changes of the skin and muscle tissue of experimental animals, resulting in the case of lifetime and postmortem traumatic injuries, depending on the time and temperature, were revealed by the author. Data obtained by the author is very necessary for improving the forensic medical diagnosis of traumatic soft tissue injuries.

  12. The effect of chronic administration of ketoconazol on spermatogenesis indices and testis tissue in mice

    Directory of Open Access Journals (Sweden)

    S.E Safavi

    2009-02-01

    Full Text Available Ketoconazole, a broad spectrum antifungal agent has been employed widely in the treatment of fungal diseases. In addition to being antifungal, studies have indicated that this drug has an inhibitory effect on steroid hormone production including glucocorticoids and sex hormones and also its administration causes reduction in the amount of blood testosterone level and histologic changes in testicular tissue of laboratory animals. The aim of this study is to determine the effect of long term ketoconazole administration on spermatogenesis indices in testicular tissue of mice. In this experimental study 50 male mice were used which were allocated to 5 groups each containing 10 animals. The mice received a 50 mg/kg dose of ketoconazole daily for a period of 15 days, 1, 2 and 3 months orally. One group was used as the control and the other 4 groups received Ketoconazole, testicular tissue samples were collected at the end of the aforementioned time period, and after preparation of tissue sections and staining with hematoxylin and coin the spermiogenesis indices including tubular differentiation index (TDI, spermatogenesis index (SI and repopulation index (RI were studied. The results indicated that SI and RI decreased significantly (p

  13. Percutaneous window chamber method for chronic intravital microscopy of sensor-tissue interactions.

    Science.gov (United States)

    Koschwanez, Heidi E; Klitzman, Bruce; Reichert, W Monty

    2008-11-01

    A dorsal, two-sided skin-fold window chamber model was employed previously by Gough in glucose sensor research to characterize poorly understood physiological factors affecting sensor performance. We have extended this work by developing a percutaneous one-sided window chamber model for the rodent dorsum that offers both a larger subcutaneous area and a less restrictive tissue space than previous animal models. A surgical procedure for implanting a sensor into the subcutis beneath an acrylic window (15 mm diameter) is presented. Methods to quantify changes in the microvascular network and red blood cell perfusion around the sensors using noninvasive intravital microscopy and laser Doppler flowmetry are described. The feasibility of combining interstitial glucose monitoring from an implanted sensor with intravital fluorescence microscopy was explored using a bolus injection of fluorescein and dextrose to observe real-time mass transport of a small molecule at the sensor-tissue interface. The percutaneous window chamber provides an excellent model for assessing the influence of different sensor modifications, such as surface morphologies, on neovascularization using real-time monitoring of the microvascular network and tissue perfusion. However, the tissue response to an implanted sensor was variable, and some sensors migrated entirely out of the field of view and could not be observed adequately. A percutaneous optical window provides direct, real-time images of the development and dynamics of microvascular networks, microvessel patency, and fibrotic encapsulation at the tissue-sensor interface. Additionally, observing microvessels following combined bolus injections of a fluorescent dye and glucose in the local sensor environment demonstrated a valuable technique to visualize mass transport at the sensor surface.

  14. The role of Toll-like receptor 2 and 4 in gingival tissues of chronic periodontitis subjects with type 2 diabetes.

    Science.gov (United States)

    Promsudthi, A; Poomsawat, S; Limsricharoen, W

    2014-06-01

    Diabetes is one important risk factor of chronic periodontitis. However, the roles of toll-like receptor (TLR) 2 and TLR4, which are implicated in the inflammatory process in both chronic periodontitis and diabetes, have not been studied. This study aimed to determine whether TLR2 and TLR4 might be involved in the relationship between chronic periodontitis and diabetes by examining TLR2 and TLR4 expression in gingival tissues from subjects with chronic periodontitis without diabetes (CP) and with diabetes (CP+DM) and from periodontally healthy subjects without diabetes (PH) and with diabetes (PH+DM). Gingival tissues were collected from 23 CP subjects, 21 CP+DM subjects, 22 PH subjects and 20 PH+DM subjects. The expression of TLR2 and TLR4 in gingival tissues was determined using an immunohistochemical method. In gingival epithelium, staining patterns and intensity levels of TLR2 and TLR4 expression were studied. In connective tissues, the percentages of TLR2- and TLR4-positive cells were calculated. The intensity levels and the percentages of positive cells were statistically analyzed. Chronic periodontitis or diabetes showed no significant effect on TLR2 expression in the oral epithelium. However, diabetes increased the expression of TLR2 in sulcular epithelium and changed the pattern of TLR2 expression in gingival epithelium. Chronic periodontitis decreased the expression of TLR4 in gingival epithelium. In connective tissue under sulcular epithelium, CP+DM subjects showed statistically significant higher percentages of TLR2- and TLR4-positive cells compared with PH and PH+DM subjects. Our results suggest that hyperglycemia and chronic periodontitis had effects on TLR2 and TLR4 expression in gingival tissue. The differences in TLR2 and TLR4 expression could contribute to a greater inflammatory response, leading to periodontal disease initiation and progression. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

    Science.gov (United States)

    Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

    2017-06-01

    Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Cadmium accumulation and elimination in tissues of juvenile olive flounder, Paralichthys olivaceus after sub-chronic cadmium exposure

    International Nuclear Information System (INIS)

    Kim, Seong-Gil; Jee, Jung-Hoon; Kang, Ju-Chan

    2004-01-01

    Cd accumulation and elimination in tissue of olive flounder. - Experiments were carried out to investigate the accumulation and elimination of cadmium (Cd) in tissues (gill, intestine, kidney, liver and muscle) of juvenile olive flounder, Paralichthys olivaceus, exposed to sub-chronic concentrations (0, 10, 50, 100 μg l -1 ) of Cd. Cd exposure resulted in an increased Cd accumulation in tissues of flounder with exposure periods and concentration, and Cd accumulation in gill and liver increased linearly with the exposure time. At 20 days of Cd exposure, the order of Cd accumulation in organs was gill > intestine > liver > kidney > muscle and after 30 days of exposure, those were intestine > gill > liver > kidney > muscle. An inverse relationship was observed between the accumulation factor (AF) and the exposure level, but AF showed an increase with exposure time. During the depuration periods, Cd concentration in the gill, intestine and liver decreased immediately following the end of the exposure periods. No significant difference was found Cd in concentration in the kidney and muscle during depuration periods. The order of Cd elimination rate in organs were decreased intestine > liver > gill during depuration periods

  17. Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture

    Energy Technology Data Exchange (ETDEWEB)

    Romano, M.; Razandi, M.; Ivey, K.J. (Long Beach VA Medical Center, CA (USA))

    1990-04-01

    The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells.

  18. Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture

    International Nuclear Information System (INIS)

    Romano, M.; Razandi, M.; Ivey, K.J.

    1990-01-01

    The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells

  19. Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

    Directory of Open Access Journals (Sweden)

    Dota A

    2013-01-01

    Full Text Available Atsuyoshi Dota, Yuko Takaoka-Shichijo, Masatsugu NakamuraOphthalmic Research and Development Center, Santen Pharmaceutical Co, Ltd, Ikoma-shi, Nara, JapanPurpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.Keywords: gefarnate, fluorescein staining, rose bengal permeability, rabbit, cat, dry eye

  20. Hair cell counts in a rat model of sound damage: Effects of tissue preparation & identification of regions of hair cell loss.

    Science.gov (United States)

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

    2015-10-01

    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.

  1. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

    Science.gov (United States)

    Chen, Lin; Cao, Zhao-long; Han, Fang; Gao, Zhan-cheng; He, Quan-ying

    2010-02-20

    The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

  2. Prospective evaluation of bone and leukocyte scintigraphy for diagnosis of chronic osteomyelitis in patients with coexistent soft-tissue pathology

    International Nuclear Information System (INIS)

    Jacobson, A.F.; Harley, J.D.; Lipsky, B.A.; Pecoraro, R.E.

    1989-01-01

    This paper reports on a study involving twenty-four patients with soft-tissue infections or wounds and radiographic abnormalities in contiguous bones possibly representing osteomyelitis who underwent three-phase T c -99 m methylene diphosphonate (MDP) bone scanning, followed by In-111 leukocyte scintigraphy (22 patients) and bone biopsy (21 patients). Chronic osteomyelitis was confirmed in 12 patients by means of biopsy cultures and in one by means of histologic findings following amputation. Four patterns of leukocyte uptake in bone were identified: definitely increased, possibly increased, normal, and decreased. The prevalence of osteomyelitis for these four leukocyte scan patterns was as follows: 89% (eight of nine patients), 40% (two of five), 20% (one of five), and 67% (two of three), respectively. A definite increase in bone uptake of In-111-labeled leukocytes usually reflects osteomyelitis, but bone biopsy may be necessary to establish the diagnosis when other scan patterns are present

  3. Identification of a cytochrome P4502E1/Bid/C1q-dependent axis mediating inflammation in adipose tissue after chronic ethanol feeding to mice.

    Science.gov (United States)

    Sebastian, Becky M; Roychowdhury, Sanjoy; Tang, Hui; Hillian, Antoinette D; Feldstein, Ariel E; Stahl, Gregory L; Takahashi, Kazue; Nagy, Laura E

    2011-10-14

    Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.

  4. The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: A study in a rat model of moderate and relatively high human exposure

    International Nuclear Information System (INIS)

    Brzoska, Malgorzata M.; Rogalska, Joanna; Kupraszewicz, Elzbieta

    2011-01-01

    It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H 2 O 2 ), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H 2 O 2 and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.

  5. Collagenous sprue: Don't forget connective tissue in chronic diarrhea evaluation

    Directory of Open Access Journals (Sweden)

    Victoria Busto-Bea

    2013-03-01

    Full Text Available Collagenous sprue is a rare disease of the small bowel characterized by mucosal atrophy and excessive subepithelial collagen deposition. The etiology remains unclear and the diagnosis is based upon patient's clinical picture and anatomopathological findings. Clinically, collagenous sprue is characterized by persistent diarrhoea, severe malabsorption, multiple nutrient deficiencies and progressive weight loss. Differential diagnosis includes celiac disease, which is mandatory to rule out because of their frequent association. Gluten-free diet is the first therapeutic step, but it usually is not effective. However, recent studies show high success rates with immunomodulators, mainly corticosteroids. We report the case of a patient presenting with chronic diarrhea and severe malabsorption who was diagnosed with collagenous sprue, with no response to gluten free diet, but with excellent response to budesonida.

  6. Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B irradiation-induced skin damage in melanin-possessing hairless mice.

    Science.gov (United States)

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2009-12-01

    Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a dietary pigment and spice, and has been traditionally used for the treatment of inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese medicine. Although the topical application or oral administration of turmeric is used to improve skin trouble, there is no evidence to support this effect. The aim of this study was to clarify whether turmeric prevents chronic ultraviolet B (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on skin damage including changes in skin thickness and elasticity, pigmentation and wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin-possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily) prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. It also prevented the formation of wrinkles and melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and length of skin blood vessels and in the expression of matrix metalloproteinase-2 (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the inhibition of increases in MMP-2 expression caused by chronic irradiation.

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

    Science.gov (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

    2015-02-01

    '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.

  8. Nuclear medicine in the detection of radiation associated normal tissue damage of kidney, brain and salivary glands

    International Nuclear Information System (INIS)

    Liu Xiaomei; Li Dongxue; Pan Liping

    2005-01-01

    The radiation induced damage of kidney, brain and salivary glands is an important complicating disease after limit radiotherapy. The routine technology of nuclear medicine, such as tracing and imaging technique conduce to dose-effect calculations used in the planning of modern radiotherapy to three major organ systems and early detection of irradiation induced organ dysfunctions, as well as increased availability of radiotherapy. (authors)

  9. Effects of high repetition rate and beam size on hard tissue damage due to subpicosecond laser pulses

    International Nuclear Information System (INIS)

    Kim, Beop-Min; Feit, Michael D.; Rubenchik, Alexander M.; Joslin, Elizabeth J.; Eichler, Juergen; Stoller, Patrick C.; Da Silva, Luiz B.

    2000-01-01

    We report the effects of the repetition rate and the beam size on the threshold for ultrashort laser pulse induced damage in dentin. The observed results are explained as cumulative thermal effects. Our model is consistent with the experimental results and explains the dependence of the threshold on repetition rate, beam size, and exposure time. (c) 2000 American Institute of Physics

  10. In-vivo optical imaging of hsp70 expression to assess collateral tissue damage associated with infrared laser ablation of skin

    Science.gov (United States)

    Wilmink, Gerald J.; Opalenik, Susan R.; Beckham, Joshua T.; Mackanos, Mark A.; Nanney, Lillian B.; Contag, Christopher H.; Davidson, Jeffrey M.; Jansen, E. Duco

    2013-01-01

    Laser surgical ablation is achieved by selecting laser parameters that remove confined volumes of target tissue and cause minimal collateral damage. Previous studies have measured the effects of wavelength on ablation, but neglected to measure the cellular impact of ablation on cells outside the lethal zone. In this study, we use optical imaging in addition to conventional assessment techniques to evaluate lethal and sublethal collateral damage after ablative surgery with a free-electron laser (FEL). Heat shock protein (HSP) expression is used as a sensitive quantitative marker of sublethal damage in a transgenic mouse strain, with the hsp70 promoter driving luciferase and green fluorescent protein (GFP) expression (hsp70A1-L2G). To examine the wavelength dependence in the mid-IR, laser surgery is conducted on the hsp70A1-L2G mouse using wavelengths targeting water (OH stretch mode, 2.94 μm), protein (amide-II band, 6.45 μm), and both water and protein (amide-I band, 6.10 μm). For all wavelengths tested, the magnitude of hsp70 expression is dose-dependent and maximal 5 to 12 h after surgery. Tissues treated at 6.45 μm have approximately 4× higher hsp70 expression than 6.10 μm. Histology shows that under comparable fluences, tissue injury at the 2.94-μm wavelength was 2× and 3× deeper than 6.45 and 6.10 μm, respectively. The 6.10-μm wavelength generates the least amount of epidermal hyperplasia. Taken together, this data suggests that the 6.10-μm wavelength is a superior wavelength for laser ablation of skin. PMID:19021444

  11. Disruption of the ECM33 Gene in Candida albicans Prevents Biofilm Formation, Engineered Human Oral Mucosa Tissue Damage and Gingival Cell Necrosis/Apoptosis

    Directory of Open Access Journals (Sweden)

    Mahmoud Rouabhia

    2012-01-01

    Full Text Available In this study we demonstrated that ΔCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen. We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida.

  12. Chronic radiation effects on dental hard tissue (''radiation carries''). Classification and therapeutic strategies

    International Nuclear Information System (INIS)

    Groetz, K.A.; Brahm, R.; Al-Nawas, B.; Wagner, W.; Riesenbeck, D.; Willich, N.; Seegenschmiedt, M.H.

    2001-01-01

    Objectives: Since the first description of rapid destruction of dental hard tissues following head and neck radiotherapy 80 years ago, 'radiation caries' is an established clinical finding. The internationally accepted clinical evaluation score RTOG/EORTC however is lacking a classification of this frequent radiogenic alteration. Material and Methods: Medical records, data and images of radiation effects on the teeth of more than 1,500 patients, who underwent periradiotherapeutic care, were analyzed. Macroscopic alterations regarding the grade of late lesions of tooth crowns were used for a classification into 4 grades according to the RTOG/EORTC guidelines. Results: No early radiation effects were found by macroscopic inspection. In the first 90 days following radiotherapy 1/3 of the patients complained of reversible hypersensitivity, which may be related to a temporary hyperemia of the pulp. It was possible to classify radiation caries as a late radiation effect on a graded scale as known from RTOG/EORTC for other organ systems. This is a prerequisite for the integration of radiation caries into the international nomenclature of the RTOG/EORTC classification. Conclusions: The documentation of early radiation effects on dental hard tissues seems to be neglectable. On the other hand the documentation of late radiation effects has a high clinical impact. The identification of an initial lesion at the high-risk areas of the neck and incisal part of the tooth can lead to a successful therapy as a major prerequisite for orofacial rehabilitation. An internationally standardized documentation is a basis for the evaluation of the side effects of radiooncotic therapy as well as the effectiveness of protective and supportive procedures. (orig.) [de

  13. 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

    2014-11-01

    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.

  14. Ageing and chronic intermittent hypoxia mimicking sleep apnea do not modify local brain tissue stiffness in healthy mice.

    Science.gov (United States)

    Jorba, Ignasi; Menal, Maria José; Torres, Marta; Gozal, David; Piñol-Ripoll, Gerard; Colell, Anna; Montserrat, Josep M; Navajas, Daniel; Farré, Ramon; Almendros, Isaac

    2017-07-01

    Recent evidence suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer´s disease (AD), with the latter promoting alterations in brain tissue stiffness, a feature of ageing. Here, we assessed the effects of age and intermittent hypoxia (IH) on brain tissue stiffness in a mouse model of OSA. Two-month-old and 18-month-old mice (N=10 each) were subjected to IH (20% O 2 40s - 6% O 2 20s) for 8 weeks (6h/day). Corresponding control groups for each age were kept under normoxic conditions in room air (RA). After sacrifice, the brain was excised and 200-micron coronal slices were cut with a vibratome. Local stiffness of the cortex and hippocampus were assessed in brain slices placed in an Atomic Force Microscope. For both brain regions, the Young's modulus (E) in each animal was computed as the average values from 9 force-indentation curves. Cortex E mean (±SE) values were 442±122Pa (RA) and 455±120 (IH) for young mice and 433±44 (RA) and 405±101 (IH) for old mice. Hippocampal E values were 376±62 (RA) and 474±94 (IH) for young mice and 486±93 (RA) and 521±210 (IH) for old mice. For both cortex and hippocampus, 2-way ANOVA indicated no statistically significant effects of age or challenge (IH vs. RA) on E values. Thus, neither chronic IH mimicking OSA nor ageing up to late middle age appear to modify local brain tissue stiffness in otherwise healthy mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Select tissue mineral concentrations and chronic wasting disease status in mule deer from North-central Colorado.

    Science.gov (United States)

    Wolfe, Lisa L; Conner, Mary M; Bedwell, Cathy L; Lukacs, Paul M; Miller, Michael W

    2010-07-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (> or = 2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populations in north-central Colorado, United States, where CWD occurs naturally; we also measured copper concentrations in brain-stem (medulla oblongata at the obex) tissue from 181 of these deer. Analyses revealed a wide range of concentrations of all three minerals among sampled deer (copper: 5.6-331 ppm in liver, 1.5-31.9 ppm in obex; manganese: 0.1-21.4 ppm in liver; molybdenum: 0.5-4.0 ppm in liver). Bayesian multiple regression analysis revealed a negative association between obex copper (-0.097; 95% credible interval -0.192 to -0.006) and the probability of sampled deer also being infected with CWD, as well as a positive association between liver manganese (0.158; 95% credible interval 0.066 to 0.253) and probability of infection. We could not discern whether the tendencies toward lower brain-stem copper concentrations or higher systemic manganese concentrations in infected deer preceded prion infection or rather were the result of infection and its subsequent effects, although the distribution of trace mineral concentrations in infected deer seemed more suggestive of the latter.

  16. Aluminium and Gamma Irradiation Induced Oxidative Damage in Brain Tissue of Male Rats - Protective Role of Ferulic Acid

    International Nuclear Information System (INIS)

    Mansour, S.Z.; Hanafi, N.; Noaman, E.

    2011-01-01

    The current study was carried out to investigate the potential role of ferulic acid (FA) against Aluminium chloride (AlCl 3 ), γ- radiation either alone or combination induced oxidative stress in brain tissue of Wistar rats. The period of the experiment was eight weeks. Animals were administrated by aluminium chloride at a dose of 8.5 mg/kg/day and exposed to a single dose (4 Gy) of γ-radiation. FA was administered orally (50 mg/Kg body weight)/day. Histopathological observations and myeloid protein distribution were recorded in brain tissue. Induction of oxidative stress was recorded after all exposures. Brain tissue of AlCl 3 and γ- irradiation treatments either alone or combined revealed many altered changes and myeloid protein distribution. Also a decrease in serotonin concentration was recorded. An increase in Malonaldialdahyde (MDA) and acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue was recorded. Reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) in blood and brain showed a significant decrease. Treatment of AlCl 3 loaded animals by FA showed simple atrophy as shrunken morphology saw in amyotrophic lateral sclerosis and a decrease in myeloid protein deposition. FA treatment of AlCl 3 loaded or irradiated animals represented a significant increase in serotonin concentration and ameliorated affects on oxidative stress markers, acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue. In conclusion FA has a role in reducing the oxidative stress of AlCl 3 and γ- irradiation on brain tissue of rats

  17. Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions.

    Science.gov (United States)

    Yao, Y; Nguyen, T D; Pandya, S; Zhang, Y; Hurtado Rúa, S; Kovanlikaya, I; Kuceyeski, A; Liu, Z; Wang, Y; Gauthier, S A

    2018-02-01

    A hyperintense rim on susceptibility in chronic MS lesions is consistent with iron deposition, and the purpose of this study was to quantify iron-related myelin damage within these lesions as compared with those without rim. Forty-six patients had 2 longitudinal quantitative susceptibility mapping with automatic zero reference scans with a mean interval of 28.9 ± 11.4 months. Myelin water fraction mapping by using fast acquisition with spiral trajectory and T2 prep was obtained at the second time point to measure myelin damage. Mixed-effects models were used to assess lesion quantitative susceptibility mapping and myelin water fraction values. Quantitative susceptibility mapping scans were on average 6.8 parts per billion higher in 116 rim-positive lesions compared with 441 rim-negative lesions ( P quantitative susceptibility mapping values of both the rim and core regions ( P Quantitative susceptibility mapping scans and myelin water fraction in rim-positive lesions decreased from rim to core, which is consistent with rim iron deposition. Whole lesion myelin water fractions for rim-positive and rim-negative lesions were 0.055 ± 0.07 and 0.066 ± 0.04, respectively. In the mixed-effects model, rim-positive lesions had on average 0.01 lower myelin water fraction compared with rim-negative lesions ( P quantitative susceptibility mapping scan was negatively associated with follow-up myelin water fraction ( P Quantitative susceptibility mapping rim-positive lesions maintained a hyperintense rim, increased in susceptibility, and had more myelin damage compared with rim-negative lesions. Our results are consistent with the identification of chronic active MS lesions and may provide a target for therapeutic interventions to reduce myelin damage. © 2018 by American Journal of Neuroradiology.

  18. 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.

  19. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  20. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  1. The design of and chronic tissue response to a composite nerve electrode with patterned stiffness

    Science.gov (United States)

    Freeberg, M. J.; Stone, M. A.; Triolo, R. J.; Tyler, D. J.

    2017-06-01

    Objective. As neural interfaces demonstrate success in chronic applications, a novel class of reshaping electrodes with patterned regions of stiffness will enable application to a widening range of anatomical locations. Patterning stiff regions and flexible regions of the electrode enables nerve reshaping while accommodating anatomical constraints of various implant locations ranging from peripheral nerves to spinal and autonomic plexi. Approach. Introduced is a new composite electrode enabling patterning of regions of various electrode mechanical properties. The initial demonstration of the composite’s capability is the composite flat interface nerve electrode (C-FINE). The C-FINE is constructed from a sandwich of patterned PEEK within layers of pliable silicone. The shape of the PEEK provides a desired pattern of stiffness: stiff across the width of the nerve to reshape the nerve, but flexible along its length to allow for bending with the nerve. This is particularly important in anatomical locations near joints or organs, and in constrained compartments. We tested pressure and volume design constraints in vitro to verify that the C-FINE can attain a safe cuff-to-nerve ratio (CNR) without impeding intraneural blood flow. We measured nerve function as well as nerve and axonal morphology following 3 month implantation of the C-FINE without wires on feline peripheral nerves in anatomically constrained areas near mobile joints and major blood vessels in both the hind and fore limbs. Main Results. In vitro inflation tests showed effective CNRs (1.93  ±  0.06) that exceeded the industry safety standard of 1.5 at an internal pressure of 20 mmHg. This is less than the 30 mmHg shown to induce loss of conduction or compromise blood flow. Implanted cats showed no changes in physiology or electrophysiology. Behavioral signs were normal suggesting healthy nerves. Motor nerve conduction velocity and compound motor action potential did not change significantly

  2. Pathological features of liver tissue in autoantibody-positive chronic hepatitis C patients after plasmaphoresis

    Directory of Open Access Journals (Sweden)

    WU Huili

    2018-02-01

    Full Text Available ObjectiveTo investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients. MethodsA total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January 1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group. Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group(n=44 and autoantibody-negative group(n=76 of these patients. The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. ResultsOf all 120 CHC patients who underwent plasmaphoresis, 44 (36.7% were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%. Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (211±0.88 vs 164±0.88, t=2.349,P=0.021 and ductular reaction inside the portal area (1.86±0.71 vs 1.13±0.66, t=4.217,P<0.001, as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2=12.129,P=0.001. There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P>0.05. ConclusionAutoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

  3. Application of TMA (Tissue micro-array) in the observation of apoptotic cascade in postradiation damage in avian medicine

    International Nuclear Information System (INIS)

    Fridman, E.; Skarda, J.; Skardova, I.

    2006-01-01

    The study of apoptotic cascade by the use of relatively new technique in avian medicine: TMA may help in early detection and prevention of acquired immunodeficiency caused by the influence of a variety of pathogenic and non-pathogenic environmental factors, which may result in severe economical losses in conditions of intensive poultry farming. There has not been any report of applying this method in veterinary medicine. Tissue micro-array (TMA) technology allows rapid visualization of molecular targets in thousands of tissue specimens at a time, either at the DNA, RNA or protein level. The technique facilitates rapid translation of molecular discoveries to clinical applications. This technology has a number of advantages compared with conventional techniques: speed and high throughput, standardization and experimental uniformity, ease of use, all histochemical and molecular detection techniques can be used, decreased assay volume, preservation of original block, and conservation of valuable tissue etc. The aim of the present work were the study of immunosuppression and apoptotic cascade and possibilities of application of tissue micro-array in chicken in experimental condition and diagnostics in avian medicine in general. The selection of samples from avian primary immune organs: thymus and Bursa Fabric was done after gamma irradiation and infectious bursal virus infection (IBDV). (authors)

  4. 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

    2000-01-01

    .... 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...

  5. Tissue-specific Bio-accumulation of Metals in Fish during Chronic Waterborne and Dietary Exposures

    Directory of Open Access Journals (Sweden)

    M. Javed

    2012-10-01

    Full Text Available Juvenile (120-day three fish species viz. Catla catla, Labeo rohita and Cirrhina mrigala were exposed to chronic sub-lethal concentrations (1/3rd of LC50/LD50 of waterborne and dietary copper (Cu, cadmium (Cd, zinc (Zn, nickel (Ni and cobalt (Co, separately, in glass aquaria under constant water temperature (29oC, pH (7.5 and hardness (225 mgL-1 for 12 weeks. Waterborne and dietary exposures caused significantly variable accumulation of metals in three fish species that followed Zn>Ni>Cd>Co>Cu. Fish liver showed significantly higher tendency to accumulate Cu (69.64±25.35 µg g-1, Cd (68.93±21.65 µg g-1, Zn (91.46±29.53 µg g-1, Ni (74.64±18.61 µg g-1 and Co (22.65±20.56 µg g-1, followed by that of kidney and gills, with significant differences while muscle and bones exhibited significantly least tendency to accumulate all metals. Labeo rohita (31.63±2.43 µg g-1 and C. mrigala (31.43±13.70 µg g-1 exhibited significantly higher ability to amass metals than that of C. catla (27.96±10.28 µg g-1. Waterborne exposure caused significantly higher accumulation of metals in fish liver (72.69±27.91 µg g-1, followed by that in kidney, gills, skin, muscle, fins and bones with the average concentrations of 45.14±18.70, 39.47±21.13, 30.81±12.64, 22.65±17.34, 22.23±11.74 and 12.14±6.25 µg g-1, respectively. Dietary exposure resulted into significant escalation of metals in fish liver (58.23±32.44 µg g-1 while it was lowest in bones. Waterborne exposure caused significantly higher accumulation of all metals in fish body than that of dietary treatments.

  6. Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: Association with connective tissue disorder severity

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Pinn, Melva E.; Osborn, Thomas G.; Petersen, Ivy A.; Brown, Paul D.

    2008-01-01

    No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk

  7. 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

    2003-01-01

    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......)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis....

  8. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury.

    Science.gov (United States)

    Bosmann, Markus; Grailer, Jamison J; Ruemmler, Robert; Russkamp, Norman F; Zetoune, Firas S; Sarma, J Vidya; Standiford, Theodore J; Ward, Peter A

    2013-12-01

    We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of acute lung injury (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all models requiring availability of both C5a receptors (C5aR and C5L2) for full development of ALI. Ligation of C5aR and C5L2 with C5a triggered the appearance of histones (H3 and H4) in bronchoalveolar lavage fluid (BALF). BALF from humans with ALI contained H4 histone. Histones were absent in control BALF from healthy volunteers. In mice with ALI, in vivo neutralization of H4 with IgG antibody reduced the intensity of ALI. Neutrophil depletion in mice with ALI markedly reduced H4 presence in BALF and was highly protective. The direct lung damaging effects of extracellular histones were demonstrated by airway administration of histones into mice and rats (Sprague-Dawley), which resulted in ALI that was C5a receptor-independent, and associated with intense inflammation, PMN accumulation, damage/destruction of alveolar epithelial cells, together with release into lung of cytokines/chemokines. High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones.

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

    International Nuclear Information System (INIS)

    Cucinotta, Francis A

    2016-01-01

    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

  10. 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

    2014-10-02

    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

  11. 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)

    2016-09-01

    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

  12. Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

    Science.gov (United States)

    2011-07-01

    glucose , hematocrit (Hct), hemoglobin (Hb), sodium (Na+), potassium (K+), and ionized calcium (iCa2+) using i-STAT cartridges ( Abbott Laboratories...animals were observed for 200 minutes. Blood chemistry and physiological parameters were recorded. Tissue samples from lung and small intestine were...seemingly acceptable medical therapy and surgical intervention.4 The first physiologic response to severe blood loss is activation of the neuroendocrine

  13. Nicotine-induced damages in testicular tissue of rats; evidences for bcl-2, p53 and caspase-3 expression

    Directory of Open Access Journals (Sweden)

    Maryam Mosadegh

    2017-02-01

    Full Text Available Objective(s: Present study was performed in order to uncover new aspects for nicotine-induced damages on spermatogenesis cell lineage. Materials and Methods: For this purpose, 36 mature male Wistar rats were divided into three groups as; control-sham (0.2 ml, saline normal, IP, low dose (0.2 mg/kg BW-1, IP nicotine-received and high dose (0.4 mg/kg BW-1, IP nicotine-received groups. Following 7 weeks, the expression of bcl-2, p53 and caspase-3 at mRNA and protein levels were investigated by using reverse-transcriptase PCR (RT-PCR and immunohistochemical (IHC analyses, respectively. Moreover, the serum level of FSH, LH and testosterone were evaluated. Finally, the mRNA damage was analyzed by using special fluorescent staining. Results: Nicotine, at both dose levels, decreased tubular differentiation, spermiogenesis and repopulation indices and enhanced cellular depletion. Animals in nicotine-received groups exhibited a significant (P

  14. Efficacy and safety of extracorporeal shock wave therapy for acute and chronic soft tissue wounds: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Li; Fu, Xiao-Bing; Chen, Shuo; Zhao, Zhan-Bo; Schmitz, Christoph; Weng, Chang-Shui

    2018-04-19

    This study aimed to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and conventional wound therapy (CWT) for acute and chronic soft tissue wounds. All English-language articles on ESWT for acute and chronic soft tissue wounds indexed in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, Physiotherapy Evidence Database, and HealthSTAR published prior to June 2017 were included, as well as corresponding articles cited in reference lists of related review articles. The methodological quality of the selected studies was assessed with the Cochrane Collaboration's "risk of bias" tool. Study design, subject demographics, wound aetiology, treatment protocols, assessment indexes, and follow-up duration were extracted. The fixed or random-effects model was used to calculate the pooled effect sizes according to studies' heterogeneity. Ten randomised controlled trials (RCTs) involving 473 patients were included in this systematic review and meta-analysis. The meta-analysis showed that ESWT statistically significantly increased the healing rate of acute and chronic soft tissue wounds 2.73-fold (odds ratio, OR = 3.73, 95% confidence interval, CI: 2.30-6.04, P SMD) = 30.45; 95% CI: 23.79-37.12; P SMD = -2.86, 95% CI:-3.78 to -1.95, P SMD = -19.11, 95% CI: -23.74 to -14.47, P infection by 53% (OR = 0.47, 95% CI: 0.24-0.92, P = .03) when compared with CWT alone. Serious adverse effects were not reported. ESWT showed better therapeutic effects on acute and chronic soft tissue wounds compared with CWT alone. However, higher-quality and well-controlled RCTs are needed to further assess the role of ESWT for acute and chronic soft tissue wounds. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  15. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  16. Preliminary Study on the Kidney Elasticity Quantification in Patients With Chronic Kidney Disease Using Virtual Touch Tissue Quantification

    International Nuclear Information System (INIS)

    Zheng, Xiao Zhi; Yang, Bin; Fu, Ning Hua

    2015-01-01

    Virtual touch tissue quantification (VTTQ) provides numerical measurements (shear wave velocity (SWV) values) of tissue stiffness. The purpose of this study was to describe the SWV values of the kidney by VTTQ and to examine the clinical usefulness of this procedure in the evaluation of elasticity changes in the kidneys of patients with chronic kidney disease (CKD). Sixty-five patients with CKD and seventy healthy participants were included in this study. A total of 270 kidneys were examined by VTTQ. The kidney elasticity was expressed as shear wave velocity. The SWV values, blood serum creatinine (Scr)/BUN and pathological findings were analyzed and compared between patients with CKD and healthy participants. In patients with CKD and healthy participants, the SWV values both gradually decreased from the renal cortex to the medulla and renal sinus The SWV value of the renal cortex in patients with CKD was less than that of healthy participants (P < 0.05), and the SWV value of the renal cortex in patients with renal insufficiency was significantly less than in those with normal renal function (2.46 ± 0.15 vs. 3.45 ± 0.26 m/s, P < 0.05). The best cutoff value for predicting renal insufficiency (Scr > 1.24 mg/dL or/and BUN > 21 mg/DL) was a SWV value of the renal cortex of less than 1.92 m/s with a sensitivity of 84.4% (95% CI: 67.2-94.7%) and a specificity of 96.8% (95% CI: 83.3-99.9%) (P < 0.001). VTTQ can sensitively detect the elasticity changes in patients with CKD, and it can effectively predict renal insufficiency. This technology provides a valuable tool for the assessment of CKD

  17. 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.

  18. Sub-chronic exposure to EOMABRS leachate induces germinal epithelial cell lesions, sperm abnormalities and oxidative damage in rats

    Directory of Open Access Journals (Sweden)

    J.K. Akintunde

    2015-12-01

    Conclusion: The study concluded that possible mechanisms by which EOMABRSL at the investigated doses elicits spermatotoxicity could be linked to the testicular oxidative stress and damage to germinal epithelial cells by mixed-metal exposure. However, this may suggest possible reproductive health hazards in subjects with environmental or industrial exposure.

  19. Alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Nasole, E.; Di Donato, F.; Borghi, B.; Neužil, Jiří; Tomasetti, M.

    2005-01-01

    Roč. 333, č. 2 (2005), s. 404-410 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-lipoic acid * chronic wound * ROS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  20. Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

    Science.gov (United States)

    Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

  1. 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

    2015-01-01

    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.

  2. DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation.

    Science.gov (United States)

    Mamur, Sevcan; Unal, Fatma; Altok, Kadriye; Deger, Serpil Muge; Yuzbasioglu, Deniz

    2016-04-01

    The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect. Copyright © 2016. Published by Elsevier B.V.

  3. High-grain diet feeding altered the composition and functions of the rumen bacterial community and caused the damage to the laminar tissues of goats.

    Science.gov (United States)

    Zhang, R Y; Jin, W; Feng, P F; Liu, J H; Mao, S Y

    2018-03-19

    In the current intensive production system, ruminants are often fed high-grain (HG) diets. However, this feeding pattern often causes rumen metabolic disorders and may further trigger laminitis, the exact mechanism is not clear. This study investigated the effect of HG diet feeding on fermentative and microbial changes in the rumen and on the expression of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) in the lamellar tissue. In all, 12 male goats were fed a hay diet (0% grain; n=6) or an HG diet (56.5% grain; n=6). On day 50 of treatment, samples of blood, rumen content, and lamellar tissue of hooves of goats were collected. The data showed that compared with the hay group, HG-fed goats had lower (Pdiet feeding altered the composition of rumen bacterial community, and correspondingly, the results suggested that their functions in the HG group were also altered. HG diet feeding increased (Pbacterial community, and lead to higher levels of LPS in the peripheral blood, and further activated the inflammatory response in lamellar tissues, which may progress to the level of laminar damage.

  4. 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

    2016-10-01

    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.

  5. TP53 Staining in Tissue Samples of Chronic Lymphocytic Lymphoma Cases: An Immunohistochemical Survey of 51 Cases

    Directory of Open Access Journals (Sweden)

    İbrahim Kulaç

    2017-03-01

    Full Text Available Objective: Chronic lymphocytic leukemia (CLL is the most common lymphoproliferative disease in adults. The aim of this study is to find out if the extent of proliferation centers or the immunohistochemical expression of p53 is related to disease prognosis. Materials and Methods: In the scope of this study, 54 biopsy specimens from 51 patients (50 of lymph nodes; the others of spleen, tonsil, orbit, and liver diagnosed with CLL at the Hacettepe University Department of Pathology in 2000-2013 were reevaluated. The clinical and demographic data of the patients were obtained from our patient database. Biopsy samples were assessed semi-quantitatively for the percentage of proliferation center/total biopsy area (PC/TBA and an immunohistochemical study was performed on representative blocks of tissues for p53 expression. Results: When the patients were divided into two categories according to Rai stage as high and low (stages 0, 1, and 2 vs. stages 3 and 4, it was seen that patients with low Rai stage had a better prognosis than those with high stages (p=0.030. However, there was no statistically significant correlation between overall survival and PC/TBA ratio or p53 expression levels. Conclusion: In our cohort, PC/TBA ratio and immunopositivity of p53 did not show correlations with overall survival.

  6. Chronic dietary toxicity of zinc oxide nanoparticles in common carp (Cyprinus carpio L.): Tissue accumulation and physiological responses.

    Science.gov (United States)

    Chupani, Latifeh; Niksirat, Hamid; Velíšek, Josef; Stará, Alžběta; Hradilová, Šárka; Kolařík, Jan; Panáček, Aleš; Zusková, Eliška

    2018-01-01

    Concerns regarding the potential toxic effects of zinc oxide nanoparticles (ZnO NPs) on aquatic organisms are growing due to the fact that NPs may be released into aquatic ecosystems. This study aimed to investigate the effects of dietary exposure to ZnO NPs on juvenile common carp (Cyprinus carpio). Fish were fed a spiked diets at doses 50 and 500mg of ZnO NPs per kg of feed for 6 weeks followed by a 2-week recovery period. Fish were sampled every 2 weeks for haematology trends, blood biochemistry measures, histology analyses, and determination of the accumulation of zinc in tissues. At the end of the exposure and post-exposure periods, fish were sampled for an assessment of lipid peroxidation levels. Dietborne ZnO NPs had no effects on haematology, blood biochemistry, and lipid peroxidation levels during the exposure period. After the recovery period, aspartate aminotransferase activity significantly (p < 0.05) increased and alanine transferase activity significantly (p < 0.05) decreased in the higher exposure group. The level of lipid peroxidation significantly (p < 0.05) decreased in liver of treated fish after 2 weeks post-exposure period. A histological examination revealed mild histopathological changes in kidneys during exposure. Our results did not show a significant increase of zinc content at the end of experiment in any of tested organs. However, chronic dietary exposure to ZnO NPs might affect kidney and liver function. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The role of pyrimidine and water as underlying molecular constituents for describing radiation damage in living tissue: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, M. C.; Ellis-Gibbings, L. [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Jones, D. B. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Brunger, M. J. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia); Blanco, F. [Departamento de Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid (Spain); Muñoz, A. [Centro de Investigaciones Energéticas Medioambientales y Tecnológicas, Avenida Complutense 22, 28040 Madrid (Spain); Limão-Vieira, P. [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Laboratório de Colisões Atómicas e Moleculares, CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); García, G., E-mail: g.garcia@csic.es [Instituto de Física Fundamental, Consejo Superior de Investigaciones Científicas (CSIC), Serrano 113-bis, 28006 Madrid (Spain); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2015-06-07

    Water is often used as the medium for characterizing the effects of radiation on living tissue. However, in this study, charged-particle track simulations are employed to quantify the induced physicochemical and potential biological implications when a primary ionising particle with energy 10 keV strikes a medium made up entirely of water or pyrimidine. Note that pyrimidine was chosen as the DNA/RNA bases cytosine, thymine, and uracil can be considered pyrimidine derivatives. This study aims to assess the influence of the choice of medium on the charged-particle transport, and identify how appropriate it is to use water as the default medium to describe the effects of ionising radiation on living tissue. Based on the respective electron interaction cross sections, we provide a model, which allows the study of radiation effects not only in terms of energy deposition (absorbed dose and stopping power) but also in terms of the number of induced molecular processes. Results of these parameters for water and pyrimidine are presented and compared.

  8. Effect of Kombucha, a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats.

    Science.gov (United States)

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

    2013-10-01

    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.

  9. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG): A biomarker of oxidative damage in yellow bullheads chronically exposed to low-level radiation

    International Nuclear Information System (INIS)

    McCreedy, C.D.; Glickman, L.T.

    1995-01-01

    8-hydroxy-2'-deoxyguanosine (8-OH-dG), an oxidation product of the nucleotide deoxyguanosine (dG) was used as a biomarker to assess oxidative damage in brain and gill tissues of yellow bullhead catfish (Ameiurus natalis; n = 18) inhabiting an abandoned reactor reservoir contaminated with low levels of d137 Cs (Pond B, Savannah River Site, SC). DNA was isolated by chloroform-isoamyl extraction, enzymatically digested with Nuclease P1/Calf Intestinal Phosphatase, and analyzed by HPLC with electrochemical detection.Length, weight, age, condition and muscle 137 Cs activity of each fish were also determined. Concentrations of 8-OH-dG were greater in brain than in gill tissues. 8-OH-dG in gill tissues decreased as condition of fish increased, but as age increased, the effect of condition declined. Brain 8-OH-dG concentration was not related to age or condition of fish, but was greater in females and the interaction between gender and 137 Cs was significant. Brain 8-OH-dG was positively associated with muscle 137 Cs concentration among females, but was unrelated to 137 Cs concentration in males. At lower 137 Cs concentrations, females tended to have fewer oxidative DNA adducts in brian than did males. Deposition of somatic lipids into eggs may provide females some anti-oxidant benefit by diminishing the contribution of lipid peroxidation to DNA damage. 8-OH-dG is a sensitive biomarker of low-level radiation exposure, however, its application in fish requires consideration of factors such as gender, age, body-condition, and the tissue type sampled

  10. Modern views on the pathogenesis of hard dental tissues and periodontium lesions and means of their treatment in children with chronic diseases of the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Krupey V.Y.

    2014-09-01

    Full Text Available Changes in the mouth covity often reflect regularities of pathogenesis of a number of disease states, and primarily from the digestive tract. Therefore, the purpose of the study was to clarify pathogenesis of certain lesions of hard dental tissues and periodontal tissues in children with chronic diseases of the gastrointestinal tract and development of schemes for their treatment. The study observed 441 children aged from 7 to 15 years with dental caries and generalized chronic catarrhal gingivitis on the background of chronic gastritis and duodenitis, duodenal ulcer and malabsorption syndrome. All the children were divided into 2 groups - basic and comparison one. The study identified the most dan¬gerous and little-known way of pathogenesis, which passes through the general processes of reducing the production of various proteins (immune system and antiseptics, is a violation of the general and local resistance and, ultimately, mineral metabolism. Such disorders impair complete mineralization of tooth enamel, reduce optimal composition and properties of saliva stimulating glycolysis processes in oral cavity. Prevention of dental caries and generalized chronic catarrhal gingivitis in children with chronic pathology of the gastrointestinal tract is based on the use of developed therapeutic and prophylactic complex, which includes mucosal gel Kvertulin, probiotic Latsidofil and drug Calcium D.

  11. Changes of lipoperoxidation and antioxidant system in pariodontal tissues in experimental bronchial asthma under conditions of chronic periodonitis and correction of these changes with thiotriazoline

    Directory of Open Access Journals (Sweden)

    Mykhailo Reheda

    2018-04-01

    Full Text Available We have analyzed the results of the research of changes in indices of lipid peroxidation (conjugated dienes and malondialdehide and antioxidant (superoxide dismutase, catalase, ceruloplasmin systems in guinea pigs’ periodontal soft tissues in experimental bronchial asthma in the dynamics of asthma under conditions of chronic periodontitis and correction of these changes with thiotriazoline. The research was conducted on 50 male guinea pigs weighting 250-270 g, divided into 5 groups: I – intact guinea pigs (n=10, II – guinea pigs (n=10 with asthma under conditions of chronic periodontitis before correction (4th day, III - guinea pigs (n=10 with asthma under conditions of chronic periodontitis before correction (18th day, IV - guinea pigs (n=10 with asthma under conditions of chronic periodontitis before correction (25 th day, V - guinea pigs (n=10 with asthma under conditions of chronic periodontitis after correction (25th day. The results of experimental studies showed the significant increase of conjugated dienes and malondialdehide levels in animal’s periodontal soft tissues at all observed stages of asthma development under conditions of chronic periodontitis before the correction as compared with control group. Intensive synthesis of LPO’s products caused increase on 4th day with further decrease on 18th and 25th days of activity levels of superoxide dismutase, catalase and ceruloplasmin in animal’s periodontal soft tissues before the correction as compared with indices of the control group. After correction with thiotriazoline the the results showed decrease of indices of LPO and increase of activity levels of antioxidant enzymes.

  12. The evaluation of HRCT in the diagnosis of chronic otitis and mastoiditis

    International Nuclear Information System (INIS)

    Tang Yong; Zhao Jun; Liu Fangying; Zhang Xuelin

    2005-01-01

    Objective: To explore the value of' HRCT in the diagnosis of chronic otitis and mastoiditis. Method: Thirty-five patients with chronic otitis and mastoiditis received high resolution CT scan (HRCT). Results: (1) In cases of cholesteatoma, the mass was seen in tympanic sinus and the tympanum area; where the positive rate of' drum damage was 92% and most of the damage of substantia ossea involved the adjacent tissue. The positive rate of the disappearance, damage and cirrhosis of otosteon was 94% in patients with granuloma-type mastoiditis. The damage of eardrum wall was revealed in 15% cases of granuloma-type, in which ossicular chain was revealed wrapped with granulation tissue. The damage of ossicular chain was 23% in cases of granuloma-type. In cases of simple type, the damage of eardrum wall and the substantia ossea adjacent the ossicular chain was rare, and there was no mass. Conclusions: The HRCT is useful in the diagnosis of chronic mastoiditis. (authors)

  13. Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

    Science.gov (United States)

    Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

    2016-12-01

    Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

  14. Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

    Directory of Open Access Journals (Sweden)

    Fernando B. R. da Silva

    2018-05-01

    Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

  15. Accumulation of free oligosaccharides and tissue damage in cytosolic α-mannosidase (Man2c1)-deficient mice.

    Science.gov (United States)

    Paciotti, Silvia; Persichetti, Emanuele; Klein, Katharina; Tasegian, Anna; Duvet, Sandrine; Hartmann, Dieter; Gieselmann, Volkmar; Beccari, Tommaso

    2014-04-04

    Free Man(7-9)GlcNAc2 is released during the biosynthesis pathway of N-linked glycans or from misfolded glycoproteins during the endoplasmic reticulum-associated degradation process and are reduced to Man5GlcNAc in the cytosol. In this form, free oligosaccharides can be transferred into the lysosomes to be degraded completely. α-Mannosidase (MAN2C1) is the enzyme responsible for the partial demannosylation occurring in the cytosol. It has been demonstrated that the inhibition of MAN2C1 expression induces accumulation of Man(8-9)GlcNAc oligosaccharides and apoptosis in vitro. We investigated the consequences caused by the lack of cytosolic α-mannosidase activity in vivo by the generation of Man2c1-deficient mice. Increased amounts of Man(8-9)GlcNAc oligosaccharides were recognized in all analyzed KO tissues. Histological analysis of the CNS revealed neuronal and glial degeneration with formation of multiple vacuoles in deep neocortical layers and major telencephalic white matter tracts. Enterocytes of the small intestine accumulate mannose-containing saccharides and glycogen particles in their apical cytoplasm as well as large clear vacuoles in retronuclear position. Liver tissue is characterized by groups of hepatocytes with increased content of mannosyl compounds and glycogen, some of them undergoing degeneration by hydropic swelling. In addition, lectin screening showed the presence of mannose-containing saccharides in the epithelium of proximal kidney tubules, whereas scattered glomeruli appeared collapsed or featured signs of fibrosis along Bowman's capsule. Except for a moderate enrichment of mannosyl compounds and glycogen, heterozygous mice were normal, arguing against possible toxic effects of truncated Man2c1. These findings confirm the key role played by Man2c1 in the catabolism of free oligosaccharides.

  16. Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

    Science.gov (United States)

    Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

    2016-11-01

    This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A Mechanobiological model for damage-induced growth in arterial tissue with application to in-stent restenosis

    Science.gov (United States)

    Fereidoonnezhad, B.; Naghdabadi, R.; Sohrabpour, S.; Holzapfel, G. A.

    In-stent restenosis (ISR) is one of the main drawbacks of stent implementation which limits the long-term success of the procedure. Morphological changes occurring within the arterial wall due to stent-induced mechanical injury are a major cause for activation of vascular smooth muscle cells (VSMCs), and the subsequent development of ISR. Considering the theory of volumetric mass growth and adopting a multiplicative decomposition of the deformation gradient into an elastic part and a growth part, we present a mechanobiological model for ISR. An evolution equation is developed for mass growth of the neointima, in which the activation of VSMCs due to stent-induced damage (injury) and the proliferation rate of the activated cells are considered. By introducing the mass evolution into the mass balance equation, we obtain the evolution of the growth tensor over time. The model is implemented in a finite element code and the procedure of angioplasty is simulated, whereby the features of the proposed growth model are illustrated.

  18. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    International Nuclear Information System (INIS)

    Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

    2004-01-01

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16 INKa and DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16 INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

  19. [Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models].

    Science.gov (United States)

    Li, X Y; Zhang, X J; Zhao, J H; Xu, J Y

    2016-12-12

    Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months.Then the rats were sacrificed and the serum and lung tissue were prepared. The levels of 4-HNE, Trx and TrxR in peripheral blood were quantitatively analyzed by enzyme-linked immunosorbent assay(ELISA), and the activities of Trx and TrxR were measured by chemical methods. Results: Compared with the normal group, the lung tissue had more apparent emphysema in the emaciation and the fat groups under light microscope, and more inflammatory cell infiltration in alveolar septum was observed in the fat group.The levels of 4-HNE in the fat group[(24.7±8.7)mg/L]was significantly higher than that in the normal group[(15.4±4.7)mg/L, P 0.05)in the levels of 4-HNE between the emaciation and the normal groups. The levels of TrxR in the emaciation group[(7.7±1.4)μg/ml]was significantly higher than that in the normal and the fat groups[(6.2±1.1), (4.9±1.4)μg/ml, all P 0.05). The activity of Trx in the emaciation group[(32.4±8.5)×10 -3 A ·min -1 ·mg -1 ]was significantly higher than that in the normal group[(19.6±3.3)×10 -3 A ·min -1 ·mg -1 ]and the fat group[(11.3±7.5)×10 -3 A ·min -1 ·mg -1 , all P 0.05). Conclusion: Both high BMI and low BMI can affect the oxidative stress of the body, resulting in increased oxidants and decreased antioxidants, and can cause damage to the lung tissue in the rat models.

  20. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  1. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-05-01

    Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

  2. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P.R. Vivek, E-mail: prvkumar06@gmail.com [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Seshadri, M. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Jaikrishan, G. [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Das, Birajalaxmi [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2015-05-15

    Highlights: • Effect of chronic low dose natural radiation in radio adaptive response studied. • PBMCs of subjects from NLNRA and HLNRA were challenged with gamma radiation. • DNA damage and repair in PBMCs was compared using the alkaline comet assay. • Significant reduction in DNA damage in subjects of high dose group from HLNRA noted. • Probable induction of an in vivo radio adaptive response in subjects from HLNRA. - Abstract: This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year{sup −1}), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N = 43, range 1.07 mSv year{sup −1} to 5.55 mSv year{sup −1}) and 9.62 mSv (N = 34, range 6.07 mSv year{sup −1} to17.41 mSv year{sup −1}), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P = 0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from

  3. Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

    Science.gov (United States)

    Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

    2016-01-01

    Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

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

    Science.gov (United States)

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

    2014-06-01

    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.

  5. Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

    Science.gov (United States)

    Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

    2015-07-09

    Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

  6. Radiation-induced brain damage in children; Histological analysis of sequential tissue changes in 34 autopsy cases

    Energy Technology Data Exchange (ETDEWEB)

    Oi, Shizuo; Kokunai, Takashi; Ijichi, Akihiro; Matsumoto, Satoshi [Kobe Univ. (Japan). School of Medicine; Raimondi, A J

    1990-01-01

    The nature and sequence of the radiation-induced changes in the brain were studied postmortem in 34 children with glioma, 22 of whom underwent central nervous system radiation therapy. Twenty received whole-brain or whole-neuroaxis radiation at a total mean dosage of 4063 cGy. Brain tissue alternations were analyzed histologically by means of various staining methods, including immunohistochemical techniques. The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. The results of this study suggest that the immature brain may be more sensitive to radiation than is the adult brain, and that the manifestations of radiation-induced injury depend on the time elapsed after irradiation. (author).

  7. Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, I

    1975-03-01

    Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

  8. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    International Nuclear Information System (INIS)

    Hamdy, Nadia; El-Demerdash, Ebtehal

    2012-01-01

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  9. Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice

    Directory of Open Access Journals (Sweden)

    Isabela Finamor

    2017-04-01

    Full Text Available No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC. Chronic administration of aspartame increased plasma alanine aminotransferase (ALT and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH, oxidized glutathione (GSSG, γ-glutamylcysteine ​​(γ-GC, and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM, and S-adenosylhomocysteine ​​(SAH. Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway.

  10. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    Energy Technology Data Exchange (ETDEWEB)

    Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  11. Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice.

    Science.gov (United States)

    Finamor, Isabela; Pérez, Salvador; Bressan, Caroline A; Brenner, Carlos E; Rius-Pérez, Sergio; Brittes, Patricia C; Cheiran, Gabriele; Rocha, Maria I; da Veiga, Marcelo; Sastre, Juan; Pavanato, Maria A

    2017-04-01

    No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine ​​(γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine ​​(SAH). Aspartame also triggered a decrease in mRNA and protein levels of the catalytic subunit of glutamate cysteine ligase (GCLc) and cystathionine γ-lyase, and in protein levels of methionine adenosyltransferase 1A and 2A. N-acetylcysteine prevented the aspartame-induced liver injury and the increase in plasma ALT activity as well as the decrease in GSH, γ-GC, cysteine, SAM and SAH levels and GCLc protein levels. In conclusion, chronic administration of aspartame caused marked hepatic GSH depletion, which should be ascribed to GCLc down-regulation and decreased cysteine levels. Aspartame triggered blockade of the trans-sulphuration pathway at two steps, cystathionine γ-lyase and methionine adenosyltransferases. NAC restored glutathione levels as well as the impairment of the trans-sulphuration pathway. Copyright © 2017. Published by Elsevier B.V.

  12. Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

    Directory of Open Access Journals (Sweden)

    Bestami Dalkilic

    2017-01-01

    Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

  13. Chronic restraint stress in rats causes sustained increase in urinary corticosterone excretion without affecting cerebral or systemic oxidatively generated DNA/RNA damage

    DEFF Research Database (Denmark)

    Jorgensen, Anders; Maigaard, Katrine; Wörtwein, Gitta

    2013-01-01

    acids, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, in rats subjected to chronic restraint stress. To reliably collect 24h urine samples, the full 3-week restraint stress paradigm was performed in metabolism cages. We further determined frontal...... and Tnf). The metabolism cage housing in itself did not significantly influence a range of biological stress markers. In the restraint stress group, there was a sustained 2.5 fold increase in 24h corticosterone excretion from day 2 after stress initiation. However, neither whole-body nor cerebral measures......Increased oxidatively generated damage to nucleic acids (DNA/RNA) may be a common mechanism underlying accelerated aging in psychological stress states and mental disorders. In the present study, we measured the urinary excretion of corticosterone and markers of systemic oxidative stress on nucleic...

  14. Machine-learning-based classification of real-time tissue elastography for hepatic fibrosis in patients with chronic hepatitis B.

    Science.gov (United States)

    Chen, Yang; Luo, Yan; Huang, Wei; Hu, Die; Zheng, Rong-Qin; Cong, Shu-Zhen; Meng, Fan-Kun; Yang, Hong; Lin, Hong-Jun; Sun, Yan; Wang, Xiu-Yan; Wu, Tao; Ren, Jie; Pei, Shu-Fang; Zheng, Ying; He, Yun; Hu, Yu; Yang, Na; Yan, Hongmei

    2017-10-01

    Hepatic fibrosis is a common middle stage of the pathological processes of chronic liver diseases. Clinical intervention during the early stages of hepatic fibrosis can slow the development of liver cirrhosis and reduce the risk of developing liver cancer. Performing a liver biopsy, the gold standard for viral liver disease management, has drawbacks such as invasiveness and a relatively high sampling error rate. Real-time tissue elastography (RTE), one of the most recently developed technologies, might be promising imaging technology because it is both noninvasive and provides accurate assessments of hepatic fibrosis. However, determining the stage of liver fibrosis from RTE images in a clinic is a challenging task. In this study, in contrast to the previous liver fibrosis index (LFI) method, which predicts the stage of diagnosis using RTE images and multiple regression analysis, we employed four classical classifiers (i.e., Support Vector Machine, Naïve Bayes, Random Forest and K-Nearest Neighbor) to build a decision-support system to improve the hepatitis B stage diagnosis performance. Eleven RTE image features were obtained from 513 subjects who underwent liver biopsies in this multicenter collaborative research. The experimental results showed that the adopted classifiers significantly outperformed the LFI method and that the Random Forest(RF) classifier provided the highest average accuracy among the four machine algorithms. This result suggests that sophisticated machine-learning methods can be powerful tools for evaluating the stage of hepatic fibrosis and show promise for clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Wen-Ting Jiang

    2015-01-01

    Full Text Available Background: It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease (COPD. The underlying mechanism of development remains uncertain so far. Nitric oxide (NO has been found to be closely associated with the pathogenesis of COPD, the alteration of NO synthase (NOS expression need to be revealed. The study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD, which might be helpful for identifying the susceptibility of smokers developing into COPD. Methods: Peripheral lung tissues were obtained from 10 nonsmoker control subjects, 15 non-COPD smokers, and 15 smokers with COPD. Neuronal NOS (nNOS, inducible NOS (iNOS, and endothelial NOS (eNOS mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Western blotting. Results: INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function (P < 0.001, P = 0.001, respectively. iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function (P < 0.01 and P = 0.01, respectively. However, expressions of nNOS and eNOS did not differ among nonsmokers, smokers with and without COPD. Furthermore, there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s (FEV 1 (% predicted (r = −0.549, P = 0.001 and FEV 1 /forced vital capacity (%, r = −0.535, P = 0.001. Conclusions: The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without COPD. The results suggest that iNOS might be involved in the pathogenesis of COPD, and may be a potential marker to identify the smokers who have more liability to suffer COPD.

  16. Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue.

    Science.gov (United States)

    Koban, Michael; Swinson, Kevin L

    2005-07-01

    A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing approximately 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.

  17. Reduced systolic performance by tissue Doppler in patients with preserved and abnormal ejection fraction: new insights in chronic heart failure.

    Science.gov (United States)

    García, Edgar H; Perna, Eduardo R; Farías, Eduardo F; Obregón, Ricardo O; Macin, Stella M; Parras, Jorge I; Agüero, Marcelo A; Moratorio, Diego A; Pitzus, Ariel E; Tassano, Eduardo A; Rodriguez, Leonardo

    2006-04-04

    Tissue Doppler imaging (TDI) is useful in the evaluation of systolic and diastolic function. It allows assessment of ventricular dynamics in its longitudinal axis. We sought to investigate the difference in systolic and diastolic longitudinal function in patients with chronic heart failure (CHF) with normal and reduced ejection fraction. One hundred ten outpatients with CHF and 68 controls were included. Ejection fraction (EF) was obtained and longitudinal systolic (S) and diastolic (E' and A') wall velocities were recorded from basal septum. Group A (controls) were normal and CHF patients were classified by EF in Group B1: > 45% and B2: < or = 45%. In A, B1 and B2 the mean S peak was 7.74; 5.45 and 4.89 cm/s (p<0.001); the mean E' peak was 8.56; 5.72 and 6.1 cm/s (p<0.001); and the mean A' peak was 10.2; 7.3 and 5.3 cm/s (p<0.001). Also, isovolumic contraction and relaxation time were different among control and CHF groups, (both p<0.001). The most useful parameters for identifying diastolic CHF were IVRT and S peak, with area under ROC curves of 0.93 and 0.89. The cut-off of 115 ms for IVRT and 5.8 cm/s for S peak showed a sensitivity of 94 and 97%, with a specificity of 82 and 73%, respectively. These findings suggest that impairment of left ventricular systolic function is present even in those with diastolic heart failure, and that abnormalities may have an important role to identifying the condition.

  18. Diagnostic value of real-time tissue elastography for liver fibrosis in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    ZHANG Guosheng

    2014-07-01

    Full Text Available ObjectiveTo investigate the diagnostic value of real-time tissue elastography (RTE in evaluating liver fibrosis in patients with chronic hepatitis B (CHB. MethodsEighty-six patients with CHB, who visited Beijing Tiantan Hospital and Beijing You′an Hospital from March to August, 2013, were grouped according to the pathological stages of liver fibrosis. They were examined by RTE, biochemical tests, and liver biopsy. Then, liver fibrosis index (LFI and aspartate aminotransferase-to-platelet ratio index (APRI were calculated. Comparison between groups was made by one-way analysis of variance, followed by LSD t-test for multiple comparisons. The correlation between LFI and pathological stage of liver fibrosis was analyzed by Spearman correlation test. The sensitivity and specificity of LFI for the diagnosis of liver fibrosis were calculated. Regarding S≥2 (significant liver fibrosis and S≥4 (early liver cirrhosis as the positive standards, the receiver operating characteristic (ROC curve was drawn and compared with APRI. ResultsLFI differed significantly across the groups (P=0.000, except the comparison between S0 and S1 (P=0.298. LFI was significantly correlated with pathological stage (r=0.831, P<0.001. The areas under the ROC curve of LFI in diagnosing significant liver fibrosis and early liver cirrhosis were 0873 (P<0.001 and 0.923 (P=0002, respectively; the diagnostic thresholds were 2.74 and 3.61, respectively; the sensitivity and specificity were 0.766/0.872 and 0.833/0.878, respectively. LFI was significantly superior to APRI. ConclusionRTE has high diagnostic values for significant liver fibrosis and early liver cirrhosis and is an important noninvasive diagnostic method for liver fibrosis in patients with CHB.

  19. Spinal cord injury after blunt cervical spine trauma: correlation of soft-tissue damage and extension of lesion.

    Science.gov (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

    2014-05-01

    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

  20. Pretreatment with AQP4 and NKCC1 Inhibitors Concurrently Attenuated Spinal Cord Edema and Tissue Damage after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Yan, Xiaodong; Liu, Juanfang; Wang, Xiji; Li, Wenhao; Chen, Jingyuan; Sun, Honghui

    2018-01-01

    Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na + -K + -Cl - cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.

  1. Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Christine Breynaert

    Full Text Available INTRODUCTION: Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS ingestion, to mimic the relapsing nature of the human disease. MATERIALS AND METHODS: C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total. Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. RESULTS: Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. CONCLUSIONS: Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of

  2. The metabolism of 32P-CP-PLLA seed implanted in the liver and its damage to the normal liver tissue: a study in the experimental dogs

    International Nuclear Information System (INIS)

    Tan Zhongbao; Liu Lu; Guo Jinhe; Zhu Guangyu; Wang Fuan; Nie Qi; Gao Hailin; Teng Gaojun

    2010-01-01

    Objective: To investigate the effects of intratumoral implantation of 32 P -CP-PLLA seeds on the normal canine liver tissue and to explore the metabolism of 32 P-CP-PLLA seeds implanted in the liver of experimental dogs. Methods: Twelve beagles were enrolled in this study. The dogs were randomly and equally divided into four groups: group A (185 MBq), group B (370 MBq), group C (740 MBq) and group D (0 MBq). By using laparotomy procedure 32 P-CP-PLLA seeds were implanted into dog's liver. CT scan was performed before operation as well as before the dog was sacrificed. All dogs were sacrificed three months after the implantation. Before the procedure and 1, 2, 4, 8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted. One dog from group B and group C was selected respectively and was fed in a metabolic cage. Within one month after the procedure the cpm in feces and in urine was determined every 24 hours. One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1, 2, 4, 8 and 12 weeks after the implantation, and SPECT imaging was also performed at the same time. Pathologic study, both macroscopic and microscopic (including optical and electronic microscopy) was made to observe the liver damage after the dog was sacrificed. The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean ± standard deviation (x ± s). Results: Two months after the procedure, serological examination found that the serum alkaline phosphatase (BKP) in both group B and group C was significantly higher than that in other groups, the difference was statistically significant (P 32 P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally. Conclusion: The implantation of 32 P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general

  3. 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)

    1996-09-01

    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.

  4. DNA damage induced in mouse tissues by organic wood preserving waste extracts as assayed by 32P-postlabeling

    International Nuclear Information System (INIS)

    Randerath, E.; Zhou, G.D.; Donnelly, K.C.; Safe, S.H.; Randerath, K.

    1996-01-01

    In the present study, a mouse bioassay was used in combination with 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 6 DNA nucleotides in skin (both extracts) and one adduct in 3.2 x 10 7 or 1.2 x 10 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 32 P-labeled derivative of the reaction product of