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Pathological Effects (pathological + effects)
Selected AbstractsVascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectivesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2003Ruth B. Caldwell Abstract Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes. Therefore, VEGF represents an exciting target for therapeutic intervention in diabetic retinopathy. This review highlights the current understanding of the mechanisms that regulate VEGF gene expression and mediate its biological effects and how these processes may become altered during diabetes. The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction. Finally, potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are considered. Copyright © 2003 John Wiley & Sons, Ltd. [source] Cytotoxicity assessment of gliotoxin and penicillic acid in Tetrahymena pyriformisENVIRONMENTAL TOXICOLOGY, Issue 2 2006C. Gräbsch Abstract Various studies have documented the associations between mold exposure and effects on health. Mycotoxins, which occur in spores and mold fragments, can be involved in processes that have pathological effects, such as adynamia of the immune system, recurrent infections of the respiratory tract, or asthma. Using Tetrahymena pyriformis, a single-cell organism well established as a suitable model for human respiratory epithelium-cell functionalities, we investigated dose,response relationships of the mycotoxins gliotoxin and penicillic acid. Our study focused on the viability (cell count, MTT assay), energy levels (adenosine-5,-triphosphate content), energy-providing processes (MTT reduction per cell), and cell respiration (oxygen consumption). Both mycotoxins acted as cytotoxins in a dose-dependent manner. Gliotoxin had a stronger inhibitory effect (EC50 0.38 ,M) than did penicillic acid (EC50 343.19 ,M). The energy-providing processes were not inhibited or were only weakly inhibited under the influence of gliotoxin, whereas penicillic acid caused stimulation of the physiological parameters. Summarizing the results, it is clear that the two investigated mycotoxins must have different modes of action. They are not only different in the strength of their toxic effects but also in a variety of physiological aspects. In addition, T. pyriformis showed differences in its ability to overcome the negative effects of particular mycotoxin exposures. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 111,117, 2006. [source] Clinical and pathological effects of short-term cyanide repeated dosing to goatsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005B. Soto-Blanco Abstract The purpose of this work is to determine and describe the effects of subacute cyanide toxicity to goats. Eight female goats were divided into two groups. The first group of five animals was treated with 8.0 mg KCN kg,1 body weight day,1 for seven consecutive days. The second group of three animals was treated with water as controls. Complete physical examination, including observation for behavior changes, was conducted before and after dosing. One treated animal was euthanized immediately after dosing. Later, two of the remaining treated animals and a control goat were euthanized after a 30-day recovery period. Euthanized animals were necropsied and tissues were collected and prepared for histologic studies. Clinical signs in treated goats were transient and included depression and lethargy, mild hyperpnea and hyperthermia, arrhythmias, abundant salivation, vocalizations, expiratory dyspnea, jerky movements and head pressing. Two goats developed convulsions after day 3 of treatment. One animal developed more permanent behavioral changes as she became less dominant and aggressive. Histologic changes included mild hepatocellular vacuolation and degeneration, mild vacuolation and swelling of the proximal convoluted tubules of the kidneys and spongiosis of the white matter (status spongiosis) of the cerebral white tracts, internal capsule, cerebellar peduncles, spinal cord and peripheral nerves. In summary, sub-lethal cyanide intoxication in goats resulted in behavioral changes, and during the treatment period animals showed delayed signs of toxicity. Significant histologic lesions in goats were observed and need to be characterized further. Copyright © 2005 John Wiley & Sons, Ltd. [source] Cadmium modulates proliferation and differentiation of human neuroblastsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2009Massimo Gulisano Abstract Cadmium is an environmental pollutant inducing numerous pathological effects, including neurological disorders and brain diseases. However, little is known about the molecular mechanisms of cadmium in affecting neurons and in inducing neurotoxicity in the development of the human brain. We have recently established, cloned, and propagated in vitro a primary long-term cell culture (FNC-B4) obtained from the human fetal olfactory neuroepithelium. In the present study, we show that different concentrations of cadmium chloride (CdCl2) induced dose-dependent biological effects in FNC-B4 cells. A low concentration (10 ,M) of CdCl2 stimulated neuroblast growth, whereas a high concentration (100 ,M) inhibited the growth and the viability of neuroblasts inducing morphological and cytoskeletal alterations as well as apoptotic cell death. We also observed that CdCl2 affected, in a dose-dependent manner, the differentiation of FNC-B4 neuroblasts, with increased mRNA and protein levels of differentiation markers and decreased expression levels of neuronal stem markers. Furthermore, differentiated cells co-expressed glial and neuronal markers. We suggest that CdCl2 in FNC-B4 neuroblasts might represent a selective cue by which, in a heterogeneous primary culture, the more differentiated mature cells die, whereas the undifferentiated cells, at the same time glial and neuronal progenitors, are forced to access a state of differentiation. © 2008 Wiley-Liss, Inc. [source] Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic StudiesALCOHOLISM, Issue 2 2009Michael A. Collins In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions,pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, ,-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways. [source] Laser induced fluorescence model of human goiterLASER PHYSICS LETTERS, Issue 3 2008Z.V. Jaliashvili Abstract Laser induced fluorescence (LIF) with wide area surveillance for resected thyroid tissue solid chunks is presented. The characteristic LIF spectra of goiter were established. The state of tissue at each point represents a superposition of normal and pathology states. To our knowledge two co-existing pathological effects were observed optically for the first time. It is demonstrated that the LIF spectral functions and their intensities well-labeled such areas and represent a good tool for medical diagnostics of goiter and for the definition of the degree of abnormality and geometrical sizes of these areas. (© 2008 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) [source] Effects of Corticosteroid Therapy on the Long-Term Outcome of Radiofrequency Lesions in the Swine Caval VeinsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2008GUILHERME FENELON M.D. Background: We explored the angiographic and pathological effects of corticosteroids on the long-term outcome of radiofrequency (RF) ablation lesions in the swine caval veins. Methods: Under fluoroscopy guidance, a single linear RF lesion (4-mm tip, 60°C, 180 seconds) was created in each vena cava (from ±2 cm into the vein to the venoatrial junction) of 20 anesthetized minipigs (35± 2 kg). Three groups were studied: acute (n = 4), killed 1 hour after RF; control (n = 8), sacrificed 83± 1 days after RF; and pigs (n = 8) receiving hydrocortisone (400 mg i.v. after RF) and prednisone (25 mg po for 30 days), killed 83± 1 days post-RF. Angiography was performed before, immediately after ablation, and at follow-up. Then, animals were sacrificed for histological analysis. Results: Mild (<40%) or moderate (41,70%) acute luminal narrowing occurred in 19/20 (95%) inferior veins and in 13/20 (65%) superior veins. Severe (>70%) stenosis and occlusions were not noted. At follow-up, in both chronic groups, mean vessel diameters returned to baseline and progression of luminal narrowing did not occur in any vein. Of note, superior and inferior vena cava angiographic diameter for control and treated pigs did not differ. The same was observed for the cross-sectional luminal area. Acute lesions displayed transmural coagulative necrosis whereas chronic lesions revealed marked fibrosis. Histological findings were similar in controls and treated pigs. Conclusion: In this model, mild and moderate stenosis, occurring immediately after ablation, seems to resolve over time. Corticosteroids do not affect the long-term outcome of such RF lesions in the caval veins. [source] Acute and Chronic Effects of Extensive Radiofrequency Lesions in the Canine Caval Veins: Implications for Ablation of Atrial ArrhythmiasPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 12 2006GUILHERME FENELON M.D. Background: Although radiofrequency (RF) ablation within the caval veins has been increasingly used to treat a variety of atrial tachyarrhythmias, the consequences of RF ablation in the caval veins are unknown. We explored the acute and chronic angiographic and pathological effects of extensive RF ablation in the caval veins. Methods: Under fluoroscopy guidance, conventional (4 mm tip, 60°C, 60 seconds) RF applications (n = 6,7) were delivered in each vena cava (from ±2 cm into the vein to the veno-atrial junction) of 15 dogs (10 ± 3 kg). Animals were killed 1 hour and 5 weeks after ablation for histological analysis. Angiography was performed before ablation (acute dogs only) and at sacrifice to assess the degree of vascular stenosis. Results: In acute dogs (n = 5), luminal narrowing was noted in 10/10 (100%) targeted veins (mild in two; moderate in three and severe in five, including two total occlusions). In the six chronic animals that completed the protocol (four died during follow-up), stenosis was also observed in 12/12 (100%) ablated veins (mild in six; moderate in four and severe in two). Of these, one superior vena cava was suboccluded with development of extensive collateral circulation. Histologically, acute lesions displayed typical transmural coagulative necrosis, whereas chronic lesions revealed intimal proliferation, necrotic muscle replaced with collagen, endovascular contraction, and disruption and thickening of the internal elastic lamina. Conclusion: In this model, extensive RF ablation in the caval veins may result in significant vascular stenosis. These findings may have implications for catheter ablation of arrhythmias originating within the caval veins. [source] T-cell recognition of a prostate specific antigen is not sufficient to induce prostate tissue destructionTHE PROSTATE, Issue 6 2006Jason R. Lees Abstract METHODS The ability of CD8+ T-cells to induce prostate inflammation was examined using a prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to prostate tissue was examined following T-cell activation via endogenous prostatic antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro antigen stimulated OT-I cells. RESULTS Ovalbumin specific OT-I cells were activated by autologous prostate antigen and trafficked to the prostate, but did not induce inflammation unless present in overwhelming numbers (,65% of CD8+ T-cells). Activation of antigen specific CD8+ T-cells in vitro (peptide pulsed antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory prostate inflammation, without induction of prostate pathology, regardless of CD4+ T-cell availability. Inflammation also was observed in OT-I,×,POET mice but again, pathological effects were not observed. CONCLUSIONS T lymphocytes specific for a prostate antigen are capable of inducing inflammatory infiltration of prostatic tissue rapidly following activation, but do not produce pathological prostate injury. Prostate 66:578,590, 2006. © 2005 Wiley-Liss, Inc. [source] From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters,APMIS, Issue 4 2001John A. McLachlan For three decades, we have known that estrogens alter the development of the mammalian reproductive system in predictable ways. In mice exposed prenatally to diethylstilbestrol (DES) or other estrogens, the male offspring exhibit structural malformations including cryptorchidism, epididymal cysts and retained Mullerian ducts. The estrogen-associated alterations in the genital tract phenotype can be usefully considered as a model called Developmental Estrogenization Syndrome. While estrogen treatment during critical periods of morphogenesis of the male reproductive system has been associated with these changes, the mechanisms at the molecular level are still being discovered. Parallel findings on the hormones involved in Mullerian duct regression and testicular descent have helped guide research on the mechanisms of developmental estrogenization of the male. Cellular localization of molecular signals associated with key steps in genital tract development, use of mice with gene disruption, and knowledge of the mechanisms underlying persistent changes in gene expression are beginning to provide a blue print for both the physiological role and pathological effects of estrogens in reproductive tract development. Since many of the same biological principles underlie genital tract morphogenesis in mammals, one may expect some of the same changes in males of other species exposed to estrogen during the appropriate developmental periods. [source] Prediction of the response to chemoradiation and prognosis in oesophageal squamous cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2002K. Kishi Background: The sensitivity of cancer cells to chemotherapy and radiation therapy depends on various biological properties. This study investigated the expression of p53, CDC25B and metallothionein (MT), and evaluated their clinical significance in chemoradiation therapy (CRT) for oesophageal squamous cell carcinoma. Methods: The expression of p53, CDC25B and MT was evaluated by immunohistochemistry using biopsy specimens taken before CRT for 77 patients with oesophageal squamous cell carcinoma, and correlated with the pathological effects of CRT and survival. Results: p53-positive tumours and MT-positive tumours had a poor response to CRT, whereas tumours with strong CDC25B expression were associated with a good response. When each patient was scored for the presence of the three biological factors, there was a strong correlation between the sensitivity score and the pathological effect of CRT (P < 0·001), and a (non-significant) difference in the 5-year survival rate between patients with a high score and those with a low score (67 versus 34 per cent respectively; P = 0·12). Conclusion: The combined evaluation of p53, CDC25B and MT may help to identify patients with advanced oesophageal squamous cell carcinoma who will benefit from preoperative CRT. © 2002 British Journal of Surgery Society Ltd [source] Internalization of Bordetella pertussis adenylate cyclase,haemolysin into endocytic vesicles contributes to macrophage cytotoxicityCELLULAR MICROBIOLOGY, Issue 11 2001Nadia Khelef Bordetella pertussis adenylate cyclase,haemolysin is a critical virulence factor in the murine model of intranasal infection, where it is required for several pathological effects, including macrophage apoptosis. Based on biochemical and immunological properties, it was proposed that the toxin was delivered directly to the cytoplasm of eukaryotic cells without trafficking through the endocytic pathway. In the present study, we analysed the cellular distribution of the adenylate cyclase,haemolysin during intoxication of macrophages. We showed that, shortly after its initial binding to the plasma membrane of macrophages, the toxin gains access to intracellular compartments that become progressively positive for the endosomal marker transferrin, but not for the lysosomal membrane protein CD107a/Lamp1. Importantly, the vesicular trafficking of the adenylate cyclase,haemolysin appears to be required for its ability to induce macrophage death. Inhibitors of actin polymerization and of macropinocytosis, as well as depletion of plasma membrane cholesterol and disruption of the Golgi network, reduce the toxin's ability to kill macrophages. Altogether, these results suggest that internalization of the adenylate cyclase,haemolysin into endocytic vesicles, at least partly through macropinocytosis, contributes to cytotoxicity. [source] | |||||||||||||