24 results on '"Necrosis physiopathology"'
Search Results
2. A rare and threatening complication in a cirrhotic patient.
- Author
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Carvalho E Branco J, Anapaz V, Santos L, and Reis J
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- Aged, Antihypertensive Agents therapeutic use, Foot physiopathology, Humans, Liver Cirrhosis physiopathology, Male, Necrosis physiopathology, Terlipressin therapeutic use, Foot blood supply, Liver Cirrhosis complications, Necrosis etiology
- Published
- 2018
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3. Utility of PET scan in diagnosis and monitoring descending necrotizing mediastinitis complicating Lemierre's syndrome.
- Author
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Carandini T, Longari V, Mendogni P, Gaffuri M, and Ceriani E
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- Aged, Female, Humans, Necrosis physiopathology, Lemierre Syndrome complications, Mediastinitis etiology, Necrosis diagnosis, Necrosis surgery, Positron-Emission Tomography methods
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- 2018
- Full Text
- View/download PDF
4. Evaluation of the parameters affecting bone temperature during drilling using a three-dimensional dynamic elastoplastic finite element model.
- Author
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Chen YC, Tu YK, Zhuang JY, Tsai YJ, Yen CY, and Hsiao CK
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- Bone Density physiology, Finite Element Analysis, Humans, Necrosis physiopathology, Orthopedic Procedures methods, Temperature, Bone and Bones physiology
- Abstract
A three-dimensional dynamic elastoplastic finite element model was constructed and experimentally validated and was used to investigate the parameters which influence bone temperature during drilling, including the drill speed, feeding force, drill bit diameter, and bone density. Results showed the proposed three-dimensional dynamic elastoplastic finite element model can effectively simulate the temperature elevation during bone drilling. The bone temperature rise decreased with an increase in feeding force and drill speed, however, increased with the diameter of drill bit or bone density. The temperature distribution is significantly affected by the drilling duration; a lower drilling speed reduced the exposure duration, decreases the region of the thermally affected zone. The constructed model could be applied for analyzing the influence parameters during bone drilling to reduce the risk of thermal necrosis. It may provide important information for the design of drill bits and surgical drilling powers.
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- 2017
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5. The immune response to secondary necrotic cells.
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Sachet M, Liang YY, and Oehler R
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- Alarmins metabolism, Animals, Apoptosis physiology, Cell Death physiology, Humans, Immunotherapy trends, Inflammation immunology, Necrosis pathology, Necrosis physiopathology, Phagocytosis immunology, Signal Transduction, Alarmins immunology, Apoptosis immunology, Cell Death immunology, Necrosis immunology
- Abstract
When apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage of immunostimulatory, danger associated molecular patterns (DAMPs), similar to accidental (or primary) necrosis. However, primary necrosis is a sudden event with an inadvertent release of almost unmodified DAMPs. Secondary necrotic cells, in contrast, have gone through various modifications during the process of apoptosis. Recent research revealed that the molecules released from the cytoplasm or exposed on the cell surface differ between primary necrosis, secondary necrosis, and regulated necrosis such as necroptosis. This review gives an overview of these differences and focusses their effects on the immune response. The implications to human physiology and diseases are manifold and will be discussed in the context of cancer, neurodegenerative disorders and autoimmunity.
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- 2017
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6. Dynamic quantitative proteomics characterization of TNF-α-induced necroptosis.
- Author
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Wang Y, Huang ZH, Li YJ, He GW, Yu RY, Yang J, Liu WT, Li B, and He QY
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- Animals, Cell Line, Tumor, Mice, Mitochondria drug effects, Mitochondria metabolism, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, Necrosis genetics, Necrosis metabolism, Proteins genetics, Proteins metabolism, Proteomics, Signal Transduction drug effects, Apoptosis drug effects, Necrosis physiopathology, Proteins chemistry, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Emerging evidence suggested that necroptosis has essential functions in many human inflammatory diseases, but the molecular mechanisms of necroptosis remain unclear. Here, we employed SILAC quantitatively dynamic proteomics to compare the protein changes during TNF-α-induced necroptosis at different time points in murine fibrosarcoma L929 cells with caspase-8 deficiency, and then performed the systematical analysis on the signaling networks involved in the progress using bioinformatics methods. Our results showed that a total of 329, 421 and 378 differentially expressed proteins were detected at three stages of necroptosis, respectively. Gene ontology and ingenuity pathway analysis (IPA) revealed that the proteins regulated at early stages of necroptosis (2, 6 h) were mainly involved in mitochondria dysfunction, oxidative phosphorylation and Nrf-2 signaling, while the expression levels of the proteins related to ubiquitin, Nrf-2, and NF-κB pathways were found to have changes at last stages of necroptosis (6, 18 h). Taken together, we demonstrated for the first time that dysfunction of mitochondria and ubiquitin-proteasome signaling contributed to the initiation and execution of necroptosis. These findings may provide clues for the identification of important regulators in necroptosis and the development of novel therapeutic strategies for the related diseases.
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- 2016
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7. Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury.
- Author
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Liu X, Zhang C, Zhang C, Li J, Guo W, Yan D, Yang C, Zhao J, Xia T, Wang Y, Xu R, Wu X, and Shi J
- Subjects
- Animals, Autophagy physiology, Cell Hypoxia, Down-Regulation, Gene Knockdown Techniques, HSP70 Heat-Shock Proteins antagonists & inhibitors, HSP70 Heat-Shock Proteins genetics, Immunohistochemistry, Microtubule-Associated Proteins genetics, Microtubule-Associated Proteins metabolism, Myocytes, Cardiac metabolism, Necrosis physiopathology, Protein Serine-Threonine Kinases, Rats, Rats, Sprague-Dawley, Receptor-Interacting Protein Serine-Threonine Kinases, HSP70 Heat-Shock Proteins physiology, Myocardial Reperfusion Injury pathology, Myocytes, Cardiac pathology
- Abstract
Irreversible damage of cardiac function arisen from myocardial ischemia/reperfusion injury (MIRI) leads to an emerging challenge in the treatments of cardiac ischemic diseases. Molecular chaperone heat shock protein 70 (HSP70) attenuates heat-stimulated cell autophagy, apoptosis, and damage in the heart. Under specific conditions, autophagy may, directly or indirectly, induce cell death including necroptosis. Whether HSP70 inhibits cardiomyocyte necroptosis via suppressing autophagy during MIRI is unknown. In our study, HSP70 expression was opposite to necroptosis marker RIP1 and autophagy marker LC3A/B expression after myocardial ischemia/reperfusion (MIR) in vivo. Furthermore, in vitro primary rat cardiomyocytes mimicked MIRI by hypoxia/reoxygenation (H/R) treatment. Knockdown of HSP70 expression promoted cardiomyocyte autophagy and necroptosis following H/R treatment, while the increase tendency was downregulated by autophagy inhibitor 3-MA, showing that autophagy-induced necroptosis could be suppressed by HSP70. In summary, HSP70 downregulates cardiomyocyte necroptosis through suppressing autophagy during myocardial IR, revealing the novel protective mechanism of HSP70 and supplying a novel molecular target for the treatment of heart ischemic diseases.
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- 2016
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8. Cell death controlling complexes and their potential therapeutic role.
- Author
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Zamaraev AV, Kopeina GS, Zhivotovsky B, and Lavrik IN
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- Apoptosomes metabolism, Caspase 2 metabolism, Death Domain Receptor Signaling Adaptor Proteins metabolism, Cell Death physiology, Models, Biological, Multiprotein Complexes metabolism, Necrosis physiopathology, Signal Transduction physiology
- Abstract
Programmed cell death plays a central role in the regulation of homeostasis and development of multicellular organisms. Deregulation of programmed cell death is connected to a number of disorders, including cancer and autoimmune diseases. Initiation of cell death occurs in the multiprotein complexes or high molecular weight platforms. Composition, structure, and molecular interactions within these platforms influence the cellular decision toward life or death and, therefore, define the induction of a particular cell death program. Here, we discuss in detail the key cell-death complexes-including DISC, complex II, and TNFRI complex I/II, and the necrosome, RIPoptosome, apoptosome, and PIDDosome-that control apoptosis or necroptosis pathways as well as their regulation. The possibility of their pharmacological targeting leading to the development of new strategies of interference with cell death programs via control of the high molecular weight platforms will be discussed.
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- 2015
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9. Quercetin and sorafenib as a novel and effective couple in programmed cell death induction in human gliomas.
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Jakubowicz-Gil J, Langner E, Bądziul D, Wertel I, and Rzeski W
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- Apoptosis physiology, Astrocytoma drug therapy, Astrocytoma physiopathology, Autophagy physiology, Cell Line, Tumor, Drug Therapy, Combination, Glioblastoma drug therapy, Glioblastoma physiopathology, Glioma physiopathology, HSP27 Heat-Shock Proteins antagonists & inhibitors, HSP27 Heat-Shock Proteins metabolism, HSP72 Heat-Shock Proteins antagonists & inhibitors, HSP72 Heat-Shock Proteins metabolism, Heat-Shock Proteins, Humans, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Mitochondria physiology, Molecular Chaperones, Necrosis chemically induced, Necrosis physiopathology, Niacinamide pharmacology, Sorafenib, Antineoplastic Agents pharmacology, Apoptosis drug effects, Autophagy drug effects, Glioma drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds pharmacology, Quercetin pharmacology
- Abstract
The aim of the present study was to investigate the effect of sorafenib and quercetin on the induction of apoptosis and autophagy in human anaplastic astrocytoma (MOGGCCM) and glioblastoma multiforme (T98G) cell lines. In MOGGCCM cells, sorafenib initiated mainly apoptosis, mediated by the mitochondrial pathway with mitochondrial membrane permeabilization, cytochrome c release to the cytoplasm, and activation of caspase 9 and 3. Additional incubation with quercetin potentiated the pro-apoptotic properties of sorafenib. In T98G cells, autophagy was observed most frequently after the sorafenib treatment. It was accompanied by increased beclin 1 and LC3II expression. Administration of quercetin after the sorafenib treatment resulted in an increased number of autophagic cells. After simultaneous drug application, the level of autophagy was lower in favour of apoptosis. Inhibition of heat shock proteins expression by specific small interfering RNA significantly increased the sensitivity of both the cell lines to induction of apoptosis, but not autophagy. We demonstrated for the first time that sorafenib and quercetin are very effective programmed cell death inducers in T98G and MOGGCCM cells, especially in cells with blocked expression of heat shock proteins.
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- 2014
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10. MicroRNAs in myocardial ischemia: identifying new targets and tools for treating heart disease. New frontiers for miR-medicine.
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Sala V, Bergerone S, Gatti S, Gallo S, Ponzetto A, Ponzetto C, and Crepaldi T
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- Apoptosis physiology, Humans, MicroRNAs genetics, Myocardial Ischemia physiopathology, Necrosis physiopathology, Neovascularization, Physiologic physiology, Regenerative Medicine trends, Feedback, Physiological physiology, Gene Expression Regulation genetics, Genetic Therapy methods, MicroRNAs therapeutic use, Myocardial Ischemia genetics, Myocardial Ischemia therapy, Myocytes, Cardiac physiology
- Abstract
MicroRNAs (miRNAs) are natural, single-stranded, small RNA molecules which subtly control gene expression. Several studies indicate that specific miRNAs can regulate heart function both in development and disease. Despite prevention programs and new therapeutic agents, cardiovascular disease remains the main cause of death in developed countries. The elevated number of heart failure episodes is mostly due to myocardial infarction (MI). An increasing number of studies have been carried out reporting changes in miRNAs gene expression and exploring their role in MI and heart failure. In this review, we furnish a critical analysis of where the frontier of knowledge has arrived in the fields of basic and translational research on miRNAs in cardiac ischemia. We first summarize the basal information on miRNA biology and regulation, especially concentrating on the feedback loops which control cardiac-enriched miRNAs. A focus on the role of miRNAs in the pathogenesis of myocardial ischemia and in the attenuation of injury is presented. Particular attention is given to cardiomyocyte death (apoptosis and necrosis), fibrosis, neovascularization, and heart failure. Then, we address the potential of miR-diagnosis (miRNAs as disease biomarkers) and miR-drugs (miRNAs as therapeutic targets) for cardiac ischemia and heart failure. Finally, we evaluate the use of miRNAs in the emerging field of regenerative medicine.
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- 2014
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11. Transient receptor potential melastatin 4 and cell death.
- Author
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Simard JM, Woo SK, and Gerzanich V
- Subjects
- Adenosine Triphosphate metabolism, Animals, Apoptosis physiology, Calcium metabolism, Humans, Necrosis metabolism, Cell Death physiology, Necrosis physiopathology, TRPM Cation Channels metabolism
- Abstract
Cell death proceeds by way of a variety of "cell death subroutines," including several types of "apoptosis," "regulated necrosis," and others. "Accidental necrosis" due to profound adenosine triphosphate (ATP) depletion or oxidative stress is distinguished from regulated necrosis by the absence of death receptor signaling. However, both accidental and regulated necrosis have in common the process of "oncosis," a physiological process characterized by Na(+) influx and cell volume increase that, in necrotic cell death, is required to produce the characteristic features of membrane blebbing and membrane rupture. Here, we review emerging evidence that the monovalent cation channel, transient receptor potential melastatin 4 (TRPM4), is involved in the cell death process of oncosis. Potential involvement of TRPM4 in oncosis is suggested by the fact that the two principal regulators of TRPM4, intracellular ATP and Ca(2+), are both altered during necrosis in the direction that causes TRPM4 channel opening. Under physiological conditions, activation of TRPM4 promotes Na(+) influx and cell depolarization. Under pathological conditions, unchecked activation of TRPM4 leads to Na(+) overload, cell volume increase, blebbing and cell membrane rupture, the latter constituting the irreversible end stage of necrosis. Emerging data indicate that TRPM4 plays a crucial role as end executioner in the accidental necrotic death of ATP-depleted or redox-challenged endothelial and epithelial cells, both in vitro and in vivo. Future studies will be needed to determine whether TRPM4 also plays a role in regulated necrosis and apoptosis.
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- 2012
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12. Antiischemic activity of new domestic antioxidant 3-hydroxypyridine etoxidol derivative.
- Author
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Blinov DS, Sernov LN, Balashov VP, Blinova EV, Pivkina LV, Gogina ED, Van'kova LV, Vertyankin MV, Boiko GG, and Krasilina TV
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- Animals, Antioxidants chemical synthesis, Catecholamines metabolism, Cats, Epinephrine administration & dosage, Female, Free Radicals antagonists & inhibitors, Heart physiopathology, Heart Conduction System drug effects, Heart Rate drug effects, Injections, Intravenous, Lipid Peroxidation drug effects, Male, Mice, Myocardial Infarction complications, Myocardial Infarction mortality, Myocardial Infarction physiopathology, Necrosis complications, Necrosis mortality, Necrosis physiopathology, Picolines administration & dosage, Pyridines chemical synthesis, Rats, Rats, Wistar, Survival Rate, Antioxidants administration & dosage, Heart drug effects, Myocardial Infarction drug therapy, Necrosis drug therapy, Pyridines administration & dosage
- Abstract
Experiments on rats with myocardium infarction showed that intravenous administration of etoxidol in a dose of 14.2 mg/kg restricted the size of necrosis area and reduced the ratio of necrosis/ischemia zones. The test compound reduced the risk of rhythm and conduction disturbances induced by administration of toxic epinephrine doses to the mice, and increased mouse survival. Etoxidol administered intravenously to cats with acute myocardial ischemia reduced epinephrine concentration and intensity of free radical oxidation in zones of myocardial lesions against the background of the increase in norepinephrine concentration and antioxidant activity in the myocardium. By antiischemic and antioxidant activity, etoxidol was superior to its structural analogue mexidol.
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- 2012
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13. Operative intervention for delayed symptomatic radionecrotic masses developing following stereotactic radiosurgery for cerebral arteriovenous malformations--case analysis and literature review.
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Foroughi M, Kemeny AA, Lehecka M, Wons J, Kajdi L, Hatfield R, and Marks S
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- Adult, Brain diagnostic imaging, Brain pathology, Central Nervous System Cysts etiology, Central Nervous System Cysts pathology, Central Nervous System Cysts surgery, Craniotomy methods, Decompression, Surgical methods, Humans, Intracranial Arteriovenous Malformations diagnostic imaging, Intracranial Arteriovenous Malformations pathology, Magnetic Resonance Imaging, Male, Necrosis pathology, Necrosis physiopathology, Neurosurgical Procedures methods, Postoperative Complications pathology, Postoperative Complications physiopathology, Postoperative Complications surgery, Radiation Injuries pathology, Radiation Injuries physiopathology, Radiosurgery methods, Reoperation, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Treatment Outcome, Brain surgery, Intracranial Arteriovenous Malformations surgery, Necrosis surgery, Radiation Injuries surgery, Radiosurgery adverse effects
- Abstract
Case Report: We report two cases of operative intervention that was beneficial in the treatment of delayed symptomatic radionecrotic masses that had developed following stereotactic radiosurgery (SRS) using the gamma knife (GK) for the treatment of cerebral arteriovenous malformations (AVM)., Discussion: Case 1 involved a small craniotomy for decompression of a large cerebral multiloculated cyst, which had become symptomatic 84 months following gamma knife treatment for a left frontal lobe AVM. Case 2 involved surgical excision of an occipital radionecrotic mass 72 months following GK treatment for an occipital AVM. This patient had suffered from longstanding symptomatic cerebral oedema, which on occasions had become life threatening. Case 2 is also the first report of a radionecrotic mass occurring post-SRS for an AVM, which conversely appeared to demonstrate increased uptake on single photon emission computed tomography (SPECT) scan. The first literature review of such delayed symptomatic radionecrotic lesions is presented. There appears to be a late onset of symptoms (average 55 months, range 12-111 months) associated with such radionecrosis. Drainage of such cysts or excision of the mass lesion appears to be consistently beneficial to the patients and appears to be uncomplicated., Conclusion: We recommend early surgical intervention for such delayed symptomatic radionecrotic masses that do not resolve following non-operative management. We also recommend caution in interpretation of SPECT scan results when attempting to differentiate radionecrosis from neoplasia.
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- 2010
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14. Apoptosis- and necrosis-induced changes in light attenuation measured by optical coherence tomography.
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van der Meer FJ, Faber DJ, Aalders MC, Poot AA, Vermes I, and van Leeuwen TG
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- Cells, Cultured, Fibroblasts pathology, Fibroblasts physiology, Humans, Light, Optical Phenomena, Scattering, Radiation, Apoptosis physiology, Necrosis physiopathology, Tomography, Optical Coherence
- Abstract
Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis had been induced. We analysed the OCT data, including both the scattering properties of the medium and the axial point spread function of the OCT system. The optical attenuation coefficient in necrotic cells decreased from 2.2 +/- 0.3 mm(1) to 1.3 +/- 0.6 mm(-1), whereas, in the apoptotic cells, an increase to 6.4 +/- 1.7 mm(-1) was observed. The results from cultured cells, as presented in this study, indicate the ability of OCT to detect and differentiate between viable, apoptotic, and necrotic cells, based on their attenuation coefficient. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment.
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- 2010
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15. Effect of nitric oxide donor, a modulator of tumor drug resistance, on cell death and p53 protein expression.
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Rajewskaya TA, Goncharova SA, Konovalova NP, Terent'ev AA, and Lapshina MA
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- Animals, Antineoplastic Agents, Alkylating pharmacology, Apoptosis physiology, Cell Count, Cell Line, Tumor, Cyclophosphamide pharmacology, Drug Resistance, Neoplasm, Leukemia P388 pathology, Leukemia P388 physiopathology, Mice, Necrosis drug therapy, Necrosis physiopathology, Time Factors, Apoptosis drug effects, Ethers, Cyclic pharmacology, Leukemia P388 drug therapy, Nitric Oxide Donors pharmacology, Tumor Suppressor Protein p53 metabolism
- Abstract
Exogenous NO donor 3,3-bis-(nitroxymethyl)oxetane (NMO) was synthesized at the Institute for Problems of Chemical Physics (Russian Academy of Sciences). This compound was shown to inhibit cell death (apoptosis and necrosis) in cyclophosphamide-sensitive and cyclophosphamide-resistant P388 murine tumor. p53 protein was expressed in both lines of tumor cells. NO donor NMO had little effect on p53 protein expression in cells of both stains. Our results suggest that the proapoptotic effect of NMO is mediated by the p53-independent molecular mechanisms.
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- 2009
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16. Differences in cell death between high and low energy brain injury in adult rats.
- Author
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Lindh C, Wennersten A, Arnberg F, Holmin S, and Mathiesen T
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- Animals, Biomarkers analysis, Biomarkers metabolism, Biomechanical Phenomena physiology, Brain anatomy & histology, Brain pathology, Brain Injuries complications, Brain Injuries pathology, Cell Count, DNA-Binding Proteins, Disease Models, Animal, Ectodysplasins metabolism, Energy Transfer physiology, Glial Fibrillary Acidic Protein metabolism, Gliosis etiology, Gliosis pathology, Gliosis physiopathology, In Situ Nick-End Labeling, Male, Necrosis etiology, Necrosis pathology, Nerve Degeneration etiology, Nerve Degeneration pathology, Nerve Tissue Proteins metabolism, Neurons metabolism, Neurons pathology, Nuclear Proteins metabolism, Rats, Rats, Sprague-Dawley, Time Factors, Apoptosis physiology, Brain physiopathology, Brain Injuries physiopathology, Necrosis physiopathology, Nerve Degeneration physiopathology
- Abstract
Background: Traumatic brain damage is dependent on energy transfer to the brain at impact. Different injury mechanisms may cause different types of brain injury. It is, however, unknown if the relative distribution between apoptotic cell-death and necrotic cell- death in different populations of brain cells varies depending on energy transfer., Method: Experimental contusions were produced with a modified weight drop onto the exposed dura of rats. Animals were divided into two groups. They received a weight drop from two different heights to vary energy transfer to be higher or lower. Animals were sacrificed at 24 hours post injury (1 DPI) or 6 days (6 DPI); brains were frozen and processed for TUNEL (TdT mediated dUTP nick end labelling), light microscopy and immunochemistry., Findings: The total number of TUNEL positive cells was higher in the higher energy group on the first day after the injury. At the same time point, relatively fewer cells were apoptotic than necrotic, while relatively more glial cells than neurons were TUNEL-positive in higher energy trauma. At 6 day after the injury fewer cells were TUNEL positive and there were no longer significant differences between the high and low energy groups., Conclusions: Increasing energy transfer in a model for brain contusion demonstrated qualitative and quantitative changes in the pattern of cell death. This complexity must be considered when evaluating brain-protection as treatment results may vary depending on which cellular population and which mechanism of cell death is treated under the exact experimental and clinical conditions.
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- 2008
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17. Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications.
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Silva MT, do Vale A, and dos Santos NM
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- Animals, Autoimmune Diseases pathology, Bacterial Infections pathology, Humans, Inflammation pathology, Necrosis pathology, Neutrophils pathology, Phagocytes cytology, Apoptosis physiology, Necrosis physiopathology
- Abstract
In metazoans apoptosis is a major physiological process of cell elimination during development and in tissue homeostasis and can be involved in pathological situations. In vitro, apoptosis proceeds through an execution phase during which cell dismantling is initiated, with or without fragmentation into apoptotic bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed by a transition to a necrotic cell elimination traditionally called "secondary necrosis". Secondary necrosis involves activation of self-hydrolytic enzymes, and swelling of the cell or of the apoptotic bodies, generalized and irreparable damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo, under normal conditions, the elimination of apoptosing cells or apoptotic bodies is by removal through engulfment by scavengers prompted by the exposure of engulfment signals during the execution phase of apoptosis; if this removal fails progression to secondary necrosis ensues as in the in vitro situation. In vivo secondary necrosis occurs when massive apoptosis overwhelms the available scavenging capacity, or when the scavenger mechanism is directly impaired, and may result in leakage of the cell contents with induction of tissue injury and inflammatory and autoimmune responses. Several disorders where secondary necrosis has been implicated as a pathogenic mechanism will be reviewed.
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- 2008
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18. HMGB1 as an autocrine stimulus in human T98G glioblastoma cells: role in cell growth and migration.
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Bassi R, Giussani P, Anelli V, Colleoni T, Pedrazzi M, Patrone M, Viani P, Sparatore B, Melloni E, and Riboni L
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- Blotting, Western, Cell Line, Tumor, Cell Proliferation, Glycation End Products, Advanced, Humans, Mitogen-Activated Protein Kinases biosynthesis, Necrosis physiopathology, Receptor for Advanced Glycation End Products, Receptors, Immunologic biosynthesis, Brain Neoplasms metabolism, Cell Movement physiology, Glioblastoma metabolism, HMGB1 Protein metabolism, Signal Transduction physiology
- Abstract
HMGB1 (high mobility group box 1 protein) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, mainly through RAGE (the receptor for advanced glycation end products); HMGB1-RAGE interactions have been found to be important in a number of cancers. We investigated whether HMGB1 is an autocrine factor in human glioma cells. Western blots showed HMGB1 and RAGE expression in human malignant glioma cell lines. HMGB1 induced a dose-dependent increase in cell proliferation, which was found to be RAGE-mediated and involved the MAPK/ERK pathway. Moreover, in a wounding model, it induced a significant increase in cell migration, and RAGE-dependent activation of Rac1 was crucial in giving the tumour cells a motile phenotype. The fact that blocking DNA replication with anti-mitotic agents did not reduce the distance migrated suggests the independence of the proliferative and migratory effects. We also found that glioma cells contain HMGB1 predominantly in the nucleus, and cannot secrete it constitutively or upon stimulation; however, necrotic glioma cells can release HMGB1 after it has translocated from the nucleus to cytosol. These findings provide the first evidence supporting the existence of HMGB1/RAGE signalling pathways in human glioblastoma cells, and suggest that HMGB1 may play an important role in the relationship between necrosis and malignancy in glioma tumours by acting as an autocrine factor that is capable of promoting the growth and migration of tumour cells.
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- 2008
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19. Calcium and cell death.
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Verkhratsky A
- Subjects
- Animals, Apoptosis physiology, Calcineurin physiology, Calcium physiology, Calcium Channels physiology, Calpain physiology, Endonucleases physiology, Homeostasis physiology, Humans, Necrosis physiopathology, Nitric Oxide Synthase physiology, Transglutaminases physiology, Type C Phospholipases physiology, Calcium Signaling physiology, Cell Death physiology
- Abstract
Calcium signalling system controls majority of cellular reactions. Calcium signals occurring within tightly regulated temporal and spatial domains, govern a host of Ca2(+)-dependent enzymes, which in turn determine specified cellular responses. Generation of Ca2+ signals is achieved through coordinated activity of several families of Ca2+ channels and transporters differentially distributed between intracellular compartments. Cell damage induced by environmental insults or by overstimulation of physiological pathways results in pathological Ca2+ signals, which trigger necrotic or apoptotic cellular death.
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- 2007
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20. Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus.
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Schindler K, Christ ER, Mindermann T, and Wieser HG
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- Acromegaly etiology, Acromegaly surgery, Adenoma diagnosis, Adenoma physiopathology, Adult, Brain Injuries diagnosis, Brain Injuries physiopathology, Cavernous Sinus pathology, Cavernous Sinus physiopathology, Cavernous Sinus surgery, Epilepsy diagnosis, Epilepsy physiopathology, Female, Growth Hormone-Secreting Pituitary Adenoma diagnosis, Growth Hormone-Secreting Pituitary Adenoma physiopathology, Humans, Magnetic Resonance Imaging, Necrosis diagnosis, Necrosis etiology, Necrosis physiopathology, Neoplasm Recurrence, Local surgery, Pituitary Gland pathology, Pituitary Gland physiopathology, Pituitary Gland surgery, Positron-Emission Tomography, Postoperative Complications diagnosis, Postoperative Complications etiology, Postoperative Complications physiopathology, Radiation Injuries diagnosis, Radiation Injuries physiopathology, Temporal Lobe diagnostic imaging, Temporal Lobe pathology, Temporal Lobe radiation effects, Adenoma surgery, Brain Injuries etiology, Epilepsy etiology, Growth Hormone-Secreting Pituitary Adenoma surgery, Radiation Injuries etiology, Radiosurgery adverse effects
- Abstract
Objective: To report a rare side effect of gamma knife treatment of pituitary macroadenoma., Case Report: In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes., Conclusion: Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.
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- 2006
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21. Vanishing pituitary mass revealed by timely magnetic resonance imaging: examples of spontaneous resolution of nonfunctioning pituitary adenoma.
- Author
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Yoshino A, Katayama Y, Watanabe T, and Hirota H
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- Adenoma physiopathology, Adult, Female, Headache etiology, Headache pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Necrosis pathology, Necrosis physiopathology, Neoplasm Regression, Spontaneous physiopathology, Pituitary Apoplexy physiopathology, Pituitary Gland physiopathology, Pituitary Neoplasms physiopathology, Sella Turcica pathology, Time Factors, Adenoma diagnosis, Neoplasm Regression, Spontaneous pathology, Pituitary Apoplexy diagnosis, Pituitary Gland pathology, Pituitary Neoplasms diagnosis
- Abstract
Spontaneous necrosis of a pituitary adenoma is not rare but represents a very unlikely way of curing a nonfunctioning pituitary adenoma. We report two cases of nonfunctioning pituitary adenoma, one of them with a family history of pituitary adenoma, in whom spontaneous complete resolution occurred through the necrosis of previously well-delineated adenoma. Sequential magnetic resonance imaging (MRI) scans provided clear evidence of the event, resulting in an empty sella. In the present cases, the pituitary necrosis was entirely asymptomatic with the exception of an initial atypical headache in one case, and cured the patients as well as a surgical procedure would have done. This exceptional curative process, however, should certainly not be relied on and does not rule out the possibility of recurrence.
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- 2005
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22. Image guided interstitial laser thermotherapy: a canine model evaluated by magnetic resonance imaging and quantitative autoradiography.
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Muacevic A, Peller M, Ruprecht L, Berg D, Fend L, Sroka R, Reulen HJ, Reiser M, Tonn JCh, and Kreth FW
- Subjects
- Aminoisobutyric Acids pharmacokinetics, Animals, Autoradiography methods, Blood-Brain Barrier physiopathology, Blood-Brain Barrier radiation effects, Body Temperature physiology, Body Temperature radiation effects, Brain Mapping instrumentation, Carbon Radioisotopes, Cerebrovascular Circulation physiology, Denervation, Dogs, Encephalitis etiology, Encephalitis pathology, Encephalitis physiopathology, Female, Frontal Lobe anatomy & histology, Laser Therapy adverse effects, Laser Therapy instrumentation, Magnetic Resonance Imaging instrumentation, Male, Microcirculation physiology, Microcirculation radiation effects, Models, Animal, Necrosis etiology, Necrosis pathology, Necrosis physiopathology, Neuronavigation instrumentation, Postoperative Complications etiology, Postoperative Complications pathology, Postoperative Complications physiopathology, Brain Mapping methods, Cerebrovascular Circulation radiation effects, Frontal Lobe surgery, Laser Therapy methods, Magnetic Resonance Imaging methods, Neuronavigation methods
- Abstract
Objective: To determine the applicability and safety of a new canine model suitable for correlative magnetic resonance imaging (MRI) studies and morphological/pathophysiological examination over time after interstitial laser thermotherapy (ILTT) in brain tissue., Material and Methods: A laser fibre (Diode Laser 830 nm) with an integrated temperature feedback system was inserted into the right frontal white matter in 18 dogs using frameless navigation technique. MRI thermometry (phase mapping i.e. chemical shift of the proton resonance frequency) during interstitial heating was compared to simultaneously recorded interstitial fiberoptic temperature readings on the border of the lesion. To study brain capillary function in response to ILTT over time quantitative autoradiography was performed investigating the unidirectional blood-to-tissue transport of carbon-14-labelled alpha amino-isobutyric acid (transfer constant K of AIB) 12, 36 hours, 7, 14 days, 4 weeks and 3 months after ILTT., Results: All laser procedures were well tolerated, laser and temperature fibres could be adequately placed in the right frontal lobe in all animals. In 5 animals MRI-based temperature quantification correlated strongly to invasive temperature measurements. In the remaining animals the temperature fibre was located in the area of susceptibility artifacts, therefore, no temperature correlation was possible. The laser lesions consisted of a central area of calcified necrosis which was surrounded by an area of reactive brain tissue with increased permeability. Quantitative autoradiography indicated a thin and spherical blood brain barrier lesion. The magnitude of K of AIB increased from 12 hours to 14 days after ILTT and decreased thereafter. The mean value of K of AIB was 19 times (2 times) that of normal white matter (cortex), respectively., Conclusion: ILTT causes transient, highly localised areas of increased capillary permeability surrounding the laser lesion. Phase contrast imaging for MRI thermomonitoring can currently not be used for reliable temperature readings in vivo. The suggested new canine model proved to be safe, accurate, easy to use, and provides clinical, radiographic, pathological and physiological correlations.
- Published
- 2005
- Full Text
- View/download PDF
23. Induction of apoptosis in bone marrow cells is mediated via purinergic receptors.
- Author
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Uspenskaya YA, Mikhutkina SV, Taksanova EI, Popova NN, Olovyannikova RY, and Salmina AB
- Subjects
- Adenosine Triphosphate pharmacology, Animals, Bone Marrow Cells cytology, Doxorubicin pharmacology, Male, Mice, Necrosis physiopathology, Pyridoxal Phosphate pharmacology, Suramin pharmacology, Apoptosis drug effects, Bone Marrow Cells drug effects, Pyridoxal Phosphate analogs & derivatives, Receptors, Purinergic physiology
- Abstract
ATP activity in mouse bone marrow cells was in vitro estimated by expression of phosphatidylserine on the outer membrane surface using FITC-labeled annexin. ATP induced apoptosis in bone marrow cells. Purinergic receptor antagonists PPADS and suramin modulated the apoptotic effect of ATP on hemopoietic cells. Acute and subacute administration of doxorubicin, an inductor of oxidative burst, decreased cell sensitivity to ATP and abolished its apoptotic effect.
- Published
- 2004
- Full Text
- View/download PDF
24. Na+/K+ pump and endothelial cell survival: [Na+]i/[K+]i-independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na+]i.
- Author
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Orlov SN, Thorin-Trescases N, Pchejetski D, Taurin S, Farhat N, Tremblay J, Thorin E, and Hamet P
- Subjects
- Animals, Aorta metabolism, Apoptosis drug effects, Apoptosis physiology, Caspases drug effects, Caspases metabolism, Cells, Cultured, Enzyme Inhibitors pharmacology, Membrane Potentials drug effects, Potassium metabolism, Sodium metabolism, Sodium-Potassium-Exchanging ATPase drug effects, Swine, Cardiotonic Agents pharmacology, Endothelial Cells drug effects, Endothelial Cells metabolism, Necrosis physiopathology, Ouabain pharmacology, Sodium-Potassium-Exchanging ATPase metabolism
- Abstract
Recent studies have demonstrated the tissue-specific effect of Na+/K+ pump inhibition by ouabain and other cardiac glycosides on cell viability. The vascular endothelium is an initial target of cardiac glycosides employed for the management of congestive heart failure as well as circulating endogenous ouabain-like substances (EOLS), the production of which is augmented in volume-expanded hypertension. This study examined the role of the Na+/K+ pump in the survival of cultured porcine aortic endothelial cells (PAEC). Complete Na+/K+ pump inhibition with ouabain led to PAEC death, indicated by cell detachment and decreased staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Based on cell swelling and resistance to benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk) a pan-caspase inhibitor, this type of cell death was classified as necrosis. In contrast to ouabain, Na+/K+ pump inhibition in K+-free medium did not affect PAEC viability and sharply attenuated apoptosis triggered by 3H decay-induced DNA damage. Necrosis evoked by ouabain was preserved after dissipation of the transmembrane gradient of K+ and Na+, whereas dissipation of the Na+ gradient abolished the antiapoptotic action of K+-free medium. Comparative analysis of these results and modulation of intracellular Na+ and K+ content by the above-listed stimuli showed that interaction of ouabain with Na+/K+-ATPase triggered necrosis independently of inhibition of Na+/K+ pump-mediated ion fluxes and inversion of the [Na+]i/[K+]i ratio, whereas protection against apoptosis under Na+/K+ pump inhibition in K+-depleted medium was mediated by [Na+]i elevation. The role of Na+/K+ pump-mediated regulation of endothelial cell survival and vascular remodelling seen in hypertension should be investigated further in context of EOLS and chronic treatment with digitalis., (Copyright 2004 Springer-Verlag)
- Published
- 2004
- Full Text
- View/download PDF
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