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Sample records for necrosis factor-a antagonists

  1. Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: An expert consensus report

    NARCIS (Netherlands)

    Feagan, Brian G.; Lémann, Marc; Befrits, Ragnar; Connell, William; D'Haens, Geert; Ghosh, Subrata; Michetti, Pierre; Ochsenkühn, Thomas; Panaccione, Remo; Schreiber, Stefan; Silverberg, Mark; Sorrentino, Dario; van der Woude, C. Janneke; Vermeire, Severine; Rutgeerts, Paul

    2012-01-01

    Background: Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD.

  2. 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

    Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased...... 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...

  3. 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

    Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased...... 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...... and an interferon-¿ 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 as it significantly...

  4. Demyelinizing Neurological Disease after Treatment with Tumor Necrosis Factor-α Antagonists

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    Claudia Bruè

    2016-07-01

    Full Text Available Purpose: Demyelinizing neurological disease is a rare complication after treatment with tumor necrosis factor (TNFα antagonists. We report on a case of multiple sclerosis after TNFα antagonist treatment and discuss its differential diagnosis. Methods: This is an observational case study. Results: A 48-year-old male was referred to Ophthalmology in January 2015 for an absolute scotoma in the superior quadrant of the visual field in his right eye. Visual acuity was 20/50 in the right eye and 20/20 in the left. Fundus examination was unremarkable bilaterally. Spectral domain optical coherence tomography revealed a normal macular retina structure. Visual field examination revealed a superior hemianopsia in the right eye. Head magnetic resonance imaging showed findings compatible with optic neuritis. The visual evoked potentials confirmed the presence of optic neuritis. The patient had been under therapy with adalimumab since January 2014, for Crohn’s disease. Suspension of adalimumab was recommended, and it was substituted with tapered deltacortene, from 1 mg/kg/day. After 1 month, the scotoma was resolved completely. Conclusions: TNFα antagonists can provide benefit to patients with inflammatory autoimmune diseases. However, they can also be associated with severe adverse effects. Therefore, adequate attention should be paid to neurological abnormalities in patients treated with TNFα antagonists.

  5. 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)

  6. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed

    NARCIS (Netherlands)

    Sands, Bruce E.; Feagan, Brian G.; Rutgeerts, Paul; Colombel, Jean-Frédéric; Sandborn, William J.; Sy, Richmond; D'Haens, Geert; Ben-Horin, Shomron; Xu, Jing; Rosario, Maria; Fox, Irving; Parikh, Asit; Milch, Catherine; Hanauer, Stephen

    2014-01-01

    There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody

  7. 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.

  8. The distribution of congenital anomalies within the VACTERL association among tumor necrosis factor antagonist-exposed pregnancies is similar to the general population

    DEFF Research Database (Denmark)

    Crijns, Hubertina J M J; Jentink, Janneke; Garne, Ester

    2011-01-01

    To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population.......To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-α (TNF-α) antagonist and the general population....

  9. 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....

  10. 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.

  11. Comparison of the Intravenous and Epidural Administration of Tumor Necrosis Factor-alpha Antagonists in an Experimental Rat Pain Model

    Science.gov (United States)

    Beyaz, Serbülent Gökhan; İnanmaz, Mustafa Erkan; Ergönenç, Tolga; Palabıyık, Onur; Tomak, Yakup; Tuna, Ayça Taş

    2017-01-01

    Introduction: Inflammatory cytokines secreted from the nucleus pulposus are thought to lead to lumbar nerve root compression-like symptoms. Tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine, likely plays an important role in lumbar disc hernia-related leg pain. In this experimental study, we compared the effectiveness of TNF-α antagonists administered through the intravenous or epidural route in lumbar spine pathologies. Materials and Methods: After ethics committee approval had been obtained, 24 Sprague Dawley male rats aged 70–90 days and weighing 250–300 g each were allocated to four groups. In Group I, only the surgical procedure was performed; in Group II, 1 ml of saline solution was administered into the epidural field; in Group III, 10 mg/kg of infliximab was administered into the coccygeal vein; and in Group IV (epidural group), 25 mg of etanercept was administered into the epidural region. Results: When the left leg pull values were analyzed on day 14, whereas there was not a significant difference among the three groups, a decreasing difference was observed in Group IV (P discopathy, TNF-α antagonists administered epidurally led to earlier recovery from radiculopathy-related allodynia compared to intravenous administration. PMID:29284846

  12. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database.

    Science.gov (United States)

    Carter, John D; Ladhani, Anil; Ricca, Louis R; Valeriano, Joanne; Vasey, Frank B

    2009-03-01

    To present any congenital anomalies with respect to tumor necrosis factor (TNF) antagonists reported to the US Food and Drug Administration (FDA) to determine if there are common findings. A review of the FDA database of reported adverse events with etanercept, infliximab, and adalimumab from 1999 through December of 2005 was performed. Key words for congenital anomalies were employed as search tools. Duplicate reports were eliminated. Any concomitant medicines were recorded. Our review of > 120,000 adverse events revealed a total of 61 congenital anomalies in 41 children born to mothers taking a TNF antagonist. Of these mothers, 22 took etanercept and 19 took infliximab. There were no reports in women taking adalimumab. The most common reported congenital anomaly was some form of heart defect. Twenty-four of the 41 (59%) children had one or more congenital anomalies that are part of vertebral abnormalities, anal atresia, cardiac defect, tracheoesophageal, renal, and limp abnormalities (VACTERL) association. There were 34 specific types of congenital anomalies in total, and 19 (56%) of those are part of the VACTERL spectrum. Nine of these 19 (47%) types of VACTERL anomalies were observed statistically significantly more than historical controls (p < 0.01); in 4 of these 9 the p value was < or = 0.0001. Thirteen (32%) of the children had more than one congenital anomaly; 7 of these 13 children had 2 defects that are part of the VACTERL spectrum. However, only 1 child was diagnosed with VACTERL. In 24/41 cases (59%) the mother was taking no other concomitant medications. A seemingly high number of congenital anomalies that are part of the VACTERL spectrum have been reported. These congenital anomalies are occurring at a rate higher than historical controls. This commonality raises concerns of a possible causative effect of the TNF antagonists.

  13. A trimeric structural fusion of an antagonistic tumor necrosis factor-α mutant enhances molecular stability and enables facile modification.

    Science.gov (United States)

    Inoue, Masaki; Ando, Daisuke; Kamada, Haruhiko; Taki, Shintaro; Niiyama, Mayumi; Mukai, Yohei; Tadokoro, Takashi; Maenaka, Katsumi; Nakayama, Taisuke; Kado, Yuji; Inoue, Tsuyoshi; Tsutsumi, Yasuo; Tsunoda, Shin-Ichi

    2017-04-21

    Tumor necrosis factor-α (TNF) exerts its biological effect through two types of receptors, p55 TNF receptor (TNFR1) and p75 TNF receptor (TNFR2). An inflammatory response is known to be induced mainly by TNFR1, whereas an anti-inflammatory reaction is thought to be mediated by TNFR2 in some autoimmune diseases. We have been investigating the use of an antagonistic TNF mutant (TNFR1-selective antagonistic TNF mutant (R1antTNF)) to reveal the pharmacological effect of TNFR1-selective inhibition as a new therapeutic modality. Here, we aimed to further improve and optimize the activity and behavior of this mutant protein both in vitro and in vivo Specifically, we examined a trimeric structural fusion of R1antTNF, formed via the introduction of short peptide linkers, as a strategy to enhance bioactivity and molecular stability. By comparative analysis with R1antTNF, the trimeric fusion, referred to as single-chain R1antTNF (scR1antTNF), was found to retain in vitro molecular properties of receptor selectivity and antagonistic activity but displayed a marked increase in thermal stability. The residence time of scR1antTNF in vivo was also significantly prolonged. Furthermore, molecular modification using polyethylene glycol (PEG) was easily controlled by limiting the number of reactive sites. Taken together, our findings show that scR1antTNF displays enhanced molecular stability while maintaining biological activity compared with R1antTNF. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 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

  15. Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Martínez-Santana V

    2013-07-01

    Full Text Available Virginia Martínez-Santana,1 E González-Sarmiento,2 MA Calleja-Hernández,3 T Sánchez-Sánchez1 1Pharmacy Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; 2Internal Medicine Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; 3Pharmacy Department, Hospital Universitario Virgen de las Nieves de Granada, Granada, Spain Background: Persistence of anti-tumor necrosis factor (TNF therapy in rheumatoid arthritis (RA is an overall marker of treatment success. Objective: To assess the survival of anti-TNF treatment and to define the potential predictors of drug discontinuation in RA, in order to verify the adequacy of current practices. Design: An observational, descriptive, longitudinal, retrospective study. Setting: The Hospital Clínico Universitario de Valladolid, Valladolid, Spain. Patients: RA patients treated with anti-TNF therapy between January 2011 and January 2012. Measurements: Demographic information and therapy assessments were gathered from medical and pharmaceutical records. Data is expressed as means (standard deviations for quantitative variables and frequency distribution for qualitative variables. Kaplan–Meier survival analysis was used to assess persistence, and Cox multivariate regression models were used to assess potential predictors of treatment discontinuation. Results: In total, 126 treatment series with infliximab (n = 53, etanercept (n = 51 or adalimumab (n = 22 were administered to 91 patients. Infliximab has mostly been used as a first-line treatment, but it was the drug with the shortest time until a change of treatment. Significant predictors of drug survival were: age; the anti-TNF agent; and the previous response to an anti-TNF drug. Limitation: The small sample size. Conclusion: The overall efficacy of anti-TNF drugs diminishes with time, with infliximab having the shortest time until a change of treatment. The management of biologic therapy in patients with

  16. 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.

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

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    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

  18. Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis.

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    Kim, Ji-Hye; Kim, Ae Ri; Choi, Yun Hui; Jang, Sungil; Woo, Gye-Hyeong; Cha, Jeong-Heon; Bak, Eun-Jung; Yoo, Yun-Jung

    2017-01-01

    Type 1 diabetes with periodontitis shows elevated TNF-α expression. Tumor necrosis factor (TNF)-α stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL) and sclerostin. The objective of this study was to determine the effect of TNF-α expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis using infliximab (IFX), a TNF-α antagonist. Rats were divided into two timepoint groups: day 3 and day 20. Each timepoint group was then divided into four subgroups: 1) control (C, n = 6 for each time point); 2) periodontitis (P, n = 6 for each time point); 3) diabetes with periodontitis (DP, n = 8 for each time point); and 4) diabetes with periodontitis treated with IFX (DP+IFX, n = 8 for each time point). To induce type 1 diabetes, rats were injected with streptozotocin (50 mg/kg dissolved in 0.1 M citrate buffer). Periodontitis was then induced by ligature of the mandibular first molars at day 7 after STZ injection (day 0). IFX was administered once for the 3 day group (on day 0) and twice for the 20 day group (on days 7 and 14). The DP group showed greater alveolar bone loss than the P group on day 20 (P = 0.020). On day 3, higher osteoclast formation and RANKL-positive osteocytes in P group (P = 0.000 and P = 0.011, respectively) and DP group (P = 0.006 and P = 0.017, respectively) than those in C group were observed. However, there was no significant difference in osteoclast formation or RANKL-positive osteocytes between P and DP groups. The DP+IFX group exhibited lower alveolar bone loss (P = 0.041), osteoclast formation (P = 0.019), and RANKL-positive osteocytes (P = 0.009) than that of the DP group. On day 20, DP group showed a lower osteoid area (P = 0.001) and more sclerostin-positive osteocytes (P = 0.000) than P group. On days 3 and 20, the DP+IFX group showed more osteoid area (P = 0.048 and 0.040, respectively) but lower sclerostin-positive osteocytes (both P = 0.000) than DP group. Taken together

  19. Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis.

    Directory of Open Access Journals (Sweden)

    Ji-Hye Kim

    Full Text Available Type 1 diabetes with periodontitis shows elevated TNF-α expression. Tumor necrosis factor (TNF-α stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL and sclerostin. The objective of this study was to determine the effect of TNF-α expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis using infliximab (IFX, a TNF-α antagonist. Rats were divided into two timepoint groups: day 3 and day 20. Each timepoint group was then divided into four subgroups: 1 control (C, n = 6 for each time point; 2 periodontitis (P, n = 6 for each time point; 3 diabetes with periodontitis (DP, n = 8 for each time point; and 4 diabetes with periodontitis treated with IFX (DP+IFX, n = 8 for each time point. To induce type 1 diabetes, rats were injected with streptozotocin (50 mg/kg dissolved in 0.1 M citrate buffer. Periodontitis was then induced by ligature of the mandibular first molars at day 7 after STZ injection (day 0. IFX was administered once for the 3 day group (on day 0 and twice for the 20 day group (on days 7 and 14. The DP group showed greater alveolar bone loss than the P group on day 20 (P = 0.020. On day 3, higher osteoclast formation and RANKL-positive osteocytes in P group (P = 0.000 and P = 0.011, respectively and DP group (P = 0.006 and P = 0.017, respectively than those in C group were observed. However, there was no significant difference in osteoclast formation or RANKL-positive osteocytes between P and DP groups. The DP+IFX group exhibited lower alveolar bone loss (P = 0.041, osteoclast formation (P = 0.019, and RANKL-positive osteocytes (P = 0.009 than that of the DP group. On day 20, DP group showed a lower osteoid area (P = 0.001 and more sclerostin-positive osteocytes (P = 0.000 than P group. On days 3 and 20, the DP+IFX group showed more osteoid area (P = 0.048 and 0.040, respectively but lower sclerostin-positive osteocytes (both P = 0.000 than DP group. Taken together, these

  20. Tumor necrosis factor-α antagonist suppresses local inflammatory reaction and facilitates olfactory nerve recovery following injury.

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    Al Salihi, Mohammed Omar; Kobayashi, Masayoshi; Tamari, Kengo; Miyamura, Tomotaka; Takeuchi, Kazuhiko

    2017-02-01

    Olfactory dysfunction is a common finding in head trauma due to injury to the olfactory nerve. We previously reported that anti-inflammatory treatment with steroids improves recovery outcome in olfactory nerve injury models. Clinically, however, steroid administration is not recommended in the acute phase of head injury cases because of concerns regarding its side effects. Tumor necrosis factor (TNF-α) is known to play a key role in inflammatory response to injury. The present study examines if the inhibition of TNF-α can facilitate functional recovery in the olfactory system following injury. Olfactory nerve transection (NTx) was performed in olfactory marker protein (OMP-tau-lacZ) mice to establish injury models. We measured TNF-α gene expression in the olfactory bulb using semi-quantitative and real time polymerase chain reaction (PCR) assays and found that they increase within hours after NTx injury. A TNF-α antagonist (etanercept) was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5-70 days. X-gal staining labeled OMP in the degenerating and regenerating olfactory nerve fibers, and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Etanercept-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Olfactory function assessments using both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in etanercept-injected animals. These findings suggest that inhibition of TNF-α could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries. Copyright © 2016. Published by Elsevier B.V.

  1. 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...

  2. 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...

  3. Early tumor necrosis factor α antagonist therapy in everyday practice for inflammatory back pain suggesting axial spondyloarthritis: results from a prospective multicenter french cohort.

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    Canouï-Poitrine, Florence; Poulain, Cécile; Molto, Anna; Le Thuaut, Aurélie; Lafon, Cécile; Farrenq, Valérie; Ferkal, Salah; Le Corvoisier, Philippe; Ghaleh, Bijan; Bastuji-Garin, Sylvie; Fautrel, B; Dougados, Maxime; Claudepierre, Pascal

    2014-09-01

    To determine the frequency of and factors associated with early tumor necrosis factor α (TNFα) antagonist therapy in everyday clinical practice in patients with suspected axial spondyloarthropathy (SpA). We used data from the prospective observational study in the French Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; Outcome of Recent Undifferentiated Spondylarthropathies) cohort of 708 patients with recent-onset (50 (OR 1.88, 95% CI 1.24-2.87, P = 0.003), current or past disease-modifying antirheumatic drug use (OR 2.09, 95% CI 1.22-3.59, P = 0.008), systemic corticosteroid use (OR 2.48, 95% CI 1.43-4.34, P = 0.002), and mild to severe radiographic hip abnormalities (OR 9.43, 95% CI 2.11-42.09, P = 0.003). After adjustment on these factors, Achilles enthesis hypervascularization by power Doppler and number of work days missed were associated with TNFα antagonist therapy. In the DESIR cohort, approximately one-fourth of patients with recent IBP suggestive of axial SpA were under anti-TNFα therapy after 1 year of followup. All factors associated with this early initiation reflected higher disease activity, refractoriness, or severity, which suggests compliance of French rheumatologists with current treatment guidelines. Copyright © 2014 by the American College of Rheumatology.

  4. An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotalineinduced pulmonary hypertensive rats model

    Directory of Open Access Journals (Sweden)

    Jung Hyun kwon

    2013-03-01

    Full Text Available Purpose: Tumor necrosis factor (TNF-?#6185;s thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-?#6177;ntagonist treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C, single subcutaneous injection of normal saline (0.1 mL/kg; monocrotaline (M, single subcutaneous injection of monocrotaline (60 mg/kg; and monocrotaline + infliximab (M+I, single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg. The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-?#6188;endothelin-1 (ET-1 , endothelin receptor A (ERA , endothelial nitric oxide synthase (eNOS , matrix metalloproteinase (MMP 2, and tissue inhibitor of matrix metalloproteinase (TIMP . Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P&lt;0.05. The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P &lt; 0.05. Expression levels of TNF-?#6944;ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28. Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-?#6944;and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

  5. Canadian Association of Gastroenterology Clinical Practice Guidelines: The use of tumour necrosis factor-alpha antagonist therapy in Crohn’s disease

    Science.gov (United States)

    Sadowski, Daniel C; Bernstein, Charles N; Bitton, Alain; Croitoru, Ken; Fedorak, Richard N; Griffiths, Anne

    2009-01-01

    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. OBJECTIVE: To review and update Canadian guidelines regarding the use of tumour necrosis factor-alpha antibody therapy in both luminal and fistulizing Crohn’s disease. METHODS: A consensus group of 25 voting participants developed a series of recommendation statements that addressed pertinent clinical questions and gaps in existing knowledge. An iterative voting and feedback process was used in advance of the consensus meeting in conjunction with a systematic literature review to refine the voting statements. These statements were brought to a formal consensus meeting held in Montreal, Quebec (March 2008), wherein each statement underwent discussion, reformulation, voting and subsequent revision until group consensus was obtained (at least 80% agreement). OUTCOME: The 47 voting statements addressed three themes: induction therapy, maintenance therapy and safety issues. As a result of the iterative process, 23 statements achieved consensus and were submitted for publication. CONCLUSION: In the past five years, tumour necrosis factor-alpha antagonist therapy has become a cornerstone in the management of moderate-to-severe Crohn’s disease refractory to conventional treatment algorithms. The evidentiary base supporting the use of these drugs in Crohn’s disease is substantial and strengthened by results from long-term clinical and molecular studies. However, significant gaps in knowledge exist, particularly with regard to treatment failure. Confidence in the safety of these drugs is increasing, provided that therapy is administered in a clinical setting in which potential complications can be readily recognized and treated. PMID:19319383

  6. The effects of dexamethasone and chlorpromazine on tumour necrosis factor-alpha, interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-10 in human volunteers.

    Science.gov (United States)

    Bleeker, M W; Netea, M G; Kullberg, B J; Van der Ven-Jongekrijg, J; Van der Meer, J W

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are pro-inflammatory cytokines that play an important role in severe infections, whereas IL-1 receptor antagonist (IL-1ra) and IL-10 are anti-inflammatory cytokines that counteract their effects. Chlorpromazine and dexamethasone protect mice against lethal endotoxaemia by decreasing circulating concentrations of TNF-alpha and IL-1 beta. We investigated whether administration of chlorpromazine or dexamethasone to human volunteers is able to modulate the lipopolysaccharide (LPS)-stimulated cytokine production capacity in whole blood. Blood samples were taken before and several time-points after medication. Circulating cytokine concentrations were low in all samples. LPS-induced TNF-alpha and IL-1 beta production in whole blood was inhibited by dexamethasone treatment, while chlorpromazine had no effect. When peripheral blood mononuclear cells were stimulated in vitro with LPS, the addition of chlorpromazine (1-100 ng/ml) had no modulatory action on TNF-alpha, IL-1 beta, IL-1ra or IL-10 synthesis. The chlorpromazine concentrations measured in circulation of volunteers were eight to 40 times lower than the concentrations shown to be effective in mice. In conclusion, chlorpromazine inhibits TNF-alpha and IL-1 beta production in mice at concentrations that cannot be reached in humans, thus precluding its usage in clinical anti-cytokine strategies. In contrast, dexamethasone is an effective inhibitor of pro-inflammatory cytokine production. PMID:9378493

  7. Transcriptional Signatures Related to Glucose and Lipid Metabolism Predict Treatment Response to the Tumor Necrosis Factor Antagonist Infliximab in Patients with Treatment-Resistant Depression

    Science.gov (United States)

    Mehta, Divya; Raison, Charles L.; Woolwine, Bobbi J.; Haroon, Ebrahim; Binder, Elisabeth B.; Miller, Andrew H.; Felger, Jennifer C.

    2013-01-01

    The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6hr, 24hr, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2 fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6hr and 24hr after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. PMID:23624296

  8. 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

    living in an area without the disease. The production of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 was investigated in culture supernatants, and the cellular sources of IFN-gamma and TNF-alpha were identified. Cells from individuals with a history of cutaneous...... 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...

  9. 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.

  10. Alopecia induced by tumour necrosis factor-alpha antagonists: description of 52 cases and disproportionality analysis in a nationwide pharmacovigilance database.

    Science.gov (United States)

    Béné, Johana; Moulis, Guillaume; Auffret, Marine; Lefevre, Guillaume; Coquerelle, Pascal; Coupe, Patrick; Péré, Patrice; Gautier, Sophie

    2014-08-01

    The aim of this research was to describe the cases of TNF-α antagonist-related alopecia reported in the French Pharmacovigilance Database (FPVD) and to investigate the association between exposure to TNF-α antagonists and occurrence of alopecia. All spontaneous reports of TNF-α antagonist-related alopecia recorded in the FPVD between January 2000 and April 2012 were colligated and described. We conducted disproportionality analyses (case/non-case method) to assess the link between the occurrence of alopecia and exposure to TNF-α antagonists. Cases were all reports of alopecia and non-cases were all other reports recorded during the study period. Exposure to TNF-α antagonists was sought in cases and in non-cases. Reporting odds ratios (RORs) were calculated to assess the association. Docetaxel was used as positive control and acetaminophen as negative control. We performed sensitivity analyses excluding cases of androgenic alopecia and those occurring in psoriatic patients. Among 282 590 spontaneous reports of adverse drug reactions (ADRs) collated in the FPVD, 1068 cases (alopecia reports) were identified. Of these cases, 52 (4.9%) occurred during exposure to TNF-α antagonists (18 involved infliximab, 17 adalimumab, 15 etanercept and 2 certolizumab). Exposure to TNF-α antagonists was more frequent among alopecia reports than among other ADR reports for all TNF-α antagonists pooled (ROR 3.0, 95% CI 2.3, 4.0) as well as for each antagonist separately, with similar values. Sensitivity analyses yielded similar results. The RORs were 29.9 (95% CI 25.3, 35.5) with docetaxel and 0.3 (95% CI 0.2, 0.4) with acetaminophen. The present study confirms a strong link between TNF-α antagonist exposure (class effect) and the occurrence of alopecia. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Estimation of Plasma Levels of Tumor Necrosis Factor-a, Interleukin-4 and 6 in Patients with Chronic Periodontitis and Type II Diabetes Mellitus.

    Science.gov (United States)

    Bakshi, Dipanshu; Kaur, Guneet; Singh, Deepinder; Sahota, Jasjit; Thakur, Ambika; Grover, Shekhar

    2018-02-01

    Both periodontitis and type II diabetes mellitus (T2DM) are common diseases with a multifactorial etiology and have influence of cytokines in their pathogenesis and thus may also influence each other. In recent times, more attention has been given to understanding the influences of these inflammatory cytokines which are a main part of oral chronic inflammation on systemic health of the individuals. Therefore, the aim of this study was to evaluate the plasma cytokine levels, specifically tumor necrosis factor-a (TNF-a), interleukin (IL)-6, and IL-4, in chronic periodontitis patients and T2DM patients, so as to investigate the influence of chronic periodontitis in systemic inflammation associated with diabetes mellitus. The present study comprised a total sample size of 60 patients. A detailed history along with complete periodontal examination were done for each person. These patients were subdivided into four study groups with 15 subjects (n = 15) in each group: group I: healthy individuals, group II: chronic periodontitis, group III: diabetes mellitus without chronic periodontitis, and group IV: diabetes mellitus with chronic periodontitis. Venous blood was withdrawn for obtaining serum samples from the subjects. Hemoglobin A1c (HbAlc) levels were measured from the automated chromatography. Using enzyme-linked immunosorbent assay kit, TNF-a, IL-4, and IL-6 were measured. It was observed that the difference between almost all the results showed statistical significance. Not much of a difference was seen when TNF-a and IL-6 findings of group II were compared with group III. Furthermore, IL-4 also did not differ when group II was compared with group IV. The inflammatory cytokines together control the inflammation process and a balance is maintained. However, in patients with diabetes mellitus, this balance is interrupted, which affects the final development and progression of the disease. Thus, hyperglycemia may be partly associated with the severity of the

  17. Tumour necrosis factor-alpha antagonists in the management of rheumatoid arthritis in the elderly: a review of their efficacy and safety.

    Science.gov (United States)

    Radovits, Beáta J; Kievit, Wietske; Laan, Roland F J M

    2009-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that frequently affects people aged >or=65 years, causing significant impairment with pain and functional disability. Elderly RA patients have specific problems, including co-morbid diseases, numerous concomitant medications, greater number of damaged joints as a result of longer disease duration and often a more severe disease presentation in elderly-onset RA. These factors, together with an age-related decline in the immune defence mechanisms, make elderly patients more vulnerable. The new era of biologic medications has made intensive treatment of RA patients possible. Anti-tumour necrosis factor-alpha (anti-TNFalpha) agents can cause a dramatic improvement in disease activity and functional capacity, making complete remission of RA a possible target. TNFalpha has been shown to play an important role in both the healthy aging process and age-related diseases such as RA. Targeting this cytokine in elderly patients is therefore reasonable. However, it is not clear whether treatment effects can be reached to the same extent in both elderly and younger patients and whether anti-TNFalpha treatment specifically increases the risk of certain adverse events in elderly RA patients. This review discusses the currently available evidence relating to the efficacy and safety of anti-TNFalpha medication in RA patients aged >or=65 years treated in clinical trials and observational studies. Despite a slightly less robust effect in elderly patients, anti-TNFalpha treatment has a similar long-term efficacy in patients aged >or=65 years and patients aged relatively safe in the treatment of elderly RA patients, treatment with corticosteroids significantly elevated the risk of serious infections. Corticosteroids are frequently used in elderly patients, but the evidence suggests that preference should increasingly be given to anti-TNFalpha agents, for which the expected benefits will mostly outweigh the modestly increased

  18. Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

    Science.gov (United States)

    García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D

    2017-03-01

    Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.

  19. Tumor necrosis factor-alpha inhibition and VATER association: a causal relationship.

    Science.gov (United States)

    Carter, John D; Valeriano, Joanne; Vasey, Frank B

    2006-05-01

    Inflammatory conditions that may require the use of a tumor necrosis factor-a (TNF-a) antagonist often involve women of child-bearing age. TNF-a antagonists are presumed to be safe in pregnancy based on animal data. However, this has never been formally studied in prospective trials involving humans. We describe a patient with psoriasis and psoriatic arthritis who took etanercept 50 mg subcutaneously (SQ) twice weekly throughout her pregnancy. She gave birth to a child with VATER association. Animal and human data exist to suggest a possible causal relationship between the mother's use of etanercept and the child's development of VATER association. We propose that the TNF antagonists, specifically etanercept, be used with caution in pregnant women. Patient registries of women who take TNF-a antagonists during pregnancy also need to be followed to see if there is an increase in the birth defects that are part of VATER association.

  20. Tumor Necrosis Factor-a In Emergency Department Patients with Systemic Inflammation as a Predictor of Severity and Outcome of Sepsis

    Directory of Open Access Journals (Sweden)

    M. Surbatovic

    2008-01-01

    Full Text Available Aim of the study was to determine whether the TNF-a levels, proximal inflammatory mediator, in septic patients presenting to the emergency department (ED and admitted to the intensive care unit (ICU are associated with progression to severe sepsis, septic shock or death. Material and methods. A retrospective observational study was performed on a sample of one hundred adult subjects presenting to the ED with systemic inflammatory response syndrome of 2 etiologies: presumed (and later confirmed in the ICU and/or operating room severe acute pancreatitis or generalized peritonitis. Blood TNF-a samples measurements were taken shortly after ED admission. TNF-a was measured by commercial ELISA test in plasma. Results. Mean values of TNF-a on admission (day zero, in ED were 191,5-fold lower in group with septic shock compared to severe sepsis group and were 63-fold higher in survivors (p<0.01. The area under the curve (AUC for the TNF-a plots for severity of clinical status was 0.813 and for outcome 0.834. Patients with TNF-a levels lower than 7.95 pg/mL had a 3.2-fold higher probability of septic shock development than those with higher values, at the cutoff level sensitivity was 83,9% and specificity 72,5%. Patients with TNF-a levels higher than 10.5 pg/mL had a 4.8-fold higher probability to survive than those with lower values, at the cutoff level sensitivity was 83,0% and specificity 77,4%. Conclusion: Decreasing in TNF-a concentration leads to the septic shock development and fatal outcome. TNF-a is very good predictor of sepsis severity and outcome. Key words: sepsis, tumor necrosis factor-alpha, emergency medical services, survival rate, severity of illness index.

  1. Role of tumour necrosis factor-a in the regulation of T-type calcium channel current in HL-1 cells.

    Science.gov (United States)

    Rao, Fang; Xue, Yu-Mei; Wei, Wei; Yang, Hui; Liu, Fang-Zhou; Chen, Shao-Xian; Kuang, Su-Juan; Zhu, Jie-Ning; Wu, Shu-Lin; Deng, Chun-Yu

    2016-07-01

    Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation (AF). Although tumour necrosis factor (TNF)-α levels are increased in patients with AF, the role of TNF-α in the pathogenesis of AF remains unclear. Besides L-type Ca(2+) currents (IC a,L ), T-type Ca(2+) currents (IC a,T ) also plays an important role in the pathogenesis of AF. This study was designed to use the whole-cell voltage-clamp technique and biochemical assays to explore if TNF-α is involved in the pathogenesis of AF through regulating IC a,T in atrial myocytes. It was found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased, while TNF-α expression levels were increased, in human atrial tissue from patients with AF. In murine atrial myocyte HL-1 cells, after culturing for 24 h, 12.5, 25 and 50 ng/mL TNF-α significantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner. The peak current was reduced by the application of 12.5 or 25 ng/mL TNF-α in a concentration-dependent manner (from -15.08 ± 1.11 pA/pF in controls to -11.89 ± 0.83 pA/pF and -8.54 ± 1.55 pA/pF in 12.5 or 25 ng/mL TNF-α group respectively). TNF-α application also inhibited voltage-dependent inactivation of IC a,T, shifted the inactivation curve to the left. These results suggest that TNF-α is involved in the pathogenesis of AF, probably via decreasing IC a,T current density in atrium-derived myocytes through impaired channel function and down-regulation of channel protein expression. This pathway thus represents a potential pathogenic mechanism in AF. © 2016 John Wiley & Sons Australia, Ltd.

  2. Impact on total population health and societal cost, and the implication on the actual cost-effectiveness of including tumour necrosis factor-α antagonists in management of ankylosing spondylitis: a dynamic population modelling study.

    Science.gov (United States)

    Tran-Duy, An; Boonen, Annelies; van de Laar, Mart A F J; Severens, Johan L

    2015-01-01

    Sequential treatment of ankylosing spondylitis (AS) that includes tumour necrosis factor-α antagonists (anti-TNF agents) has been applied in most of the Western countries. Existing cost-effectiveness (CE) models almost exclusively presented the incremental CE of anti-TNF agents using a closed cohort while budget impact studies are mainly lacking. Notwithstanding, information on impact on total population health and societal budget as well as on actual incremental CE for a given decision time span are important for decision makers. This study aimed at quantifying, for different decision time spans starting from January 1, 2014 in the Dutch society, (1) impact of sequential drug treatment strategies without and with inclusion of anti-TNF agents (Strategies 1 and 2, respectively) on total population health and societal cost, and (2) the actual incremental CE of Strategy 2 compared to Strategy 1. Dynamic population modelling was used to capture total population health and cost, and the actual incremental CE. Distinguishing the prevalent AS population on January 1, 2014 and the incident AS cohorts in the subsequent 20 years, the model tracked individually an actual number of AS patients until death or end of the simulation time. During the simulation, data on patient characteristics, history of drug use, costs and health at discrete time points were generated. In Strategy 1, five nonsteroidal anti-inflammatory drugs (NSAIDs) were available but anti-TNF agents withdrawn. In Strategy 2, five NSAIDs and two anti-TNF agents continued to be available. The predicted size of the prevalent AS population in the Dutch society varied within the range of 67,145-69,957 with 44-46 % of the patients receiving anti-TNF agents over the period 2014-2034. The use of anti-TNF agents resulted in an increase in the annual drug costs (168.54-205.28 million Euros), but at the same time caused a decrease in the annual productivity costs (12.58-31.21 million Euros) and in annual costs of

  3. 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

  4. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P

    1994-01-01

    chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S......)-baclofen and the antagonist (-)-(R)-phaclofen suggests that these ligands interact with the GABAB receptor sites in a similar manner. Thus, it may be concluded that the different pharmacological effects of these compounds essentially result from the different spatial and proteolytic properties of their acid groups....

  5. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor a inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Sørensen, Inge Juul; Lambert, Robert G. W.

    2011-01-01

    metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy.......To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix...

  6. 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

  7. 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 f...

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.)

  14. 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)

  15. [A case report of progressive penile necrosis].

    Science.gov (United States)

    Haba, Tomomi; Koike, Hiroshi

    2014-05-01

    The penis is provided with blood by multiple arteries. Penile necrosis is uncommon. Penile necrosis sporadically occurs in patients with progressive diabetes mellitus and/or end stage renal failure. Penile necrosis is often considered a poor prognostic feature. We present a case of penile necrosis in a patient with mild diabetes mellitus.

  16. 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 ...

  17. 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

  18. Targeting of regulated necrosis in kidney disease.

    Science.gov (United States)

    Martin-Sanchez, Diego; Poveda, Jonay; Fontecha-Barriuso, Miguel; Ruiz-Andres, Olga; Sanchez-Niño, María Dolores; Ruiz-Ortega, Marta; Ortiz, Alberto; Sanz, Ana Belén

    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. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  19. 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.)

  20. 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

  1. Studies on antagonistic marine streptomycetes

    Digital Repository Service at National Institute of Oceanography (India)

    Chandramohan, D.; Nair, S.

    Sixty nine strains of Streptomyces sp. isolated from the sediments of Andaman and Nicobar islands (Bay of Bengal) were screened for their antagonistic property against a number of test cultures (Vibrio sp., Klebsiella sp., Escherichia coli, Shigella...

  2. Sex differences in response to anti-tumor necrosis factor therapy in early and established rheumatoid arthritis -- results from the DANBIO registry

    DEFF Research Database (Denmark)

    Jawaheer, Damini; Olsen, Jørn; Hetland, Merete Lund

    2012-01-01

    To investigate sex differences in response to anti-tumor necrosis factor-a (TNF-a) therapy over time in early versus established rheumatoid arthritis (RA).......To investigate sex differences in response to anti-tumor necrosis factor-a (TNF-a) therapy over time in early versus established rheumatoid arthritis (RA)....

  3. 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

  4. 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

  5. [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.

  6. 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.

  7. 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...

  8. ANTAGONISTIC POTENTIAL OF FLUORESCENT Pseudomonas ...

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    This study focused on the antagonistic potential of fluorescent Pseudomonas in vitro, and its inoculation effect on growth performance of Lycopersicon esculentum in Fusarium oxysporum and Rhizoctonia solani infested soil. Biochemical characteristics of fluorescent Pseudomonas showed that all ten isolates were positive ...

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. [Profile of use of anti tumor necrosis factor in Colombian patients].

    Science.gov (United States)

    Machado, Jorge; Moncada, Juan Carlos; Pineda, Ricardo

    2011-06-01

    Tumor necrosis factor-alpha antagonists (anti-TNFα) have shown an increasing consumption and generate a significant economic burden on health systems. The prescribing patterns of tumor necrosis factor-alpha antagonists were determined in a patient population associated with the Sistema General de Seguridad Social en Salud in Colombia. A descriptive observational study was conducted in 316 patients with respect to use of tumor necrosis factor-alpha antagonists during a treatment period from January 2008 to June 2009. The database examined contained indications of use, inclusion criteria to medication, duration of illness, co-morbidities and adverse reactions. The data were retrieved from the clinical histories. Student's t test was used for the comparison of quantitative variables, and the chi-square test was used to establish associations between categorical variables and multivariate analysis were used. Mean age was 44.613.9 years; 63.9% of participants were female. Of the 316 patients, 17.1% received monotherapy. The order of prescription drugs was as follows: adalimumab (37.3%), infliximab (37.3%) and etanercept (25.4%), all were prescribed in appropriately defined daily doses. Co-medication drugs most frequently prescribed were: disease-modifying anti-rheumatic (82.9%), NSAIDs (29.1%), omeprazole (22.5%), antihypertensives (21.2%), folic acid (19.9%) calcium plus vitamin D (9.8%), calcitriol (6.0%). 10.4% of patients had a record of some adverse drug reaction. The average cost of therapy per patient per year was US$23,464. Anti-TNFα are being used at recommended doses, particularly in rheumatoid arthritis and in combination with other anti-rheumatic drugs. The direct cost of therapy was high for the country's health system.

  15. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    Directory of Open Access Journals (Sweden)

    D. Lévigne

    2013-01-01

    Full Text Available Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.. In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.

  16. 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

  17. Extrapancreatic necrosis without pancreatic parenchymal necrosis: a separate entity in necrotising pancreatitis?

    NARCIS (Netherlands)

    Bakker, Olaf J.; van Santvoort, Hjalmar; Besselink, Marc G. H.; Boermeester, Marja A.; van Eijck, Casper; Dejong, Kees; van Goor, Harry; Hofker, Sijbrand; Ahmed Ali, Usama; Gooszen, Hein G.; Bollen, Thomas L.

    2013-01-01

    In the revised Atlanta classification of acute pancreatitis, the term necrotising pancreatitis also refers to patients with only extrapancreatic fat necrosis without pancreatic parenchymal necrosis (EXPN), as determined on contrast-enhanced CT (CECT). Patients with EXPN are thought to have a better

  18. Smac mimetics as IAP antagonists.

    Science.gov (United States)

    Fulda, Simone

    2015-03-01

    As the Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in human cancers, they represent promising targets for therapeutic intervention. Small-molecule inhibitors of IAP proteins mimicking the endogenous IAP antagonist Smac, called Smac mimetics, neutralize IAP proteins and thereby promote the induction of cell death. Smac mimetics have been shown in preclinical models of human cancer to directly trigger cancer cell death or to sensitize for cancer cell death induced by a variety of cytotoxic stimuli. Smac mimetics are currently undergoing clinical evaluation in phase I/II trials, demonstrating that therapeutic targeting of IAP proteins has reached the clinical stage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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.)

  1. Synthetic peptide antagonists of glucagon

    International Nuclear Information System (INIS)

    Unson, C.G.; Andreu, D.; Gurzenda, E.M.; Merrifield, R.B.

    1987-01-01

    Several glucagon analogs were synthesized in an effort to find derivatives that would bind with high affinity to the glucagon receptor of rat liver membranes but would not activate membrane-bound adenylate cyclase and, therefore, would serve as antagonists of the hormone. Measurements on a series of glucagon/secretin hybrids indicated that replacement of Asp 9 in glucagon by Glu 9 , found in secretin, was the important sequence difference in the N terminus of the two hormones. Further deletion of His 1 and introduction of a C-terminal amide resulted in des-His 1 -[Glu 9 ]glucagon amide, which had a 40% binding affinity relative to that of native glucagon but caused no detectable adenylate cyclase activation in the rat liver membrane. This antagonist completely inhibited the effect of a concentration of glucagon that alone gave a full agonist response. It had an inhibition index of 12. The pA 2 was 7.2. An attempt was made to relate conformation with receptor binding. The peptides were synthesized by solid-phase methods and purified to homogeneity by reverse-phase high-performance liquid chromatography on C 18 -silica columns

  2. 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.)

  3. Avascular necrosis ofbone following renal transplantation

    African Journals Online (AJOL)

    include a direct toxic effect on bone, alcohol-induced calcium diuresis, poor nutritional status, hypogonadism and reduced physical'activity. Pre-existing or persistent hyperparathyroidism after transplantation is regarded by some authors7 as playing an important role in the pathogenesis of avascular necrosis. It is speculated ...

  4. [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.

  5. 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.)

  6. Peripancreatic fat necrosis mimicking pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thurnher, M.M.; Schima, W.; Turetschek, K.; Thurnher, S.A. [Vienna Univ. (Austria). Inst. fuer Radiologie; Fuegger, R. [Dept. of Surgery, University of Vienna (Austria); Oberhuber, G. [Dept. of Pathology, University of Vienna (Austria)

    2001-06-01

    A case of peripancreatic fat necrosis, after an episode of acute pancreatitis, which mimicked pancreatic cancer with lymph node metastases, is presented. We describe the imaging findings with helical CT scanning and with unenhanced and mangafodipir-enhanced MR imaging, with special emphasis on the differential diagnoses. (orig.)

  7. New antagonist agents of neuropeptide y receptors

    Directory of Open Access Journals (Sweden)

    Ignacio Aldana

    2000-12-01

    Full Text Available In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists will be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.

  8. S179D prolactin: antagonistic agony!

    Science.gov (United States)

    Walker, Ameae M

    2007-09-30

    The aims of this review are three-fold: first, to collate what is known about the production and activities of phosphorylated prolactin (PRL), the latter largely, but not exclusively, as illustrated through the use of the molecular mimic, S179D PRL; second, to apply this and related knowledge to produce an updated model of prolactin-receptor interactions that may apply to other members of this cytokine super-family; and third, to promote a shift in the current paradigm for the development of clinically important growth antagonists. This third aim explains the title since, based on results with S179D PRL, it is proposed that agents which signal to antagonistic ends may be better therapeutics than pure antagonists-hence antagonistic agony. Since S179D PRL is not a pure antagonist, we have proposed the term selective prolactin receptor modulator (SPeRM) for this and like molecules.

  9. [Extracorporeal life support in calcium antagonist intoxication].

    Science.gov (United States)

    Groot, M W; Grewal, S; Meeder, H J; van Thiel, R J; den Uil, C A

    2017-01-01

    Intoxication with calcium antagonists is associated with poor outcome. Even mild calcium antagonist overdose may be fatal. A 51-year-old woman and a 51-year-old man came to the Accident and Emergency Department in severe shock after they had taken a calcium antagonist overdose. After extensive medicinal therapy had failed, they both needed extracorporeal life support (ECLS) as a bridge to recovery. In severe calcium antagonist overdose, the combination of vasoplegia and cardiac failure leads to refractory shock. ECLS temporarily supports the circulation and maintains organ perfusion. In this way ECLS functions as a bridge to recovery and may possibly save lives. Timely consultation with and referral to an ECLS centre is recommended in patients with calcium antagonist overdose.

  10. 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.

  11. [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.

  12. 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, ...

  13. 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.

  14. Uterine Necrosis Associated with Fusobacterium necrophorum Infection

    Directory of Open Access Journals (Sweden)

    T. Widelock

    2015-01-01

    Full Text Available Fusobacterium necrophorum is infrequently implicated as a pathogenic organism. When pathogenic, the typical clinical presentation is that of pharyngitis, cervical adenopathy, and unilateral thrombophlebitis of the internal jugular vein. Infections caused by Fusobacterium necrophorum within the fields of obstetrics and gynecology have been infrequently reported. We describe a 19-year-old woman who underwent a cesarean delivery complicated by sepsis and purulent uterine necrosis secondary to Fusobacterium necrophorum infection.

  15. Opioid antagonists for alcohol dependence.

    Science.gov (United States)

    Rösner, Susanne; Hackl-Herrwerth, Andrea; Leucht, Stefan; Vecchi, Simona; Srisurapanont, Manit; Soyka, Michael

    2010-12-08

    Alcohol dependence belongs to the globally leading health risk factors. Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene. To determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2010 and inquired manufacturers and researchers for unpublished trials. All double-blind randomised controlled trials (RCTs) which compare the effects of naltrexone or nalmefene with placebo or active control on drinking-related outcomes. Two authors independently extracted outcome data. Trial quality was assessed by one author and cross-checked by a second author. Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD - 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD - 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD - 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication

  16. 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.

  17. 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.

  18. 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.

  19. PXR antagonists and implication in drug metabolism

    Science.gov (United States)

    Mani, Sridhar; Dou, Wei; Redinbo, Matthew R.

    2013-01-01

    Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno- and endobiotic metabolism. Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e.g., cholestasis, hypercholesterolemia, and inflammation). However, more recently, it is clear that PXR is also an important mediator of adverse xeno- (e.g., enhances acetaminophen toxicity) and endobiotic (e.g., hepatic steatosis) metabolic phenotypes. Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue-specific enhancement of the malignant phenotype. Thus, in these instances, there may be a role for PXR antagonists. However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described. The mode of action of these antagonists (e.g., sulforaphane) remains less clear. Our laboratory efforts have focused on this question. Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. In this review, we describe our published and unpublished findings on recent structure-function studies involving the azole chemical scaffold. Further work in the future is needed to fully define potent, more-selective PXR antagonists that may be useful in clinical application. PMID:23330542

  20. 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.)

  1. 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.

  2. 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 and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  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. Antagonist wear by polished zirconia crowns.

    Science.gov (United States)

    Hartkamp, Oliver; Lohbauer, Ulrich; Reich, Sven

    The aim of this in vivo study was to measure antagonist wear caused by polished monolithic posterior zirconia crowns over a 24-month period using the intraoral digital impression (IDI) technique. Thirteen zirconia crowns were placed in nine patients. The crowns and adjacent teeth were captured using an intraoral scanner (Lava C.O.S.). The corresponding antagonist teeth and the respective neighboring teeth were also scanned. Scanning was performed immediately after the restoration (baseline) as well as 12 and 24 months after crown placement. Geomagic Qualify software was used to superimpose the follow-up data sets onto the corresponding baseline data set, identify wear sites, and measure maximum vertical height loss in each individual wear site. Overall antagonist wear was then determined as the mean of wear rates measured in all of the individual antagonist units. In addition, wear rates in enamel and ceramic antagonists were analyzed as part of the scope of this study. The maximum mean wear with standard deviation (SD) in the overall sample with a total of nine patients, 13 antagonist units, and 98 evaluable wear sites was 86 ± 23 µm at 12 months, and 103 ± 39 µm at 24 months. The maximum mean wear in the enamel antagonist subgroup was 87 ± 41 µm at 12 months, and 115 ± 71 µm at 24 months; and in the ceramic antagonist subgroup 107 ± 22 µm at 12 months, and 120 ± 27 µm at 24 months. The wear rates determined in this study are comparable to those of existing studies. The IDI technique of wear analysis can be carried out in a practical manner and produces useful results.

  5. Activity and tissue-specific expression of lipases and tumor-necrosis factor alpha in lean and obese cats.

    NARCIS (Netherlands)

    Hoenig, M.; McGoldrick, J.B.; Beer, M. de; Demacker, P.N.M.; Ferguson, D.C.

    2006-01-01

    Post-heparin plasma activity of lipoprotein lipase (LPL) and hepatic lipase (HL), and fat and muscle activity of LPL were measured in neutered lean and obese cats. Lipoprotein lipase, hormone-sensitive lipase (HSL), and tumor necrosis factor a (TNF) mRNA were measured in muscle and fat tissue with

  6. 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.)

  7. 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

  8. 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.)

  9. Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    A. Rodriguez-Barbero

    1992-01-01

    Full Text Available To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-β-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.

  10. Concomitant disseminated histoplasmosis and disseminated tuberculosis after tumor necrosis factor inhibitor treatment: a case report.

    Science.gov (United States)

    Muñoz-Oca, Juan E; Villarreal Morales, Martha L; Nieves-Rodriguez, Aracelis; Martínez-Bonilla, Lemuel

    2017-01-13

    Tumor necrosis factor antagonist inhibitors have transformed the approach to patients with severe autoimmune conditions, such as rheumatoid arthritis. Although the therapy can be highly effective, TNF-α inhibitors are associated with an increased risk of opportunistic infections. Here, we report a case of concomitant disseminated histoplasmosis and tuberculosis in a 65-year-old female with rheumatoid arthritis treated with TNF-α inhibitor. Both conditions can be found in disseminated form in immunosuppressed hosts, but co-infection is rare with only a few cases having been reported, to our knowledge, all in HIV patients. This case posed a considerable challenge for diagnosis and treatment due to the unusual disseminated co-infection, the overlapping symptoms, and the interactions between medications.

  11. 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)

  12. 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)

  13. 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.

  14. Coronary dilation with nitrocompounds and calcium antagonists.

    Science.gov (United States)

    Jost, S; Rafflenbeul, W; Lichtlen, P R

    1990-01-01

    The vasodilatory effects of nitrocompounds and calcium antagonists on epicardial coronary arteries represent substantial antianginal mechanisms in the presence of coronary vasospasm or eccentric coronary stenoses. With high doses of nitrocompounds, angiographically normal coronary segments can be dilated by an average of approx. 30%, some coronary stenoses even by up to 100%, usually without severe reduction of blood pressure. With calcium antagonists, a similar extent of dilation of normal coronary arteries and eccentric stenoses can be obtained. Our own group demonstrated an average dilation of normal coronary arteries of about 20% after intravenous administration of dihydropyridine calcium antagonists; however, the average systolic blood pressure dropped below 100 mmHg after these compounds. Hence, although in isolated human coronary arteries high concentrations of calcium antagonists were shown to induce a considerably greater vasodilation than nitrocompounds, the early drop in blood pressure prohibits a higher dosage of calcium antagonists in vivo. In the presence of coronary artery disease, particularly when associated with coronary vasospasm, a combination of the two groups of compounds might be recommendable, since an addition of the effects of coronary vasomotor tone is likely. Furthermore, the antianginal effects of a reduction of preload and afterload are complementary.

  15. 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

  16. 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.)

  17. Laryngeal necrosis after combined chemotherapy and radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Miyaguchi, Mamoru; Kubo, Takeshi [Osaka Univ., Suita (Japan). School of Medicine; Takashima, Hitoshi [Kagawa Medical School (Japan)

    1997-08-01

    Post-radiation necrosis of the larynx is a major complication after irradiation and has become rare. Recently, combined chemotherapy and radiation therapy has been introduced for head and neck tumours. The authors report a case of laryngeal necrosis after combination therapy for a patient with cervical lymph node metastases of nasopharyngeal carcinoma and review the literature on late laryngeal necrosis. Although radiation-induced laryngeal necrosis has become a rare complication, the combination of chemotherapy and radiation therapy may increase its incidence. (author).

  18. 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)

  19. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter

    2011-01-01

    . In resistance arteries, the long-lasting contractile effects can only be partly and reversibly relaxed by low-molecular-weight ET(A) antagonists (ERAs). However, the neuropeptide calcitonin-gene-related peptide selectively terminates binding of ET1 to ET(A). We propose that ET1 binds polyvalently to ET......(A) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

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

    African Journals Online (AJOL)

    Background. A biofilm is defined as a collection of organisms attached to a surface and surrounded by a matrix. Objective. To present three cases in which bowel necrosis coexisted with biofilm. Methods. The medical records, bacteriological findings and tissue biopsies from three infants with bowel necrosis who ...

  1. Acute esophageal necrosis: a case report and review | Lahbabi ...

    African Journals Online (AJOL)

    Acute esophageal necrosis, commonly referred to as "black esophagus" or "acute necrotizing esophagitis", is a rare clinical disorder with an unclear etiology. The definition excludes patients with a history of recent caustic ingestion. Oesophageal necrosis can be diagnosed at endoscopy by the presence of black necroting ...

  2. Severe diaphragmatic necrosis in 4 horses with degenerative myopathy

    OpenAIRE

    Valentine, Beth A.; Hammock, Phillip D.; Lemiski, David; Hughes, Faith E.; Gerstner, Lonna; Bird, Karyn E.

    2002-01-01

    Severe diaphragmatic necrosis occurred in horses with degenerative myopathy due to polysaccharide storage myopathy (n = 2), nutritional myopathy (n = 1), and vasculitis (n = 1). Blood gas analysis performed in 1 horse indicated development of respiratory acidosis. Respiratory muscle necrosis can be severe in horses with degenerative myopathy and can lead to respiratory failure.

  3. Severe diaphragmatic necrosis in 4 horses with degenerative myopathy.

    Science.gov (United States)

    Valentine, Beth A; Hammock, Phillip D; Lemiski, David; Hughes, Faith E; Gerstner, Lonna; Bird, Karyn E

    2002-08-01

    Severe diaphragmatic necrosis occurred in horses with degenerative myopathy due to polysaccharide storage myopathy (n = 2), nutritional myopathy (n = 1), and vasculitis (n = 1). Blood gas analysis performed in 1 horse indicated development of respiratory acidosis. Respiratory muscle necrosis can be severe in horses with degenerative myopathy and can lead to respiratory failure.

  4. Total Gastric Necrosis: A Case Report and Literature Review

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... Pancreas 2012;41:325-7. 2. Patocskai EJ, Thomas JM. Gastric necrosis in a patient with bulimia. Eur J Surg 2002;168:302-4. 3. Davis LL, Raffensperger J, Novak GM. Necrosis of the stomach secondary to ingestion of corrosive agents: Report of three cases requiring total gastrectomy. Chest 1972;62:48-51.

  5. 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 ...

  6. CRTH2 antagonists in asthma: current perspectives

    Directory of Open Access Journals (Sweden)

    Singh D

    2017-12-01

    Full Text Available Dave Singh, Arjun Ravi, Thomas Southworth Division of Infection, Immunity and Respiratory Medicine, The Medicines Evaluation Unit, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK Abstract: Chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2 binds to prostaglandin D2. CRTH2 is expressed on various cell types including eosinophils, mast cells, and basophils. CRTH2 and prostaglandin D2 are involved in allergic inflammation and eosinophil activation. Orally administered CRTH2 antagonists are in clinical development for the treatment of asthma. The biology and clinical trial data indicate that CRTH2 antagonists should be targeted toward eosinophilic asthma. This article reviews the clinical evidence for CRTH2 involvement in asthma pathophysiology and clinical trials of CRTH2 antagonists in asthma. CRTH2 antagonists could provide a practical alternative to biological treatments for patients with severe asthma. Future perspectives for this class of drug are considered, including the selection of the subgroup of patients most likely to show a meaningful treatment response. Keywords: CRTH2, clinical trial, eosinophilic asthma, prostaglandin D2

  7. 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 ...

  8. Calcium antagonists for aneurysmal subarachnoid haemorrhage

    NARCIS (Netherlands)

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

    2005-01-01

    BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm and have

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. Antagonist-Elicited Cannabis Withdrawal in Humans

    Science.gov (United States)

    Gorelick, David A.; Goodwin, Robert S.; Schwilke, Eugene; Schwope, David M.; Darwin, William D.; Kelly, Deanna L.; McMahon, Robert P.; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A.

    2013-01-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ9-tetrahydrocannabinol (THC) dosages (40–120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0–8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses. PMID:21869692

  14. Antagonist-elicited cannabis withdrawal in humans.

    Science.gov (United States)

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2011-10-01

    Cannabinoid CB1 receptor antagonists have potential therapeutic benefits, but antagonist-elicited cannabis withdrawal has not been reported in humans. Ten male daily cannabis smokers received 8 days of increasingly frequent 20-mg oral Δ⁹-tetrahydrocannabinol (THC) dosages (40-120 mg/d) around-the-clock to standardize cannabis dependence while residing on a closed research unit. On the ninth day, double-blind placebo or 20- (suggested therapeutic dose) or 40-mg oral rimonabant, a CB1-cannabinoid receptor antagonist, was administered. Cannabis withdrawal signs and symptoms were assessed before and for 23.5 hours after rimonabant. Rimonabant, THC, and 11-hydroxy-THC plasma concentrations were quantified by mass spectrometry. The first 6 subjects received 20-mg rimonabant (1 placebo); the remaining 4 subjects received 40-mg rimonabant (1 placebo). Fourteen subjects enrolled; 10 completed before premature termination because of withdrawal of rimonabant from clinical development. Three of 5 subjects in the 20-mg group, 1 of 3 in the 40-mg group, and none of 2 in the placebo group met the prespecified withdrawal criterion of 150% increase or higher in at least 3 visual analog scales for cannabis withdrawal symptoms within 3 hours of rimonabant dosing. There were no significant associations between visual analog scale, heart rate, or blood pressure changes and peak rimonabant plasma concentration, area-under-the-rimonabant-concentration-by-time curve (0-8 hours), or peak rimonabant/THC or rimonabant/(THC + 11-hydroxy-THC) plasma concentration ratios. In summary, prespecified criteria for antagonist-elicited cannabis withdrawal were not observed at the 20- or 40-mg rimonabant doses. These data do not preclude antagonist-elicited withdrawal at higher rimonabant doses.

  15. Combining elements from two antagonists of formyl peptide receptor 2 generates more potent peptidomimetic antagonists

    DEFF Research Database (Denmark)

    Skovbakke, Sarah Line; Holdfeldt, Andre; Nielsen, Christina

    2017-01-01

    Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, Rh......B-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective...... antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4–6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease....

  16. Molecular Mechanism of Apoptosis and Necrosis

    Directory of Open Access Journals (Sweden)

    Gulfidan Coskun

    2011-06-01

    Full Text Available Organismal homeostasis depends on an intricate balance between cell death and renewal. Apoptosis is a process of programmed cell death that plays a critical role in some normal and pathologic conditions beginning from embryologic development and ends at death. Apoptosis is initiated by morphological changes at the cell membrane, surface organels and nucleus. Apoptosis starts with death signals coming from outside or inside of the cell and continue to activate the mechanisms of apoptosis via cell death receptor or mitochondrial pathways. During apoptosis a group proteases are activated which cause DNA fragmentation, cytoplasmic shrinkage and membrane blebbing. Apoptotic cells divide into apoptotic bodies and then these apoptotic bodies are removed from tissue by phagocytes and adjacent cells In contrast to the “programmed” nature of apoptosis, necrotic cell death has always been believed to be a random, uncontrolled process that leads to death of the cell. Also necrosis, which is an other type of cell death, came to be used to describe pathologic cell death which cause inflamation. [Archives Medical Review Journal 2011; 20(3.000: 145-158

  17. Immunization with viral antigens: Infectious haematopoietic necrosis

    Science.gov (United States)

    Winton, J.R.; Midtlyng, Paul J.; Brown, F.

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease.

  18. 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

  19. Similarities and differences between calcium antagonists: pharmacological aspects

    NARCIS (Netherlands)

    van Zwieten, P. A.; Pfaffendorf, M.

    1993-01-01

    Characteristics of three different calcium antagonist groups: Most important calcium antagonists used to treat cardiovascular disease belong to one of three main groups, phenylalkylamines, dihydropyridines and benzothiazepines. The best known drug in each group is verapamil, nifedipine and

  20. Protective effects of calcium antagonists in different organs and tissues

    NARCIS (Netherlands)

    van Zwieten, P. A.

    1993-01-01

    The therapeutic efficacy of calcium antagonists in ischemic disorders of various tissues is attributed to vasodilator and antivasoconstrictor activities. A direct, energy-conserving, antiischemic effect of certain calcium antagonists has been claimed repeatedly by basic scientists. The clinical

  1. 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.

  2. Diagnosis and treatment of acute tubular necrosis.

    Science.gov (United States)

    Esson, Matthew L; Schrier, Robert W

    2002-11-05

    Acute tubular necrosis (ATN) is common in hospitalized patients, particularly in the intensive care unit. Over the past four decades, the mortality rate from ATN has remained at 50% to 80%. To review recent studies of diagnosis and treatment strategies for ATN. MEDLINE search for all clinical studies of therapies for ATN, supplemented by a review of the references of the identified articles. Prospective studies and major retrospective studies evaluating therapies for ATN. Data on the study sample, interventions performed, results, side effects, and duration of follow-up. Early diagnosis of ATN by exclusion of prerenal and postrenal causes of acute renal failure, examination of urinary sediment, and analysis of urine measures (for example, fractional excretion of sodium in the absence of diuretics) can allow the early involvement of nephrologists and improve survival. Enteral rather than parenteral hyperalimentation in severely malnourished patients may improve survival. Sepsis causes 30% to 70% of deaths in patients with ATN; therefore, avoidance of intravenous lines, bladder catheters, and respirators is recommended. Because septic patients are vasodilated, large volumes of administered fluid accumulate in the lung interstitium of these patients. This condition necessitates ventilatory support, which when prolonged leads to acute respiratory distress syndrome, multiorgan failure, and increased mortality. More aggressive dialysis (for example, given daily) with biocompatible membranes may improve survival in some patients with acute renal failure. New information about the importance of early diagnosis and supportive care for patients with ATN has emerged. However, randomized trials of these interventions are needed to test their effect on the morbidity and mortality of ATN.

  3. 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

  4. Acute esophageal necrosis: an uncommon cause of hematemesis.

    Science.gov (United States)

    Zacharia, George Sarin; Sandesh, K; Ramachandran, Tm

    2014-07-01

    Acute esophageal necrosis or black esophagus is an uncommon clinical entity, diagnosed at the upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. Very often no definite etiology will be identified even though a large list of potential associations has been postulated. Upper gastrointestinal bleeding is the most common clinical presentation, others being epigastric pain, retrosternal chest discomfort and dysphagia. Only about a hundred cases of acute esophageal necrosis have been described in medical literature till this date. We report a case of acute esophageal necrosis in an elderly female who had presented with hematemesis.

  5. Acute Esophageal Necrosis: An Uncommon Cause of Hematemesis

    Directory of Open Access Journals (Sweden)

    George Sarin Zacharia

    2014-07-01

    Full Text Available Acute esophageal necrosis or black esophagus is an uncommon clinical entity, diagnosed at the upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. Very often no definite etiology will be identified even though a large list of potential associations has been postulated. Upper gastrointestinal bleeding is the most common clinical presentation, others being epigastric pain, retrosternal chest discomfort and dysphagia. Only about a hundred cases of acute esophageal necrosis have been described in medical literature till this date. We report a case of acute esophageal necrosis in an elderly female who had presented with hematemesis.

  6. 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)

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Samuel T., E-mail: chaos@ccf.org [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States); Ahluwalia, Manmeet S. [Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States); Barnett, Gene H. [Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States); Stevens, Glen H.J. [Department of Neurology, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States); Murphy, Erin S. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States); Stockham, Abigail L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Shiue, Kevin [Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Suh, John H. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio (United States)

    2013-11-01

    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.

  9. 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.

  10. Antagonist potential of Trichoderma indigenous isolates for ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... Full Length Research Paper. Antagonist potential of Trichoderma indigenous isolates for biological control of Phytophthora palmivora the causative agent of black pod disease on cocoa (Theobroma cacao L.) in Côte d'Ivoire. J. Mpika1,4*, I. B. Kébé1, A. E. Issali2, F.K. N'Guessan1, S. Druzhinina3, ...

  11. 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

  12. The sexually antagonistic genes of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Paolo Innocenti

    2010-03-01

    Full Text Available When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection.

  13. 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

  14. NMDA Receptor Antagonists for Treatment of Depression

    Directory of Open Access Journals (Sweden)

    Zeynep Ates-Alagoz

    2013-04-01

    Full Text Available Depression is a psychiatric disorder that affects millions of people worldwide. Individuals battling this disorder commonly experience high rates of relapse, persistent residual symptoms, functional impairment, and diminished well-being. Medications have important utility in stabilizing moods and daily functions of many individuals. However, only one third of patients had considerable improvement with a standard antidepressant after 2 months and all patients had to deal with numerous side effects. The N-methyl-d-aspartate (NMDA receptor family has received special attention because of its critical role in psychiatric disorders. Direct targeting of the NMDA receptor could result in more rapid antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists have been demonstrated in different animal models. MK-801 (a use-dependent channel blocker, and CGP 37849 (an NMDA receptor antagonist have shown antidepressant properties in preclinical studies, either alone or combined with traditional antidepressants. A recent development is use of ketamine clinically for refractory depression. The purpose of this review is to examine and analyze current literature on the role of NMDA receptor antagonists for treatment of depression and whether this is a feasible route in drug discovery.

  15. 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.

  16. '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

  17. 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

  18. 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)

  19. From the Cover: Glutamate antagonists limit tumor growth

    Science.gov (United States)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy

    2001-05-01

    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  20. A Case of Bilateral Aseptic Necrosis of the Femoral Head

    OpenAIRE

    KAMAL, DIANA; TR?ISTARU, RODICA; KAMAL, C.K.; ALEXANDRU, D.O.; MOGOANT?, L.; GRECU, D.C.

    2014-01-01

    Aseptic necrosis of the femoral head is a disease whose etiology is not completely elucidated and generally affects young adults aged between 30 and 50 years. In a significant number of patients bilateral disease occurs, which makes detection in its early stages constitute an important objective. We present the case of a male patient, aged 23 years, with the following risk factors: smoking and chronic alcohol consumption, who is diagnosed with aseptic necrosis of the left femoral head, ARCO s...

  1. [The asterisk sign and adult ischemic femur head necrosis].

    Science.gov (United States)

    Dihlmann, W; Heller, M

    1985-04-01

    The asterisk sign is a stellate density, which is seen normally in the femoral head on computed tomography. It is due to the demonstration of the trabeculae in the femoral head. In adult ischaemic necrosis of the femoral head, there are characteristic changes in the asterisk sign at an early stage, even before there is collapse of the head. The changes are described and the indications for performing CT of the hip for diagnosing adult ischaemic necrosis are discussed.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Lim, Heejin; Lee, Sang Hyung; Lee, Hyun Tae; Lee, Jee Un; Son, Ji Young; Shin, Woori; Heo, Yong-Seok

    2018-03-07

    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. 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

  6. Effect of TNF antagonists on the productivity of daily work of patients with rheumatoid arthritis.

    Science.gov (United States)

    Furuya, Hidekazu; Kasama, Tsuyoshi; Isozaki, Takeo; Umemura, Masayu; Otsuka, Kumiko; Isojima, Sakiko; Tsukamoto, Hiroyuki; Tokunaga, Takehiro; Yanai, Ryo; Takahashi, Ryo

    2013-01-01

    Rheumatoid arthritis (RA) is a significant cause of work disability and job loss. The resulting economic burden experienced by patients has received considerable research attention. This research assesses the effect of tumor necrosis factor (TNF) antagonists (infliximab, etanercept) on the ability of RA patients living in Japan to work and participate in society. A total of 42 patients with active RA were enrolled and given biological therapy for 12 months (mo). Of these patients, 14 were employed full-time, 6 were employed part-time, and 22 were not employed. Twenty-six patients were given infliximab, and sixteen were given etanercept. The amount of domestic labor performed before the biologics served as a baseline and was assigned a value of 0%. After treatment with biologics, the productivity was evaluated using the visual analog scale (VAS; -100 to +100 mm). The administration of TNF antagonists to RA patients who exhibited an insufficient response to medical treatment significantly improved the Disease Activity Score 28 (DAS 28) after both 6 mo and 12 mo (P Productivity VAS) (P Productivity VAS that was observed after 6 mo and 12 mo (P productivity is an important contributor to the indirect costs of RA, our findings are relevant for the pharmacoeconomic assessment of treatments.

  7. 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.

  8. Investigation of orexin-2 selective receptor antagonists: Structural modifications resulting in dual orexin receptor antagonists.

    Science.gov (United States)

    Skudlarek, Jason W; DiMarco, Christina N; Babaoglu, Kerim; Roecker, Anthony J; Bruno, Joseph G; Pausch, Mark A; O'Brien, Julie A; Cabalu, Tamara D; Stevens, Joanne; Brunner, Joseph; Tannenbaum, Pamela L; Wuelfing, W Peter; Garson, Susan L; Fox, Steven V; Savitz, Alan T; Harrell, Charles M; Gotter, Anthony L; Winrow, Christopher J; Renger, John J; Kuduk, Scott D; Coleman, Paul J

    2017-03-15

    In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX 2 R subtype and culminating in the discovery of 23, a highly potent, OX 2 R-selective molecule that exhibited a promising in vivo profile. Further structural modification led to an unexpected restoration of OX 1 R antagonism. Herein, these changes are discussed and a rationale for selectivity based on computational modeling is proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Reduction of periodontal pathogens adhesion by antagonistic strains.

    Science.gov (United States)

    Van Hoogmoed, C G; Geertsema-Doornbusch, G I; Teughels, W; Quirynen, M; Busscher, H J; Van der Mei, H C

    2008-02-01

    Periodontitis results from a shift in the subgingival microflora into a more pathogenic direction with Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans considered as periodontopathogens. In many cases, treatment procures only a temporary shift towards a less pathogenic microflora. An alternative treatment could be the deliberate colonization of pockets with antagonistic microorganisms to control the adhesion of periodontopathogens. The aim of this study was to identify bacterial strains that reduce adhesion of periodontopathogens to surfaces. Streptococcus sanguinis, Streptococcus crista, Streptococcus salivarius, Streptococcus mitis, Actinomyces naeslundii, and Haemophilus parainfluenzae were evaluated as potential antagonists against P. gingivalis ATCC 33277, P. intermedia ATCC 49046, and A. actinomycetemcomitans ATCC 43718 as periodontopathogens. Adhesion of periodontopathogens to the bottom plate of a parallel plate flow chamber was studied in the absence (control) and the presence of pre-adhering antagonistic strains up to a surface coverage of 5%. The largest reduction caused by antagonistic strains was observed for P. gingivalis. All antagonistic strains except S. crista ATCC 49999 inhibited the adhesion of P. gingivalis by at least 1.6 cells per adhering antagonist, with the largest significant reduction observed for A. naeslundii ATCC 51655 (3.8 cells per adhering antagonist). Adhering antagonists had a minimal effect on the adhesion of A. actinomycetemcomitans ATCC 43718. Intermediate but significant reductions were perceived for P. intermedia, most notably caused by S. mitis BMS. The adhesion of P. gingivalis was inhibited best by antagonistic strains, while S. mitis BMS appeared to be the most successful antagonist.

  10. Subacute cutaneous lupus erythematosus in the course of rheumatoid arthritis: a relationship with TNF-α antagonists and rituximab therapy?

    Science.gov (United States)

    Lis-Święty, Anna; Brzezińska-Wcisło, Ligia; Widuchowska, Małgorzata; Kucharz, Eugeniusz

    2013-06-01

    Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is caused by different medicines, first of all: calcium channel blockers, angiotensin converting enzyme inhibitors, thiazides, terbinafine, statins and antagonists of tumor necrosis factor-α (TNF-α). DI-SCLE does not distinguish from idiopathic form of the disease, clinically, histopathologically and immunologically. However, receding of symptoms is observed after recapture of the provoking drug. To present a patient with rheumatoid arthritis (RA), who developed SCLE after treatment with TNF-α antagonists and rituximab. In a 31-year-old woman with RA leucopenia due to treatment with etanercept and adalimumab was observed. Therefore, the treatment was changed to rituximab, but after starting the therapy, erythematous and oedematous skin lesions of an oval or annular shape appeared on the cheeks, auricles, lips and the decolette. Histopathological evaluation of the skin lesions revealed SCLE. Ro/SS-A and La/SS-B antibodies were detected in serum. Regression of skin lesions and hematologic disturbances was achieved after starting corticosteroid therapy. Co-existence of SCLE with RA should be considered in some patients. The role of TNF-α antagonists and rituximab therapy in induction of idiopathic form of SCLE requires further investigations.

  11. Diphenyl Purine Derivatives as Peripherally Selective Cannabinoid Receptor 1 Antagonists

    Science.gov (United States)

    Fulp, Alan; Bortoff, Katherine; Zhang, Yanan; Seltzman, Herbert; Mathews, James; Snyder, Rodney; Fennell, Tim; Maitra, Rangan

    2015-01-01

    Cannabinoid receptor 1 (CB1) antagonists are potentially useful for the treatment of several diseases. However, clinical development of several CB1 antagonists was halted due to central nervous system (CNS)-related side effects including depression and suicidal ideation in some users. Recently, studies have indicated that selective regulation of CB1 receptors in the periphery is a viable strategy for treating several important disorders. Past efforts to develop peripherally selective antagonists of CB1 have largely targeted rimonabant, an inverse agonist of CB1. Reported here are our efforts toward developing a peripherally selective CB1 antagonist based on the otenabant scaffold. Even though otenabant penetrates the CNS, it is unique among CB1 antagonists that have been clinically tested because it has properties that are normally associated with peripherally selective compounds. Our efforts have resulted in an orally absorbed compound that is a potent and selective CB1 antagonist with limited penetration into the CNS. PMID:23098108

  12. Glans Necrosis Following Penile Prosthesis Implantation: Prevention and Treatment Suggestions.

    Science.gov (United States)

    Wilson, Steven K; Mora-Estaves, Cesar; Egydio, Paulo; Ralph, David; Habous, Mohamad; Love, Christopher; Shamsodini, Ahmad; Valenzuela, Robert; Yafi, Faysal A

    2017-09-01

    To examine possible etiology and treatment outcomes in 21 patients with glans necrosis following penile prosthesis implantation. Glans necrosis typically presented with a dusky glans on the first postoperative day following prosthesis implantation. The blood supply to the glans penis consists of the dorsal arteries and the terminal branches of the spongiosal arteries. Using the cohort in our study, we compiled preoperative comorbidities and adjunctive surgical maneuvers that might compromise glans vascularity, leading to glans necrosis. Preoperative risk factors were arteriosclerotic cardiovascular disease (90%), diabetes mellitus (81%), smoking (81%), previous prosthesis explantation (57%), and previous radiation therapy (48%). The most prevalent intraoperative and postoperative factor was subcoronal incision for reasons as simple as coincident circumcision or as complex as for penile degloving (86%). Other factors detected were penile wrapping with an occlusive elastic bandage (62%), use of a sliding technique for penile lengthening (33%), and coincident distal urethral injury repair (29%). Seventeen patients (81%) managed expectantly with preservation of implanted prosthesis sustained significant glandular loss. Four patients managed with immediate prosthesis removal healed without sequelae. Patients with preoperative risk factors undergoing penile prosthesis implantation should avoid high-risk adjunctive surgical maneuvers. Upon development of signs of glans necrosis postoperatively, in the setting of these high-risk factors, immediate implant removal may prevent subsequent glans necrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Conservative management of distal leg necrosis in lung transplant recipients.

    Science.gov (United States)

    Aigner, F; Husmann, M; Huber, L C; Benden, C; Schuurmans, M M

    2017-05-01

    Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Sexually Antagonistic Selection in Human Male Homosexuality

    Science.gov (United States)

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    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. PMID:18560521

  19. 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.

  20. 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

  1. Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    M.C. Nogueira

    2007-12-01

    Full Text Available Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximabfor the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6 for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5. Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600 after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

  2. 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.

  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. 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

    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...

  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. 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.)

  8. 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.)

  9. 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.

  10. 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.

  11. 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

  12. Calcium antagonists and the diabetic hypertensive patient

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P

    1993-01-01

    reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion......Roughly 40% of all diabetic patients, whether insulin dependent or not, develop persistent albuminuria (over 300 mg/24 hr), a decrease in the glomerular filtration rate, and elevated blood pressure, ie, diabetic nephropathy. Diabetic nephropathy is the single most important cause of end stage renal...... disease in the Western world, and accounts for over a quarter of all end stage renal disease. It also is a major cause of the increased morbidity and mortality seen in diabetic patients; for example, the cost of end stage renal care in the United States currently exceeds +1.8 billion per year for diabetic...

  13. 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

  14. 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

  15. Carvedilol, a nonselective beta-blocker, suppresses the production of tumor necrosis factor and tissue factor by inhibiting early growth response factor-1 expression in human monocytes in vitro.

    Science.gov (United States)

    Mizuochi, Yuichiro; Okajima, Kenji; Harada, Naoaki; Molor-Erdene, Perenlei; Uchiba, Mitsuhiro; Komura, Hidefumi; Tsuda, Takako; Katsuya, Hirotada

    2007-04-01

    Tumor necrosis factor (TNF) and tissue factor (TF) produced by monocytes and macrophages have been shown to be among the aggravating factors for chronic heart failure (CHF), because they induce cardiac dysfunction and thrombotic complications, respectively. Carvedilol, a nonselective beta-adrenoceptor antagonist with alpha(1)- adrenoceptor blockade action, has been demonstrated to improve the outcome of patients with severe CHF, suggesting that carvedilol might inhibit the production of TNF and TF. In this study, this possibility is examined using isolated human monocytes stimulated with lipopolysaccharide (LPS) in vitro. Carvedilol (10 muM) significantly inhibited LPS-induced production of TNF and TF by monocytes, whereas prazosin (a selective alpha(1)-adrenoceptor antagonist), bisoprolol (a selective beta(1)-adrenoceptor antagonist), ICI-118,551 (a selective beta(2)-adrenoceptor antagonist), and arotinolol (a nonselective beta-adrenoceptor antagonist with alpha(1)-adrenoceptor blockade action) did not. Carvedilol inhibited both expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but it did not inhibit activation of either nuclear factor-kappaB or activator protein-1 in monocytes stimulated with LPS. These results suggest that carvedilol inhibits LPS-induced production of TNF and TF by inhibiting activation of the ERK1/2-Egr-1 pathway independent of its adrenoceptor inhibitory activities in monocytes.

  16. Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

    Science.gov (United States)

    2013-12-18

    Effectiveness Directorate, Biosciences and Protection Division, Warfighter Fatigue Countermeasures Branch. 35. Golden, C.J. (1978). Stroop Color and Word Test: A...0080 TITLE: Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance PRINCIPAL INVESTIGATOR: Dr. Thomas Neylan...31August2013 4. TITLE AND SUBTITLE Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance 5a. CONTRACT NUMBER W81XWH

  17. Using waste of Tofu production improved antagonistic activities of a ...

    African Journals Online (AJOL)

    Mrs. Hoa

    2012-10-04

    Oct 4, 2012 ... screened for their antagonistic activity against 10 races of Xoo causing rice bacterial blight disease. Three actinomycete strains ... antagonistic activity of VN10-A-44 against the Xoo pathogen and to make use of tofu waste for large- ..... vitamins and some essential amino acids which are very important for ...

  18. 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....

  19. 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 ...

  20. Calcium antagonists for ischemic stroke: a systematic review

    NARCIS (Netherlands)

    Horn, J.; Limburg, M.

    2001-01-01

    BACKGROUND AND PURPOSE: Stroke is a common disease, and many trials with calcium antagonists as possible neuroprotective agents have been conducted. The aim of this review is to determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. METHODS: Acute

  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. 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.

  3. 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)

  4. 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.

  5. The Link Between Oxidative Stress Response and Tumor Necrosis ...

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    Factor-Alpha (TNF-alpha) in Hepatic Tissue of Rats With Induced. Thyroid Dysfunction. 1Suzan Hazzaa ... Tumor necrosis factor-alpha (TNF-α) is a cytokine with numerous immunological and metabolic activities. Several studies ... However, when free radical generation exceeds the antioxidant capacity of cells, oxidative ...

  6. Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and ...

    Indian Academy of Sciences (India)

    2Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University,. Nanning, Guangxi 530021, People's Republic of China. Abstract. Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)-308G/A and (TNF-α)-. 238G/A ...

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

    African Journals Online (AJOL)

    Generation of truncated recombinant form of tumor necrosis factor receptor-1 to produce cancer vaccine. Hamide Hatamihanza1, Mehrdad Hashemi1*, Azim Akbarzadeh2, Fatemeh. Fotouhi3, Behrokh Farahmand3, Hasan Ebrahimi Shahmabadi4. 1Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad ...

  8. Cytokines and Chemokines Involved in Acute Retinal Necrosis

    NARCIS (Netherlands)

    de Boer, JH; de Visser, L; Rijkers, G.; Wiertz, K.; van den Ham, H.J.; van Loon, A.M.; Rothova, Aniki; Mijnes, JDF

    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. 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

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

    African Journals Online (AJOL)

    Key words: Female gender, microscopic hematuria, renal papillary necrosis, sickle cell anemia. Date of Acceptance: 12-Nov-2015. Address for correspondence: Dr. AJ Madu, ..... Diagn Imaging 1983;52:259-63. 2. Davies PJ. Beethoven's deafness: A new theory. Med J Aust. 1988;149(11-. 12):644–9. 3. Friedrich N. Ueber ...

  11. 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

  12. Tumour necrosis factor-alpha gene polymorphisms in Iranian ...

    African Journals Online (AJOL)

    ... progressive inflammatory destructive process of the bile ducts. This study evaluated the relationship between single-nucleotide polymorphisms in the promoter region of tumour necrosis factor-alpha (TNF-α) gene and bilaiary atresia. Materials and Methods: Genomic deoxyribonucleic acid from 16 patients with established ...

  13. 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

  14. Electrocorticography in patients with delayed radiation necrosis of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Morioka, Takato; Nishio, Shunji; Ishibashi, Hideaki; Inoue, Tooru; Tashima, Takatoshi; Fukui, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine; Hachisuga, Shoji

    1998-02-01

    In the 2 cases of delayed radiation necrosis of the brain, electrocorticography (ECoG) was recorded during craniotomy, and the condition of patients was investigated electrophysiologically. Patients had received whole-brain irradiation total 30-40 Gy and local irradiation 20-30 Gy. ECoG was recorded during surgery by overlaying of grid electrode on the surface of brain lesion. Slow wave was recorded in electroencephalogram on the scalp around lesion, and depression of cortex was suggested. In ECoG of a patient whose necrosis manifested after 20 years from radiation, continuous slow wave was recorded, but cataplectic anomaly wave wasn`t recorded. In ECoG of a patient whose necrosis manifested after two years and six months, extremely high irritability of cortex, such as electrical seizure activity, was shown even under general anesthesia. There is limit in diagnoses by scalp electroencephalogram in order to grasp the condition of a patient of each stage of delayed radiation necrosis of the brain, and diagnoses by ECoG is important. (K.H.)

  15. Tumour necrosis factor alpha and interleukin 10 gene ...

    Indian Academy of Sciences (India)

    Tumour necrosis factor alpha and interleukin 10 gene polymorphisms and the risk of ischemic stroke in south Indian population. Shehnaz Sultana Venkata K. Kolla Yasovanthi Jeedigunta Pranay K. Penagaluru Sindhu Joshi P. Usha Rani P. P. Reddy. Research Note Volume 90 Issue 2 August 2011 pp 361-364 ...

  16. Correlation Between Tumor Necrosis Factor Alpha and Proteinuria ...

    African Journals Online (AJOL)

    Serum tumor necrosis factor-α (TNF-α), urine TNF-α and C-reactive protein (CRP) levels were measured in all subjects. Correlations between these inflammatory parameters and degree of proteinuria, duration of diabetes and degree of glycemic control were examined. Results: Levels of the three inflammatory parameters ...

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

    African Journals Online (AJOL)

    He has a keen interest in neonatal surgery. Associate ... The medical records, bacteriological findings and tissue biopsies from three infants with bowel necrosis who subsequently died from sepsis were ... needed to evaluate all resected necrotic bowel for biofilms and the clinical implications of this finding. S Afr Med J 2016 ...

  18. 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

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. The Link Between Oxidative Stress Response and Tumor Necrosis ...

    African Journals Online (AJOL)

    Thyroid hormones are essential for normal organ growth, development and function. They regulate the basal metabolic rate of different types of cells, including hepatocytes. Oxidative stress plays an essential role in the pathogenesis of thyroid disorders and disturbed tissue functions. Tumor necrosis factor-alpha (TNF-α) is a ...

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis.

    Science.gov (United States)

    Janero, David R; Makriyannis, Alexandros

    2009-03-01

    The endogenous cannabinoid (CB) (endocannabinoid) signaling system is involved in a variety of (patho)physiological processes, primarily by virtue of natural, arachidonic acid-derived lipids (endocannabinoids) that activate G protein-coupled CB1 and CB2 receptors. A hyperactive endocannabinoid system appears to contribute to the etiology of several disease states that constitute significant global threats to human health. Consequently, mounting interest surrounds the design and profiling of receptor-targeted CB antagonists as pharmacotherapeutics that attenuate endocannabinoid transmission for salutary gain. Experimental and clinical evidence supports the therapeutic potential of CB1 receptor antagonists to treat overweight/obesity, obesity-related cardiometabolic disorders, and substance abuse. Laboratory data suggest that CB2 receptor antagonists might be effective immunomodulatory and, perhaps, anti-inflammatory drugs. One CB1 receptor antagonist/inverse agonist, rimonabant, has emerged as the first-in-class drug approved outside the United States for weight control. Select follow-on agents (taranabant, otenabant, surinabant, rosonabant, SLV-319, AVE1625, V24343) have also been studied in the clinic. However, rimonabant's market withdrawal in the European Union and suspension of rimonabant's, taranabant's, and otenabant's ongoing development programs have highlighted some adverse clinical side effects (especially nausea and psychiatric disturbances) of CB1 receptor antagonists/inverse agonists. Novel CB1 receptor ligands that are peripherally directed and/or exhibit neutral antagonism (the latter not affecting constitutive CB1 receptor signaling) may optimize the benefits of CB1 receptor antagonists while minimizing any risk. Indeed, CB1 receptor-neutral antagonists appear from preclinical data to offer efficacy comparable to or better than that of prototype CB1 receptor antagonists/inverse agonists, with less propensity to induce nausea. Continued

  10. 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.

  11. 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......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...... antagonists behind the blood-brain barrier (BBB), i.e. in the central nervous system (CNS)....

  12. Histamine H1-receptor antagonists inhibit nuclear factor-kappaB and activator protein-1 activities via H1-receptor-dependent and -independent mechanisms.

    Science.gov (United States)

    Roumestan, C; Henriquet, C; Gougat, C; Michel, A; Bichon, F; Portet, K; Jaffuel, D; Mathieu, M

    2008-06-01

    Histamine H1-receptor antagonists are used to relieve the symptoms of an immediate allergic reaction. They have additional anti-inflammatory effects that could result from an inhibition of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). The implication of the H1-receptor in these effects is controversial. Diphenhydramine is a first-generation H1-receptor antagonist while mizolastine and desloratadine are second-generation compounds. Mizolastine is also an inhibitor of 5-lipoxygenase (5-LO), an enzyme that has been involved in NF-kappaB activation. We measured the ability of antihistamines to reverse histamine-induced smooth muscle contraction, an effect that involves the H1-receptor. We then investigated whether these drugs affect NF-kappaB and AP-1 activities in A549 lung epithelial cells, and whether this potential regulation involves H1-receptor and 5-LO. Muscle tone was measured on tracheal segments of guinea-pigs. The H1-receptor was overexpressed by transfection and detected by Western blotting and immunofluorescence microscopy. NF-kappaB and AP-1 activities were assessed by reporter gene assays in cells overexpressing or not overexpressing the H1-receptor. Production of regulated upon activation, normal T cell expressed andsecreted (RANTES), a chemokine whose expression is induced through NF-kappaB, was measured using an immunoassay. H1-receptor antagonists reversed histamine-induced contraction in a dose-dependent manner. Induction of AP-1 and NF-kappaB activities by histamine and the down-regulatory effect of antihistamines required overexpression of the H1-receptor. In contrast, when tumour necrosis factor-alpha and a phorbol ester were used to stimulate NF-kappaB and AP-1 activities, respectively, repression of these activities did not involve the H1-receptor. Indeed, repression was triggered only by a subset of H1-receptor antagonists and was not stronger after overexpression of the H1-receptor. Mizolastine

  13. 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.

  14. 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.

  15. 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.

  16. Avascular necrosis of the femoral head and M. R. I

    Energy Technology Data Exchange (ETDEWEB)

    Gires, F.; Leroy-Willig, A; Chevrot, A.; Wolff, J.L. and others

    Normal and pathologic femoral heads have been studied by MRI at 1.5 Tesla. The study was centered upon avascular necrosis (53 lesions). Twenty normal subjects and three patients with algodystrophy were examined. The osteonecrosis patterns were established from known lesions. A low signal rim surrounds an upper polar zone of conserved (Type I) or decreased (Type II) signal. The lesions age correlates significatively with their type: amongst type I lesions, 6 are asymptomatic and the 21 others have a mean age of 5.5 months; Type II lesions have a mean age of 12.7 months. Fourteen lesions were not seen on plain radiographs and six were not detected by bone scan. The older lesions with femoral head deformation are better depicted by standard radiologic techniques. Conservely MRI is the most efficient examination for recent avascular necrosis lesions.

  17. 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

  18. 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.

  19. 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.

  20. 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.)

  1. HOW to Differentiate Dutch Elm Disease from Elm Phloem Necrosis

    Science.gov (United States)

    Lester Paul Gibson; Arthur R. Hastings; Leon A. LeMadeliene

    1981-01-01

    Dutch elm disease (DED) and elm phloem necrosis are the two most serious diseases of elm in the United States (Figs. 1 and 2). Most native species of elm are susceptible to both diseases. Dutch elm disease is caused by a fungus, Ceratocystis u1mi (Buisman) C. Moreau, and is transmitted by two species of elm bark beetles-the smaller European elm bark beetle, Scolytus...

  2. [Avascular necrosis of the hip - diagnosis and treatment].

    Science.gov (United States)

    Drescher, W; Pufe, T; Smeets, R; Eisenhart-Rothe, R V; Jäger, M; Tingart, M

    2011-04-01

    Femoral head necrosis is an ischaemic bone necrosis of traumatic or nontraumatic pathogenesis which can lead to hip joint destruction in young age. It is today the indication for 10 % of all the total hip joint replacements. Known aetiologies of nontraumatic femoral head necrosis are alcoholism, steroids, sickle cell anaemia, caisson, and Gaucher's disease. Further risk factors are chemotherapy, chronic inflammatory bowel disease, systemic lupus erythematosus, and multiple sclerosis, in which also steroids are involved. Gravidity is another risk factor, but still idiopathic pathogenesis is found. In diagnosis, the ARCO-classification of the Association for the Research of Osseous Circulation is essential. While stage 0 can only be found histologically, the reversible early stage 1 shows MR signal changes. In the irreversible early stage 2, first native x-ray changes are seen as lower radiolucency reflects new bone apposition on dead trabeculae. In stage 3, subchondral fracture follows, and in stage 4 secondary arthritis of the hip. Established therapy in stage 1 is core decompression, physiotherapy, and more and more also bisphosphonates. Sufficient data to support extracorporeal shock wave therapy are still lacking. Stem cell therapy seems to be a promising new therapy method in stage 2. In stage 2 and 3 mainly proximal femoral osteotomies and (non)vascularised bone transplantation are performed. In stage 4, depending on size and location of the necrotic zone and pathology of the adjacent bone, resurfacing or short stem hip arthroplasty can be performed. However, conventional THA is still golden standard. The problem and challenge, however, is the often young patient age in femoral head necrosis. Especially chemotherapy-associated osteonecrosis in leukaemia is found in patients in their second decade of life. Therefore, the hip should be preserved as long as possible. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Glaucomatous neurodegeneration: An eye on tumor necrosis factor-alpha

    OpenAIRE

    Renu Agarwal; Puneet Agarwal

    2012-01-01

    Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expressi...

  4. Spleen necrosis virus, an avian retrovirus, can infect primate cells.

    OpenAIRE

    Koo, H M; Brown, A M; Ron, Y; Dougherty, J P

    1991-01-01

    Spleen necrosis virus (SNV) is an avian retrovirus that can infect some mammalian cells such as dog cells as well as all avian cells tested to date. We were interested in testing whether SNV could also infect primate cells. For these experiments, we used HeLa and COS-7 cells. Initially, we determined whether the SNV long terminal repeat promoter was functional in HeLa and COS-7 cells. In transient transfection assays, the SNV promoter efficiently directed chloramphenicol acetyltransferase gen...

  5. 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 ...

  6. 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.

  7. 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

  8. 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.

  9. 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.)

  10. 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.

  11. The radiological features of necrosis in bronchial carcinomas and their metastases

    International Nuclear Information System (INIS)

    Goerich, J.; Beyer-Enke, S.A.; Zuna, I.; Kayser, K.; Gueckel, F.; Kaick, G. van

    1989-01-01

    Necrosis in bronchial carcinomas and in their soft tissue metastases was studied in 368 patients by means of CT and ultrasound. In primary bronchial carcinomas (59 cases) there was clear correlation between tumour necrosis and the histology. There was a significant preponderance amongst squamous carcinomas, whereas small cell carcinomas rarely show radiologically visible necrosis (p [de

  12. 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.

  13. Evidence of a role of tumor necrosis factor alpha in refractory asthma.

    Science.gov (United States)

    Berry, Mike A; Hargadon, Beverley; Shelley, Maria; Parker, Debbie; Shaw, Dominick E; Green, Ruth H; Bradding, Peter; Brightling, Christopher E; Wardlaw, Andrew J; Pavord, Ian D

    2006-02-16

    The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma. We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study. As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01). Patients with refractory asthma have evidence of up-regulation of the TNF-alpha axis. (ClinicalTrials.gov number, NCT00276029.). Copyright 2006 Massachusetts Medical Society.

  14. Effect of TNF antagonists on the productivity of daily work of patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Furuya H

    2013-01-01

    Full Text Available Hidekazu Furuya,1 Tsuyoshi Kasama,1 Takeo Isozaki,1,2 Masayu Umemura,1 Kumiko Otsuka,1 Sakiko Isojima,1 Hiroyuki Tsukamoto,1 TakehiroTokunaga,1 Ryo Yanai,1 Ryo Takahashi11Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan; 2Department of Rheumatology,University of Michigan Medical School, Ann Arbor, MI, USAAbstract: Rheumatoid arthritis (RA is a significant cause of work disability and job loss. The resulting economic burden experienced by patients has received considerable research attention. This research assesses the effect of tumor necrosis factor (TNF antagonists (infliximab, etanercept on the ability of RA patients living in Japan to work and participate in society. A total of 42 patients with active RA were enrolled and given biological therapy for 12 months (mo. Of these patients, 14 were employed full-time, 6 were employed part-time, and 22 were not employed. Twenty-six patients were given infliximab, and sixteen were given etanercept. The amount of domestic labor performed before the biologics served as a baseline and was assigned a value of 0%. After treatment with biologics, the productivity was evaluated using the visual analog scale (VAS; −100 to +100 mm. The administration of TNF antagonists to RA patients who exhibited an insufficient response to medical treatment significantly improved the Disease Activity Score 28 (DAS 28 after both 6 mo and 12 mo (P < 0.0001. A significant correlation was found between the improvement in their DAS 28 and improvements in their work situation (Productivity VAS (P < 0.05. Of particular interest is the significant correlation between the values of baseline mHAQ and the percent changes of Productivity VAS that was observed after 6 mo and 12 mo (P < 0.05. Our findings indicate that medical treatment of RA with TNF antagonists improves the patients' ability to perform their jobs and housekeeping. Because loss of productivity is an important

  15. Practical recommendations for calcium channel antagonist poisoning.

    Science.gov (United States)

    Rietjens, S J; de Lange, D W; Donker, D W; Meulenbelt, J

    2016-02-01

    Calcium channel antagonists (CCAs) are widely used for different cardiovascular disorders. At therapeutic doses, CCAs have a favourable side effect profile. However, in overdose, CCAs can cause serious complications, such as severe hypotension and bradycardia. Patients in whom a moderate to severe intoxication is anticipated should be observed in a monitored setting for at least 12 hours if an immediate-release formulation is ingested, and at least 24 hours when a sustained-release formulation (or amlodipine) is involved, even if the patient is asymptomatic. Initial treatment is aimed at gastrointestinal decontamination and general supportive care, i.e., fluid resuscitation and correction of metabolic acidosis and electrolyte disturbances. In moderate to severe CCA poisoning, a combined medical strategy might be indispensable, such as administration of vasopressors, intravenous calcium and hyperinsulinaemia/euglycaemia therapy. Especially hyperinsulinaemia/euglycaemia therapy is an important first-line treatment in CCA-overdosed patients in whom a large ingestion is suspected. High-dose insulin, in combination with glucose, seems to be most effective when used early in the intoxication phase, even when the patient shows hardly any haemodynamic instability. Intravenous lipid emulsion therapy should only be considered in patients with life-threatening cardiovascular toxicity, such as refractory shock, which is unresponsive to conventional therapies. When supportive and specific pharmacological measures fail to adequately reverse refractory conditions in CCA overdose, the use of extracorporeal life support should be considered. The efficacy of these pharmacological and non-pharmacological interventions generally advocated in CCA poisoning needs further in-depth mechanistic foundation, in order to improve individualised treatment of CCA-overdosed patients.

  16. 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)

  17. 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.

  18. Development of KGF Antagonist as a Breast Cancer Therapeutic

    National Research Council Canada - National Science Library

    Sugimoto, Yasuro

    2003-01-01

    .... We were able to show some potential intracellular KGFR target small molecules whereas extracellular target synthetic peptide antagonist was not able to do during this period We also added a new...

  19. Recent Development of Non-Peptide GnRH Antagonists

    Directory of Open Access Journals (Sweden)

    Feng-Ling Tukun

    2017-12-01

    Full Text Available The decapeptide gonadotropin-releasing hormone, also referred to as luteinizing hormone-releasing hormone with the sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 plays an important role in regulating the reproductive system. It stimulates differential release of the gonadotropins FSH and LH from pituitary tissue. To date, treatment of hormone-dependent diseases targeting the GnRH receptor, including peptide GnRH agonist and antagonists are now available on the market. The inherited issues associate with peptide agonists and antagonists have however, led to significant interest in developing orally active, small molecule, non-peptide antagonists. In this review, we will summarize all developed small molecule GnRH antagonists along with the most recent clinical data and therapeutic applications.

  20. Complications of TNF-α antagonists and iron homeostasis

    Science.gov (United States)

    TNF-α is a central regulator of inflammation and its blockade downregulates other proinflammatory cytokines, chemokines, and growth factors. Subsequently, TNF-α antagonists are currently used in treatment regimens directed toward several inflammatory diseases. Despite a beneficia...

  1. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists

    Science.gov (United States)

    2016-08-01

    AWARD NUMBER: W81XWH-15 1-0252 TITLE: Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists PRINCIPAL INVESTIGATOR...14 Jul 2016 4. TITLE AND SUBTITLE Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists 5a. CONTRACT NUMBER 5b. GRANT...Center for Substance Abuse Research Lewis Katz School of Medicine at Temple University 3500 N, Broad Street Philadelphia, PA 19140 AND ADDRESS(ES) 8

  2. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian

    2008-01-01

    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras.......About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  3. 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)

  4. Analytical ultracentrifugation with fluorescence detection system reveals differences in complex formation between recombinant human TNF and different biological TNF antagonists in various environments.

    Science.gov (United States)

    Krayukhina, Elena; Noda, Masanori; Ishii, Kentaro; Maruno, Takahiro; Wakabayashi, Hirotsugu; Tada, Minoru; Suzuki, Takuo; Ishii-Watabe, Akiko; Kato, Masahiko; Uchiyama, Susumu

    A number of studies have attempted to elucidate the binding mechanism between tumor necrosis factor (TNF) and clinically relevant antagonists. None of these studies, however, have been conducted as close as possible to physiologic conditions, and so the relationship between the size distribution of TNF-antagonist complexes and the antagonists' biological activity or adverse effects remains elusive. Here, we characterized the binding stoichiometry and sizes of soluble TNF-antagonist complexes for adalimumab, infliximab, and etanercept that were formed in human serum and in phosphate-buffered saline (PBS). Fluorescence-detected sedimentation velocity analytical ultracentrifugation analyses revealed that adalimumab and infliximab formed a range of complexes with TNF, with the major complexes consisting of 3 molcules of the respective antagonist and one or 2 molcules of TNF. Considerably greater amounts of high-molecular-weight complexes were detected for infliximab in human serum. The emergence of peaks with higher sedimentation coefficients than the adalimumab monomer as a function of added human serum albumin (HSA) concentration in PBS suggested weak reversible interactions between HSA and immunoglobulins. Etanerept exclusively formed 1:1 complexes with TNF in PBS, and a small amount of complexes with higher stoichiometry was detected in human serum. Consistent with these biophysical characterizations, a reporter assay showed that adalimumab and infliximab, but not etanercept, exerted FcγRIIa- and FcγRIIIa-mediated cell signaling in the presence of TNF and that infliximab exhibited higher potency than adalimumab. This study shows that assessing distribution profiles in serum will contribute to a more comprehensive understanding of the in vivo behavior of therapeutic proteins.

  5. Platelet-activating factor (PAF)-antagonists of natural origin.

    Science.gov (United States)

    Singh, Preeti; Singh, Ishwari Narayan; Mondal, Sambhu Charan; Singh, Lubhan; Garg, Vipin Kumar

    2013-01-01

    Presently herbal medicines are being used by about 80% of the world population for primary health care as they stood the test of time for their safety, efficacy, cultural acceptability and lesser side effects. The discovery of platelet activating factor antagonists (PAF antagonists) during these decades are going on with different framework, but the researchers led their efficiency in studying in vitro test models. Since it is assumed that PAF play a central role in etiology of many diseases in humans such as asthma, neuronal damage, migraine, cardiac diseases, inflammatory, headache etc. Present days instinctively occurring PAF antagonist exists as a specific grade of therapeutic agents for the humans against these and different diseases either laid hold of immunological or non-immunological types. Ginkgolide, cedrol and many other natural PAF antagonists such as andrographolide, α-bulnesene, cinchonine, piperine, kadsurenone, different Piper species' natural products and marine origin plants extracts or even crude drugs having PAF antagonist properties are being used currently against different inflammatory pathologies. This review is an attempt to summarize the data on PAF and action of natural PAF antagonists on it, which were evaluated by in vivo and in vitro assays. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. 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

  7. Does route of administration affect the outcome of TNF antagonist therapy?

    Science.gov (United States)

    Schwartzman, Sergio; Morgan, G James

    2004-01-01

    The tumor necrosis factor (TNF) antagonists are parenterally administered biologic response modifiers indicated for the management of rheumatoid arthritis. Although infliximab, etanercept, and adalimumab are all members of this class, they differ in route of administration and dosing regimen. In the USA and in Europe, infliximab, in combination with oral methotrexate, is administered intravenously, initially at a dose of 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. The US Food and Drug Administration (FDA) has further approved that the dosage can be increased to 10 mg/kg and the doses can be given as often as every 4 weeks to optimize patient outcome (information based on the US package insert dated June 2002). Etanercept and adalimumab are given subcutaneously and can be self-injected. The FDA-approved dose of etanercept is 25 mg twice weekly, and of adalimumab is 40 mg every 2 weeks with methotrexate, or 40 mg alone. Medication adherence, possibly the most important factor in maintaining the benefits of anti-TNF therapy, is influenced by the interaction between the patient and his or her healthcare team, the patient's attitude toward the disease and medication regimen, and the choice of therapy.

  8. NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation.

    Science.gov (United States)

    Lee, Jae-Won; Park, Hyun Ah; Kwon, Ok-Kyoung; Park, Ji-Won; Lee, Gilhye; Lee, Hee Jae; Lee, Seung Jin; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2017-10-01

    NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-κB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-κB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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.

  10. alpha2-Adrenoceptor antagonists reverse the 5-HT2 receptor antagonist suppression of head-twitch behavior in mice.

    Science.gov (United States)

    Matsumoto, K; Mizowaki, M; Thongpraditchote, S; Murakami, Y; Watanabe, H

    1997-03-01

    The alpha2-adrenoceptor agonist clonidine, as well as 5-HT2 receptor antagonists, reportedly suppress 5-HT2 receptor-mediated head-twitch behavior. We investigated the effect of alpha2-adrenoceptor antagonists on the suppressive action of 5-HT2 receptor antagonists in mice pretreated with the noradrenaline toxin 6-hydroxydopamine (6-OHDA) or the 5-HT synthesis inhibitor p-chlorophenylalanine (p-CPA). In normal mice, idazoxan (0.08-0.2 mg/kg, IP) or yohimbine (0.2-2.0 mg/kg, IP), both alpha2-adrenoceptor antagonists, had no effect on the head-twitch response caused by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; 16 mg/kg, IP), but idazoxan significantly enhanced the response at 0.5 mg/kg. On the other hand, these alpha2-adrenoceptor antagonists, at doses that had no effect on the basal number of head-twitches (idazoxan 0.2 mg/kg and yohimbine 0.5 mg/kg), significantly attenuated not only the suppressive effect of clonidine (0.01 mg/kg, IP) on head-twitch response but also that of the 5-HT2 receptor antagonist ritanserin (0.03 mg/kg, IP). Moreover, idazoxan (0.2 mg/kg) also significantly reversed the inhibition by 0.01 mg/kg (IP) ketanserin, a selective 5-HT2 receptor antagonist. Pretreatment with 6-OHDA plus nomifensine but not with p-CPA significantly attenuated the effect of idazoxan (0.2-0.5 mg/kg) on the ritanserin inhibition of the head-twitch response. Prazosin, an alpha1-adrenoceptor antagonist, dose-dependently suppressed the response, and the effect of prazosin (1.25 mg/kg) was significantly attenuated by 0.5 mg/kg idazoxan. These results indicate that endogenous noradrenaline is involved in the apparent antagonistic interaction between selective alpha2-adrenoceptor antagonists and 5-HT2 receptor antagonists in the head-twitch response, and suggest that noradrenaline stimulation of alpha1-adrenoceptors may be involved in this apparent antagonism.

  11. The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment

    DEFF Research Database (Denmark)

    Björkman, Lena; Mårtensson, Jonas; Winther, Malene

    2016-01-01

    by tumor necrosis factor alpha (TNF-α) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation......Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca(2......+), and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased...

  12. Vitamin K antagonist use and mortality in dialysis patients.

    Science.gov (United States)

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

    2018-01-01

    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 scores in a cohort of end-stage renal disease patients receiving dialysis treatment. We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use. Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increased mortality risk after adjustment. Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  13. 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

  14. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry

    DEFF Research Database (Denmark)

    Glintborg, Bente; Østergaard, Mikkel; Krogh, Niels Steen

    2010-01-01

    To use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual patients maintained treatment) and clinical response among patients ...... with ankylosing spondylitis (AS) receiving their first treatment series with a tumour necrosis factor a (TNFa) inhibitor....

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

    Directory of Open Access Journals (Sweden)

    Emmanuel Broussolle

    2015-09-01

    Full Text Available 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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)

  2. [Septum necrosis following CPAP treatment of preterm infant].

    Science.gov (United States)

    Fjaeldstad, Alexander; Cipliene, Rasa; Ramsgaard-Jensen, Trine; Ebbesen, Finne

    2014-05-26

    This case describes the complications of intensive respiratory support in a preterm infant. During two months of rigorous nasal continuous positive airway pressure (CPAP) therapy with intermittent use of CPAP-mask and -prongs, an ulcer in the nasal mucus membrane developed into septum necrosis. Preterm infants are in high risk of needing long-term respiratory support, why it is important to bear in mind that binasal CPAP-prongs have proved to be more effective than mononasal therapy, and that CPAP-prongs and -mask have different sites of injury.

  3. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    Ali Duran

    2013-01-01

    Full Text Available 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-old woman.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Keratocyte loss in Acanihamoeba Keratitis: Phagocytosis, necrosis or apoptosis?

    Directory of Open Access Journals (Sweden)

    Vemuganti Geeta

    2000-01-01

    Full Text Available Purpose: Pathogenesis of Acanthamoeba keratitis involves breakdown of epithelial barrier, stromal invasion by Acanthamoeba, loss of keratocytes, inflammatory response and finally stromal necrosis. The loss of keratocytes, believed to be due to the phagocytic activity of the parasite, occurs disproportionate to and independent of the parasite load, thereby suggesting additional modes of cell loss. To test our hypothesis that the loss of keratocytes in Acanthamoeba keratitis is due to apoptosis, we did both histology and histochemistry on the corneal tissues. Methods: Routine Haematoxylin and Eosin, Gomori′s Methenamine Silver and Periodic acid Schiff stained sections of five corneal tissues from penetrating keratoplasty and eviscerated eyes were reviewed. TUNEL staining was done for morphological detection of apoptosis in three cases, using formalin-fixed, paraffin-processed tissues. Results: Histological changes were epithelial ulceration, loss of keratocytes in all layers, inflammation in anterior two-thirds of the stroma with necrosis, and deeper quiet stroma. Acanthamoeba trophozoites were found in the anterior stroma while the cysts were more in the deeper stroma, with minimal or no inflammatory response. TUNEL staining was positive in keratocytic nuclei in all layers. Conclusions: This study demonstrates that one of the modes of keratocyte loss in Acanthamoeba keratitis is by apoptosis, possibly in addition to the necrotic process and phagocytic activity of the parasite. The death of inflammatory cells also appears to be mediated by apoptosis.

  12. 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.

  13. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    of proliferation and angiogenesis. Specific histamine receptors have been identified on the surface of bone marrow cells, immune competent cells, endothelial cells, fibroblasts, and also on malignant cells. This has prompted research in regulation by specific histamine receptor agonists and antagonists. Results...... from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  14. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

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

    2017-01-01

    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......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...... METHODS: The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols...

  15. 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.

  16. Histamine H4 receptor antagonists: the new antihistamines?

    Science.gov (United States)

    Fung-Leung, Wai-Ping; Thurmond, Robin L; Ling, Ping; Karlsson, Lars

    2004-11-01

    Antihistamines (histamine H1 receptor antagonists) are a mainstay treatment for atopic allergy, yet they are only partially effective in relieving the symptoms of the disease. They also have very limited value for the treatment of asthma, despite the well-characterized bronchoconstrictory effects of histamine. The recent discovery of a fourth histamine receptor (H4), and the realization that it is exclusively expressed on hematopoietic cell types that are most implicated in the development and symptomatology of allergy and asthma, suggests that pharmacological targeting of the H4 receptor, either alone or in combination with H1 receptor antagonists, may prove useful for treating both allergy and asthma. Here we review the known biology associated with the H4 receptor, as well the effects of a highly selective H1 receptor antagonist.

  17. Clinical Development of Histamine H4Receptor Antagonists.

    Science.gov (United States)

    Thurmond, Robin L; Venable, Jennifer; Savall, Brad; La, David; Snook, Sandra; Dunford, Paul J; Edwards, James P

    2017-01-01

    The discovery of the histamine H 4 receptor (H 4 R) provided a new avenue for the exploration of the physiological role of histamine, as well as providing a new drug target for the development of novel antihistamines. The first step in this process was the identification of selective antagonists to help unravel the pharmacology of the H 4 R relative to other histamine receptors. The discovery of the selective H 4 R antagonist JNJ 7777120 was vital for showing a role for the H 4 R in inflammation and pruritus. While this compound has been very successful as a tool for understanding the function of the receptor, it has drawbacks, including a short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies. Further research let to the discovery of JNJ 39758979, which, similar to JNJ 7777120, was a potent and selective H 4 R antagonist and showed anti-inflammatory and anti-pruritic activity preclinically. JNJ 39758979 advanced into human clinical studies and showed efficacy in reducing experimental pruritus and in patients with atopic dermatitis. However, development of this compound was terminated due to the occurrence of drug-induced agranulocytosis. This was overcome by developing another H 4 R antagonist with a different chemical structure, toreforant, that does not appear to have this side effect. Toreforant has been tested in clinical studies in patients with rheumatoid arthritis, asthma, or psoriasis. In conclusions there have been many H 4 R antagonists reported in the literature, but only a few have been studied in humans underscoring the difficulty in finding ligands with all of the properties necessary for testing in the clinic. Nevertheless, the clinical data to date suggests that H 4 R antagonists can be beneficial in treating atopic dermatitis and pruritus.

  18. Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling.

    Science.gov (United States)

    Singhal, Hari; Greene, Marianne E; Zarnke, Allison L; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B; Nickisch, Klaus J; Long, Henry W; Becker, Lev; Brown, Myles; Greene, Geoffrey L

    2018-01-12

    Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR

  19. Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling

    Science.gov (United States)

    Singhal, Hari; Greene, Marianne E.; Zarnke, Allison L.; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G.; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B.; Nickisch, Klaus J.; Long, Henry W.; Becker, Lev; Brown, Myles; Greene, Geoffrey L.

    2018-01-01

    Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR

  20. 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.

  1. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

    Energy Technology Data Exchange (ETDEWEB)

    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. (GSKNC)

    2010-08-12

    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.

  2. 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...

  3. 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....

  4. 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

  5. Embarazo luego de necrosis espontanea de un macroadenoma pituitario

    Directory of Open Access Journals (Sweden)

    V. Dobrovsky

    2003-08-01

    Full Text Available La recuperación de la función pituitaria luego de necrosis de un macroadenoma es infrecuente pero no excepcional. Se presenta el caso de una mujer de 32 años de edad, previamente operada de una tumoración adrenal con signos sugestivos de hipercortisolismo que no revirtieron luego de cirugía. Más tarde presentó un cuadro de apoplejía pituitaria seguido de hipopituitarismo probado por mediciones hormonales. Una resonancia nuclear magnética (RNM evidenció un macroadenoma pituitario con signos necróticos comprimiendo el quiasma óptico, realizándose su exéresis por vía transesfenoidal. Nueve meses después los estudios hormonales indicaron la casi total recuperación de la función pituitaria. La paciente tuvo un embarazo y parto normales tres años después. Luego de 5 años de seguimiento permanecía clínicamente asintomática, un test de hipoglucemia insulínica mostró reducción moderada en la respuesta del cortisol pero mayor en la de somatotrofina (GH y una RMN demostró un aracnoidocele parcial, sin evidencia de tumor.Although infrequent, recovery of pituitary function after necrosis of a pituitary adenoma is not an exceptional event. We report the case of a 32-year-old woman with previous surgery for an adrenal mass and signs of hypercortisolism which failed to revert postoperatively. She then developed pituitary apoplexy followed by hypopituitarism, as confirmed by hormonal measurements. Magnetic resonance imaging (MRI showed evidence of a pituitary macroadenoma with signs of necrosis, impinging on the optic chiasm, which was excised by the trans-sphenoidal approach. Nine months later, hormone tests indicated a near total recovery of pituitary functions. The patient had a successful pregnancy three years later. After a 5-year follow-up, she remained clinically asymptomatic, with moderate reduction in cortisol and blunted growth hormone (GH response to hypoglycemia and MRI failed to disclose any residual tumor, except for a

  6. Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.

    Science.gov (United States)

    Feng, Bao-Zhen; Zhu, Xiao-Ping; Fu, Li; Lv, Rong-Fei; Storey, Dylan; Tooley, Paul; Zhang, Xiu-Guo

    2014-05-08

    Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may

  7. 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.

  8. Acquired-resistance of bevacizumab treatment for radiation brain necrosis: a case report

    OpenAIRE

    Zhuang, Hongqing; Yuan, Xiangkun; Sun, Dayong; Bian, Jianliang; Chang, Joe Y.; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-tre...

  9. 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.

  10. 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.

  11. 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.

  12. Ischaemic necrosis of the tongue as a rare complication of cardiogenic shock.

    Science.gov (United States)

    Hulstaert, E; Roggeman, E; Beeckman, A-S; Moerman, M; Vanderstraeten, E; Rasquin, K; Monsaert, E; Baert, D; Dewint, P; Burvenich, P; Van Steenkiste, C

    2015-12-01

    Ischaemic necrosis of the tongue is an unusual clinical finding. In most cases it is associated with vasculitis, particularly giant cell arteritis (GCA). Other causes include profound cardiogenic shock. We report a case of tongue necrosis in an 81-year-old Caucasian woman. The patient was admitted to the intensive care unit (ICU) for cardiogenic shock. Swelling of the tongue was reported before intubation and evolved into tongue ischaemia and necrosis of the tip of the tongue. After surgical debridement the patient recovered. To our knowledge, this is the second report of a patient surviving tongue necrosis resulting from cardiogenic shock.

  13. 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.

  14. 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.

  15. 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)

  16. Acute Tubular Necrosis and Interstitial Nephritis during Pemetrexed Therapy

    Directory of Open Access Journals (Sweden)

    Judith Michels

    2009-03-01

    Full Text Available We report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy. Despite drug withdrawal, renal function remained altered and the patient experienced chronic renal insufficiency. Pemetrexed disodium (Alimta™ is a multitargeted antifolate agent approved by the Food and Drug Administration (FDA for patients diagnosed with mesothelioma and non-small cell lung cancer. This drug is almost exclusively cleared by renal excretion [1]. The most common side effects are hematologic dose-limiting toxicities and nonhematologic toxicities including fatigue, diarrhea, nausea, mucositis and rash. Although few cases of renal failure have been published, no study has reported on the renal pathological findings in this setting. We present a case of acute tubular necrosis associated with interstitial fibrosis after pemetrexed therapy.

  17. Palatal perforation: A rare complication of postanesthetic necrosis

    Directory of Open Access Journals (Sweden)

    Vidisha Gargi

    2017-01-01

    Full Text Available 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.

  18. 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.)

  19. 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.

  20. Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis

    DEFF Research Database (Denmark)

    Ciurea, A.; Weber, U.; Stekhoven, D.

    2015-01-01

    in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings. (First Release Nov 1 2014; J Rheumatol 2015; 42:101-5; doi 10.3899/jrheum.140229).......Objective. To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. The Journal of Rheumatology, Methods.We compared newly initiated TNF inhibition for axSpA in 363 patients...... was slightly higher in the hospital setting. Mean levels (+/- SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 +/- 1.0 vs 3.4 +/- 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response...

  1. 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

  2. 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

  3. [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.

  4. 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...

  5. Ultrasonographic findings of epipericardial fat necrosis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Hwang, Hye Jeon; Lee, Kwan Seop; Lee, In Jae; Park, Kyoung Ha [Dept. of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2016-04-15

    Epipericardial fat necrosis (EFN) is an infrequent cause of acute chest pain. In rare cases like these, conservative treatment is necessary. Clinically, EFN may mimic emergent cardiopulmonary conditions, such as acute myocardial infarction. Computed tomography (CT) and magnetic resonance imaging characteristics of EFN is well described as encapsulated fatty lesion with perilesional soft tissue strands and thickening of adjacent pericardium in the epipericardial area. For confirmation of the diagnosis, involution of this lesion on follow-up is important. We present a case of EFN observed with ultrasonography (USG). This lesion was shown as a well-defined ovoid shaped mass with heterogeneous echogenicity in the left side of cardiophrenic space on USG. There was no color flow on Doppler USG. Follow-up USG and CT revealed decrease in the size of the lesion.

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

    Directory of Open Access Journals (Sweden)

    Farzaneh Pouya

    2015-07-01

    Full Text Available 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 continuesto 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.

  7. 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.

  8. 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

    1995-01-01

    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. Images Figure 1 Figure 4 PMID:8550079

  9. 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.

  10. 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

  11. Indications for the use of parenteral H2-receptor antagonists.

    Science.gov (United States)

    Thompson, J C; Walker, J P

    1984-11-19

    Development of acute mucosal ulceration is a complex series of catabolic interactions. Hospitalized patients with duodenal or gastric ulcer, pathologic gastric hypersecretory states (such as Zollinger-Ellison syndrome), gastric outlet obstruction, esophagitis, severe gastritis or duodenitis, sepsis, trauma (particularly head injury or burns), and some patients receiving high-dose corticosteroids are at risk of developing acute stress ulcers. Treatment should be initiated as soon as the patient is identified as being at risk, because measures designed to prevent bleeding or perforation are more effective than those designed to stop bleeding once it supervenes and the cascade of multiple organ failure commences. The presence of acid will trigger the onset of this condition; however, ulceration will not occur if the intraluminal pH can be maintained above 5 by periodic antacid treatment or by H2-receptor blockade. The dosing regimen of antacid or of H2-receptor antagonist should not be fixed, but should be sufficient to keep the gastric pH higher than 5. Antagonists administered via a nasogastric tube are the first line of defense, but 30 to 50 percent of the most ill patients will also be treated parenterally with H2-receptor antagonists. Parenteral H2-receptor blockade therapy is indicated in these patients when the risk of acute or continued ulceration of esophageal, gastric, or duodenal mucosa is high and the oral administration of medication is either not possible or the response to such therapy is unreliable. Parenteral H2-receptor antagonists are rarely administered alone.

  12. 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...

  13. 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 ...

  14. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology.

    Science.gov (United States)

    Al-Inany, Hesham G; Youssef, Mohamed A; Ayeleke, Reuben Olugbenga; Brown, Julie; Lam, Wai Sun; Broekmans, Frank J

    2016-04-29

    Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimens have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006 and 2011. To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists compared with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched from inception to May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to 28 April 2015), Ovid MEDLINE (1966 to 28 April 2015), EMBASE (1980 to 28 April 2015), PsycINFO (1806 to 28 April 2015), CINAHL (to 28 April 2015) and trial registers to 28 April 2015, and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for

  15. Diversity, distribution, and antagonistic activities of rhizobacteria of Panax notoginseng

    Directory of Open Access Journals (Sweden)

    Ze-Yan Fan

    2016-04-01

    Conclusion: The results suggest that diverse bacteria exist in the P. notoginseng rhizosphere soil, with differences in community in the same field, and antagonistic isolates may be good potential biological control agent for the notoginseng root-rot diseases caused by F. oxysporum, Fusarium solani, and Panax herbarum.

  16. Antagonistic effect of brevicin on Gram positive and Gram negative ...

    African Journals Online (AJOL)

    B. Senthil Kumar

    phylogenetic tree was constructed, based on evolutionary distances that were calculated by following the distance matrix method, using the Phylip package. Preparation and analysis of crude extract of protein (CEP) for their antagonistic activity against food borne pathogens. 24 h old MRS broth culture was prepared and ...

  17. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.

    Science.gov (United States)

    Palmer, G C

    2001-09-01

    Because of adverse reactions, early efforts to introduce high affinity competitive or use-dependent NMDA receptor antagonists into patients suffering from stroke, head trauma or epilepsy met with failure. Later it was discovered that both low affinity use-dependent NMDA receptor antagonists and compounds with selective affinity for the NR2B receptor subunit met the criteria for safe administration into patients. Furthermore, these low affinity antagonists exhibit significant mechanistic differences from their higher affinity counterparts. Success of the latter is attested to the ability of the following low affinity compounds to be marketed: 1) Cough suppressant-dextromethorphan (available for decades); 2) Parkinson's disease--amantadine, memantine and budipine; 3) Dementia--memantine; and 4) Epilepsy--felbamate. Moreover, Phase III clinical trials are ongoing with remacemide for epilepsy and Huntington's disease and head trauma for HU-211. A host of compounds are or were under evaluation for the possible treatment of stroke, head trauma, hyperalgesia and various neurodegenerative disorders. Despite the fact that other drugs with associated NMDA receptor mechanisms have reached clinical status, this review focuses only on those competitive and use-dependent NMDA receptor antagonists that reached clinical trails. The ensuing discussions link the in vivo pharmacological investigations that led to the success/mistakes/ failures for eventual testing of promising compounds in the clinic.

  18. Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists

    DEFF Research Database (Denmark)

    Henderson, Alan J; Guzzo, Peter R; Ghosh, Animesh

    2012-01-01

    A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found ...

  19. 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

  20. 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

  1. Calcium antagonists: a ready prescription for treating infectious diseases?

    Science.gov (United States)

    Clark, Kevin B; Eisenstein, Edward M; Krahl, Scott E

    2013-01-01

    Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca(2+) molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca(2+), and downstream binding proteins and sensors of Ca(2+)-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis.

  2. 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

  3. How Hybrid Organizations Turn Antagonistic Assets into Complementarities

    DEFF Research Database (Denmark)

    Hockerts, Kai

    2015-01-01

    This article focuses on people excluded from traditional markets as employees, producers, or consumers on the grounds that they lack the appropriate skills. It describes the processes through which these perceived liabilities can be overcome by so-called hybrid organizations. Hybrids pursue expli...... for complementarities, and by creating demands for antagonistic assets, or by using partnerships....

  4. 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 ...

  5. 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.

  6. Contrasting effects of intralocus sexual conflict on sexually antagonistic coevolution

    NARCIS (Netherlands)

    Pennell, Tanya M; de Haas, Freek J H; Morrow, Edward H; van Doorn, G Sander

    2016-01-01

    Evolutionary conflict between the sexes can induce arms races in which males evolve traits that are detrimental to the fitness of their female partners, and vice versa. This interlocus sexual conflict (IRSC) has been proposed as a cause of perpetual intersexual antagonistic coevolution with

  7. 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-.

  8. Effects of alpha(1)-adrenoceptor antagonists on male sexual function

    NARCIS (Netherlands)

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

    2006-01-01

    alpha(1)-Adrenoceptor antagonists such as alfuzosin, doxazosin, tamsulosin and terazosin are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), but are only second-line agents (doxazosin and terazosin only) for the treatment of

  9. 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 ...

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

    African Journals Online (AJOL)

    user

    Results showed reduction in disease incidence of charcoal rot on sunflower cultivar G-66 with antagonist, A. flavus (100%) followed by A. niger (64.86%) P. capsulatum (63.79%) and T. viride (31.89%) over control. Decrease in disease incidence over control was 100% where seed was treated with combination of A. niger ...

  11. Non-NMDA receptor antagonist-induced drinking in rat

    Science.gov (United States)

    Xu, Z.; Johnson, A. K.

    1998-01-01

    Glutamate has been implicated in the central control of mechanisms that maintain body fluid homeostasis. The present studies demonstrate that intracerebroventricular (i.c.v.) injections of the non-N-methyl-d-aspartate (NMDA) receptor antagonists 6, 7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) induce drinking in rats. The dipsogenic effect of i.c.v. DNQX was antagonized by the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The water intake induced by DNQX was also blocked by pretreatment with a NMDA receptor antagonist, MK-801, but not by angiotensin type 1 (AT1) or acetylcholine muscarinic receptor antagonists (losartan and atropine). The results indicate that non-NMDA receptors may exert a tonic inhibitory effect within brain circuits that control dipsogenic activity and that functional integrity of NMDA receptors may be required for the non-NMDA receptor antagonists to induce water intake. Copyright 1998 Published by Elsevier Science B.V.

  12. 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, ...

  13. About the use of antagonistic bacteria and fungi

    OpenAIRE

    Tilcher, R.; Schmidt, C.; Lorenz, D.; Wolf, G. A.

    2002-01-01

    Microorganisms isolated from the phylloplane of vine and cereal plants inhibiting different phytopathogenic fungi were tested as biological control agents against Plasmopara viticola (downy mildew of grapevine). Based on screening in vitro against Phytophthora infestans, P. parasitica, Pythium ultimum, Botrytis cinerea 62 bacterial isolates were selected for tests with Plasmopara viticola.. Antifungal bacterial strains were assayed for antagonistic activity towards the grapevine dieback fungu...

  14. 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.

  15. 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.

  16. Antagonistic potential of fluorescent Pseudomonas and its impact on ...

    African Journals Online (AJOL)

    This study focused on the antagonistic potential of fluorescent Pseudomonas in vitro, and its inoculation effect on growth performance of Lycopersicon esculentum in Fusarium oxysporum and Rhizoctonia solani infested soil. Biochemical characteristics of fluorescent Pseudomonas showed that all ten isolates were positive ...

  17. Vasopressin receptor antagonists: pharmacological tools and potential therapeutic agents

    NARCIS (Netherlands)

    Streefkerk, J. O.; van Zwieten, P. A.

    2006-01-01

    The present survey deals with the development and applications of non-peptidergic vasopressin receptor antagonists. The existence of at least three vasopressin receptors (V(1), V(2) and V(3) respectively) is firmly established. V(1)-receptors play a relevant role in the regulation of vascular tone,

  18. 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 ...

  19. 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.

  20. Antagonistic activity of selected strains of Bacillus thuringiensis ...

    African Journals Online (AJOL)

    The aim of this work was to determine, in vitro, the antagonistic effectiveness of 60 strains of Bacillus thuringiensis against damping-off and root and stem rot caused by Rhizoctonia solani. The strains were obtained from the International Collection of Entomopathogenic Bacillus at the FCB-UANL. During the in vitro dual ...

  1. 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.

  2. Isolation of Fusarium fujikuroi antagonistic bacteria and cloning of its ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-01

    Dec 1, 2009 ... effects of volatile metabolites produced by antagonistic P. fluorescens found in the isolates inhibited growth of F. fujikuroi in vitro. ... secondary metabolites play critical roles in many aspects of bacterium-host interactions. ... Nocardia, Sorangium, Brevibacterium, and Burkholderia. (Mavrodi et al., 2006; ...

  3. Case report 549: Case 1: Ischemic necrosis femoral heads with pathological fracture right femur. Case 2: Ischemic necrosis femoral heads with fracture bilaterally

    Energy Technology Data Exchange (ETDEWEB)

    McGlade, C.T.; Bassett, L.W.; Mirra, J.; Gold, R.H. (California Univ., Los Angeles (USA). Dept. of Radiological Sciences)

    1989-07-01

    Two cases have been presented in which ischemic necrosis was the cause of pathologic fractures of the femoral necks. Because these patients had primary malignancies that frequently seed in bone, metastatic disease was suspected to be responsible for the pathologic fractures. However, a history of use of corticosteroids and the absence of other skeletal lesions were the clues to the correct diagnosis in both cases. In Case 1, a patient with unilateral femoral head fracture, an MRI examination revealed ischemic necrosis in the asymptomatic contralateral hip. Currently, MRI and SPECT scanning are the most sensitive imaging methods for the diagnosis of ischemic necrosis. Ischemic necrosis should be considered in the differential diagnosis of pathological fracture of the femoral head when a patient has a history of predisposition for osteonecrosis. (orig.).

  4. Case report 549: Case 1: Ischemic necrosis femoral heads with pathological fracture right femur. Case 2: Ischemic necrosis femoral heads with fracture bilaterally

    International Nuclear Information System (INIS)

    McGlade, C.T.; Bassett, L.W.; Mirra, J.; Gold, R.H.

    1989-01-01

    Two cases have been presented in which ischemic necrosis was the cause of pathologic fractures of the femoral necks. Because these patients had primary malignancies that frequently seed in bone, metastatic disease was suspected to be responsible for the pathologic fractures. However, a history of use of corticosteroids and the absence of other skeletal lesions were the clues to the correct diagnosis in both cases. In Case 1, a patient with unilateral femoral head fracture, an MRI examination revealed ischemic necrosis in the asymptomatic contralateral hip. Currently, MRI and SPECT scanning are the most sensitive imaging methods for the diagnosis of ischemic necrosis. Ischemic necrosis should be considered in the differential diagnosis of pathological fracture of the femoral head when a patient has a history of predisposition for osteonecrosis. (orig.)

  5. Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Zach, P.; Bielavská, Edita

    2006-01-01

    Roč. 169, č. 1 (2006), s. 50-57 ISSN 0014-4819 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z5011922 Keywords : learning * microdialysis * glutamate antagonists Subject RIV: FH - Neurology Impact factor: 1.959, year: 2006

  6. Study on correlation between bone marrow edema, stage of necrosis and area ratio of necrosis with the hip pain grading in nontraumatic osteonecrosis of the femoral head

    Directory of Open Access Journals (Sweden)

    Jianchuan Wang

    2015-01-01

    Full Text Available The objective of this study was to explore the correlation between bone marrow edema, stage of necrosis, and area ratio of necrosis with the hip pain grading in non-traumatic osteonecrosis of the femoral head. Bone marrow edema grading at all levels and the hip pain grade differences were statistically significant (P < 0.001. Bone marrow edema grading increased by levels of 0, 1, and 2, whereas average pain rating increased as well to 40.73, 104.66 and 143.49. I ~ III period stage of necrosis and the hip pain grade difference was statistically significant (P < 0.001, with the average grade progress pain stage by the death of a rank gradually increased, I period, II period, III period was 57.00, 88.58 and 120.62, respectively. Area ratio of necrosis between 0 ~ 3 were positively correlated with pain, compared the two was statistically significant (P < 0.001, and with the degree of pathological changes is aggravating, increase the average rank of levels of pain. 0, 1, 2 and 3 are 36.88, 98.03, 123.87 and 151.93 respectively. We can choose the treatment method and evaluate treatment effect by considering a patients’ degree of bone marrow edema, stage of necrosis and area ratio of necrosis.

  7. Good response to infliximab in rheumatoid arthritis following failure of interleukin-1 receptor antagonist.

    Science.gov (United States)

    Bao, Jun; Yue, Tao; Li, Ting; He, Dong-Yi; Bao, Yi-Xiao

    2016-04-01

    To evaluate the efficacy of tumor necrosis factor inhibitor infliximab in patients with rheumatoid arthritis (RA) who were disease-resistant to recombinant human interleukin-1 receptor antagonist (IL-1Ra). A total of 104 patients with active RA despite methotrexate (MTX) treatment were enrolled in the open trial. Among them, 27 IL-1Ra nonresponders 'Switchers' and 51 biologic-naive patients 'Naivers' received an infusion of 3 mg/kg infliximab at weeks 0, 2, 6 and 14, combined with concurrent MTX therapy, while the other 26 patients who had never received any biologics 'Controls' continued MTX monotherapy. Clinical outcomes and safety were assessed at weeks 0, 2 and every 4 weeks thereafter for 18 weeks with the American College of Rheumatology (ACR) core set criteria, the Disease Activity Score in 28 joints, and records of adverse events (AEs) and abnormal laboratory findings. At week 18, an ACR20 response was achieved in 56% of Switchers and 61% of Naivers, compared with 23% of Controls (P = 0.0013 and 0.0126, respectively). Compared with Controls, both Switchers and Naivers achieved a significant improvement in tender-joint count, swollen-joint count, patient's assessment of pain, patient's and physician's global assessment of disease activity, erythrocyte sedimentation rate and C-reactive protein. Switchers even achieved a greater benefit from health assessment questionnaire (HAQ) scores than Naivers. Infliximab was well tolerated, with a similar incidence of AEs across all study groups. Switching from IL-1Ra to infliximab is effective in improving disease activity and maintaining joint function. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  8. 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...

  9. Case report: Subcutaneous fat necrosis: report of a case and a ...

    African Journals Online (AJOL)

    Case report: Subcutaneous fat necrosis: report of a case and a concise review. Amor Khachemoune, Khalid Al Aboud, Khalid Al Hawsawi, Ahmad Al Aboud. Abstract. Subcutaneous fat necrosis (SCFN) occurs in term newborn with history of difficult delivery. Apart from the soft tissue lesions, the infants may suffer from life ...

  10. 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...

  11. 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.

  12. 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.

  13. Necrosis de médula espinal, edema cerebral y glioblastoma

    OpenAIRE

    Iglesias Rozas, José Rafael, 1942-

    1987-01-01

    Cinco imágenes de una necrosis de la médula espinal, un edema cerebral y un glioblastoma en una paciente de 76 años. Five pictures of a spinal cord necrosis, a cerebral edema and a glioblastoma in a 76-year-old female patient.

  14. Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation

    Science.gov (United States)

    Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y.; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

    2016-01-01

    Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible. PMID:26934327

  15. 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.

  16. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2007-01-01

    Full Text Available The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antagonists is stressed.

  17. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2015-12-01

    Full Text Available The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antagonists is stressed.

  18. 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)

  19. [Logistic regression analysis of high-risk factors for neonatal incarcerated hernia with intestinal necrosis].

    Science.gov (United States)

    Zeng, Cheng; Yu, Lei; Chen, Yu; Bian, Hong-Qiang; Zheng, Kai; Ye, Guo-Gang

    2012-12-01

    To investigate the high-risk factors for neonatal incarcerated hernia with intestinal necrosis by logistic regression analysis. Retrospective analysis was performed on the clinical data of 131 neonates with incarcerated oblique inguinal hernia containing the intestine. Of the 131 cases, 14 suffered from intestinal necrosis. The high risk factors for neonatal incarcerated hernia with intestinal necrosis were determined by logistic regression analysis. Manual reduction after incarceration (>2 times) (χ2 = 69.289, P2 times) (χ2 = 84.731, Pneonatal incarcerated hernia with intestinal necrosis. Intestinal necrosis tends to occur in neonates with incarcerated hernia who have incarceration or received manual reduction more than twice and suffer from mesentery incarceration. Manual reduction is prohibited for these cases, which should be surgically treated immediately.

  20. 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.

  1. 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

  2. [Partial and total joint replacement in femur head necrosis].

    Science.gov (United States)

    Fink, B; Rüther, W

    2000-05-01

    In literature, the results of hip arthroplasty in patients with avascular osteonecrosis of the femoral head vary. The main reason may be the nonhomogeneous patient groups concerning etiology of the femoral head necrosis (FHN). Analyzing the results of hip endoprosthesis in relation to the etiology of FHN leads to the assumption that steroid-induced FHN and FHN with underlying systemic bone diseases (renal osteodystrophy, sickle-cell hemoglobinopathy) have the highest loosening rates. Diseases with immunosuppressive medication and sickle-cell hemoglobinopathy have the highest risk of joint infection. Therefore etiology plays an important role in the long-term results of hip endoprostheses in FHN. Modern cement techniques of the second generation and new non-cemented total hip endoprostheses seem to have better results than older prostheses and cement techniques. We followed-up 52 non-cemented thrust plate prostheses in 45 patients with FHN, prospectively, for at least 2 years (3.7 +/- 1.6 years). The revision rate was 9.6% (two aseptic loosenings in one patient with renal osteodystrophy and one patient with alcohol abuse, as well as three late infections in one patient with alcohol abuse and two patients with renal osteodystrophy). Additionally, five prostheses showed radiologic lines of a minimum of 2 mm. Future studies with longer follow-up are needed to find out whether these prosthetic designs with proximal fixation of the femoral component preserving the diaphysial bone have advantages in young FHN patients.

  3. Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha

    Directory of Open Access Journals (Sweden)

    Weibo Cai Ph.D.

    2008-01-01

    Full Text Available Tumor necrosis factor-alpha (TNF-α, a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

  4. 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)

  5. 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

  6. 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

  7. 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.)

  8. 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.

  9. Infectious pancreatic necrosis virus enters CHSE-214 cells via macropinocytosis.

    Science.gov (United States)

    Levican, Jorge; Miranda-Cárdenas, Camila; Soto-Rifo, Ricardo; Aguayo, Francisco; Gaggero, Aldo; León, Oscar

    2017-06-08

    Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry. Consistent with this idea, viral infection was significantly reduced when the Na+/H+ exchanger NHE1 was inhibited with 5-(N-Ethyl-N-isopropyl) amiloride (EIPA). Neither chlorpromazine nor filipin complex I affected IPNV infection. To examine the role of macropinocytosis regulators, additional inhibitors were tested. Inhibitors of the EGFR pathway and the effectors Pak1, Rac1 and PKC reduced viral infection. Together, our results indicate that IPNV is mainly internalized into CHSE-214 cells by macropinocytosis.

  10. Photosensitizer absorption coefficient modeling and necrosis prediction during Photodynamic Therapy.

    Science.gov (United States)

    Salas-García, Irene; Fanjul-Vélez, Félix; Arce-Diego, José Luis

    2012-09-03

    The development of accurate predictive models for Photodynamic Therapy (PDT) has emerged as a valuable tool to adjust the current therapy dosimetry to get an optimal treatment response, and definitely to establish new personal protocols. Several attempts have been made in this way, although the influence of the photosensitizer depletion on the optical parameters has not been taken into account so far. We present a first approach to predict the spatio-temporal variation of the photosensitizer absorption coefficient during PDT applied to dermatological diseases, taking into account the photobleaching of a topical photosensitizer. This permits us to obtain the photons density absorbed by the photosensitizer molecules as the treatment progresses and to determine necrosis maps to estimate the short term therapeutic effects in the target tissue. The model presented also takes into account an inhomogeneous initial photosensitizer distribution, light propagation in biological media and the evolution of the molecular concentrations of different components involved in the photochemical reactions. The obtained results allow to investigate how the photosensitizer depletion during the photochemical reactions affects light absorption by the photosensitizer molecules as the optical radiation propagates through the target tissue, and estimate the necrotic tumor area progression under different treatment conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The propeptide of yeast cathepsin D inhibits programmed necrosis.

    Science.gov (United States)

    Carmona-Gutiérrez, D; Bauer, M A; Ring, J; Knauer, H; Eisenberg, T; Büttner, S; Ruckenstuhl, C; Reisenbichler, A; Magnes, C; Rechberger, G N; Birner-Gruenberger, R; Jungwirth, H; Fröhlich, K-U; Sinner, F; Kroemer, G; Madeo, F

    2011-05-19

    The lysosomal endoprotease cathepsin D (CatD) is an essential player in general protein turnover and specific peptide processing. CatD-deficiency is associated with neurodegenerative diseases, whereas elevated CatD levels correlate with tumor malignancy and cancer cell survival. Here, we show that the CatD ortholog of the budding yeast Saccharomyces cerevisiae (Pep4p) harbors a dual cytoprotective function, composed of an anti-apoptotic part, conferred by its proteolytic capacity, and an anti-necrotic part, which resides in the protein's proteolytically inactive propeptide. Thus, deletion of PEP4 resulted in both apoptotic and necrotic cell death during chronological aging. Conversely, prolonged overexpression of Pep4p extended chronological lifespan specifically through the protein's anti-necrotic function. This function, which triggered histone hypoacetylation, was dependent on polyamine biosynthesis and was exerted via enhanced intracellular levels of putrescine, spermidine and its precursor S-adenosyl-methionine. Altogether, these data discriminate two pro-survival functions of yeast CatD and provide first insight into the physiological regulation of programmed necrosis in yeast.

  12. Tactical Approaches to Interconverting GPCR Agonists and Antagonists.

    Science.gov (United States)

    Dosa, Peter I; Amin, Elizabeth Ambrose

    2016-02-11

    There are many reported examples of small structural modifications to GPCR-targeted ligands leading to major changes in their functional activity, converting agonists into antagonists or vice versa. These shifts in functional activity are often accompanied by negligible changes in binding affinity. The current perspective focuses on outlining and analyzing various approaches that have been used to interconvert GPCR agonists, partial agonists, and antagonists in order to achieve the intended functional activity at a GPCR of therapeutic interest. An improved understanding of specific structural modifications that are likely to alter the functional activity of a GPCR ligand may be of use to researchers designing GPCR-targeted drugs and/or probe compounds, specifically in cases where a particular ligand exhibits good potency but not the preferred functional activity at the GPCR of choice.

  13. 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.

  14. 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.

  15. 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......, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events. CONCLUSIONS: The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic...

  16. Non-imidazole histamine NO-donor H3-antagonists.

    Science.gov (United States)

    Tosco, Paolo; Bertinaria, Massimo; Di Stilo, Antonella; Cena, Clara; Fruttero, Roberta; Gasco, Alberto

    2005-01-01

    Recently a series of H3-antagonists related to Imoproxifan was realised (I); in these products the oxime substructure of the lead was constrained in NO-donor furoxan systems and in the corresponding furazan derivatives. In this paper, a new series of compounds derived from I by substituting the imidazole ring with the ethoxycarbonylpiperazino moiety present in the non-imidazole H3-ligand A-923 is described. For all the products synthesis and preliminary pharmacological characterisation, as well as their hydrophilic-lipophilic balance, are reported. The imidazole ring replacement generally results in a decreased H3-antagonist activity with respect to the analogues of series I and, in some cases, induces relaxing effects on the electrically contracted guinea-pig ileum, probably due to increased affinity for other receptor systems.

  17. 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.

  18. 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.

  19. State Estimation For An Agonistic-Antagonistic Muscle System

    OpenAIRE

    Nguyen, Thang; Warner, Holly; La, Hung; Mohammadi, Hanieh; Simon, Dan; Richter, Hanz

    2017-01-01

    Research on assistive technology, rehabilitation, and prosthesis requires the understanding of human machine interaction, in which human muscular properties play a pivotal role. This paper studies a nonlinear agonistic-antagonistic muscle system based on the Hill muscle model. To investigate the characteristics of the muscle model, the problem of estimating the state variables and activation signals of the dual muscle system is considered. In this work, parameter uncertainty and unknown input...

  20. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    Considerable evidence has emerged to suggest that histamine participates in the regulation of the inflammatory response, immune reaction, coagulation cascade, and cardiovascular function. Furthermore, histamine may play a major role in the growth of normal and malignant tissue as a regulator...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  1. Chitinolytic Enterobacter agglomerans Antagonistic to Fungal Plant Pathogens

    OpenAIRE

    Chernin, L.; Ismailov, Z.; Haran, S.; Chet, I.

    1995-01-01

    Three Enterobacter agglomerans strains which produce and excrete proteins with chitinolytic activity were found while screening soil-borne bacteria antagonistic to fungal plant pathogens. The chitinolytic activity was induced when the strains were grown in the presence of colloidal chitin as the sole carbon source. It was quantitated by using assays with chromogenic p-nitrophenyl analogs of disaccharide, trisaccharide, and tetrasaccharide derivatives of N-acetylglucosamine. A set of three flu...

  2. ANTIHYPERTENSIVE TREATMENT IN ELDERLY PATIENTS WITH DIHYDROPYRIDINE CALCIUM ANTAGONISTS

    OpenAIRE

    Y. A. Karpov; V. V. Buza

    2006-01-01

    The proofs of necessity of active arterial hypertension (AH) treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA) for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Ana...

  3. Renoprotective effects of calcium antagonists on kidney disease

    OpenAIRE

    Mochammad Sja'bani, Mochammad Sja'bani

    2015-01-01

    There has been a growing number of evidence that calcium antagonists provide a salutary effects in preserving kidneys against acute renal ischemia in patients at increasing risk. Their beneficial effects on cellular and mitochondrial calcium may explain the effects on renal hemodynamics and metabolics. It seems, that they do not directly vasodilate kidney vessels but alter the response towards vasoconstrictor agents. This effect may mediate diuretic and natriuretic effect of calcium antagonis...

  4. 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

  5. Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists.

    Science.gov (United States)

    Raufman, Jean-Pierre; Chen, Ying; Zimniak, Piotr; Cheng, Kunrong

    2002-08-01

    In the course of examining the actions of major human bile acids on cholinergic receptors, we discovered that conjugates of lithocholic acid are partial muscarinic agonists. In the present communication, we report that conjugates of deoxycholic acid (DC) act as cholinergic muscarinic receptor antagonists. Chinese hamster ovary (CHO) cells expressing rat M3-muscarinic receptors were used to test bile acids for inhibition of radioligand [N- (3)H-methylscopolamine ((3)H-NMS)] binding; alteration of inositol phosphate (IP) formation; mitogen-activated protein (MAP) kinase phosphorylation and cell toxicity. We observed approximately 18.8, 30.3 and 37.1% inhibition of (3)H-NMS binding with DC and its glycine (DCG) and taurine (DCT) conjugates, respectively (all 100 micromol/l, p exclusion or lactate dehydrogenase release from CHO-M3 cells. We observed the following rank order of potency (IC(50) micromol/l) for inhibition of (3)H-NMS by muscarinic antagonists and bile acids: NMS (0.0004) > 4-DAMP (0.009) > atropine (0.012) > DCT (170) > DCG (250). None of the bile acids tested were hydrolyzed by recombinant cholinesterase. At concentrations achieved in human bile, DC derivatives are natural muscarinic antagonists. Copyright 2002 S. Karger AG, Basel

  6. Glutamate receptor antagonists with the potential for migraine treatment.

    Science.gov (United States)

    Ferrari, Anna; Rustichelli, Cecilia; Baraldi, Carlo

    2017-12-01

    Preclinical, clinical, and other (e.g., genetic) evidence support the concept that migraine susceptibility may at least partially result from a glutamatergic system disorder. Therefore, the receptors of the glutamatergic system are considered relatively new targets for investigational drugs to treat migraine. Investigational and established glutamate receptor antagonists (GluRAs) have been shown to possess antinociceptive properties in preclinical models of trigeminovascular nociception and have been evaluated in clinical trials. This review focuses on preclinical and clinical studies of GluRAs for the treatment of migraine. Areas covered: A PubMed database search (from 1987 to December 2016) and a review of published studies on GluRAs in migraine were conducted. Expert opinion: All published clinical trials of investigational GluRAs have been unsuccessful in establishing benefit for acute migraine treatment. Clinical trial results contrast with the preclinical data, suggesting that glutamate (Glu) does not play a decisive role after the attack has already been triggered. These antagonists may instead be useful for migraine prophylaxis. Improving patient care requires further investigating and critically analyzing the role of Glu in migraine, designing experimental models to study more receptors and their corresponding antagonists, and identifying biomarkers to facilitate trials designed to target specific subgroups of migraine patients.

  7. Non-genetic inheritance and the patterns of antagonistic coevolution

    Directory of Open Access Journals (Sweden)

    Mostowy Rafal

    2012-06-01

    Full Text Available Abstract Background Antagonistic species interactions can lead to coevolutionary genotype or phenotype frequency oscillations, with important implications for ecological and evolutionary processes. However, direct empirical evidence of such oscillations is rare. The rarity of observations is generally attributed to inherent difficulties of ecological and evolutionary long-term studies, to weak or absent interaction between species, or to the absence of negative frequency-dependence. Results Here, we show that another factor – non-genetic inheritance, mediated for example by epigenetic mechanisms – can completely eliminate oscillations in the presence of such negative frequency dependence, even if only a small fraction of offspring are affected. We analytically derive the threshold value of this fraction at which the dynamics change from oscillatory to stable, and investigate how selection, mutation and generation times differences between the two species affect the threshold value. These results strongly suggest that the lack of phenotype frequency oscillations should not be attributed to the lack of strong interactions between antagonistic species. Conclusions Given increasing evidence of non-genetic effects on the outcomes of antagonistic species interactions, we suggest that these effects should be incorporated into ecological and evolutionary models of interacting species.

  8. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Directory of Open Access Journals (Sweden)

    Zolaly MA

    2012-03-01

    Full Text Available Mohammed A ZolalyDepartment of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaBackground: The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures.Methods: The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever.Results: Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine.Conclusion: Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.Keywords: antihistamine, nonantihistamine, histamine H1 antagonist, febrile seizures

  9. 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.

  10. Tachykinin NK2 receptor antagonists. A patent review (2006 - 2010).

    Science.gov (United States)

    Altamura, Maria

    2012-01-01

    Tachykinins are endogenous peptide neurotransmitters, acting through the NK1, NK2 and NK3 receptors, at central and peripheral level. At peripheral level, they are involved in contraction of smooth muscle, secretion of water and ion from epithelia, as well as modulation of visceral pain sensitivity. Tachykinin NK2 receptor antagonists have the potential to be useful in the treatment of various gastrointestinal, genitourinary and CNS diseases. In this review, an overview of the patenting activity in the last 5 years is provided. Patents from different companies and research groups are discussed for their novelty and evaluated in relation to proposed indications and clinical studies. Relevant biological data are also presented. Patents claiming new therapeutic indications are included in a dedicated section. Although there is still no tachykinin NK2 receptor antagonist approved for use in human therapy, research in the field is still proposing new compounds and possible uses. A number of candidates are being evaluated in Phase II clinical studies, in indications ranging from gastrointestinal disorders to inflammatory diseases. The results of these studies will indicate the role of tachykinin NK2 receptor antagonists in human therapy.

  11. Correlated EMG Oscillations between Antagonists during Cocontraction in Men.

    Science.gov (United States)

    Yoshitake, Yasuhide; Kanehisa, Hiroaki; Shinohara, Minoru

    2017-03-01

    The purpose of this study was to determine the modulation of common low-frequency oscillations in pools of motor units across antagonistic muscles because of the difference in the activation level of pools of spinal motor neurons and the presence of neuromuscular fatigue during intended cocontraction. Ten healthy young men (21.8 ± 1.5 yr) performed intended steady cocontractions of elbow flexors and extensors at maximal and a submaximal (10% of maximal EMG) effort. The submaximal cocontraction was repeated after sustained maximal contraction of elbow flexors. Surface EMG was recorded from the biceps brachii and triceps brachii muscles. Correlated EMG oscillations between the antagonistic muscles were quantified by the cross-correlation function (CCF) using rectified EMG for the EMG for the 3- to 15-Hz bands. The positive CCF peak in rectified EMG EMG, a negative CCF peak (i.e., out-of-phase oscillations) during submaximal cocontraction was smaller compared with maximal cocontraction but increased after the sustained contraction. Across subjects, the degree of reduction in maximal EMG amplitude after the sustained contraction was correlated with the amount of change in the CCF peak in EMG oscillations between antagonistic muscles occur during intended cocontraction, and 2) the magnitude of these correlated oscillations increases with the activation level of pools of spinal motor neurons and neuromuscular fatigue.

  12. 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

  13. 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....

  14. 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.

  15. Abiotic conditions affect floral antagonists and mutualists of Impatiens capensis (Balsaminaceae).

    Science.gov (United States)

    Soper Gorden, Nicole L; Adler, Lynn S

    2013-04-01

    While the effect of abiotic factors on leaf herbivory is well known, the relative importance of abiotic conditions influencing both mutualists and antagonists is less well understood. Species interactions could enhance or reduce the direct effects of abiotic factors, depending on how mutualists and antagonists respond to abiotic conditions. We manipulated soil nutrients and shade in a factorial design and measured soil moisture in the annual Impatiens capensis. We then measured interactions with mutualists (two pollinating species) and antagonists (herbivores, florivores, nectar thieves, and flower bud gallers), as well as plant growth, floral rewards, and plant reproduction. Fertilizer increased plant growth, floral attractiveness, mutualist and antagonist interactions, and plant reproduction. Shade had no effects, and soil moisture was negatively associated with plant growth and reproduction. All effects were additive. Mutualist and antagonist floral interactions both increased on fertilized plants, but antagonists increased at a greater rate, leading to a larger ratio of antagonist to mutualist interactions on fertilized plants. Despite having more antagonists, fertilized plants still had significantly higher reproduction, suggesting higher tolerance to antagonists. Abiotic effects can have consistent effects on antagonists and mutualists, and on both floral and leaf antagonists. However, tolerance to antagonisms increased in favorable conditions. Thus, the direct positive effects of favorable abiotic conditions on plants outweighed negative indirect effects via increased antagonisms, which may lead to selection to grow in high-nutrient microsites in spite of increased herbivory.

  16. Effect of D-003 on isoproterenol-induced myocardial necrosis in rats.

    Science.gov (United States)

    Carbajal, Daisy; Noa, Miriam; Molina, Vivian; Arruzazabala, Maria Lourdes; Más, Rosa; Mendoza, Sarahí; González, Jorge

    2003-01-01

    D-003 is a mixture of high-molecular-weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isoproterenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objective of this study was to determine whether D-003 shows protective effects against ISO-induced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25-400 mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5-200 mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investigated. D-003 administered as single doses dose-dependently decreased necrosis area, percent of infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, but only the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment with ASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs was unchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necrosis indicators in a dose-dependent manner, with results effective from 25 mg/kg to the highest dose tested, indicating that the repeated dose scheme was more effective to prevent the damage. It is concluded that D-003 shows a protective effect on the myocardial necrosis induced by ISO in rats.

  17. 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.

  18. [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.

  19. 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.

  20. Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

    Science.gov (United States)

    Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

    2013-11-28

    To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

  1. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    International Nuclear Information System (INIS)

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-01-01

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  2. 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

  3. The Role of Excitotoxic Programmed Necrosis in Acute Brain Injury

    Directory of Open Access Journals (Sweden)

    Denson G. Fujikawa

    2015-01-01

    Full Text Available Excitotoxicity involves the excessive release of glutamate from presynaptic nerve terminals and from reversal of astrocytic glutamate uptake, when there is excessive neuronal depolarization. N-methyl-d-aspartate (NMDA receptors, a subtype of glutamate receptor, are activated in postsynaptic neurons, opening their receptor-operated cation channels to allow Ca2+ influx. The Ca2+ influx activates two enzymes, calpain I and neuronal nitric oxide synthase (nNOS. Calpain I activation produces mitochondrial release of cytochrome c (cyt c, truncated apoptosis-inducing factor (tAIF and endonuclease G (endoG, the lysosomal release of cathepsins B and D and DNase II, and inactivation of the plasma membrane Na+–Ca2+ exchanger, which add to the buildup of intracellular Ca2+. tAIF is involved in large-scale DNA cleavage and cyt c may be involved in chromatin condensation; endoG produces internucleosomal DNA cleavage. The nuclear actions of the other proteins have not been determined. nNOS forms nitric oxide (NO, which reacts with superoxide (O2− to form peroxynitrite (ONOO−. These free radicals damage cellular membranes, intracellular proteins and DNA. DNA damage activates poly(ADP-ribose polymerase-1 (PARP-1, which produces poly(ADP-ribose (PAR polymers that exit nuclei and translocate to mitochondrial membranes, also releasing AIF. Poly(ADP-ribose glycohydrolase hydrolyzes PAR polymers into ADP-ribose molecules, which translocate to plasma membranes, activating melastatin-like transient receptor potential 2 (TRPM-2 channels, which open, allowing Ca2+ influx into neurons. NADPH oxidase (NOX1 transfers electrons across cellular membranes, producing O2−. The result of these processes is neuronal necrosis, which is a programmed cell death that is the basis of all acute neuronal injury in the adult brain.

  4. Allogeneic corneoscleral limbus tissue transplantation for treatment of the necrosis in porphyria eye disease

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2014-08-01

    Full Text Available Porphyria cutanea tarda (PCT with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these. Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.

  5. Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases

    Directory of Open Access Journals (Sweden)

    Li Xiang-Pan

    2015-01-01

    Full Text Available To analyze the therapeutic effect of bevacizumab on radiation-induced brain necrosis. Four radiation-induced brain necrosis patients, administered with bevacizumab at a dose of 7.5 mg/kg every 3 weeks, 2 times. One case of brain metastasis of lung cancer and one case of nasopharyngeal carcinoma with brain necrosis after radiotherapy. However, their physical signs disappeared after the treatment with bevacizumab. One case of brainstem lesion and one case of brain glioma patient showed a transient improvement in signs and symptoms after treatment with bevacizumab. Bevacizumab can significantly alleviate the radiation-induced brain edema, and can improve the symptoms successively.

  6. 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.

  7. Livedoid dermatitis and severe necrosis (Nicolau's syndrome) after intramuscular hydroxyzine injection.

    Science.gov (United States)

    Gayken, Jon; Westanmo, Anders; Knutsen, Amy; Ahrenholz, David H; Mohr, William J; Solem, Lynn D

    2006-01-01

    Nicolau's syndrome, also called embolica cutis medicamentosa, is characterized by well- circumscribed livedoid dermatitis with aseptic necrosis after intramuscular injection. We report the case of a 45-year-old woman with severe necrosis of the thigh several days after a routine intramuscular injection of hydroxyzine who was transferred to and treated at our Regional Burn Center. Although there has been one case report and numerous voluntarily reported instances of intramuscular hydroxyzine-induced necrosis to the Food and Drug Administration Spontaneous Reporting System, this phenomenon is rare.

  8. 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...

  9. First report of circulating microRNAs in tumour necrosis factor receptor-associated periodic syndrome (TRAPS.

    Directory of Open Access Journals (Sweden)

    Orso Maria Lucherini

    Full Text Available Tumor necrosis factor-receptor associated periodic syndrome (TRAPS is a rare autosomal dominant autoinflammatory disorder characterized by recurrent episodes of long-lasting fever and inflammation in different regions of the body, such as the musculo-skeletal system, skin, gastrointestinal tract, serosal membranes and eye. Our aims were to evaluate circulating microRNAs (miRNAs levels in patients with TRAPS, in comparison to controls without inflammatory diseases, and to correlate their levels with parameters of disease activity and/or disease severity. Expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and from 8 controls without inflammatory diseases. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software. We identified a 6 miRNAs signature able to discriminate TRAPS from controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukin (IL-1 receptor antagonist, anakinra, and untreated patients. Of these, miR-92a-3p and miR-150-3p expression was found to be significantly reduced in untreated patients, while their expression levels were similar to controls in samples obtained during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1(st year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA circulating levels. Our data suggest that serum miRNA levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention.

  10. 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.

  11. 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...

  12. Predictions of in vivo prolactin levels from in vitro k I values of d 2 receptor antagonists using an agonist-antagonist interaction model

    NARCIS (Netherlands)

    Petersson, K.J.; Vermeulen, A.M.J.; Friberg, L.E.

    2013-01-01

    Prolactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess

  13. Unexpected Potency Differences between B-Cell-Activating Factor (BAFF) Antagonist Antibodies against Various Forms of BAFF: Trimer, 60-Mer, and Membrane-Bound.

    Science.gov (United States)

    Nicoletti, Amy M; Kenny, Cynthia Hess; Khalil, Ashraf M; Pan, Qi; Ralph, Kerry L M; Ritchie, Julie; Venkataramani, Sathyadevi; Presky, David H; DeWire, Scott M; Brodeur, Scott R

    2016-10-01

    Therapeutic agents antagonizing B-cell-activating factor/B-lymphocyte stimulator (BAFF/BLyS) are currently in clinical development for autoimmune diseases; belimumab is the first Food and Drug Administration-approved drug in more than 50 years for the treatment of lupus. As a member of the tumor necrosis factor superfamily, BAFF promotes B-cell survival and homeostasis and is overexpressed in patients with systemic lupus erythematosus and other autoimmune diseases. BAFF exists in three recognized forms: membrane-bound and two secreted, soluble forms of either trimeric or 60-mer oligomeric states. To date, most in vitro pharmacology studies of BAFF neglect one or more of these forms. Here, we report a comprehensive in vitro cell-based analysis of BAFF in assay systems that measure all forms of BAFF-mediated activation. We demonstrate the effects of these BAFF forms in both a primary human B-cell proliferation assay and in nuclear factor κB reporter assay systems in Chinese hamster ovary cells expressing BAFF receptors and transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI). In contrast to the mouse system, we find that BAFF trimer activates the human TACI receptor. Further, we profiled the activities of two clinically advanced BAFF antagonist antibodies, belimumab and tabalumab. Unexpectedly, we revealed differences in inhibitory potencies against the various BAFF forms, in particular that belimumab does not potently inhibit BAFF 60-mer. Through this increased understanding of the activity of BAFF antagonists against different forms of BAFF, we hope to influence the discovery of BAFF antagonist antibodies with distinct therapeutic mechanisms for improvement in the treatment of lupus or other related autoimmune pathologies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. Association between tobacco smoking and response to tumour necrosis factor α inhibitor treatment in psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Glintborg, Bente; Hetland, Merete Lund

    2015-01-01

    OBJECTIVES: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses among patients with psoriatic arthritis (PsA) initiating the first tumour necrosis factor α inhibitor therapy (TNFi) in routine care. METHODS: Observational cohort...

  19. 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.

  20. The length of necrosis and renal insufficiency predict the outcome of acute mesenteric ischemia

    Directory of Open Access Journals (Sweden)

    Hızır Yakup Akyıldız

    2015-01-01

    Conclusion: The length of the necrosis and renal insufficiency are the primary factors that result in a poor outcome in AMI patients. Prompt diagnostic evaluation and early therapeutic interventions may help to prevent the development of these fatal predictors.

  1. Retroperitoneal laparoscopic debridement and drainage of infected retroperitoneal necrosis in severe acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Yuliang Tu

    2013-10-01

    Conclusion: Retroperitoneal laparoscopic debridement and drainage is an SAP surgical treatment with a minimally invasive procedure and a good effect, and can be applied for infected retroperitoneal necrosis in early SAP.

  2. HIV-associated fulminating herpes zoster infection with alveolar necrosis and tooth exfoliation: a case report.

    Science.gov (United States)

    Chindia, M L

    1997-04-01

    This paper presents a case of HIV-associated fulminating herpes zoster infection (HZI) that culminated in right mandibular necrosis and tooth exfoliation. The occurrence of such infection in immunosuppression and the impending clinical features are briefly reviewed and discussed.

  3. 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.

  4. 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

  5. [Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence].

    Science.gov (United States)

    Li, Yu-ming; Wang, Shi-xin; Gao, Hong-sheng; Wang, Jing-gui; Wei, Chuan-she; Chen, Li-ming; Hui, Wu-li; Yuan, Shu-ling; Jiao, Zhen-shan; Yang, Zhen; Su, Bin

    2004-08-17

    To explore the factors affecting the pathogenesis of avascular necrosis of femoral head and osteoporosis of SARS patients during convalescent stage. The clinical data of 40 SARS patients, 12 males and 28 females, aged 29 +/- 9, hospitalized from April to June 2003, were reviewed, targeted on the use of glucocorticoids. Three months after the discharge ELISA and indirect immunofluorescent antibody (IFA) assay were used to detect the serum IgG. Magnetic resonance imaging (MRI) was used to detect the damage of the head of femur and quantitative ultrasound (QUS) was used to detect osteoporosis at the left heel. The average total dosage of methylprednisolone was (4949 +/- 2959) mg, and the average course of treatment was (24 +/- 5) days (16 to 30 days). Twenty-three patients underwent ictus therapy of corticosteroids for (8 +/- 4) days. The extenuation time of corticosteroid' dosage was (33 +/- 26) mg/d. Of the 40 patients, 36 were IgG positive with an average A value of (0.91 +/- 0.24) and 4 patients were IgG negative. Twelve patients (30%) were with type I avascular necrosis of femoral head, including 3 cases with unilateral left--necrosis and 9 cases of bilateral necrosis. The other 28 patients were without necrosis. Two patients were suffering from osteoporosis and 30 patients were with bone density decrement. The average Z values of the parameter BUA and VOS were (-1.26 +/- 0. 53) and (-0.53 +/- 0.30) respectively. The corresponding T values of the parameter BUA and VOS were (-1.49 +/- 0.59) and (-0.65 +/- 0.05) respectively. The influencing factors of femoral necrosis included the degree of healing activity, the dosage summation of corticosteroids, and length of ictus therapy. The influencing factors of bone density included age, dosage summation, and length of ictus therapy. The influencing factors of the bone fabric and flexibility included the use and length of ictus therapy. Statistics showed that serum IgG was not related with avascular necrosis of femoral

  6. 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

  7. 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.

  8. 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

  9. Classification and virtual screening of androgen receptor antagonists.

    Science.gov (United States)

    Li, Jiazhong; Gramatica, Paola

    2010-05-24

    Computational tools, such as quantitative structure-activity relationship (QSAR), are highly useful as screening support for prioritization of substances of very high concern (SVHC). From the practical point of view, QSAR models should be effective to pick out more active rather than inactive compounds, expressed as sensitivity in classification works. This research investigates the classification of a big data set of endocrine-disrupting chemicals (EDCs)-androgen receptor (AR) antagonists, mainly aiming to improve the external sensitivity and to screen for potential AR binders. The kNN, lazy IB1, and ADTree methods and the consensus approach were used to build different models, which improve the sensitivity on external chemicals from 57.1% (literature) to 76.4%. Additionally, the models' predictive abilities were further validated on a blind collected data set (sensitivity: 85.7%). Then the proposed classifiers were used: (i) to distinguish a set of AR binders into antagonists and agonists; (ii) to screen a combined estrogen receptor binder database to find out possible chemicals that can bind to both AR and ER; and (iii) to virtually screen our in-house environmental chemical database. The in silico screening results suggest: (i) that some compounds can affect the normal endocrine system through a complex mechanism binding both to ER and AR; (ii) new EDCs, which are nonER binders, but can in silico bind to AR, are recognized; and (iii) about 20% of compounds in a big data set of environmental chemicals are predicted as new AR antagonists. The priority should be given to them to experimentally test the binding activities with AR.

  10. 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

  11. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

    DEFF Research Database (Denmark)

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... by TNFR1 deficiency. Overall, these results suggest that TNFR1 is involved in the early establishment of the inflammatory response and that its deficiency causes a decreased inflammatory response and tissue damage following brain injury....

  12. Comparative Transcriptome Analysis to Reveal Genes Involved in Wheat Hybrid Necrosis

    OpenAIRE

    Zhang, Yong; Cheng, Yan; Guo, Jiahui; Yang, Ennian; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Zhou, Jianping

    2014-01-01

    Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469) were investigated using digital gene expression (DGE). A total of 1300 differentially expressed genes were identified, indicating that the response ...

  13. 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

  14. Real-time magnetic resonance imaging texture characterization of necrosis during laser interstitital thermotherapy procedures

    Science.gov (United States)

    Betrouni, N.; Lopes, R.; Colin, P.; Mordon, S.

    2010-02-01

    This paper aims to describe the development of a method to monitor laser interstitial thermo therapy by MR images. The method is based on the texture analysis using fractal geometry features of the images to estimate the size of the induced necrosis. The method was validated by comparing the results to macroscopic measurements. It demonstrates the ability to achieve good estimation of the necrosis in ex-vivo experimentations involving pig liver and in vivo experimentations done on tumors grown on Copenhagen rats.

  15. 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.)

  16. 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.

  17. Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.

    Science.gov (United States)

    Torres, Jaime R; Córdova, Leopoldo G; Saravia, Víctor; Arvelaez, Joanne; Castro, Julio S

    2016-01-01

    Three adult Venezuelan patients with virologically confirmed Chikungunya fever, who developed extensive acute nasal skin necrosis early in the course of a life-threatening illness characterized by shock and multiple organ dysfunction syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis has not previously been associated with the disease. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. 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.

  19. Synthesis of carbon-11 labelled calcium channel antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Holschbach, M.; Roden, W.; Hamkens, W. (Kernforschungsanlage Juelich GmbH (Germany). Inst. fuer Medizin)

    1991-04-01

    A useful synthetic approach to carbon-11 labelled 1,4-dihydropyridines is described. Carbon-11 labelled calcium channel antagonists {sup 11}C-Nifedipine, {sup 11}C-Nisoldipine, {sup 11}C-nitrendipine and {sup 11}C-CF{sub 3}-Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with {sup 11}CH{sub 3}I produced the labelled compounds in very good chemical and radiochemical yields (94%). (author).

  20. 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...

  1. Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists

    DEFF Research Database (Denmark)

    Pottegård, Anton; Christensen, R. D.; Wang, S. 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...... definitions, and other drugs. ResultsWe identified 513 VKA users with at least 1 INR measurement 4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53-2.10), with a stronger association among users of phenprocoumon compared...

  2. ANTIHYPERTENSIVE TREATMENT IN ELDERLY PATIENTS WITH DIHYDROPYRIDINE CALCIUM ANTAGONISTS

    Directory of Open Access Journals (Sweden)

    Y. A. Karpov

    2006-01-01

    Full Text Available The proofs of necessity of active arterial hypertension (AH treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Analysis of target levels of blood pressure for antihypertensive treatment in elderly hypertensive patients is made. As a conclusion DPCA are the medicines of choice for AH treatment in elderly patients.

  3. 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.

  4. Comparative Transcriptome Analysis to Reveal Genes Involved in Wheat Hybrid Necrosis

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2014-12-01

    Full Text Available Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469 were investigated using digital gene expression (DGE. A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO revealed that most of the up-regulated genes belong to “universal stress related”, “DNA/RNA binding”, “protein degradation” functional groups, while the down-regulated genes belong to “carbohydrate metabolism” and “translation regulation” functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  5. Comparative transcriptome analysis to reveal genes involved in wheat hybrid necrosis.

    Science.gov (United States)

    Zhang, Yong; Cheng, Yan; Guo, Jiahui; Yang, Ennian; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Zhou, Jianping

    2014-12-16

    Wheat hybrid necrosis is an interesting genetic phenomenon that is found frequently and results in gradual death or loss of productivity of wheat. However, the molecular basis and mechanisms of this genetic phenomenon are still not well understood. In this study, the transcriptomes of wheat hybrid necrosis F1 and its parents (Neimai 8 and II469) were investigated using digital gene expression (DGE). A total of 1300 differentially expressed genes were identified, indicating that the response to hybrid necrosis in wheat is complicated. The assignments of the annotated genes based on Gene Ontology (GO) revealed that most of the up-regulated genes belong to "universal stress related", "DNA/RNA binding", "protein degradation" functional groups, while the down-regulated genes belong to "carbohydrate metabolism" and "translation regulation" functional groups. These findings suggest that these pathways were affected by hybrid necrosis. Our results provide preliminarily new insight into the underlying molecular mechanisms of hybrid necrosis and will help to identify important candidate genes involved in wheat hybrid necrosis.

  6. 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.)

  7. Imaging of avascular necrosis of femoral head: familiar methods and newer trends.

    Science.gov (United States)

    Stoica, Zoia; Dumitrescu, Daniela; Popescu, M; Gheonea, Ioana; Gabor, Mihaela; Bogdan, N

    2009-01-01

    Avascular necrosis of the femoral head (AVN) is an increasingly common cause of musculoskeletal disability, and it poses a major diagnostic and therapeutic challenge. Although patients are initially asymptomatic, AVN usually progresses to joint destruction, requiring total hip replacement, usually before the fifth decade. Avascular necrosis is characterized by osseous cell death due to vascular compromise. Avascular necrosis of bone results generally from corticosteroid use, trauma, pancreatitis, alcoholism, radiation, sickle cell disease, infiltrative diseases (e.g. Gaucher's disease), and Caisson disease. The most commonly affected site is the femoral head and patients usually present with hip and referred knee pain. The aim of diagnostic imaging procedures in avascular femoral head necrosis is to provide the patient with a stage-adapted therapy. Therefore, a differentiated diagnostic work-up is needed. Native radiography of the hip in two planes is still the first step. Over the past years, the diagnosis of femoral head necrosis has experienced tremendous improvement due to the use of MRI and CT scans. Because of these improvements the correct stage can be diagnosed early and the appropriate therapy can be initiated immediately. Today, MRI is the most sensitive diagnostic imaging procedure. CT scans can be particularly useful to exclude subchondral fractures. The use of bone scintigraphy is restricted to exceptional cases. In Europe, the ARCO classification of avascular femoral head necrosis has been widely accepted. In this overview, we describe the specific characteristics of the different diagnostic imaging procedures and illustrate them with appropriate imaging material.

  8. Serial imaging of bilateral striatal necrosis associated with acidaemia in adults

    International Nuclear Information System (INIS)

    Kamei, S.; Takasu, T.; Mori, N.; Yoshihashi, K.; Shikata, E.

    1996-01-01

    Bilateral striatal necrosis in acute encephalopathy has been reported in a small number of adults with methanol or cyanide intoxication, hypoxic encephalopathy or haemolytic-uraemic syndrome. Acute encephalopathy with bilateral striatal necrosis has been reported in infants and children. However, the pathogenesis of the necrosis remains unclear. This is the first report of serial imaging from the very early yo chronic stage in two acute encephalopathic adults with bilateral striatal necrosis. A clinicoradiological study is presented for clarification of the pathological process and pathogenesis. Striatal lesions were not detected in the very early stages, but only thereafter. Serial studies suggested that the lesions were caused by delayed neuronal death. These patients had severe lactic acidosis, near the limit for survival. There hav ebeen few reports of adults with acute encephalopathy and bilateral striatal necrosis in whom arterial pH was described; all these exhibited marked acidosis. The common pathophysiological condition among these encephalopathies with bilateral striatal necrosis could be lactic acidosis elicited by impairnment of ATP generation through the Krebs cycle. The striatum might represent one of the target areas of Krebs-cycle blockade. (orig.)

  9. Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization

    International Nuclear Information System (INIS)

    Sonomura, Tetsuo; Yamada, Ryusaku; Kishi, Kazushi; Nishida, Norifumi; Yang, Ren J.; Sato, Morio

    1997-01-01

    Purpose. To determine the optimal size of gelatin sponge particles (GSPs) to produce maximum tumor necrosis with minimum side effects after canine hepatic artery embolization (HAE). Methods. GSPs were separated into four size ranges: A, up to 200 μm (mean 152) as Gelfoam powder; B, 200-500 μm (mean 336) as Gelfoam powder; C, 500-1000 μm (mean 649) as Spongel; and D, 1000-2000 μm (mean 1382) as Spongel. Three mongrel dogs were assigned randomly to HAE with each particle size. On day 7 after HAE, the livers were removed and subjected to pathological examination. Results. The mean volume of liver necrosis was 11% after embolization, with particle size A, 36.3% with B, 0% with C, and 1% with D. Coagulation necrosis was found in all livers with particles of sizes A and B, and in 1 of 6 with sizes C and D. Bile duct injury was found in five of six dogs with sizes A and B and in none with sizes C and D. Gallbladder necrosis was found in one dog with size B and pancreas necrosis in one with size A. Conclusion. GSPs of 500 μm are considered optimally effective for tissue necrosis according to this model

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Histamine H1 antagonists and clinical characteristics of febrile seizures.

    Science.gov (United States)

    Zolaly, Mohammed A

    2012-01-01

    The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever. Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine. Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.

  15. 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.

  16. Human Homosexuality: A Paradigmatic Arena for Sexually Antagonistic Selection?

    Science.gov (United States)

    Ciani, Andrea Camperio; Battaglia, Umberto; Zanzotto, Giovanni

    2015-01-01

    Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait. PMID:25635045

  17. Biological Control of Sclerotinia sclerotiorum in Lettuce Using Antagonistic Bacteria

    Directory of Open Access Journals (Sweden)

    Bong-Goan Chon

    2013-03-01

    Full Text Available To isolate antagonistic bacteria against sclerotinia rot of lettuce, caused by Sclerotinia sclerotiorum, soil samples were collected from the diseased greenhouse field in Namyangju city, Gyeong-gi province from 2007 to 2008. A total of 196 bacterial isolates were isolated using serial dilution method. In dual culture assay in vitro, 26 isolates showed more than 80% of inhibition rates of mycelial growth of S. sclerotiorum. Based on 16S rDNA sequence analysis, the 26 isolates were identified as Bacillus megaterium, B. cereus, B. subtilis, Arthrobacter nicotianae, A. ramosus, Pseudomonas filiscindens, Stenotrophomonas maltophilia, Brevibacterium frigoritolerans and Sphingobacterium faecium. The 26 isolates inhibited the mycelial growth of S. sclerotiorum up to 80% and the sclerotial germination 0−100%. In the greenhouse pot test of ten isolates conducted in summer, 2 isolates B. megaterium (DK6 and B. cereus (C210 showed control efficacy on sclerotia viability of S. sclerotiorum, 20% and 35%, respectively. In the greenhouse pot test in winter, the disease incidence of the control group was 80%, whereas those of 9 isolates among 26 were approximately 20%. From the result, the 9 isolates are expected as potentially antagonistic bacteria for biological control of sclerotinia rot of lettuce caused by S. sclerotiorum.

  18. Discovery of Novel Proline-Based Neuropeptide FF Receptor Antagonists.

    Science.gov (United States)

    Nguyen, Thuy; Decker, Ann M; Langston, Tiffany L; Mathews, Kelly M; Siemian, Justin N; Li, Jun-Xu; Harris, Danni L; Runyon, Scott P; Zhang, Yanan

    2017-10-18

    The neuropeptide FF (NPFF) system has been implicated in a number of physiological processes including modulating the pharmacological activity of opioid analgesics and several other classes of drugs of abuse. In this study, we report the discovery of a novel proline scaffold with antagonistic activity at the NPFF receptors through a high throughput screening campaign using a functional calcium mobilization assay. Focused structure-activity relationship studies on the initial hit 1 have resulted in several analogs with calcium mobilization potencies in the submicromolar range and modest selectivity for the NPFF1 receptor. Affinities and potencies of these compounds were confirmed in radioligand binding and functional cAMP assays. Two compounds, 16 and 33, had good solubility and blood-brain barrier permeability that fall within the range of CNS permeant candidates without the liability of being a P-glycoprotein substrate. Finally, both compounds reversed fentanyl-induced hyperalgesia in rats when administered intraperitoneally. Together, these results point to the potential of these proline analogs as promising NPFF receptor antagonists.

  19. Opioid antagonists in broadly defined behavioral addictions: a narrative review.

    Science.gov (United States)

    Piquet-Pessôa, Marcelo; Fontenelle, Leonardo F

    2016-01-01

    Naltrexone (NTX), a mu-opioid receptor antagonist, has been approved for the treatment of alcoholism and opioid dependence. More recently, however, NTX and a related drug, nalmefene (NMF), have also shown positive results for the treatment of gambling disorders. In this study, we reviewed the trials testing the effect of opioid antagonists (OA) in gambling disorders and in other broadly defined behavioral addictions, including selected DSM-5 disruptive, impulse-control, and conduct disorders, obsessive-compulsive and related disorders, eating disorders, and other conditions not currently recognized by official classification schemes. We found six randomized controlled trials (RCTs) of OA in gambling disorder, two RCTs of OA in trichotillomania (hair pulling disorder), two RCTs of OA in binge eating disorder, and one RCT of OA for kleptomania. We also reviewed case reports on hypersexual disorder, compulsive buying and skin picking disorders. The reviewed data supported the use of OA, namely NTX and NMF, in gambling disorder (both) and kleptomania (NTX). We did not find enough evidence to support the use of NTX or NMF in trichotillomania (hair pulling disorder), excoriation (skin-picking) disorder, compulsive buying disorder, hypersexual disorder, or binge eating disorder.

  20. Human homosexuality: a paradigmatic arena for sexually antagonistic selection?

    Science.gov (United States)

    Camperio Ciani, Andrea; Battaglia, Umberto; Zanzotto, Giovanni

    2015-01-29

    Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. 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.

  2. 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

  3. 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

  4. CALCIUM ANTAGONISTS IN CLINICAL PRACTICE: FOCUS ON METABOLIC AND VASCULAR EFFECTS

    OpenAIRE

    D. V. Nebieridze

    2007-01-01

    The efficacy of calcium antagonists widely used in cardiological practice is proved both by placebo-controlled studies and in comparative trials with end-point control. Calcium antagonists are the most effective vasoprotective medicines. In our study we had shown antihypertensive efficacy and ability to improve endothelium function of non-dihydropyridine calcium antagonist, diltiazem (Altiazem RR). Altiazem RR can be drug of choice in wide profile of patients with arterial hypertension, espec...

  5. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

    OpenAIRE

    S. Y. Martsevich

    2015-01-01

    The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antag...

  6. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

    OpenAIRE

    S. Y. Martsevich

    2007-01-01

    The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antag...

  7. How European cardiologists perceive the role of calcium antagonists in follow-up after myocardial infarction

    OpenAIRE

    Opie, L. H.; Lüscher, T. F.; Ferrari, R.; Hansen, J. Fischer

    2017-01-01

    About one hundred European cardiologists discussed the role of calcium antagonists in the follow-up management of myocardial infarction, β-blockers are the treatment of choice. Where these are contra-indicated or otherwise unsuitable, many clinicians would use a non-dihydropyridine calcium antagonist alone or in combination with an ACE inhibitor. There is broad agreement that calcium antagonists should not be used in patients with concomitant left ventricular failure. Cholesterol estimation i...

  8. Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt

    OpenAIRE

    Chen, Yi-Cun; Zhu, Wei; Zhong, Shu-Ping; Zheng, Fu-Chun; Gao, Fen-Fei; Zhang, Yan-Mei; Xu, Han; Zheng, Yan-Shan; Shi, Gang-Gang

    2015-01-01

    BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. ...

  9. CALCIUM ANTAGONISTS IN CLINICAL PRACTICE: FOCUS ON METABOLIC AND VASCULAR EFFECTS

    OpenAIRE

    D. V. Nebieridze

    2015-01-01

    The efficacy of calcium antagonists widely used in cardiological practice is proved both by placebo-controlled studies and in comparative trials with end-point control. Calcium antagonists are the most effective vasoprotective medicines. In our study we had shown antihypertensive efficacy and ability to improve endothelium function of non-dihydropyridine calcium antagonist, diltiazem (Altiazem RR). Altiazem RR can be drug of choice in wide profile of patients with arterial hypertension, espec...

  10. Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats

    DEFF Research Database (Denmark)

    Huang, W.; Sjöquist, M.; Skøtt, O.

    2001-01-01

    antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted...... afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats....

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Design of potent and specific integrin antagonists. Peptide antagonists with high specificity for glycoprotein IIb-IIIa.

    Science.gov (United States)

    Scarborough, R M; Naughton, M A; Teng, W; Rose, J W; Phillips, D R; Nannizzi, L; Arfsten, A; Campbell, A M; Charo, I F

    1993-01-15

    Members of the snake venon-derived, "disintegrin" peptide family containing the Arg-Gly-Asp (RGD) amino acid sequence are among the most potent inhibitors of the binding of adhesive proteins to platelet glycoprotein (GP) IIb-IIIa. However, GPIIb-IIIa antagonists containing the RGD sequence are not integrin specific and inhibit the adhesive functions of many other RGD-dependent integrins. The single disintegrin peptide, barbourin, containing a conservative amino acid substitution of Lys (K) for Arg (R) in the RGD sequence, is however, highly specific for GPIIb-IIIa. Using this information we have tested the hypothesis that both structural and conformational elements of barbourin are important for its high affinity and selectivity for platelet GPIIb-IIIa by synthesizing a series of conformationally constrained, disulfide-bridged peptides containing the KGD amino acid sequence. Incorporation of the KGD sequence into a cyclic peptide template, followed by systematic optimization of the cyclic ring size, optimization of secondary hydrophobic binding site interactions, and the derivatization of the lysyl side chain functionality of the KGD sequence has resulted in peptide analogs which display inhibitory potency and GPIIb-IIIa selectivity comparable to that of barbourin. This study demonstrates that the specificity and potency of the disintegrin family of antagonists, in particular barbourin, can be mimicked by small, conformationally restrained peptides.

  16. Functionalized Congeners of P2Y1 Receptor Antagonists:

    Energy Technology Data Exchange (ETDEWEB)

    de Castro, Sonia [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Maruoka, Hiroshi [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hong, Kunlun [ORNL; Kilbey, II, S Michael [ORNL; Costanzi, Stefano [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hechler, Béatrice [University of Strasbourg; Gachet, Christian [EFS-Alsace, Strasbourg, France; Harden, T. Kendall [University of North Carolina School of Medicine; Jacobson, Kenneth A. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor

  17. Clinical experience in Europe with uroselective alpha1-antagonists.

    Science.gov (United States)

    Debruyne, F M; Van der Poel, H G

    1999-01-01

    alpha1-Adrenoreceptors are thought to be involved in prostate smooth muscle contractions and could hence play a role in the dynamic component of intravesical obstruction associated with symptomatic BPH. Consequently, since the mid-eighties alpha receptor blocking agents have been used for the treatment of BPH. Non-selective alpha blockers are usually associated with systemic side-effects which resulted in an exclusion or withdrawal of many patients from this form of treatment. With the availability of so-called uroselective alpha blockers the management picture has changed since it was anticipated that these compounds cause lesser side-effects with at least the same, or even better, efficacy. Comparative clinical studies are essential for determining the eventual advantages of the uroselective alpha1-antagonists and a large number of such studies have been performed worldwide studying the various available compounds. European studies with terazosin showed clear superiority of the drug over the placebo while causing only limited side-effects. Various other studies using alpha-blocking agents such as doxazosin, tamsulosin and alfuzosin yielded identical results. Especially with tamsulosin and alfuzosin, the side-effects were comparable with those encountered in the placebo group. About 7% of the patients using tamsulosin experienced retrograde ejaculation in one study which did not occur in the alfuzosin studies. Important studies in Europe have also investigated the value of a combination of an alpha blocker with a 5alpha-reductase inhibitor. Comparable studies in which both alfuzosin and doxazosin were combined with the 5alpha-reductase inhibitor Proscar have shown that a combination is not superior to a blocker monotherapy and especially in the ALFIN study the results show that alfuzosin monotherapy is superior to Proscar in the management of symptomatic BPH. European studies have evaluated Quality of Life, sexuality as well as socio-economical outcome of the

  18. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

  19. Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death

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    Evgeniy R. Galimov

    2018-03-01

    Full Text Available Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence. Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC. This phenomenon is accompanied by a wave of intramuscular Ca2+ release and, subsequently, of intestinal necrosis. Correlation of directions of the DC and intestinal necrosis waves implies coupling of these death processes. Long-lived insulin/IGF-1-signaling mutants show reduced DC and delayed intestinal necrosis, suggesting possible resistance to organismal death. DC resembles mammalian rigor mortis, a postmortem necrosis-related process in which Ca2+ influx promotes muscle hyper-contraction. In contrast to mammals, DC is an early rather than a late event in C. elegans organismal death.

  20. A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

    Directory of Open Access Journals (Sweden)

    Juan Lin

    2013-01-01

    Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.