WorldWideScience

Sample records for necrosis factor-a antagonists

  1. Genetically engineered bacteriophage delivers a tumor necrosis factor alpha antagonist coating on neural electrodes

    International Nuclear Information System (INIS)

    Kim, Young Jun; Nam, Chang-Hoon; Jin, Young-Hyun; Stieglitz, Thomas; Salieb-Beugelaar, Georgette B

    2014-01-01

    This paper reports a novel approach for the formation of anti-inflammatory surface coating on a neural electrode. The surface coating is realized using a recombinant f88 filamentous bacteriophage, which displays a short platinum binding motif and a tumor necrosis factor alpha antagonist (TNF-α antagonist) on p3 and p8 proteins, respectively. The recombinant bacteriophages are immobilized on the platinum surface by a simple dip coating process. The selective and stable immobilization of bacteriophages on a platinum electrode is confirmed by quartz crystal microbalance with dissipation monitoring, atomic force microscope and fluorescence microscope. From the in vitro cell viability test, the inflammatory cytokine (TNF-α) induced cell death was prevented by presenting recombinant bacteriophage coating, albeit with no significant cytotoxic effect. It is also observed that the bacteriophage coating does not have critical effects on the electrochemical properties such as impedance and charge storage capacities. Thus, this approach demonstrates a promising anti-apoptotic as well as anti-inflammatory surface coating for neural implant applications. (paper)

  2. Effects of a Tumor Necrosis Factor-α Antagonist on Experimentally Induced Rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Kim

    2011-01-01

    Full Text Available This prospective, randomized, and controlled study examined the effects of tumor necrosis factor soluble receptor type I (sTNFRI, a TNF-α antagonist on experimentally induced rhinosinusitis in rats. The experimental groups received an instillation of lipopolysaccharide (LPS plus an intramuscular injection of amoxicillin/clavulanate (antibiotic group, an instillation of sTNFRI (sTNFRI group, an instillation of sTNFRI and an injection of amoxicillin/clavulanate (sTNFRI/antibiotic group, or no additional treatment (LPS group. Histopathological changes were determined using hematoxylin-eosin and periodic acid-Schiff (PAS staining. Leakage of exudate was determined using fluorescence microscopy. Vascular permeability was measured using the Evans blue dye technique. Expression of MUC5AC was measured using reverse transcriptase PCR. The sTNFRI, antibiotic, and sTNFRI/antibiotic groups had significantly less capillary permeability, mucosal edema, PAS staining, and expression of MUC5AC than the LPS group. There were no differences in capillary permeability, mucosal edema, PAS staining, and MUC5AC expression between the sTNFRI and sTNFRI/antibiotic groups. The antibiotic group had PAS staining similar to that of the sTNFRI and sTNFRI/antibiotic groups but had a greater increase in capillary permeability, mucosal edema, and MUC5AC expression. This study shows that sTNFRI reduces inflammatory activity and mucus hypersecretion in LPS-induced rhinosinusitis in rats.

  3. Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease

    NARCIS (Netherlands)

    Michelakakis, H.; Spanou, C.; Kondyli, A.; Dimitriou, E.; van Weely, S.; Hollak, C. E.; van Oers, M. H.; Aerts, J. M.

    1996-01-01

    Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients with different types of Gaucher disease (GD) and patients with other lysosomal storage diseases. The highest TNF-a levels were observed in the most severe neuronopathic type of GD, exceeding those found in healthy

  4. Infective endocarditis following tumor necrosis factor-α antagonist therapy for management of psoriatic erythroderma: a case report.

    Science.gov (United States)

    Mizuno, Takuro; Kiyosawa, Jun; Fukuda, Akihiro; Watanabe, Seiji; Kurose, Nozomu; Nojima, Takayuki; Kanda, Tsugiyasu

    2017-02-09

    The introduction of biological agents, such as infliximab, which act against tumor necrosis factor-α was a major advance for the treatment of an increasing number of chronic diseases. Tumor necrosis factor-α antagonists represent a major therapeutic advance for the management of chronic inflammatory diseases, such as psoriasis. Previous studies have reported that the use of tumor necrosis factor-α antagonists increased the risk of opportunistic infections and reactivation of latent bacterial infections. Cardiac involvement, such as infective endocarditis, is very rare in the literature. A 77-year-old Asian man with a 10-year history of psoriatic erythroderma was referred due to high fever and general malaise. He was treated with Predonine (prednisolone) and infliximab. After treatment, cardiac echography showed mitral valve vegetation and brain magnetic resonance imaging indicated multiple fresh infarctions. He died from large brain infarction in October 2013. An autopsy showed fresh thrombosis in his left middle cerebral artery, mitral valve vegetations, and septic micro-embolisms in multiple organs. Lethal bacterial endocarditis was revealed after administration of tumor necrosis factor-α inhibitor, infliximab, for the treatment of psoriatic erythroderma. An autopsy showed vegetation in his mitral valve and brain infarction with fresh purulent embolism in his left middle cerebral artery and septic micro-embolisms.

  5. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I; Sester, M; Gomez-Reino, J J

    2010-01-01

    risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-¿ release assays or, as an alternative in individuals without a history...... of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test...

  6. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

    DEFF Research Database (Denmark)

    Solovic, I.; Sester, M.; Gomez-Reino, J.J.

    2010-01-01

    risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-gamma release assays or, as an alternative in individuals without...... a history of bacille Calmette-Guerin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test...... and an interferon-gamma release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy...

  7. Nonselective matrix metalloproteinase but not tumor necrosis factor-a inhibition effectively preserves the early critical colon anastomotic integrity

    DEFF Research Database (Denmark)

    Ågren, Magnus S.; Andersen, Thomas L.; Andersen, Line

    2011-01-01

    Increased matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor-a (TNF-a) induces MMPs and may influence anastomosis repair....

  8. Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Angel Descalzo, Miguel

    2007-06-15

    To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

  9. Effects of tumor necrosis factor alpha antagonist, platelet activating factor antagonist, and nitric oxide synthase inhibitor on experimental otitis media with effusion.

    Science.gov (United States)

    Kim, Dong-Hyun; Park, Yong-Soo; Jeon, Eun-Ju; Yeo, Sang-Won; Chang, Ki-Hong; Lee, Seung Kyun

    2006-08-01

    We studied the inflammatory responses in otitis media with effusion induced by lipopolysaccharide (LPS) in rats, and compared the preventive effects of tumor necrosis factor (TNF) soluble receptor type I (sTNFRI, a TNF-alpha antagonist), platelet activating factor antagonist, and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). We used 2 control groups of Sprague Dawley rats (untreated and saline-treated) and 4 experimental groups, which all received an intratympanic injection of LPS, followed in 3 groups by experimental treatment of the same ear. The LPS group had no additional treatment. The L-NAME group received intraperitoneal injection of L-NAME and was reinjected after 12 hours. The A-85783 group was first given an intraperitoneal injection of A-85783. The sTNFRI group was first given an intratympanic injection of sTNFRI. Twenty-four hours after the initial intratympanic injection of LPS, temporal bones from each group were examined histopathologically and the vascular permeability of the middle ear mucosa was measured by Evans blue vital dye staining. The L-NAME, A-85783, and sTNFRI groups showed significantly reduced capillary permeability, subepithelial edema, and infiltration of inflammatory cells in comparison with the LPS group. There were no differences in capillary permeability, subepithelial edema, or infiltration of inflammatory cells between the A-85783 and sTNFRI groups. The L-NAME group showed no difference in vascular permeability or subepithelial edema in comparison with the A-85783 and sTNFRI groups, but showed more infiltration of inflammatory cells. We conclude that sTNFRI, A-85783, and L-NAME can be proposed as alternative future treatments for otitis media with effusion. However, L-NAME may be the least effective of these agents.

  10. Reactivation of pulmonary tuberculosis (TBC) with the use of antagonist of the tumor necrosis factor alpha (FNTα) in rheumatoid arthritis: On purpose of a case

    International Nuclear Information System (INIS)

    Martinez V, Jose B; Medina V, Yimy F; Parga, Roberto; Restrepo, Jose Felix; Iglesias G, Antonio; Rondon, Federico

    2005-01-01

    Woman 56 years old, with history of rheumatoid arthritis who develops reactivation of pulmonary tuberculosis (TBC) after 1 year of treatment with biological therapy (antagonist of the tumor necrosis factor alpha). It is discussed pathophysiologic mechanisms, diagnostic approach, treatment of TBC and some recommendations for the use of biological therapy in patients with rheumatic disease

  11. Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

    Science.gov (United States)

    Kok, Beverley; Lester, Erica L W; Lee, William M; Hanje, A James; Stravitz, R Todd; Girgis, Safwat; Patel, Vaishali; Peck, Joshua R; Esber, Christopher; Karvellas, Constantine J

    2018-03-21

    Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

  12. Necrose cutânea induzida por antagonistas da vitamina K Skin necrosis induced by vitamin K antagonists

    Directory of Open Access Journals (Sweden)

    Jose Manoel da Silva Silvestre

    2009-12-01

    Full Text Available Os anticoagulantes orais que atuam através do antagonismo à vitamina K são utilizados na prática clínica há muito tempo, porém ainda há dificuldades no seu manejo e na condução das complicações. Entre as complicações, as mais conhecidas são os transtornos hemorrágicos, mas outras também devem ser reconhecidas, tais como a necrose induzida por varfarina. Esta é uma grave, porém rara complicação, cuja fisiopatologia é ainda obscura e cujas causas são indefinidas. Dentre as possíveis causas, as mais prováveis são a deficiência de proteína C e de proteína S, reações de hipersensibilidade e deficiência de fator VII. Há maior incidência desta complicação entre mulheres de meia-idade, acometendo preferencialmente mamas e glúteos. As medidas mais importantes para o tratamento são: suspensão imediata da droga, uso de heparina não fracionada ou de baixo peso molecular em doses terapêuticas, emprego da vitamina K e, eventualmente, infusão de plasma fresco congelado ou de proteína C ativada recombinante.Oral anticoagulants acting via vitamin K antagonists have long been employed in the clinical practice. However, difficulties related to the management of treatment regimens and complications still persist. Among the complications, bleeding disorders are widely known, but others should also be taken into consideration, such as warfarin-induced skin necrosis. The pathophysiology of this rare but severe complication is still obscure, and its causes remain to be defined. Among possible causes, protein C and protein S deficiency, hypersensitivity reactions and VII factor deficiency are the most probable ones. There is an increased incidence of warfarin-induced skin necrosis among middle-aged women, usually affecting breasts and buttocks. The most important treatment measures are immediate discontinuation of the drug, use of unfractionated or low-molecular-weight heparin at therapeutic doses, use of vitamin K and

  13. Production of tumor necrosis factor-a is increased in urinary tract infections

    Directory of Open Access Journals (Sweden)

    Neni Susilaningsih

    2015-12-01

    Full Text Available BACKGROUND Urinary tract infection (UTI is a common source of bacteriemia. The most common cause of UTI is Escherichia coli (E. coli. Tumor Necrosis Factor (TNF-á gene polymorphism has been reported to be responsible for an excessive production of TNF-á and eventual disruption of pro-inflammatory cytokine regulation. The aim of this study was to compare TNF-á serum levels and TNF-á allele polymorphisms in patients with UTI due to E.coli and in non- UTI controls. METHODS A cross-sectional study was conducted at Dr. Kariadi Central Hospital and the Center for Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang. In 68 patients with UTI the TNF-á serum levels were determined by means of ELISA and compared to those of non-UTI controls (n=55. TNFá- 308G>A gene polymorphism was analyzed by polymerase chain reaction restriction fragment length using the NcoI enzyme. Fragments were visualized on polyacrylamide gel with silver staining. RESULTS TNF-á serum level in patients with UTI had a median of 8.9 pg/mL, which was significantly higher than the median of 3.7 pg/mL in the control group (pA gene polymorphisms found in the patient group were G/G=61 (90%, G/A=7(10% and A/A=0, while in the control group were G/G=48 (87%, G/A=7 (13% and A/A =0. There was no significant differences (p=0.578 in gene polymorphisms between the two groups. CONCLUSIONS TNF-á serum levels in patients with UTI due to E. coli were significantly higher than in non-UTI controls, but for the TNF-á-380 gene polymorphisms no significant difference was found between the two groups. There are presumably more important factors than host genotype that influence UTI pathogenesis.

  14. Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis.

    Science.gov (United States)

    Qiu, Yun; Mao, Ren; Chen, Bai-Li; Zhang, Sheng-Hong; Guo, Jing; He, Yao; Zeng, Zhi-Rong; Ben-Horin, Shomron; Chen, Min-Hu

    2017-09-01

    It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59; P immunomodulators (standardized mean difference, 0.11; 95% confidence interval, 0.19-0.41; P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction); the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I 2  = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation of antibodies against TNF antagonists in patients with inflammatory bowel disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nyboe Andersen, Nynne; Pasternak, Björn; Basit, Saima

    2014-01-01

    antagonist users and nonusers, estimated using Poisson regression adjusted for age, calendar year, disease duration, propensity scores, and use of other IBD medications. RESULTS: During 489,433 person-years of follow-up (median, 9.3 years [interquartile range, 4.2-14.0]), 81 of 4553 patients exposed to TNF......-α antagonists (1.8%) (median follow-up, 3.7 years [interquartile range, 1.8-6.0]) and 3465 of 51,593 unexposed patients (6.7%) developed cancer, yielding a fully adjusted RR of 1.07 (95% CI, 0.85-1.36). There was no significantly increased risk of cancer in analyses according to time since first TNF...

  16. Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

    DEFF Research Database (Denmark)

    Andreassen, B. U.; Pærregaard, Anders; Michaelsen, Kim F.

    2008-01-01

    To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels...... during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days -3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy...... intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm(2) (day -3) vs 1477 mm(2) (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm(2) (day -3) vs 648 mm(2) (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation...

  17. Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases.

    Science.gov (United States)

    Hernández, M Victoria; Sanmartí, Raimon; Cañete, Juan D; Descalzo, Miguel A; Alsina, Mercè; Carmona, Loreto; Gomez-Reino, Juan J

    2013-12-01

    To analyze the incidence rate (IR) and risk factors of cutaneous adverse events (CAE) in patients with chronic inflammatory rheumatic diseases treated with tumor necrosis factor (TNF) antagonists. We analyzed all patients from the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) registry treated with a TNF antagonist (infliximab, etanercept, or adalimumab). Data collected included age, sex, diagnosis and duration of rheumatic disease, type of TNF antagonist, and concomitant treatment. Type of CAE was classified as local or systemic cutaneous manifestation related to treatment administration (infusion reaction), infection, malignancy, or autoimmune skin disease. Time of onset of CAE and outcome were also recorded. The IRs of CAE per 1,000 patient-years of exposure with 95% confidence intervals (95% CIs) were estimated. Multivariable analysis was performed to identify potential risk factors for CAE. A total of 5,437 patients were included, representing 17,330 patient-years of exposure. A total of 920 CAE were reported; the IRs per 1,000 patient-years were 53 (95% CI 50-57) for CAE, 28 (95% CI 25-30) for infection, 15 (95% CI 13-17) for infusion reactions, 5 (95% CI 4-6) for autoimmune skin diseases, and 3 (95% CI 2-4) for skin malignancy. The mean time between starting TNF antagonist treatment and CAE was 1.78 years. In 32% of patients, CAE required TNF antagonist withdrawal. The main risk factors for CAE were female sex and treatment with infliximab, leflunomide, and glucocorticoids. The IR of CAE in patients treated with TNF antagonists is significant and should be addressed carefully, and withdrawal of therapy is required in some cases. Copyright © 2013 by the American College of Rheumatology.

  18. Avascular Necrosis

    Science.gov (United States)

    ... Financial Reports Watchdog Ratings Feedback Contact Select Page Avascular Necrosis Home > Cancer Resources > Late Effects of Treatment > Avascular Necrosis Avascular necrosis (AVN) is a disorder resulting from ...

  19. Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate.

    Science.gov (United States)

    Prasad, Ananda S; Beck, Frances W J; Bao, Bin; Snell, Diane; Fitzgerald, James T

    2008-03-15

    Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial. Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5. Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc.

  20. Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

    Science.gov (United States)

    Ikonomidis, Ignatios; Papadavid, Evangelia; Makavos, George; Andreadou, Ioanna; Varoudi, Maria; Gravanis, Kostas; Theodoropoulos, Kostas; Pavlidis, George; Triantafyllidi, Helen; Moutsatsou, Paraskevi; Panagiotou, Christina; Parissis, John; Iliodromitis, Efstathios; Lekakis, John; Rigopoulos, Dimitrios

    2017-09-01

    Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis. One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment ( P psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857. © 2017 American Heart Association, Inc.

  1. Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months after start of treatment with tumour necrosis factor antagonists: a population-based controlled cohort study.

    Science.gov (United States)

    Olofsson, Tor; Englund, Martin; Saxne, Tore; Jöud, Anna; Jacobsson, Lennart T H; Geborek, Pierre; Allaire, Saralynn; Petersson, Ingemar F

    2010-12-01

    To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden. All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their first treatment with a TNF antagonist between January 2004 and December 2007 and were 18-58 years at treatment start (n = 365), were identified. For each patient with RA, four matched reference subjects from the general population were randomly selected. Data were linked to the Swedish Social Insurance Agency register and the point prevalence of SL and DP as well as days of SL and DP per month were calculated from 360 days before until 360 days after treatment start. At treatment start 38.6% of the patients with RA were registered for SL. During the first 6 months this share dropped to 28.5% (decrease by 26.2%, ptreatment year. Comparing patients with RA to the reference group the relative risk of being on SL was 6.6 (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to 6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to 4.2) and 3.2 (95% CI 2.7 to 3.9). There was a marked decline in SL during the first 6 months of TNF antagonist treatment in patients with RA in southern Sweden, maintained throughout the first year, which was not offset by a corresponding increase in DP.

  2. A CD1d-dependent lipid antagonist to NKT cells ameliorates atherosclerosis in ApoE-/- mice by reducing lesion necrosis and inflammation.

    Science.gov (United States)

    Li, Yi; Kanellakis, Peter; Hosseini, Hamid; Cao, Anh; Deswaerte, Virginie; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

    2016-02-01

    Atherosclerosis-related deaths from heart attacks and strokes remain leading causes of global mortality, despite the use of lipid-lowering statins. Thus, there is an urgent need to develop additional therapies. Reports that NKT cells promote atherosclerosis and an NKT cell CD1d-dependent lipid antagonist (DPPE-PEG350, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethyleneglycol)-350]) reduces allergen-induced inflammation led us to investigate its therapeutic potential in preventing the development and progression of experimental atherosclerosis. DPPE-PEG350 was administered to hyperlipidaemic ApoE(-/-) mice with/without established atherosclerosis. Atherosclerosis and immune cells were assessed in the aortic sinus lesions. Lesion expression of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) responsible for inflammatory immune cell recruitment as well as mRNA expression of IFNγ and its plasma levels were investigated. Necrotic cores and lesion smooth muscle and collagen contents important in plaque stability were determined as were plasma lipid levels. DPPE-PEG350 reduced atherosclerosis development and delayed progression of established atherosclerosis without affecting plasma lipids. CD4 and CD8 T cells and B cells in atherosclerotic lesions were decreased in DPPE-PEG350-treated mice. Lesion MCP-1 and VCAM-1 protein expression and necrotic core size were reduced without affecting lesion smooth muscle and collagen content. IFNγ and lymphocytes were unaffected by the treatment. The attenuation of progression of established atherosclerosis together with reduced development of atherosclerosis in hyperlipidaemic mice by the NKT antagonist, without affecting NKT cell or other lymphocyte numbers, suggests that targeting lesion inflammation via CD1d-dependent activation of NKT cells using DPPE-PEG350 has a therapeutic potential in treating atherosclerosis. Published on behalf of the European Society of

  3. Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

    Directory of Open Access Journals (Sweden)

    R. Dong

    2007-08-01

    Full Text Available The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a. To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB inhibitor aspirin while not affected by the reactive oxygen species (ROS scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

  4. Renal papillary necrosis

    Science.gov (United States)

    ... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

  5. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor a inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie; Landewé, Robert; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jürgen; Murphy, Frederick T.; Xu, Stephen; Zhou, Yiying; Hsia, Elizabeth C.

    2015-01-01

    Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-alpha (TNF)-inhibitor(s). Methods: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active

  6. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  7. Differences in pharmacology of tumor necrosis factor (TNF antagonists

    Directory of Open Access Journals (Sweden)

    S. Bombardieri

    2011-09-01

    Full Text Available The commercially available inhibitors of TNF are constituted by two classes of molecules: the soluble receptors (Etanercept: Amgen Inc. Wyeth and the monoclonal antibodies (Adalimumab: Abbott Laboratories and Infliximab: Centocor, Inc.. The differences in their molecular structure, mechanism of action, pharmacokinetics (PK and pharmacodynamics (PD are discussed, along with the differences concerning dose, administration regimens, drug concentrations and pharmacological interactions. In order to explain the clinical differences observed when these agents are used in the “real world”, which can arise from the respective PK characteristics (kinetics, route and frequency of administration, type of TNF binding, effects on cytokines and PD responses and peculiar mechanisms of action, with distinctive immune function (LFTa inactivation; apoptosis induction, TNF immunoprecipitation, C1q binding and CDC induction; Fcg cross-linking and ADCC induction, the dynamics of interaction of the two classes of neutralizing molecules with TNF, and the ability in restoring TNF homeostasis, are outlined.

  8. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review

    NARCIS (Netherlands)

    Tracey, Daniel; Klareskog, Lars; Sasso, Eric H.; Salfeld, Jochen G.; Tak, Paul P.

    2008-01-01

    During the past 30 years, elucidation of the pathogenesis of rheumatoid arthritis, Crohn's disease, psoriasis, psoriatic arthritis and ankylosing spondylitis at the cellular and molecular levels has revealed that these diseases share common mechanisms and are more closely related than was previously

  9. ORIGINAL ARTICLES Warfarin-induced skin necrosis in HIV-1 ...

    African Journals Online (AJOL)

    F Bhaijee, H Wainwright, G Meintjes, R J Wilkinson, G Todd, E de Vries, D J Pepper. Warfarin-induced skin necrosis (WISN) is a rare complication of warfarin ..... first few days of warfarin therapy.2,11 Warfarin is a vitamin K antagonist and ...

  10. Ischemic necrosis and osteochondritis

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    Osteonecrosis indicates that ischemic death of the cellular constituents of bone and marrow has occurred. Historically, this first was thought to be related to sepsis in the osseous segments. However, continued studies led to the use of the term aseptic necrosis. Subsequent observations indicated that the necrotic areas of bone were not only aseptic, but were also avascular. This led to the terms ischemic necrosis, vascular necrosis and bone infarction. Ischemic necrosis of bone is discussed in this chapter. It results from a significant reduction in or obliteration of blood supply to the affected area. The various bone cells, including osteocytes, osteoclasts, and osteoblasts, usually undergo anoxic death in 12 to 48 hours after blood supply is cut off. The infarct that has thus developed in three-dimensional and can be divided into a number of zones: a central zone of cell death; an area of ischemic injury, most severe near the zone of cell death, and lessening as it moves peripherally; an area of active hyperemia and the zone of normal unaffected tissue. Once ischemic necrosis has begun, the cellular damage provokes an initial inflammatory response, which typically is characterized by vasodilatation, transudation of fluid and fibrin, and local infiltration of flammatory cells. This response can be considered the first stage in repair of the necrotic area

  11. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    Science.gov (United States)

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  12. Subcutaneous encapsulated fat necrosis

    DEFF Research Database (Denmark)

    Aydin, Dogu; Berg, Jais O

    2016-01-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help...

  13. Femoral head avascular necrosis

    International Nuclear Information System (INIS)

    Chrysikopoulos, H.; Sartoris, D.J.; Resnick, D.L.; Ashburn, W.; Pretorius, T.

    1988-01-01

    MR imaging has been shown to be more sensitive and specific than planar scintigraphy for avascular necrosis (AVN) of the femoral head. However, experience with single photon emission CT (SPECT) is limited. The authors retrospectively compared 1.5-T MR imaging with SPECT in 14 patients with suspected femoral head AVN. Agreement between MR imaging and SPECT was present in 24 femurs, 14 normal and ten with AVN. MR imaging showed changes of AVN in the remaining four femoral heads. Of these, one was normal and the other three inconclusive for AVN by SPECT. The authors conclude that MR imaging is superior to SPECT for the evaluation of AVN of the hip

  14. Skin Flap Necrosis After Mastectomy With Reconstruction: A Prospective Study.

    Science.gov (United States)

    Matsen, Cindy B; Mehrara, Babak; Eaton, Anne; Capko, Deborah; Berg, Anastasia; Stempel, Michelle; Van Zee, Kimberly J; Pusic, Andrea; King, Tari A; Cody, Hiram S; Pilewskie, Melissa; Cordeiro, Peter; Sclafani, Lisa; Plitas, George; Gemignani, Mary L; Disa, Joseph; El-Tamer, Mahmoud; Morrow, Monica

    2016-01-01

    Rates of mastectomy with immediate reconstruction are rising. Skin flap necrosis after this procedure is a recognized complication that can have an impact on cosmetic outcomes and patient satisfaction, and in worst cases can potentially delay adjuvant therapies. Many retrospective studies of this complication have identified variable event rates and inconsistent associated factors. A prospective study was designed to capture the rate of skin flap necrosis as well as pre-, intra-, and postoperative variables, with follow-up assessment to 8 weeks postoperatively. Uni- and multivariate analyses were performed for factors associated with skin flap necrosis. Of 606 consecutive procedures, 85 (14 %) had some level of skin flap necrosis: 46 mild (8 %), 6 moderate (1 %), 31 severe (5 %), and 2 uncategorized (0.3 %). Univariate analysis for any necrosis showed smoking, history of breast augmentation, nipple-sparing mastectomy, and time from incision to specimen removal to be significant. In multivariate models, nipple-sparing, time from incision to specimen removal, sharp dissection, and previous breast reduction were significant for any necrosis. Univariate analysis of only moderate or severe necrosis showed body mass index, diabetes, nipple-sparing mastectomy, specimen size, and expander size to be significant. Multivariate analysis showed nipple-sparing mastectomy and specimen size to be significant. Nipple-sparing mastectomy was associated with higher rates of necrosis at every level of severity. Rates of skin flap necrosis are likely higher than reported in retrospective series. Modifiable technical variables have limited the impact on rates of necrosis. Patients with multiple risk factors should be counseled about the risks, especially if they are contemplating nipple-sparing mastectomy.

  15. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

    Science.gov (United States)

    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  16. Anti-tumor necrosis factor-alpha therapies attenuate adaptive arteriogenesis in the rabbit

    NARCIS (Netherlands)

    Grundmann, Sebastian; Hoefer, Imo; Ulusans, Susann; van Royen, Niels; Schirmer, Stephan H.; Ozaki, C. Keith; Bode, Christoph; Piek, Jan J.; Buschmann, Ivo

    2005-01-01

    The specific antagonists of tumor necrosis factor-alpha (TNF-alpha), infliximab and etanercept, are established therapeutic agents for inflammatory diseases such as rheumatoid arthritis and Crohn's disease. Although the importance of TNF-alpha in chronic inflammatory diseases is well established,

  17. Avascular Necrosis of the Capitate

    OpenAIRE

    Bekele, Wosen; Escobedo, Eva; Allen, Robert

    2011-01-01

    Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma.

  18. Avascular Necrosis of the Capitate

    Science.gov (United States)

    Bekele, Wosen; Escobedo, Eva; Allen, Robert

    2011-01-01

    Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma. PMID:22470799

  19. Dual antagonists of integrins.

    Science.gov (United States)

    Nadrah, K; Dolenc, M Sollner

    2005-01-01

    The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.

  20. Femoral head necrosis; Hueftkopfnekrose

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, J.; Scheurecker, G.; Scheurecker, A.; Stoeger, A.; Huber, A. [Roentgeninstitut am Schillerpark, Linz (Austria); Hofmann, S. [Orthopaedisches Landeskrankenhaus Stolzalpe (Austria)

    2009-05-15

    The epidemiology and pathohistogenesis of avascular femoral head necrosis has still not been clarified in detail. Because the course of the disease runs in stages and over a long time period nearly always culminates in the necessity for a total hip prosthesis, an exact radiological evaluation is of paramount importance for the treatment. There is a need for a common staging system to enable comparison of different therapy concepts and especially their long-term results. In this article the ARCO staging system is described in full detail, which includes all radiological modalities as well as histopathological alterations. (orig.) [German] Bei der avaskulaeren Femurkopfnekrose handelt es sich um ein Krankheitsbild, dessen Ursachen noch immer nicht vollstaendig geklaert sind. Da die Erkrankung stadienhaft verlaeuft und ueber einen laengeren Zeitraum betrachtet nahezu immer in einem prothetischen Hueftersatz muendet, ist eine genaue radiologische Abklaerung fuer die Behandlung von enormer Bedeutung. Um Langzeiterfolge verschiedener Therapiekonzepte vergleichen zu koennen, sind eine exakte Beschreibung und darauf basierend die Verwendung einer einheitlichen Stadieneinteilung wuenschenswert. In der vorliegenden Arbeit wird die ARCO-Stadieneinteilung im Detail beschrieben, die alle bildgebenden Methoden beruecksichtigt und histopathologische Veraenderungen mit einbezieht. (orig.)

  1. Airway necrosis after salvage esophagectomy

    International Nuclear Information System (INIS)

    Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

    2010-01-01

    Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

  2. Clinical value of D-Dimer,tumor necrosis factor-a and interleukin-6 levels in type 2 diabetic patients with diabetic retinopathy%2型糖尿病视网膜病变患者血清D-二聚体与肿瘤坏死因子α和白细胞介素6的检测价值

    Institute of Scientific and Technical Information of China (English)

    王晓丽

    2011-01-01

    目的 研究2型糖尿病视网膜病变(DR)患者血清D-二聚体(D-D)、肿瘤坏死因子α(TNF-α和白细胞介素-6(IL-6)水平检测的临床价值.方法 通过眼底血管荧光造影和眼底检查,将80例糖尿病患者分为糖尿病视网膜病变(DR)组(42例)和糖尿病无视网膜病变(NDR)组(38例),另选健康体检者30例作为对照(对照组),对3组D-D、TNF-α和IL-6进行检测.结果 对照组、NDR组及DR组的D-D、TNF-α、IL-6水平分别为(0.34±0.12)mg/L、(4.5±1.7)ng/L、(66.5±19.3)ng/L;(0.59±0.19)mg/L、(15.5±7.9)ng/L、(101.18±30.1)ng/L;(1.08±0.27)ms/L、(42.1±12.6)ng/L、(161.2±48.8)ng/L.糖尿病患者血清D-D、TNF-α和IL-6水平均明显高于对照组(均P<0.05),DR组血清D-D、TNF.仅和IL-6水平均高于NDR组(均P<0.05).结论 DR患者D-D、TNF-α和IL-6水平明显升高,提示此类患者处于高凝状态,且炎症反应可能在糖尿病视网膜DR发展中起重要作用.%Objective To investigate the clinical value of D-dimer (D-D),tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels in type 2 diabetic patients with diabetic retinopathy. Methods All the patients had routine FFA and examination of fundus and were divided into two groups based on the results: normal fundus( NDR group n = 38 ) , diabetic retinopathy( DR group n = 42 ). Thirty healthy subjects were used as control group. The serum levels of D-D, IL-6 and TNF-a was detected. Results The serum levels of D-D, IL-6 and TNF-a of type 2 diabetic patients were higher than those of control group statistically (P < 0.05). The serum levels of D-D, IL-6 and TNF-a of DR group were higher than those of NDR group(P <0.05). Conclusions The levels of D-D, IL-6 and TNF-a in type 2 diabetic patients with diabetic retinopathy are higher than those of normal fundus group. The inflammatory reaction may play an important role in the initiation and sustainment of DR.

  3. Naloxone : actions of an antagonist

    NARCIS (Netherlands)

    Dorp, Eveline Louise Arianna van

    2009-01-01

    The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

  4. Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.

    Science.gov (United States)

    Shinohara, Mayuka; Sumino, Yasuhiro; Sato, Fuminori; Kiyono, Tohru; Hashimoto, Naohiro; Mimata, Hiromitsu

    2017-06-01

    To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored. Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner. Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence. © 2017 The Japanese Urological Association.

  5. Widespread marrow necrosis during pregnancy

    International Nuclear Information System (INIS)

    Knickerbocker, W.J.; Quenville, N.F.

    1982-01-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported. (orig.)

  6. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... INTRODUCTION. The use of antagonistic bacteria to control soil-borne ... plant was used to evaluate the antifungal activities of antagonistic bacteria. ..... antagonistic bacteria and cloning of its phenazine carboxylic acid genes.

  7. Development of delayed radiation necrosis

    International Nuclear Information System (INIS)

    Ohara, ShigFeki; Takagi, Terumasa; Shibata, Taichiro; Nagai, Hajime.

    1983-01-01

    The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later. (author)

  8. Anti-Tumor Necrosis Factor With a Glyco-Engineered Fc-Region Has Increased Efficacy in Mice With Colitis

    NARCIS (Netherlands)

    Bloemendaal, Felicia M.; Levin, Alon D.; Wildenberg, Manon E.; Koelink, Pim J.; Mcrae, Bradford L.; Salfeld, Jochen; Lum, Jenifer; van der Neut Kolfschoten, Marijn; Claassens, Jill W.; Visser, Remco; Bentlage, Arthur; D'Haens, Geert R. A. M.; Verbeek, J. Sjef; Vidarsson, Gestur; van den Brink, Gijs R.

    2017-01-01

    Although tumor necrosis factor (TNF) antagonists reduce many clinical features of inflammatory bowel disease, complete mucosal healing occurs in fewer than 50% of patients. The Fc-region of monoclonal antibodies against TNF has immunosuppressive properties via effects on macrophage polarization. We

  9. Levels of inhibitors of tumor necrosis factor alpha and interleukin 1beta in urine and sera of patients with urosepsis

    NARCIS (Netherlands)

    Olszyna, D. P.; Prins, J. M.; Buis, B.; van Deventer, S. J.; Speelman, P.; van der Poll, T.

    1998-01-01

    The antiinflammatory cytokine response during urosepsis was determined by measurement of concentrations of soluble tumor necrosis factor receptor (sTNFR) types I and II, interleukin 1 receptor antagonist (IL-1ra), soluble IL-1 receptor type II (sIL-1RII), and interleukin 10 in sera and urine of 30

  10. ANTAGONISTIC POTENTIAL OF FLUORESCENT Pseudomonas ...

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    GROWTH OF TOMATO CHALLENGED WITH PHTOPATHOGENS ... This study focused on the antagonistic potential of fluorescent Pseudomonas in vitro, and its inoculation effect on growth .... the 5 days old culture in starch agar with Lugol's.

  11. Necrosis

    Science.gov (United States)

    ... Updated by: Frank A. Greco, MD, PhD, Director, Biophysical Laboratory, Edith Nourse Rogers Memorial Hospital, Bedford, MA. ... any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should ...

  12. Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

    Science.gov (United States)

    Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

    2017-09-01

    Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

  13. [Necrotic leg ulcer revealing vasculitis induced by vitamin K antagonists].

    Science.gov (United States)

    Chabli, H; Hocar, O; Akhdari, N; Amal, S; Hakkou, M; Hamdaoui, A

    2015-12-01

    Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Pathological investigation of radiation necrosis

    International Nuclear Information System (INIS)

    Nakamura, Nishio; Yoshimura, Noriaki; Ikuta, Fusahiro

    1975-01-01

    The brain and spinal cord of an 18-year-old male, who suffered from cerebellar medulloblastoma with subarachnoid spread, had been irradiated by a large amount of Linac X-ray: 14,450 rads to the lower thoracic segments and 7,400 rads to the lumbar segments. The tumor at the roof of the 4th ventricle had disseminated along the ventricular system but was limited to the subarachnoid space of the cervical spinal cord. No remarkable changes were found in the volume or consistency of the thoracic and lumbar cord. Elasticity of the lower thoracic segment was greatly diminished and the cut surfaces were yellowish white and fragile. Microscopically extensive coagulation necrosis was observed with complete disintegration of myelin and axon. Vascular changes were most prominent in the smaller vessels, eg. hyalinous thickening, concentric cleavage, adventitial fibrosis and edema of small artery perivascular spaces, fibrin thrombi occulusion of arterioles and capillaries, and telangiectasia. In the lumbar spinal cord, moderate neuronal degeneration and protoplasmic astrocytosis were observed. Changes in the lumbar posterior white column were considered to be not only secondary degeneration but also a primary lesion caused by irradiation. Liquefactive necrosis in the gray matter of the cervical cord was thought to be a nonspecific circulatory disturbance because of the absence of vascular changes. Vascular changes were thought to be very important in the histological diagnosis of radiation myelopathy and it was supposed that increased permeability of the vessel walls was a factor in coagulation necrosis. They considered this case to have typical histology of radiation myelopathy. (Evans, J.)

  15. Avascular necrosis of the hip

    International Nuclear Information System (INIS)

    Lang, P.; Genant, H.K.; Lindquist, T.; Chafetz, N.; Steiger, P.; Sanny, J.; Rhodes, M.L.; Rothman, S.L.G.; Delamarter, R.; Kilgus, D.

    1988-01-01

    T1-weighted (repetition time [TR] = 450 msec, echo time [TE] = 20 msec), T2-weighted (TR = 1,800 msec, TE = 20 and 80 msec), and T2*-weighted gradient-echo gradient recalled acquisition in a steady state, TR = 70 msec, TE = 30 msec, theta = 15 0 ) MR images (General Electric Signa, 1.5 T) were generated in 11 patients with avascular necrosis of the hip. Three-dimensional MR image reconstruction was performed on an independent imaging system (IIS, Dimensional Medicine Inc). Pelvic and femoral bone contours were computed based on either the T1-weighted or the T2*-weighted images. Three-dimensional displays of necrotic zones and areas of granulation tissue were computed on the basis of the T2-weighted images. The tissues were simultaneously displayed in the three-dimensional images using different colors and transparencies. The three-dimensional MR images generated demonstrated the extent of the necrotic zone and adjacent granulation tissue and their position relative to the weight-bearing surface. They may soon prove to be useful in preoperative planning and intraoperative localization of complex surgical interventions in avascular necrosis of the hip

  16. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  17. [Tuberculosis in rheumatic patients treated with tumour necrosis factor alpha antagonists: the Portuguese experience].

    Science.gov (United States)

    Fonseca, João Eurico; Canhão, Helena; Silva, Cândida; Miguel, Cláudia; Mediavilla, Maria Jesus; Teixeira, Ana; Castelão, Walter; Nero, Patrícia; Bernardes, Miguel; Bernardo, Alexandra; Mariz, Eva; Godinho, Fátima; Santos, Maria José; Bogas, Mónica; Oliveira, Margarida; Saavedra, Maria João; Barcelos, Anabela; Cruz, Margarida; Santos, Rui André; Maurício, Luís; Rodrigues, Mário; Figueiredo, Guilherme; Quintal, Alberto; Patto, José Vaz; Malcata, Armando; da Silva, José Canas; Araújo, Domingos; Ventura, Francisco; Branco, Jaime; Queiroz, Mário Viana

    2006-01-01

    In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.

  18. Influence of tumor necrosis factor α in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    von der Schulenburg, Johann-Matthias

    2005-12-01

    Full Text Available Objective: Rheumatoid arthritis (RA is the most prevalent inflammatory rheumatic disorder. It is a chronic and incurable disease that leads to painful inflammation, often irreversible joint damage, and eventually to functional loss. Conventional treatment is based on unspecific immunosuppressive agents, e.g. Methotrexate, Azathioprin or Gold. However, the longterm outcomes of these approaches have been poor with frequently ongoing inflammatory disease activity, functional decline, and temporary or permanent work disability. More recently, antagonists of the human cytokine Tumor Necrosis Factor α (TNF-α have been introduced that are potent suppressors of inflammatory processes. Infliximab is a chimeric antibody against TNF-α. Etanercept is a soluble human TNF-α receptor. The report assesses the efficacy of TNF-α-antagonists to down-regulate inflammation, improve functional status and prevent joint damage in RA with particular regard to the following indications: Treatment of severe, refractory and ongoing disease activity despite adequate use of conventional antirheumatic agents; and treatment of early RA before conventional treatment failure has been demonstrated. Methods: A systematic review of the literature is been performed using established electronic databases. The literature search is supplemented by a hand search of journals and publications relevant to RA, reviews of websites of national and international rheumatologic expert societies, as well as contacts to manufacturers. A priori defined inclusion and exclusion criteria are used for literature selection. Analysis and evaluation of included publications are based on standardised criteria sets and checklists of the German Scientific Working Group for Technology Assessment in Health Care. Results: Health Technology Assessment reports and metaanalyses cannot be identified. A total of 12 clinical trials are analysed, as well as national and international expert recommendations and

  19. Targeting of regulated necrosis in kidney disease

    Directory of Open Access Journals (Sweden)

    Diego Martin-Sanchez

    2018-03-01

    Full Text Available The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention. Resumen: La idea de que el término necrosis tubular aguda supone una denominación inapropiada se deriva de estudios morfológicos de necropsias humanas. La opinión generalizada ha sido que la necrosis representa una forma pasiva de muerte celular no regulada que no es susceptible de manipulación terapéutica. Los recientes avances han mejorado nuestra comprensión de la muerte celular en la lesión renal aguda. En primer lugar, la apoptosis origina una pérdida celular, pero no desencadena una respuesta inflamatoria. Sin embargo, los intentos rudimentarios de interferir en la apoptosis

  20. Mastectomy skin necrosis after microsurgical breast reconstruction.

    Science.gov (United States)

    Vargas, Christina R; Koolen, Pieter G; Anderson, Katarina E; Paul, Marek A; Tobias, Adam M; Lin, Samuel J; Lee, Bernard T

    2015-10-01

    Mastectomy skin necrosis represents a significant clinical morbidity after immediate breast reconstruction. In addition to aesthetic deformity, necrosis of the native mastectomy skin may require debridement, additional reconstruction, or prolonged wound care and potentially delay oncologic treatment. This study aims to evaluate patient and procedural characteristics to identify predictors of mastectomy skin necrosis after microsurgical breast reconstruction. A retrospective review was performed of all immediate microsurgical breast reconstructions performed at a single academic center. Patient records were queried for age, diabetes, active smoking, previous breast surgery, preoperative radiation, preoperative chemotherapy, body mass index, mastectomy type, mastectomy weight, flap type, autologous flap type, and postoperative mastectomy skin flap necrosis. There were 746 immediate autologous microsurgical flaps performed by three plastic surgeons at our institution during the study period. The incidence of mastectomy skin flap necrosis was 13.4%. Univariate analysis revealed a significantly higher incidence of mastectomy skin necrosis in patients with higher mastectomy weight (P mastectomy type. Multivariate analysis demonstrated statistically significant associations between mastectomy skin necrosis and both increasing mastectomy weight (odds ratio 1.348 per quartile increase, P = 0.009) and diabetes (odds ratio 2.356, P = 0.011). Increasing mastectomy weight and coexisting diabetes are significantly associated with postoperative mastectomy skin necrosis after microsurgical reconstruction. These characteristics should be considered during patient counseling, procedure selection, operative planning, and intraoperative tissue viability assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Programmed necrosis and necroptosis – molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Agata Giżycka

    2015-12-01

    Full Text Available Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

  2. Regulation of Tumor Progression by Programmed Necrosis

    Directory of Open Access Journals (Sweden)

    Su Yeon Lee

    2018-01-01

    Full Text Available Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1, which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

  3. ROLE OF THE MITOCHONDRION IN PROGRAMMED NECROSIS

    Directory of Open Access Journals (Sweden)

    Christopher eBaines

    2010-11-01

    Full Text Available In contrast to the programmed nature of apoptosis and autophagy, necrotic cell death has always been believed to be a random, uncontrolled process that leads to the accidental death of the cell. This dogma, however, is being challenged and the concept of necrosis also being programmed is gaining ground. In particular, mitochondria appear to play a pivotal role in the mediation of programmed necrosis. The purpose of this review, therefore, is to appraise the current concepts regarding the signaling mechanisms of programmed necrosis, with specific attention to the contribution of mitochondria to this process.

  4. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

    Science.gov (United States)

    del Hierro, Piedad Magdalena

    2011-01-01

    Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

  5. Piroxicam induced submassive necrosis of the liver.

    Science.gov (United States)

    Paterson, D; Kerlin, P; Walker, N; Lynch, S; Strong, R

    1992-01-01

    Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction. Images Figure 1 Figure 2 Figure 3 PMID:1446877

  6. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  7. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels

    2015-01-01

    to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

  8. Intracellular serpins, firewalls and tissue necrosis.

    Science.gov (United States)

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

  9. Imaging Tumor Necrosis with Ferumoxytol.

    Directory of Open Access Journals (Sweden)

    Maryam Aghighi

    high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron.Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment.

  10. Interleukin-1 antagonists for diabetes

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, Thomas

    2013-01-01

    pathways. The testing of specific anti-inflammatory biologics targeting single pro-inflammatory cytokines has provided clinical proof-of-concept. EXPERT OPINION: IL-1 antagonists have so far failed to meet primary end points in recent-onset type 1 diabetes in Phase IIa, and promising Phase I and IIa trials......INTRODUCTION: Diabetes is a currently incurable, epidemically growing global health concern. Contemporary symptomatic treatment targets acute and chronic metabolic consequences of relative or absolute insulin deficiency. Intensive multifactorial therapy is required to attenuate morbidity...... and mortality from late micro- and macrovascular complications, and despite current best clinical practice diabetes is still associated with shortened lifespan. There is an unmet need for interventions targeting pathogenetic mechanisms in diabetes, and the market for such therapies is huge. AREAS COVERED...

  11. Bilateral acute retinal necrosis after herpetic meningitis

    Directory of Open Access Journals (Sweden)

    Katsura T

    2012-04-01

    Full Text Available Keisho Hirota1,2, Masayuki Akimoto1,3, Toshiaki Katsura21Department of Ophthalmology, Kyoto Medical Center, National Hospital Organization, 2Internal Medicine, Kyoto Medical Center, 3Clinical Research Center, Kyoto Medical Center, Kyoto, JapanPurpose: The report of a case of bilateral acute retinal necrosis after herpetic meningitis.Case report: A 47-year-old man was admitted with the chief complaint of persistent high fever and transient loss of consciousness. Although his general condition improved after intravenous acyclovir administration, the patient presented with visual loss in both eyes 4 days after admission. Visual acuity in his right eye was 20/200 and his left eye had light perception alone. Both eyes showed panretinal arteritis diagnosed as acute retinal necrosis. Panretinal photocoagulation was performed for both eyes. Progression of retinal detachment was prevented in both eyes; however, visual acuity of the left eye was totally lost because of neovascular glaucoma. Visual acuity of the right eye recovered to 20/20.Conclusion: Although cases of bilateral acute retinal necrosis have been reported after herpetic encephalitis, this condition is rare after herpetic meningitis. Prophylactic acyclovir therapy and early panretinal photocoagulation may prevent retinal detachment and improve the prognosis. Neurologists and ophthalmologists should be aware that not only herpetic encephalitis but also herpetic meningitis can lead to acute retinal necrosis within a very short interval.Keywords: acute retinal necrosis, herpetic meningitis, herpes simplex, varicella zoster virus

  12. Tracheal stoma necrosis: a case repor

    Directory of Open Access Journals (Sweden)

    Pak S

    2017-04-01

    Full Text Available Acute tracheal dilatation, due to an overinflated cuff, has been reported early in the course of mechanical ventilation through an endotracheal tube. Tracheal stoma necrosis is a rare complication, but such can accompany acute tracheal dilation. Herein, we report a case of tracheal necrosis 9 days following tracheostomy placement in a 71-year old woman associated with overinflation of the tracheal tube cuff. This case report aims to 1 add to the scant body of knowledge about the diagnosis and management for the patients with tracheal stoma necrosis and 2 raise awareness for error-traps in interpreting diagnostic images, specifically satisfaction of search error, inattentional blindness error, and alliterative error.

  13. Subcutaneous fat necrosis of the newborn.

    Science.gov (United States)

    Oswalt, G C; Montes, L F; Cassady, G

    1978-08-01

    Subcutaneous fat necrosis of the newborn (SFNN) developed in a 1-week-old black boy. His mother had received numerous medications for eclampsia. Birth was by Caesarean section and complicated by meconium aspiration. There were numerous nodules over the back, buttocks and extremities that yielded a caseous-like material. Microscopically, these nodules showed crystallization and necrosis of the fat. Hypoglycemia, pneumonia, oliguria, thrombocytopenia, seizures and urinary infection were associated with the cutaneous problem and led to a fatal outcome 2 weeks after birth.

  14. Breast necrosis associated with thromboembolic disorders

    International Nuclear Information System (INIS)

    Andersson, I.; Adler, D.D.; Ljungberg, O.; Malmoe Allmaenna Sjukhus; Michigan Univ., Ann Arbor

    1987-01-01

    Two obese women with thrombotic disease complicated by necrosis of the breast are described. In one patient the reaction started after a few days of coumarin treatment and progressed to severe necrosis requiring mastectomy. The other patient was not on anticoagulant therapy when the breast reaction started and the clinical course was less severe. The radiographic appearance was characterized by thickening of the breast trabeculae, increased density of the breast and skin thickening. Although the radiographic findings are non-specific, the correct diagnosis can be suggested if combined with appropriate clinical information. The disease process may mimic breast cancer of the inflammatory type, clinically as well as radiographically. (orig.)

  15. Antagonistic Phenomena in Network Dynamics

    Science.gov (United States)

    Motter, Adilson E.; Timme, Marc

    2018-03-01

    Recent research on the network modeling of complex systems has led to a convenient representation of numerous natural, social, and engineered systems that are now recognized as networks of interacting parts. Such systems can exhibit a wealth of phenomena that not only cannot be anticipated from merely examining their parts, as per the textbook definition of complexity, but also challenge intuition even when considered in the context of what is now known in network science. Here, we review the recent literature on two major classes of such phenomena that have far-reaching implications: (a) antagonistic responses to changes of states or parameters and (b) coexistence of seemingly incongruous behaviors or properties - both deriving from the collective and inherently decentralized nature of the dynamics. They include effects as diverse as negative compressibility in engineered materials, rescue interactions in biological networks, negative resistance in fluid networks, and the Braess paradox occurring across transport and supply networks. They also include remote synchronization, chimera states, and the converse of symmetry breaking in brain, power-grid, and oscillator networks as well as remote control in biological and bioinspired systems. By offering a unified view of these various scenarios, we suggest that they are representative of a yet broader class of unprecedented network phenomena that ought to be revealed and explained by future research.

  16. Avascular necrosis ofbone following renal transplantation

    African Journals Online (AJOL)

    and avascular necrosis was reported in 1957 in a patient ... Onset of pain ranged from 2 months to 36 months .... and corticosteroid-induced diabetes); (iv) severe sec- ... reponed in the shoulder and elbow joints, i.e. humeral head, distal ...

  17. Aseptic necrosis of femoral head complicating thalassemia

    International Nuclear Information System (INIS)

    Orzincolo, C.; Castaldi, G.; Scutellary, P.N.; Bariani, L.; Pinca, A.

    1986-01-01

    Aseptic necrosis of the femoral head is described in 4 patients, selected from 280 patients with homozygous β-thalassemia (Cooley anemia). The incidence of the complication appears to be very high (14.5per mille) in thalassemia, compared to the general population. The possible mechanism are discussed. (orig.)

  18. Colonic ischemic necrosis following therapeutic embolization

    International Nuclear Information System (INIS)

    Shenoy, S.S.; Satchidanand, S.; Wesp, E.H.; State Univ. of New York, Buffalo

    1981-01-01

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding. (orig.)

  19. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  20. Colonic ischemic necrosis following therapeutic embolization

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, S S; Satchidanand, S; Wesp, E H

    1981-07-15

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding.

  1. Development of delayed radiation necrosis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, ShigFeki; Takagi, Terumasa [Meitetsu Hospital, Nagoya (Japan); Shibata, Taichiro; Nagai, Hajime

    1983-04-01

    The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later.

  2. Clinical and CT imaging features of abdominal fat necrosis

    International Nuclear Information System (INIS)

    Zhao Jinkun; Bai Renju

    2013-01-01

    Fat necrosis is a common pathological change at abdominal cross-sectional imaging, and it may cause abdominal pain, mimic pathological change of acute abdomen, or be asymptomatic and accompany other pathophysiologic processes. Fat necrosis is actually the result of steatosis by metabolism or mechanical injury. Common processes that are present in fat necrosis include epiploic appendagitis, infarction of the greater omentum, pancreatitis, and fat necrosis related to trauma or ischemia. As a common fat disease, fat necrosis should be known by clinicians and radiologists. Main content of this text is the clinical symptoms and CT findings of belly fat necrosis and related diseases. (authors)

  3. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

    Dorhout Mees, S. M.; Rinkel, G. J. E.; Feigin, V. L.; Algra, A.; van den Bergh, W. M.; Vermeulen, M.; van Gijn, J.

    2007-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse

  4. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  5. Regulated necrosis and its implications in toxicology.

    Science.gov (United States)

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-03

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. A Case of Unresectable Rectal Necrosis

    Directory of Open Access Journals (Sweden)

    Mohammed Nassif

    2011-01-01

    Full Text Available Introduction. Necrosis of the rectum is an uncommon finding due to abundant collateral vasculature. Its management remains challenging, without clear consensus in the literature. Case Report. We describe a case of a 53-year-old woman with multiple medical comorbidities that presented in septic shock and hematochezia. Colonoscopy revealed ischemic colitis. Conservative management was instituted. At two weeks, she presented evidence of peritonitis. Exploratory laparotomy revealed extensive necrosis of the left colon and rectum. Due to dense inflammation, resection was deemed unsafe. Therefore, a transverse ostomy with mucosal fistula was preformed. Multiple drains were left in place. The patient healed uneventfully. Conclusion. This case illustrates that, if extensive dissection of the distal colon and rectum is unsafe due to the patient's critical condition or technical feasibility, then a diverting ostomy of the proximal viable bowel along with a mucus fistula and good drainage of the abdomen represents an acceptable alternative.

  7. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    OpenAIRE

    Williams, P L; Corbett, M

    1983-01-01

    Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement.

  8. Integrated management of sunflower necrosis disease

    OpenAIRE

    Shirshikar S.P.

    2008-01-01

    Sunflower necrosis disease (SND) is a new threat for sunflower cultivation in India. The disease was observed during 1997 in Karnataka, a major sunflower growing state of India. Later, its occurrence was reported from almost all sunflower growing states of India, posing threat to sunflower cultivation. Presently no reliable resistant sources are available. The disease being viral in nature is very much difficult to combat by single approach. At Oilseeds Research Station, Latur (M.S.), India, ...

  9. Maxillary Necrosis: A Sequelae of Fungal Osteomyelitis

    Directory of Open Access Journals (Sweden)

    K Anbarasi

    2010-01-01

    Full Text Available Osteomyelitis is designated to a variety of bone diseases having inflammation as a common denominator. Persistent infection progresses to inflammation of marrow space, haversian system and periostium of affected region. Thrombosis of endothelial vessels cause necrosis and sequestrum formation. Both pyogenic and nonpyogenic infections of jaw lead to this condition. Immunosuppressed patients are more prone to mycelial infections, whereas their occurrence in immunocompetent individuals are highly unusual.

  10. [Avascular necrosis of the femoral head].

    Science.gov (United States)

    Porubský, Peter; Trč, Tomáš; Havlas, Vojtěch; Smetana, Pavel

    Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

  11. Paraneoplastic digital necrosis associated with rectum carcinoma

    Directory of Open Access Journals (Sweden)

    Ali Alkan

    2015-12-01

    Full Text Available Paraneoplastic vascular pathologies are rare in daily practice. There is limited data about this phenomenon. Patient with a diagnosis of metastatic rectum carcinoma presented with digital necrosis. The work up for vascular and rheumatological pathology was inconclusive. Lesions progressively improved with steroid therapy. Paraneoplastic vascular lesions are rare in oncology practice. Our case points out important parts of a rare clinical entity. J Clin Exp Invest 2015; 6 (4: 391-392

  12. Bladder necrosis: 'A man without a bladder'.

    Science.gov (United States)

    Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

    2018-02-17

    Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Partial avascular necrosis after talar neck fracture.

    Science.gov (United States)

    Babu, Nina; Schuberth, John M

    2010-09-01

    Recently, it has been shown that avascular necrosis of the talus can occur in only a portion of the talar body. There is little information regarding the geographic location of the avascular segment and the clinical significance of an incomplete avascular process. Seven patients with partial avascular necrosis after Hawkins type II or III fracture dislocations were evaluated with magnetic resonance scans. The precise anatomic location of the avascular segment was determined and assigned to a specific quadrant of the talar body. The operative exposure, incidence of collapse, and time to operative intervention was recorded. The avascular segment of the talar body was located predominantly in the anterior lateral and superior portion in six of the seven patients. Collapse occurred in three of the patients in the area of avascular process. There were no observable trends with regard to operative exposure, Hawkins classification, incidence of collapse, or time to operative intervention to the location of the avascular segment. Partial avascular necrosis can occur after fracture dislocation of the talus. The predominant location of the avascular segment was the anterior lateral and superior portion of the talar body. This observation corresponds to regional damage to the blood supply of the talus and may help clarify the pathogenesis of partial avascular process.

  14. NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

    Science.gov (United States)

    Moore, N A; Blackman, A; Awere, S; Leander, J D

    1993-06-11

    In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

  15. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    Energy Technology Data Exchange (ETDEWEB)

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  16. MRI study of avascular necrosis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Simizu, Koh; Suguro, Toru; Tsuchiya, Akihiro; Moriya, Hideshige; Nishikawa, Satoru; Arimizu, Noboru [Chiba Univ. (Japan). School of Medicine

    1990-10-01

    Magnetic resonance (MR) images of 70 joints were reviewed in 38 patients with avascular necrosis of the knee or hip joint, whose ages ranged from 19 to 62 years with an average of 41 years. According to causes, steroid induced avascular necrosis was the commonest, accounting for 87% of cases. The remainer of the cases were alcoholic avascular necrosis (8%) and idiopathic avascular necrosis (5%). Steroid induced avascular necrosis was greatly different from idiopathic avascular necrosis in view of clinical manifestations, common sites, and complications of femur head necrosis. Idiopathic avascular necrosis was common in the central part of internal condyle and was confined to one joint. Steroid induced avascular necrosis was common in the posterior part of external condyle and was frequently associated with multiple necroses of the diaphysis. Seventy five percent of the cases were associated with avascular necrosis of the knee. The diagnostic accuracy of the other imaging modalities in avascular necrosis was low (33% for plain roentgenography and 50% for RI examination). Thus, MR was the imaging procedure of choice for detecting avascular necrotic lesions. (N.K.).

  17. MRI study of avascular necrosis of the knee

    International Nuclear Information System (INIS)

    Simizu, Koh; Suguro, Toru; Tsuchiya, Akihiro; Moriya, Hideshige; Nishikawa, Satoru; Arimizu, Noboru

    1990-01-01

    Magnetic resonance (MR) images of 70 joints were reviewed in 38 patients with avascular necrosis of the knee or hip joint, whose ages ranged from 19 to 62 years with an average of 41 years. According to causes, steroid induced avascular necrosis was the commonest, accounting for 87% of cases. The remainer of the cases were alcoholic avascular necrosis (8%) and idiopathic avascular necrosis (5%). Steroid induced avascular necrosis was greatly different from idiopathic avascular necrosis in view of clinical manifestations, common sites, and complications of femur head necrosis. Idiopathic avascular necrosis was common in the central part of internal condyle and was confined to one joint. Steroid induced avascular necrosis was common in the posterior part of external condyle and was frequently associated with multiple necroses of the diaphysis. Seventy five percent of the cases were associated with avascular necrosis of the knee. The diagnostic accuracy of the other imaging modalities in avascular necrosis was low (33% for plain roentgenography and 50% for RI examination). Thus, MR was the imaging procedure of choice for detecting avascular necrotic lesions. (N.K.)

  18. Tumor necrosis factor alpha inhibitors in the treatment of toxic epidermal necrolysis.

    Science.gov (United States)

    Woolridge, Katelyn F; Boler, Patrick L; Lee, Brian D

    2018-01-01

    Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction for which there is no standardized or consistently effective treatment. Due to a greater understanding of disease pathogenesis and the identification of tumor necrosis factor (TNF) α as a mediator of keratinocyte death, TNF-α antagonists have been used in the treatment of TEN. Specifically, infliximab and etanercept have been shown to be effective at halting disease progression. The objective of this study is to review published case reports and case series using anti-TNF-α medications in the treatment of TEN. Results of many of the articles reviewed support the use of TNF-α inhibitors in TEN in both adult and pediatric populations; however, the risks caused by these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

  19. VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist.

    Science.gov (United States)

    Torrente-Segarra, Vicenç; Acosta Pereira, Asunción; Morla, Rosa; Ruiz, José Miguel; Clavaguera, Teresa; Figuls, Ramon; Corominas, Hector; Geli, Carme; Roselló, Rosa; de Agustín, Juan José; Alegre, Cayetano; Pérez, Carolina; García, Angel; Rodríguez de la Serna, Arturo

    to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. Apoptosis and Necrosis in the Liver

    Science.gov (United States)

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  1. Delayed radiation necrosis in the optochiasmatic region

    International Nuclear Information System (INIS)

    Andoh, Takashi; Yokoyama, Kazutoshi; Kumagai, Morio

    1984-01-01

    Two cases with delayed radiation necrosis of the chiasmatic region following irradiation of the hypophysis for treatment of Cushing's disease were presented. Case 1 was a 36-year-old female who had reduction of visual acuity and bitemporal hemianopsia 2 years after 60 Co-irradiation therapy (total 8000 rads) for Cushing's disease. CT scans showed low density in the pituitary fossa and irregular contrast-enhanced suprasellar mass, and metrizamide CT cisternography revealed the pituitary fossa filled with contrast medium. From those findings, secondary empty sella syndrome was suspicious. Case 2 was a 35-year-old male who had progressive visual disturbance 3 years after 60 Co-irradiation therapy (total 9050 rads) for Cushing's disease. The right visual acuity was 0.05 and the left one was 0.1. Examination of visual field showed left homonymous hemianopsia. CT scans showed the contrast enhanced suprasellar mass extending to the right anterior thalamic region, and metrizamide CT cisternography detected secondary empty sella as same as that of Case 1. Authors reviewed and analyzed literatures of delayed radiation necrosis. The incidence of this condition was 4% to 9% and onset of the symptoms occured approximately 2 years after irradiation to hypophysis. Administration of steroid hormone and surgical treatment for the radiation necrosis involving the chiasmatic region were almost ineffective and also the prognosis of radionecrotic lesions involving the hypothalamus was very poor. Therefore, radiotherapy for hypophyseal region must be carried out by means of a rotation or arching technique in order to avoid this condition and further total dosage and its fractionation in radiation therapy should not exceed 6000 rads and 200 rads a day. (J.P.N.)

  2. Reye's syndrome with cortical laminar necrosis: MRI

    International Nuclear Information System (INIS)

    Kinoshita, T.; Takahashi, S.; Ishii, K.; Higano, S.; Matsumoto, K.; Sakamoto, K.; Haginoya, K.; Iinuma, K.

    1996-01-01

    Serial MRI findings are described in two patients with Reye's syndrome, demonstrating diffuse cortical and white matter changes. In the acute stage, T2-weighted images showed subtle but definite laminar high signal and contrast-enhanced T1-weighted images laminar enhancement, along the entire cerebral cortex bilaterally. In the chronic stage, unenhanced T1-weighted images showed diffuse cortical laminar high signal. These characteristic MRI features seemed very similar to those of laminar cortical necrosis in hypoxic brain damage. MRI also displayed delayed white matter changes with cerebral atrophy. (orig.)

  3. Antagonistic properties of microogranisms associated with cassava ...

    African Journals Online (AJOL)

    The antagonistic properties of indigenous microflora from cassava starch, flour and grated cassava were investigated using the conventional streak, novel ring and well diffusion methods. Antagonism was measured by zone of inhibition between the fungal plug and bacterial streak/ring. Bacillus species were more effective ...

  4. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Influences of carbon adaptation on antagonistic activities of three Pseudomonas aeruginosa strains V4, V7 and V10 against Fusarium oxysporum f. sp. melonis were determined in this study. Results from this study showed that the P. aeruginosa strains and their adapted strains significantly inhibited the growth of mycelium ...

  5. Small molecule antagonists of integrin receptors.

    Science.gov (United States)

    Perdih, A; Dolenc, M Sollner

    2010-01-01

    The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

  6. An avascular necrosis in Gaucher's disease

    International Nuclear Information System (INIS)

    Mansberg, R.; Uren, R.; Howman-Giles, R.

    1999-01-01

    Full text: Avascular necrosis is frequently associated with sickle cell disease and other haemoglobinopathies. It is less commonly associated with Gaucher's disease. A case with multi-modality imaging is presented. A 33-year-old male patient presented with a 4-day history of severe right knee pain. He was a febrile with mild swelling of the right knee. A diagnosis of Gaucher's disease had been made by bone marrow biopsy on a clinical picture of hepatosplenomegaly and thrombocytopenia some years earlier. A radiograph of the knee demonstrated an Erlenmeyer flask deformity of the distal femur. A bone scan demonstrated reduced perfusion to the distal right femoral shaft and femoral condyles. Delayed images demonstrated decreased tracer uptake in the distal right femur extending to the right medial femoral condyle consistent with a vascular necrosis. An MRI of the thighs demonstrated lipid accumulation in the marrow space of both femora consistent with Gaucher's disease associated with changes of bone oedema in the metadiaphysis and epiphysis of the right femur. The patient was treated with supportive measures and made an uneventful recovery and is being commenced on enzyme replacement therapy (Algucerase)

  7. Avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Kokubo, Takeshi; Takatori, Yoshio; Kamogawa, Morihide; Nakamura, Toshitaka; Ninomiya, Setsuo; Yoshikawa, Kohki; Itai, Yuji; Iio, Masahiro; Mitamura, Tadayuki

    1990-01-01

    T1-weighted MR images of thirty-six hips in 25 patients with avascular necrosis of the femoral head were obtained two to five times during the course of 2 to 26 months. We investigated these MR images in the light of the chronological change and compared them with plain radiographs. MR images changes in 16 femoral head; in general, the abnormal low intensity area in the femoral head reduced in extent and the internal high intensity area became smaller of disappeared. Thirteen femoral heads among them became more flattened on plain radiographs in the same period. It is noted that four different zones are defined in the femoral head after bone necrosis takes place: the dead bone marrow, the dead marrow which still contains fat, the reactive interface and the hyperemic bone marrow. In T1-weighted MR images, the dead bone marrow, the reactive interface and the hyperemic bone marrow are demonstrated as low intensity area, while the dead marrow containing fat may remain high in intensity. On the basis of this knowledge of histopathology and MR images of this disease, we suggest that reduction of the abnormal low intensity area and disappearance of the internal high intensity area on MR images can be regarded as diminution of hyperemia in the living bone marrow and loss of fat in the dead bone marrow, respectively. (author)

  8. Myoglobinaemia in relation to cardiac necrosis

    Energy Technology Data Exchange (ETDEWEB)

    McComb, J M

    1981-01-01

    An evaluation of the usefulness of estimation of the serum myoglobin in the detection of myocardial necrosis was made in patients with suspected acute ischemic heart disease and in patients in whom elective cardiac catheterization was performed. Measurement of serum myoglobin, by radioimmunoassay, in patients admitted with suspected acute myocardial infarction, suggested that a raised serum myoglobin level was a sensitive indicator of myocardial necrosis. It also showed that the serum myoglobin rose to abnormal levels before the serum creatine kinase. A study of 70 consecutive patients confirmed that the serum myoglobin level is a sensitive indicator of acute myocardial infarction and showed that its sensitivity was greater, and its specificity similar to that of serum creatine kinase. This study allowed calculation of a predictive index for the diagnosis of acute myocardial infarction from the serum myoglobin and serum creatine kinase six hours after the onset of symptoms. The use of a single myoglobin measurement in 114 patients admitted to a coronary care unit was then studied. The proposition that myocardial damage might results from cardiac catheterization was investigated in 115 patients.

  9. antagonistic effect of native bacillus isolates against black root rot

    African Journals Online (AJOL)

    ACSS

    A number of fungi and bacteria are known to be very effective .... Round. Convex. Smooth. Wrinkled. Slow. BS024. Irregular and spreading. Flat. Wavy .... Antibiotic effect of bacterial antagonist ..... antagonistic Bacillus and Trichoderma isolates ...

  10. MRI Findings of Pericardial Fat Necrosis: Case Report

    International Nuclear Information System (INIS)

    Lee, Hyo Hyeok; Ryu, Dae Shick; Jung, Sang Sig; Jung, Seung Mun; Choi, Soo Jung; Shin, Dae Hee

    2011-01-01

    Pericardial fat necrosis is an infrequent cause of acute chest pain and this can mimic acute myocardial infarction and acute pericarditis. We describe here a patient with the magnetic resonance imaging (MRI) findings of pericardial fat necrosis and this was correlated with the computed tomography (CT) findings. The MRI findings may be helpful for distinguishing pericardial fat necrosis from other causes of acute chest pain and from the fat-containing tumors in the cardiophrenic space of the anterior mediastinum.

  11. Identification of avascular necrosis in the dysplastic proximal femoral epiphysis

    International Nuclear Information System (INIS)

    Mandell, G.A.; Harcke, H.T.; MacKenzie, W.G.; Bassett, G.S.; Scott, C.I. Jr.; Wills, J.S.

    1989-01-01

    Bilateral radiographic irregularities and deformities of the proximal femoral epiphyses are features of both multiple epiphyseal dysplasia and bilateral idiopathic avascular necrosis. In the past these entities have been difficult to differentiate. This report documents radiographically the occurrence of avascular necrosis in 10 patients with multiple epiphyseal dysplasia by recognizing the superimposition of sclerosis and subchondral fissuring on pre-existing symmetrically irregular proximal femoral ossification centers. Scintigraphic (photopenia) or magnetic resonance (loss of signal) criteria of avascular necrosis confirm its added presence and help to establish an imaging scheme to identify avascular necrosis superimposed on multiple epiphyseal dysplasia. (orig.)

  12. Identification of avascular necrosis in the dysplastic proximal femoral epiphysis

    Energy Technology Data Exchange (ETDEWEB)

    Mandell, G A; Harcke, H T [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Medical Imaging; MacKenzie, W G; Bassett, G S [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Orthopaedics; Scott, Jr, C I [Alfred I. duPont Inst., Wilmington, DE (USA). Dept. of Genetics; Wills, J S [Medical Center of Delaware, Newark, DE (USA). Dept. of Radiology

    1989-07-01

    Bilateral radiographic irregularities and deformities of the proximal femoral epiphyses are features of both multiple epiphyseal dysplasia and bilateral idiopathic avascular necrosis. In the past these entities have been difficult to differentiate. This report documents radiographically the occurrence of avascular necrosis in 10 patients with multiple epiphyseal dysplasia by recognizing the superimposition of sclerosis and subchondral fissuring on pre-existing symmetrically irregular proximal femoral ossification centers. Scintigraphic (photopenia) or magnetic resonance (loss of signal) criteria of avascular necrosis confirm its added presence and help to establish an imaging scheme to identify avascular necrosis superimposed on multiple epiphyseal dysplasia. (orig.).

  13. Indomethacin induced avascular necrosis of head of femur

    Science.gov (United States)

    Prathapkumar, K; Smith, I; Attara, G

    2000-01-01

    Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present.
The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.


Keywords: indomethacin; avascular necrosis PMID:10964124

  14. Avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Kokubo, Takashi; Takatori, Yoshio; Ninomiya, Setsuo; Sasaki, Yasuhito

    1993-01-01

    Magnetic resonance (MR) images and conventional radiographs were compared in 142 hips with avascular necrosis, and a staging system for the disease based on MR imaging was developed. MR images were classified into three patterns: a band of low signal intensity (class I); an area of low signal intensity with internal spot(s) of high signal (class II); and an area of low signal intensity without internal spots of high signal (class III). Most MR class I lesions were in radiographic stage I (normal) or II (sclerotic or cystic changes without collapse). Most MR class II lesions were in radiographic stage III (segmental collapse), and most MR class III lesions were in stage III or IV (secondary degenerative changes). The MR image classification was closely correlated with radiographic staging (p<0.01, using χ square test). We considered that this classification closely reflected the different stages of the disease according to the histopathology of the bone marrow. (author)

  15. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    2010-01-01

    Full Text Available In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  16. Medicinal Chemistry of Competitive Kainate Receptor Antagonists

    Science.gov (United States)

    2010-01-01

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1−5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure−activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  17. Pharmacological analysis of calcium antagonist receptors

    International Nuclear Information System (INIS)

    Reynolds, I.J.

    1987-01-01

    This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

  18. Avascular necrosis of bone following renal transplantation | Naiker ...

    African Journals Online (AJOL)

    Alcohol conswnption and radiological evidence of osteoporosis were more prevalent in the avascular necrosis group (42,8% v. 29,0% and 28,5% v. 7,2% respectively). Avascular necrosis did not correlate with age, sex, renal function at 1 year or severe secondary hyperparathyroidism. This study suggests that corticosteroid ...

  19. Skin Necrosis from Intra-articular Hyaluronic Acid Injection.

    Science.gov (United States)

    Kim, Whan B; Alhusayen, Raed O

    2015-01-01

    Tissue necrosis is a rare yet potentially serious complication of intra-articular (IA) hyaluronic acid (HA) injections for treatment of knee osteoarthritis. To report a case of a patient with cutaneous necrosis after IA HA injection for treatment of knee osteoarthritis, presenting as a livedoid violaceous patch on the right knee. We report a case of cutaneous necrosis as a rare complication of IA HA injection for treatment of knee osteoarthritis. A literature review was undertaken of similar cases. Use of HA IA injections in the treatment of osteoarthritis can result in similar skin necrosis at uncommon anatomic locations corresponding to the site of HA injection. Although tissue necrosis is a rare complication, physicians need to be aware of this possibility as a complication of HA IA injections in the treatment of osteoarthritis and should be mindful of potential treatment options to manage this adverse event. © 2014 Canadian Dermatology Association.

  20. NecroQuant: quantitative assessment of radiological necrosis

    Science.gov (United States)

    Hwang, Darryl H.; Mohamed, Passant; Varghese, Bino A.; Cen, Steven Y.; Duddalwar, Vinay

    2017-11-01

    Clinicians can now objectively quantify tumor necrosis by Hounsfield units and enhancement characteristics from multiphase contrast enhanced CT imaging. NecroQuant has been designed to work as part of a radiomics pipelines. The software is a departure from the conventional qualitative assessment of tumor necrosis, as it provides the user (radiologists and researchers) a simple interface to precisely and interactively define and measure necrosis in contrast-enhanced CT images. Although, the software is tested here on renal masses, it can be re-configured to assess tumor necrosis across variety of tumors from different body sites, providing a generalized, open, portable, and extensible quantitative analysis platform that is widely applicable across cancer types to quantify tumor necrosis.

  1. Atraumatic Pantalar Avascular Necrosis in a Patient With Alcohol Dependence.

    Science.gov (United States)

    Callachand, Fayaz; Milligan, David; Wilson, Alistair

    2016-01-01

    In the United States, an estimated 10,000 to 20,000 new cases of avascular necrosis are diagnosed each year. We present an unusual case of atraumatic avascular necrosis with widespread hindfoot and midfoot involvement. A 62-year-old female with a history of alcohol dependence and smoking, who had previously been treated for avascular necrosis of the knee, presented with right-sided foot pain and difficulty weightbearing. Imaging studies revealed extensive avascular necrosis of the hindfoot and midfoot, which precluded simple surgical intervention. The patient was followed up for 18 months. In the last 8 months of the 18-month period, the patient managed her symptoms using an ankle-foot orthosis. A diagnosis of avascular necrosis should be considered in patients with atraumatic foot and ankle pain, especially in the presence of risk factors such as alcohol excess and smoking. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  2. A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS

    International Nuclear Information System (INIS)

    Sun Jian; Feng Jiannan; Li Yan; Shen Beifen

    2006-01-01

    B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family. Because of its roles in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome (SS), BLyS antagonists have been tested to treat SLE- and RA-like symptoms in mice and obtained optimistic results. So far, reported BLyS antagonists were mostly decoyed BLyS receptors or anti-BLyS antibodies. In this study, a novel BLyS antagonist peptide, PT, was designed based on the modeling 3-D complex structure of BCMA and BLyS. The interaction mode of PT with BLyS was analyzed theoretically. The results of competitive ELISA demonstrated that PT could inhibit the binding of BCMA-Fc and anti-BLyS antibody to BLyS in vitro. In addition, PT could partly block the proliferating activity of BLyS on mice splenocytes. The BLyS antagonizing activity of PT was significant (p < 0.05). This study highlights the possibility of using BLyS antagonist peptide to neutralize BLyS activity. Further optimization of PT with computer-guided molecular design method to enhance its biopotency may be useful in developing new BLyS antagonists to treat BLyS-related autoimmune diseases

  3. Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist

    International Nuclear Information System (INIS)

    Fielding, S.; Wilker, J.C.; Chernack, J.; Ramirez, V.; Wilmot, C.A.; Martin, L.L.; Payack, J.F.; Cornfeldt, M.L.; Rudolphi, K.A.; Rush, D.K.

    1990-01-01

    8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia

  4. Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Heejin Lim

    2018-03-01

    Full Text Available The binding of the tumor necrosis factor α (TNFα to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel®, infliximab (Remicade®, adalimumab (Humira®, certolizumab-pegol (Cimzia®, and golimumab (Simponi®, are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.

  5. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

  6. Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-alpha antibody

    NARCIS (Netherlands)

    Jansen, J.; van der Poll, T.; Levi, M. [=Marcel M.; ten Cate, H.; Gallati, H.; ten Cate, J. W.; van Deventer, S. J.

    1995-01-01

    The role of tumor necrosis factor-alpha in the shedding of soluble tumor necrosis factor receptors in endotoxemia was investigated. The appearance of the soluble tumor necrosis factor receptors was assessed in four healthy volunteers following an intravenous injection of tumor necrosis factor-alpha

  7. Necrosis, a regulated mechanism of cell death La necrosis, un mecanismo regulado de muerte celular

    Directory of Open Access Journals (Sweden)

    Mauricio Rojas López

    2010-05-01

    Full Text Available

    Three types of cellular death have been defined by morphological and biochemical criteria: apoptosis, necrosis and autophagy. Apoptosis is a regulated cell death, mainly mediated by caspases; autophagy induces degradation of intracellular damaged organelles through the formation of vesicles that fuse with hydrolytic vacuoles.

     

    Necrosis has been traditionally defined by the rupture the cytoplasmic membrane with subsequent release of intracellular material, triggering localized inflammatory Intrinsic cellular activities and the events preceding cellular collapse are critical to determine the type of tissue damage.

     

    The fact that all three types of cellular death can coexist in any organ and tissue with different availabilities of ATP, suggests that necrosis can be conceived as an active event and that to some extent it may be regulated. Alterations in the structure of proteins and in the

  8. Predictive value of histologic tumor necrosis after radiation.

    Science.gov (United States)

    Chen, Y; Taghian, A G; Rosenberg, A E; O'Connell, J; Okunieff, P; Suit, H D

    2001-12-20

    Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS-26, SCC-21, and HGL-21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One-half of the tumor was divided into 1-mm(3) fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCD(p) (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. Copyright 2001 Wiley-Liss, Inc.

  9. United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

    Science.gov (United States)

    Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

    2015-02-01

    We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    International Nuclear Information System (INIS)

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-01-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis

  11. Avascular necrosis of the femoral head presenting as trochanteric bursitis.

    Science.gov (United States)

    Mandell, B F

    1990-01-01

    Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement. PMID:2241294

  12. Mandibular bone necrosis after use of paraformaldehyde-containing paste

    Directory of Open Access Journals (Sweden)

    Chi-hwan Lee

    2016-11-01

    Full Text Available Paraformaldehyde has been used in the past as a pulpotomy agent. However, it has a severe cytotoxic effect and may cause alveolar bone necrosis. Depulpin, a devitalizing agent containing 49% paraformaldehyde, is no longer used frequently due to its severe side effects. In the two cases described in the present study, Depulpin was used as a devitalizing agent during root canal treatment. It caused a gradual loss of sensibility in adjacent teeth, gingival necrosis, and osteomyelitis. This case report demonstrates the serious side effects of using a paraformaldehyde-containing paste as a devitalizing agent for pulp, particularly mandibular bone necrosis.

  13. MR imaging of avascular necrosis of carpal bones

    International Nuclear Information System (INIS)

    Taniguchi, Yasunori; Funaoka, Nobuhiko; Yoshida, Munehito; Iwahashi, Toshiyuki; Egawa, Hiromitsu; Shima, Kimihiro; Tamaoki, Tetsuya.

    1991-01-01

    The usefulness of MRI in carpal avascular necrosis was investigated in 20 cases, 16 in lunates, 3 in scaphoids and 1 in triquetrum, with T1 and T2 weighted images of the spin echo and T2 weighted images of the field echo. Early diagnosis of carpal bone necrosis was possible when the T1 weighted image showed a moderate low intensity signal. A high intensity signal in the T2 weighted image indicated the onset of revascularization, and a favorable prognosis. A normal signal indicated healing of carpal avascular necrosis. MRI was found to be very useful in establishing the diagnosis and in determining the prognosis of carpal osteonecrosis. (author)

  14. MR imaging of avascular necrosis of carpal bones

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yasunori; Funaoka, Nobuhiko; Yoshida, Munehito [Kinan General Hospital, Wakayama (Japan); Iwahashi, Toshiyuki; Egawa, Hiromitsu; Shima, Kimihiro; Tamaoki, Tetsuya

    1991-03-01

    The usefulness of MRI in carpal avascular necrosis was investigated in 20 cases, 16 in lunates, 3 in scaphoids and 1 in triquetrum, with T1 and T2 weighted images of the spin echo and T2 weighted images of the field echo. Early diagnosis of carpal bone necrosis was possible when the T1 weighted image showed a moderate low intensity signal. A high intensity signal in the T2 weighted image indicated the onset of revascularization, and a favorable prognosis. A normal signal indicated healing of carpal avascular necrosis. MRI was found to be very useful in establishing the diagnosis and in determining the prognosis of carpal osteonecrosis. (author).

  15. Avascular necrosis of the trapezoid bone following carpometacarpal arthroplasty.

    Science.gov (United States)

    Kane, Patrick; Waryasz, Greg; Katarincic, Julie

    2014-03-03

    A 58-year-old female developed avascular necrosis of her trapezoid approximately 3 months after undergoing carpometacarpal arthroplasty. The patient was treated conservatively with immobilization and had complete resolution of her clinical symptoms during her year of follow-up. Additionally, radiographic examination showed complete restoration of the height of her trapezoid approximately 1 year after the index procedure. Avascular necrosis of the trapezoid is extremely rare with very few cases described in the literature. This is the first description of avascular necrosis following carpometacarpal arthroplasty.

  16. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  17. Hypocretin antagonists in insomnia treatment and beyond.

    Science.gov (United States)

    Ruoff, Chad; Cao, Michelle; Guilleminault, Christian

    2011-01-01

    Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

  18. Plaquing procedure for infectious hematopoietic necrosis virus

    Science.gov (United States)

    Burke, J.A.; Mulcahy, D.

    1980-01-01

    A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.

  19. Management Options in Avascular Necrosis of Talus.

    Science.gov (United States)

    Dhillon, Mandeep S; Rana, Balvinder; Panda, Inayat; Patel, Sandeep; Kumar, Prasoon

    2018-01-01

    Avascular necrosis (AVN) of the talus can be a cause of significant disability and is a difficult problem to treat. The most common cause is a fracture of the talus. We have done a systematic review of the literature with the following aims: (1) identify and summarize the available evidence in literature for the treatment of talar AVN, (2) define the usefulness of radiological Hawkins sign and magnetic resonance imaging in early diagnosis, and (3) provide patient management guidelines. We searched MEDLINE and PUBMED using keywords and MESH terminology. The articles' abstracts were read by two of the authors. Forty-one studies met the inclusion criteria of the 335 abstracts screened. The interventions of interest included hindfoot fusion, conservative measures, bone grafting, vascularized bone graft, core decompression, and talar replacement. All studies were of Level IV evidence. We looked to identify the study quality, imprecise and sparse data, reporting bias, and the quality of evidence. Based on the analysis of available literature, we make certain recommendations for managing patients of AVN talus depending on identified disease factors such as early or late presentation, extent of bone involvement, bone collapse, and presence or absence of arthritis. Early talar AVN seems best treated with protected weight bearing and possibly in combination with extracorporeal shock wave therapy. If that fails, core decompression can be considered. Arthrodesis should be saved as a salvage procedure in late cases with arthritis and collapse, and a tibiotalocalcaneal fusion with bone grafting may be needed in cases of significant bone loss. Role of vascularized bone grafting is still not defined clearly and needs further investigation. Future prospective, randomized studies are necessary to guide the conservative and surgical management of talar AVN.

  20. Management options in avascular necrosis of talus

    Directory of Open Access Journals (Sweden)

    Mandeep S Dhillon

    2018-01-01

    Full Text Available Avascular necrosis (AVN of the talus can be a cause of significant disability and is a difficult problem to treat. The most common cause is a fracture of the talus. We have done a systematic review of the literature with the following aims: (1 identify and summarize the available evidence in literature for the treatment of talar AVN, (2 define the usefulness of radiological Hawkins sign and magnetic resonance imaging in early diagnosis, and (3 provide patient management guidelines. We searched MEDLINE and PUBMED using keywords and MESH terminology. The articles' abstracts were read by two of the authors. Forty-one studies met the inclusion criteria of the 335 abstracts screened. The interventions of interest included hindfoot fusion, conservative measures, bone grafting, vascularized bone graft, core decompression, and talar replacement. All studies were of Level IV evidence. We looked to identify the study quality, imprecise and sparse data, reporting bias, and the quality of evidence. Based on the analysis of available literature, we make certain recommendations for managing patients of AVN talus depending on identified disease factors such as early or late presentation, extent of bone involvement, bone collapse, and presence or absence of arthritis. Early talar AVN seems best treated with protected weight bearing and possibly in combination with extracorporeal shock wave therapy. If that fails, core decompression can be considered. Arthrodesis should be saved as a salvage procedure in late cases with arthritis and collapse, and a tibiotalocalcaneal fusion with bone grafting may be needed in cases of significant bone loss. Role of vascularized bone grafting is still not defined clearly and needs further investigation. Future prospective, randomized studies are necessary to guide the conservative and surgical management of talar AVN.

  1. Management Options in Avascular Necrosis of Talus

    Science.gov (United States)

    Dhillon, Mandeep S; Rana, Balvinder; Panda, Inayat; Patel, Sandeep; Kumar, Prasoon

    2018-01-01

    Avascular necrosis (AVN) of the talus can be a cause of significant disability and is a difficult problem to treat. The most common cause is a fracture of the talus. We have done a systematic review of the literature with the following aims: (1) identify and summarize the available evidence in literature for the treatment of talar AVN, (2) define the usefulness of radiological Hawkins sign and magnetic resonance imaging in early diagnosis, and (3) provide patient management guidelines. We searched MEDLINE and PUBMED using keywords and MESH terminology. The articles' abstracts were read by two of the authors. Forty-one studies met the inclusion criteria of the 335 abstracts screened. The interventions of interest included hindfoot fusion, conservative measures, bone grafting, vascularized bone graft, core decompression, and talar replacement. All studies were of Level IV evidence. We looked to identify the study quality, imprecise and sparse data, reporting bias, and the quality of evidence. Based on the analysis of available literature, we make certain recommendations for managing patients of AVN talus depending on identified disease factors such as early or late presentation, extent of bone involvement, bone collapse, and presence or absence of arthritis. Early talar AVN seems best treated with protected weight bearing and possibly in combination with extracorporeal shock wave therapy. If that fails, core decompression can be considered. Arthrodesis should be saved as a salvage procedure in late cases with arthritis and collapse, and a tibiotalocalcaneal fusion with bone grafting may be needed in cases of significant bone loss. Role of vascularized bone grafting is still not defined clearly and needs further investigation. Future prospective, randomized studies are necessary to guide the conservative and surgical management of talar AVN. PMID:29887631

  2. History of the 'geste antagoniste' sign in cervical dystonia.

    Science.gov (United States)

    Poisson, A; Krack, P; Thobois, S; Loiraud, C; Serra, G; Vial, C; Broussolle, E

    2012-08-01

    The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

  3. Avascular necrosis in sickle cell (homozygous S) patients: Predictive ...

    African Journals Online (AJOL)

    2013-04-24

    Apr 24, 2013 ... Results: The prevalence of AVN in sickle cell patients was ... Key words: Avascular necrosis, homozygous S, platelet count, sickle cell anemia, white cell count .... frequency of vaso‑occlusive crisis, platelet, and white cell.

  4. 'Femoral head necrosis' in metabolic and hormonal osteopathies

    International Nuclear Information System (INIS)

    Heuck, F.H.W.; Treugut, H.

    1984-01-01

    The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. (orig.) [de

  5. Prevalence and associations of symptomatic renal papillary necrosis ...

    African Journals Online (AJOL)

    2015-11-12

    Nov 12, 2015 ... Diagnosis was based on microscopic hematuria and positive ultrasound findings. Their steady ... until recently the most widely accepted first account was documented by ... papillary necrosis in sickle cell anemia patients in.

  6. Mammographic and sonographic features of fat necrosis of the breast

    International Nuclear Information System (INIS)

    Upadhyaya, Vidya S; Uppoor, Raghuraj; Shetty, Lathika

    2013-01-01

    Imaging features of fat necrosis vary depending on its stage of evolution and can mimic malignancy in late stages. Imaging may suffice to differentiate fat necrosis in the early stages from malignancy and thus avoid unnecessary biopsy. In this pictorial essay, we present combination of benign features in mammography and/or ultrasonography (USG) that can lead to imaging diagnosis of fat necrosis. The follow-up imaging features of fat necrosis which mirror its pathophysiological evolution have also been demonstrated. To summarize, in the appropriate clinical setting, no mammographic features suspicious for malignancy should be present. When the typical mammographic features are not present, USG can aid with the diagnosis and follow up USG can confirm it

  7. A Case of Trapezium Avascular Necrosis Treated Conservatively.

    Science.gov (United States)

    Petsatodis, Evangelos; Ditsios, Konstantinos; Konstantinou, Panagiotis; Pinto, Iosafat; Kostretzis, Lazaros; Theodoroudis, Ioannis; Pilavaki, Mayia

    2017-01-01

    Avascular necrosis (AVN) of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

  8. A Case of Trapezium Avascular Necrosis Treated Conservatively

    Directory of Open Access Journals (Sweden)

    Evangelos Petsatodis

    2017-01-01

    Full Text Available Introduction. Avascular necrosis (AVN of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. Case Presentation. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. Conclusion. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

  9. Bilateral streptococcal corneoscleritis complicating β irradiation induced scleral necrosis

    International Nuclear Information System (INIS)

    Moriarty, A.P.; Crawford, G.J.; McAllister, I.L.; Constable, I.J.

    1993-01-01

    Bacterial corneoscleritis may complicate scleral necrosis induced by β irradiation following pterygium removal. Previous cases have been unilateral. The authors report a case of severe bilateral corneoscleritis caused by Streptococcus pneumoniae. (author)

  10. Gastric Necrosis due to Acute Massive Gastric Dilatation

    Directory of Open Access Journals (Sweden)

    Ibrahim Aydin

    2013-01-01

    Full Text Available Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

  11. Gastric Necrosis due to Acute Massive Gastric Dilatation.

    Science.gov (United States)

    Aydin, Ibrahim; Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

    2013-01-01

    Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

  12. Gastric volvulus with partial and complete gastric necrosis

    Science.gov (United States)

    Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

    2014-01-01

    Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature. PMID:24604987

  13. Gastric volvulus with partial and complete gastric necrosis

    Directory of Open Access Journals (Sweden)

    Ram Mohan Shukla

    2014-01-01

    Full Text Available Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature.

  14. Genetic ablation of soluble tumor necrosis factor with preservation of membrane tumor necrosis factor is associated with neuroprotection after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Madsen, Pernille M; Clausen, Bettina H; Degn, Matilda

    2016-01-01

    Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored tumor necrosis factor and as cleaved soluble tumor necrosis factor forms. We previously demonstrated that tumor necrosis factor...... reduced infarct volumes at one and five days after stroke. This was associated with improved functional outcome after experimental stroke. No changes were found in the mRNA levels of tumor necrosis factor and tumor necrosis factor-related genes (TNFR1, TNFR2, TACE), pro-inflammatory cytokines (IL-1β, IL-6...... knockout mice display increased lesion volume after focal cerebral ischemia, suggesting that tumor necrosis factor is neuroprotective in experimental stroke. Here, we extend our studies to show that mice with intact membrane-anchored tumor necrosis factor, but no soluble tumor necrosis factor, display...

  15. Implication of snail in metabolic stress-induced necrosis.

    Directory of Open Access Journals (Sweden)

    Cho Hee Kim

    2011-03-01

    Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

  16. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  17. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

    The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

  18. Antagonistic activity of marine sponges associated Actinobacteria

    Directory of Open Access Journals (Sweden)

    Selvakumar Dharmaraj

    2016-06-01

    Full Text Available Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology, nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance, physiological (pH, temperature and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate, soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are

  19. Assay method for organic calcium antagonist drugs and a kit for such an assay

    International Nuclear Information System (INIS)

    Snyder, S. H.; Gould, R. J.

    1985-01-01

    A method for measuring the level of organic calcium antagonist drug in a body fluid comprises preparing a mixture of a radioactive calcium antagonist drug, a body fluid containing a calcium antagonist drug and a calcium antagonist receptor material, measuring the radioactivity of the radioactive calcium antagonist drug bound to said calcium antagonist receptor material and deriving the concentration of the calcium antagonist drug in the body fluid from a standard curve indicating the concentration of calcium antagonist drug versus inhibition of binding of said radioactive calcium antagonist drug to said receptor sites caused by the calcium antagonist drug in said body fluid. A kit for measuring the level of an organic calcium drug comprises a receptacle containing a radioactive calcium antagonist drug, a calcium antagonist receptor material and a standard amount of a nonradioactive calcium antagonist drug

  20. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

    DEFF Research Database (Denmark)

    Tricoci, Pierluigi; Huang, Zhen; Held, Claes

    2012-01-01

    Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.......Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation....

  1. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    Science.gov (United States)

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  2. Vitamin K antagonist use and mortality in dialysis patients

    NARCIS (Netherlands)

    Voskamp, Pauline W.M.; Rookmaaker, Maarten B.; Verhaar, Marianne C.; Dekker, Friedo W.; Ocak, Gurbey

    2018-01-01

    Background. The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc

  3. Evaluation of antagonistic fungi against charcoal rot of sunflower ...

    African Journals Online (AJOL)

    In vitro, sensitivity of Macrophomina phaseolina (Tassi) Goid determined through inhibition zone technique to various antagonistic fungi viz., Aspergillus niger, Aspergillus flavus, Trichoderma viride, Trichoderma harzianum and Penicillium capsulatum amended into PDA medium. All the antagonists reduced the colony ...

  4. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat

    Directory of Open Access Journals (Sweden)

    Alireza Komaki

    2014-07-01

    Full Text Available Introduction: Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP injection of cannabinoid CB1 receptor antagonist (AM251 in the presence of alpha-1 adrenergic antagonist (Prazosin on rat behavior in the EPM. Methods: In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg, Prazosin (0.3 mg/kg and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg. Results: Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Discussion: Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  5. Interaction between Antagonist of Cannabinoid Receptor and Antagonist of Adrenergic Receptor on Anxiety in Male Rat.

    Science.gov (United States)

    Komaki, Alireza; Abdollahzadeh, Fatemeh; Sarihi, Abdolrahman; Shahidi, Siamak; Salehi, Iraj

    2014-01-01

    Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in the presence of alpha-1 adrenergic antagonist (Prazosin) on rat behavior in the EPM. In this study, the data were obtained from male Wistar rat, which weighing 200- 250 g. Animal behavior in EPM were videotaped and saved in computer for 10 min after IP injection of saline, AM251 (0.3 mg/kg), Prazosin (0.3 mg/kg) and AM251 + Prazosin, subsequently scored for conventional indices of anxiety. During the test period, the number of open and closed arms entries, the percentage of entries into the open arms of the EPM, and the spent time in open and closed arms were recorded. Diazepam was considered as a positive control drug with anxiolytic effect (0.3, 0.6, 1.2 mg/kg). Diazepam increased the number of open arm entries and the percentage of spent time on the open arms. IP injection of AM251 before EPM trial decreased open arms exploration and open arm entry. Whereas, Prazosin increased open arms exploration and open arm entry. This study showed that both substances in simultaneous injection have conflicting effects on the responses of each of these two compounds in a single injection. Injection of CB1 receptor antagonist may have an anxiogenic profile in rat, whereas adrenergic antagonist has an anxiolytic effect. Further investigations are essential for better understanding of anxiolytic and anxiogenic properties and neurobiological mechanisms of action and probable interactions of the two systems.

  6. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    Science.gov (United States)

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  7. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  8. Effects of Tumor Necrosis Factor Blocker on Salicylate-Induced Tinnitus in Mice.

    Science.gov (United States)

    Hwang, Juen-Haur; Huang, David Chang-Wei; Lu, Yin-Chang; Yang, Wei-Shiung; Liu, Tien-Chen

    2017-06-01

    Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control. The tinnitus score significantly decreased in the Enbrel® treated group. The mRNA levels of both TNFR1 and TNFR2 were significantly lower in the treatment than in the control group. The mRNA levels of NR2B and DREAM followed a similar trend. we found that treatment with 30 mg/ kg Enbrel® decreased salicylate-induced behavior associated with tinnitus and reduced the mRNA expression levels of TNFR1/R2, NR2B, and DREAM in the cochlea of mice. These findings supported the hypothesis that neuroinflammation might be a novel mechanism for salicylate-induced tinnitus.

  9. Immobilization increases interleukin-6, but not tumour necrosis factor-a, release from the leg during exercise in humans

    DEFF Research Database (Denmark)

    Reihmane, Dace; Hansen, Andreas Vigelsø; Jensen, Martin Gram

    2013-01-01

    have now studied the temporal relationship of leg IL-6 and TNF-a release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.......6 ± 0.7 kg m; and maximal oxygen uptake, 46.8 ± 1.4 ml kg min) performed 45 min of two-legged dynamic knee-extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler...

  10. Interferon-¿- and tumour necrosis factor-a-producing cells in humans who are immune to cutaneous leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, K; Theander, T G; Hviid, L

    1999-01-01

    Individuals infected with Leishmania major usually acquire immunity to cutaneous leishmaniasis. In this study we have investigated peripheral blood mononuclear cells (PBMC) stimulated by Leishmania antigens in two groups of Sudanese individuals, one with a history of cutaneous leishmaniasis and one...... leishmaniasis produced significantly higher levels of IFN-gamma and TNF-alpha than cells from individuals without a history of the disease. Similar levels of IL-10 were found in the two groups. Flow cytometric analysis revealed high numbers of CD3+ cells producing IFN-gamma and TNF-alpha, and only a few CD3......+ cells containing IL-10, in the PBMC cultures from the individuals with a history of cutaneous leishmaniasis. Interferon-gamma and TNF-alpha were predominantly produced by CD4+ T cells rather than CD8+ T cells. The results suggest that cellular immunity against cutaneous leishmaniasis is mediated...

  11. Diclofenac inhibits tumor necrosis factor-a-induced nuclear factor-kB activation causing synergic hepatocyte apoptosis

    NARCIS (Netherlands)

    Frederiksson, L; Herpers, B; Benedetti, G; Matadin, Q; Puigvert, J.C.; de Bont, H; Dragovic, S.; Vermeulen, N.P.E.; Commandeur, J.N.M.; Danen, E; de Graauw, M; van de Water, B.

    2011-01-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by

  12. Study on radiation necrosis following intraoperative radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Tanaka, Yoshiaki; Takeshita, Nagayuki; Niwa, Kohkichi; Kamata, Noriko; Matsuda, Tadayoshi; Matsutani, Masao

    1989-01-01

    Ninety-five patients with primary or metastatic brain tumors were treated with the intraoperative radiotherapy (IORT). In seven cases, surgery was performed a second time because of suspected of tumor recurrence, later found to be a radiation necrosis. Tumorous lesions were irradiated by IORT in the range of 15 Gy to 20 Gy together with external radiotherapy in the 30 Gy to 72 Gy range. In follow-up postcontrast CT studies, irregularly-shaped lesions appeared at the IORT site and increased in size with the perifocal low density area on subsequent scans. The images resembled those seen in tumor recurrence. Histopathologic changes seen during the follow-up surgery were thought to be mainly the result of radiation necrosis, though viable tumor cells at the marginal tumor site were one possible etiology. A coagulation necrosis with a fibrin exudate was observed in the IORT portal area and the vascular walls exhibited marked degeneration which is symptomatic of delayed radiation necrosis. Thus, post-IORT radiation necrosis is thought to be a direct reaction to this technique, and the delayed absorption of necrotic tissue to be a direct reaction to this technique, and the delayed absorption of necrotic tissue clearly indicates the possibility of adverse effects in its use for treatment of brain tumors. (author)

  13. Effect of bevacizumab on radiation necrosis of the brain

    International Nuclear Information System (INIS)

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A.

    2007-01-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% (±22 SD), and the average change in the FLAIR images was 60% (±18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg (±3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment

  14. The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

    Science.gov (United States)

    Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Uterine Necrosis after Uterine Artery Embolization for Symptomatic Fibroids

    Directory of Open Access Journals (Sweden)

    Steve Kyende Mutiso

    2018-01-01

    Full Text Available Introduction. Uterine artery embolization (UAE is a minimally invasive intervention that is used in the treatment of fibroids. UAE can lead to complications including postembolization syndrome, postprocedure pain, infection, endometrial atrophy leading to secondary amenorrhea, and uterine necrosis. Uterine necrosis after UAE is very rare and hence poses a clinical dilemma for any clinician in its identification and management. We document a case of uterine necrosis after UAE and conduct a literature review on its causation, clinical features, and management principles. Case. A patient presented one month after UAE with abdominal pain and abdominal vaginal discharge. Her work-up revealed features of possible uterine necrosis with sepsis and she was scheduled for a laparotomy and a subtotal hysterectomy was performed. She was subsequently managed with broad spectrum antibiotic and recovered well. Conclusion. Uterine necrosis after UAE is a rare occurrence and we hope the documentation of this case will add to the body of knowledge around it. Theories that explain its occurrence include the use of small particles at embolization, the use of Contour-SE a spherical poly-vinyl alcohol, and lack of collateral supply to the uterus. Its symptoms may be nonspecific but unremitting abdominal pain is invariably present. Finally although conservative management may be successful at times, surgical management with hysterectomy will be required in some cases. The prognosis is good after diagnosis and surgical management.

  16. Management of infected pancreatic necrosis: state of the art

    Directory of Open Access Journals (Sweden)

    Roberto Rasslan

    Full Text Available ABSTRACT Pancreatic necrosis occurs in 15% of acute pancreatitis. The presence of infection is the most important factor in the evolution of pancreatitis. The diagnosis of infection is still challenging. Mortality in infected necrosis is 20%; in the presence of organic dysfunction, mortality reaches 60%. In the last three decades, there has been a real revolution in the treatment of infected pancreatic necrosis. However, the challenges persist and there are many unsolved questions: antibiotic treatment alone, tomography-guided percutaneous drainage, endoscopic drainage, video-assisted extraperitoneal debridement, extraperitoneal access, open necrosectomy? A step up approach has been proposed, beginning with less invasive procedures and reserving the operative intervention for patients in which the previous procedure did not solve the problem definitively. Indication and timing of the intervention should be determined by the clinical course. Ideally, the intervention should be done only after the fourth week of evolution, when it is observed a better delimitation of necrosis. Treatment should be individualized. There is no procedure that should be the first and best option for all patients. The objective of this work is to critically review the current state of the art of the treatment of infected pancreatic necrosis.

  17. Antagonistic neural networks underlying differentiated leadership roles

    Science.gov (United States)

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  18. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  19. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  20. Pediatric Digital Necrosis Secondary to Dressing Application: A Case Series.

    Science.gov (United States)

    Bjorklund, Kim A; Rice, Dahlia M; Amalfi, Ashley N

    2018-04-01

    Pediatric digital necrosis resulting in revision amputation is a devastating outcome following digital dressing application. We report a series of 4 pediatric patients (age: 21 months-11 years) who presented for surgical consultation related to digital ischemia and irreversible necrosis following the application of Coban digital dressings. A review of the literature demonstrated that such injuries had not previously been described. In our case series, Coban dressing was utilized as a deterrent for thumb sucking, fingertip tuft fractures with nail bed lacerations, and a phalanx fracture secondary to crush injury. All 4 children suffered digital necrosis secondary to Coban dressings and ultimately required revision amputation. We discuss risks factors, application practices, and strategies to minimize complications with digital dressings in the pediatric population with the intent of creating awareness among hand surgeons to help promote safe practices and improve patient outcomes.

  1. A Rare Cause of Acute Abdomen: Idiopathic Isolated Cecal Necrosis

    Directory of Open Access Journals (Sweden)

    Ender Özer

    2015-03-01

    Full Text Available Idiopathic isolated cecal necrosis is a clinical problem characterized by right-sided inferior abdominal pain. It is rarely seen, develops due to decreased blood flow to the colon and, imitates acute appendicitis. Its clinical signs are similar to many illnesses causing sensitivity in the right inferior quadrant and, the diagnosis is generally determined during surgery. An 86-year-old male patient presented with the complaints of abdominal pain, trichiniasis, nausea and vomiting. Surgical intervention was decided when physical examination and laboratory results were taken into consideration. After diagnostic laparoscopy, right hemicolectomy was performed because of cecal necrosis. While the mortality and morbidity rates for ischemic bowel disease are high, prognosis for early diagnosed patients with isolated cecal necrosis is better, provided that timely surgical treatment is decided.

  2. Magnetic resonance imaging of the femoral head necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Shinya; Asada, Kanji; Yoshida, Kenjiro and others

    1986-06-01

    Ten patients with avascular femoral head necrosis and four normal adults were examined by magnetic resonance imaging (MRI). In addition, the relationship between MRI and pathophysiology of three operated-on avascular femoral heads was evaluated. The medullary cavities of the normal femoral heads had a strong signal intensity on the saturation recovery (SR) image due to fat marrow, and the T/sub 1/ relaxation time was 160 +- 11 msec. In avascular femoral head necrosis, the necrotic area had a low signal intensity on the SR image and a prolonged T/sub 1/ relaxation time, while the reactive fibrous area had more prolonged T/sub 1/ relaxation time. For these reasons, MRI was found to show the pathological changes of avascular femoral head necrosis and can be expected to be useful for making early diagnoses and operation planning.

  3. Magnetic resonance imaging of the femoral head necrosis

    International Nuclear Information System (INIS)

    Narita, Shinya; Asada, Kanji; Yoshida, Kenjiro

    1986-01-01

    Ten patients with avascular femoral head necrosis and four normal adults were examined by magnetic resonance imaging (MRI). In addition, the relationship between MRI and pathophysiology of three operated-on avascular femoral heads was evaluated. The medullary cavities of the normal femoral heads had a strong signal intensity on the saturation recovery (SR) image due to fat marrow, and the T 1 relaxation time was 160 ± 11 msec. In avascular femoral head necrosis, the necrotic area had a low signal intensity on the SR image and a prolonged T 1 relaxation time, while the reactive fibrous area had more prolonged T 1 relaxation time. For these reasons, MRI was found to show the pathological changes of avascular femoral head necrosis and can be expected to be useful for making early diagnoses and operation planning. (author)

  4. Contemporary management of infected necrosis complicating severe acute pancreatitis

    Science.gov (United States)

    Jamdar, Saurabh; Siriwardena, Ajith K

    2006-01-01

    Pancreatic necrosis complicating severe acute pancreatitis is a challenging scenario in contemporary critical care practice; it requires multidisciplinary care in a setting where there is a relatively limited evidence base to support decision making. This commentary provides a concise overview of current management of patients with infected necrosis, focusing on detection, the role of pharmacologic intervention, and the timing and nature of surgical interventions. Fine-needle aspiration of necrosis remains the mainstay for establishment of infection. Pharmacological intervention includes antibiotic therapy as an adjunct to surgical debridement/drainage and, more recently, drotrecogin alfa. Specific concerns remain regarding the suitability of drotrecogin alfa in this setting. Early surgical intervention is unhelpful; surgery is indicated when there is strong evidence for infection of necrotic tissue, with the current trend being toward 'less drastic' surgical interventions. PMID:16356213

  5. Radiation necrosis of the mandible: a 10 year study. Part II. Dental factors; onset, duration and management of necrosis

    International Nuclear Information System (INIS)

    Murray, C.G.; Herson, J.; Daly, T.E.; Zimmerman, S.

    1980-01-01

    In a review of patients receiving radiation for cancer in the oral region the rate of radiation necrosis of the mandible was found to be similar for patients who had dental extractions before radiation therapy and for the remainder of the dentate population. It was suggested that diseased teeth should be removed prior to irradiation and sufficient healing time should be allowed. Teeth should not be extracted after irradiation. Dental prostheses can be provided for most irradiated patients if adequate care is exercised. The probability of necrosis commencing was highest three to twelve months after the start of therapy; it diminished gradually after that period. The duration of necrosis was depicted as an exponential curve with a constant probability of necrosis termination at each time point after onset. In 46.8% of the patients in study II (1971-1975), the necrosis was healed by conservative means. This was a significant increase over study I (1966-1969), and a complementary reduction in the necessity for surgical intervention was also found

  6. Imaging of cavitary necrosis in complicated childhood pneumonia

    International Nuclear Information System (INIS)

    Hodina, M.; Schnyder, P.; Gudinchet, F.; Hanquinet, S.; Cotting, J.

    2002-01-01

    The aim of this study was to illustrate the chest radiographs (CR) and CT imaging features and sequential findings of cavitary necrosis in complicated childhood pneumonia. Among 30 children admitted in the Pediatric Intensive Care Unit for persistent or progressive pneumonia, respiratory distress or sepsis despite adequate antibiotic therapy, a study group of 9 children (5 girls and 4 boys; mean age 4 years) who had the radiographic features and CT criteria for cavitary necrosis complicated pneumonia was identified. The pathogens identified were Streptococcus pneumoniae (n=4), Aspergillus (n=2), Legionella (n=1), and Staphylococcus aureus (n=1). Sequential CR and CT scans were retrospectively reviewed. Follow-up CR and CT were evaluated for persistent abnormalities. Chest radiographs showed consolidations in 8 of the 9 patients. On CT examination, cavitary necrosis was localized to 1 lobe in 2 patients and 7 patients showed multilobar or bilateral areas of cavitary necrosis. In 3 patients of 9, the cavitary necrosis was initially shown on CT and visualization by CR was delayed by a time span varying from 5 to 9 days. In all patients with cavities, a mean number of five cavities were seen on antero-posterior CR, contrasting with the multiple cavities seen on CT. Parapneumonic effusions were shown by CR in 3 patients and in 5 patients by CT. Bronchopleural fistulae were demonstrated by CT alone (n=3). No purulent pericarditis was demonstrated. The CT scan displayed persistent residual pneumatoceles of the left lower lobe in 2 patients. Computed tomography is able to define a more specific pattern of abnormalities than conventional CR in children with necrotizing pneumonia and allows an earlier diagnosis of this rapidly progressing condition. Lung necrosis and cavitation may also be associated with Aspergillus or Legionella pneumonia in the pediatric population. (orig.)

  7. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  8. Bullous lesions, sweat gland necrosis and rhabdomyolysis in alcoholic coma

    Directory of Open Access Journals (Sweden)

    Neelakandhan Asokan

    2014-01-01

    Full Text Available A 42-year-old male developed hemorrhagic bullae and erosions while in alcohol induced coma. The lesions were limited to areas of the body in prolonged contact with the ground in the comatose state. He developed rhabdomyolysis, progressing to acute renal failure (ARF. Histopathological examination of the skin showed spongiosis, intraepidermal vesicles, and necrosis of eccrine sweat glands with denudation of secretory epithelial lining cells. With supportive treatment and hemodialysis, the patient recovered in 3 weeks time. This is the first reported case of bullous lesions and sweat gland necrosis occurring in alcohol-induced coma complicated by rhabdomyolysis and ARF.

  9. Avascular necrosis of the epiphysis of the first metatarsal bone

    Energy Technology Data Exchange (ETDEWEB)

    Souverijns, G.; Peene, P.; Cleeren, P. [Department of Radiology, Virga Jesse Hospital, Hasselt (Belgium); Raes, M. [Department of Pediatrics, Virga Jesse Hospital, Hasselt (Belgium); Steenwerckx, A. [Department of Orthopaedics, Virga Jesse Hospital, Hasselt (Belgium)

    2002-06-01

    We report a case of avascular necrosis of the epiphysis of the right first metatarsal in a 6-year-old boy. Radiographs showed sclerosis, collapse and a crescent sign in the epiphysis. The diagnosis was confirmed by magnetic resonance imaging and scintigraphy. Arch support was the therapy of choice. Six months after the onset of symptoms, a definite reossification was present. To our knowledge, this is the first radiological report of avascular necrosis of the epiphysis of the first metatarsal bone in the world literature, which prompted a review of the osteochondroses and their etiology. (orig.)

  10. Viral erythrocytic necrosis: Chapter 2.2.7

    Science.gov (United States)

    Winton, James R.; Hershberger, Paul K.

    2014-01-01

    Viral erythrocytic necrosis (VEN), originally termed piscine erythrocytic necrosis, is a condition that has been reported to affect the red blood cells (RBCs) of many species of marine and anadromous fishes in both the Atlantic and Pacific Oceans (Nicholson and Reno 1981; Smail 1982; Wolf 1988; Dannevig and Thorud 1999). Fish with VEN may develop a severe anemia that can reduce their stamina, predispose them to other infections or increase the impact of other stressors (MacMillan et al. 1980; Nicholson and Reno 1981; Meyers et al. 1986; Haney et al. 1992) resulting in population-scale impacts in susceptible species (Hershberger et al. 2009).

  11. Avascular necrosis of the epiphysis of the first metatarsal bone

    International Nuclear Information System (INIS)

    Souverijns, G.; Peene, P.; Cleeren, P.; Raes, M.; Steenwerckx, A.

    2002-01-01

    We report a case of avascular necrosis of the epiphysis of the right first metatarsal in a 6-year-old boy. Radiographs showed sclerosis, collapse and a crescent sign in the epiphysis. The diagnosis was confirmed by magnetic resonance imaging and scintigraphy. Arch support was the therapy of choice. Six months after the onset of symptoms, a definite reossification was present. To our knowledge, this is the first radiological report of avascular necrosis of the epiphysis of the first metatarsal bone in the world literature, which prompted a review of the osteochondroses and their etiology. (orig.)

  12. A SELECTIVE ANTAGONIST OF MINERALOCORTICOID RECEPTOR EPLERENONE IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    B. B. Gegenava

    2015-01-01

    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  13. Characterization and design of antagonistic shape memory alloy actuators

    International Nuclear Information System (INIS)

    Georges, T; Brailovski, V; Terriault, P

    2012-01-01

    Antagonistic shape memory actuators use opposing shape memory alloy (SMA) elements to create devices capable of producing differential motion paths and two-way mechanical work in a very efficient manner. There is no requirement for additional bias elements to ‘re-arm’ the actuators and allow repetitive actuation. The work generation potential of antagonistic shape memory actuators is determined by specific SMA element characteristics and their assembly conditions. In this study, the selected SMA wires are assembled in antagonistic configuration and characterized using a dedicated test bench to evaluate their stress–strain characteristics as a function of the number of cycles. Using these functional characteristics, a so-called ‘working envelope’ is built to assist in the design of such an actuator. Finally, the test bench is used to simulate a real application of an antagonistic actuator (case study). (paper)

  14. 5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.

    Science.gov (United States)

    Ates, Ali; Burssens, Pierre; Lorthioir, Olivier; Lo Brutto, Patrick; Dehon, Gwenael; Keyaerts, Jean; Coloretti, Francis; Lallemand, Bénédicte; Verbois, Valérie; Gillard, Michel; Vermeiren, Céline

    2018-04-23

    Selective leads: In this study, we generated a new series of serotonin 5-HT 7 receptor antagonists. Their synthesis, structure-activity relationships, and selectivity profiles are reported. This series includes 5-HT 7 antagonists with unprecedented high selectivity for the 5-HT 7 receptor, setting the stage for lead optimization of drugs acting on a range of neurological targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Autopsy case of delayed radiation necrosis of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Ihara, Katsuo; Otsutomo, Michinori; Takeshita, Gen (Aomori Rosai Hospital (Japan))

    1984-06-01

    A 48-year-old housewife underwent radiation therapy with 5,000 rad of cobalt following surgery for craniopharyngioma. One year later she developed symptoms of increased intracranial pressure, so that recurrence or occurrence of cerebral tumor was suspected. She died two years after the occurrence of the disease and was found to have had delayed radiation necrosis of the brain at autopsy.

  16. A case report of radiation necrosis of the larynx

    International Nuclear Information System (INIS)

    Tanaka, Eiichi; Inouye, Tetsuzo; Hiraide, Fumihisa; Tsubaki, Yasukiyo; Miyakogawa, Norimasa; Sawada, Masamichi

    1983-01-01

    A case of radiation necrosis of the larynx is reported. The patient was a 79-year-old man who was radiated with the dosis of 3900 rad for suspected carcinoma of the larynx in 1976 and 5300 rad for carcinoma of the larynx in 1980. After completion of radiation therapy, he started to have hoarseness. He was admitted to the hospital because of severe dyspnea. Fiberoptic examination revealed almost complete obstruction of the laryngeal lumen by necrotic tissues due to radiation necrosis. There was little space reserved for respiration. No motility of the vocal cords and arytenoids was observed. After tracheostomy, conservative local and systemic treatments and repeated removal of necrotic tissues through laryngomicrosurgery were performed. However, an advanced necrosis with infection could not be controlled. Therefore, total laryngectomy was performed. Microscopically, no malignant cells were noted in the larynx. As most soft tissues were degenerated into fibrosis, the pharynx was left open. When infection was entirely controlled, the lining flap method from the anterior chest was applied to close the pharynx. When severe radiation necrosis occurs in the larynx, laryngectomy is sometimes mandatory to be performed. It is important that infection should be controlled before and after laryngectomy. Delayed skin flap method is advised. (author)

  17. Expression of human soluble tumor necrosis factor (TNF)-related ...

    African Journals Online (AJOL)

    DR NJ TONUKARI

    2011-06-06

    Jun 6, 2011 ... bio-technique in bacterial (Lin et al., 2007), yeast (Xu et al., 2003) ... biological activity, such as human somatotropin (hST) .... sion way with chloroplast transit peptide (Wang et al., .... chloroplast protein synthesis capacity by massive expression of a ... necrosis factor-related apoptosis-inducing ligand in vivo.

  18. Generation of truncated recombinant form of tumor necrosis factor ...

    African Journals Online (AJOL)

    7. Original Research Article. Generation of truncated recombinant form of tumor necrosis factor ... as 6×His tagged using E.coli BL21 (DE3) expression system. The protein was ... proapoptotic signaling cascade through TNFR1. [5] which is ...

  19. Pituitary necrosis and vasospasm following removal of craniopharyngioma

    Directory of Open Access Journals (Sweden)

    Linda Ratanaprasatporn

    2015-03-01

    Full Text Available We report a case of vasospasm complicating delayed pituitary necrosis after craniopharyngioma resection in an 18-year old female. This is the first reported case that utilizes aggressive blood pressure management, fluid optimization, and rheologic doses of mannitol to successfully treat severe symptomatic vasospasm.

  20. Cytokines and chemokines involved in acute retinal necrosis

    NARCIS (Netherlands)

    L. De Visser (Lenneke); J.H. de Boer (Joke); G.T. Rijkers; Wiertz, K. (Karin); H.J. van den Ham; de Boer, R. (Rob); van Loon, A.M. (Anton M.); A. Rothová (Aniki); J.D.F. de Groot-Mijnes (Jolanda )

    2017-01-01

    textabstractPURPOSE. To investigate which cytokines and chemokines are involved in the immunopatho-genesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. METHODS. Serum and aqueous humor (AH) samples of 19 patients

  1. Case report of radiation necrosis of the larynx

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Eiichi; Inouye, Tetsuzo; Hiraide, Fumihisa; Tsubaki, Yasukiyo; Miyakogawa, Norimasa; Sawada, Masamichi (National Defence Medical Coll., Tokorozawa, Saitama (Japan))

    1983-02-01

    A case of radiation necrosis of the larynx is reported. The patient was a 79-year-old man who was radiated with the dosis of 3900 rad for suspected carcinoma of the larynx in 1976 and 5300 rad for carcinoma of the larynx in 1980. After completion of radiation therapy, he started to have hoarseness. He was admitted to the hospital because of severe dyspnea. Fiberoptic examination revealed almost complete obstruction of the laryngeal lumen by necrotic tissues due to radiation necrosis. There was little space reserved for respiration. No motility of the vocal cords and arytenoids was observed. After tracheostomy, conservative local and systemic treatments and repeated removal of necrotic tissues through laryngomicrosurgery were performed. However, an advanced necrosis with infection could not be controlled. Therefore, total laryngectomy was performed. Microscopically, no malignant cells were noted in the larynx. As most soft tissues were degenerated into fibrosis, the pharynx was left open. When infection was entirely controlled, the lining flap method from the anterior chest was applied to close the pharynx. When severe radiation necrosis occurs in the larynx, laryngectomy is sometimes mandatory to be performed. It is important that infection should be controlled before and after laryngectomy. Delayed skin flap method is advised.

  2. Biofilms associated with bowel necrosis: A newly recognised ...

    African Journals Online (AJOL)

    role of biofilms has been established for oral infections, chronic wounds, indwelling ... bowel in infants and may be of significance in the pathogenesis of bowel necrosis and the ... implications in the understanding of the disease process. .... showed areas of mucosal ulceration and ... venous and urinary catheters, and dental.

  3. El factor de necrosis de los tumores o caquectina

    Directory of Open Access Journals (Sweden)

    Jorge Eliécer Ossa Londoño

    1988-02-01

    Full Text Available

    Se presenta una revisión de la literatura sobre el Factor de Necrosis de los Tumores o Caquectina, con base en artículos publicados durante los anos 1986-1987, haciendo hincapié en las diferencias funcionales y moleculares entre el FNT Alfa, la Linfotoxina o FNT Beta y la Caquectina. Se enfatizan los mecanismos del shock, de la necrosis tumoral y de la caquexia; se Indican las propiedades antitumorales del FNT in vivo e in vitro y se esbozan esquemas terapéuticos experimentales que permiten colegir que el FNT tendrá un papel Importante en la Inmunoterapia del cáncer en el hombre.

    This is a review of the 1986-1987 Literature on the Tumor Necrosis Factor (TNF or Cachectin, emphasizing functional and molecular differences among TNF alpha, Iymphotoxin or TNF beta and Cachectin. Mechanisms of shock, tumor necrosis and cachexia are discussed. In vivo and ín vítro antitumoral properties of TNF are indicated, as well as some experimental therapeutic regimens. These facts allow the suggestion that TNF might become an Important aid for Immunotherapy of cancer In humans.

  4. Biofilms associated with bowel necrosis: A newly recognised ...

    African Journals Online (AJOL)

    All specimens showed varying degrees of bowel necrosis and an organising acute peritoneal reaction. In addition, all showed colonies of Gram-negative bacteria within a mucopolysaccharide matrix. Conclusions. The identification of biofilms in necrotic bowel has raised questions regarding their clinical implications. Further ...

  5. Total gastric necrosis: A case report and literature review | Huang ...

    African Journals Online (AJOL)

    During the surgery, we found a total of 3500ml unclotted blood in the abdomen, splenic infarction and gastric necrosis. Total gastrectomy with Roux-en-Y esophagojejunostromy and splenectomy was performed. However, the patient died on the second day after the surgery. This case suggests that surgical treatment should ...

  6. Vascularized bone grafting in a canine carpal avascular necrosis model

    NARCIS (Netherlands)

    Willems, Wouter F.; Alberton, Gregory M.; Bishop, Allen T.; Kremer, Thomas

    2011-01-01

    Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting. A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone. In seven mongrel dogs, AVN was induced by removal of the radial

  7. Avascular necrosis of the hip in multiple epiphyseal dysplasia

    International Nuclear Information System (INIS)

    Mackenzie, W.G.; Bassett, G.S.; Mandell, G.A.; Scott, C.I. Jr.

    1989-01-01

    We observed radiographic changes of avascular necrosis (AVN) of the capital femoral epiphysis in 9 hips of 11 patients with multiple epiphyseal dysplasia (MED). Plain roentgenography, bone scintigraphy, and magnetic resonance imaging (MRI) studies all revealed characteristic asymmetric changes in the presence of AVN superimposed on dysplastic femoral heads

  8. Cytokines and Chemokines Involved in Acute Retinal Necrosis

    NARCIS (Netherlands)

    de Visser, Lenneke; H de Boer, Joke; T Rijkers, Ger; Wiertz, Karin; van den Ham, Henk-Jan; de Boer, Rob; M van Loon, Anton; Rothova, Aniki; de Groot-Mijnes, Jolanda D F

    2017-01-01

    Purpose: To investigate which cytokines and chemokines are involved in the immunopathogenesis of acute retinal necrosis (ARN), and whether cytokine profiles are associated with clinical manifestations, such as visual outcome. Methods: Serum and aqueous humor (AH) samples of 19 patients with ARN were

  9. Cerebral radiation necrosis: limits and prospects of experimental models

    International Nuclear Information System (INIS)

    Lefaix, J.L.

    1992-01-01

    Cerebral radiation necrosis is the major CNS hazard of clinical treatment therapy involving delivery of high doses of radiation to the brain. It is generally irreversible and frequently leads to death from brain necrosis. Necrosis has been reported with total doses of 60 Gy, delivered in conventional fractions. Symptoms depend upon the volume of brain irradiated and are frequently those of an intracranial mass and may be present as an area of gliosis or frank necrosis. Possible causes include some direct effect of radiation on glial cells, vascular changes and the action of an immunological mechanism. The weight of evidence suggests that demyelination is important in the early delayed reaction, and that vascular changes gradually become more important in the late delayed reactions, from several months to years after treatment. The advent of sophisticated radiographic technologies such as computed tomography, magnetic resonance imaging and spectroscopy, and positron emission tomography have facilitated serial non invasive examination of morphologic or physiologic parameters within the brain after irradiation. Limits and prospects of these technologies are reviewed in experimental animal models of late radiation injuries of the brain, which were carried out in many species ranging from mouse to monkey

  10. Pathological features of cerebral radiation necrosis - Part I

    International Nuclear Information System (INIS)

    Lefaix, J.L.

    1992-01-01

    Cerebral radiation necrosis is a major hazard of radiation therapy involving delivery of high doses of radiation to the brain. It is generally irreversible and frequently leads to death from brain necrosis. Necrosis has been reported with total doses of 50-60 Gy, delivered in conventional fractions of 1.7 to 2 Gy daily. Signs and symptoms depend upon the volume of brain irradiated and are frequently those of an intracranial mass. Injury tends to be more severe in white matter and may be present as an area of gliosis or frank necrosis. Possible causes include some direct effect of radiation on glial cells, vascular changes and the action of an immunological mechanism. The weight of evidence suggests that demyelination is important in the early delayed reaction, and that vascular changes gradually become more important in the late delayed reactions, several months to years after treatment. Late delayed radiation injuries of the brain and spinal cord are reviewed in man, dog, monkey and rat

  11. Fibrinolytic response to tumor necrosis factor in healthy subjects

    NARCIS (Netherlands)

    van der Poll, T.; Levi, M. [=Marcel M.; Büller, H. R.; van Deventer, S. J.; de Boer, J. P.; Hack, C. E.; ten Cate, J. W.

    1991-01-01

    Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men,

  12. Prevalence and associations of symptomatic renal papillary necrosis ...

    African Journals Online (AJOL)

    Aim: To assess the prevalence and associations of symptomatic renal papillary necrosis (RPN) in sickle cell anemia patients. Patients and Methods: The case notes of homozygous hemoglobin (Hb) S patients diagnosed with RPN were retrospectively assessed. Diagnosis was based on microscopic hematuria and positive ...

  13. Avascular necrosis in sickle cell (homozygous S) patients: Predictive ...

    African Journals Online (AJOL)

    ... with the development of AVN. Conclusion: In conclusion, patients with a raised steady state platelet count may have a higher tendency to develop AVN and may require closer orthopedic review and prophylactic intervention. Key words: Avascular necrosis, homozygous S, platelet count, sickle cell anemia, white cell count ...

  14. Pravastatin Protects Against Avascular Necrosis of Femoral Head via Autophagy.

    Science.gov (United States)

    Liao, Yun; Zhang, Ping; Yuan, Bo; Li, Ling; Bao, Shisan

    2018-01-01

    Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro . An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro . We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

  15. Morphometric findings in avascular necrosis of the femoral head.

    Science.gov (United States)

    Kamal, Diana; Trăistaru, Rodica; Alexandru, D O; Kamal, C K; Pirici, D; Pop, O T; Mălăescu, D Gh

    2012-01-01

    Avascular necrosis of the femoral head is an illness with a controversial etiology, the trigger event being the suppression of blood flow to the femoral head. The disease affects mostly young adults within their third and fifth decade, the majority of the patients being men. The main risk factors are trauma, chronic alcohol consumption, smoking, corticotherapy. The main goal of our study is to describe the morphometric changes found in the bone tissue of patients diagnosed with avascular necrosis of the femoral head, with different risk factors, by comparing the area of bone trabeculae inside the area of necrosis with that from the adjacent viable tissue. The morphometric study used biological material from 16 patients with ages between 29 and 57 years, who underwent surgery for avascular necrosis of the femoral head. They were admitted in the Orthopedics Department at the Emergency County Hospital in Craiova between 2010 and 2011 and were split into four groups. Group I presented trauma as the main risk factor, Group II had corticotherapy as the defining risk factor, Group III presented chronic alcohol consumption and Group IV was represented by the patients who smoked and exhibited chronic alcohol consumption. There was not a significant statistical difference between the areas of bone trabeculae of the four groups when we compared viable bone tissue to the necrotized one. Knowing the risk factors of the avascular necrosis of the femoral head is critical to the management of the disease, because diagnosing it in an early stage is a necessity for obtaining a good result for conservative treatment.

  16. Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists

    Directory of Open Access Journals (Sweden)

    Urbano PCM

    2014-07-01

    Full Text Available Paulo César Martins Urbano,1 Vanete Thomaz Soccol,1 Valderilio Feijó Azevedo2 1Biotechnology and Bioprocess Engineering Program, Federal University of Parana, Curitiba, Parana, Brazil; 2Hospital de Clínicas, Federal University of Parana, Curitiba, Parana, Brazil Abstract: Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products. This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation. Keywords: anti-TNF drugs, rheumatoid arthritis, apoptosis, NF-κB, FLIP

  17. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    Science.gov (United States)

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  18. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  19. Gonadotrophin releasing hormone antagonist in IVF/ICSI

    Directory of Open Access Journals (Sweden)

    M S Kamath

    2008-01-01

    Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

  20. NF-κB Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death.

    Science.gov (United States)

    Kumar, Amrendra; Gordy, Laura E; Bezbradica, Jelena S; Stanic, Aleksandar K; Hill, Timothy M; Boothby, Mark R; Van Kaer, Luc; Joyce, Sebastian

    2017-11-15

    Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-x L -coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas.

  1. Possible cause underlying gastric necrosis and perforation: Celiac artery thrombosis

    Directory of Open Access Journals (Sweden)

    Ahmet Peker

    2017-12-01

    Full Text Available In this article, we are sharing a case of a 76-year-old woman with known hypertension, atrial fibrillation,diabetes mellitus, coronary artery disease, who is presenting with stomach necrosis and perforation possibly due to celiac artery thrombosis after newly developed abdominal pain and bloody vomiting. In our case, emergency surgery was planned and the patient refused the operation and was lost at 48 hours of clinical follow-up. We aimed to discuss the etiology of celiac artery thrombosis, briefly. We believe that necrosis and perforation of the stomach due to celiac artery thrombosis deserves to be shared because it is a rare and difficult case to manage.

  2. Perilesional edema in radiation necrosis reflects axonal degeneration

    International Nuclear Information System (INIS)

    Perez-Torres, Carlos J; Yuan, Liya; Schmidt, Robert E; Rich, Keith M; Ackerman, Joseph JH; Garbow, Joel R

    2015-01-01

    Recently, we characterized a Gamma Knife® radiation necrosis mouse model with various magnetic resonance imaging (MRI) protocols to identify biomarkers useful in differentiation from tumors. Though the irradiation was focal to one hemisphere, a contralateral injury was observed that appeared to be localized in the white matter only. Interestingly, this injury was identifiable in T2-weighted images, apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) maps, but not on post-contrast T1-weighted images. This observation of edema independent of vascular changes is akin to the perilesional edema seen in clinical radiation necrosis. The pathology underlying the observed white-matter MRI changes was explored by performing immunohistochemistry for healthy axons and myelin. The presence of both healthy axons and myelin was reduced in the contralateral white-matter lesion. Based on our immunohistochemical findings, the contralateral white-matter injury is most likely due to axonal degeneration

  3. Metabolic epidermal necrosis in two dogs with different underlying diseases.

    Science.gov (United States)

    Bond, R; McNeil, P E; Evans, H; Srebernik, N

    1995-05-06

    Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

  4. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

    Science.gov (United States)

    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. 2015 BMJ Publishing Group Ltd.

  5. Diagnostic ultrasonography in cattle with abdominal fat necrosis.

    Science.gov (United States)

    Tharwat, Mohamed; Buczinski, Sébastien

    2012-01-01

    This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

  6. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    Science.gov (United States)

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. 2016 BMJ Publishing Group Ltd.

  7. Intestinal volvulus with coagulative hepatic necrosis in a chicken.

    Science.gov (United States)

    Haridy, Mohie; Goryo, Masanobu; Sasaki, Jun; Okada, Kosuke

    2010-04-01

    A 7-week-old SPF chicken inoculated at 4 weeks of age with chicken anemia virus was puffed up depressed and had ruffled feathers and a good body condition. Intestinal volvulus involving the jejunum and part of the duodenum forming two loops with one knob was observed. Microscopically, venous infarction of the obstructed loops, periportal and sublobular multifocal coagulative hepatic necrosis and granulomatous inflammation of the cecal tonsils were observed. Gram staining revealed no bacteria in hepatic tissue; however, gram-positive bacilli were detected in the necrotic debris in the intestinal lumen. Immunosuppression might have predisposed the chicken to intestinal and cecal tonsil infection that then progressed to volvulus. Loss of the mucosal barrier in infarction might allow bacterial toxins and vasoactive factors to escape into the systemic circulation (toxemia) and be responsible for the hepatic necrosis.

  8. Intraductal membranous fat necrosis in a fibroadenoma of breast: a case report.

    Science.gov (United States)

    Coyne, John D

    2014-09-01

    Membranous fat necrosis is an unusual type of fat necrosis occurring in the breast and normally involves the parenchyma. This report describes an apparently unique intraductal focus in a fibroadenoma following prior needling. Displacement of fatty tissue in the form of membranous fat necrosis within ducts could be added to the list of histological features following core biopsy. © The Author(s) 2013.

  9. Generation of truncated recombinant form of tumor necrosis factor ...

    African Journals Online (AJOL)

    Purpose: To produce truncated recombinant form of tumor necrosis factor receptor 1 (TNFR1), cysteine-rich domain 2 (CRD2) and CRD3 regions of the receptor were generated using pET28a and E. coli/BL21. Methods: DNA coding sequence of CRD2 and CRD3 was cloned into pET28a vector and the corresponding ...

  10. Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

    Science.gov (United States)

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  11. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  12. An autopsy case of delayed radiation necrosis of the brain

    International Nuclear Information System (INIS)

    Ihara, Katsuo; Otsutomo, Michinori; Takeshita, Gen

    1984-01-01

    A 48-year-old housewife underwent radiation therapy with 5,000 rad of cobalt following surgery for craniopharyngioma. One year later she developed symptoms of increased intracranial pressure, so that recurrence or occurrence of cerebral tumor was suspected. She died two years after the occurrence of the disease and was found to have had delayed radiation necrosis of the brain at autopsy. (Namekawa, K.)

  13. Intestinal necrosis in young patient due to arterial tumour embolism

    DEFF Research Database (Denmark)

    Dahle, Einar; Gögenur, Ismail; Nørgaard, Peter

    2012-01-01

    A patient in the thirties, currently undergoing chemotherapy for metastatic osteosarcoma diagnosed 3 years earlier, was admitted with in the emergency department with abdominal pain. Laparoscopic surgery revealed severe inflammation and an abscess. 18 cm of small intestine was removed because...... of intestinal necrosis. Histological examination showed several arterial tumour emboli, morphologically similar to the primary sarcoma. The patient died 1 year after successful surgery. Because of the improved survival of patients with osteosarcoma, acute mesenteric ischaemia should be considered in acute...

  14. Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis

    OpenAIRE

    HARRIS, JAMES; HARRIS, JAMES

    2008-01-01

    PUBLISHED umor necrosis factor (TNF)?? is a proinflammatory cytokine that mediates inflammation in response to various pathogens, including Mycobacterium tuberculosis, but is also a key factor in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. Three TNF???suppressing drugs have been approved to treat selected autoimmune diseases; 2 are monoclonal antibodies against TNF?? (adalimumab and infliximab), and the other is a soluble TNF receptor/Fc fusion protein (etanerce...

  15. Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Ainsworth, Mark Andrew

    2013-01-01

    A 35-year-old man presents with an exacerbation of Crohn's ileocolitis. He received a diagnosis of Crohn's disease 8 years ago and has been treated on three previous occasions with prednisone. Because of a recurrent need for glucocorticoids, treatment with azathioprine (150 mg per day) was starte...... colonoscopy show acute and chronic granulomatous inflammation, and the gastroenterologist recommends treatment with a tumor necrosis factor (TNF) inhibitor....

  16. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn [College of Biological Sciences, China Agricultural University, Beijing 100094 (China); National Institute of Biological Sciences, Beijing 102206 (China); Jin, Wei [Institute for Immunology, Tsinghua University, Beijing 100084 (China); Wang, Yuhui [Institute of Cardiovascular Sciences, Health Science Center, Peking University, Beijing 100191 (China); Huang, Huanwei; Li, Jia; Zhang, Cai [National Institute of Biological Sciences, Beijing 102206 (China)

    2016-04-29

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  17. Progressive skin necrosis of a huge occipital encephalocele

    Science.gov (United States)

    Andarabi, Yasir; Nejat, Farideh; El-Khashab, Mostafa

    2008-01-01

    Objects: Progressive skin necrosis of giant occipital encephalocoele is an extremely rare complication found in neonates. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocoele showing progressive necrosis during the first day of his life. Methods: A newborn baby was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the last hours of the first day of his life, the sac started becoming ulcerated accompanied with a rapid color change in the skin, gradually turning darker and then black. The neonate was taken up for urgent excision and repair of the encephalocele. Two years after the operation, he appears to be well-developed without any neurological problems. Conclusion: Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocoele may be another predisposing factor. In view of the risk of ulceration and subsequent infection, urgent surgery of the necrotizing encephalocele is suggested. PMID:19753210

  18. Progressive skin necrosis of a huge occipital encephalocele

    Directory of Open Access Journals (Sweden)

    Andarabi Yasir

    2008-01-01

    Full Text Available Objects: Progressive skin necrosis of giant occipital encephalocoele is an extremely rare complication found in neonates. Infection and ulceration of the necrosed skin may lead to meningitis or sepsis. We present here a neonate with giant occipital encephalocoele showing progressive necrosis during the first day of his life. Methods: A newborn baby was found to have a huge mass in the occipital region, which was covered by normal pink-purplish skin. During the last hours of the first day of his life, the sac started becoming ulcerated accompanied with a rapid color change in the skin, gradually turning darker and then black. The neonate was taken up for urgent excision and repair of the encephalocele. Two years after the operation, he appears to be well-developed without any neurological problems. Conclusion: Necrosis may have resulted from arterial or venous compromise caused by torsion of the pedicle during delivery or after birth. The high pressure inside the sac associated with the thin skin of the encephalocoele may be another predisposing factor. In view of the risk of ulceration and subsequent infection, urgent surgery of the necrotizing encephalocele is suggested.

  19. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    Science.gov (United States)

    Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

    2011-01-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

  20. Delayed radiation necrosis of the brain simulating a brain tumor

    International Nuclear Information System (INIS)

    Ikeda, Hiroya; Kanai, Nobuhiro; Kamikawa, Kiyoo

    1976-01-01

    Two cases of delayed radiation necrosis of the brain are reported. Case 1 was a 50-year-old man who had right hemiparesis and disorientation 26 months after Linac irradiation (5,000 rad), preceded by an operation for right maxillar carcinoma. A left carotid angiogram demonstrated a left temporal mass lesion, extending to the frontal lobe. Case 2 was a 41-year-old man who had previously had an operation for right intraorbital plasmocytoma, followed by two Co irradiations (6,400 rad, and 5,000 rad). He had the signs and symptoms of intracranial hypertension 36 months after his last irradiation. A left carotid angiogram demonstrated a left temporal mass lesion. Both cases were treated by administration of steroid hormone (which alleviated the signs and symptoms) and by temporal lobectomy. Microscopic examinations showed necrosis of the brain tissues associated with hyaline degeneration of blood vessel walls and perivascular cell infiltration. The signs and symptoms of intracranial hypertension subsided postoperatively. Thirteen other cases the same as ours were collected from literature. They showed the signs and symptoms simulating a brain tumor (like a metastatic brain tumor) after irradiation to extracranial malignant tumors. Diagnosis of radiation necrosis was made by operation or autopsy. A follow-up for a long time is necessary, because the pathological changes in the brain may be progressive and extending in some cases, although decompressive operations for mass lesions give excellent results. (auth.)

  1. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    International Nuclear Information System (INIS)

    Meng, Lingjun; Jin, Wei; Wang, Yuhui; Huang, Huanwei; Li, Jia; Zhang, Cai

    2016-01-01

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.

  2. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V

    2012-02-01

    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  3. ANTAGONISTIC BACTERIA AGAINST SCHIZOPHYLLUM COMMUNE FR. IN PENINSULAR MALAYSIA

    Directory of Open Access Journals (Sweden)

    ANTARJO DIKIN

    2006-01-01

    Full Text Available Schizophyllum commune Fr., is one of the important fungi, causes brown germ and seed rot of oil palm. Biodiversity of antagonistic bacteria from oil palm plantations in Peninsular Malaysia is expected to support in development of biopesticide. Isolation with liquid assay and screening antagonistic bacteria using dual culture assay were carried out in the bioexploration. A total of 265 bacterial isolates from plant parts of oil palm screened 52 antagonistic bacterial isolates against 5. commune. Bacterial isolates were identified by using Biolog* Identification System i.e. Bacillus macroccanus, B. thermoglucosidasius, Burkholderia cepacia, B. gladioli, B. multivorans, B pyrrocinia, B. spinosa, Corynebacterium agropyri, C. misitidis, Enterobacter aerogenes, Microbacterium testaceum, Pseudomonas aeruginosa, P. citronellolis, Rhodococcus rhodochrous, Serratia ficaria, Serratia sp., S. marcescens, Staphylococcus sciuri, Sternotrophomonas maltophilia.

  4. Histopathological investigation of radiation necrosis. Coagulation necrosis in the irradiated and non-irradiated brain tumors and in the normal brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, N [Niigata Univ. (Japan). Brain Research Inst.

    1977-01-01

    Eighty four irradiated tumors (including 59 gliomas) and the surrounding brain tissue were analyzed. In 'normal' brain tissue, typical coagulation necrosis attributable to irradiation was observed in the cerebral white matter, presenting a whitish-yellow color but no remarkable changes in volume. Histologically there was complete desintegration of myelin and axon. Vascular changes included hyalinous thickening, concentric cleavage, fibrinoid degeneration, adventitial fibrosis and edema of small arteries, fibrin thrombi or occlusion of arterioles and capillaries, and telangiectasia of small veins and venules. While other tumors showed hyalinous or fibrous scar tissue and decrease in volume, the gliomas maintained their original volume without residual tumor cells. Massive coagulation necrosis was occasionally found even in full volume, non-irradiated gliomas (controls), although the changes were fewer and not so varied as in typical radiation necrosis. With small dosages, it was difficult to judge whether the necrosis was caused by irradiation or occurred spontaneously. Coagulation necrosis in tumor tissue was found in 25 of 59 cases (42%) of irradiated gliomas, but in only 2 of 49 cases (4%) of the nonirradiated gliomas. In 49 cases no coagulation necrosis of the surrounding tissue was found. Although histopathological judgement is difficult, it is suggested that there is a significant correlation between coagulation necrosis and irradiation. Discussion of the relationship between coagulation necrosis and NSD (nominal standard dose) led to the conclusion that coagulation necrosis will not be caused by irradiation of less than 1400 rets in NSD.

  5. Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.

    Science.gov (United States)

    Nabokov, A V; Amann, K; Wessels, S; Münter, K; Wagner, J; Ritz, E

    1999-02-01

    In is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown. We morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30 mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30 mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1 mg/kg/day). Eight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals. The ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP.

  6. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    Science.gov (United States)

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  7. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    Science.gov (United States)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  8. Diagnostic methods in ischemic necrosis of the femoral head. Metodos de diagnostico en la necrosis isquemica de la cabeza femoral

    Energy Technology Data Exchange (ETDEWEB)

    Parra Blanco, J.A.; Pagola Serrano, M.A.; Delgado Macias, M.T. (Hospital Universitario Marques de Valdecilla, Santander (Spain))

    1994-01-01

    Ischemic necrosis of the femoral head (INFH) must be diagnosed at an early stage of development, when therapeutic approaches such as forage biopsy or osteotomy can prevent or slow the normal progression of the disease to arthrosis. In this article, on the basis of the pathological changes that characterize process, we review the advantages and limitations of the principal diagnostic techniques (table I) currently employed in the study of INFH. (Author)

  9. Early Diagnosis of Avascular Necrosis of Bone Following Renal Transplantation By Bone Scan

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyun Ho; Kim, Han Su; Ihn, Chun Gyoo; Kim, Myung Jae [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    1982-09-15

    Avascular necrosis of bone has become a well-recognized complication of renal transplantation. While preexisting metabolic bone disease, especially hyperparathyroidism, and metabolic disturbances induced by steroids have been implicated as etiological factors, the pathogenesis is controversial. The diagnosis of avascular necrosis of bone had been based on a history of joint pain and radiographic demonstration of bone necrosis. Recently the bone scan using {sup 99m}Tc-methylene diphosphonate is helpful in determining the early stage of bone necrosis. We report two cases of avascular necrosis of femur head, of which diagnosis was made by the bone scan using {sup 99m}Tc-methylene diphosphonate.

  10. Early Diagnosis of Avascular Necrosis of Bone Following Renal Transplantation By Bone Scan

    International Nuclear Information System (INIS)

    Shin, Hyun Ho; Kim, Han Su; Ihn, Chun Gyoo; Kim, Myung Jae

    1982-01-01

    Avascular necrosis of bone has become a well-recognized complication of renal transplantation. While preexisting metabolic bone disease, especially hyperparathyroidism, and metabolic disturbances induced by steroids have been implicated as etiological factors, the pathogenesis is controversial. The diagnosis of avascular necrosis of bone had been based on a history of joint pain and radiographic demonstration of bone necrosis. Recently the bone scan using 99m Tc-methylene diphosphonate is helpful in determining the early stage of bone necrosis. We report two cases of avascular necrosis of femur head, of which diagnosis was made by the bone scan using 99m Tc-methylene diphosphonate.

  11. Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.

    Science.gov (United States)

    Hero, M; Suomalainen, A; Hagström, J; Stoor, P; Kontio, R; Alapulli, H; Arte, S; Toiviainen-Salo, S; Lahdenne, P; Mäkitie, O

    2013-01-01

    Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

    Science.gov (United States)

    Rosen, Lauren E; Karrison, Theodore; Ananthanarayanan, Vijayalakshmi; Gallan, Alexander J; Adusumilli, Prasad S; Alchami, Fouad S; Attanoos, Richard; Brcic, Luka; Butnor, Kelly J; Galateau-Sallé, Françoise; Hiroshima, Kenzo; Kadota, Kyuichi; Klampatsa, Astero; Stang, Nolween Le; Lindenmann, Joerg; Litzky, Leslie A; Marchevsky, Alberto; Medeiros, Filomena; Montero, M Angeles; Moore, David A; Nabeshima, Kazuki; Pavlisko, Elizabeth N; Roggli, Victor L; Sauter, Jennifer L; Sharma, Anupama; Sheaff, Michael; Travis, William D; Vigneswaran, Wickii T; Vrugt, Bart; Walts, Ann E; Tjota, Melissa Y; Krausz, Thomas; Husain, Aliya N

    2018-04-01

    A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple

  13. NMDA receptor antagonists for the treatment of neuropathic pain

    NARCIS (Netherlands)

    Collins, S.; Sigtermans, M.J.; Dahan, A.; Zuurmond, W.W.A.; Perez, R.S.G.M.

    2010-01-01

    Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response

  14. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists

    Science.gov (United States)

    2016-08-01

    approximately halfway into the solution. All animals were tested at 60, 15 and 0 min before drug injection. For each animal , the first reading was discarded...approval (December 31, 2015), hiring new personnel, conducting baseline testing for procedures not involving animals , testing equipment, developing...treatment; Analgesia; Nociception; Antinociception; Inflammation; Chemokines; Chemokine receptor antagonists; Opioid analgesics; Animal models of pain

  15. Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists

    DEFF Research Database (Denmark)

    Pottegård, Anton; Christensen, Rene dePont; Wang, Shirley V

    2014-01-01

    PurposeWe present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. MethodsWe used...

  16. Komplikationer til langtidsbehandling med vitamin K-antagonister

    DEFF Research Database (Denmark)

    May, O; Garne, E; Mickley, H

    1990-01-01

    Long-term treatment with vitamin K antagonists (vKA) frequently involves complications. The commonest complication is haemorrhage and cases of serious haemorrhage are stated in the literature to occur with a frequency per 1,000 treatment years of 12-108, of which 2-17 are fatal. The majority...

  17. Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy

    NARCIS (Netherlands)

    Roscioni, Sara S.; de Zeeuw, Dick; Bakker, Stephan J. L.; Lambers Heerspink, Hiddo J.

    2012-01-01

    Mineralocorticoid-receptor antagonists (MRAs) reduce blood pressure and albuminuria in patients treated with angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor blockers. The use of MRAs, however, is limited by the occurrence of hyperkalaemia, which frequently occurs in patients

  18. Effect of Three Calmodulin Antagonists on Subpopulations of CD44 ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical ... cancer stem cells. It is not known, however, whether targeting CD44 can alter the fate of cancer stem cells themselves. In this study, the effect of the calmodulin antagonists (N-(10-.

  19. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

  20. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  1. Antagonistic bioactivity of an endophytic bacterium isolated from ...

    African Journals Online (AJOL)

    Antagonistic bioactivity of an endophytic bacterium isolated from Epimedium brevicornu Maxim. R He, G Wang, X Liu, C Zhang, F Lin. Abstract. Endophytic bacteria are one of the most potential biological control agents in plant disease protection. The aim of this work was to evaluate the antimicrobial activities of a strain of ...

  2. Multiple sclerosis following treatment with a cannabinoid receptor-1 antagonist

    NARCIS (Netherlands)

    van Oosten, B. W.; Killestein, J.; Mathus-Vliegen, E. M. H.; Polman, C. H.

    2004-01-01

    Laboratory research including animal models of human disease suggests that cannabinoids might have therapeutic potential in multiple sclerosis (MS). We have recently seen a 46-year-old woman who developed MS after starting treatment with a cannabinoid receptor antagonist for obesity. The occurrence

  3. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: wangmw@mail.shcnc.ac.cn [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  4. Manumycin from a new Streptomyces strain shows antagonistic ...

    African Journals Online (AJOL)

    Manumycin from a new Streptomyces strain shows antagonistic effect against methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant enterococci (VRE) strains from Korean Hospitals. Yun Hee Choi, Seung Sik Cho, Jaya Ram Simkhada, Chi Nam Seong, Hyo Jeong Lee, Hong Seop Moon, Jin Cheol Yoo ...

  5. Effects of calcium antagonists on hypertension and diastolic function ...

    African Journals Online (AJOL)

    Calcium antagonists are known to decrease blood pressure acutely and chronically in hypertensive patients with hypertensive heart disease, and also to improve their systolic function. However, disorders of diastolic function may occur early in hypertensive heart disease. The improvement of diastolic function by nifedipine ...

  6. Sympatho-inhibitory properties of various AT1 receptor antagonists

    NARCIS (Netherlands)

    Balt, Jippe C.; Mathy, Marie-Jeanne; Pfaffendorf, Martin; van Zwieten, Peter A.

    2002-01-01

    It is well known that angiotensin II (Ang II) can facilitate the effects of sympathetic neurotransmission. In the present study, using various experimental models, we investigated the inhibitory effects of several Ang II subtype 1 receptor (AT1) antagonists on this Ang II-induced facilitation. We

  7. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagoni...

  8. Christianity and Antagonistic Challenges in Igbo Land of Nigeria: A ...

    African Journals Online (AJOL)

    Christianity and Antagonistic Challenges in Igbo Land of Nigeria: A Reflection. ... The church mission society (CMS) along side the Royal Niger Company was working ... is to win the confidence of the people by establishing agricultural settlements, ... FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use ...

  9. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP...

  10. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...... antagonists for hepatic encephalopathy, but the results are conflicting....

  11. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Bruce Lyeth

    2013-06-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.

  12. Antagonistic bioactivity of endophytic strains isolated from Salvia ...

    African Journals Online (AJOL)

    The antibiotic-producing potential of endophytic populations from medical plant of Salvia miltiorrhiza was examined. A total of 63 isolates was screened against five fungal and three bacterial species for the production of antimicrobial compounds. It showed that more isolates was antagonistic to fungi than to bacteria.

  13. Screening and Mechanism of Trapping Ligand Antagonist Peptide ...

    African Journals Online (AJOL)

    Purpose: The aim of the present study was to develop peptide H9 as an efficient antagonist of human cytomegalovirus (HCMV) chemokine receptor US28. Methods: US28 gene was amplified from HCMV, and a stable expression system was constructed using NIH/3T3 cells. Interaction between peptide H9 and receptor ...

  14. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, Adrian R.; Di Napoli, Mario; Goldstein, Joshua N.; Schreuder, Floris H B M; Tetri, Sami; Tatlisumak, Turgut; Yan, Bernard; Van Nieuwenhuizen, Koen M.; Dequatre-Ponchelle, Nelly; Lee-Archer, Matthew; Horstmann, Solveig; Wilson, Duncan; Pomero, Fulvio; Masotti, Luca; Lerpiniere, Christine; Godoy, Daniel Agustin; Cohen, Abigail S.; Houben, Rik; Al-Shahi Salman, Rustam; Pennati, Paolo; Fenoglio, Luigi; Werring, David; Veltkamp, Roland; Wood, Edith; Dewey, Helen M.; Cordonnier, Charlotte; Klijn, Catharina J M; Meligeni, Fabrizio; Davis, Stephen M.; Huhtakangas, Juha; Staals, Julie; Rosand, Jonathan; Meretoja, Atte

    2015-01-01

    Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  15. Role of muscarinic receptor antagonists in urgency and nocturia

    NARCIS (Netherlands)

    Michel, Martin C.; de La Rosette, Jean J. M. C. H.

    2005-01-01

    The overactive bladder (OAB) syndrome is defined as urgency, with or without urgency incontinence, usually accompanied by frequency and nocturia. Muscarinic receptor antagonists are the most established form of treatment for OAB, but until recently their effectiveness was only confirmed for symptoms

  16. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    International Nuclear Information System (INIS)

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-01

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K i = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  17. Efficacy and safety of histamine-2 receptor antagonists

    NARCIS (Netherlands)

    van der Pol, Rachel; Langendam, Miranda; Benninga, Marc; van Wijk, Michiel; Tabbers, Merit

    2014-01-01

    Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable. To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD. PubMed,

  18. NK-1 receptor antagonists as anti-cancer drugs

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  19. An Antagonistic Dialogue about Chaordic Systems Thinking: Part I

    Science.gov (United States)

    Wafler, Toni

    2004-01-01

    This paper explores the added value of chaordic systems Thinking for organizational renewal, which is defined as transformation instead of reformation. The exploration is presented in the form of an antagonistic dialogue between two "voices," which develop commentaries from distinct theoretical inspirations, namely chaordic systems thinking (CST)…

  20. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

  1. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G

    2000-01-01

    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...

  2. Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

    Science.gov (United States)

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakano, Takashi; Nishizaki, Tomoyuki

    2015-09-01

    The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells. DAPE-induced reduction of NCI-H28 cell viability was partially inhibited by necrostatin-1, an inhibitor of RIP1 kinase to induce necroptosis, or knocking-down RIP1. DAPE generated reactive oxygen species (ROS) followed by disruption of mitochondrial membrane potentials in NCI-H28 cells. DAPE-induced mitochondrial damage was attenuated by cyclosporin A, an inhibitor of cyclophilin D (CypD). DAPE did not affect expression and mitochondrial localization of p53 protein in NCI-H28 cells. DAPE significantly decreased intracellular ATP concentrations in NCI-H28 cells. Overall, the results of the present study indicate that DAPE induces necroptosis and necrosis of MPM cells; the former is mediated by RIP1 kinase and the latter is caused by generating ROS and opening CypD-dependent mitochondrial permeability transition pore, to reduce intracellular ATP concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Ultrasound and MRI findings in appendicular and truncal fat necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Philip [Leeds Teaching Hospitals, Department of Radiology, Leeds (United Kingdom); Leeds Teaching Hospitals, Musculoskeletal Centre, X-Ray Department, Chapel Allerton Hospital, Leeds (United Kingdom); Farrant, Joanna M.; McKie, Scott [Leeds Teaching Hospitals, Department of Radiology, Leeds (United Kingdom); Bourke, Grainne [Leeds Teaching Hospitals, Department of Plastic Surgery, Leeds (United Kingdom); Merchant, William [Leeds Teaching Hospitals, Department of Pathology, Leeds (United Kingdom); Horgan, Kieran J. [Leeds Teaching Hospitals, Department of Surgery, Leeds (United Kingdom)

    2008-03-15

    The objective was to evaluate ultrasound and MRI in clinical appendicular and truncal fat necrosis. Thirty-three patients (14 men, 19 women, median age 55, range 29-95) were retrospectively evaluated. Histologically, three groups were seen: Group 1 (n = 18) consisted of patients with subcutaneous masses with septal and extrinsic oedema; in Group 2 (n = 11) necrosis occurred within lipomatous tumours and little oedema; and in Group 3 (n = 4) there were large complex masses consistent with Morel-Lavallee lesions. Two experienced radiologists reviewed MR (n = 30) and ultrasound (n = 32) images with consensus agreement. MRI was performed on a 1.5T system with T1-weighted, T2-weighted fat-suppressed and T1-weighted fat-suppressed post-intravenous gadolinium sequences obtained in two orthogonal planes. Ultrasound (linear 5- to 13.5-MHz probe) was performed in the longitudinal and short axis. Anatomical position, size, shape (oval, linear, ill-defined), internal architecture (lobules, septi or stranding), intrinsic signal characteristics, presence of surrounding pseudocapsule, extrinsic linear stranding and vascularity (gadolinium enhancement or power Doppler) were recorded. Anatomical locations were buttock/thigh (n = 17), leg (n = 6), upper limb (n = 5) and thoracic/abdominal wall (n = 5) with the majority of lesions (30 out of 33) oval/linear in shape. On ultrasound and MRI most lesions showed internal fat lobules, intervening septi and a surrounding pseudocapsule. Fat necrosis can usually be identified as containing multiple fat lobules on ultrasound and MRI despite a varying degree of inflammatory change surrounding and within the mass. (orig.)

  4. Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

    Science.gov (United States)

    Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

    1996-04-01

    1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice

  5. Antagonistic interactions between plant competition and insect herbivory.

    Science.gov (United States)

    Schädler, Martin; Brandl, Roland; Haase, Josephine

    2007-06-01

    Interspecific competition between plants and herbivory by specialized insects can have synergistic effects on the growth and performance of the attacked host plant. We tested the hypothesis that competition between plants may also negatively affect the performance of herbivores as well as their top-down effect on the host plant. In such a case, the combined effects of competition and herbivory may be less than expected from a simple multiplicative response. In other words, competition and herbivory may interact antagonistically. In a greenhouse experiment, Poa annua was grown in the presence or absence of a competitor (either Plantago lanceolata or Trifolium repens), as well as with or without a Poa-specialist aphid herbivore. Both competition and herbivory negatively affected Poa growth. Competition also reduced aphid density on Poa. This effect could in part be explained by changes in the biomass and the nitrogen content of Poa shoots. In treatments with competitors, reduced aphid densities alleviated the negative effect of herbivory on above- and belowground Poa biomass. Hence, we were able to demonstrate an antagonistic interaction between plant-plant interspecific competition and herbivory. However, response indices suggested that antagonistic interactions between competition and herbivory were contingent on the identity of the competitor. We found the antagonistic effect only in treatments with T. repens as the competitor. We conclude that both competitor identity and the herbivore's ability to respond with changes in its density or activity to plant competition affect the magnitude and direction (synergistic vs. antagonistic) of the interaction between competition and herbivory on plant growth.

  6. Facial fat necrosis following autologous fat transfer and its management

    Directory of Open Access Journals (Sweden)

    Sweta Rai

    2014-01-01

    Full Text Available Autologous fat transfer (AFT is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the benefits and risks of AFT highlighting common causes of fat graft failure.

  7. Supraspinatus Intramuscular Calcified Hematoma or Necrosis Associated with Tendon Tear

    Directory of Open Access Journals (Sweden)

    Alexandre Lädermann

    2015-01-01

    Full Text Available Introduction. Rotator cuff intramuscular calcification is a rare condition usually caused by heterotopic ossification and myositis ossificans. Case Presentation. We describe a patient with voluminous calcified mass entrapped in supraspinatus muscle associated with corresponding tendon tear. Histological examination corresponded to a calcified hematoma or necrosis. Patient was surgically managed with open excision of the calcified hematoma and rotator cuff arthroscopic repair. At 6 months, supraspinatus muscle was healed, and functional outcome was good. Discussion and Conclusion. We hypothesized that supraspinatus intramuscular calcified hematoma was responsible for mechanical stress on the tendon. This association has never been described.

  8. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

    Directory of Open Access Journals (Sweden)

    Mohit Dogra

    2018-01-01

    Full Text Available We report a case of progressive outer retinal necrosis (PORN in a patient of microscopic polyangitis (MPA, being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  9. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

    Science.gov (United States)

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-04-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  10. Delayed radiation-induced necrosis of the brain stem

    International Nuclear Information System (INIS)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi; Uozumi, Toru.

    1993-01-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author)

  11. Avascular necrosis associated with nailing of femoral neck fracture

    International Nuclear Information System (INIS)

    Stroemqvist, B.; Hansson, L.I.

    1983-01-01

    Two patients with femoral neck fractures, one displaced and one undisplaced, are presented. Preoperative intravital staining with tetracycline and Tc-MDP scintimetry both showed intact femoral head circulation while Tc-MDP-scintimetry 1 week after operation showed pronounced circulatory deficiency. SR 85 -scintimetry performed at the same time was inconclusive. Segmental collapse was observed radiographically, 8 and 12 months postoperatively. The major vascular injury resulting in avascularity most probably occured during the procedure of osteosynthesis, and Tc-MDP-scintimetry was found suitable for early postoperative recognition of avascular necrosis in both fractures. (author)

  12. Avascular necrosis associated with nailing of femoral neck fracture

    Energy Technology Data Exchange (ETDEWEB)

    Stroemqvist, B; Hansson, L I [Department of Orthopaedic Surgery, University Hospital in Lund, Sweden

    1983-01-01

    Two patients with femoral neck fractures, one displaced and one undisplaced, are presented. Preoperative intravital staining with tetracycline and Tc-MDP scintimetry both showed intact femoral head circulation while Tc-MDP-scintimetry 1 week after operation showed pronounced circulatory deficiency. Sr/sup 85/-scintimetry performed at the same time was inconclusive. Segmental collapse was observed radiographically, 8 and 12 months postoperatively. The major vascular injury resulting in avascularity most probably occured during the procedure of osteosynthesis, and Tc-MDP-scintimetry was found suitable for early postoperative recognition of avascular necrosis in both fractures.

  13. Neural network diagnosis of avascular necrosis from magnetic resonance images

    Science.gov (United States)

    Manduca, Armando; Christy, Paul S.; Ehman, Richard L.

    1993-09-01

    We have explored the use of artificial neural networks to diagnose avascular necrosis (AVN) of the femoral head from magnetic resonance images. We have developed multi-layer perceptron networks, trained with conjugate gradient optimization, which diagnose AVN from single sagittal images of the femoral head with 100% accuracy on the training data and 97% accuracy on test data. These networks use only the raw image as input (with minimal preprocessing to average the images down to 32 X 32 size and to scale the input data values) and learn to extract their own features for the diagnosis decision. Various experiments with these networks are described.

  14. Intestinal Necrosis due to Giant Ovarian Cyst: A Case Report

    OpenAIRE

    Duran, Ali; Duran, Fulay Yilmaz; Cengiz, Fevzi; Duran, Ozgur

    2013-01-01

    Intestinal pathologies due to ovarian cyst are observed rarely. Although a limited number of cases in neonatal and adolescent periods have been observed, no adult case has been reported in the literature. Two mechanisms are involved in intestinal complications due to ovarian cysts: torsion due to adhesion or compression of giant ovarian mass with a diameter of 9-10 cm. We report here a terminal ileum necrosis case due to compression by an ovarian cyst with 11 × 10 × 7 cm size in an 81-year-ol...

  15. Acute hepatic encephalopathy presenting as cortical laminar necrosis: Case report

    International Nuclear Information System (INIS)

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young

    2013-01-01

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  16. Acute hepatic encephalopathy presenting as cortical laminar necrosis: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jong Mun; Kim, Yoon Hee; Roh, Sook Young [Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam (Korea, Republic of)

    2013-04-15

    We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

  17. Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten

    2017-01-01

    Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran...

  18. Canadian Association of Gastroenterology Clinical Practice Guidelines: The Use of Tumour Necrosis Factor-Alpha Antagonist Therapy in Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Daniel C Sadowski

    2009-01-01

    Full Text Available BACKGROUND: Guidelines regarding the use of infliximab in Crohn’s disease were previously published by the Canadian Association of Gastroenterology in 2004. However, recent clinical findings and drug developments warrant a review and update of these guidelines.

  19. A role for b-cell-depleting agents in treating psoriatic skin lesions induced by tumor necrosis factor-alpha antagonists: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Ancuta Codrina Mihaela

    2014-01-01

    Full Text Available Despite recent advances in understanding the pathological pathways, clinical pattern and management opportunities for new-onset psoriasis as a paradoxical adverse event in patients receiving TNF inhibitors for their immune-mediated disorder, there is a subset of patients who are either partial responders or non-responders, whatever the therapeutic scenario. We present the case of new-onset psoriasis and severe alopecia development in a case study of long-standing rheumatoid arthritis (RA treated with adalimumab (ADA and leflunomide. Since skin lesions and alopecia are resistant to the classic protocol (topical treatment, ADA discontinuation and RA becomes highly active, rituximab (RTX was started. Dramatic improvement in joint disease, total remission of alopecia and partial remission of pustular psoriasis were described after the first RTX cycle. Although B-cell-depleting agents result in controversial effects on psoriatic skin lesions, this is the first case of ADA-induced psoriasis and alopecia that improved under RTX, suggesting a possible role in treating such a patient population.

  20. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    Science.gov (United States)

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  1. Role of tumour necrosis factor in pathogenesis of radicular cyst

    International Nuclear Information System (INIS)

    Qureshi, W.U.R.; Idris, M.; Khan, S.A.

    2011-01-01

    Background: The radicular cyst is very common odontogenic cyst of the jaws, which is usually associated with a tooth with necrotic pulp. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. The wall of the cyst contains epithelial cells, macrophages, fibroblasts and other cells. TNF is one of inflammatory mediators, which is produced by macrophages and monocytes. This study was carried out to investigate the role of tumour necrosis factor in the pathogenesis of radicular cyst, which is by far the commonest cystic lesion of the jaws. Methods: Explants from 20 radicular cysts were cultured in vitro to grow the epithelial cells. However, the cultures were rapidly contaminated with fibroblasts and it was impossible to grow the epithelial cells separately. Therefore, the proliferative effect of Tumour Necrosis Factor (TNF) was studied on mammalian epithelial cells. Results: TNF at low concentration had a proliferative effect on the epithelial cells, which may play some role in pathogenesis of radicular cyst. Conclusion: TNF stimulated the epithelial cell proliferation in low concentration and inhibit the proliferation in higher concentrations. These two effects may have some implications in the pathogenesis of radicular cyst. (author)

  2. Foot Skin Ischemic Necrosis following Heel Prick in a Newborn

    Directory of Open Access Journals (Sweden)

    Esad Koklu

    2013-01-01

    Full Text Available There are only a few reports on side effects after heel prick in neonates although heel prick has been performed all over the world for many years. The medicine staff had obtained only a drop of blood by pricking the baby’s heel using a lancet without compressing the heel or foot to measure his blood glucose level 3 hours after birth. However he developed a severe and hemorrhagic skin reaction on his entire left foot, beginning 30 minutes after obtaining the drop of blood by pricking the baby’s heel using a lancet. The lesion, which was treated with topical mupirocin and povidone-iodine solution daily, slowly decreased in size and had almost fully resolved within 3 weeks. He was healthy and 9 months old at the time of writing this paper. We herein report a case of foot skin ischemic necrosis following heel prick in a newborn. To our knowledge this patient is the first case of foot skin ischemic necrosis due to heel prick in newborns.

  3. Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

    Science.gov (United States)

    Ngajilo, D; Ehrlich, R

    2017-07-01

    Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Association of myocardial cell necrosis with experimental cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N W; Cameron, A J.V.

    1979-01-01

    Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

  5. Cortical laminar necrosis in dengue encephalitis-a case report.

    Science.gov (United States)

    Garg, Ravindra Kumar; Rizvi, Imran; Ingole, Rajan; Jain, Amita; Malhotra, Hardeep Singh; Kumar, Neeraj; Batra, Dhruv

    2017-04-20

    Dengue encephalitis is a rare neurological manifestation of dengue fever. Its clinical presentation is similar to other viral encephalitides and encephalopathy. No single specific finding on magnetic resonance imaging of dengue encephalitis has yet been documented. They are highly variable and atypical. A 15-year boy presented with fever, the headache and altered sensorium of 12-day duration. On neurological examination, his Glasgow Coma Scale score was 10 (E3M4V3). There was no focal neurological deficit. Laboratory evaluation revealed leukopenia and marked thrombocytopenia. Dengue virus IgM antibody was positive both in serum and cerebrospinal fluid. Magnetic resonance imaging of the brain revealed signal changes in bilateral parietooccipital and left frontal regions (left hemisphere more involved than the right hemisphere). There was gyriform enhancement bilateral parietooccipital regions consistent with cortical laminar necrosis. Bilaterally diffuse subcortical white matter was also involved and subtle T2 hyperintensity involving both basal ganglia was noted. Gradient echo sequence revealed presence of hemorrhage in the subcortical white matter. Patient was treated conservatively and received platelet transfusion. Patient became fully conscious after 7 days. In a patient with highly suggestive dengue e\\ephalitis, we describe an unusual magnetic resonance imaging finding. This report is possibly the first instance of cortical laminar necrosis in such a setting.

  6. Bilateral acute retinal necrosis-A case report

    Directory of Open Access Journals (Sweden)

    Prasad Palimar

    1992-01-01

    Full Text Available A 42 year old man presented with acute bilateral uveitis and necrotizing retinitis. Systemic investigations including test for AIDS and CMV retinitis were negative. Despite oral Acyclovir, both eyes progressed rapidly to retinal detachment with loss of vision. Early recognition is necessary to diagnose the bilateral acute retinal necrosis syndrome and initiate treatment. Bilateral acute retinal necrosis (BARN is a term first coined by Young and Bird in 1978 although the syndrome had been originally described by Urayama et al as an unilateral condition. This syndrome is characterized by the triad of acute confluent peripheral necrotizing retinitis, moderate to severe vasculitis and vitritis in an otherwise healthy individual. Rhegmatogenous retinal detachment occurs within two to three months of the onset of the disease and the second eye is involved in 36% of patients, usually within 6 weeks. We herein report a patient who presented with simultaneous BARN leading to retinal detachment in a matter of days. Also, to our knowledge this is the first report of this condition in India.

  7. Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

    Science.gov (United States)

    Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

    2016-06-10

    Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted.

  8. Avascular necrosis of the femoral head in HIV infected patients

    Directory of Open Access Journals (Sweden)

    Marcos Almeida Matos

    Full Text Available Avascular necrosis (AVN of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

  9. Role of tumor necrosis factor-α and interleukin-1β in anorexia induction following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the mouse.

    Science.gov (United States)

    Wu, Wenda; Zhang, Haibin

    2014-01-01

    The trichothecene deoxynivalenol (DON), a foodborne mycotoxin found in grain-based foods, has been associated with human and animal food poisoning. Although induction of anorexia has been described as a hallmark of DON-induced toxicity in many animal species, the mechanistic basis for this adverse effect is not fully understood. The purpose of this research was to determine the role of two proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in DON-induced anorexia. In a nocturnal mouse food consumption model, DON-induced anorectic response occurred at 1 hr and lasted up to 6 hr. Similar anorectic effects were observed following acute administration of exogenous TNF-α and IL-1β. Oral exposure to DON at 5 mg/kg bw stimulated splenic and hepatic mRNA and plasma protein elevations of TNF-α and IL-1β that corresponded to anorexia induction. Pretreatment with the TNF-α receptor (TNFR) antagonist R-7050 dose-dependently attenuated both TNF-α- and DON-induced anorexia. While, the type 1 IL-1 receptor (IL-1R1) antagonist IL-1RA dose-dependently attenuated both IL-1β- and DON-induced anorexia. Taken together, the results suggest that both TNF-α and IL-1β play contributory role in anorexia induction following oral exposure to DON.

  10. Mammary fat necrosis following radiotherapy in the conservative management of localized breast cancer: Does it matter?

    International Nuclear Information System (INIS)

    Trombetta, Mark; Valakh, Vladimir; Julian, Thomas B.; Werts, E. Day; Parda, David

    2010-01-01

    Purpose: Fat necrosis is a well-described and relatively common complication arising from post-lumpectomy irradiation of the breast, most commonly breast brachytherapy. We wish to assess the clinical significance of fat necrosis resulting from post-lumpectomy breast irradiation. Methods: We reviewed the literature to determine the overall incidence and significance of fat necrosis to determine whether or not fat necrosis poses a significant clinical problem. Results: Fat necrosis occurs in up to one-quarter of patients following post-lumpectomy breast irradiation. Only rarely is invasive intervention required however, it does significantly degrade the quality of all modalities of breast imaging. Conclusions: Fat necrosis is a common complication of radiotherapy which rarely requires therapeutic intervention. However, post-therapeutic clinical imaging such as mammography, ultrasound and magnetic resonance imaging are affected which may result in additional diagnostic procedures up to and including biopsy.

  11. Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis

    DEFF Research Database (Denmark)

    Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik

    2016-01-01

    Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare......,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk...... of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients....

  12. Angiographic analysis of avascular necrosis of a femoral head -selective angiography of medial femoral circumflex artery-

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Kyung Nam; Yoon, Yup; Lee, Sun Wha; Lim, Jae Hoon [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1991-07-15

    The degree of anatomical revascularization of a necrotic femoral head and traumatic hip would provide information about treatment and prognosis. The authors analyzed the vascular changes of femoral head among unilateral avascular necrosis, bilateral avascular necrosis, and traumatic hips. Forty - four patients with avascular necrosis and 19 patients with traumatic hips were examined by selective angiography of the medial femoral circumflex artery. In the traumatic hip cases, 12 (63%) showed occlusion, 2 (11%) hypertrophy of the capsular branches, and 5 ( 26 % ) were normal . In the avascular necrosis cases, 15 (25%) showed occlusion, 39 (67%) had hypertrophy of the capsular branches, and 4 (7%) had normal findings. Hypertrophy of the superior capsular branch of the medial femoral circumflex artery is more frequently observed in avascular necrosis than in traumatic hip. Bilateral avascular necrosis reveals more frequent incidences than unilateral cases. Selective angiography could help in the therapy plan and also provide information about the contralateral side.

  13. Angiographic analysis of avascular necrosis of a femoral head -selective angiography of medial femoral circumflex artery-

    International Nuclear Information System (INIS)

    Ryu, Kyung Nam; Yoon, Yup; Lee, Sun Wha; Lim, Jae Hoon

    1991-01-01

    The degree of anatomical revascularization of a necrotic femoral head and traumatic hip would provide information about treatment and prognosis. The authors analyzed the vascular changes of femoral head among unilateral avascular necrosis, bilateral avascular necrosis, and traumatic hips. Forty - four patients with avascular necrosis and 19 patients with traumatic hips were examined by selective angiography of the medial femoral circumflex artery. In the traumatic hip cases, 12 (63%) showed occlusion, 2 (11%) hypertrophy of the capsular branches, and 5 ( 26 % ) were normal . In the avascular necrosis cases, 15 (25%) showed occlusion, 39 (67%) had hypertrophy of the capsular branches, and 4 (7%) had normal findings. Hypertrophy of the superior capsular branch of the medial femoral circumflex artery is more frequently observed in avascular necrosis than in traumatic hip. Bilateral avascular necrosis reveals more frequent incidences than unilateral cases. Selective angiography could help in the therapy plan and also provide information about the contralateral side

  14. Opioid antagonists with minimal sedation for opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M

    2017-05-29

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies. We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants. We used standard methodological procedures expected by Cochrane. Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha 2 -adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient

  15. Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis.

    Directory of Open Access Journals (Sweden)

    Barbara Renga

    Full Text Available BACKGROUND: The farnesoid-x-receptor (FXR is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. PRINCIPAL FINDINGS: Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTα, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. CONCLUSIONS: FXR antagonism in vivo

  16. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    Science.gov (United States)

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

  17. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

    Lambalk, C B; Banga, F R; Huirne, J A

    2017-01-01

    BACKGROUND: Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist...... was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF...

  18. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan

    2007-01-01

    BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...... proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive...... placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary...

  19. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn

    2011-01-01

    Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered......: Preclinical, clinical and post-mortem studies of the serotonin 5-HT2A system in schizophrenia are reviewed. The implications of a combined D2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A...... receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...

  20. Cyclic degradation of antagonistic shape memory actuated structures

    International Nuclear Information System (INIS)

    Sofla, A Y N; Elzey, D M; Wadley, H N G

    2008-01-01

    Antagonistic shape memory actuated structures exploit opposing pairs of one-way shape memory alloy (SMA) linear actuators to create devices capable of a fully reversible response. Unlike many conventional reversible SMA devices they do not require bias force components (springs) to return them to their pre-actuated configuration. However, the repeated use of SMA antagonistic devices results in the accumulation of plastic strain in the actuators which can diminish their actuation stroke. We have investigated this phenomenon and the effect of shape memory alloy pre-strain upon it for near equi-atomic NiTi actuators. We find that the degradation eventually stabilizes during cycling. A thermomechanical treatment has been found to significantly reduce degradation in cyclic response of the actuators

  1. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  2. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  3. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  4. Construction, purification, and characterization of a chimeric TH1 antagonist

    Directory of Open Access Journals (Sweden)

    Javier-González Luís

    2006-05-01

    Full Text Available Abstract Background TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-γ are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses. Results A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-γ and IL-2, was designed, engineered, expressed in E. coli, purified and evaluated for its in vitro biological activities. The TH1 antagonist molecule consists of the extracellular region for the human IFNγ receptor chain 1 fused by a four-aminoacid linker peptide to human 60 N-terminal aminoacid residues of IL-2. The corresponding gene fragments were isolated by RT-PCR and cloned in the pTPV-1 vector. E. coli (W3110 strain was transformed with this vector. The chimeric protein was expressed at high level as inclusion bodies. The protein was partially purified by pelleting and washing. It was then solubilized with strong denaturant and finally refolded by gel filtration. In vitro biological activity of chimera was demonstrated by inhibition of IFN-γ-dependent HLA-DR expression in Colo 205 cells, inhibition of IFN-γ antiproliferative effect on HEp-2 cells, and by a bidirectional effect in assays for IL-2 T-cell dependent proliferation: agonism in the absence versus inhibition in the presence of IL-2. Conclusion TH1 antagonist is a chimeric protein that inhibits the in vitro biological activities of human IFN-γ, and is a partial agonist/antagonist of human IL-2. With these attributes, the chimera has the potential to offer a new opportunity for the treatment of autoimmune and inflammatory diseases.

  5. [Leukotriene antagonists: a new approach in the treatment of asthma].

    Science.gov (United States)

    Devillier, P; Bessard, G; Advenier, C

    1997-06-01

    Inflammation plays an essential role in the genesis of airflow obstruction and bronchial hyper-reactivity in the early stages of clinical asthma. The treatment of bronchial inflammation has become an essential element in the therapeutic strategy and principally rests on inhaled glucocorticoids. Amongst a number of inflammatory mediators leukotrienes occupy a privileged place by the power of their inflammatory and constrictor effects on bronchial smooth muscles. These properties have justified the clinical development of inhibitors of their synthesis and of specific antagonists to their receptors. Leukotriene antagonists are specific for a sub type of leukotriene receptors C4, D4 and E4 which is implicated in the majority of the bronchial constrictor and inflammatory effects of leukotrienes. The antagonists of Cys-LT1 receptor but also the inhibitors of the leukotriene synthesis exert an additive bronchodilator effect to those of B2 stimulants confirming an efficacious protection vis a vis bronchial provocation tests and above all they improve the clinical scores, lung function and also enable a decrease in the consumption of beta 2 agonists. The marketing of these products represents a major event because it corresponds to the advent of a new therapeutic class. The ease of administration by the oral route, their demonstrated efficacy and their good tolerance profile (in particular for ICI 204.219, and antagonists to Cys-LT1 receptors) are elements which foresee a success for this new asthmatic treatment. However numerous studies, notably comparative studies vis a vis reference treatments will be necessary to define their place in the strategic approach to the treatment of asthma.

  6. Suvorexant: The first orexin receptor antagonist to treat insomnia

    OpenAIRE

    Dubey, Ashok K.; Handu, Shailendra S.; Mediratta, Pramod K.

    2015-01-01

    Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, hav...

  7. A prototypical Sigma-1 receptor antagonist protects against brain ischemia

    OpenAIRE

    Schetz, John A.; Perez, Evelyn; Liu, Ran; Chen, Shiuhwei; Lee, Ivan; Simpkins, James W.

    2007-01-01

    Previous studies indicate that the Sigma-1 ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects the brain from ischemia. Less clear is whether protection is mediated by agonism or antagonism of the Sigma-1 receptor, and whether drugs already in use for other indications and that interact with the Sigma-1 receptor might also prevent oxidative damage due to conditions such as cerebral ischemic stroke. The antipsychotic drug haloperidol is an antagonist of Sigma-1 receptors and in this s...

  8. LA NECROSIS AVASCULAR EN LA DISPLASIA DE LA CADERA

    Directory of Open Access Journals (Sweden)

    Valentín Malagón

    1978-10-01

    Full Text Available

    Presentado en el III Congreso Nacional de la Sociedad Colombiana de Cirugía Infantil y XXIII Curso de Ortopedia para Post Graduados. Bogotá. Marzo 1978.

    1. La Necrosis Avascular de la extremidad proximal del fémur es una de las complicaciones más frecuentes y temibles en el tratamiento de la displasia de la cadera.

    2. Un mejor conocimiento de su etiopatogenia, de su historia natural, de su patología y
    de su cuadro radiológico, aporta bases para prevenirla y tratarla en forma adecuada.

    3. Por ser una lesión esencialmente iatrogénica relacionada con la aplicación de conductas
    inapropiadas de tratamiento, la depuración de esas técnicas puede evitar su aparición.

    4. Un diagnóstico precoz de la displasia de la cadera, un programa adecuado de tracción
    previa a la reducción, con tenotomía de los músculos aductores, en el momento de la
    reducción, maniobras suaves de reducción e inmovilización en una posición fisiológica
    humana (flexión de 900, abducción de 450 reducen notablemente la frecuencia de la
    necrosis avascular como complicación en el tratamiento de la displasia de la cadera.

    5. La reducción abierta de la cadera, asociada a la osteotomía del hueso innominado, precedida de una tracción adecuada y en niños mayores de 18 meses, reduce igualmente en este tipo de pacientes el porcentaje de esta complicación.

    El seguimiento de los principios enumerados en el Departamento de Ortopedia del Hospital
    Infantil, ha conseguido en el curso de 20 años disminuir la incidencia de necrosis avascular
    del 35 al 5.20/0.

  9. Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors.

    Science.gov (United States)

    Shi, Xiaodong; Lin, Xiaotian; Hu, Rui; Sun, Nan; Hao, Jingru; Gao, Can

    2016-08-01

    Cholinesterase inhibitors (ChEIs), represented by donepezil, rivastigmine, and galantamine, used to be the only approved class of drugs for the treatment of Alzheimer's disease. After the approval of memantine by the Food and Drug Administration (FDA), N-methyl-d-aspartic acid (NMDA) receptor antagonists have been recognized by authorities and broadly used in the treatment of Alzheimer's disease. Along with complementary mechanisms of action, NMDA antagonists and ChEIs differ not only in therapeutic effects but also in adverse reactions, which is an important consideration in clinical drug use. And the number of patients using NMDA antagonists and ChEIs concomitantly has increased, making the matter more complicated. Here we used the FDA Adverse Event Reporting System for statistical analysis , in order to compare the adverse events of memantine and ChEIs. In general, the clinical evidence confirmed the safety advantages of memantine over ChEIs, reiterating the precautions of clinical drug use and the future direction of antidementia drug development. © The Author(s) 2016.

  10. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  11. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer

    Science.gov (United States)

    Suzuki, H; Toyota, M; Caraway, H; Gabrielson, E; Ohmura, T; Fujikane, T; Nishikawa, N; Sogabe, Y; Nojima, M; Sonoda, T; Mori, M; Hirata, K; Imai, K; Shinomura, Y; Baylin, S B; Tokino, T

    2008-01-01

    Although mutation of APC or CTNNB1 (β-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a β-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis. PMID:18283316

  12. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    Full Text Available Abstract Background One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire resistance against Trastuzumab. Antibodies directed to different epitopes on the extracellular domain of HER2 are promising candidates for replacement or combinatorial therapy. For example, Pertuzumab that binds to subdomain II of HER2 extracellular domain and inhibits receptor dimerization is under clinical trial. Alternative antibodies directed to novel HER2 epitopes may serve as additional tools for breast cancer therapy. Our aim was to generate novel anti-HER2 monoclonal antibodies inhibiting the growth of breast cancer cells, either alone or in combination with tumor necrosis factor-α (TNF-α. Methods Mice were immunized against SK-BR-3 cells and recombinant HER2 extracellular domain protein to produce monoclonal antibodies. Anti-HER2 antibodies were characterized with breast cancer cell lines using immunofluorescence, flow cytometry, immunoprecipitation, western blot techniques. Antibody epitopes were localized using plasmids encoding recombinant HER2 protein variants. Antibodies, either alone or in combination with TNF-α, were tested for their effects on breast cancer cell proliferation. Results We produced five new anti-HER2 monoclonal antibodies, all directed against conformational epitope or epitopes restricted to the native form of the extracellular domain. When tested alone, some antibodies inhibited modestly but significantly the growth of SK-BR-3, BT-474 and MDA-MB-361 cells displaying ERBB2 amplification. They had no detectable effect on MCF-7 and T47D cells lacking ERBB2 amplification. When tested in combination with TNF-α, antibodies acted synergistically on SK-BR-3 cells

  13. Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration.

    Science.gov (United States)

    Neis, Vivian Binder; Manosso, Luana Meller; Moretti, Morgana; Freitas, Andiara E; Daufenbach, Juliana; Rodrigues, Ana Lúcia S

    2014-03-15

    Agmatine, an endogenous cationic amine, has been shown to exert antidepressant-like effects. This study investigated the ability of agmatine administered orally to abolish the depressive-like behavior induced by the administration of the pro-inflammatory cytokine, tumor necrosis factor (TNF-α) in mice. In control animals, agmatine (0.001, 0.01, 0.1, and 1 mg/kg) reduced the immobility time in the tail suspension test (TST). Acute administration of TNF-α (0.001 fg/mouse, i.c.v.) increased immobility time in the TST, indicative of a depressive-like behavior, and agmatine (0.0001, 0.1, and 1 mg/kg) prevented this effect. Additionally, we examined the effects of the combined administration of sub-effective doses of agmatine with antidepressants, the NMDA receptor antagonist MK-801 and the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) in mice exposed to either TNF-α or saline. In control mice, administration of a sub-effective dose of agmatine (0.0001 mg/kg) combined with sub-effective doses of either fluoxetine (5 mg/kg, p.o.), imipramine (0.1 mg/kg, p.o.), bupropion (1 mg/kg, p.o.), MK-801 (0.001 mg/kg, p.o.) or 7-NI (25 mg/kg, i.p.) produced a synergistic antidepressant-like effect in the TST. All these administrations prevented the increased immobility time induced by TNF-α. The effect of agmatine in the TNF-α model of depression appears to be associated, at least partially, with an activation of the monoaminergic systems and inhibition of NMDA receptors and nitric oxide synthesis, although converging signal transduction pathways that may underlie the effect of agmatine should be further investigated. This set of results indicates that agmatine may constitute a new therapeutic alternative for the treatment of depression associated with inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Tumor Necrosis Factor-Alpha and Pregnancy: Focus on Biologics. An Updated and Comprehensive Review.

    Science.gov (United States)

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel; Llurba, Elisa; Gris, Josep Maria

    2017-08-01

    Tumor necrosis factor-α (TNF-α) is a central regulator of inflammation, and TNF-α antagonists may be effective in treating inflammatory disorders in which TNF-α plays a major pathogenic role. TNF-α has also been associated with inflammatory mechanisms related to implantation, placentation, and pregnancy outcome. TNF-α is secreted by immune cells and works by binding to TNFR1 and TNFR2 cell receptors. TNF-α is also related to JAK/STAT pathways, which opens up hypothetical new targets for modifying. The accurate balance between Th1 cytokines, mainly TNF-α, Th17, and Th2, particularly IL-10 is essential to achieve good obstetric outcomes. TNF-α targeted therapy could be rational in treating women with obstetric complication related to overproduction of TNF-α, such as recurrent pregnancy loss, early and severe pre-eclampsia, and recurrent implantation failure syndrome, all "idiopathic" or related to aPL positivity. Along the same lines, Th1 cytokines, mainly TNF- α, play a leading pathogenic role in rheumatic and systemic autoimmune diseases occurring in women and, to a lesser extent, in men of reproductive age. These disorders have to be clinically silent before pregnancy can be recommended, which is usually only possible to achieve after intensive anti-inflammatory and immunosuppressive treatment, TNF-α blockers included. Physicians should be aware of the theoretic potential but low embryo-fetal toxicity risk of these drugs during pregnancy. From an updated review in May 2016, we can conclude that TNF-α blockers are useful in certain "refractory" cases of inflammatory disorders related to poor obstetric outcomes and infertility. Furthermore, TNF-α blockers can be safely used during the implantation period and pregnancy. Breastfeeding is also permitted with all TNF-α inhibitors. Since data on the actual mechanism of action of JAK-STAT in inflammatory obstetric disorders including embryo implantation are scarce, for the time being, therapeutic

  15. Tumor necrosis factor (TNF) biology and cell death.

    Science.gov (United States)

    Bertazza, Loris; Mocellin, Simone

    2008-01-01

    Tumor necrosis factor (TNF) was the first cytokine to be used in humans for cancer therapy. However, its role in the treatment of cancer patients is debated. Most uncertainties in this field stem from the knowledge that the pathways directly activated or indirectly affected upon TNF engagement with its receptors can ultimately lead to very different outcomes in terms of cell survival. In this article, we summarize the fundamental molecular biology aspects of this cytokine. Such a basis is a prerequisite to critically approach the sometimes conflicting preclinical and clinical findings regarding the relationship between TNF, tumor biology and anticancer therapy. Although the last decade has witnessed remarkable advances in this field, we still do not know in detail how cells choose between life and death after TNF stimulation. Understanding this mechanism will not only shed new light on the physiological significance of TNF-driven programmed cell death but also help investigators maximize the anticancer potential of this cytokine.

  16. Renal transplantant blood flow in patients with acute tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Huic, D; Crnkovic, S; Bubic-Filipi, L J; Grosev, D; Dodig, P; Porapat, M; Puretic, Z [Univ. Hospital Rebro, Zagreb (Croatia)

    1997-09-01

    The aim of this study was to investigate the quantity of renal transport blood flow in patients affected by acute tubular necrosis (ATN). During the four years period two hundred and thirty-three studies were performed using {sup 99m}Tc pertechnetate and {sup 131}I - OIH. Renal blood flow was calculated from the first-pass time activity curves generated over the kidney and aorta and expressed as a percentage of cardiac output (RBF/CO). Renal transplant blood flow is clearly diminished in ATN, similar as in acute rejection, and significantly related to the graft function, what means that RBF/CO value could potentially serve as a prognostic factor in the graft function recovery from ATN.

  17. [A case of nasal tip necrosis after hyaluronic acid injection].

    Science.gov (United States)

    Honart, J-F; Duron, J-B; Mazouz Dorval, S; Rausky, J; Revol, M

    2013-12-01

    Hyaluronic acid (HA) is the most used dermal filler. Some complications associated with its use have been described, but most of them are rare and benign. We report an exceptional case of skin necrosis of the tip of the nose, in a 22-year-old patient, after HA injection. The initial appearance may occurred subsequent aesthetic sequels. After necrotic tissue excision, patient was followed in rapid succession. Daily local care has led to wound healing, without any important sequel. This rare complication reminds us that HA injections are not without risk, despite their apparent simplicity of use. Moreover, the case presented confirms the potential healing of the nasal tip, allowing treatment with wound healing, rather than other early invasive procedure. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Preradiation dental extractions and the incidence of bone necrosis

    International Nuclear Information System (INIS)

    Beumer, J.; Harrison, R.; Sanders, B.; Kurrasch, M.

    1983-01-01

    Studies were done with 120 patients submitting to preradiation dental extraction within the radiation treatment volume. Bone necroses developed at the extraction sites in 17 patients (14.1%). The risk of bone necrosis in these patients is primarily dependent upon the size of the radiation treatment volume, radiation dose to mandibular bone, and healing time for the extraction wounds. Of the 13 mandibular bone necroses occurring at preradiation extraction sites, only two have not responded favorably to conservative management. Our data indicates that a policy of selected tooth removal, before radiation treatment, will minimize the risk of osteoradionecrosis. Mandibular molars with advanced chronic periodontal bone loss, residing within the proposed radiation field should be considered for removal before commencement of radiation treatment

  19. Progressive outer retinal necrosis presenting as cherry red spot.

    Science.gov (United States)

    Yiu, Glenn; Young, Lucy H

    2012-10-01

    To report a case of progressive outer retinal necrosis (PORN) presenting as a cherry red spot. Case report. A 53-year-old woman with recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis developed rapid sequential vision loss in both eyes over 2 months. Her exam showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary changes, consistent with PORN. Due to her late presentation and the rapid progression of her condition, she quickly developed end-stage vision loss in both eyes. PORN should be considered within the differential diagnosis of a "cherry red spot." Immune-deficient patients with a history of herpetic infection who present with visual loss warrant prompt ophthalmological evaluation.

  20. Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

    Science.gov (United States)

    Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O

    2015-06-01

    Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Partial pulp necrosis caused by excessive orthodontic force

    Directory of Open Access Journals (Sweden)

    Min-Young Kim

    2011-03-01

    Full Text Available As the dental pulp is encased with a rigid, noncompliant shell, changes in pulpal blood flow or vascular tissue pressure can have serious implication for the health of pulp. Numerous studies have demonstrated that orthodontic force application may influence both blood flow and cellular metabolism, leading degenerative and/or inflammatory responses in the dental pulp. The aim of this case report is to present a case about tooth with chronic periapical abscess which showed normal vital responses. Excessive orthodontic force is thought to be the prime cause of partial pulp necrosis. Owing to remaining vital tissue, wrong dianosis can be made, and tooth falsely diagnosed as vital may be left untreated, causing the necrotic tissue to destroy the supporting tissuses. Clinician should be able to utilize various diagnostic tools for the precise diagnosis, and be aware of the endodontic-orthodontic inter-relationship.

  2. Late bilateral temporal lobe necrosis after conventional radiotherapy. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Michio; Hayashi, Toshiyuki; Kagami, Hiroshi; Murase, Ikurou; Nakatsukasa, Masashi [Saiseikai Utsunomiya Hospital (Japan)

    2003-04-01

    A 63-year-old woman presented with radionecrosis in the bilateral temporal lobes manifesting as dementia about 30 years after undergoing conventional radiotherapy for pituitary adenoma. Computed tomography and magnetic resonance (MR) imaging showed edema and cystic lesions in both temporal lobes. The mass in the left temporal lobe was excised. MR imaging 12 days after surgery showed reduced edema. Her dementia had improved. Radionecrosis usually occurs between several months and a few years after radiotherapy. The incidence of radionecrosis is estimated as 5%, but may be higher with longer follow-up periods. Clinical reports have suggested that larger total doses of radiation are associated with earlier onset of delayed necrosis and the fractional dose is the most significant factor causing cerebral radionecrosis. Radionecrosis can occur long after conventional radiotherapy or stereotactic radiosurgery using a linac-based system or a gamma knife unit. (author)

  3. Palatal Perforation: A Rare Complication of Postanesthetic Necrosis

    Science.gov (United States)

    Gargi, Vidisha; Mohan, Ravi Prakash Sasankoti; Kamarthi, Nagaraju; Gupta, Swati

    2017-01-01

    The everyday practice of dentistry relies heavily on achieving adequate local anesthesia. Even though the safety record of local anesthetic agents is high, complications do occur. Palate is a favorable site for soft-tissue lesions. Various factors such as direct effects of the drug, blanching of the tissues during injection, relatively poor blood supply, and reactivation of the latent forms of herpes can all promote to tissue ischemia and a lesion in the palate. Among various complications, anesthetic necrotic ulcer is a rare and uncommon condition occurring mostly in the hard palate possibly after a local anesthetic infiltration. The ulceration is often deep and shows spontaneous but delayed healing. If proper treatment is not instituted on time, the necrosis can reach deep into the bone causing sequestrum formation and ultimately leading to palatal perforation. Here, we report a case of palatal perforation in a male patient followed by surgical interventions and follow-up. PMID:29042744

  4. Cortical laminar necrosis in brain infarcts: chronological changes on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Komiyama, M. [Department of Neurosurgery, Osaka City General Hospital, 2-13-22, Miyakojima-Hondouri, Miyakojima, Osaka 534 (Japan); Nishikawa, M. [Department of Neurosurgery, Osaka City General Hospital, 2-13-22, Miyakojima-Hondouri, Miyakojima, Osaka 534 (Japan); Yasui, T. [Department of Neurosurgery, Osaka City General Hospital, 2-13-22, Miyakojima-Hondouri, Miyakojima, Osaka 534 (Japan)

    1997-07-10

    We studied the MRI characteristics of cortical laminar necrosis in ischaemic stroke. We reviewed 13 patients with cortical laminar high signal on T1-weighted images to analyse the chronological changes in signal intensity and contrast enhancement. High-density cortical lesions began to appear on T1-weighted images about 2 weeks after the ictus. At 1-2 months they were prominent. They began to fade from 3 months but could be seen up to 11 months. These cortical lesions showed isointensity or high intensity on T2-weighted images and did not show low intensity at any stage. Contrast enhancement of the laminar lesions was prominent at 1-2 months and became less apparent from 3 months, but could be seen up to 8 months. (orig.). With 6 figs., 1 tab.

  5. Cortical laminar necrosis in brain infarcts: serial MRI

    Energy Technology Data Exchange (ETDEWEB)

    Siskas, N.; Lefkopoulos, A.; Ioannidis, I.; Charitandi, A.; Dimitriadis, A.S. [Radiology Department, AHEPA University Hospital, Aristotele University of Thessaloniki (Greece)

    2003-05-01

    High-signal cortical lesions are observed on T1-weighted images in cases of brain infarct. Histological examination has demonstrated these to be ''cortical laminar necrosis'', without haemorrhage or calcification. We report serial MRI in this condition in 12 patients with brain infarcts. We looked at high-signal lesions on T1-weighted images, chronological changes in signal intensity and contrast enhancement. High-signal cortical lesions began to appear about 2 weeks after the ictus, were prominent at 1 - 2 months, then became less evident, but occasionally remained for up to 1.5 years. They gave high signal or were isointense on T2-weighted images and did not give low signal at any stage. Contrast enhancement of these lesions was prominent at 1 - 2 months, and less apparent from 3 months, but was seen up to 5 months. (orig.)

  6. Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Eranga S Wijewickrama

    2013-01-01

    Full Text Available Acute renal failure (ARF is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH. The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham′s test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

  7. Phylogeography of infectious haematopoietic necrosis virus in North America

    DEFF Research Database (Denmark)

    Kurath, G.; Garver, K.A.; Troyer, R.M.

    2003-01-01

    Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323...... IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8(.)6%, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which...... varied in topography and geographical range. Intragenogroup genetic. diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors...

  8. Avascular necrosis of the femoral head; Staging by MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kokubo, Takashi; Takatori, Yoshio; Ninomiya, Setsuo; Sasaki, Yasuhito [Tokyo Univ. (Japan). Faculty of Medicine

    1993-03-01

    Magnetic resonance (MR) images and conventional radiographs were compared in 142 hips with avascular necrosis, and a staging system for the disease based on MR imaging was developed. MR images were classified into three patterns: a band of low signal intensity (class I); an area of low signal intensity with internal spot(s) of high signal (class II); and an area of low signal intensity without internal spots of high signal (class III). Most MR class I lesions were in radiographic stage I (normal) or II (sclerotic or cystic changes without collapse). Most MR class II lesions were in radiographic stage III (segmental collapse), and most MR class III lesions were in stage III or IV (secondary degenerative changes). The MR image classification was closely correlated with radiographic staging (p<0.01, using [chi] square test). We considered that this classification closely reflected the different stages of the disease according to the histopathology of the bone marrow. (author).

  9. CT study of avascular necrosis of femoral head in adults

    International Nuclear Information System (INIS)

    Liu Jihua; Du Yuqing; Xu Aide

    2000-01-01

    Objective: To study the early and new CT signs of avascular necrosis of femoral head in adults. Methods: The CT scans of 127 cases with this condition were analyzed. Results: There were 90 hip joints with femoral head normal in shape, including 67 femoral heads with only high-density sclerosis and 23 ones with high-density and low-density areas. In 111 hip joints, the femoral head was depressed and manifested purely high-density sclerosis in 25 and mixed-density areas in 86. Air-filled cysts appeared in 43 femoral heads. In follow-up cases, the changes in shape and density of femoral head followed some rules. Conclusion: Purely high-density sclerosis is an early sign and is of great diagnostic value combined with its special shape. Air in femoral heads is also a sign of the disease

  10. Avascular Necrosis of the Femoral Head: Are Any Genes Involved?

    Science.gov (United States)

    Pouya, Farzaneh; Kerachian, Mohammad Amin

    2015-01-01

    Avascular necrosis of the femoral head (ANFH) is a pathologic process that results from interruption of blood supply to the femur bone resulting in the death of bone cells and collapse of the femoral head. Nontraumatic ANFH continues to be a significant challenge to orthopedic surgeons. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that has given us a clearer picture of the pathogenesis of nontraumatic ANFH. Progression to the end stage of ANFH appears to be related to five main mechanisms: hypercoagulable conditions, angiogenesis suppressions, hyperadipogenesis, heritable states, and switching the bone remodelling into bone resorption. Researchers have been examining the pathogenic mechanisms of ANFH but none of these theories have been firmly confirmed although some appear more plausible than the others. All of these factors can switch bone remodelling into bone resorption, which can further lead to ANFH progression ending up to femoral head collapse. PMID:26213697

  11. MR imaging of avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Wan; Cho, Won Soo; Hong, Hyun Sook; Lee, Hae Kyung; Choi, Deuk Lin; Kim, Ki Jung [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    1993-09-15

    We evaluated the magnetic resonance imaging (MRI) findings of femoral heads in 20 normal and 45 abnormal patients. The bone marrow in the healthy adults consisted of a combination of hematopoietic and fatty marrow, which showed age-related dirtribation, that is the component of fatty marrow was increased and the marrow vascularity was decreased with age. Avascular necrosis (AVN) showed a decreased bone marrow signal within an normal appearing femoral head on T1 and T2 -weighted images. In addition, we could see inhomogeneous low signal intensive (31 cases), a ring of low intensive with central normal signal intensity (25 cases), focal low signal intensity (12 case), or a band of low signal intensity (4 cases). MRI findings were abnormal in 10 cases with normal radiographic findings as well as in all the cases with abnormal ones. In conclusion, MRI should be the choice of the imaging modality for the evaluation of early bone marrow changes of AVN.

  12. MR imaging of avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Choi, Eun Wan; Cho, Won Soo; Hong, Hyun Sook; Lee, Hae Kyung; Choi, Deuk Lin; Kim, Ki Jung

    1993-01-01

    We evaluated the magnetic resonance imaging (MRI) findings of femoral heads in 20 normal and 45 abnormal patients. The bone marrow in the healthy adults consisted of a combination of hematopoietic and fatty marrow, which showed age-related dirtribation, that is the component of fatty marrow was increased and the marrow vascularity was decreased with age. Avascular necrosis (AVN) showed a decreased bone marrow signal within an normal appearing femoral head on T1 and T2 -weighted images. In addition, we could see inhomogeneous low signal intensive (31 cases), a ring of low intensive with central normal signal intensity (25 cases), focal low signal intensity (12 case), or a band of low signal intensity (4 cases). MRI findings were abnormal in 10 cases with normal radiographic findings as well as in all the cases with abnormal ones. In conclusion, MRI should be the choice of the imaging modality for the evaluation of early bone marrow changes of AVN

  13. Studies on structural features of human tumor necrosis factor

    International Nuclear Information System (INIS)

    Yin Chuanyuan; Guo Donglin; Xi Tao; Xu Xianxiu; Gu Qingchao

    1997-01-01

    The microstructure of human tumor necrosis factor alpha (TNF-α) and its mutant (TNF-b) has been investigated by utilizing positron annihilation lifetime spectroscopy, radioiodination of human TNF and L929 cells assay. The experimental results show that the long lifetime (Τ 2 ) and corresponding intensity (I 2 ) of lower ortho-positronium annihilation in TNF-α are longer and less than those in the TNF-b, respectively. It suggests that the TNF-b is smaller in free volume and higher in density than the TNF-α. The TNF-b may maintain a more favorable conformation for binding to TNF receptors, thus increasing its biological activity. It is then concluded that the increases in the cytotoxicity and in the density for the TNF-b result from the decreases in the free volume in the TNF-b

  14. Tumor necrosis factor alpha production in irradiated cells in vitro

    International Nuclear Information System (INIS)

    Koeteles, G.J.; Bognar, G.; Kubasova, T.

    1994-01-01

    Normal and tumor cell lines were used to investigate tumor necrosis factor (TNFα) production and its radiation sensitivity. The cells were irradiated with gamma rays using different doses from 0.25 Gy up to 5 Gy. The number of plated cells, changes of proliferation and TNFα production were determined during the following four post-irradiation days. For TNFα quantity measurement immuno-radiometric assay (IRMA) and enzyme amplified sensitivity assay (EASIA) was used. The results suggest that though gamma irradiation decreased cell proliferation in a dose dependent manner, the quantity produced in the post-irradiation period increased considerably in each irradiated sample. (N.T.) 3 refs.; 2 figs.; 1 tab

  15. Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

    Science.gov (United States)

    Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

    1995-11-01

    Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways.

  16. Microbial Herd Protection Mediated by Antagonistic Interaction in Polymicrobial Communities

    Science.gov (United States)

    Wong, Megan J. Q.; Liang, Xiaoye; Smart, Matt; Tang, Le; Moore, Richard; Ingalls, Brian

    2016-01-01

    ABSTRACT In host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist, despite significant antagonistic interactions between species, are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through the delivery of toxic effectors. It is well established that intraspecies protection is conferred by immunity proteins that neutralize effector toxicities. In contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS-active antagonistic bacterial species, Aeromonas hydrophila and Vibrio cholerae, to demonstrate that interspecies protection is dependent on effectors. A. hydrophila and V. cholerae do not share conserved immunity genes but could coexist equally in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the competing wild-type strain. Time-lapse microscopic analyses showed that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interactions inside each cluster and restricting the interactions to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulated our experimental observations. These results provide mechanistic insights regarding the general role of microbial weapons in determining the structures of complex multispecies communities. IMPORTANCE Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in

  17. Microbial herd protection mediated by antagonistic interaction in polymicrobial communities.

    Science.gov (United States)

    Wong, Megan; Liang, Xiaoye; Smart, Matt; Tang, Le; Moore, Richard; Ingalls, Brian; Dong, Tao G

    2016-09-16

    In the host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist - despite significant antagonistic interactions between species - are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through delivery of toxic effectors. It is well established that intra-species protection is conferred by immunity proteins that neutralize effector toxicities. By contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS active antagonistic bacteria, Aeromonas hydrophila (AH) and Vibrio cholerae (VC), to demonstrate that interspecies protection is dependent on effectors. AH and VC do not share conserved immunity genes but could equally co-exist in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the other competing wild type. Time-lapse microscopy analyses show that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interaction inside each cluster and restricting it to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulate our experimental observation. These results provide mechanistic insights for the general role of microbial weapons in determining the structures of complex multispecies communities. Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in determining community structures and exchange of genetic materials

  18. Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse.

    Science.gov (United States)

    Papamichael, Konstantinos; Gils, Ann; Rutgeerts, Paul; Levesque, Barrett G; Vermeire, Séverine; Sandborn, William J; Vande Casteele, Niels

    2015-01-01

    : Primary nonresponse and primary nonremission are important limitations of tumor necrosis factor (TNF) antagonists, occurring in 10% to 40% and 50% to 80% of patients with inflammatory bowel disease, respectively. The magnitude of primary nonresponse differs between phase III clinical trials and cohort studies, indicating differences, e.g., in definition, patient population or blinding. The causes of nonresponse can be attributed to the drug (pharmacokinetics, immunogenicity), the patient (genetics, disease activity), the disease (type, location, severity), and/or the treatment strategy (dosing regimen, combination therapy). Primary nonresponse has been attributed to "non-TNF-driven disease" which is an overly simplified and potentially misleading approach to the problem. Many patients with primary nonresponse could successfully be treated with dose optimization during the induction phase or switching to another TNF antagonist. Therefore, primary nonresponse is frequently not a non-TNF-driven disease. Recent studies from rheumatoid arthritis and preliminary data from inflammatory bowel disease evaluating therapeutic drug monitoring have suggested that early measurement of drug and anti-drug antibody concentrations could help to define primary nonresponse and rationalize patient management of this problem. Moreover, a modeling approach including pharmacological parameters and patient-related covariants could potentially be predictive for response to the treatment. We describe an overview of this evolution in thinking, underpinned by previous findings, and assess the potential role of early measurement of drug and antidrug antibody concentrations in the definition and management of primary nonresponse.

  19. Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat

    NARCIS (Netherlands)

    de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

    1995-01-01

    Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of

  20. Ischemia leads to apoptosis--and necrosis-like neuron death in the ischemic rat hippocampus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Stadelmann, Christine; Bastholm, Lone

    2004-01-01

    necrosis; its expression peaked on days 3 to 4. Silver staining for nucleoli, which are a substrate for caspase-3, revealed a profound loss of nucleoli in cells with apoptosis-like morphology, whereas cells with necrosis-like morphology showed intact nucleoli. Overall, cells with apoptosis-like morphology...

  1. Prediction and measurement of thermally induced cambial tissue necrosis in tree stems

    Science.gov (United States)

    Joshua L. Jones; Brent W. Webb; Bret W. Butler; Matthew B. Dickinson; Daniel Jimenez; James Reardon; Anthony S. Bova

    2006-01-01

    A model for fire-induced heating in tree stems is linked to a recently reported model for tissue necrosis. The combined model produces cambial tissue necrosis predictions in a tree stem as a function of heating rate, heating time, tree species, and stem diameter. Model accuracy is evaluated by comparison with experimental measurements in two hardwood and two softwood...

  2. Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

    DEFF Research Database (Denmark)

    Johansson, Tove; Einer-Jensen, Katja; Batts, William

    2009-01-01

    Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11...

  3. Late temporal lobe necrosis after conventional radiotherapy for carcinoma of maxillary sinus.

    Science.gov (United States)

    Kanakamedala, Madhava R; Mahta, Ali; Liu, Jianlin; Kesari, Santosh

    2012-12-01

    Cerebral radiation necrosis is a serious late complication after conventional radiotherapy that can present with focal neurologic deficits or with more generalized signs and symptoms of increased intracranial pressure, depending on the location. The incidence and severity of radionecrosis are dose-volume dependent. We report a case of cerebral radiation necrosis 5 years after radiotherapy for a maxillary sinus carcinoma.

  4. Fat necrosis Secondary to Pancreatitis Mimicking Transverse Colon Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    S. Mirmomen

    2007-02-01

    Full Text Available Fat necrosis secondary to pancreatitis can be either mild and self limited or create severe organ damage,but may rarely lead to abdominal opancreatic pseudotumor.We report a case of fat necrosis secondary to pancreatitis which clinically simulates transverse colon cancer.

  5. Mandibular Bone and Soft Tissues Necrosis Caused by an Arsenical Endodontic Preparation Treated with Piezoelectric Device

    Directory of Open Access Journals (Sweden)

    A. Giudice

    2013-01-01

    Full Text Available This paper describes a case of wide mandibular bone necrosis associated with significant soft tissues injury after using an arsenical endodontic preparation in the right lower second molar for endodontic purpose. Authors debate about the hazardous effects of the arsenic paste and the usefulness of piezosurgery for treatment of this drug related bone necrosis.

  6. Increased Flap Weight and Decreased Perforator Number Predict Fat Necrosis in DIEP Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Carolyn L. Mulvey, BS

    2013-05-01

    Conclusions: Flaps with increasing weight have increased risk of fat necrosis. These data suggest that inclusion of more than 1 perforator may decrease odds of fat necrosis in large flaps. Perforator flap breast reconstruction can be performed safely; however, considerations concerning race, body mass index, staging with tissue expanders, perforator number, and flap weight may optimize outcomes.

  7. Using computed tomography to assist with diagnosis of avascular necrosis complicating chronic scaphoid nonunion.

    Science.gov (United States)

    Smith, Michael L; Bain, Gregory I; Chabrel, Nick; Turner, Perry; Carter, Chris; Field, John

    2009-01-01

    The primary aim of our study was to investigate use of long axis computed tomography (CT) in predicting avascular necrosis of the proximal pole of the scaphoid and subsequent fracture nonunion after internal fixation. In addition, we describe a new technique of measuring the position of a scaphoid fracture and provide data on its reproducibility. Thirty-one patients operated on by the senior author for delayed union or nonunion of scaphoid fracture were included. Preoperative CT scans were independently assessed for increased radiodensity of the proximal pole, converging trabeculae, degree of deformity, comminution, and fracture position. Intraoperative biopsies of the proximal pole were obtained and histologically assessed for evidence of avascular necrosis. The radiologic variables were statistically compared with the histologic findings. The presence of avascular necrosis was also compared with postoperative union status, identified on longitudinal CT scans. Preoperative CT features that statistically correlated with histologic evidence of avascular necrosis were increased radiodensity of the proximal pole and the absence of any converging trabeculae between the fracture fragments. The radiologic changes of avascular necrosis and the histologic confirmation of avascular necrosis were associated with persistent nonunion. Preoperative longitudinal CT of scaphoid nonunion is of great value in identifying avascular necrosis and predicting subsequent fracture union. If avascular necrosis is suspected based on preoperative CT, management options include vascularized bone grafts and bone morphogenic protein for younger patients and limited wrist arthrodesis for older patients. Diagnostic II.

  8. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Brock, C; Brock, B; Aziz, Q

    2017-01-01

    -VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which...

  9. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M; Appel, K; Sauter, A; GebickeHaerter, PJ; Boddeke, HWGM

    Induction of tumor necrosis factor alpha was studied in the brain of rats after focal cerebral ischaemia by occlusion of the left middle cerebral artery. Using a specific antisense riboprobe for in situ hybridization histochemistry, cells positive for tumor necrosis factor alpha messenger RNA were

  10. Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Zumsteg, U; Reimers, J

    1993-01-01

    In this review we propose that the balance between the action of interleukin 1 (IL-1) and its natural antagonist IL-1ra on the level of the insulin-producing pancreatic beta-cell may play a decisive role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We argue that IL-1...... potentiated by other cytokines (tumor necrosis factor alpha, interferon gamma) is an important effector molecule involved in both early and late events in the immune-mediated process that leads to beta-cell destruction and IDDM. We also point out that surprisingly high molar excesses of IL-1ra over IL-1...... are necessary to block the action of IL-1 on islet beta-cells compared to islet alpha-cells in vitro and in animals. We suggest that the selectivity of beta-cell destruction in IDDM may be conferred on several levels: (1) homing of beta-cell antigen specific T cells, (2) targeted delivery of cytokines...

  11. Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute

    International Nuclear Information System (INIS)

    Elgamal, B.M.; Rashed, R.A.; Raslan, H.N.

    2011-01-01

    Bone marrow necrosis; Egyptian cancer patients Abstract Background: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. Methods: study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). Results: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. Conclusion: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome

  12. Research and advancement of treating avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Wang Kaibing; Bai Bin; Wang Honghui; Sui Hong

    2006-01-01

    To undertake retrospective analysis of the research and advancement of treating avascular necrosis of the femoral head. After comparing the superiority and inferiority of different treatments and the present therapeutic status many therapeutic methods for avascular necrosis of the femoral head have been performed, commonly according to the staging of necrosis. Conservative therapy is suitable for stage 0-I, interventional therapy is suitable for stage II-III, operation is adapted for stage II-III and femoral head collapse or degenerative changes. Avascular necrosis of the femoral head is a chronic and dysfunctional illness. Comprehensive treatment according to different stage is now the most popular. Interventional therapy is the study focus of the avascular necrosis of the femoral head meanwhile. (authors)

  13. Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

    Science.gov (United States)

    Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

    2005-05-01

    An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

  14. Does protein binding modulate the effect of angiotensin II receptor antagonists?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  15. Sexually antagonistic "zygotic drive" of the sex chromosomes.

    Directory of Open Access Journals (Sweden)

    William R Rice

    2008-12-01

    Full Text Available Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive", because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race" between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.

  16. Central actions of a novel and selective dopamine antagonist

    International Nuclear Information System (INIS)

    Schulz, D.W.

    1985-01-01

    Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D 1 class, which is linked to the stimulation of adenylate cyclase-activity, and the D 2 class which is not. There is much evidence suggesting that it is the D 2 class which is not. There is much evidence suggesting that it is the D 2 dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D 1 class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of [ 3 H]-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D 1 receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for [ 3 H]-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D 1 receptors and [ 3 H]-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D 1 dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated

  17. Modulation of myometrium mitochondrial membrane potential by calmodulin antagonists

    Directory of Open Access Journals (Sweden)

    S. G. Shlykov

    2014-02-01

    Full Text Available Influence of calmodulin antagonists on mitochondrial membrane potential was investigated using­ a flow cytometry method, confocal microscopy and fluorescent potential-sensitive probes TMRM and MTG. Influence of different concentrations of calmodulin antagonists on mitochondrial membrane potential was studied using flow cytometry method and a fraction of myometrium mitochondria of unpregnant rats. It was shown that 1-10 µМ calmidazolium gradually reduced mitochondria membrane potential. At the same time 10-100 µМ trifluope­razine influenced as follows: 10 µМ – increased polarization, while 100 µМ – caused almost complete depolarization of mitochondrial membranes. In experiments which were conducted with the use of confocal microscopy method and myometrium cells it was shown, that MTG addition to the incubation medium­ led to the appearance of fluorescence signal in a green range. Addition of the second probe (ТМRM resulted in the appearance of fluorescent signal in a red range. Mitochondrial membrane depolarization by 1µМ СССР or 10 mМ NaN3 was accompanied by the decline of “red” fluo­rescence intensity, “green” fluorescence was kept. The 10-15 minute incubation of myometrium cells in the presen­ce 10 µМ calmidazolium or 100 µМ trifluoperazine was accompanied by almost complete decrease of the TMRM fluorescent signal. Thus, with the use of potential-sensitive fluorescent probes TMRM and MTG it was shown, that calmodulin antagonists modulate mitochondrial membrane potential of myometrium cells.

  18. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-15

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

  19. Sickle-cell hip necrosis and intraosseous pressure.

    Science.gov (United States)

    Mukisi, M M; Bashoun, K; Burny, F

    2009-04-01

    Osteonecrosis of the femoral head (ONFH) is a frequent complication of sickle-cell disease. Numerous studies have demonstrated increased intraosseous pressure (IOP) in idiopathic necrosis and necrosis secondary to corticotherapy or alcohol poisoning. Several reports have testified to the clinical interest of decompression by drilling which, when performed in the early course of the pathology, can arrest or slow evolution. To the best of our knowledge, no studies have reported IOP increase in sickle-cell ONFH. The present study sought to show that intraosseous hyperpressure plays a role in the physiopathology of sickle-cell, like idiopathic, ONFH. Sixteen intraosseous pressure (IOP) measurements were taken: eight in adult sickle-cell disease patients, four in sickle-cell trait carrying ONFH patients (AS) and four in non-sickle-cell ONFH patients (AA). Arterial blood-pressure equipment with bone-puncture needle was used to measure IOP in the great trochanter body. Three IOP measurements were made after zero calibration: before drilling (direct pressure: IOP-1), after hyperpressure test but before drilling (IOP-2), and after drilling (IOP-3). The present, admittedly short, series displayed elevated predrilling IOP-1 and IOP-2, reduced after drilling (IOP-3). Abnormal IOP fell after drilling performed for evolutive symptomatic ONFH. Significant differences in IOP-1 and IOP-2 were found, these being higher in the "sickle-cell disease" and "sickle-cell trait carriers" groups (pintraosseous hyperpressure is the cause of the pain and of the onset and evolution of ONFH. The drilling tunnel acts as a safety valve, achieving real decompression of the segment involved and immediate postoperative reduction in or disappearance of pain. Measuring pressure is of diagnostic interest in sickle-cell disease patients with symptomatic hips. Manometry can be performed independently of surgery, under local anesthesia, and provides early confirmation of ONFH in geographic regions in which

  20. Membrane formation in liquids by adding an antagonistic salt

    Science.gov (United States)

    Sadakane, Koichiro; Seto, Hideki

    2018-03-01

    Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a binary mixture, such as water and organic solvent, these ion pairs preferentially dissolve to those phases, respectively, and there is a coupling between the charge density and the composition. The heterogeneous distribution of ions forms a large electric double layer at the interface between these solvents. This reduces the interfacial tension between water and organic solvent, and stabilizes an ordered structure, such as a membrane. These phenomena have been extensively studied from both theoretical and experimental point of view. In addition, the numerical simulations can reproduce such ordered structures.

  1. Effect of a Hypocretin/Orexin Antagonist on Neurocogniive Performance

    Science.gov (United States)

    2014-09-01

    time: Tuesday , Nov 12, 2013, 4:00 PM - 5:00 PM Topic: ++E.08.e Sleep: Systems and behavior Authors: W. LINCOLN1, J. PALMERSTON1, T. NEYLAN2, T...functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL... Morris Water Maze. Although the concentrations of ALM and ZOL adminis- tered prior to these tests were equipotent in hypnotic efficacy, the

  2. Membrane Formation in Liquids by Adding an Antagonistic Salt

    Directory of Open Access Journals (Sweden)

    Koichiro Sadakane

    2018-03-01

    Full Text Available Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a binary mixture, such as water and organic solvent, these ion pairs preferentially dissolve to those phases, respectively, and there is a coupling between the charge density and the composition. The heterogeneous distribution of ions forms a large electric double layer at the interface between these solvents. This reduces the interfacial tension between water and organic solvent, and stabilizes an ordered structure, such as a membrane. These phenomena have been extensively studied from both theoretical and experimental point of view. In addition, the numerical simulations can reproduce such ordered structures.

  3. The discovery of tropane-derived CCR5 receptor antagonists.

    Science.gov (United States)

    Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

    2006-04-01

    The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

  4. The opiate antagonist, naltrexone, in the treatment of trichotillomania

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2014-01-01

    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were...... randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly...

  5. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  6. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    Science.gov (United States)

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  7. Molecular diagnosis of infectious hematopoietic necrosis and viral hemorrhagic septicemia

    Science.gov (United States)

    Winton, James R.; Einer-Jensen, Katja

    2002-01-01

    The fish rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), cause extensive losses among salmon and trout in several areas of the world (Bootland and Leong, 1999; Smail, 1999; Wolf, 1988). Historically, IHNV was endemic among wild anadromous salmonids in the western portion of North America, but the virus has spread to stocks of cultured rainbow trout (Oncorhynchus mykiss) in the United States, Asia and Western Europe, probably as a result of the movement of infected fish or eggs (Winton, 1991). Prior to 1989, VHSV was thought to be largely restricted to freshwater fishes in Western Europe (Wolf, 1988); however, in the last decade, VHSV has been isolated from an increasing number of free-living marine fish species in the North Pacific and North Atlantic Oceans (Dixon et al., 1997; Dixon, 1999; Kent et al., 1998; Meyers and Winton, 1995; Meyers et al., 1999; Mortensen et al., 1999; Smail; 2000, Takano et al., 2000). These findings have lead to the conclusion that both viruses are principally endemic among marine or anadromous fish species, but have established themselves in freshwater among cultured salmonids where their effects are most frequently observed.

  8. Extensive necrosis of visceral melanoma metastases after immunotherapy

    Directory of Open Access Journals (Sweden)

    Poston Graeme J

    2008-03-01

    Full Text Available Abstract Background The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909 is currently being evaluated for its potential. Case presentation We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909, a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET. Conclusion Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.

  9. Radioactive labelling with 125 I of infectious pancreatic necrosis virus

    International Nuclear Information System (INIS)

    Soler Ch, M.; Farias O, G.; Kuznar H, J.

    1993-01-01

    In order to understand the interaction between a cellular receptor and a ligand the photochemical crosslinking method has been widely used. This method has been utilized as an approach to determine the presence or absence of virus receptors in susceptible cells. Successful detection of crosslinks is achieved if one of the components, in the crosslinked product, has been radioactively labeled. The incorporation of a radioactive isotope, in the virus-receptor complex, enables the identification of the receptor. To undertake this study in the future, in this communication the radioactive labeling of virus particles is presented. The infectious necrosis pancreatic virus (IPN virus) was the chosen moiety to be in vitro labeled with 125 I using a direct method. Three oxidizing agents were used in the iodination procedure for comparison: an enzyme, lactoperoxidase and two chemical reagents, N-Chloro-benceno-sulfonamide (Iodo-Beads) and 1,3,4,6-Tetra chloro-3a,6a-diphenyl glycouril (Iodo-Gen). The results are analysed to select the method which guarantee the incorporation of 125 I in the viral capsid protein, while preserving its full infectivity. (author)

  10. Molecular epidemiology of Epizootic haematopoietic necrosis virus (EHNV).

    Science.gov (United States)

    Hick, Paul M; Subramaniam, Kuttichantran; Thompson, Patrick M; Waltzek, Thomas B; Becker, Joy A; Whittington, Richard J

    2017-11-01

    Low genetic diversity of Epizootic haematopoietic necrosis virus (EHNV) was determined for the complete genome of 16 isolates spanning the natural range of hosts, geography and time since the first outbreaks of disease. Genomes ranged from 125,591-127,487 nucleotides with 97.47% pairwise identity and 106-109 genes. All isolates shared 101 core genes with 121 potential genes predicted within the pan-genome of this collection. There was high conservation within 90,181 nucleotides of the core genes with isolates separated by average genetic distance of 3.43 × 10 -4 substitutions per site. Evolutionary analysis of the core genome strongly supported historical epidemiological evidence of iatrogenic spread of EHNV to naïve hosts and establishment of endemic status in discrete ecological niches. There was no evidence of structural genome reorganization, however, the complement of non-core genes and variation in repeat elements enabled fine scale molecular epidemiological investigation of this unpredictable pathogen of fish. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Magnetic resonance imaging of avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Thickman, D.; Axel, L.; Kressel, H.Y.; Velchick, M.; Dalinka, M.; Steinberg, M.; Chen, H.; Fallon, M.

    1986-01-01

    This study investigates the role of magnetic resonance imaging (MR) in identifying avascular necrosis (AVN) of the femoral head and in monitoring its therapy. The detection of AVN, particularly in its early stages, is imperative to give therapeutic intervention the best opportunity for successful management. The results of magnetic resonance imaging are compared with those of the standard diagnostic modalities in evaluation of patients with the lesion. Examinations were performed at 0.12 T with a repetition time (TR) of 143 ms and times to echo (TE's) of 10 or 20 ms. This study represents a retrospective review of 90 hips which were examined in 45 consecutive patients. Of these, 52 hips were biopsied as part of treatment. MR was shown to be sensitive in the detection of AVN. Comparison of MR with radionuclide imaging showed comparable sensitivity and specificity. MR was also noted to be sensitive in the detection of early AVN. Preliminary results suggest that MR can monitor treatment of the affected hip, and may even be able to predict patient response to therapy. Although further work is necessary to determine the role of MR in the evaluation of the patient presenting with hip pain, MR is a sensitive method in detecting AVN and in monitoring its course in patients suspected of having the disease. (orig.)

  12. Magnetic resonance imaging of avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Ozono, Kenji; Takaoka, Kunio [Osaka Univ. (Japan). Faculty of Medicine

    1989-07-01

    To evaluate the diagnostic value and limitation of magnetic resonance imaging (MRI) in avascular necrosis of the femoral head (ANF), clinical stages and types were examined on MRI scans of 68 femoral heads of 46 ANF patients. Stage 1 patients fell into two groups: (1) stage 1-A group of real ANF in which abnormal findings were observed on both MRI and bone scanning and (2) stage 1-B group of asymptomatic ANF in which MRI detected abnormality that was missed by bone scanning. In these groups, MRI showed inhomogeneous, band, and spotty patterns. Stage 2 or 3 patients tended to have homogeneous or ring-pattern hypointensities on MRI. Histological examination showed that repair reaction at the marginal site of hypointensity was partly responsible for the occurrence of hypointensities. In Stage 4 patients, not only femoral head but also acetabular site was visible as homogeneous hypointensity, which was similar to that in osteoarthritis. Because repair areas, as well as necrotic areas, were frequently visualized as hypointensities in Stages 2 or more, MRI might overestimate necrotic areas. (N.K.).

  13. Magnetic resonance imaging of avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Thickman, D; Axel, L; Kressel, H Y; Velchick, M; Dalinka, M; Steinberg, M; Chen, H; Fallon, M

    1986-02-01

    This study investigates the role of magnetic resonance imaging (MR) in identifying avascular necrosis (AVN) of the femoral head and in monitoring its therapy. The detection of AVN, particularly in its early stages, is imperative to give therapeutic intervention the best opportunity for successful management. The results of magnetic resonance imaging are compared with those of the standard diagnostic modalities in evaluation of patients with the lesion. Examinations were performed at 0.12 T with a repetition time (TR) of 143 ms and times to echo (TE's) of 10 or 20 ms. This study represents a retrospective review of 90 hips which were examined in 45 consecutive patients. Of these, 52 hips were biopsied as part of treatment. MR was shown to be sensitive in the detection of AVN. Comparison of MR with radionuclide imaging showed comparable sensitivity and specificity. MR was also noted to be sensitive in the detection of early AVN. Preliminary results suggest that MR can monitor treatment of the affected hip, and may even be able to predict patient response to therapy. Although further work is necessary to determine the role of MR in the evaluation of the patient presenting with hip pain, MR is a sensitive method in detecting AVN and in monitoring its course in patients suspected of having the disease.

  14. Glucocorticoid-Induced Avascular Bone Necrosis: Diagnosis and Management

    Science.gov (United States)

    Chan, KL; Mok, CC

    2012-01-01

    Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty. PMID:23115605

  15. Simultaneous avascular necrosis of both medial and lateral femoral condyles

    International Nuclear Information System (INIS)

    Mansberg, R.

    2002-01-01

    Full text: Avascular necrosis (AVN) of a femoral condyle is a common orthopaedic condition. While both medial and lateral femoral condyles may be involved either singly or sequentially the simultaneous occurrence of AVN of both femoral condyles is extremely uncommon. A 57-year-old male is presented who developed the onset of severe left sided knee pain suddenly at rest. Plain and tomographic radiography was unremarkable and a bone scan was performed. Markedly increased vascularity was demonstrated in the left knee with intense osteoblastic activity in the left medial and femoral condyles more marked in the lateral femoral condyle. A diagnosis of AVN of both femoral condyles was made and a MRI exam was performed to confirm this unusual diagnosis. The MRI showed a diffuse increase in intensity bilaterally with subtle bony change in the subarticular bone consistent with AVN more marked in the left lateral femoral condyle. The patients' symptoms resolved with supportive treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  16. Avascular necrosis after chemotherapy for haematological malignancy in childhood.

    Science.gov (United States)

    Salem, K H; Brockert, A-K; Mertens, R; Drescher, W

    2013-12-01

    Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin's lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

  17. Bone scintigraphy in idiopathic aseptic femoral head necrosis (IAFHN)

    Energy Technology Data Exchange (ETDEWEB)

    Dodig, D; Ugarkovic, B; Orlic, D

    1983-01-01

    Idiopathic aseptic femoral head necrosis (IAFHN) is a disease of unknown aetiology most commonly affecting adults, producing functional impairment of the hip joint and immobility. Characteristic macroscopic, microscopic and radiologic features include: (1) changes in joint cartilage, (2) subchondral necrotic area, (3) changes in fibrous tissue, and (4) osteosclerosis and vascular proliferation. The diagnosis is based on clinical and X-ray examinations. More recently scintigraphy has been used in diagnosing IAFHN. It is a very sensitive, but non-specific method. Nineteen patients aged 25-57 years were included in our study. Scintigrams were divided in four groups: (1) normal, (2) uniformly increased activity in the femoral head, (3) non-uniformly increased activity in the femoral head, and (4) a photon deficient area in the femoral head. A comparison of scintigraphy and radiological examination suggests that a photon deficient area corresponds with stage III of radiological classification, non-uniformly increased activity with stage II, and uniformly increased activity with stage I. These results indicate that scintigraphy can be used for staging of disease.

  18. Glucocorticoid-induced avascular bone necrosis: diagnosis and management.

    Science.gov (United States)

    Chan, K L; Mok, C C

    2012-01-01

    Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty.

  19. Excessive heat-associated gingival necrosis: a case report.

    Science.gov (United States)

    Barnes, P L; Rossi-Fedele, G

    2017-09-01

    Heat-delivery devices have been associated with relatively high temperatures. Previous basic research studies suggest that the risk for periodontal tissues is negligible, as the presence of the root filling materials, amongst other factors, reduce the risk of overheating. This report describes the case of a 45 year old male, who was undergoing restorative treatment in a multi-specialty dental practice. As part of his overall treatment planning, orthograde root canal retreatment for his maxillary left incisor teeth was deemed necessary, due to chronic apical periodontitis. Following cold lateral compaction, the coronal portion of the core material was severed using a System B Heat Source (Kerr Dental, Orange, CA, USA), with the patient reporting pain as well as a burning sensation. The following day the patient was seen by a periodontist and gingival necrosis in relation to the central incisor was found. The most likely cause of the complication was considered to be excessive heat during the operative procedure. The patient was followed up for a 2-year period and the soft tissues returned to their original condition without the need for periodontal treatment. © 2017 Australian Dental Association.

  20. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Kruse, Lars S; Chen, Qing-Wen

    2011-01-01

    Tumour necrosis factor-a (TNF-a) is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-a acts by binding to its receptors, TNF-R1 (p55) and TNF-R2 (p75), on the cell surface. The aim of this study was first to investigate if there is altered expre...... expression of TNF-a and TNF-a receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway....

  1. The role of ecology, neutral processes and antagonistic coevolution in an apparent sexual arms race.

    Science.gov (United States)

    Perry, Jennifer C; Garroway, Colin J; Rowe, Locke

    2017-09-01

    Some of the strongest examples of a sexual 'arms race' come from observations of correlated evolution in sexually antagonistic traits among populations. However, it remains unclear whether these cases truly represent sexually antagonistic coevolution; alternatively, ecological or neutral processes might also drive correlated evolution. To investigate these alternatives, we evaluated the contributions of intersex genetic correlations, ecological context, neutral genetic divergence and sexual coevolution in the correlated evolution of antagonistic traits among populations of Gerris incognitus water striders. We could not detect intersex genetic correlations for these sexually antagonistic traits. Ecological variation was related to population variation in the key female antagonistic trait (spine length, a defence against males), as well as body size. Nevertheless, population covariation between sexually antagonistic traits remained substantial and significant even after accounting for all of these processes. Our results therefore provide strong evidence for a contemporary sexual arms race. © 2017 John Wiley & Sons Ltd/CNRS.

  2. Novel quinolinone-phosphonic acid AMPA antagonists devoid of nephrotoxicity.

    Science.gov (United States)

    Cordi, Alex A; Desos, Patrice; Ruano, Elisabeth; Al-Badri, Hashim; Fugier, Claude; Chapman, Astrid G; Meldrum, Brian S; Thomas, Jean-Yves; Roger, Anita; Lestage, Pierre

    2002-10-01

    We reported previously the synthesis and structure-activity relationships (SAR) in a series of 2-(1H)-oxoquinolines bearing different acidic functions in the 3-position. Exploiting these SAR, we were able to identify 6,7-dichloro-2-(1H)-oxoquinoline-3-phosphonic acid compound 3 (S 17625) as a potent, in vivo active AMPA antagonist. Unfortunately, during the course of the development, nephrotoxicity was manifest at therapeutically effective doses. Considering that some similitude exists between S 17625 and probenecid, a compound known to protect against the nephrotoxicity and/or slow the clearance of different drugs, we decided to synthesise some new analogues of S 17625 incorporating some of the salient features of probenecid. Replacement of the chlorine in position 6 by a sulfonylamine led to very potent AMPA antagonists endowed with good in vivo activity and lacking nephrotoxicity potential. Amongst the compounds evaluated, derivatives 7a and 7s appear to be the most promising and are currently evaluated in therapeutically relevant stroke models.

  3. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    Science.gov (United States)

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  5. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Yu, Hui; Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi; Wang, Zhanli; Liang, Huaping

    2010-01-01

    Research highlights: → Evodiamine interacted with the AhR. → Evodiamine inhibited the specific binding of [ 3 H]-TCDD to the AhR. → Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K i value of 28.4 ± 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  6. Rogue sperm indicate sexually antagonistic coevolution in nematodes.

    Directory of Open Access Journals (Sweden)

    Ronald E Ellis

    2014-07-01

    Full Text Available Intense reproductive competition often continues long after animals finish mating. In many species, sperm from one male compete with those from others to find and fertilize oocytes. Since this competition occurs inside the female reproductive tract, she often influences the outcome through physical or chemical factors, leading to cryptic female choice. Finally, traits that help males compete with each other are sometimes harmful to females, and female countermeasures may thwart the interests of males, which can lead to an arms race between the sexes known as sexually antagonistic coevolution. New studies from Caenorhabditis nematodes suggest that males compete with each other by producing sperm that migrate aggressively and that these sperm may be more likely to win access to oocytes. However, one byproduct of this competition appears to be an increased probability that these sperm will go astray, invading the ovary, prematurely activating oocytes, and sometimes crossing basement membranes and leaving the gonad altogether. These harmful effects are sometimes observed in crosses between animals of the same species but are most easily detected in interspecies crosses, leading to dramatically lowered fitness, presumably because the competitiveness of the sperm and the associated female countermeasures are not precisely matched. This mismatch is most obvious in crosses involving individuals from androdioecious species (which have both hermaphrodites and males, as predicted by the lower levels of sperm competition these species experience. These results suggest a striking example of sexually antagonistic coevolution and dramatically expand the value of nematodes as a laboratory system for studying postcopulatory interactions.

  7. Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity

    International Nuclear Information System (INIS)

    Maton, P.N.; Sutliff, V.E.; Jensen, R.T.; Gardner, J.D.

    1985-01-01

    The authors used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ- lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125 I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain

  8. Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

    Science.gov (United States)

    Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

    2005-08-01

    Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

  9. Fires can benefit plants by disrupting antagonistic interactions.

    Science.gov (United States)

    García, Y; Castellanos, M C; Pausas, J G

    2016-12-01

    Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant-insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants.

  10. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  11. Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs.

    Science.gov (United States)

    Zhang, Qiang; Cheng, Cheng-Kung; Wei, Hung-Wen; Dong, Xiang; Chen, Yi-Ting; Lai, Yu-Shu; Wang, Yan

    2013-01-01

    There is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis. We designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems. The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)). This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

  12. Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.

    Science.gov (United States)

    Zhang, Dongjian; Huang, Dejian; Ji, Yun; Jiang, Cuihua; Li, Yue; Gao, Meng; Yao, Nan; Liu, Xuejiao; Shao, Haibo; Jing, Su; Ni, Yicheng; Yin, Zhiqi; Zhang, Jian

    2015-02-01

    Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

  13. Analysis of hip perfusion at early and reversible stages of aseptic hip necrosis

    International Nuclear Information System (INIS)

    Predic, P.; Dodig, D.; Karner, I.

    2002-01-01

    Aim: A proper early diagnosis of aseptic hip necrosis is very important for further therapy.Since there has always been a question of the amount of perfusion in hips at different stages of aseptic hip necrosis we tried to impartially examine the perfusion in hips at early and reversible stages of aseptic hip necrosis. Material and Methods:Study included 143 patients with aseptic hip necrosis.The 550-740 MBq of Tc-99m-DPD were on bolus injected.All patients were subjected to 3-phase scintigraphy of hips and quantitative calculation of relative perfusion in the artery phase (3T) at early and repeated at reversible stages of aseptic hip necrosis. Results: At the early stage of aseptic hip necrosis the obtained 3T was decreased from 0.94-0.69 (3T=0.80).Scintigrams showed a moderate increase or diffuse accumulation. At the reversible stages we obtained 3T decreased from 0.92-0.71 (3T=0.79) thus evidencing hypoperfusion.Scintigrams showed an diffuse increased accumulation. Conclusion: With the aseptic hip necrosis quantitative analysis of perfusion in the artery phase-3T indicates that the perfusion is decreased at all stages of the process which however shows a significantly falling trend with the progress of the disease

  14. [Is the Hawkins sign able to predict necrosis in fractures of the neck of the astragalus?].

    Science.gov (United States)

    Rodríguez-Paz, S; Muñoz-Vives, J M; Froufe-Siota, M Á

    2013-01-01

    To assess if the Hawkins sign can predict whether or not astragalus fractures of the neck will develop avascular necrosis. It is also assessed whether the occurrence of this complication is related to the displacement of the fracture, soft tissue injury, or delay in the reduction or surgery. The results were compared with those found in the literature. A retrospective study was conducted on 23 talar neck fractures recorded over a a period of thirteen years. The following variables were analysed: displacement of the fracture, soft tissue injury, delay and type of treatment, complications, observation of the Hawkins sign, and functional outcome. There were 7 type I Hawkins fractures, 11 type II, and 4 type III and 1 type IV. Four cases developed avascular necrosis (2 Hawkins type II and 2 type III). Hawkins sign was observed in 12 cases, of which none developed necrosis. Four cases with negative Hawkins sign developed necrosis. No statistically significant differences were found when comparing the development of avascular necrosis with the displacement of the fracture, soft tissue injury, or delay in treatment. Differences were found when comparing the development of avascular necrosis with the Hawkins sign (P=.03). A positive Hawkins sign rules out that the fractured talus has developed avascular necrosis, but its absence does not confirm it. © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  15. Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Raul Chavez-Valdez

    2012-01-01

    Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

  16. Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis.

    Science.gov (United States)

    Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik; Jepsen, Peter

    2016-06-01

    Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994-2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results - We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients.

  17. Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

    Science.gov (United States)

    Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

    2015-12-01

    Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

  18. Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.

    Directory of Open Access Journals (Sweden)

    Evgenii Germanovich Skurikhin

    Full Text Available Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA. To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL. Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem /progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF-β, interleukin (IL-1β, tumor necrosis factor (TNF-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/ progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31‒ CD34‒ CD45‒ CD44+ CD73+ CD90+ CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan

  19. Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

    Science.gov (United States)

    Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

    2017-12-18

    Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

  20. The Cultivation of Antagonistic Bacteria in Irradiated Sludge for Biological Control of Soft Rot Erwinias : Screening of Antagonistic Bacteria for biological Control of Soft Rot Erwinias

    International Nuclear Information System (INIS)

    Sermkiattipong, Ng.; Sangsuk, L; Rattanapiriyakul, P; Dejsirilert, S.; Thaveechai, N.

    1998-01-01

    Pure cultures of 57 bacterial isolates for antagonistic activity screening were isolated from three areas of soft rot infested vegetable soil and 58 isolates were obtained from commercial seed compost and seed compost product of Division of Soil and Water Conservation, Department of Land Development. A total of 115 bacterial isolates were evaluated for antagonizing activity against Erwinia carotovora subsp. atroceptica in vitro. Out of them, 18 isolates were antagonists by showing zone of inhibition ranging from 1 to 17 mm by diameter. Most of antagonistic bacteria were identified as Bacillus spp. whereas only one isolate was Pseudomonas vesicularis

  1. Simultaneous canine distemper encephalitis and canine parvovirus infection with distemper-associated cardiac necrosis in a pup

    OpenAIRE

    Headley,Selwyn Arlington; Saito,Taís Berelli

    2003-01-01

    Simultaneous infection of canine distemper virus and canine parvovirus associated with distemper myocardial degeneration and necrosis is described in a pup. The dog demonstrated myoclonus, nystagmus, enamel hypoplasia, abdominal pustules, and bilateral corneal ulceration clinically. Demyelinating encephalitis, myocardial degeneration and necrosis with mineralization, and necrosis, hemorrhage and fusion of intestinal villi were observed. The lesions observed in this dog are characteristic of a...

  2. Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

    Science.gov (United States)

    Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

    2014-09-01

    Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

  3. Successful Treatment of Anterior Tracheal Necrosis after Total Thyroidectomy Using Vacuum-Assisted Closure Therapy

    Directory of Open Access Journals (Sweden)

    Grégory Philippe

    2012-01-01

    Full Text Available Total thyroidectomy involving the adjacent structures of the trachea can cause tracheal damage such as early tracheal necrosis. The authors describe the first case of anterior tracheal necrosis following total thyroidectomy treated using vacuum-assisted closure device. After two weeks of VAC  therapy, there was no evidence of ongoing infection and the trachea was partially closed around a tracheotomy cannula, removed after 3 months. The use of a VAC  therapy to reduce and close the tracheal rent and to create a rapid granulation tissue over tracheal structure appeared as a good opportunity after anterior tracheal necrosis.

  4. Operative treatment and avascular necrosis of the hip development disorder.

    Science.gov (United States)

    Gavrankapetanović, Ismet; Hadžimehmedagić, Amel; Papović, Adnan; Baždar, Elvir

    2014-07-01

    , the duration of previous conservative treatments and repeated hospitalization. In group 1, 86.6 % were female patients and 80 % in group 2. Family history was positive in 15.6 % in group 1 and 13.3 % in group 2. A total of 51.6 % of all patients started walking on time, while the rest had problems with verticalization. Of all patients, 47 % did not undergo any kind of prior treatment. Only 62.2 % of group 1 patients had ossification nucleus present, while the entire group 2 had it present. Results showed that 24.32 % of group 1 patients had none or minimal signs of avascular necrosis (AVN) while 39.47 % of group 2 had none or minimal signs of AVN; 60.52 % of group 2 patients had signs of AVN. The results of this study show that the performance of a surgical treatment during the age between 12 and 20 months is burdened by the highest percentage of avascular necrosis. Even though AVN can be noticed in other age groups, according to the results of our research, it seems that vascular supply of the hip is the most vulnerable in the period between 12 and 20 months.

  5. Vasculitis Associated With Tumor Necrosis Factor-α Inhibitors

    Science.gov (United States)

    Sokumbi, Olayemi; Wetter, David A.; Makol, Ashima; Warrington, Kenneth J.

    2012-01-01

    Objective To describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors. Patients and Methods This is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti–TNF-α therapy. Results Of 8 patients with vasculitis associated with anti–TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti–TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation. Conclusion Cutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed. PMID:22795634

  6. Regulation of bitter taste responses by tumor necrosis factor.

    Science.gov (United States)

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Avascular Necrosis of Trochlea After Supracondylar Humerus Fractures in Children.

    Science.gov (United States)

    Etier, Brian E; Doyle, J Scott; Gilbert, Shawn R

    2015-10-01

    Avascular necrosis (AVN) is a rare but important complication after supracondylar humerus fractures. Posttraumatic humerus deformity was first reported in 1948 and sporadically thereafter. AVN deformity has been classified as type A (AVN of the lateral ossification center) and type B (AVN of the entire medial crista and a metaphyseal portion). In this article, we present 5 cases of AVN after supracondylar humerus fracture, discuss the importance of late clinical findings, and postulate a mechanism of AVN in nondisplaced fractures. Five cases of AVN after supracondylar humerus fracture were reviewed from the Children's of Alabama database. Four of the 5 patients were female. Four patients sustained a Gartland type III fracture, and 1 patient sustained a nondisplaced Gartland type I fracture. Age at time of injury ranged from 5 years to 10 years. All patients had an asymptomatic clinical period after treatment and re-presented 6 months to 7 years later with elbow pain or loss of motion. All patients were treated symptomatically. AVN of the trochlea has a late clinical presentation. The cause of this complication is interruption of the trochlea blood supply. In displaced fractures, the medial and/or lateral vessels are injured, leading to type A or type B deformity. In nondisplaced fractures, the lateral vessels are interrupted by tamponade because of encased fracture hematoma; this presents as a type A deformity. Both type A and type B deformities can be clinically significant. AVN of the trochlea should be considered in patients with late presentation of pain or loss of motion after treatment of supracondylar humerus fractures.

  8. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

    Science.gov (United States)

    Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

    2011-04-01

    Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

  9. Research progress of antagonistic interactions among root canal irrigations disease

    Directory of Open Access Journals (Sweden)

    Chen QU

    2013-07-01

    Full Text Available Root canal therapy is the most effective way to treat various pulposis and periapical disease. Simple mechanical apparatus can not clean root canal thoroughly, but may affect tight filling instead. It can achieve a satisfactory cleansing effect only when it is combined with a chemical solution. Irrigation fluid for root canal should possess the properties of tissue dissolution, antimicrobial, lubrication, and removal of smear layer. So far, no solution is able to fulfill all these functions. Therefore, a combined use of multiple irrigation solutions is suggested. It can not only achieve good effect in cleaning and disinfection, also it can lower the concentration of different solutions, thus reducing the side effects. Nevertheless, some experiments proved that antagonism existed among the chemicals used for irrigations. The purpose of present article is to review the antagonistic effect among the chemicals used for irrigation when they are used together for root canal treatment.

  10. Effects of TNF antagonists on immune and neuroendocrine system

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available In the article, the literature on the effects of TNFa-antagonists (etanercept, infliximab and adalimumab on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn’s disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo- pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

  11. Identification of Bexarotene as a PPARγ Antagonist with HDX

    Directory of Open Access Journals (Sweden)

    David P. Marciano

    2015-01-01

    Full Text Available The retinoid x receptors (RXRs are the pharmacological target of Bexarotene, an antineoplastic agent indicated for the treatment of cutaneous T cell lymphoma (CTCL. The RXRs form heterodimers with several nuclear receptors (NRs, including peroxisome proliferator-activated receptor gamma (PPARγ, to regulate target gene expression through cooperative recruitment of transcriptional machinery. Here we have applied hydrogen/deuterium exchange (HDX mass spectrometry to characterize the effects of Bexarotene on the conformational plasticity of the intact RXRα:PPARγ heterodimer. Interestingly, addition of Bexarotene to PPARγ in the absence of RXRα induced protection from solvent exchange, suggesting direct receptor binding. This observation was confirmed using a competitive binding assay. Furthermore, Bexarotene functioned as a PPARγ antagonist able to alter rosiglitazone induced transactivation in a cell based promoter:reporter transactivation assay. Together these results highlight the complex polypharmacology of lipophilic NR targeted small molecules and the utility of HDX for identifying and characterizing these interactions.

  12. Rational use of calcium-channel antagonists in Raynaud's phenomenon.

    Science.gov (United States)

    Sturgill, M G; Seibold, J R

    1998-11-01

    Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

  13. Antagonistic Bioactivity of Endophytic Actinomycetes Isolated from Medicinal Plants

    Directory of Open Access Journals (Sweden)

    M. Gangwar

    2011-10-01

    Full Text Available Endophytic actinomycetes are promising biocontrol agents for use in agriculture and have been isolated from various plant species. In the present study, 40 endophytic actinomycetes were isolated from roots, stems and leaves of three medicinal plants viz. Aloe vera, Mentha arvensis and Ocimum sanctum. The identification revealed that the majority of the isolates were Streptomyces spp. and the rest were identified as Saccharopolyspora spp., Micromonospora spp. and Actinopolyspora spp. The dual tests revealed that nine endophytic actinomycete isolates displayed a wide spectrum activity against nine fungal phytopathogens. Out of 8 isolates, 90% inhibited the growth of at least one or more phytopathogenic fungi and Saccharopolyspora 0-9 (Out of 8 isolates, 90% inhibited the growth of at least one or more phytopathogenic fungi and Saccharopolyspora 0-9 exhibited antagonistic activity against Aspergillus niger, Aspergillus flavus, Alternaria brassicicola, Botrytis cinerea, Penicillium digitatum, Fusarium oxysporum, Penicillium pinophilum, Phytophthora dresclea and Colletotrichum falcatum.

  14. The diagnostic value of contrast-enhanced CT in Acute bilateral renal cortical necrosis: a case report

    International Nuclear Information System (INIS)

    Choi, Pil Youb; Lee, Su Han; Lee, Woo Dong

    1996-01-01

    Acute renal cortical necrosis in which there is destruction of the renal cortex and sparing of the renal medulla, is a relatively rare cause of acute renal failure. A definitive diagnosis of acute renal cortical necrosis is based on renal biopsy, but on CT(computed tomography) the rather specific contrast-enhanced appearance of acute renal cortical necrosis has been described. As renal biopsy is not available, contrast-enhanced CT is a useful, noninvasive investigate modality for the early diagnosis of acute renal cortical necrosis. We report the characteristic CT findings of acute renal cortical necrosis in a patient with acute renal failure following an operation for abdominal trauma

  15. LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer.

    Directory of Open Access Journals (Sweden)

    Anamika Basu

    Full Text Available Prostate cancer (PCa mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3, whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.

  16. High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists

    Science.gov (United States)

    Fung, Eileen; Sugianto, Priscilla; Hsu, Jason; Damoiseaux, Robert; Ganz, Tomas

    2013-01-01

    Anemia of inflammation (AI) is common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease. Unless the underlying condition can be reversed, treatment options are limited to erythropoiesis-stimulating agents with or without intravenous iron therapy, modalities that are not always effective and can cause serious adverse effects. Hepcidin, the iron regulatory hormone, has been identified as a pathogenic factor in the development of AI. To explore new therapeutic options for AI and other iron-related disorders caused by hepcidin excess, we developed a cell-based screen to identify hepcidin antagonists. Of the 70,000 small molecules in the library, we identified 14 compounds that antagonized the hepcidin effect on ferroportin. One of these was fursultiamine, a Food and Drug Administration (FDA)–approved thiamine derivative. Fursultiamine directly interfered with hepcidin binding to its receptor, ferroportin, by blocking ferroportin C326 thiol residue essential for hepcidin binding. Consequently, fursultiamine prevented hepcidin-induced ferroportin ubiquitination, endocytosis, and degradation in vitro and allowed continuous cellular iron export despite the presence of hepcidin, with IC50 in the submicromolar range. Thiamine, the fursultiamine metabolite, and benfotiamine, another thiamine derivative, did not interfere with the effect of hepcidin on ferroportin. Other FDA-approved thiol-reactive compounds were at least 1000-fold less potent than fursultiamine in antagonizing hepcidin. In vivo, fursultiamine did not reproducibly antagonize the effect of hepcidin on serum iron, likely because of its rapid conversion to inactive metabolites. Fursultiamine is a unique antagonist of hepcidin in vitro that could serve as a template for the development of drug candidates that inhibit the hepcidin-ferroportin interaction. PMID:23292796

  17. Alpha antagonists and intraoperative floppy iris syndrome: A spectrum

    Directory of Open Access Journals (Sweden)

    Sharif A Issa

    2008-07-01

    Full Text Available Sharif A Issa, Omar H Hadid, Oliver Baylis, Margaret DayanDepartment of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, UKBackground: To determine occurrence of features of intraoperative floppy iris syndrome (IFIS during cataract surgery in patients taking systemic alpha-antagonists (AA.Methods: We prospectively studied patients on AA and who underwent phacoemulsification. The following were recorded: pupil diameter preoperatively, iris flaccidity, iris prolapse and peroperative miosis.Results: We studied 40 eyes of 31 subjects. Mean age was 78 years. Overall, 14 eyes (13 patients showed signs of IFIS: 9/13 (69% eyes of patients on tamsulosin, 1/18 (6% eyes in the doxazosin group, 2/2 prazosin patients, 1/4 eyes in the indoramin group, and 1/2 eyes in two patients on a combination of doxazosin and tamsulosin. Most cases (92% had only one or two signs of IFIS. Bilateral cataract surgery was undertaken in 9 patients but only one patient (on tamsulosin had features of IFIS in both eyes, while 4 patients (2 on tamsulosin and 2 on other AA showed signs of IFIS in one eye only, and 4 patients did not show IFIS in either eye.Conclusion: Most AA were associated with IFIS, but it tends to present as a spectrum of signs rather than full triad originally described. Tamsulosin was most likely to be associated with IFIS; however, its intake does not necessarily mean that IFIS will occur. For patients on AA, the behavior of the iris intraoperatively in one eye is a poor predictor of the other eye. Surgeons should anticipate the occurrence of IFIS in any patient on AA.Keywords: alpha blocker, alpha antagonist, cataract surgery, intraoperative floppy iris syndrome, tamsulosin.

  18. 'Femoral head necrosis' in metabolic and hormonal osteopathies

    Energy Technology Data Exchange (ETDEWEB)

    Heuck, F.H.W.; Treugut, H.

    1984-07-01

    The pathogenesis of bone necrosis is discussed with special attention and with respect to metabolic, hormonal, and vascular factors. The influence of statics and dynamics of the hip joint bones for the development of aseptic necrosis are discussed. 45 patients with ''idiopathic femoral head necroses'' were observed, including 6 cases of renal osteopathy following renal transplantation and immune suppression therapy, 14 cases of long term corticoid therapy, and 11 cases of liver diseases of different genesis. The femoral head necrosis understood as complication of an osteopathy. In our patients there were 31 males and 14 females - which means higher involvement of males. Plain radiological findings and CT-findings of changes of the femoral heat structure in different stages of the disease are described. Early diagnosis of metabolic and hormonal osteopathies is demanded for a joint keeping therapy of the beginning femoral head necrosis. 90 refs.

  19. Which factors influence radiographic progression during treatment with tumor necrosis factor inhibitors in clinical practice?

    DEFF Research Database (Denmark)

    Ørnbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille

    2014-01-01

    OBJECTIVE: To investigate baseline characteristics associated with radiographic progression and the effect of disease activity, drug, switching, and withdrawal on radiographic progression in tumor necrosis factor (TNF) inhibitor-naive patients with rheumatoid arthritis (RA) followed for about 2...

  20. Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis

    NARCIS (Netherlands)

    Ridwan, B. U.; Koning, C. J. M.; Besselink, M. G. H.; Timmerman, H. M.; Brouwer, E. C.; Verhoef, J.; Gooszen, H. G.; Akkermans, L. M. A.

    2008-01-01

    AIMS: Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. METHODS AND RESULTS: Using the well-diffusion

  1. Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report

    Directory of Open Access Journals (Sweden)

    Bogdan Deleanu

    2016-02-01

    Conclusion: The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty.

  2. Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

    Science.gov (United States)

    Parra, Estefanía; Vergara, Andrea; Silva, Raúl F

    2017-03-01

    Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. [RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

    Science.gov (United States)

    Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

    2015-12-01

    To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

  4. Post Traumatic Avascular Necrosis of the Proximal Carpal Row--A Case Report.

    Science.gov (United States)

    Manohara, Ruben; Sebastin, Sandeep Jacob; Puhaindran, Mark Edward

    2015-10-01

    We report a case of avascular necrosis of the scaphoid, lunate and triquetrum in a young 21-year-old patient, after a purely ligamentous peri-lunate dislocation of the wrist. He presented with a Mayfield III peri-lunate dislocation after a road traffic accident and underwent an open reduction and internal fixation. Post-operatively, the scapho-lunate gap widened after removal of the temporary K-wires, and he gradually developed avascular necrosis of the scaphoid, lunate and triquetrum, and osteoarthritis of his wrist. We present this unusual case of simultaneous avascular necrosis of multiple carpal bones and discuss the possible risk factors and subsequent management plans for this complex injury. Our patient has no identifiable contributing factors to developing avascular necrosis. We suspect that the violence of the injury and surgery may have compromised the circulation, and advise caution when treating and counseling these patients pre-operatively.

  5. Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

    NARCIS (Netherlands)

    Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P.; Petrides, Francine; Cuesta Torres, Luisa F.; Hou, Liming; Cook, Adam; Barter, Philip J.; Weninger, Wolfgang; Rye, Kerry-Anne

    2015-01-01

    Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo)

  6. Endoscopic treatment of multilocular walled-off pancreatic necrosis with the multiple transluminal gateway technique.

    Science.gov (United States)

    Jagielski, Mateusz; Smoczyński, Marian; Adrych, Krystian

    2017-06-01

    The development of minimally invasive techniques allowed access to the necrotic cavity through transperitoneal, retroperitoneal, transmural and transpapillary routes. The choice of access to walled-off pancreatic necrosis (WOPN) should depend not only on the spread of necrosis, but also on the experience of the clinical center. Herein we describe treatment of a patient with multilocular symptomatic walled-off pancreatic necrosis using minimally invasive techniques. The single transmural access (single transluminal gateway technique - SGT) to the necrotic collection of the patient was ineffective. The second gastrocystostomy was performed using the same minimally invasive technique as an extra way of access to the necrosis (multiple transluminal gateway technique - MTGT). In the described case the performance of the new technique consisting in endoscopic multiplexing transmural access (MTGT) was effective enough and led to complete recovery of the patient.

  7. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis

    NARCIS (Netherlands)

    Baert, F. J.; D'Haens, G. R.; Peeters, M.; Hiele, M. I.; Schaible, T. F.; Shealy, D.; Geboes, K.; Rutgeerts, P. J.

    1999-01-01

    Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. Thirteen patients with steroid-refractory Crohn's

  8. Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model.

    Science.gov (United States)

    Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad R; Shariati, Mehdi; Rahmani, Mohammad R; Allahtavakoli, Mohammad

    2017-08-01

    Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  9. A case of severe acute pancreatitis with near total pancreatic necrosis diagnosed by dynamic CT scanning

    International Nuclear Information System (INIS)

    Takeda, Kazunori; Kakugawa, Yoichiro; Amikura, Katsumi; Miyagawa, Kikuo; Matsuno, Seiki; Sato, Toshio

    1987-01-01

    A 42 year-old woman with severe acute pancreatitis had drainage of the pancreatic bed, cholecystostomy and jejunostomy on admission, but symptoms were not improved. Fourteen days after admission, clinical sepsis and septisemia were recognized. Dynamic CT scanning of the pancreas showed near total pancreatic necrosis. Symptoms were improved after necrosectomy of the pancreas and debridement of the peripancreatic necrotic tissue were performed. Our experience suggests the usefulness of dynamic CT scanning for detection of pancreatic necrosis in severe acute pancreatitis. (author)

  10. Extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia

    International Nuclear Information System (INIS)

    Labbe, R.; Lindsay, T.; Walker, P.M.

    1987-01-01

    The management of an acutely ischemic extremity requires knowledge of the response of skeletal muscle (the largest component of the lower limb) to prolonged periods of complete normothermic ischemia. We have used the canine gracilis muscle model to evaluate the extent and distribution of ischemic necrosis after 3 and 5 hours of ischemia and 48 hours of reperfusion. Each muscle was cut into six slices, and the extent and distribution of postischemic necrosis identified by means of nitroblue tetrazolium staining and 99mTc pyrophosphate uptake. After 3, 4, and 5 hours of ischemia the extent of necrosis was 2.0% +/- 0.9%, 30.3% +/- 6.0%, and 90.1% +/- 3.5% (mean +/- SEM), respectively. A statistically significant correlation exists between the extent of necrosis and the uptake of 99mTc pyrophosphate uptake per gram of tissue (y = 1574.9x - 8.4, r = 0.84, p less than 0.001). Most necrosis was centrally located and found in the thickest portion of the muscle. We conclude that there is a graded response in the extent of skeletal muscle necrosis related to the length of ischemic stress rather than an ''all-or-none'' phenomenon. This central distribution of necrosis makes the usual external evaluation of ischemic damage clinically unreliable. In addition, since there was no enveloping fascia in this model, a compartment release alone may not prevent the development of skeletal muscle necrosis. This knowledge of the response of skeletal muscle to ischemia may lead to an improved clinical approach to an extremity suffering a prolonged ischemic insult

  11. Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

    International Nuclear Information System (INIS)

    Kakite, Suguru; Dyvorne, Hadrien A.; Lee, Karen M.; Jajamovich, Guido H.; Knight-Greenfield, Ashley; Taouli, Bachir

    2015-01-01

    To correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. In this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0 T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. 79 HCCs were assessed (mean size 2.5 cm). D, PF and ADC were significantly higher in HCC vs. liver (p < 0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p < 0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC > 0.95, p < 0.002). D has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging

  12. Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

    Science.gov (United States)

    Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

    2018-03-01

    Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

  13. MRI and US findings of subcutaneous fat necrosis of the newborn

    Energy Technology Data Exchange (ETDEWEB)

    Vasireddy, Syam; Long, Scott D. [Southern Illinois University, Department of Radiology, Springfield, IL (United States); St. John' s Hospital, Department of Radiology, Springfield, IL (United States); Sacheti, Bhavna [Medical College of Wisconsin, Department of Pediatric Critical Care, Milwaukee, WI (United States); Children' s Hospital Wisconsin, Department of Critical Care, Milwaukee, WI (United States); Mayforth, Ruth D. [Southern Illinois University, Department of Surgery, Springfield, IL (United States); St. John' s Hospital, Department of Surgery, Springfield, IL (United States)

    2009-01-15

    Subcutaneous fat necrosis of the newborn (SCFN) is an uncommon, benign disorder found in full-term or post-mature neonates. It usually presents in neonates who have experienced perinatal difficulty such as asphyxia, peripheral hypoxemia, hypothermia, meconium aspiration or trauma. We present a newborn with abnormal findings on MRI and US within the axilla, neck, and abdominal walls that were pathologically proved via biopsy to be subcutaneous fat necrosis. (orig.)

  14. Common bile duct cancer with massive necrosis mimicking choledochal dilatation on CT

    International Nuclear Information System (INIS)

    Miyake, H.; Matsumoto, S.; Ueda, S.; Maeda, T.; Aikawa, H.; Mori, H.

    1991-01-01

    Carcinomas of the common bile duct are usually seen as dilatation of the bile duct proximal to a solid mass on CT. In the case reported here, the common bile duct cancer itself mimicked dilated common bile duct on CT because of massive necrosis. In a case of simulating dilated common bile duct on CT, and discrepancy between CT and ultrasonography or endoscopic retrograde cholangiopancreatography, a common bile duct cancer with massive necrosis should be included in the differential diagnosis. (orig.)

  15. Diagnostic scope of computer tomography in hip disease - Paget's disease, femoral head necrosis, coxarthrosis, coxarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Nebel, G; Lingg, G; Reid, W

    1982-10-01

    The value of computer tomography was investigated in Paget's disease of the hip, femoral head necrosis (adult avascular and osteoradionecrosis), coxarthrosis and coxarthritis (bacterial and rheumatoid). The greatest value of CT is in the diagnosis of adult avascular necrosis of the femoral head and is valuable for localising the necrotic area in the axial plane. This is of value in planning surgical treatment (displacement osteotomy or endoprosthesis). In Paget's disease, coxarthrosis and coxarthritis, CT provides only additional or more precise information.

  16. Ranking of computed tomography in diagnosis of avascular necrosis of femoral head in adults

    International Nuclear Information System (INIS)

    Nebel, G.

    1982-01-01

    On 12 patients (7 males, 5 females) with the diagnosis of avascular (aseptic) necrosis of the femoral head the value of computed tomography was investigated. Stages II-IV were observed (following the staging of Ficat and Arlet). Exept for 2 cases the findings of necrosis on axial CT-slices were always located in the anterior part of the femoral head. The problems of early diagnosis of the disease are discussed. (orig.) [de

  17. Ranking of computed tomography in diagnosis of avascular necrosis of femoral head in adults

    Energy Technology Data Exchange (ETDEWEB)

    Nebel, G

    1982-01-01

    On 12 patients (7 males, 5 females) with the diagnosis of avascular (aseptic) necrosis of the femoral head the value of computed tomography was investigated. Stages II-IV were observed (following the staging of Ficat and Arlet). Exept for 2 cases the findings of necrosis on axial CT-slices were always located in the anterior part of the femoral head. The problems of early diagnosis of the disease are discussed.

  18. Diagnostic scope of computer tomography in hip disease - Paget's disease, femoral head necrosis, coxarthrosis, coxarthritis

    International Nuclear Information System (INIS)

    Nebel, G.; Lingg, G.; Reid, W.

    1982-01-01

    The value of computer tomography was investigated in Paget's disease of the hip, femoral head necrosis (adult avascular and osteoradionecrosis), coxarthrosis and coxarthritis (bacterial and rheumatoid). The greatest value of CT is in the diagnosis of adult avascular necrosis of the femoral head and is valuable for localising the necrotic area in the axial plane. This is of value in planning surgical treatment (displacement osteotomy or endoprosthesis). In Paget's disease, coxarthrosis and coxarthritis, CT provides only additional or more precise information. (orig.) [de

  19. Purification and reconstitution of the calcium antagonist receptor of the voltage-sensitive calcium channel

    International Nuclear Information System (INIS)

    Curtis, B.M.

    1986-01-01

    Treatment with digitonin solubilized the calcium antagonist receptor as a stable complex with [ 3 H]nitrendipine from rat brain membranes. The solubilized complex retains allosteric coupling to binding sites for diltiazem, verapamil, and inorganic calcium antagonist sites. The calcium antagonist receptor from cardiac sarcolemma and the transverse-tubule membrane of skeletal muscle is also efficiently solubilized with digitonin and the receptor in all three tissues is a large glycoprotein with a sedimentation coefficient of 20 S. The T-tubule calcium antagonist receptor complex was extensively purified by a combination of chromatography on WGA-Sepharose, ion exchange chromatography, and sedimentation on sucrose gradients to yield preparations estimated to be 41% homogeneous by specific activity and 63% homogeneous by SDS gel electrophoresis. Analysis of SDS gels detect three polypeptides termed α(Mr 135,000), β(Mr 50,000), and γ(Mr 32,000) as noncovalently associated subunits of the calcium antagonist receptor. The α and γ subunits are glycosylated polypeptides, and the molecular weight of the core polypeptides are 108,000 and 24,000 respectively. The calcium antagonist receptor was reconstituted into a phospholipid bilayer by adding CHAPS and exogeneous lipid to the purified receptor followed by rapid detergent removal. This procedure resulted in the incorporation of 45% of the calcium antagonist receptor into closed phospholipid vesicles. Data suggests that the α, β, and γ subunits of the T-tubule calcium antagonist receptor are sufficient to form a functional calcium channel

  20. Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

    DEFF Research Database (Denmark)

    Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund

    2007-01-01

    We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced ...

  1. Agar composition affects in vitro screening of biocontrol activity of antagonistic microorganisms

    NARCIS (Netherlands)

    Bosmans, Lien; De Bruijn, I.; de Mot, Rene; Readers, Hans; Lievens, Bart

    2016-01-01

    Agar-based screening assays are the method of choice when evaluating antagonistic potential of bacterial biocontrol-candidates against pathogens.Weshowed thatwhen using the samemedium, but different agar compositions, the activity of a bacterial antagonist against Agrobacteriumwas strongly affected.

  2. Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.

    Science.gov (United States)

    Cherney, Robert J; Mo, Ruowei; Meyer, Dayton T; Pechulis, Anthony D; Guaciaro, Michael A; Lo, Yvonne C; Yang, Gengjie; Miller, Persymphonie B; Scherle, Peggy A; Zhao, Qihong; Cvijic, Mary Ellen; Barrish, Joel C; Decicco, Carl P; Carter, Percy H

    2012-10-01

    We describe the design, synthesis, and evaluation of benzimidazoles as benzamide replacements within a series of trisubstituted cyclohexane CCR2 antagonists. 7-Trifluoromethylbenzimidazoles displayed potent binding and functional antagonism of CCR2 while being selective over CCR3. These benzimidazoles were also incorporated into lactam-containing antagonists, thus completely eliminating the customary bis-amide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Avascular necrosis of the femoral head after renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hae Woong; Yoon, Jeong Hee; Kim, Chang Soo [Maryknoll Hospital, Pusan (Korea, Republic of)

    1999-08-01

    To determine the incidence of avascular necrosis (AVN) of the femoral head after renal transplantation, evaluate plain radiographic and MR findings, and compare known predisposing factors between the AVN group and the control group. Between August 1990 and June 1998, 256 renal transplantations were carried out at the Maryknoll hospital. The incidence of AVN was determined clinically, and in the AVN group, plain radiographic and MR findings were evaluated. A control group of 29 cases was randomly selected from among the remaining 241 patients, and acute rejection, mean daily steroid dose and osteopenia were compared between the AVN group and the control group. The incidence of AVN of the femoral head was 5.9%(15/256). Involvement was bilateral in nine cases and unilateral in six and 24 femoral heads were thus affected. The mean period required for diagnosis of this condition was 10.7 months(within 6 months: 2 hips, between 6-12 months: 10, between 12-24 months: 9, over 24 months: 3). Plain radiographs showed that three cases were Ficat stage I, five were stage II, seven were stage III, and nine were stage IV. MRI indicated that 15 cases were Mitchell class A, one was class C, and three were class D. Correlation between Ficat stage and the period required for diagnosis showed that the longer the latter, the higher the Ficat stage. A comparison of risk factors between the AVN group and the control group showed that the incidence of acute rejection and osteopenia, and the mean daily steroid dose, were higher in the AVN group than in the rejection group and that the difference was statistically significant. The incidence of AVN of the femoral head after renal transplantation was 5.9%. The longer the period required for diagnosis of AVN, the higher the Ficat stage. A comparison of risk factors between the AVN group and the rejection group showed that the incidence of acute rejection and osteopenia as well as the mean daily steroid dose, were higher in the AVN group than

  4. Avascular necrosis of the femoral head after renal transplantation

    International Nuclear Information System (INIS)

    Jeong, Hae Woong; Yoon, Jeong Hee; Kim, Chang Soo

    1999-01-01

    To determine the incidence of avascular necrosis (AVN) of the femoral head after renal transplantation, evaluate plain radiographic and MR findings, and compare known predisposing factors between the AVN group and the control group. Between August 1990 and June 1998, 256 renal transplantations were carried out at the Maryknoll hospital. The incidence of AVN was determined clinically, and in the AVN group, plain radiographic and MR findings were evaluated. A control group of 29 cases was randomly selected from among the remaining 241 patients, and acute rejection, mean daily steroid dose and osteopenia were compared between the AVN group and the control group. The incidence of AVN of the femoral head was 5.9%(15/256). Involvement was bilateral in nine cases and unilateral in six and 24 femoral heads were thus affected. The mean period required for diagnosis of this condition was 10.7 months(within 6 months: 2 hips, between 6-12 months: 10, between 12-24 months: 9, over 24 months: 3). Plain radiographs showed that three cases were Ficat stage I, five were stage II, seven were stage III, and nine were stage IV. MRI indicated that 15 cases were Mitchell class A, one was class C, and three were class D. Correlation between Ficat stage and the period required for diagnosis showed that the longer the latter, the higher the Ficat stage. A comparison of risk factors between the AVN group and the control group showed that the incidence of acute rejection and osteopenia, and the mean daily steroid dose, were higher in the AVN group than in the rejection group and that the difference was statistically significant. The incidence of AVN of the femoral head after renal transplantation was 5.9%. The longer the period required for diagnosis of AVN, the higher the Ficat stage. A comparison of risk factors between the AVN group and the rejection group showed that the incidence of acute rejection and osteopenia as well as the mean daily steroid dose, were higher in the AVN group than

  5. Bevacizumab as a treatment option for radiation-induced cerebral necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

    2011-02-15

    Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

  6. Mucoperiosteal Flap Necrosis after Primary Palatoplasty in Patients with Cleft Palate

    Science.gov (United States)

    Cotrina-Rabanal, Omar; Barrenechea-Tarazona, Luis; Vargas-Chanduvi, Roberto; Paredes-Aponte, Luis; Romero-Narvaez, Carolina

    2017-01-01

    Background The prevalence of flap necrosis after palatoplasty in patients with cleft palate. The prevalence of mucoperiosteal flap necrosis after palatoplasty remains unknown, and this complication is rare. This event is highly undesirable for both the patient and the surgeon. We present here a new scale to evaluate the degree of hypoplasia of the palate and identify patients with cleft palate at high risk for the development of this complication. Methods In this case series, a 20-year retrospective analysis (1994–2014) identified patients from our records (medical records and screening day registries) with nonsyndromic cleft palate who underwent operations at 3 centers. All of these patients underwent operations using 2-flap palatoplasty and also underwent a physical examination with photographs and documentation of the presence of palatal flap necrosis after primary palatoplasty. Results Palatal flap necrosis was observed in 4 cases out of 1,174 palatoplasties performed at these centers. The observed prevalence of palatal flap necrosis in these groups was 0.34%. Conclusions The prevalence of flap necrosis can be reduced by careful preoperative planning, and prevention is possible. The scale proposed here may help to prevent this complication; however, further studies are necessary to validate its utility. PMID:28573096

  7. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    International Nuclear Information System (INIS)

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H; Lawrence, Theodore S; Ten Haken, Randall K; Tsien, Christina I; Cao, Yue; Chenevert, Thomas

    2014-01-01

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose–volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials. (paper)

  8. Differential diagnosis of metastases in bone scans: chemotherapy induced bone necrosis

    International Nuclear Information System (INIS)

    Reuland, P.

    1999-01-01

    Aim: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors. Methods: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis. Results: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy. Conclusion: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimikry metastases. (orig.) [de

  9. A Review on Fat Necrosis of the Breast: The Dilemma of Differential Diagnosis with Cancer

    Directory of Open Access Journals (Sweden)

    Toktam Beheshtian

    2015-05-01

    Full Text Available Fat necrosis is a benign inflammatory process which can involve adipose tissue anywhere in the body. A previous history of trauma or surgery may or may not be present. Information about the clinical and radiological appearance of this lesion is very important because it can mimic breast cancer.In this article, we review the features of fat necrosis in different imaging modalities including mammography, ultrasound, and magnetic resonance imaging (MRI, and compare them with histopathologic findings; then, we try to provide a logical approach for fat necrosis management.The appearance of fat necrosis at imaging is variable from definitely benign type to highly suspicious for malignancy. The specificity of mammography is higher than that of ultrasonography; therefore, for a definite diagnosis of fat necrosis, emphasis should be mainly based on mammography rather than ultrasonography.Finally, fat necrosis is not a common disease; however, regarding unusual and atypical findings in different imaging modalities, differentiation from a cancer may be difficult, especially in patients with a previous history of malignancy. Therefore, a multimodality approach is required for a definite diagnosis.

  10. Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone.

    Science.gov (United States)

    Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

    2017-02-01

    To present our experience in the management of patients with infected pancreatic necrosis without drainage. The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration.

  11. Bevacizumab as a treatment option for radiation-induced cerebral necrosis

    International Nuclear Information System (INIS)

    Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried; Nawatny, Jens; Hoffmann, Thomas K.; Peiper, Matthias; Orth, Klaus; Gerber, Peter Arne; Rusnak, Ethelyn; Lammering, Guido; MAASTRO Clinic, Maastricht

    2011-01-01

    Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

  12. Mucoperiosteal Flap Necrosis after Primary Palatoplasty in Patients with Cleft Palate

    Directory of Open Access Journals (Sweden)

    Percy Rossell-Perry

    2017-05-01

    Full Text Available BackgroundThe prevalence of flap necrosis after palatoplasty in patients with cleft palate. The prevalence of mucoperiosteal flap necrosis after palatoplasty remains unknown, and this complication is rare. This event is highly undesirable for both the patient and the surgeon. We present here a new scale to evaluate the degree of hypoplasia of the palate and identify patients with cleft palate at high risk for the development of this complication.MethodsIn this case series, a 20-year retrospective analysis (1994–2014 identified patients from our records (medical records and screening day registries with nonsyndromic cleft palate who underwent operations at 3 centers. All of these patients underwent operations using 2-flap palatoplasty and also underwent a physical examination with photographs and documentation of the presence of palatal flap necrosis after primary palatoplasty.ResultsPalatal flap necrosis was observed in 4 cases out of 1,174 palatoplasties performed at these centers. The observed prevalence of palatal flap necrosis in these groups was 0.34%.ConclusionsThe prevalence of flap necrosis can be reduced by careful preoperative planning, and prevention is possible. The scale proposed here may help to prevent this complication; however, further studies are necessary to validate its utility.

  13. Lysozyme as an alternative to antibiotics improves growth performance and tumor necrosis factor-a levels during an indirect immune challenge

    Science.gov (United States)

    Lysozyme is a 1,4-ß-N-acetylmuramidase that has antimicrobial properties. The objective of this study was to determine the effect of lysozyme and antibiotics on growth performance and immune response during an indirect disease challenge. Two replicates of 720 pigs each were weaned from the sow at ...

  14. [Effect of vascular endothelial growth factor and tumor necrosis factor receptor for treatment of avascular necrosis of the femoral head in rabbits].

    Science.gov (United States)

    Hu, Zhi-ming; Zhou, Ming-qian; Gao, Ji-min

    2008-12-01

    To evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits. Avascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head. Compared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity. Percutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

  15. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were ...

  16. Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechukwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Calley, Cynthia S.J. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana (United States)

    2015-02-01

    Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

  17. Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Sadek B

    2016-11-01

    , in which 3-piperidinopropan-1-ol in ligand 2 was replaced by (4-(3-(piperidin-1-ylpropoxyphenylmethanol, and its (S-enantiomer (4 significantly and in a dose-dependent manner reduced convulsions or exhibited full protection in MES and PTZ convulsions model, respectively. Interestingly, the protective effects observed for the (R-enantiomer (3 in MES model were significantly greater than those of the standard H3R inverse agonist/antagonist pitolisant, comparable with those observed for PHT, and reversed when rats were pretreated with the selective H3R agonist R-(α-methyl-histamine. Comparisons of the observed antagonistic in vitro affinities among the ligands 1–6 revealed profound stereoselectivity at human H3Rs with varying preferences for this receptor subtype. Moreover, the in vivo anticonvulsant effects observed in this study for ligands 1–6 showed stereoselectivity in different convulsion models in male adult rats. Keywords: histamine, H3 receptor, isomeric antagonists, anticonvulsant activity, stereo­selectivity

  18. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

    NARCIS (Netherlands)

    van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

    2002-01-01

    BACKGROUND: People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory

  19. Antagonistic studies and hyphal interactions of the new antagonist Aspergillus piperis against some phytopathogenic fungi in vitro in comparison with Trichoderma harzianum.

    Science.gov (United States)

    El-Debaiky, Samah A

    2017-12-01

    The present study represents, for the first time, the detailed studies about the hyphal interactions of Aspergillus piperis, as a new antagonist, against some isolated plant pathogenic fungi (Alternaria alternata, Alternaria solani, Botrytis cinerea, Sclerotium cepivorum and Sclerotinia sclerotiorum) in vitro. The bio-controlling capability of A. piperis against the tested phytopathogens was tested using the dual culture method. This experiment revealed that A. piperis had antagonistic activity and reduced the growth of the tested phytopathogens and grew over their mycelia in the paired plates. Also, several antagonistic mechanisms were recorded, in this study, between A. piperis and the tested phytopathogens using the microscopic examination. The bio-controlling activity and the antagonistic mechanisms exhibited by the new antagonist, A. piperis were compared with those obtained by the common antagonist, Trichoderma harzianum against the same phytopathogens. The obtained results showed that, A. piperis was more effective than T. harzianum in inhibiting all the tested species in the dual culture plates. The best result was 81.85% inhibition percentage against S. sclerotiorum by A. piperis while, T. harzianum exhibits only 45.18%. Moreover, several antagonistic mechanisms and hyphal interactions were investigated among the hyphae of both A.piperis and T. harzianum and the hyphae of the tested phytopathogens. These mechanisms were summarized as; mycoparasitism (coiling and penetration of the hyphae) and antibiosis in the form of lysis of the hyphal cells and spores, denaturation and breaking of the hyphae. The indirect interaction (antibiosis) and the direct mycoparasitism were observed by A. piperis against all the tested phytopathogens, but it attacked the hyphae and conidiophores of A. alternata by only the antibiosis interaction. The microscopic examination revealed also that T. harzianum attacked the tested phytopathogens by both antibiosis and mycoparasitism

  20. Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France); Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr [Institut Gustave Roussy, Department of Epidemiology (France); Tselikas, Lambros, E-mail: lambros.tselikas@gmail.com; Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Farouil, Geoffroy, E-mail: g.farouil@gmail.com [Institut Gustave Roussy, Department of Interventional Radiology (France); Boige, Valérie, E-mail: boige@igr.fr; Malka, David, E-mail: david.malka@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Leboulleux, Sophie, E-mail: sophie.leboulleux@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Ducreux, Michel, E-mail: ducreux@igr.fr [Institut Gustave Roussy, Department of Digestive Oncology (France); Baudin, Eric, E-mail: baudin@igr.fr [Institut Gustave Roussy, Department of Nuclear Medicine and Endocrine Oncology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave Roussy, Department of Interventional Radiology (France)

    2015-04-15

    PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developed after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.

  1. Increase of tumor necrosis factor receptor 1 expression in women with unexplained early spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    YAN Chun-fang; YU Xue-wen; JIN Hui; LI Xu

    2004-01-01

    To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua andconcentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion,threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplainedearly spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortionof pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing arti-ficial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 indecidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was mea-sured with an enzyme-linked immunosorbent assay. Results: The ercentages of membrane tumor necrosis factor receptor 1positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13.14 ±6.30 for healthy pregnant women ( P < 0.05). Serum oncentration of soluble tumor necrosis factor receptor 1 was signifi-cantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women withthreatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion.Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosisfactor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may cont-ribute to the development of early spontaneous abortion.

  2. Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral Femoroplasty.

    Science.gov (United States)

    Rupp, Robert E; Rupp, Sasha N

    2016-05-01

    This study was conducted to identify the risk of avascular necrosis of the femoral head after arthroscopic femoroplasty extending to the posterolateral femoral neck, the source of the primary blood supply to the femoral head. Cam lesions of femoroacetabular impingement are typically anterior along the junction of the femoral head and neck. However, anatomic variations can involve the posterolateral vascular region of the femoral head and neck. Femoroplasty involving this vascular region can lead to injury to the blood supply to the femoral head, with subsequent avascular necrosis. If the posterolateral portion of the cam lesion is preserved, persistent femoroacetabular impingement may occur. A retrospective review identified 112 patients who underwent arthroscopic femoroplasty for femoroacetabular impingement over a 2-year period. Of these patients, 14 had femoroplasty that extended to the posterolateral femoral head. Of this group, 5 had undergone magnetic resonance imaging (MRI) after femoroplasty and the other 9 were contacted to undergo MRI of the hip to evaluate for avascular necrosis. A radiologist and the senior author evaluated all MRI scans specifically for avascular necrosis of the femoral head. All procedures were performed by the senior author. Mean age of the 14 patients (8 women and 6 men) with femoroplasty that extended into the posterolateral vascular region of the femoral head was 44 years (range, 23-69 years). All 14 patients underwent MRI evaluation of the affected hip a mean of 25 months (range, 7-44 months) after femoroplasty. No MRI scans showed evidence of avascular necrosis of the femoral head. Femoroplasty of the posterolateral vascular region of the femoral head is not associated with avascular necrosis. Patients with femoroacetabular impingement and a cam lesion extending to the posterolateral femoral head can undergo femoroplasty of this region without the development of avascular necrosis. [Orthopedics. 2016; 39(3):177-180.]. Copyright

  3. Avascular necrosis of the femoral head after osteosynthesis of femoral neck fracture.

    Science.gov (United States)

    Min, Byung-Woo; Kim, Sung-Jin

    2011-05-18

    The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. We evaluated the incidence of avascular necrosis of the femoral head with the use of contemporary techniques for femoral neck fracture fixation. We then sought to determine what potential risk factors influenced the development of avascular necrosis.Between 1990 and 2005, one hundred sixty-three intracapsular femoral neck fractures in 163 patients were treated with internal fixation at our level-I trauma center. All patients were monitored until conversion to total hip arthroplasty or for a minimum of 2 years postoperatively. Ten patients (10 hips) died and 7 patients (7 hips) were lost to follow-up. The remaining 146 patients (146 hips) had a mean 5.2 years of follow-up (range, 3 months to 17 years). The incidence of avascular necrosis was 25.3% (37 hips). The average time to diagnosis of avascular necrosis was 18.8 months (range, 3-47 months). Patient sex, age, interval from injury to surgery, and mechanism of injury were statistically not associated with the development of avascular necrosis. The quality of fracture reduction, adequacy of fixation, degree of displacement, and comminution of the posterior cortex were significantly associated. After we controlled for patient and radiographic characteristics, multivariate analyses indicated that the important predictors for avascular necrosis are poor reduction (odds ratio=13.889) and initial displacement of the fracture (odds ratio=4.693). Copyright 2011, SLACK Incorporated.

  4. Infliximab TNF-alpha antagonist decreases intraabdominal adhesions

    International Nuclear Information System (INIS)

    Kurukahvecioglu, O.; Koksal, H.; Yazicioglu, O.; Kerem, M.; Taneri, F.; Gulbahar, O.; Erdem, O.; Engin, D.

    2007-01-01

    Objective was to evaluate the effect of infliximab on adhesion formation and its associated morbidity and complications. This study was performed in the Faculty of Medicine, Gaze University, Turkey between July 2005 and October 2005. Thirty-five rats were randomly divided into 4 groups. Laparotomy was performed in the Sham group (n=5), whereas cecal abrasion was carried out in all other groups. After cecal abrasion 0.9% sodium chloride was administered in the saline group (n=10), infliximab was administered to the study group (n=10) and nothing was administered to the last group (n=10). Adhesion formation was evaluated with macroscopic adhesion scoring systems. Peritoneal fluid samples and mesenteric lymph node biopsies were taken to rule out bacterial peritonitis. Blood and peritoneal irrigation fluids samples were taken to measure the Tumor necrosis factor-alpha (TNF-alpha) levels. Macroscopic adhesion scores showed fewer adhesions in the infliximab group. The infliximab group had significantly fewer adhesions than the abrasion control and saline groups. According to the histological findings, there were no statistically significant differences between the groups. Early blocking of the activity of TNF-alpha after cecal abrasion resulted in lower rates of adhesion formation, macroscopically. The TNF-alpha, a proinflammatory cytokine appears to be an important mediator for postoperative adhesion formation. (author)

  5. Exploitation of microbial antagonists for the control of postharvest diseases of fruits: a review.

    Science.gov (United States)

    Dukare, Ajinath Shridhar; Paul, Sangeeta; Nambi, V Eyarkai; Gupta, Ram Kishore; Singh, Rajbir; Sharma, Kalyani; Vishwakarma, Rajesh Kumar

    2018-01-16

    Fungal diseases result in significant losses of fruits and vegetables during handling, transportation and storage. At present, post-production fungal spoilage is predominantly controlled by using synthetic fungicides. Under the global climate change scenario and with the need for sustainable agriculture, biological control methods of fungal diseases, using antagonistic microorganisms, are emerging as ecofriendly alternatives to the use of fungicides. The potential of microbial antagonists, isolated from a diversity of natural habitats, for postharvest disease suppression has been investigated. Postharvest biocontrol systems involve tripartite interaction between microbial antagonists, the pathogen and the host, affected by environmental conditions. Several modes for fungistatic activities of microbial antagonists have been suggested, including competition for nutrients and space, mycoparasitism, secretion of antifungal antibiotics and volatile metabolites and induction of host resistance. Postharvest application of microbial antagonists is more successful for efficient disease control in comparison to pre-harvest application. Attempts have also been made to improve the overall efficacy of antagonists by combining them with different physical and chemical substances and methods. Globally, many microbe-based biocontrol products have been developed and registered for commercial use. The present review provides a brief overview on the use of microbial antagonists as postharvest biocontrol agents and summarises information on their isolation, mechanisms of action, application methods, efficacy enhancement, product formulation and commercialisation.

  6. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    International Nuclear Information System (INIS)

    Chen, Yi; Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi; Jing, Qian; Yue, Jiaqi; Liu, Yang; Cheng, Zhong; Li, Jingyi; Song, Haixing; Li, Guoyu; Liu, Rui; Wang, Jinhui

    2016-01-01

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  7. FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yi [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Xie, Xiaoyan; Li, Xinyi; Wang, Peiqi [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Jing, Qian; Yue, Jiaqi; Liu, Yang [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Cheng, Zhong [Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu (China); Li, Jingyi, E-mail: li--jingyi@hotmail.com [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Song, Haixing [The School of Biomedical Sciences, Chengdu Medical College, Chengdu 610083 (China); Li, Guoyu, E-mail: liguoyulisa@163.com [School of Pharmacy, Shihezi University, Shihezi 832003 (China); Liu, Rui, E-mail: liurui_scu@hotmail.com [State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University (China); Wang, Jinhui [School of Pharmacy, Shihezi University, Shihezi 832003 (China)

    2016-05-20

    Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.

  8. Extract of corn silk (stigma of Zea mays) inhibits the tumour necrosis factor-alpha- and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1 expression.

    Science.gov (United States)

    Habtemariam, S

    1998-05-01

    Treatment of human endothelial cells with cytokines such as tumour necrosis factor-alpha (TNF) or E. coli lipopolysaccharide (LPS) induces the expression of several adhesion molecules and enhances leukocyte adhesion to endothelial cell surface. Interfering with this leukocyte adhesion or adhesion molecules upregulation is an important therapeutic target for the treatment of bacterial sepsis and various inflammatory diseases. In the course of screening marketed European anti-inflammatory herbal drugs for TNF antagonistic activity, a crude ethanolic extract of corn silk (stigma of Zea mays) exhibited significant activity. The extract at concentrations of 9-250 micrograms/ml effectively inhibited the TNF- and LPS-induced adhesiveness of EAhy 926 endothelial cells to monocytic U937 cells. Similar concentration ranges of corn silk extract did also block the TNF and LPS but not the phorbol 12-myristate 13-acetate-induced ICAM-1 expression on EAhy 926 endothelial cell surface. The extract did not alter the production of TNF by LPS-activated macrophages and failed to inhibit the cytotoxic activity of TNF. It is concluded that corn silk possesses important therapeutic potential for TNF- and LPS-mediated leukocyte adhesion and trafficking.

  9. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  10. Novel Abscisic Acid Antagonists Identified with Chemical Array Screening.

    Science.gov (United States)

    Ito, Takuya; Kondoh, Yasumitsu; Yoshida, Kazuko; Umezawa, Taishi; Shimizu, Takeshi; Shinozaki, Kazuo; Osada, Hiroyuki

    2015-11-01

    Abscisic acid (ABA) signaling is involved in multiple processes in plants, such as water stress control and seed dormancy. Major regulators of ABA signaling are the PYR/PYL/RCAR family receptor proteins, group A protein phosphatases 2C (PP2Cs), and subclass III of SNF1-related protein kinase 2 (SnRK2). Novel ABA agonists and antagonists to modulate the functions of these proteins would not only contribute to clarification of the signaling mechanisms but might also be used to improve crop yields. To obtain small molecules that interact with Arabidopsis ABA receptor PYR1, we screened 24 275 compounds from a chemical library at the RIKEN Natural Products Depository by using a chemical array platform. Subsequent SnRK2 and PP2C assays narrowed down the candidates to two molecules. One antagonized ABA in a competitive manner and inhibited the formation of the PYR1-ABA-PP2C ternary complex. These compounds might have potential as bioprobes to analyze ABA signaling. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Streptomycetes and micromycetes as perspective antagonists of fungal phytopathogens.

    Science.gov (United States)

    Postolaky, O; Syrbu, T; Poiras, N; Baltsat, K; Maslobrod, S; Boortseva, S

    2012-01-01

    Among natural factors that permanently influence on the plants, the soil microorganisms play a special role for the growing of plants as habitants of their rhizosphere. Mainly they are the representatives of actinomycetes genus Streptomyces and fungal genus Penicillium and their metabolic products stimulate plant growth and inhibit the growth of pathogenic fungi and bacteria. The aim of our study was to determine the antagonism of actinomycetes and micromycetes isolated from soils of R. Moldova against the fungal pathogens of agricultural plants. The strains were isolated from 5 types of chernozem (black soil) from central zone of R. Moldova, with different concentration of humus. Most of micromycetes and streptomycetes were isolated from soil sample 1 (monoculture of maize) and soil sample 2 (Poltava road border) with similar humus content (2.4-2.6%). The antifungal activity of micromycetes strains was occurring mostly against Fusarium solani and Thelaviopsis basicola, at streptomycetes against Alternaria alternata and Botrytis cinerea. It was revealed the strains completely inhibit the growth of Alt. alternata (streptomycetes strains 23, 33, 37), B. cinerea (Streptomyces sp. 17), and F. solani (Penicillium sp. 104). Our results allow to consider the actinomycetes Streptomyces sp.9, Streptomyces sp. 12, Streptomyces sp. 17, Streptomyces sp. 37 Streptomyces sp. 66 and micromycetes Penicillium sp. 5, Penicillium sp. 65, Penicillium sp. 104 isolated from soils of R. Moldova, as prospective strains-antagonists against the phytopathogenic fungus, the causative agents of agricultural plants deseasis.

  12. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua

    2013-12-01

    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  13. Blood flow distribution with adrenergic and histaminergic antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Baker, C.H.; Davis, D.L.; Sutton, E.T.

    1989-03-01

    Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects.

  14. Blood flow distribution with adrenergic and histaminergic antagonists

    International Nuclear Information System (INIS)

    Baker, C.H.; Davis, D.L.; Sutton, E.T.

    1989-01-01

    Superficial fibular nerve stimulation (SFNS) causes increased pre- and post-capillary resistances as well as increased capillary permeability in the dog hind paw. These responses indicate possible adrenergic and histaminergic interactions. The distribution of blood flow between capillaries and arteriovenous anastomoses (AVA) may depend on the relative effects of these neural inputs. Right hind paws of anesthetized heparinized dogs were vascularly and neurally isolated and perfused with controlled pressure. Blood flow distribution was calculated from the venous recovery of 85Sr-labeled microspheres (15 microns). The mean transit times of 131I-albumin and 85Sr-labeled microspheres were calculated. The effects of adrenergic and histaminergic antagonists with and without SFNS were determined. Phentolamine blocked the entire response to SFNS. Prazosin attenuated increases in total and AVA resistance. Yohimbine prevented increased total resistance, attenuated the AVA resistance increase, and revealed a decrease in capillary circuit resistance. Pyrilamine attenuated total resistance increase while SFNS increased capillary and AVA resistances. Metiamide had no effect on blood flow distribution with SFNS. The increase in AVA resistance with SFNS apparently resulted from a combination of alpha 1 and alpha 2 receptor stimulation but not histaminergic effects

  15. Iontophoresis of endothelin receptor antagonists in rats and men.

    Directory of Open Access Journals (Sweden)

    Matthieu Roustit

    Full Text Available The treatment of scleroderma-related digital ulcers is challenging. The oral endothelin receptor antagonist (ERA bosentan has been approved but it may induce liver toxicity. The objective of this study was to test whether ERAs bosentan and sitaxentan could be locally delivered using iontophoresis.Cathodal and anodal iontophoresis of bosentan and sitaxentan were performed on anaesthetized rat hindquarters without and during endothelin-1 infusion. Skin blood flow was quantified using laser-Doppler imaging and cutaneous tolerability was assessed. Iontophoresis of sitaxentan (20 min, 20 or 100 µA was subsequently performed on the forearm skin of healthy men (n = 5.In rats neither bosentan nor sitaxentan increased skin blood flux compared to NaCl. When simultaneously infusing endothelin-1, cathodal iontophoresis of sitaxentan increased skin blood flux compared to NaCl (AUC(0-20 were 44032.2 ± 12277 and 14957.5 ± 23818.8 %BL.s, respectively; P = 0.01. In humans, sitaxentan did not significantly increase skin blood flux as compared to NaCl. Iontophoresis of ERAs was well tolerated both in animals and humans.This study shows that cathodal iontophoresis of sitaxentan but not bosentan partially reverses endothelin-induced skin vasoconstriction in rats, suggesting that sitaxentan diffuses into the dermis. However, sitaxentan does not influence basal skin microvascular tone in rats or in humans.

  16. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton

    Science.gov (United States)

    Kinnaird, Catherine R.; Ferris, Daniel P.

    2013-01-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to “fight” the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

  17. Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

    International Nuclear Information System (INIS)

    Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

    1987-01-01

    In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

  18. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Science.gov (United States)

    Meuwese, Julia D I; van Loon, Anouk M; Scholte, H Steven; Lirk, Philipp B; Vulink, Nienke C C; Hollmann, Markus W; Lamme, Victor A F

    2013-01-01

    Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  19. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Directory of Open Access Journals (Sweden)

    Julia D I Meuwese

    Full Text Available Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  20. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

    Science.gov (United States)

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

    2013-04-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.