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Sample records for bep protocol bleomycin

  1. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer : intergroup study EORTC 30983

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona

    2012-01-01

    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).

  2. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske; De Santis, Maria; Garin, August; Aass, Nina; Witjes, Alfred J; Albers, Peter Hjorth; White, Jeffery D; Germa-Lluch, José R; Marreaud, Sandrine; Collette, Laurence

    2012-01-01

    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).......To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC)....

  3. Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and cisplatin): case report / Trombose venosa profunda extensa como complicação de um tumor do testículo tratado com o protocolo BEP (cisplatina, bleomicina e etoposide): relato de caso

    Scientific Electronic Library Online (English)

    Max Senna, Mano; José Luiz Miranda, Guimarães; Sören Franz Marian Chicata, Sutmöller; André Borba, Reiriz; Christian Sandor Svend Chicata, Sutmöller; Angelo, Di Leo.

    2006-11-01

    Full Text Available CONTEXTO: Não há relatos na literatura de trombose venosa profunda (TVP) extensa associada ao protocolo de quimioterapia cisplatina, bleomicina e etoposite (BEP). RELATO DO CASO: O paciente era um adolescente de 18 anos com um tumor germinativo não-seminomatoso no testículo direito, com metástases p [...] ulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira para TVP). No quarto dia do ciclo, TVP massiva foi diagnosticada, estendendo-se das veias poplíteas até o segmento inferior da veia cava torácica. Tratamento trombolítico foi iniciado imediatamente com estreptoquinase. No segundo dia da terapia trombolítica, o paciente desenvolveu insuficiência renal aguda, devido ao acometimento das veias renais pela trombose. Estroptoquinase foi mantida por seis dias e o paciente teve evolução surpreendentemente favorável. Abstract in english CONTEXT: There are no reports in the literature of massive deep venous thrombosis (DVT) associated with cisplatin, bleomycin and etoposide (BEP) cancer treatment. CASE REPORT: The patient was a 18-year-old adolescent with a nonseminomatous germ cell tumor of the right testicle, with the presence of [...] pulmonary, liver, and massive retroperitoneal metastases. Following radical orchiectomy, the patient started chemotherapy according to the BEP protocol (without routine prophylaxis for DVT). On day 4 of the first cycle, massive DVT was diagnosed, extending from both popliteal veins up to the thoracic segment of the inferior vena cava. Thrombolytic therapy with streptokinase was immediately started. On day 2 of thrombolytic therapy, the patient developed acute renal failure, due to extension of the thrombosis to the renal veins. Streptokinase was continued for six days and the outcome was remarkably favorable.

  4. The effects of chemotherapy with bleomycin, etoposide, and cis-platinum (BEP) on rat sperm chromatin remodeling, fecundity and testicular gene expression in the progeny.

    Science.gov (United States)

    Maselli, Jennifer; Hales, Barbara F; Robaire, Bernard

    2013-10-01

    During spermiogenesis, histones are replaced first by transition proteins and then by protamines, resulting in a very condensed sperm DNA structure that is absolutely critical for normal sperm function. We have demonstrated previously that, despite a 9-wk recovery period, mature sperm from rats treated for 9 wk with bleomycin, etoposide, and cis-platinum (BEP), the drugs used to treat testicular cancer, have reduced levels of protamine 1 and a concomitant upregulation of specific histones, highlighting a problem in histone eviction. Here, we demonstrate that regulators of histone removal are increased in elongating spermatids following recovery; however, Ac-H4 and gamma H2AX histones remain elevated in elongating spermatids or caudal epididymal spermatozoa 9 wk post-BEP treatment. This indicates that chromatin remodelers and effector proteins that respond to histone removal cues may be a target of BEP treatment. A decrease in the expression of SMARCE1 in elongating spermatids may explain the persistent retention of histones in cauda epididymal sperm 9 wk after the cessation of BEP treatment. Remarkably, proteins implicated in the translational control and posttranslational processing of protamine 1 are also significantly elevated 9 wk post-BEP treatment, suggesting that histone eviction may dictate the DNA availability for protamine binding. Males mated to control females 9 wk after BEP treatment have reduced litter sizes; moreover, the profile of gene expression in the developing testes of their pups is altered. Altering the proportion of histones to protamine in mature spermatozoa has an adverse impact on male fecundity, with modifications to epigenetic marks potentially threatening normal progeny development. PMID:23986570

  5. Radioiodinated bleomycin

    International Nuclear Information System (INIS)

    Radioiodinated bleomycin is a useful imaging agent for body tissues. Its production by iodination of bleomycin with radioactive iodide ions in the presence of an oxidizing agent is described. 7 claims, no drawings

  6. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria Gry Gundgaard; Bandak, Mikkel; Mortensen, Mette Saksø; Thomsen, Frederik Birkebæk; Mortensen, Jann; Daugaard, Gedske

    2016-01-01

    PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring...... expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all...... PFT. CONCLUSION: After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group....

  7. Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics.

    Science.gov (United States)

    2004-01-01

    Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions. Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy. In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001. In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted. The MedPulsar Electroporation Therapy System with bleomycin is currently in phase III pivotal studies in the US as a treatment for recurrent and second primary squamous cell carcinomas of the head and neck. Genetronics received approval for the Electroporation Therapy system as a device in March 1999 when it achieved CE Mark certification. In February 2004, Genetronics announced that it had completed a Special Protocol Assessment review process with the US FDA for two new trials that will compare bleomycin electroporation therapy to surgery. The primary endpoint will be tissue and function preservation rather than survival. One proposal is for recurrent head and neck cancer, and the other is for disfiguring cutaneous cancer. Three Institutional Review Boards in the US have approved the two protocols and Genetronics has initiated enrollment. In June 2004, Genetronics was granted fast-track status for its MedPulsar Electroporation Therapy System clinical development programme for patients with head and neck cancer. Shifting from a primary endpoint of survival to a quality-of-life outcome will enable those clinical trials to be carried out faster with less cost and with a higher likelihood of success. As a result, Genetronic's phase III trials focussing on survival as a primary endpoint have been discontinued. This includes a phase III trial for late-stage, recurrent head and neck cancer in combination with the normal standard of treatment compared with normal standard of treatment alone. Interim results from this trial had suggested bleomycin electroporation therapy demonstrated local tumour control and preservation of organ function, as well as non-inferiority when compared with surgery. This trial was initiated in May 2002. In March 2004, Genetronics initiated a post-European regulatory approval clinical study in patients with primary or recurrent squamous cell carcinoma of the head and neck (SCCHN). This study aims to enroll approximately 100 patients at 12-15 hospitals located in the UK, Germany, Italy, France, Austria and other western European countries. The study is designed to support the commercialisation o

  8. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC). Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual.

  9. Progress of Bep Treatments on Nb at JLAB

    Energy Technology Data Exchange (ETDEWEB)

    A.T. Wu, S. Jin, R.A. Rimmer,X.Y. Lu, K. Zhao

    2010-05-01

    Recent experimental results have indicated that Buffered Electropolishing (BEP) is a promising candidate for the next generation of surface treatment technique for Nb superconducting radio frequency (SRF) cavities to be used in particle accelerators. In order to lay the foundation for using BEP as the next generation surface treatment technique for Nb SRF cavities, some fundamental aspects of BEP treatments for Nb have to be investigated. In this report, recent progress on BEP study at JLab is shown. Improvements on the existing vertical BEP are made to allow water cooling from outside of a Nb single cell cavity in addition to cooling provided by acid circulation so that the temperature of the cavity can be stable during processing. Some investigation on the electrolyte mixture was performed to check the aging effect of the electrolyte. It is shown that good polishing results can still be obtained on Nb at a current density of 171 mA/cm when the BEP electrolyte was at the stationary condition and was more than 1.5 years old.

  10. Metastatic testicular cancer presenting with liver and kidney dysfunction treated with modified BEP chemotherapy combined with continuous hemodiafiltration and rasburicase.

    Science.gov (United States)

    Kimakura, Mai; Abe, Toyofumi; Nagahara, Akira; Fujita, Kazutoshi; Kiuchi, Hiroshi; Uemura, Motohide; Nonomura, Norio

    2016-04-01

    A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum ?-fetoprotein (11?997?ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively. PMID:26736135

  11. Bleomycin-induced flagellate dermatitis

    Scientific Electronic Library Online (English)

    Guilherme Devidé, Mota; Adriana Marques Damasco, Penna; Regina Cláudia, Soares; Otávio Carvalho Guimarães, Baiocchi.

    2014-07-01

    Full Text Available A 29-year-old woman with stage IVB Hodgkin's lymphoma was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine. Two weeks after the first cycle was completed, she developed pruritic, linear erythematous lesions in a flagellate-like pattern on the trunk, neck and arms. After oral prednis [...] one therapy and cessation of bleomycin, the lesions started to recede.

  12. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference to the tolerability and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database search without date restriction was performed and over 500 articles were found. Twenty-five articles were us...

  13. Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG): toward integrated treatment of symptoms related to traumatic loss

    Science.gov (United States)

    Smid, Geert E.; Kleber, Rolf J.; de la Rie, Simone M.; Bos, Jannetta B. A.; Gersons, Berthold P. R.; Boelen, Paul A.

    2015-01-01

    Background Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD) with comorbid (symptoms of) posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends). Current evidence-based treatments for PTSD do not focus on traumatic grief. Objective To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. Method To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG) for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. Results Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. Conclusion Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components. PMID:26154434

  14. Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG: toward integrated treatment of symptoms related to traumatic loss

    Directory of Open Access Journals (Sweden)

    Geert E. Smid

    2015-07-01

    Full Text Available Background: Traumatic events such as disasters, accidents, war, or criminal violence are often accompanied by the loss of loved ones, and may then give rise to traumatic grief. Traumatic grief refers to a clinical diagnosis of persistent complex bereavement disorder (PCBD with comorbid (symptoms of posttraumatic stress disorder (PTSD and/or major depressive disorder (MDD following confrontation with a traumatic loss. Trauma survivors, who are frequently from different cultural backgrounds, have often experienced multiple losses and ambiguous loss (missing family members or friends. Current evidence-based treatments for PTSD do not focus on traumatic grief. Objective: To develop a treatment for traumatic grief combining treatment interventions for PTSD and PCBD that may accommodate cultural aspects of grief. Method: To provide a rationale for treatment, we propose a cognitive stress model of traumatic grief. Based on this model and on existing evidence-based treatments for PTSD and complicated grief, we developed Brief Eclectic Psychotherapy for Traumatic Grief (BEP-TG for the treatment of patients with traumatic grief. The treatment is presented along with a case vignette. Results: Processes contributing to traumatic grief include inadequately integrating the memory of the traumatic loss, negative appraisal of the traumatic loss, sensitivity to matching triggers and new stressors, and attempting to avoid distress. BEP-TG targets these processes. The BEP-TG protocol consists of five parts with proven effectiveness in the treatment of PCBD, PTSD, and MDD: information and motivation, grief-focused exposure, memorabilia and writing assignments, finding meaning and activation, and a farewell ritual. Conclusion: Tailored to fit the needs of trauma survivors, BEP-TG can be used to address traumatic grief symptoms related to multiple losses and ambiguous loss, as well as cultural aspects of bereavement through its different components.

  15. Bleomycin treatment of brain tumors: an evaluation

    DEFF Research Database (Denmark)

    Linnert, Mette; Gehl, Julie

    2009-01-01

    Bleomycin has been used in the treatment of brain tumors for over 30 years. Currently, we are evaluating electrochemotherapy (the use of electric pulses to enhance uptake of bleomycin) for patients with secondary brain tumors. We, therefore, reviewed the literature with specific reference to the...... tolerability and toxicity of bleomycin. Using the keywords 'brain' and 'bleomycin', a database search without date restriction was performed and over 500 articles were found. Twenty-five articles were used for this study based on relevance determined by: (i) clinical studies, (ii) use of bleomycin, and (iii...

  16. Labeled bleomycin as a tumor localizing agent

    International Nuclear Information System (INIS)

    The antitumor antibiotics bleomycins labeled with 57Co are known to possess excellent tumor localizing properties but the rather long halflife of 57Co prevents its use in clinical routine. It is therefore desirable to label cobalt-bleomycin with a more suitable radionuclide, e.g. 123I. This thesis reports on further studies on cobalt-bleomycin. It appears from the studies on the structure of cobalt-bleomycin described in this thesis (Chapter B), that cobalt is able to form different complexes with bleomycin (the forms I and II). The difference in structure is not clear, but the biological behavior of both forms is studied (Chapter C). In Chapter D the iodination of cobalt-bleomycin is described. Iodination of free bleomycin yields a product with bad tumor localizing properties, and straight-on iodination of cobalt-bleomycin is prevented by the presence of cobalt. To retain the good tumor-localizing properties of cobalt-bleomycin, possibilities were explored to incorporate the iodine in the terminal amine (a side chain, not involved in complexation). Alkylation of cobalt-bleomycin demethyl A2 with N-bromoacetyl-3-iodoaniline yielded a product; unfortunately this product possessed bad tumor localizing properties and moreover, was not stable in vivo. The structure of a possibly successful iodinated cobalt-bleomycin is outlined but could not be realized during this research. (Auth.)

  17. BEPS redesign of 168 commercial buildings: summary report

    Energy Technology Data Exchange (ETDEWEB)

    Stoops, J.L.; Deringer, J.J.; Moreno, S.; Misuriello, H.P.

    1984-05-01

    The objective of this report is to present, in usable form, summary data from the Building Energy Performance Standards (BEPS) Phase II commercial buildings energy research conducted in 1978-1979. Summary data presented were obtained from two major research efforts: the BEPS Phase II Redesign experiment; and the related research on ASHRAE Standard 90-75R. The bulk of this report consists of data tabulations of key energy parameters for the 168 sample buildings, which were tabulated from computer-stored files of the 1978-1979 data. Two kinds of tabulations are included: numerical tabulations that extracted information from the computer-stored data base for the 168 sample buildings; and graphic presentations of the computer-generated data, plus data extracted from other sources. The intent is to provide a single data compendium of key energy-related factors from the 1978 redesign experiment and the associated 1978-1979 ASHRAE Standard 90-75R research. This report also supplements the information for which there was not space in the magazine articles. Thus, for some building types, additional analysis, comments, and data tabulations are included that could not be included in the articles because space was limited. These additional analysis items are not consistent across building types because both the energy conservation opportunities and the design strategies applied by the building designers varied considerably by building type. The chapters have been entered individually into EDB and ERA.

  18. Scintigraphy of ORL tumours with cobalt bleomycin

    International Nuclear Information System (INIS)

    Our experiences with cobalt bleomycin scintigraphy in the treatment planning of ORL tumors are described. 142 scintigrams taken from 127 patients have been examined. As is shown by our investigation, cobalt bleomycin scintigraphy is a good examination method, however, too much expenditure is needed to have the necessary data for therapy planning. To our opinion, the information obtained in oto-rhino-laryngology by an exact clinical examination is as good as that of cobalt bleomycin scintigraphy. Our treatment schemes had only to be revised in some exceptional cases. (orig.)

  19. 57Co-bleomycin and *I-bleomycin in Ehrlich's carcinoma model of the mouse

    International Nuclear Information System (INIS)

    The tumour concentration, distribution of activity and whole body retention of bleomycin labeled with iodine-125 or iodine-131 was contrasted with that of 57Co-bleomycin following administration to mice showing tumours. Additional investigations were carried out to determine the stability of iodinated bleomyin in vivo and in vitro. As regards the beahaviour of I-bleomycin in mice showing solid carcinomas according to Ehrlich it was established that its absolute tumour concentration was lower and its relative tumour concentration just slightly less pronounced than that of 57Co-bleomycin during the period between 2 and 48 hours following administration. Investigations into whole body retention showed the elimination of activity to be more rapid for 131I-bleomycin as compared to 57Co-bleomycin. Bleomycin that was radioiodinated according to the iodine monochloride method proved to be more stable in vivo than bleomycin labeled with 57Co. Further studies, in particular clinical trials, will have to be carried out before definite conclusions can be drawn as to the diagnostic value of radioiodinated bleomycin in tumour localisation. (TRV)

  20. Tumor-specific radiopharmaceuticals: radiolabeled bleomycin

    International Nuclear Information System (INIS)

    Acid solutions of 59Fe and carrier-free 203Pb, /sup 99m/Te, 57Co, 111In, 67Ga, /sup 99m/Zn, and 64Cu were added to bleomycin and the pH adjusted to 6.5. Distribution data were obtained in rats bearing Ehrlich ascites carcinoma and transplanted mammary adenocarcinoma. Comparative studies were made on patients using 57Co- and 111In-bleomycin, 67Ga-citrate, and /sup 99m/Tc-Sn-pyrophosphate. Results indicated that 57Co-bleomycin had the best biological properties for imaging. Gallium-67 citrate concentration is highest at 2 to 2.5 hr in the transplanted mammary carcinoma, but the concentration in other organs and blood is quite high. The concentration of 57Co-bleomycin is comparable to 67Ga and the ratios of tumor to blood, fat, and muscle is higher. Bleomycin labeled with 64Cu also shows favorable distribution. Studies with patients also show that 57Co-bleomycin is the most sensitive compound of the group in agreement with animal data

  1. Radiotherapy using bleomycin, ACNU, and vincristine for malignant brain tumors

    International Nuclear Information System (INIS)

    Radiotherapy combined with bleomycin, ACNU, and vincristine was performed on 106 patients with malignant brain tumors. The treatment protocol was based on the concept of combination chemotherapy or chemoradiotherapy and synchronized chemoradiotherapy. For the purpose of synchronized chemoradiotherapy, bleomycin, ACNU, and vincristine were used as G2M cell cycle phase accumulator, and radiation and bleomycin were used as agents to which G2M or G2 phase cells are sensitive. The short-term results of the chemoradiotherapy were evaluated by measuring tumor regression by computerized tomography (CT) in 80 patients with evaluable CT lesions. The response rate (complete response+partial response) was 67% (6/9) for astrocytoma, 29% (7/24) for anaplastic glioma, 67% (4/6) for pontine glioma, 100%(5/5) for malignant lymphoma, 100% (8/8) for germ cell tumors and 65% (15/23) for metastatic tumors. A control study was performed using radiation alone on another 18 patients with metastatic tumors, and the response rate was 50% (9/18). Among the 106 patients treated with chemoradiotherapy, the major side effects observed were as follows: leucopenia in 33 patients (31%), thrombocytopenia in 14 (13%), paralytic ileus in 2 (2%), peripheral neuropathy in 2 (2%), and lung fibrosis in 1 (1%). Contrary to expectation, low-grade astrocytomas responded much better to the chemoradiotherapy than high-grade astrocytomas. Chemoradiotherapy seems to be more effective in causing regression of malignant brain tumors than radiation alone, but further studies on the long-term results of this treatment are necessary. (author)

  2. Intracellular distribution of 57Bleomycin

    International Nuclear Information System (INIS)

    Since the first promising results of Nouel et al. 1972, additional positive experience has been obtained with 57Co-Bleomycin (57Co-BLM) as a tumour-localizing agent. In this preclinical study, mice with transplanted osteosarcoma and lymphosarcoma were used and rats with transplanted rhabdomyosarcoma. 57CoCl2 served as a control substance. 57Co-BLM had concentrated in the tumours with a factor 2 to 10 as compared to the (normal) liver of the animals. No preferential concentration in the tumours was found when 57CoCl2 was used. The highest specific activity of 57Co-BLM (cpm/mg protein) was found in a fraction containing mitochondria and lysosomes. Evidence for a lysosomal localization of this diagnostic compound was obtained from experiments in which the mitochondrial-lysosomal fraction was treated with hypertonic media of different osmolarities. Conditions could be found in which many lysosomes burst while almost all mitochondria were intact. From these experiments it appeared that the radioactivity in the particles obtained from animals injected with 57Co-BLM was released very rapidly. (Auth.)

  3. Failure of 111In-labeled bleomycin tumor scanning to predict response to bleomycin (NSC-125066) treatment

    International Nuclear Information System (INIS)

    The question of whether or not 111In-labeled bleomycin is predictive of the response of tumors to bleomycin treatment is answered in the negative. The real test of the value of labeled bleomycin as a predictor of response will be possible only when a tightly labeled bleomycin with fully preserved biologic activity is synthesized. The negative results of this study do not invalidate further investigations of the predictive values of labeled anticancer drugs

  4. Ultraviolet enhancement of DNA base release by bleomycin

    International Nuclear Information System (INIS)

    The effect of UV irradiation on base-releasing activity of bleomycin was studied on bleomycin A2-DNA reaction mixture in the presence of Fe(II) and 2-mercaptoethanol. This effect was measured by the release of free bases from calf thymus DNA with high-performance liquid chromatography. UV irradiation enhanced DNA base-releasing activity of bleomycin and simultaneously caused disappearance of fluorescence emission maximum at 355 nm assigned to bithiazole rings and increase in the intensity of a peak at 400 nm. UV irradiation at 295 nm, the UV absorption maximum of bleomycin, is the most effective in releasing free bases and in changing fluorescence emission patterns. From these results, we suggest that some alterations in the bithiazole group of bleomycin molecule were initiated by UV irradiation and contributed to increased base-releasing activity of bleomycin through a yet unexplained mechanism, presumably through bleomycin dimer formation. (orig.)

  5. An Investigation of the Impact of Function of Problem Behavior on Effectiveness of the Behavior Education Program (BEP)

    Science.gov (United States)

    Hawken, Leanne S.; O'Neill, Robert E.; MacLeod, K. Sandra

    2011-01-01

    The Behavior Education Program (BEP) is a check-in, check-out intervention implemented with students who are at-risk for engaging in more severe problem behavior. Previous research with middle and elementary school students found that the BEP was more effective with students who had adult attention maintained problem behavior. The purposes of this…

  6. Excretion and organic distribution of 57Co-bleomycin emulsions

    International Nuclear Information System (INIS)

    Excretion and organic distributions of 57Co-bleomycin were studied in normal and tumour-bearing mice with the objective of obtaining high 57Co-bleomycin concentrations in the tumour and the regional lymph nodes. Aqueous 57Co-bleomycin and various 57Co-bleomycin emulsions were used for the studies and applied either locally or systemically. Excretion of 57Co-bleomycin was slowest after local administration of 57Co-bleomycin oil-in-water emulsion and fastest after systemic application of aqueous 57Co-bleomycin. Organic distribution studies showed the highest values in the tumour and the regional lymph nodes after local injection of 57Co-bleomycin oil-in-water emulsion while the lowest values were measured after systemic application of aqueous 57Co-bleomycin. These kinetic studies suggest that intratumoral treatment with oil-in-water emulsions of bleomycin may be a new approach in the therapy of epithelial tumours with lymphogenic metastases. (orig.)

  7. A favorable maternal and neonatal outcome following chemotherapy with etoposide, bleomycin, and cisplatin for management of grade 3 immature teratoma of the ovary

    Science.gov (United States)

    Abbasi, Fatemeh; Abadi, Akram Ghahghai Nezam

    2009-01-01

    Ovarian cancer rarely complicates pregnancy. Usually these malignancies consist of germ cell tumors. Preserving maternal safety along with favorable neonatal outcome is a subject of debate in the management of ovarian cancer during pregnancy. In this report, the authors describe a 25-year-old primigravid woman who was diagnosed to with an ovarian immature teratoma which was diagnosed at 13th weeks of pregnancy during a routine sonography. She underwent oophorectomy at week 21 of her gestation. Then she received three cycles of BEP regimen (bleomycin, etoposide, and cisplatin) during her pregnancy until week 37 of gestation. At 36 weeks she delivered a male baby with mild glandular hypospadia who was otherwise normal. Management of immature teratoma after the first trimester of pregnancy is similar to non-pregnant patients and is safe for both the mother and the fetus. PMID:20041106

  8. Study on oxidative lipid and DNA damages in the malignant transformed BEP2D cells induced by ?-particle exposure

    International Nuclear Information System (INIS)

    Objective: To investigate the mechanism of malignant transformation in human bronchial epithelial cell line BEP2D exposed to ?-particles. Methods: The levels of intracellular ROS and malonaldehyde (MDA) in BEP2D, RH22 (passage 22 of ?-particle-irradiated BEP2D cells) and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from the passage 35 of ?-particle-irradiated BEP2D cells) were assayed with DCFH-DA and MDA kit, respectively. The expressions of 8-OH-dG and ?-H2AX in BEP2D, RH23 (passage 23 of ?-particle-irradiated BEP2D cells) and BERP35T-1 cells were also measured with immunocytochemistry and immunofluorescence staining. Results: Compared to BEP2D cells, the levels of ROS (t=4.30 and 3.94, P<0.05) and MDA (t=4.89 and 15.10, P<0.05) increased in RH22 and BERP35T-1 cells. The expressions of 8-OH-dG (t=3.80 and 2.92, P<0.05) and ?-H2AX (t=7.61 and 12.67, P<0.05) in RH23 and BERP35T-1 cells were also higher than those in BEP2D cells. Conclusions: Oxidative stress induces lipid peroxidation and DNA damage leading to genomic instability, which could contribute to cellular malignant transforming process in the human bronchial epithelial cell line BEP2D with ?-particle exposure. (authors)

  9. Consecutive radiation-bleomycin therapy of cancer

    International Nuclear Information System (INIS)

    A consecutive administration of bleomycin 0.5 to 1.0 hr after irradiation enhances the therapeutic effect of the radiotherapy. This was demonstrated in an in vivo experiment and in a case of Hodgkin's disease. This radiation synergism of bleomycin can be designated as perpetuation principle of radiation damage. The radiation synergism can be categorized into 3 principles: (1) transference, (2) perpetuation and (3) biological amplification. The present categorization would encourage future development of various anticancer means. The idea of this consecutive strategy is expected to cultivate a way of overcoming the cell-cycle dependency of the current anticancer chemotherapy, too: Irradiation induces DNA damage regardless of the age in the cell cycle of cancer cells, and the same principle may be applicable to radiomimetic chemotherapeutics. (author)

  10. Radiation doses from 51Cr-bleomycin

    International Nuclear Information System (INIS)

    Extensive studies were made of long-term whole-body retention, plasma concentration and urinary excretion of 51Cr in rats, rabbits and patients after injection of 51Cr-bleomycin. Integrated whole-body and organ retention, corrected for radioactive decay, is similar in man and rabbit, and higher by a factor of about 2 in the rat. Doses to organs and whole body in man were calculated using the MIRD methodology and assuming conservatively that the kinetic data derived in rats are applicable to man. The organ and whole-body MIRD doses after 51Cr-bleomycin administration are comparable to those after 67Ga-citrate and the effective dose equivalent from a diagnostic amount of 740 MBq of the 51Cr complex amounts to about 6 mSv. However, the subcellular distribution in the liver of 51Cr, administered in the form of 51Cr-bleomycin, indicated a significant enrichment of 51Cr in the nuclei and in the DNA over mean concentrations in the liver cells. Also, the quality factor for Auger electrons, emitted by 51Cr, when assessed on the basis of the Q vs. LET relationship, as proposed by ICRP, was substantially higher than unity. Doses calculated for cell nuclei and the DNA in the liver cells were higher than the cell-averaged values by a factor 2.5 and 5, respectively, and the corresponding dose equivalents by a factor of 9 and 24. The effective dose equivalent, estimated on the basis of dose equivalents to cell nuclei and the DNA, amounted to 33 and 83 mSv per examination (740 MBq of 51Cr-bleomycin), respectively. (orig.)

  11. Indirect measurement of 9Be(p, ?)6Li reaction by means of Trojan Horse Method

    International Nuclear Information System (INIS)

    The beryllium abundance acts as a key role for understanding the inhomogeneous Big Bang nucleosynthesis. In order to measure the 9Be(p, ?)6Li bare nucleus cross section and S(E) factor at astrophysical energies, the Trojan Horse Method (THM) can be applied. The main feature of the method is that it allows to extract the energy dependence for the astrophysical S(E) factor of bare nuclei at very low energies without any extrapolation, by measuring the cross section of an appropriate three body process. Thus the 9Be(p, ?)6Li has been studied by means of the THM applied to the 2H(9Be, ?6Li)n at INFN-LNS, Catania, Italy. The two body reaction cross section has been studied in the energy range of Ecm=0-1000 keV, Preliminary results are discussed and a comparison with direct data is made. (authors)

  12. Asymptotic normalization coefficients and the 7Be(p,?)8B astrophysical S factor

    International Nuclear Information System (INIS)

    We consider the results of two proton transfer reactions, 10B(7Be,8B)9Be and 14N(7Be,8B)13C, to obtain a weighted average of the measured asymptotic normalization coefficients for the virtual transition 7Be+pleftrightarrow8B. These coefficients specify the amplitude of the tail of the 8B overlap function in the 7Be+p channel, and are used to calculate the astrophysical S factor for the direct capture reaction 7Be(p,?)8B at solar energies, S17(0). In light of recent improvements in the determination of optical-model potentials, including detailed understanding of the correlations between the DWBA analyses of the two experiments, and a new experimental measurement of the asymptotic normalization coefficients for the virtual transition 13C+pleftrightarrow14N,y we report a weighted average asymptotic normalization coefficient of Cp3/22=0.388±0.039 fm-1 for 8B?7Be+p, which implies S17(0)=17.3±1.8 eVb

  13. Oxidative damage of BEP2D cells irradiated 60Co ?-rays

    International Nuclear Information System (INIS)

    Objective: To study reactive oxygen species (ROS) productions and oxidative DNA damage in HPV-16 immortalized human bronchial epithelial cells (BEP2D) irradiated with 60Co ?-rays. Methods: The measurement of extracellular superoxide anions was based on the reduction of ferricytochrome C as assayed by the increase in its absorbance at 550 nm. Quantitation of extracellular hydrogen peroxides (H2O2) was based on the horseradish peroxidase-dependent oxidation of phenol red which is assayed by its increased absorbance at 620 nm. The determination of extracellular hydroxyl radicals (·OH) was based on de-coloration of safranine T as assayed by the decrease in its absorbance at 520 nm. Ethidium bromide and 2', 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes-hydro-ethine and 2', 7'-dichlorofluorescein diacetate, were used to monitor the intracellular production of H2O2 and superoxide anions respectively by flow cytometry. 8-hydroxy-deoxygunosine (OH8dG) was examined with HPLC-ECD from extracted DNA. Results: the ROS production including H2O2, superoxide anions and ·OH, and DNA adduct OH8dG in 60Co ?-rays-irradiated BEP2D cells increased remarkably, and these increments could be inhibited effectively by 1 ?mol/L of selenium. Conclusion: 60Co ?-irradiation causes oxidative damage to BEP2D cells, which can be protected by selenium

  14. Tumor scanning with 57Co-bleomycin

    International Nuclear Information System (INIS)

    The clinical application of 57Co-bleomycin as a tumor scanning radiopharmaceutical was firstly reported by Nouel and Maeda respectively. The authors conducted studies on the diagnostic significance of this tumor scanning agent and presented the results obtained in 40 patients with malignant and non malignant lesions. Six hours and 24 hours after the injection of 500 μCi of 57Co-bleomycin, scintigrams were taken with a 3-inch scintiscanner. Positive scans were found in 20 out of 36 patients with various malignant tumors. Of 20 patients with lung cancer, positive scans were obtained in 17 cases (85%) and of 6 with breast cancer, 3 cases showed positive scans. False negative scans were obtained in another 10 cases of malignant tumors (3 cases of thyroid carcinoma, 4 cases of hepatoma, and 1 case each of gastric carcinoma, peritoneal carcinomatosis, and reticulum cell sarcoma). Of 4 patients with non malignant disease, one case of pulmonary tuberculosis showed a positive scan. In 8 cases of lung cancer and 6 of breast cancer, the relationship between the size of the excised tumor and the scintigram findings was studied. The smallest tumors detected by scintigram were 2 cm in lung cancer and 3.2 cm in breast cancer. (author)

  15. The effects of Bleomycin A5 on infantile maxillofacial haemangioma

    Directory of Open Access Journals (Sweden)

    Zhao Fu-yun

    2011-07-01

    Full Text Available Abstract Objective To examine the effects of bleomycin A5 on infantile maxillofacial haemangiomas. Methods Bleomycin A5 was given by multiple intralesinoal injections and the dosage was given according to the age of the patient and size of the lesion. Parts of patients were accompanied by prednisone treatment(2-5 mg/kg, po, QOD. Results All the haemangiomas involuted completely after treated with bloemycin A5 with better recovery of skin color and less scar forming in small haemangiomas. Conclusion Infantile haemangioma could be effectively treated with bleomycin A5 without serious side effects.

  16. Distribution of Fe-bleomycin, Co-bleomycin in tumor tissue

    International Nuclear Information System (INIS)

    Ferric bleomycin (Fe-BLM) complex was found stable in the region of BLM excess and in the region of pH greater than 4.8. When this was injected intravenously into a mouse, it did not dissociate during the period of observation. Localization of Fe-BLM complex in mammary carcinoma of the C3H mouse and MC-induced squamous cell carcinoma was investigated by histochemical analysis of iron. In the tumor tissue, the iron as was identified by the Berlin blue reaction was seen localized in the stroma cells, histiocyte-like cells in granulation tissue and hair roots, but not in the tumor nests. On the contrary, Co-BLM was seen localized in the tumor nests, especially in the nuclear part of the tumor cells as investigated by cobalt straining. There was a clear-cut difference in the distribution pattern between 59Fe-BLM and 60Co-BLM. While Fe-BLM retained much of ''bleomycin'' character, the Co-BLM behaved like cobalt itself in vivo in the mouse. Thus, the chelating metal would greatly influence the distribution pattern of bleomycin. (auth.)

  17. Development of 166Ho bleomycin as a possible therapeutic complex

    International Nuclear Information System (INIS)

    Due to interesting therapeutic properties of 166Ho and the antineoblastic antibiotic, bleomycin (BLM), 166Ho-bleomycin (166Ho-BLM) was developed as a possible therapeutic compound. 166Ho chloride was obtained by thermal neutron irradiation (1 x 1013 n cm-2 s-1) of natural Ho(NO3)3 samples (specific activity = 3-5 GBq mg-1), dissolved in acidic media. At optimized conditions (room temperature, 12 h, 0.15-0.3 mg bleomycin for 74 MBq 166HoCl3) a radiochemical purity of 94-97% was obtained as shown by ITLC and HPLC (specific activity, 700-740 GBq mmol-1). Biodistribution studies of 166Ho chloride and 166Ho-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. (author)

  18. Pulmonary toxicity after radiation and bleomycin: a review

    International Nuclear Information System (INIS)

    The effects of bleomycin (BLM) and radiation on the lung are histologically similar. Animal studies have indicated additive or synergistic effects from these 2 agents. Review of the literature regarding clinical studies using BLM and irradiation indicates that the incidence of pulmonary toxicity increases when bleomycin is administered in conjunction with radiotherapy to the thorax. Of 115 patients treated simultaneously with BLM and radiation to the thorax, 22 (19%) suffered pulmonary toxicity that was fatal in 11

  19. Effects of bone marrow depression on the development of bleomycin-induced pulmonary fibrosis

    International Nuclear Information System (INIS)

    The effects of blood leukocyte depression on the development of bleomycin-induced pulmonary fibrosis were studied in F344/N rats injected with 89Sr to destroy bone marrow cells. The 89Sr injections were followed in 7 days by intratracheal instillation of bleomycin. At 3 to 30 days after bleomycin, the lung injury in rats given both 89Sr and bleomycin was compared to animals given bleomycin alone. The 89Sr treated rats had reduced numbers of circulating granulocytes, a less severe pulmonary inflammatory response, and a delayed, but not abrogated, pulmonary fibrosis compared to animals given bleomycin alone. 4 references, 4 figures, 2 tables

  20. Mitochondrial DNA damage by bleomycin induces AML cell death.

    Science.gov (United States)

    Yeung, ManTek; Hurren, Rose; Nemr, Carine; Wang, Xiaoming; Hershenfeld, Samantha; Gronda, Marcela; Liyanage, Sanduni; Wu, Yan; Augustine, Jeevan; Lee, Eric A; Spagnuolo, Paul A; Southall, Noel; Chen, Catherine; Zheng, Wei; Jeyaraju, Danny V; Minden, Mark D; Laposa, Rebecca; Schimmer, Aaron D

    2015-06-01

    Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease. PMID:25820141

  1. Proteome analysis for effects of radiation on BEP2D cell

    International Nuclear Information System (INIS)

    The study analyzed the differential expression of proteins profile of the normal BEP2D cell and the BEP2D cell radiated with 1.5 Gy, 3 Gy ? rays by Proteomics technique. The results showed that approximately 1000 analyzed proteins per 2-D gel were isolated with molecular weights ranging between 14.4-94 kD and pI 3-10. Image analysis showed that irradiation with 1.5 Gy ?-rays contracting with control image caused down-regulation of 104 kinds of cell proteins and up-regulation of 15 proteins. Irradiation with 3 Gy ?-rays contracting with control image caused down-regulation of 144 kinds of cell proteins and up-regulation of 26 proteins. Irradiation with the two dimensional electrophoresis contracting with control image both caused down-regulation of 15 kinds of cell proteins and up-regulation of 3 proteins. Using mass spectrometry, a protein MLC was identified within the two protein spots (spot D and spot 660). All of this change of proteins expressing may result in the lung cancer, and the study can provide baisis for the study of lung cancer pathogenesis. (authors)

  2. Trojan horse method applied to 9Be(p,?)6Li at astrophysical energies

    International Nuclear Information System (INIS)

    The low-energy bare-nucleus cross section for 9Be(p,?)6Li has been extracted by means of the Trojan horse method (THM) applied to the 2H(9Be, ?,6Li)n reaction at a beam energy of 9Be of 22.35 MeV. For the first time, we assume an intermediate process, 9Be+2H?9Be+p+n, and considered this process as one criterion of the quasifree condition. Accordingly, sequential decay processes were eliminated. The derived astrophysical S(E) factor for the two-body process 9Be(p,?)6Li is compared with that obtained from direct experiments. We have found good agreement between the two results, leading to an improved determination of the S(E) with S(0)=21.0±0.8 MeV b. Furthermore, the electron screening potential energy Ue=676±86 eV has also been extracted in a model-independent way by comparing the direct and THM data. The value is significantly higher than that predicted by current theoretical models, whereas it is lower than Ue?830 eV, which was extracted from direct measurements with inclusion of the Ec.m.=-23 keV subthreshold resonance

  3. Bleomycin and radiation-induced lung damage in mice

    International Nuclear Information System (INIS)

    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction. (author)

  4. Irradiation and bleomycin in the treatment of inoperable vulval carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Iversen, T. (The Norwegian Radium Hospital, Oslo (Norway). Dept. of Gynecology)

    1982-01-01

    Fifteen patients with inoperable squamous cell carcinoma of the vulva were treated with Bleomycin and irradiation. Only 2 patients were also treated with vulvectomy and bilateral lymphadenectomy 2 weeks later. One patient survived more than 4 years without signs of recurrence, another survived 2 1/2 years and 2 more 18 and 12 months respectively. The rest died less than 6 months after the treatment. Three patients developed signs of lung fibrosis. Bleomycin and irradiation may render a tumor operable, but in most cases this regime merely aims at palliation.

  5. Distribution of 64Cu-Bleomycin in normal and tumor-bearing rats

    International Nuclear Information System (INIS)

    Accumulation of a radioactive label in tumor tissue is required for scintigraphic visualization of the tumor and has been achieved by application of bleomycin as carrier. This chemotherapeutic polypeptide drug has been labeled with 64Cu. Thin layer chromatography of 64Cu-bleomycin which was incubated for 22 hours at 370C showed no changes of the chelate. When urine of the 64Cu-bleomycin treated animals was chromatographed considerable amounts (9.3%) of free 64Cu appeared 2 hours after injection of the chelate and dissociation was found to be almost complete 4 hours after injection of labeled bleomycin. The distribution of 64Cu-bleomycin is similar to that found with sup(99m)Tc-bleomycin with long lasting accumulation in kidneys and liver. Highest concentration ratios of the activity in mesenchymal tumor (Yoshida) and blood respectively were found 6 hours after intravenous administration of 64Cu-bleomycin. (author)

  6. Synthesis of non-ionic and ionic resins for BEP intaglio inks curing by electron-beam radiation. Annual report

    International Nuclear Information System (INIS)

    The inks currently used to print US postage stamps on web presses are dried by heat evaporation of solvents. Emission of solvents into the atmosphere is governed by Local and Federal Government Regulations. Reduction of these emissions to acceptable levels can be accomplished by either of two methods available to the BEP. The work was part of a continuing effort to produce resins for use in formulation of intaglio inks for the printing of postage stamps and security documents. The inks are to be cured by exposure to an electron beam. The uncured inks are cleaned from the roller and wiping blade by washing the wiping blade with neutral water or with caustic water. Laboratory scale work on the urethane/polyethylene oxide/methacrylate resins has now been concluded and information on the synthesis has been provided to BEP for patenting and scaleup. Some effort on nonionic resins continued into FY88

  7. Acute respiratory failure induced by bleomycin and hyperoxia

    International Nuclear Information System (INIS)

    Bleomycin, a chemotherapeutic agent, and oxygen at concentrations greater than 20%, induce acute pulmonary damage separately and when administered together. The interaction of 5 U/kg intratracheal bleomycin and 24 hours of exposure to 80% oxygen in hamsters produces delayed onset acute respiratory distress syndrome three days after treatment. As little as 12 hours of 80% O2 exposure, after intratracheal bleomycin, induces severe pulmonary damage. Lung lesions are characterized as diffuse alveolar damage. Significantly pulmonary edema, measured by iodine-125-bovine serum albumin and technetium-99m-diethylenetriaminepentaacetate, occurs 72 hours after treatment. Lesions progress from focal mild alveolar interstitial and air-space macrophage and granulocyte infiltrates at 24 hours to marked infiltrates and severe interstitial and air space edema with hemorrhages and hyaline membranes at 96 hours. Significant changes measured by electron microscopy morphometry are increases in volume fractions of neutrophils, alveolar tissue and mononuclear leukocytes. Surfactant assay of bronchoalveolar lavage fluid shows a marked decrease in the lecithin/sphingomyelin ratio at 72 hours. Proposed mechanisms of bleomycin and hyperoxia synergism include enhanced production of superoxide radicals either directly or indirectly by increasing neutrophil activity or numbers, or by alteration of cell mediators. The pulmonary edema, without evidence of severe morphological changes, may be secondary to alterations of transalveolar transport mechanisms

  8. Structure of 8B from elastic and inelastic 7Be+p scattering

    CERN Document Server

    Mitchell, J P; Johnson, E D; Baby, L T; Kemper, K W; Moro, A M; Peplowski, P; Volya, A S; Wiedenhoever, I

    2013-01-01

    Motivation: Detailed experimental knowledge of the level structure of light weakly bound nuclei is necessary to guide the development of new theoretical approaches that combine nuclear structure with reaction dynamics. Purpose: The resonant structure of 8B is studied in this work. Method: Excitation functions for elastic and inelastic 7Be+p scattering were measured using a 7Be rare isotope beam. Excitation energies ranging between 1.6 and 3.4 MeV were investigated. An R-matrix analysis of the excitation functions was performed. Results: New low-lying resonances at 1.9, 2.5, and 3.3 MeV in 8B are reported with spin-parity assignment 0+, 2+, and 1+, respectively. Comparison to the Time Dependent Continuum Shell (TDCSM) model and ab initio no-core shell model/resonating-group method (NCSM/RGM) calculations is performed. This work is a more detailed analysis of the data first published as a Rapid Communication. [J.P. Mitchell, et al, Phys. Rev. C 82, 011601(R) (2010)] Conclusions: Identification of the 0+, 2+, 1+...

  9. Statistical theory of light nucleus reaction and application to $^9$Be(p, xn) reaction

    CERN Document Server

    Sun, Xiaojun

    2016-01-01

    A statistical theory of light nucleus reaction (STLN) is proposed to describe both neutron and light charged particle induced nuclear reactions with 1p-shell light nuclei involved. The dynamic of STLN is described by the unified Hauser-Feshbach and exciton model, of which the angular momentum and parity conservations are considered in equilibrium and pre-equilibrium processes. The Coulomb barriers of the incident and outgoing charged particles, which seriously influence the open reaction channels, could be reasonably considered in the incident channel and the different outgoing channels. In kinematics, the recoiling effects in various emission processes are taken strictly into account. Taking $^9$Be(p, xn) reaction as an example, we calculate the double-differential cross sections of outgoing neutrons and charged particles using PUNF code in the frame of STLN. The calculated results agree very well with the existing experimental neutron double-differential cross sections at $E_p=18$ MeV, and indicate that PUN...

  10. Anti-myeloma activity of the novel 2-aminothienopyrimidine Hsp90 inhibitor NVP-BEP800.

    Science.gov (United States)

    Stühmer, Thorsten; Chatterjee, Manik; Grella, Evelyn; Seggewiss, Ruth; Langer, Christian; Müller, Sabine; Schoepfer, Joseph; Garcia-Echeverria, Carlos; Quadt, Cornelia; Jensen, Michael R; Einsele, Hermann; Bargou, Ralf C

    2009-11-01

    The 90 kD heat shock protein (Hsp90) molecular chaperone sustains multiple components of oncogenic pathways and has recently emerged as a therapeutic target that is now being clinically tested in a number of malignancies. In order to address formulation issues and to deal with possible resistance mechanisms against small molecule Hsp90 inhibitors, a range of compounds based on different molecular scaffolds are now being developed. The present study preclinically tested the effects of the novel 2-aminothienopyrimidine class Hsp90 inhibitor NVP-BEP800, which is suitable for oral formulations, on multiple myeloma cells from established cell lines and on a larger cohort (n = 40) of primary myeloma samples. The drug effectively and specifically killed the majority of primary myeloma cells in coculture with bone marrow stromal cells and reliably entailed molecular consequences of Hsp90 blockade - such as survival pathway breakdown and client protein depletion - in multiple myeloma cells from cell lines as well as from patients. Collectively, the properties of this novel drug support clinical testing in multiple myeloma. PMID:19686236

  11. Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

    OpenAIRE

    Sentjurc Marjeta; Grosel Alenka; Cemazar Maja; Kranjc Simona; Sersa Gregor

    2005-01-01

    Abstract Background Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo. Methods LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, w...

  12. Preparation and Quality Control of Scandium-46 Bleomycin as a Possible Therapeutic Agent

    OpenAIRE

    Mohammad Ghannadi-Maragheh; Mohammad Mazidi; Ali Bahrami-Samani; Mohammadreza Pourjavid; Amir Reza Jalilian; Leila Moghaddam-Banaem

    2012-01-01

    Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM), 46Sc-bleomycin (46Sc-BLM) was developed as a possible therapeutic compound. Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural metallic scandium sample followed by dissolution in acidic media as a substitute for 47Sc in radiolabeling studies which was further used for labeling of bleomycin (BLM) followed by stability studies ...

  13. Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Chilakapati, Shanmuga Reddy; Serasanambati, Mamatha; Manikonda, Pavan Kumar; Chilakapati, Damodar Reddy; Watson, Ronald Ross

    2014-08-01

    Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized by excessive collagen deposition, with no effective treatments. We investigated the efficacy of natural products with high anti-inflammatory activity, such as passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal instillation of bleomycin to induce PF. Daily PFPE treatment significantly reduced loss of body mass and mortality rate in mice compared with those treated with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid on both days 7 and 21, PFPE administration significantly attenuated these phenomena compared with bleomycin group. On day 7, the decreased superoxide dismutase and myeloperoxidase activities observed in the bleomycin group were significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline deposition in the bleomycin group was also suppressed by PFPE administration. PFPE treatment significantly attenuated extensive inflammatory cell infiltration and accumulation of collagen in lung tissue sections of bleomycin-induced mice on days 7 and 21, respectively. Our results indicate that administration of PFPE decreased bleomycin-induced PF because of anti-inflammatory and antioxidant activities. PMID:24933624

  14. 89Strontium-induced bone marrow depression suppresses the early inflammatory response and fibrosis caused by intratracheal bleomycin

    International Nuclear Information System (INIS)

    To investigate the effect of bone marrow depression on the development of bleomycin-induced lung injury, F-344/Crl rats were given an intraperitoneal (IP) injection of 89SrCl2 (2 mCi/kg body weight) 7 days prior to the intratracheal (IT) instillation of 7.0 U/kg body weight bleomycin (Sr-bleomycin group). A second group of rats was given an IP injection of saline followed 7 days later by IT bleomycin (bleomycin group). Additional rats were given 89Sr IP and saline IT (Sr group) or saline IP and saline IT (saline group). Rats were sacrificed at 0, 3, 10, 21, and 30 days after the intratracheal instillations. 89Sr administration resulted in significantly lower numbers of circulating blood neutrophils and monocytes in the Sr-bleomycin group compared with the bleomycin group through at least the first 21 days following the IT instillations. Lymphocyte numbers were also depressed in the Sr-bleomycin group at days 3 and 21. Analysis of bronchoalveolar lavage fluid (BALF) revealed significantly reduced protein and lymphocyte numbers in the BALF from the 89Sr-bleomycin group compared with the bleomycin group at day 3, but not at later time points. Neutrophils in BALF were also lower (though not significantly) in the 89Sr-Bleomycin group at day 3. There was no difference in the number of BALF macrophages between the Sr-bleomycin and bleomycin groups at any time point throughout the study. Histology and morphometry showed the same trends as the BALF data with much less severe lesions in the 89SR-Bleomycin group compared with the bleomycin group at day 3, but not at later time points. At day 10, hydroxyproline values were significantly higher in the bleomycin group (47% increase above saline group) than the Sr-bleomycin group (only 18% increase above Sr group), but by day 21, there was no longer a significant difference between these two groups

  15. Pharmacology and therapeutic efficacy of bleomycin administered by continuous infusion

    International Nuclear Information System (INIS)

    A study was done at Memorial Hospital in which Bleomycin was given by continuous intravenous infusion to radiation therapy patients with a variety of far advanced unresectable malignant neoplastic diseases. Smaller doses than usual were administered initially, approximately 1/10 the dose that had been previously studied. The dose was gradually escalated when it was shown that there was no acute toxicity from the smaller dose. Bleomycin blood levels were measured by bioassay and pulmonary function was studied by measurement of total lung capacity and carbon monoxide diffusing capacity. In this study, therapeutic activity in cervix cancer appeared to be significantly better than in earlier studies by the same group of investigators. However, in vitro and animal studies in the author's own clinical pharmacologic studies support the logic of continuous intravenous administration in the effort to decrease pulmonary toxicity and to improve therapeutic effect

  16. Radiologic-pathologic correlation of experimental bleomycin-induced pneumonitis

    International Nuclear Information System (INIS)

    Radiologic-pathologic correlative study of bleomycin-induced pneumonitis was performed using inflated and fixed lung specimens. Sixteen male Japanese white rabbits (body weight: 2.0-2.5 kg) were given a single intratracheal injection of 10 mg/kg bleomycin. On day 3, 10, 21, and 42 after bleomycin administration, 4 rabbits were killed, and each lung was inflated and fixed for radiologic-pathologic correlation. Early pathologic change involved a markedly exudative lesion like DAD, corresponding to the finding of markedly increased density on soft X-ray. As intraalveolar organization progressed, fibrotic changes of the alveolar septum, and atelectatic change evolved pathologically, the finding of markedly increased density developed the nature of contraction, and finally the finding of an abnormal linear shadow and air space dilatation were formed. The finding of markedly increased density and slightly increased density, respectively, did not simply correspond to the alveolar lesion and interstitial lesion pathologically. We considered that the degree of increased density depended on the degree of air content in the alveoli of the lesion. The finding of an abnormal linear shadow corresponded to the band of fibrotic tissue, and band-shaped atelectasis of alveoli. The finding of air space dilatation corresponded to the dilatation of respiratory bronchioli and alveolar ducts in the fibrotic stage, and this may show the mechanism of honeycomb lung formation. The finding of a clearly demarcated shadow with linear margins could be recognized as a lobular lesion and disappeared as fibrotic change evolved. (author)

  17. Bleomycin induced epithelial–mesenchymal transition (EMT) in pleural mesothelial cells

    International Nuclear Information System (INIS)

    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial–mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis. - Highlights: • Bleomycin induces collagen-I synthesis in pleural mesothelial cells (PMCs). • Bleomycin induces increases in vimentin and α-SMA protein in PMCs. • Bleomycin induces decreases in cytokeratin-8 and E-cadherin protein in PMCs • TGF-β1-Smad2/3 signaling pathway is involved in the PMC EMT induced by bleomycin

  18. Large angle proton emission in the 9Be(p,2p) reaction at 300 MeV

    International Nuclear Information System (INIS)

    A 9Be(p,2p) coincidence experiment performed to to further elucidate the reaction mechanism for the production of energetic wide-angle protons in intermediate energy proton induced reactions is reported. Detectors in a coplanar geometry were used to measure coincidences between trigger protons at 90 degrees to the beam and forward angle protons on the opposite side of the beam. The incident proton energy was 300 MeV. The authors report both the inclusive spectra for the trigger protons and the differential mean multiplicities for the coincidence events

  19. Antioxidant ability and radiosensitivity in malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle irradiation

    International Nuclear Information System (INIS)

    Objective: To investigate the antioxidant ability and radiosensitivity in the malignant transformed human bronchial epithelial cell line BEP2D induced by α-particle exposure. Methods: Glutathione Peroxidase (GPX), Catalase (CAT) and Glutathione (GSH) assay kits were employed to detect GPX and CAT enzyme abilities and the levels of GSH in BEP2D, RH21 (passage 21 of α-particle-irradiated BEP2D cells), and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of α-particle-irradiated BEP2D cells). MTT assay were used to test the growth rate of BEP2D, RH21 and BERP35T-1 cells treated with 0, 30, 60, 90, 120, and 150 μmoL/L H2O2. Colony-forming test and MTT assay were used to examine the cell survival fraction and the growth rate of BEP2D, RH21 and BERP35T-1 cells exposed to 0, 2, 4, and 8 Gy of γ-rays,respectively. Results: GPX and CAT enzyme activities in RH21 and BERP35T-1 cells were obviously lower than in BEP2D (t=5.75-67.92, P<0.05). CAT enzyme activity in BERP35T-1 was lower than that in RH21 cells (t=22.25, P<0.01). Compared to BEP2D cells, decreased level of GSH was detected in BERP35T-1 cells (t=7.76, P<0.05), but there was no change in RH21. After treatment with 30, 60, 90, 120, and 150 μmol/L H2O2, the growth rates of BEP2D were all higher than those of BERP35T-1 cells (t=10.37-58.36, P<0.01). Meanwhile,the growth rates of BEP2D were all higher than those of RH21 cells after treatment with 60, 90, 120, and 150 μ mol/L H2O2 (t =29.90-84.68, P<0.01). In addition,compared to BEP2D cells,decreased cell survival fraction and growth rate of BERP35T-1 cells were observed after irradiation with 2, 4, and 8 Gy of y-rays (t=5.87-34.17, P<0.05). The cell survival fraction and growth rate of RH21 were all lower than those of BEP2D cells at 4 and 8 Gy post-irradiation (t=6.33- 45.00, P<0.05). Conclusion: The function of antioxidant system decreased in the α-particle-induced transformed cells, which could contribute to the acceleration of cellular malignant transforming process and radiosensitivity. (authors)

  20. Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices

    Energy Technology Data Exchange (ETDEWEB)

    Giri, S.N.

    1987-12-01

    Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of (/sup 14/C) acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on (/sup 14/C) acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of (/sup 14/C) acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production.

  1. Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices

    International Nuclear Information System (INIS)

    Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of [14C] acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on [14C] acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of [14C] acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production

  2. Clinical usefulness of bleomycin combined with preoperative irradiation for cancer of the esophagus

    International Nuclear Information System (INIS)

    The clinical usefulness of bleomycin combined with irradiation was evaluated using 154 preoperatively treated cases with cancer of the esophagus. With the appearance rate Ef-3 (highly effective: no viable tumor cell in the esophageal specimen resected after preoperative treatment) the radiation effect was observed, in comparison with those three groups (30 Gy alone, 40 Gy alone and 30 Gy + 67.5 mg of bleomycin). Dose modifying actor (DMF) of bleomycin for the preoperatively irradiated esophageal cancer was 1.2 - 1.3. As a serious interstitial pneumonitis was sometimes caused by the administration of bleomycin, it was concluded that the usage of bleomycin combind with preoperative irradiation for cancer of the esophagus, is less useful than that for cancer of the uterine cervix and the head and neck region. (author)

  3. Intralesional bleomycin for the treatment of periocular capillary hemangiomas

    Directory of Open Access Journals (Sweden)

    Derrick P Smit

    2012-01-01

    Full Text Available Periocular infantile capillary hemangiomas do not always respond well to conventional treatment modalities such as systemic or intralesional corticosteroids, radiotherapy or debulking surgery. The authors describe the use of intralesional bleomycin injections (IBIs to treat potentially amblyogenic lesions in two cases where other modalities have failed. In both cases monthly IBIs successfully cleared the visual axis of the affected eye before the age of 1 year thus preventing permanent sensory deprivation amblyopia. A total of five and nine injections, respectively, were used and no significant side effects were noted. IBI appears to be a useful alternative in the treatment of periocular capillary hemangiomas refractory to more conventional modalities.

  4. Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

    International Nuclear Information System (INIS)

    Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo. LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50). Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry. Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia. Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin

  5. Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice

    Directory of Open Access Journals (Sweden)

    Sentjurc Marjeta

    2005-09-01

    Full Text Available Abstract Background Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo. Methods LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50. Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry. Results Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia. Conclusion Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin.

  6. Effects of ICRF-187 and L-Carnitine on bleomycin-induced lung toxicity in rats

    International Nuclear Information System (INIS)

    The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin-induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin (10 mg/kg, twice weekly for 6 consecutive weeks) produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide (LPO, 91.7%) reduced glutathione (GSH, 73.2%) and oxidized glutathione (GSSG, 135.4%) as well as the activity of superoxide dismutase (SOD, 222.7%). Thirty minutes prior to bleomycin treatment, other groups of rats received either ICRF-187 (95 mg/kg) or L-carnitine (500 mg/kg) adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand, treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters. (author)

  7. 57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer

    International Nuclear Information System (INIS)

    In the investigation of suspected lung cancer, bleomycin labelled with cobalt-57, and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radiopharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67Ga-citrate in 34 (54%) (p 57Co-bleomycin and 1.5 with 67Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with 57Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with 67Ga-citrate scintigraphy in only eight (45%) (p 57Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is 67Ga-citrate. 57Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When 57Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy. (author)

  8. Impaired wound healing in bleomycin-induced murine scleroderma: a new model of wound retardation.

    Science.gov (United States)

    Maeda, Tatsuo; Yamamoto, Toshiyuki; Imamura, Toru; Tsuboi, Ryoji

    2016-03-01

    Bleomycin-induced scleroderma in mice is an established model for human scleroderma. Making use of this, we have established a new model for wound retardation. After inducing dermal sclerosis by local bleomycin treatment in nude mice, a full-thickness wound was made by punch excision on the bleomycin application site. Mice pretreated with bleomycin showed a significant delay in wound closure, as compared with mice pretreated with phosphate-buffered saline. Proliferation of keratinocytes was significantly inhibited and the number of Ki-67-positive keratinocytes was significantly lower in the bleomycin-pretreated skin. Also, the number of CD31-positive blood vessels was markedly reduced in the bleomycin-treated skin. The topical daily application of basic fibroblast growth factor (bFGF) significantly promoted wound closure, while increasing blood vessel formation and reducing transforming growth factor-? and alpha-smooth muscle actin mRNA levels. Furthermore, only two applications of PG-FGF1, a fusion protein of FGF1 with heparan sulfate proteoglycan, overcame the delay in wound closure. Wound delay in this model mainly occurred as a result of decreased vessel formation and keratinocyte migration following bleomycin treatment. It is expected that this model will provide novel insights into the pathogenesis of wound healing and the exploration of possible candidate drugs for refractory or chronic wounds in the clinical setting. PMID:26660455

  9. Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer

    International Nuclear Information System (INIS)

    Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

  10. Computer simulation of 57Fe bleomycin Auger effects in DNA

    International Nuclear Information System (INIS)

    The antibiotic bleomycin binds to the DNA and induces double strand breaks (DSBs). To increase the cleavages, 57Fe is used to form a complex suitable for Moessbauer effect. The de-excitation of the resonant excited 57Fe nucleus releases Auger electrons and X rays. The goal of this work is to evaluate the increase in yield of DSBs due to the 57Fe, using Monte Carlo simulation methods. Particles spectra and the yields of single strand breaks (SSBs) and DSBs were calculated by considering direct events on DNA and reaction of all radical species generated in the radiolysis of its environment. The Auger spectrum shows a large number of electrons with energies below 100 eV, mainly responsible for direct damage, while another group around 600-700 eV is responsible for indirect damage effects. Bleomycin receives about one fourth of the energy deposited in DNA and an average of 0.65 DSBs per de-excitation is observed. (author)

  11. Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, B.M., E-mail: bmm@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Mendes, T.M.; Campos, T.P.R., E-mail: campos@nuclear.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2011-07-01

    Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

  12. Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells.

    Science.gov (United States)

    Calvet, Christophe Y; Famin, Delphine; André, Franck M; Mir, Lluis M

    2014-01-01

    Electrochemotherapy (ECT) is a local cancer treatment that has been used over the course of more than 2 decades for the removal of cutaneous and subcutaneous tumors. Several lines of evidence support the premise that the immune system is an important factor underlying anticancer treatment efficacy, potentially including patient responses to ECT. The concept of immunogenic cell death (ICD) arose a few years ago, stating that some cancer treatments generate danger-associated molecular patterns (DAMPs) that trigger an adaptive immune response against tumors. Hence, dying cancer cells behave as a therapeutic vaccine, eliciting a cytotoxic immune response against surviving malignant cells. In our study, we sought to evaluate the ability of ECT to generate cancer cell death encompassing the immunostimulatory characteristics of ICD. To this end, we assayed CT26 murine colon cancer cells in vitro in response to either electric pulses (EPs) application only or in combination with the anticancer drug bleomycin (that is ECT) by quantification of calreticulin (CRT) membrane externalization, as well as the liberation of adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1) protein. We show here that cell permeabilizing yet non-lethal electric pulses induce CRT exposure on the cell surface of EP-only treated cancer cells, as well as ATP release. However, the association of electric pulses along with the chemotherapeutic agent bleomycin was mandatory for HMGB1 release coincident with regimen-induced cell death. These data obtained in vitro were then substantiated by vaccination protocols performed in immunocompetent mice, showing that the injection of dying ECT-treated cells elicits an antitumor immune response that prevents the growth of a subsequent administration of viable cancer cells. We also confirmed previous results showing ECT treatment is much more efficient in immunocompetent animals than in immunodeficient ones, causing complete regressions in the former but not in the latter. This supports a central role for immunity in this beneficial outcome. In conclusion, we show that ECT not only possesses an intrinsic cytotoxic property toward cancer cells but also generates a systemic anticancer immune response via the activation of ICD. Hence, ECT may represent an interesting approach to treat solid tumors while preventing recurrence and metastasis, possibly in combination with immunostimulating agents. PMID:25083316

  13. Indium (111In)-labelled bleomycin for the detection of intracranial lesions

    International Nuclear Information System (INIS)

    Brain scans with sup(99m)Tc pertechnetate were compared with scans made after administration of 111Indium bleomycin in 38 patients scanned on 41 occasions. They gave similar results in 34 pairs of examinations, including cases in which both failed to detect the tumour. In seven cases, the two agents differed. In two of these bleomycin distinguished residual tumour from the effects of craniotomy more clearly than did pertechnetate; in three bleomycin apparently detected tumour not seen with pertechnetate, and in two the differences may have been due to technical factors, or are unexplained. (orig.)

  14. Bleomycin labelled with sup(99m)Tc for differentiation of breast tumors

    International Nuclear Information System (INIS)

    Bleomycin labelled with sup(99m)Tc was used to differentiate benign and malignant breast tumors. Breast scintigraphy was performed 15 and 60 min following the IV injection of 5 mCisup(99m)Tc bleomycin. Thirty-two patients with breast tumor (14 carcinomas and 18 benign nodular lesions) were examined. Cytologic or histologic verification of the tumor was carried out in all cases. All malignant tumors of the breast in the investigated group of patients revealed significantly increased accumulation of sup(99m)Tc-bleomycin. (orig.)

  15. Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin

    Directory of Open Access Journals (Sweden)

    Fadi Atwan

    2012-07-01

    Full Text Available Intralesional sclerotherapy as a primary modality of management for cystic hygroma is successfully described in literature. It has many benefits over surgical approach; recurrence being the concern of as much as 20% of patients in which apparent complete excision has been performed. Bleomycin is one of sclerosing agents used as intralesional therapy in cystic hygroma. Complete response usually occurs in multiple sessions of sclerotherapy. Rarely, complete resolution occurs with single session of bleomycin sclerotherapy. We share our experience of managing a case of cystic hygroma of neck that completely resolved with single session of bleomycin sclerotherapy.

  16. Beamed-Energy Propulsion (BEP): Considerations for Beaming High Energy-Density Electromagnetic Waves Through the Atmosphere

    Science.gov (United States)

    Manning, Robert M.

    2015-01-01

    A study to determine the feasibility of employing beamed electromagnetic energy for vehicle propulsion within and outside the Earth's atmosphere was co-funded by NASA and the Defense Advanced Research Projects Agency that began in June 2010 and culminated in a Summary Presentation in April 2011. A detailed report entitled "Beamed-Energy Propulsion (BEP) Study" appeared in February 2012 as NASA/TM-2012-217014. Of the very many nuances of this subject that were addressed in this report, the effects of transferring the required high energy-density electromagnetic fields through the atmosphere were discussed. However, due to the limitations of the length of the report, only a summary of the results of the detailed analyses were able to be included. It is the intent of the present work to make available the complete analytical modeling work that was done for the BEP project with regard to electromagnetic wave propagation issues. In particular, the present technical memorandum contains two documents that were prepared in 2011. The first one, entitled "Effects of Beaming Energy Through the Atmosphere" contains an overview of the analysis of the nonlinear problem inherent with the transfer of large amounts of energy through the atmosphere that gives rise to thermally-induced changes in the refractive index; application is then made to specific beamed propulsion scenarios. A brief portion of this report appeared as Appendix G of the 2012 Technical Memorandum. The second report, entitled "An Analytical Assessment of the Thermal Blooming Effects on the Propagation of Optical and Millimeter- Wave Focused Beam Waves For Power Beaming Applications" was written in October 2010 (not previously published), provides a more detailed treatment of the propagation problem and its effect on the overall characteristics of the beam such as its deflection as well as its radius. Comparisons are then made for power beaming using the disparate electromagnetic wavelengths of 1.06 microns and 2.0 millimeters..

  17. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ye-Ji [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Lee, Seung-Hae [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Youn, Young-So; Choi, Ji-Yeon [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Song, Keung-Sub [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Cho, Min-Sun [Department of Pathology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Kang, Jihee Lee, E-mail: jihee@ewha.ac.kr [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

    2012-08-15

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  18. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    International Nuclear Information System (INIS)

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  19. Cobolt and bleomycin against carcinomas of head and neck. A controlled clinical study

    International Nuclear Information System (INIS)

    In our controlled study, combined preoperative treatment with cobalt and Bleomycin produced better results than same dosis of cobalt alone. However, no conclusions can be drawn concerning the synergistic effect of the combined treatment or superiority to an increased irradiation dose of cobalt only. We consider that Bleomycin's greatest potential in the treatment of head and neck carcinomas lies in its preoperative use in combination with radiotherapy. Radical surgery is essential to achieve optimal tumour control. (author)

  20. Intercellular Adhesion Molecule-1 and L-Selectin Regulate Bleomycin-Induced Lung Fibrosis

    OpenAIRE

    Hamaguchi, Yasuhito; Nishizawa, Yoriko; Yasui, Masahide; Hasegawa, Minoru; Kaburagi, Yuko; Komura, Kazuhiro; Nagaoka, Tetsuya; Saito, Eriko; Shimada, Yuka; Takehara, Kazuhiko; Kadono, Takafumi; Steeber, Douglas A.; Tedder, Thomas F.; Sato, Shinichi

    2002-01-01

    The development of bleomycin-induced lung injury, a model of pulmonary fibrosis, results from inflammatory cell infiltration, a process highly regulated by the expression of multiple adhesion molecules. At present, the identity and role of the adhesion molecules involved in the fibrotic process are unknown. Therefore, bleomycin-induced pulmonary fibrosis was examined in mice lacking L-selectin (L-selectin?/?) expression, intercellular adhesion molecule-1 (ICAM-1) expression, or both. After 16...

  1. Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin

    OpenAIRE

    Lawson, William E; Polosukhin, Vasiliy V.; Stathopoulos, Georgios T.; Zoia, Ornella; Wei HAN; Lane, Kirk B.; Li, Bo; Donnelly, Edwin F.; Holburn, George E.; Lewis, Kenneth G.; Collins, Robert D.; Hull, William M.; Glasser, Stephan W.; Whitsett, Jeffrey A; Blackwell, Timothy S

    2005-01-01

    Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC?/?) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight loss d...

  2. Effects of bleomycin and irradiation on euoxic and hypoxic cells

    International Nuclear Information System (INIS)

    EMT6 cells in vitro were exposed to bleomycin (BLM), either alone (under euoxic or hypoxic conditions) or in conjunction with x-radiation. Hypoxic and euoxic cells were equally sensitive to the drug in both of the systems used to induce hypoxia (ampules or chambers). Exposure to BLM immediately before x-irradiation altered the shape of the radiation survival curve decreasing the D0 by a factor of 1.3. Simultaneous exposure to x-ray and BLM resulted in lower survivals than when radiation was given either before or after drug treatment. Cells recovered quickly from BLM damage if trypsinization was delayed. The results indicate that BLM and x-rays interact to lower cell survival but that cells recover from this effect if trypsinization is delayed

  3. Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy

    Directory of Open Access Journals (Sweden)

    Dhar S

    2009-01-01

    Full Text Available Background: Though not in regular practice, intralesional (IL bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Methods: Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle or IL bleomycin (0.1% solution with concurrent anesthesia for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Results: Of the 73 patients completing the study, 39 (53% were treated with IL bleomycin and 34 (47% were treated with cryotherapy. Out of 155 treated warts, 87 (56% were treated with IL beomycin and 68 (44% were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively ( P < 0.05 by x 2 analysis and RR = 7.67. Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

  4. Different Cell Viability Assays Reveal Inconsistent Results After Bleomycin Electrotransfer In Vitro.

    Science.gov (United States)

    Jakštys, Baltramiejus; Ruzgys, Paulius; Tamoši?nas, Mindaugas; Šatkauskas, Saulius

    2015-10-01

    The aim of this study was to compare different and commonly used cell viability assays after CHO cells treatment with anticancer drug bleomycin (20 nM), high voltage (HV) electric pulses (4 pulses, 1200 V/cm, 100 µs, 1 Hz), and combination of bleomycin and HV electric pulses. Cell viability was measured using clonogenic assay, propidium iodide (PI) assay, MTT assay, and employing flow cytometry modality to precisely count cells in definite volume of the sample (flow cytometry assay). Results showed that although clonogenic cell viability drastically decreased correspondingly to 57 and 3 % after cell treatment either with HV pulses or combination of bleomycin and HV pulses (bleomycin electrotransfer), PI assay performed ~15 min after the treatments indicated nearly 100 % cell viability. MTT assay performed at 6-72 h time points after these treatments revealed that MTT cell viability is highly dependent on evaluation time point and decreased with later evaluation time points. Nevertheless, in comparison to clonogenic cell viability, MTT cell viability after bleomycin electrotransfer at all testing time points was significantly higher. Flow cytometry assay if used at later times, 2-3 days after the treatment, allowed reliable evaluation of cell viability. In overall, our results showed that in order to estimate cell viability after cell treatment with combination of the bleomycin and electroporation the most reliable method is clonogenic assay. Improper use of PI and MTT assays can lead to misinterpretation of the experimental results. PMID:26077843

  5. Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis.

    OpenAIRE

    Swiderski, R. E.; Dencoff, J. E.; Floerchinger, C. S.; Shapiro, S. D.; Hunninghake, G.W.

    1998-01-01

    Exposure to the chemotherapeutic drug bleomycin leads to pulmonary fibrosis in humans and has been widely used in animal models of the disease. Using C57BL/6 bleomycin-sensitive mice, pulmonary fibrosis was induced by multiple intraperitoneal injections of the drug. An increase in the relative amounts of steady-state alpha1(I) procollagen, alpha1(III) procollagen, and fibronectin mRNA as well as histopathological evidence of fibrosis was observed. The effect of bleomycin on the expression of ...

  6. Investigation of therapeutic efficiency of bleomycin and bleomycin-glucuronide labeled with (131)I on the cancer cell lines.

    Science.gov (United States)

    Ediz, Melis; Avc?ba??, U?ur; Unak, Perihan; Müftüler, Fazilet Zümrüt Biber; Medine, Emin ?lker; Yurt K?lçar, Ayfer; Demiro?lu, Hasan; Gümü?er, Fikriye Gül; Sakarya, Serhan

    2013-05-01

    The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ?-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells. PMID:23350895

  7. Study of the 7Be(p,?)8B and 7Li(n,?)8Li capture reactions using the shell model embedded in the continuum

    International Nuclear Information System (INIS)

    The realistic shell model which includes the coupling between many-particle (quasi-)bound states and the continuum of one-particle scattering states is applied to the spectroscopy of mirror nuclei: 8B and 8Li, as well as to the description of low energy cross sections (the astrophysical S factors) in the capture reactions: 7Be(p,?)8B and 7Li(n,?)8Li. (author)

  8. Phylogenomic Analyses of Nuclear Genes Reveal the Evolutionary Relationships within the BEP Clade and the Evidence of Positive Selection in Poaceae

    OpenAIRE

    ZHAO, LEI; Zhang, Ning; Ma, Peng-Fei; Qi LIU; Li, De-Zhu; Guo, Zhen-Hua

    2013-01-01

    BEP clade of the grass family (Poaceae) is composed of three subfamilies, i.e. Bambusoideae, Ehrhartoideae, and Pooideae. Controversies on the phylogenetic relationships among three subfamilies still persist in spite of great efforts. However, previous evidence was mainly provided from plastid genes with only a few nuclear genes utilized. Given different evolutionary histories recorded by plastid and nuclear genes, it is indispensable to uncover their relationships based on nuclear genes. Her...

  9. Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.

    Science.gov (United States)

    de Almeida, Cecilia J G; Jasmin, Jean-François; Del Galdo, Francesco; Lisanti, Michael P

    2013-07-15

    Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1(-/-)) and Cav-2-deficient mice (Cav-2(-/-)) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2(-/-) mice, but not Cav-1(-/-) mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2(-/-) mice was not associated with alterations in the TGF-? signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2(-/-) mice. Since Cav-1(-/-) mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process. PMID:24067367

  10. Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury

    Science.gov (United States)

    de Almeida, Cecilia JG; Jasmin, Jean-François; Del Galdo, Francesco; Lisanti, Michael P

    2013-01-01

    Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1?/?) and Cav-2-deficient mice (Cav-2?/?) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2?/? mice, but not Cav-1?/? mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2?/? mice was not associated with alterations in the TGF-? signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2?/? mice. Since Cav-1?/? mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process. PMID:24067367

  11. Structure of the excited states of 11Be reached through the reaction d(10Be,p)11Be

    International Nuclear Information System (INIS)

    The one-neutron transfer reaction d(10Be,p)11Be has been studied at 32 A.MeV at GANIL with a 10Be secondary beam. Protons were detected by the silicon strip array MUST. The ground state and excited states of 11Be at 0.32, 1.78 and 3.41 MeV were populated, demonstrating the feasibility of transfer reactions induced by radioactive beams leading to bound and unbound states. A DWBA (distorted wave born approximation) analysis indicates for the 3.41 MeV state spin and parity 3/2+ or 5/2+ and a spectroscopic factor of 0.18 or 0.11, respectively. A broad structure centered at 10 MeV is also observed and corresponds to transfer to the 1d sub-shells. If one assumes that only the 1d3/2 orbital contributes to this structure, the splitting of the 1d neutron states in 11Be is estimated to be 6.3 MeV. Using a 2-particle-RPA (random phase approximation) model, we have shown that neutron-neutron correlations play an important role in the inversion between the 2s1/2 and 1p1/2 neutron states in 11Be. (author)

  12. Precision measurement of the $^{7}$Be(p, $\\gamma$)$\\,^{8}$B cross section with an implanted $^{7}$Be target

    CERN Document Server

    Baby, L T; Goldring, G; Hass, M; Weissman, L; Fedosseev, V; Köster, U; Nir-El, Y; Haquin, G; Gäggeler, H W; Weinreich, R

    2003-01-01

    The $^{7}$Be(p, $\\gamma$) $\\,^{8}$B reaction plays a central role in the evaluation of solar neutrino fluxes. We report on a new precision measurement of the cross section of this reaction, following our previous experiment with an implanted $^{7}$Be target, a raster- scanned beam, and the elimination of the backscattering loss. The new measurement incorporates a more abundant $^{7}$Be target and a number of improvements in design and procedure. The point at E$_{lab}$ = 991 keV was measured several times under varying experimental conditions, yielding a value of S$_{17}$(E$_{c.m.}$ = 850 keV) = 24.0 $\\pm$ 0.5 eV b. Measurements were carried out at lower energies as well. Because of the precise knowledge of the implanted $^{7}$Be density profile, it was possible to reconstitute both the off- and on-resonance parts of the cross section and to obtain from the entire set of measurements an extrapolated value of S$_{17}$(0)=21.2 $\\pm$ 0.7 eV b.

  13. Static and dynamic mechanics of the murine lung after intratracheal bleomycin

    Directory of Open Access Journals (Sweden)

    Papiris Spyridon

    2011-05-01

    Full Text Available Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 ?L or bleomycin (2 mg/Kg in 50 ?L saline were administered to C57BL/6 (n = 40 and Balb/c (n = 32 mice. Injury/fibrosis score, tissue volume density (TVD, collagen content, airway resistance (RN, tissue damping (G and elastance coefficient (H, hysteresivity (?, and area of pressure-volume curve (PV-A were determined after 7 and 21 days (inflammation and fibrosis stage, respectively. Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.

  14. Study of the cellular uptake and distribution of 57cobalt bleomycin in Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    We investigated the dependence of the cellular uptake of 57 cobalt-bleomycin on the exposure time and on the dose. In addition we observed the influences due to the incubation temperature, to the growth phase of the tumor cells and due to the composition of the suspensory medium. In supplementary experiments we investigated the binding of the labelled cytostatic agent to erythrocytes, its adsorption to broken Ehrlich ascites tumor cells and the 57 cobalt-bleomycin outflow from pre-loaded intact Ehrlich ascites tumor cells. The 57 cobalt-bleomycin uptake of intact Ehrlich ascites tumor cells is determined by characteristic kinetics. Moreover, the erythrocytes and injured Ehrlich ascites tumor cells show a qualitatively similar graph of the 57 cobalt-bleomycin binding, which can clearly be distinguished from the kinetics found with intact Ehrlich ascites tumor cells. The uptake of this cytostatic agent depends on an unequivocal time-dose-temperature relationship. The transport mechanism of the 57 cobalt-bleomycin uptake was considered as endocytosis. An endocytosis-stimulating inducer could not be detected. However, we obtained indications that the cell-bound cytostatic agent is taken up in two compartments: on the cellular surface and in the interior of the cell. (orig./MG)

  15. Treatment of hypovascular hepatic cavernous hemangiomas by percutaneous intratumoral bleomycin injection after selective hepatic arterial embolization

    International Nuclear Information System (INIS)

    Objective: To assess the safety and effectiveness of treatment of cavernous hemangiomas of liver(CHL) by percutaneous intratumoral bleomycin injection after transarterial embolization (TAE). Methods: 9 cases of hypovascular CHL treated by percutaneous intratumoral bleomycin injection after TAE were studied prospectively. All the cases were diagnosed as hypovascular CHL(diameter > 5 cm) by CT/MRI. With only spotty or few patchy enhancement in arterial phase persisting into the delayed phase were shown on enhanced CT. TAE with emulsion of ultra-fluid lipiodol(10 ml) and bleomycin(8 mg) was performed in every patient, with dosage of 5-10 ml depending on the vascular space of different lesions. Percutaneous intratumoral multi- point injection with bleomycin (8-16 mg) solution was undertaken 4 days after TAE, and repeated every 3-4 days for 2-3 times. Each case undertook upper abdominal CT scan 1 month later, and then with 3, 6 month to 1 year periodic follow-up. Results: DSA features of all the 9 cases demonstrated as same as those on enhanced CT scanning with dispersion of lipiodol within the lesions. All the lesions decreased in volume markedly 1 month after the therapy, and kept on until 1 year later. 2 patients developed post-TAE acute cholecystitis and one intrahepatic biloma. Conclusion: TAE combined with percutaneous intra-tumoral bleomycin injection is a safe and effective method in treating hypovascular CHL. (authors)

  16. 111In-bleomycin breast and axilla imaging

    International Nuclear Information System (INIS)

    111Indium-Bleomycin (111In-Blm), a new radiopharmaceutical, was administered intravenously to 37 patients with benign and malignant breast lesions. Early and delayed images of both the breasts and axillae were made, and results were correlated with physical examination, histopathology of the excised lesion, mammography, and thermography. In 18 patients with malignant disease, clinical examination of the breast and axilla correlated with histopathology in 78 and 54 percent of the cases, respectively. Images of the breast were accurate (true positives) in 83 percent of the cases. Images of the axilla were accurate in 62 percent of the cases. Mammography was correct and suggested malignancy in 88 percent, and thermography in 73 percent of the cases. In 19 patients with benign breast lesions, clinical examination of the breast and axilla correlated with histopathology in 68 and 95 percent of the cases, respectively. Scans of the breast and axilla were correct (true negative) 79 and 95 percent of the time, respectively. Mammography was correct, and suggested benignancy, in 53 percent and thermography in 25 percent of the cases. Imaging of the breasts using 111In-Blm appears to be as accurate as physical examination and mammography for palpable benign and malignant breast tumors

  17. The combined effects of 60Co gamma-rays and continuous low concentrations of bleomycin on cultured mammalian cells

    International Nuclear Information System (INIS)

    The combined effects of 60Co gamma-rays and continuous, low concentrations of bleomycin on FM3A (mouse mammary adenocarcinoma cells) were examined, and the clinical application of this combination was reported in this paper. The combined effect appeared to be synergistic, and bleomycin seemed to interfere with Elkind recovery. (author)

  18. Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203, and copper-67

    International Nuclear Information System (INIS)

    The radiochemical purity of the cobalt-57 complex of bleomycin could be enhanced by adjusting the pH of the final product to a value between 5 and 6. This radiopharmaceutical appeared to have better tumor visualizing properties compared to the not neutralized preparation. The clinical use of the cobalt-57 bleomycin complex is however limited by the long physical half-life of the label, causing a risk of radioactive contamination. It appeared to be possible to label bleomycin with radioactive cations (111In3+, sup(99m)Tc4+, 197Hg2+ and 67Cu2+) having suitable gamma ray energies and short half-lifes. These bleomycin complexes showed a high radiochemical purity judged by their behaviour on thin layer chromatography, paper chromatography, and electrophoresis, but their application as tumor visualizing radiopharmaceutical turned out to be disappointing compared with cobalt-57 bleomycin. (orig.)

  19. The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells

    International Nuclear Information System (INIS)

    Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid lines, suggesting that the capacity to repair the induced DNA lesion is present

  20. Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer

    International Nuclear Information System (INIS)

    In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy of the lung

  1. Contribution of cobalt 57 labelled bleomycin in the diagnosis of pulmonary round intraparenchymatous lesions

    International Nuclear Information System (INIS)

    One hundred and eleven patients with a round lesion within the lung parenchyma were submitted to a lung scan using cobalt 57 labelled bleomycin. In all cases, the diagnosis of benign or malignant disease was made definitely by bronchoscopy, fiber endoscopy, transparietal needle biopsy or thoracotomy. Out of 89 neoplasic foci, 87 took up labelled bleomycin with a fixation ratio greater than 13. On the other hand, the 22 benign round foci, except for the large silico-tuberculous nodule, remained silent on radio-isotope scanning. The great value of scanning using cobalt 57 labelled bleomycin in the detection of the malignant or benign nature of round images within the lung is emphasized, the clinical and radiological pre-operative diagnosis remains one of the most difficult in lung disease problems

  2. Clinical Evaluation of 57Co-labelled Bleomycin for Tumor Localization

    International Nuclear Information System (INIS)

    Investigation with 57Co-Bleomycin in patients with the various cancers and in tumor bearing animals are described. In the patients, 57Co-Bleomycin appears to be one of the useful tumor- seeking radiopharmaceuticals, and worth applicable to clinical uses. Labelled yield of 57Co-Bleo was about 97% by thin layer chromatography. The pyrogen free tests were performed to meet U.S.P. critical ranges. In clinical studies with 57Co-Bleo, 4 cases out of 5 patients with lung cancer, 2 cases among 3 thyroid cancer patients, and all 3 hepatoma patients showed positive tumor scans. The patients with stomach cancer, and the esophageal cancer showed false negative scintigraphy. A case with pulmonary tuberculosis showed a positive scan while liver abscess showed a negative picture. The merits of 57Co-Bleomycin scintigraphy seems to be its relatively high affinity to tumors and low radiation hazard in spite of long physical half life.

  3. Pulmonary complications of irradiation and bleomycin after radical surgery for esophageal cancer

    International Nuclear Information System (INIS)

    From 1978 to 1980, 52 patients underwent radical surgery for esophageal cancer, and they given radiotherapy of 300-500 rads and/or 50-100 mg of bleomycin prophylatically during the postoperative period. Of the total cases, five patients developed acute interstitial pneumonitis. All cases were controlled successfully by the administration of prednisolone, but one patient died of a complication of systemic aspergillosis. Pneumonitis occurred during the early course of irradiation, i.e.two cases during irradiation and one cases three days after irradiation. Pneumonitis also occurred with a low dose of bleomycin (70 mg) in two cases. Clinical signs of radiation pneumonitis were more severe in cases of esophageal cancer than in cases of lung cancer and breast cancer as had been previously reported. These results suggest that surgery for esophageal cancer tends to sensitize the lung and leads to pulmonary complications after radiotherapy and chemotherapy employing bleomycin. (author)

  4. Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Crimi Nunzio

    2006-11-01

    Full Text Available Abstract Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-? were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i loss of body weight, (ii mortality rate, (iii lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts, (iv lung edema, (v histological evidence of lung injury and collagen deposition, (vi lung myeloperoxidase, IL-1 and TNF-? staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.

  5. Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Bleomycin is a widely accepted cancer drug but may induce life-threatening interstitial lung disease in a subset of patients. We evaluated the effect of bleomycin administration on pulmonary surfactant function and composition in rabbit lungs. In order to obtain a uniform response to bleomycin, aerosol technology was employed for bronchoalveolar delivery of 1.8 U/kg b.w. bleomycin. On days 4, 8, 16, 24, 32, and 64 after challenge, bronchoalveolar lavages were performed. Sham-aerosolized rabbits served as controls. In the early acute respiratory distress syndrome (ARDS)-like post-bleomycin period (4-16 days), marked loss of surface activity of the large surfactant aggregate (LA) fraction of surfactant was noted. In parallel, reduced percentages of LA, but only minor changes in surfactant apoproteins (SP)-A, SP-B, and SP-C, were encountered. Analysis of the surfactant lipid profile showed impressively enhanced cholesterol and significantly decreased phosphatidylglycerol (PG) levels. The relative content of dipalmitoyl-PC (DPPC) was slightly increased, and a several-fold increase within the 1-O-alkyl-2-acyl subclass of PC was observed. During the prolonged fibroproliferative period, a highly significant downregulation of SP-B and SP-C levels was observed. This was paralleled by an upregulation of the total extracellular phospholipid pool, with a far-reaching normalization of the (phospho)-lipid profile. The biophysical surfactant function never fully normalized within the 64-day observation period. In conclusion, bleomycin caused marked abnormalities of pulmonary surfactant, with the profile of changes being different between the early ARDS and the late fibrotic phase

  6. Induction of Apoptosis and Micronuclei by Bleomycin Sulfate in Different Cell Cycle Stages of Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Saify B

    2004-01-01

    Full Text Available Introduction: Bleomycin sulfate is a DNA damaging agent used in cancer chemotherapy. The effect of this drug on various cell cycle stages might be different, thus inducing different modes of death (apoptotic or mitotic death. The aim of this investigation was to study the effects of bleomycin on human peripheral blood lymphocytes at various cell cycle stages by two different end points (induction of apoptosis or micronuclei. Material and Methods: Human peripheral blood lymphocytes were treated with various doses of bleomycin at G0, G1, and G2 phases of the cell cycle and the percentages of apoptosis (AP and micronuclei (MN were determined. The peripheral lymphocytes were isolated by ficoll hypaque and suspended in RPMI-1640 containing 15 % fetal calf serum. The isolated lymphocytes were stimulated by phytohemagglutinin (PHA, cultured again inRPMI-1640, harvested after 64 hrs and 96 hrs, and stained with acridine orange and ethidiumbromide to determine the percentage of apoptotic cells. MN assay was done according to the standard in vitro micronucleus assay. Results: The results showed that the percentages of apoptotic cells and MN at G2 stage were significantly higher than those of G0 and G1 stages. At higher doses, MN formation and apoptotic cells were increased; however with increasing time, the percentage of MN decreased while the percentage of apoptotic cells generally increased in all the cell cycle stages. Conclusion: The results indicate that bleomycin is a potent inducer of both micronuclei and apoptosis. The incidence of apoptotic cells following bleomycin treatment in G0 and G1 was much higher than the incidence of micro nucleated cells at the two sampling times. The percentage of AP cells following bleomycin treatment remained constant across cell cycle stages.

  7. Enhanced cough reflex in a model of bleomycin-induced lung fibrosis in guinea pigs.

    Science.gov (United States)

    Fernández-Blanco, Joan Antoni; Aguilera, Mònica; Domènech, Anna; Tarrasón, Gema; Prats, Neus; Miralpeix, Montse; De Alba, Jorge

    2015-12-01

    Fibrotic lung diseases, such as idiopathic pulmonary fibrosis, are associated with spontaneous dry cough and hypersensitivity to tussive agents. Understanding the pathophysiology driving enhanced cough may help us to define better therapies for patients. We hypothesized that lung fibrosis induced by intratracheal bleomycin would exacerbate the cough reflex induced by tussive agents in guinea pigs. Disease progression in the lungs was characterized at days 1, 7, 14, 21 and 28 after bleomycin administration. Inflammatory and fibrotic markers, as well as neurotrophin levels, were assessed in bronchoalveolar lavage fluid and/or lung tissue. Cough sensitivity to citric acid, capsaicin and allylisothiocyanate was evaluated in conscious animals at days 14 and 21 after bleomycin administration. Pulmonary lesions evolved from an early inflammatory phase (from day 1 to day 7) to a fibrotic stage (between days 14 and 28). Fibrosis was related to increased levels of matrix metalloproteinase-2 in bronchoalveolar lavage fluid (day 21: saline, 0.26 ng/ml; bleomycin, 0.49 ng/ml). At day 14, we also observed increased cough reflexes to citric acid (163%), capsaicin (125%) and allylisothiocyanate (178%). Cough exacerbation persisted, but at a lower extent, by day 21 for capsaicin (100%) and allylisothiocyanate (54%). Moreover, bronchoalveolar lavage fluid concentrations of brain-derived neurotrophic factor, suggested to induce nerve remodelling in chronic cough, were also enhanced (day 1: saline, 14.21 pg/ml; bleomycin, 30.09 pg/ml). In summary, our model of bleomycin-induced cough exacerbation may be a valuable tool to investigate cough hypersensitivity and develop antitussive therapies for fibrotic lung diseases. PMID:26275723

  8. Long term follow-up in patients with a naso-pharynx carcinoma after induction chemotherapy by cisplatin, 5-fluoro-uracil and bleomycin (pbf) followed by a bi-fractionated radiotherapy and a consolidation chemotherapy

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficiency and the long term survival after neoadjuvant chemotherapy by cisplatin, 5-fluoro-uracil and bleomycin, followed by a bi fractionated radiotherapy and an adjuvant chemotherapy. The protocol associating a P.B.F. type chemotherapy in the locally evolved disease is justified by its efficiency in terms of objective response rate and local control rate, that expressed by an improvement of the global survival rate and survival without disease at five and ten years. The adjuvant chemotherapy is very toxic and did not show any benefit. (N.C.)

  9. E- and P-Selectins Synergistically Inhibit Bleomycin-Induced Pulmonary Fibrosis

    OpenAIRE

    Horikawa, Mayuka; Fujimoto, Manabu; Hasegawa, Minoru; Matsushita, Takashi; Hamaguchi, Yasuhito; Kawasuji, Ayako; Matsushita, Yukiyo; Fujita, Tomoyuki; Ogawa, Fumihide; Takehara, Kazuhiko; Steeber, Douglas A.; Sato, Shinichi

    2006-01-01

    The development of bleomycin-induced lung injury, which is a model of pulmonary fibrosis, results from inflammatory cell infiltration, a process highly regulated by the expression of multiple adhesion molecules. Therefore, bleomycin-induced lung fibrosis was examined in E-selectin?/? mice, P-selectin?/? mice, and E-selectin?/? mice treated with anti-P-selectin monoclonal antibody (mAb) in comparison of wild-type mice. E-selectin?/? mice treated with anti-P-selectin mAb exhibited augmented lun...

  10. Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Kang, Hyeon Hui; Yoon, Hyung Kyu; Kim, Young Kyoon; Kim, Kwan Hyung; Moon, Hwa Sik; Park, Sung Hak

    2010-01-01

    CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease o...

  11. Evaluation of cold areas on the thyroid scan with sup(99m)Tc-bleomycin

    International Nuclear Information System (INIS)

    The value of sup(99m)Tc-bleomycin scintigraphy in the evaluation of cold areas on a sup(99m)Tc-pertechnetate scan was investigated in 35 patients. A histological diagnosis was obtained in 31 patients. Only one of the six malignant lesions was considered as positive and two as doubtful. Of the remaining 25 patients with non-toxic colloid goitre, one was clearly positive and four were doubtful. These results indicate that sup(99m)Tc-bleomycin scintigraphy is not a valuable procedure in the further evaluation of patients with cold lesions. (orig.)

  12. Effects of radiotherapy combined with daily intramuscular injection of bleomycin for uterine cervical cancer

    International Nuclear Information System (INIS)

    A total of 103 cases of cancer of the uterine cervix, untreated previously, were treated with radiotherapy combined with daily intramuscular injection of Bleomycin 30 minutes before irradiation (BR therapy) in 12 institutions. Result showed that especially in cases of stage III, BR therapy was superior in primary local control rate (89.6%), recurrence rate (20.8%) and crude 5-year survival rate (56.5%) to that of nationwide statistics. No severe side effects were found. It was concluded that external radiotherapy could control advanced cancers of uterine cervix combining with intramuscular injection of Bleomycin. (author)

  13. Dietary Flaxseed Oil Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats

    OpenAIRE

    Joshua Lawrenz; Betty Herndon; Afrin Kamal; Aaron Mehrer; Dim, Daniel C.; Cletus Baidoo; David Gasper; Jonathan Nitz; Agostino Molteni; Baybutt, Richard C.

    2012-01-01

    Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short-chain omega-3 fatty acids, α-linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney. To test this hypothesis, 72 rats were divided between diets receiving either 15% (w/w) flaxseed oil or 15% ...

  14. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

    Science.gov (United States)

    Rey-Parra, G J; Vadivel, A; Coltan, L; Hall, A; Eaton, F; Schuster, M; Loibner, H; Penninger, J M; Kassiri, Z; Oudit, G Y; Thébaud, B

    2012-06-01

    Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes ?-smooth muscle actin (?-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS. PMID:22246130

  15. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

    Science.gov (United States)

    Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J

    2003-12-01

    Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model. PMID:14680076

  16. Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

    Directory of Open Access Journals (Sweden)

    Araújo Maria Cristina P.

    1999-01-01

    Full Text Available Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM were investigated in Chinese hamster ovary (CHO cells. Three concentrations of each drug, turmeric (100, 250 and 500 mg/ml and curcumin (2.5, 5 and 10 mg/ml, were combined with BLM (10 mg/ml in CHO cells treated during the G1/S, S or G2/S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G2/S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.

  17. Studies on bleomycin-induced repair DNA synthesis in permeable mouse ascites sarcoma cells.

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    Mori,Shigeru

    1989-04-01

    Full Text Available To study the mechanism of DNA excision repair, a DNA repair system employing permeable mouse sarcoma (SR-C3H/He cells was established and characterized. SR-C3H/He cells were permeabilized with a 0.0175% Triton X-100 solution. The permeable cells were treated with 1 mM ATP and 0.11 mM bleomycin, and then washed thoroughly to remove ATP and bleomycin. Repair DNA synthesis occurred in the bleomycin-damaged, permeable SR-C3H/He cells when incubated with ATP and four deoxyribonucleoside triphosphates. The repair nature of the DNA synthesis was confirmed by the BrdUMP density shift technique, and by the reduced sensitivity of the newly synthesized DNA to Escherichia coli exonuclease III. The DNA synthesis was optimally enhanced by addition of 0.08 M NaCl. Studies using selective inhibitors of DNA synthesis showed that aphidicolin-sensitive DNA polymerase (DNA polymerase alpha and/or delta and DNA polymerase beta were involved in the repair process. The present DNA repair system is thought to be useful to study nuclear DNA damage by bleomycin, removal of the damaged ends by an exonuclease, repair DNA synthesis by DNA polymerases and repair patch ligation by DNA ligase(s.

  18. Comparison of gamma radiation and radiomimmetic chemical, bleomycin in leukocytes from certain genetic disorders

    International Nuclear Information System (INIS)

    Full text: To compare the frequency and distribution pattern of bleomycin and gamma radiation induced chromosomal aberrations in human genetic disorders. To study if the induced chromosomal break points are specific for specific human genetic disorders. Human genetics disorders such as; retinitis pigmentosa, retinoblastoma, xeroderma pigmentosa and gonadal dysgenesis were used in our study. Suitable controls were maintained. The frequency and distribution pattern of chromosomal break points in individual chromosomes were determined in lymphocytes exposed to 50r of gamma radiation and 10?g/ml of bleomycin for 3h at G2. In normal individuals none of the unirradiated leukocyte cultures of any syndrome showed any accountable number of chromosomal aberrations. The frequency of radiation induced chromosomal break points showed a non random distribution pattern and frequently clustered at some specific chromosome regions to form hot spots. Lack of linear-quadratic dose response was observed in the lymphocyte exposed to bleomycin in normal individual. The frequency of chromosomal aberrations in the whole genome for the genetic disorders were higher than the controls and a varying distribution pattern of bleomycin induced breaks per cell was observed

  19. Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

    Directory of Open Access Journals (Sweden)

    Bartholomei-Santos Marlise Ladvocat

    1997-01-01

    Full Text Available Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21. Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

  20. The use of isotopic labels to probe the mechanism of DNA oxidation by iron bleomycin

    International Nuclear Information System (INIS)

    When the antitumor antibiotic bleomycin is activated anaerobically with Fe(III) and hydrogen peroxide or with Fe(II) and limiting oxygen, the DNA products are free nucleic acid base and an oxidatively damaged sugar lesion which undergoes strand scission when treated with alkali. Stabilization of the initial product by borohydride reduction and digestion by P1 nuclease and alkaline phosphatase afforded 2 double-prime-deoxypentitol-3 double-prime-O-5'-phospho-2'-deoxypurine nucleosides that accounted for 99, 81 and 48% of the pyrimidine base released from d(CGCGCG), poly(dA-dU) and poly(dG-dC), respectively. Further enzymatic degradation yielded 2-deoxy-D-erythro-pentitol and 2-deoxy-L-threo-pentitol which were identified by mass spectrometry. The 2'-deoxypentos-4'-ulose product arising from the interaction of d(CGCGCG) with bleomycin was 86 and 97% 18O-labeled at C-4' at pH 9.0 and 7.8, respectively, when limiting 16O-labeled oxygen was used to activate bleomycin in 18O-water. Either complete isotopic exchange between solvent and a high-valent iron-oxo species of bleomycin or the equivalent of a 1e- oxidation of the presumed 4 carbon-centered radical of DNA are required to account for these findings. When oxygen is supplied in excess of what is required to activate bleomycin, the C3'-C4' bond of DNA is ruptured to yield transbase propenals and oligonucleotides bearing 5-phosphate and 3-phosphoglycolate termini. Kinetics study of base propenal formation from a DNA-bound precursor and release of 3H from pro R and pro S poly(dA-[2-3H]dU) showed that reported rapid release compared penal formation was the result of specific release from the pro R position and was not a consequence of the base release pathway nor nonstereospecific enolization of 2' hydrogens

  1. A Systematic Review of Talc Compared with Bleomycin for Patients with Malignant Pleural Effusions

    Directory of Open Access Journals (Sweden)

    Yonggang WEI

    2009-03-01

    Full Text Available Background and objective Malignant pleural effusions are a common complication in advanced malignancy. Talc, bleomycin and the tetracyclines are the three most frequently used sclerosants. The aim of this study is to evaluate the efficacy and adverse effects of patients with malignant pleural effusions treated with talc and bleomycin. Methods We searched PubMed, Embase, the Cochrane Library, Chinese biomedicine literature database (CBM, CNKI, VIP, references of included studies for randomized controlled trials comparing talc with bleomycin for patients with malignant pleural effusions. The quality of included studies was assessed independently by two reviewers, discrepancies were resolved by discussion with the third person. We analyzed the data using Review Manager (version 5.0 software. Results Six studies totaling 224 patients were included. Meta analysis results were as follows: there was significantdifference in treatment success (RR=1.22, 95%CI: 1.05-1.42, recurrence rate (RR=0.31, 95%CI: 0.11-0.87 between talc group and bleomycin group, there was no significant difference between the two groups in case fatality rate (RR=1.39, 95%CI: 0.84-2.30, fever (RR=0.68, 95%CI: 0.24-1.94, pain (RR=0.22, 95%CI: 0.01-4.32. Conclusion Current evidence indicate that talc is super to bleomycin for patients with malignant pleural effusions in terms of improvingtreatment success and reducing recurrence rate, there is no significant difference between the two group with regard to casefatality rate, fever, pain, the results mentioned above still need to be confirmed by high quality, large sample, multicenter randomized controlled trial.

  2. IL-33 precursor and bleomycin synergize in inducing lymphocyte accumulation and fibrosis in the lungs

    Directory of Open Access Journals (Sweden)

    Sergei P. Atamas

    2013-06-01

    Full Text Available We and others have previously found that precursor IL-33 (PRIL33 protein is biologically active without proteolytic activation. We reported that the levels of PRIL33 are substantially elevated in the lungs of patients with interstitial lung disease (ILD, which is associated with idiopathic pulmonary fibrosis and systemic sclerosis. PRIL33 remains intranuclear and promotes inflammation in a non-Th2 fashion by not engaging the mature IL-33 receptor T1/ST2. To further assess the biological role of the elevated expression of PRIL33 in ILD, intratracheal bleomycin injury to the lung, alone or in combination with recombinant adenovirus delivery of PRIL33, was used to model ILD in mice. Combined PRIL33 gene delivery and bleomycin challenge had a potentiating effect on pulmonary lymphocytosis; accumulation of collagen; expression of HSP70; and the levels of TGF-?, CCL6, MCP-1, and MIP-1?, with these combined effects significantly exceeding the sum of the effects of PRIL33 gene delivery or bleomycin challenge alone (p < 0.05. By contrast, the combined effects of PRIL33 expression and bleomycin on bronchoalveolar lavage counts of macrophages and neutrophils in these mice were additive of the effects of each of these factors alone. The Th2 cytokines IL-4, IL-5, and IL-13 were not part of this synergy, and gene deficiency of T1/ST2 did not affect the synergistic nature of the “double-hit” from PRIL33 expression and bleomycin injury. It was concluded that elevated PRIL33 expression in ILD is a likely contributor to inflammatory and fibrotic lung injury, and that this contribution is independent of the T1/ST2 receptor or Th2 cytokines.

  3. Microscopic study of the 7Li(n,?)8Li and 7Be(p,?)8B reactions in a multiconfiguration three-cluster model

    International Nuclear Information System (INIS)

    The three-cluster generator coordinate method is applied to the 7Li(n,?)8Li and 7Be(p,?)8B capture reactions. The 8B (or 8Li) nucleus is defined by a mixing of (?+3He)+p and (?+p)+3He (or mirror) configurations. We investigate the sensitivity of different observables with respect to the nucleon-nucleon interaction by considering four different Volkov forces. For all of them, the model fairly reproduces most of the experimentally known spectroscopic properties of the 8B and 8Li mirror nuclei. Recent measurements of the quadrupole moments are well explained without a halo structure. The 7Li(n,?)8Li cross section supports the data of Imhof et al. rather than those of Wiescher et al. At zero energy, the 7Be(p,?)8B astrophysical S-factors slightly depend on the nucleon-nucleon interaction. They are consistent with the currently accepted value, but contradict lower estimates. (orig.)

  4. Phylogenomic analyses of nuclear genes reveal the evolutionary relationships within the BEP clade and the evidence of positive selection in Poaceae.

    Science.gov (United States)

    Zhao, Lei; Zhang, Ning; Ma, Peng-Fei; Liu, Qi; Li, De-Zhu; Guo, Zhen-Hua

    2013-01-01

    BEP clade of the grass family (Poaceae) is composed of three subfamilies, i.e. Bambusoideae, Ehrhartoideae, and Pooideae. Controversies on the phylogenetic relationships among three subfamilies still persist in spite of great efforts. However, previous evidence was mainly provided from plastid genes with only a few nuclear genes utilized. Given different evolutionary histories recorded by plastid and nuclear genes, it is indispensable to uncover their relationships based on nuclear genes. Here, eleven species with whole-sequenced genome and six species with transcriptomic data were included in this study. A total of 121 one-to-one orthologous groups (OGs) were identified and phylogenetic trees were reconstructed by different tree-building methods. Genes which might have undergone positive selection and played important roles in adaptive evolution were also investigated from 314 and 173 one-to-one OGs in two bamboo species and 14 grass species, respectively. Our results support the ((B, P) E) topology with high supporting values. Besides, our findings also indicate that 24 and nine orthologs with statistically significant evidence of positive selection are mainly involved in abiotic and biotic stress response, reproduction and development, plant metabolism and enzyme etc. from two bamboo species and 14 grass species, respectively. In summary, this study demonstrates the power of phylogenomic approach to shed lights on the evolutionary relationships within the BEP clade, and offers valuable insights into adaptive evolution of the grass family. PMID:23734211

  5. Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo

    OpenAIRE

    Farahnaz Fatemi; Jamshid Najafian; Koroush Ahmadpour

    2005-01-01

    Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients) was treated with bleomycin tattoo and the group B ...

  6. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-? signaling in lung fibroblasts

    OpenAIRE

    Inagaki Hirofumi; Hirata Yukiyo; Shimizu Takako; Sunazuka Toshiaki; Matsuda Kuniko; Abe Shinji; Usuki Jiro; Azuma Arata; Li Ying Ji; Kawada Tomoyuki; Takahashi Satoru; Kudoh Shoji; Omura Satoshi

    2006-01-01

    Abstract Background Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM) without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods Seven-week-old male ICR mi...

  7. Preparation of [6lCu]Bleomycin Complexes as a Potential PET radiopharmaceutical and it's biological evaluation in normal and tumor-bearing rodents

    International Nuclear Information System (INIS)

    [61Cu]Bleomycin ([61Cu]Bleomycin) was prepared using [61Cu]CuCl2, produced via natZn(p,x)61Cu (180?A proton irradiation, 22 MeV, 3.2 h), purified by ion chromatography method. [61Cu]Bleomycin was prepared at optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 2-10 mCi 61CuCl2) with radiochemical purity over 98% determined by HPLC and radio-thin layer chromatography. [61Cu]Bleomycin was administered into the normal and tumor bearing rodents up to 210 minutes followed by biodistribution and co incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal scarification or imaging method. [61Cu] Bleomycin can be a potential PET radiotracer for tumor imaging.

  8. CD19 Regulates Skin and Lung Fibrosis via Toll-Like Receptor Signaling in a Model of Bleomycin-Induced Scleroderma

    OpenAIRE

    Yoshizaki, Ayumi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Fumihide; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Tedder, Thomas F; Sato, Shinichi

    2008-01-01

    Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general “rheostat” that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis model, we investigated the development of fibrosis and autoimmunity in CD19-deficient mice. Bleomycin-treated wild-ty...

  9. Bleomycin-induced pulmonary fibrosis in hamsters. An alveolar macrophage product increases fibroblast prostaglandin E2 and cyclic adenosine monophosphate and suppresses fibroblast proliferation and collagen production.

    OpenAIRE

    Clark, J G; Kostal, K M; Marino, B A

    1983-01-01

    Bleomycin-induced pulmonary fibrosis in hamsters is associated with collagen accumulation that results from increased lung collagen synthesis rates. However, 1-2 wk after intratracheal instillation of bleomycin, lung collagen synthesis rates decline toward control values. To evaluate the potential role of the bronchoalveolar macrophage in regulating lung collagen production, we studied the effects of macrophages from normal and bleomycin-treated hamsters upon fibroblasts in vitro. We observed...

  10. Suppression of a DNA base excision repair gene, hOGG1, increases bleomycin sensitivity of human lung cancer cell line

    International Nuclear Information System (INIS)

    Bleomycin (BLM) has been found to induce 8-oxoguanine and DNA strand breaks through producing oxidative free radicals, thereby leading to cell cycle arrest, apoptosis and cell death. Cellular DNA damage repair mechanisms such as single strand DNA break repair/base excision repair (BER) are responsible for removing bleomycin-induced DNA damage, therefore confer chemotherapeutic resistance to bleomycin. In this study, we have investigated if down-regulation of human 8-oxoguanine DNA glycosylase (hOGG1), an important BER enzyme, could alter cellular sensitivity to bleomycin, thereby reducing chemotherapeutic resistance in human tumor cell. A human lung cancer cell line with hOGG1 deficiency (A549-R) was created by ribozyme gene knockdown technique. Bleomycin cellular sensitivity and DNA/chromosomal damages were examined using MTT, colony forming assay, comet assay as well as micronucleus assay. We demonstrated that hOGG1 gene knockdown enhanced bleomycin cytotoxicity and reduced the ability of colony formation of the lung cancer cell lines. We further demonstrated that bleomycin-induced DNA strand breaks resulted in an increase of micronucleus rate. hOGG1 deficiency significantly reduced DNA damage repair capacity of the lung cancer cell lines. Our results indicated that hOGG1 deficiency allowed the accumulation of bleomycin-induced DNA damage and chromosomal breaks by compromising DNA damage repair capacity, thereby increasing cellular sensitivity to bleomycin

  11. 51Cr-bleomycin in the diagnosis of tumours of the chest

    International Nuclear Information System (INIS)

    51Cr-bleomycin was used for the scintigraphic diagnosis of primary and secondary tumours of the thorax. The study was based on observations in 104 patients. The scintigraphy was performed using a gamma camera coupled to an on-line computer. Active lesions were scored using a semiquantitative scale of scores 0 to 5. Images were subdivided into 222 regions considered. In 72 of these, the presence of disease was diagnosed (64 malignant, 8 non-malignant) and 150 regions were classified as free from disease. At the decision threshold of score 2, over-all sensitivity and specificity of the scintigraphic detection of malignant tumours amounted to 97 and 79%, respectively. Inflammatory changes displaced some detectable accumulation of 51Cr-bleomycin but scores attributed to these lesions did not exceed the value of 2. (orig.)

  12. Survival of diploid yeast cells to bleomycin in combination with UV-light or hyperthermia

    International Nuclear Information System (INIS)

    In the present work we have investigated the possible interaction between Bleomycin (B) and UV light or hyperthermia (HT) in the induction of lethal events in diploid yeast populations in the stationary phase of growth. UV and B acting as single agents determine sigmoid survival curves. The combination of UV+B produces different degrees of sensitization depending on dose ranges. For [B]=7.5 ?g/ml combined with different UV fluences an exponential course is observed, suggesting overlapping lesion specificity of the involved repair pathways (excision and recombination). The hyperthermia plus Bleomycin treatment produces different degrees of inactivation depending on the sequences. Maximal inactivation effect was obtained for the sequence B+HT. In the case of HT+B ([B]>7.5 ?g/ml) the obtained sensitization is lower. (orig.)

  13. Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

    International Nuclear Information System (INIS)

    A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

  14. Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Greene, M.H.; Goedert, J.J.; Bech-Hansen, N.T.; McGuire, D.; Paterson, M.C.; Fraumeni, J.F. Jr.

    1983-01-01

    A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis.

  15. Structural studies on metallobleomycins: The interaction of Pt(II and Pd(II with bleomycin

    Directory of Open Access Journals (Sweden)

    NIKOS KATSAROS

    2003-05-01

    Full Text Available Two of the most successful chemotherapeutic agents used in the treatment of several neoplasias are bleomycin and cisplatin. Both drugs attack the DNA leading to the cancer cells death via different mechanisms. In view of the fact that the combination with each other leads to enhanced activity with less sever side effects, we have undertaken NMR studies on the complexes formed between bleomycin and PtII, PdII, cisplatin and transplatin. Herein we present a brief review of the studies on metallobleomycins which were carried out by our lab and others, as an outline of the results obtained using NMR in combination to circular dichroism spectroscopy. Our data indicate that in most cases and under several conditions studied, both metal ions form similar complexes with BLM, while more than one species are present in the solution. Structural implications and comparisons with other metallobleomycins are being discussed.

  16. In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats

    OpenAIRE

    Serrano-Mollar, Anna; Closa, Daniel; Morcillo, E. J.; Bulbena, Oriol

    2003-01-01

    This study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase. Rats receiving N-acetylcysteine (300 mg kg?1 day?1, intraperitoneal) had less augmented lung wet weight, and lower levels of proteins, lactate dehydrogenase, neutrophil and macrophage counts in bronchoalveolar lavage fluid and lung myeloperoxidase activity with a betterment of histological score at 3 days postbleomycin. A dim...

  17. Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2015-01-01

    Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, affects on the cellular response to DNA damage induced by exposures to radiation or other toxic chemicals will have an impact on the radiation risks for the astronauts, as well as on the mutation rate in microorganisms, is still an open question. Although the possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate the effects of spaceflight on the cellular response to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induces DNA damages including the double strand breaks (DSB) similar to the ionizing radiation. Damage in the DNA was measured by the phosphorylation of a histone protein H2AX (-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in the DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ti-67 signals. Our results suggested that the difference in -H2AX between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect the response of the DNA damage response genes to bleomycin treatment.

  18. Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats

    OpenAIRE

    Liu Dai-Shun; Li Ji-Qiong; Sun Bei-Bei; Wang Xun; Wang Tao; Chen Lei; Zhang Shang-Fu; Liu Lin; Xu Dan; Chen Ya-Juan; Wen Fu-Qiang

    2009-01-01

    Abstract Background Advanced glycation end products (AGEs) have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM)-stimulated rat model treated with aminoguanidine (AG), a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg) and orally administered with AG (40, 80, 120 mg/kg) once daily for two we...

  19. Efficacy of intralesional bleomycin in palmo-plantar and periungual warts

    Directory of Open Access Journals (Sweden)

    Prasoon Soni

    2011-01-01

    Full Text Available Background/Aim : Intralesional bleomycin gained increasing popularity in the recent past for treatment of warts particularly in palmo-plantar and periungual regions as other modalities are not very effective. Hence we evaluated the role of intralesional bleomycin in periungual and palmo-plantar warts to know its efficacy in Indian patients. Settings and Design : This was a placebo-controlled study. Materials and Methods : Fifty patients of multiple palmo-plantar and periungual warts were included in this study and categorized in groups A and B of 25 each. Alternate patients were included in groups A and B and treated respectively with intralesional bleomycin (1 mg/mL solution and normal saline as placebo, fortnightly for maximum up to two injections. Patients were followed up weekly for 1 month, fortnightly up to 12 weeks, and then quarterly for 1 year. If warts persisted after 12 weeks of starting treatment, it was considered a failure. Statistical analysis was done by the chi-square test using M-stat software. Results : Group A and B patients were having 85 warts and 72 warts, respectively. The cure rate in group A and B patients was 96.47% (82/85 warts and 11.11% (8/72 warts, respectively, after one or two injections within 12 weeks. The difference in the cure rate between two groups was statistically highly significant (<0.0001. In group A patients, a haemorrhagic eschar was formed which gradually healed in 8-12 weeks without atrophy or pigmentation; this phenomenon was not seen in group B. Only moderate pain was observed by most of the patients during injection in both groups. Conclusion : The intralesional injection of bleomycin is highly effective, safe, and non-toxic in periungual and palmo-plantar warts.

  20. Bleomicina: un modelo de fibrosis pulmonar / Bleomycin: a lung fibrosis animal model

    Scientific Electronic Library Online (English)

    Sandra, Cabrera Benítez.

    2006-03-01

    Full Text Available La bleomicina es un glicopéptido utilizado para el tratamiento del cáncer cuyo potencial terapéutico está limitado por su toxicidad pulmonar. El efecto citotóxico depende de la dosis e involucra el desarrollo de neumonitis que progresa a fibrosis; las células epiteliales alveolares son el blanco pri [...] ncipal del daño inducido por la bleomicina. Se considera que la muerte de células epiteliales alveolares por apoptosis es un evento clave en el inicio y la progresión de la fibrosis pulmonar (FP) que se caracteriza por el depósito excesivo de moléculas de la matriz extracelular, principalmente de colágenas fibrilares en el parénquima pulmonar. En la investigación básica de la FP, la bleomicina se ha utilizado como el principal agente fibrogénico en modelos animales. Durante los últimos años, el modelo de bleomicina desarrollado en ratones trasgénicos se ha empleado para elucidar in vivo el papel de un gran número de biomoléculas involucradas en la FP. Abstract in english Bleomycin is a glycopeptide used for cancer treatment, but the therapeutic potencial of this drug is limited by its lung toxicity. The cytotoxic effect of bleomycin is dose-dependent and involves pneumonitis that proceeds to lung fibrosis (LF). Alveolar epithelial cells are the main target of bleomy [...] cin induced injury. Alveolar epithelial cell death by apoptosis is considered as a key event in the initiation and progression of LF, that is characterized by excessive deposition of extracellular matrix, mainly fibrilar collagens in the lung parenchyma. Bleomycin has been used as the main fibrogenic agent in animal models in LF basic research; in recent years, a bleomycin model developed in transgenic mice has been used to elucidate the in vivo role of a great number of biomolecules involved in LF.

  1. Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice

    OpenAIRE

    Tao Zhu; Wei Zhang; Min Xiao; Hongying Chen; Hong Jin

    2013-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B) is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induce...

  2. Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin

    OpenAIRE

    Matsunaga Hirofumi; Ishizaki Shunsuke; Tsuyusaki Junichi; Tanaka Kensuke; Kuroda Fuminobu; Kasuya Yoshitoshi; Yamauchi Keita; Iwamura Chiaki; Nakayama Toshinori; Tatsumi Koichiro

    2011-01-01

    Abstract Background Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice. Methods Th...

  3. Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice

    OpenAIRE

    Ghofrani Hossein A; Weissmann Norbert; Al-tamari Hamza M; Pullamsetti Soni S; Dumitrascu Rio; Udalov Sergey; Guenther Andreas; Voswinckel Robert; Seeger Werner; Grimminger Friedrich; Schermuly Ralph T

    2010-01-01

    Abstract Background Pulmonary fibrosis (PF) is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE) 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE...

  4. Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

    Science.gov (United States)

    Kelsen, D; Hilaris, B; Coonley, C; Chapman, R; Lesser, M; Dukeman, M; Heelan, R; Bains, M

    1983-10-01

    Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen. PMID:6194685

  5. Radiation nephritis following combined abdominal radiation and chemotherapy (bleomycin-vinblastine)

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, D.N.; Hong, K.; Gault, M.H.

    1978-06-01

    A 29-year-old man presented with acute glomerulonephritis five weeks following completion of combined chemotherapy (bleomycin-vinblastine) and abdominal radiation for testicular carcinoma. There was no evidence for a post-infectious cause or a systemic collagen disorder. The renal biopsy showed changes consistent with radiation nephritis. The combined radiation and chemotherapy may have, by additive or synergistic action, caused the early appearance of radiation nephritis.

  6. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

    OpenAIRE

    Sersa, G.; Jarm, T.; Kotnik, T; Coer, A; Podkrajsek, M; Sentjurc, M.; Miklavcic, D.; Kadivec, M; Kranjc, S; Secerov, A; Cemazar, M

    2008-01-01

    Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1?m...

  7. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases

    OpenAIRE

    BERNENGO, Maria Grazia; OSELLA ABATE, Simona; SAVOIA, Paola; QUAGLINO, Pietro

    2008-01-01

    BACKGROUND: Electrochemotherapy (ECT) combines chemotherapy and electroporation to increase drug uptake. Its role in cutaneous melanoma metastasis treatment is not well defined; indeed, few studies have been reported, without complete follow-up data. AIM: To prospectively evaluate clinical activity and tolerability of ECT with i.v. bleomycin, and to analyze the response increase associated to repeated sessions, in the largest series of cutaneous melanoma metastases reported to date (n = 233)....

  8. Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?

    DEFF Research Database (Denmark)

    Sørensen, Peter G; Rømer, F K; Cortes, Dina

    1984-01-01

    In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a tota...

  9. Reduction of Bleomycin-Induced Pulmonary Fibrosis by Serum Amyloid P

    OpenAIRE

    Pilling, Darrell; Roife, David; wang, Min; Ronkainen, Sanna D.; Crawford, Jeff R.; Travis, Elizabeth L.; Gomer, Richard H

    2007-01-01

    Fibrotic diseases such as scleroderma, severe chronic asthma, pulmonary fibrosis, and cardiac fibrosis kill tens of thousands of people each year in the U.S. alone. Growing evidence suggests that in fibrotic lesions, a subset of blood monocytes enters the tissue and differentiates into fibroblast-like cells called fibrocytes, causing tissue dysfunction. We previously found that a plasma protein called serum amyloid P (SAP) inhibits fibrocyte differentiation in vitro. Bleomycin treatment is a ...

  10. Discovery in PET/CT of an acute pulmonary toxicity with rapidly fatal bleomycin

    International Nuclear Information System (INIS)

    Purpose: we report the case of a patient treated by chemotherapy for a Hodgkin disease showing after treatment an important pulmonary uptake that appears bilateral and symmetric on PET in connection with an acute toxicity at the preclinical stage. Conclusions: an intense and diffuse pulmonary uptake of the 18F.D.G. during the chemotherapy, including particularly the bleomycin, can reveal an acute serious pulmonary toxicity and potentially deadly at the pre-symptomatic stage. (N.C.)

  11. Low dose irradiation, tegafur and bleomycin in oil for rectal cancer

    International Nuclear Information System (INIS)

    A histopathological survey of surgical materials from 143 patients with rectal carcinoma subjected to chemotherapy or to low-dose radiotherapy combined with tegafur and bleomycin in oil was carried out. The radiotherapy brought about better results than chemotherapy alone. In 4 out of the 58 patients treated with the radiochemotherapy, no cancer cells could be found. Exfoliation of cohorts of cancer cells may occur into the rectal lumina in selected cases of rectal carcinoma thus treated, resulting in cancer cell elimination. (author)

  12. Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis

    OpenAIRE

    Fenoglio, C; Vitulo, P.; G Palladini; R. Tozzi; S Inghilleri; MORBINI, P.; T Oggionni

    2006-01-01

    To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP a...

  13. Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin

    OpenAIRE

    Fadi Atwan; Isam Elamin Elsiddig; Muhammad Sharif

    2012-01-01

    Intralesional sclerotherapy as a primary modality of management for cystic hygroma is successfully described in literature. It has many benefits over surgical approach; recurrence being the concern of as much as 20% of patients in which apparent complete excision has been performed. Bleomycin is one of sclerosing agents used as intralesional therapy in cystic hygroma. Complete response usually occurs in multiple sessions of sclerotherapy. Rarely, complete resolution occurs with single session...

  14. Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2015-01-01

    Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to bleomycin treatment.

  15. Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

    International Nuclear Information System (INIS)

    In this work, a potential therapeutic DNA targeting agent, 153Sm-bleomycin complex (153Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. 153Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq 153SmCl3, radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). 153Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. 153Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor:blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor:muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of 153Sm-BLM in tumor tissues. (orig.)

  16. Effects of acronycine, bleomycin and cytosine arabinoside on the cell cycle

    International Nuclear Information System (INIS)

    The influence of three chemotherapeutic agents, acronycine, bleomycin and cytosine arabinoside, alone and combined with radiation, on cell cycle progression and viability of L-cells was examined. The percentages of cells in G1, S and (G2 + M)-phases as derived from pulse cytophotometric DNA distribution patterns were recorded as a function of exposure time. After 24-h treatment with 10 ?g/ml acronycine, 46.4% of cells were accumulated in (G2 + M)-phase compared to 12.1% in the controls. This accumulation was significantly enhanced by an irradiation with 150 rads of X-rays resulting in arresting 63.1% of cells in this phase. Similar findings were obtained after a 24-h treatment with 100 ?g/ml bleomycin. 54.4 % of cells were arrested in (G2 + M)-phase by the chemical treatment alone, while the combined treatment, bleomycin and radiation, yielded an accumulation of 66.3% of cells in G2 + M. A 24-h exposure to 0.2 ?g/ml cytosine arabinoside (Ara-C) produced a reversible block of 72.8% of cells in S phase compared to 27.4% in the control cultures. This S block was less pronounced after the combined treatment (51.1%). Some implications of the results for combined therapy are discussed. (orig.)

  17. Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease.

    Science.gov (United States)

    Lee, Rebecca; Reese, Charles; Bonner, Michael; Tourkina, Elena; Hajdu, Zoltan; Riemer, Ellen C; Silver, Richard M; Visconti, Richard P; Hoffman, Stanley

    2014-04-15

    The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration. Here we have compared the effects in mice of bleomycin delivered directly into the lungs (direct model) or systemically using osmotic minipumps (pump model) to determine which more closely resembles human ILD. The pump model is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to the subpleural portion of the lung in the pump model and in SSc ILD, whereas the entire lung is affected in the direct model; 2) conversely, there is massive inflammation throughout the lung in the direct model, whereas inflammation is limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar epithelial cells are present at high levels in SSc ILD and in the pump model but not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis. The pump model is also move convenient and humane than the direct model because there is less weight loss and mortality. PMID:24583879

  18. Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent

    International Nuclear Information System (INIS)

    Due to interesting therapeutic properties of 177Lu and antineoblastic antibiotic, bleomycin (BLM), 177Lu-bleomycin (177Lu-BLM) was developed as a possible therapeutic compound. Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of a natural Lu2O3 sample with a thermal neutron flux of 4 · 1013 n · cm-2 · s-1. The product was converted into chloride form which was further used for labeling of BLM. In optimized conditions a radiochemical purity of 98% was obtained for 177Lu-BLM shown by instant thin-layer chromatography (ITLC) (specific activity, 740 GBq/mmole). Biodistribution studies of Lu-177 chloride and 177Lu-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a pattern similar to the other radiolabeled bleomycins. Lu-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models. (authors)

  19. Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    T Oggionni

    2009-06-01

    Full Text Available To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry in lung tissue. MMP activity (zymography and TIMP concentration (ELISA were evaluated in lung tissue homogenate (LTH, BAL supernatant (BALs and BAL cell pellet (BALp 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

  20. Intralesional bleomycin sclerotherapy: an effective treatment of cystic hygroma in children

    International Nuclear Information System (INIS)

    Objective: To study the outcome of intralesional sclerotherapy with injection Bleomycin in cystic hygroma in children. Study Design: A case series. Place and Duration of Study: The department of Pediatric Surgery at Military Hospital, Rawalpindi, Pakistan from Jan 2011 to Dec 2012. Patients and Methods: All patients with peripheral cystic hygroma (CH) presenting to us, were enrolled in the study. The cyst was aspirated in the operation theater under sedation. Injection bleomycin 0.5 mg /kg diluted in 10-15 cc of distilled water was injected in the cyst at multiple sites. Injection was repeated after every month depending upon the response. Results: A total of 30 patients reported to the department with superficial cystic hygroma, 12 were males (40%) and 18 were females (60%), age ranged from 15 days to 8 years. Cervico-facial was the most common site. Results were assessed in terms of excellent (complete resolution), good (> 50% reduction in size) and poor (< 50% reduction in size). In 2 patients, complete resolution was achieved after maximum seven shots of intra-lesional bleomycin injections (IBI), while 18/30 (60%) resolved after single dose. Twenty seven patients (90%) resolved completely, 2 (6.6%) had good response, 1 (3.3%) showed poor response. Minor complications were noted which were treated by ymptomatic treatment. No major side effects or recurrence were noted in maximum 2 years follow up. (author)

  1. New tumor imaging agent--111In-bleomycin complex. Comparison with 67Ga-citrate and 57Co-bleomycin in tumor-bearing animals

    International Nuclear Information System (INIS)

    A new 111In-bleomycin complex (BLMC) has been found which has high affinity to tumor, does not bind to transferrin and is stable in vivo. Distribution in animals bearing glioma, hepatoma, or mammary adenocarcinoma at 48 hours showed: the ratios of tumor to blood, brain, heart, lung, liver, pancreas, stomach, and femur were 1.4-22.4 times as high for 111In-BLMC as for 67Ga-citrate. In mammary adenocarcinoma, 111In-BLMC bound more to viable and 57Co-Bleomycin (BLM) more to necrotic tumor. In viable tumor, the concentration of 111In-BLMC was similar to that of 57Co-BLM. The ratios of tumor to stomach and pancreas were higher, to blood, brain, muscle, heart, and femur were lower for 111In-BLMC than those for 57Co-BLM. The ratios of tumor to lung, liver, spleen, skin, and kidney were similar for the two compounds. Tumors were imaged more distinctly with the new 111In-BLMC and 57Co-BLM than with 67Ga-citrate. 111In-BLMC is promising for tumor imaging

  2. Geneva protocols

    International Nuclear Information System (INIS)

    The First Protocol Additional to the Geneva Conventions of 1949 and relating to the Protection of Victims of International Armed Conflicts contains provisions prohibiting indiscriminate attacks. Nuclear warfare as such is not mentioned in the Protocol. It has been asserted that the Protocol does not apply to nuclear weapons for several reasons. However, close analysis shows that the rules governing the application of means and methods of warfare cannot exempt the nuclear weapons. If nuclear weapons are applied in a manner not consistent with article 51 of Protocol I, their use is forbidden by this article even in situations in which general international law might grant an exception from the ban on nuclear weapons, as in the case of reprisal. (orig./HSCH)

  3. A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.

    Directory of Open Access Journals (Sweden)

    Seki,Shuji

    1989-04-01

    Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I, ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

  4. Calcium electroporation in three cell lines : a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne

    2014-01-01

    BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore, the effects of electrical pulsing parameters and calcium compound on treatment efficacy were determined. RESULTS: Electroporation with either calcium or bleomycin significantly reduced cell survival (p<0.0001), without evidence of a synergistic effect. Cellular death following calcium or bleomycin treatment occurred at similar applied voltages, suggesting that similar parameters should be applied. At equimolar concentrations, calcium chloride and calcium glubionate resulted in comparable decreases in cell viability. CONCLUSIONS: Calcium electroporation and bleomycin electroporation significantly reduce cell survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound. GENERAL SIGNIFICANCE: This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials.

  5. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.

    Science.gov (United States)

    Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

    2015-03-15

    Arginase is an enzyme that limits substrate L-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces L-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased L-arginine and L-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. PMID:25595650

  6. Comparing the Effect of Physical Modalities on Permeabilisation of Cells to Bleomycin in Balb/C Mice

    Directory of Open Access Journals (Sweden)

    Bahram Yousefian

    2012-07-01

    Full Text Available Background: Some physical factors may facilitate the entry of chemotherapeutic drugs to the cells. In this study, permeability level of tumor cells of murine breast adenocarcinoma to Bleomycin was compared with 5 minutes ultrasonic exposure vs. magnetic field of 3.5 Tesla in Balb/c mice.Materials and Methods: In this experimental-applied study, 80 five-week female Balb/c mice were purchased from Pasteur Institute of Tehran. After 10 days, skin tumors of mice were induced through Homograft, and they were randomly classified after tumor reached a treatable size. In ultrasound combination group, intratumoral injection of bleomycin was performed on anesthetized mice and three minutes later, the mice, which were placed in the sonication chamber, were put in a water tank in the exposure position, and the tumor was exposed to ultrasound for 5 minutes. In the magnetic field group, mice were placed in a handmade chamber after intratumoral injection of bleomycin. Three minutes after injection of bleomycin, eight pulses of 3.5 Tesla magnetic fields with 1Hz frequency were applied to each one of the tumors.Results: It yield that, eight 3.5 Tesla pulses of magnetic field, was slightly more effective than 5 min ultrasonic irradiation in cells permeability to bleomycin, but these two physical factors had no statistically significant difference.Conclusion: Tests showed that these two physical factors have similar effects and use of each depends on the position of the patient and the medical center's facilities.

  7. Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines

    International Nuclear Information System (INIS)

    The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1?, IL-8, and tumor necrosis factor (TNF)-? during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-?B) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-?B activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-?B activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study

  8. The growth of hemopoietic precursor cells (CFU-C) of adriamycin-treated or whole-body-irradiated dogs with or without bleomycin in vitro

    International Nuclear Information System (INIS)

    The effect of the cytostatic drug bleomycin (BLM) on the growth of canine hemopoietic stem-cells in vitro was tested in order to detect a stem-cell deficiency after in vivo-treatment with adriamycin (ADM) or whole-body-irradiation. Stem-cells damaged by irradiation or cytostatics are suppressed by bleomycin-induced strand-breaks in vitro. After stem-cell recovery the increased sensitivity towards bleomycin can no longer be detected. After whole-body-irradiation and cytostatical treatment the stem-cells who remained intact have to compensate the quantitative change of the stem-cells by increased proliferation. The proliferating cells show a particular bleomycin-sensitivity. Especially after irradiation a long persistence of the bleomycin-sensitivity can be reckoned on. (orig./MG)

  9. Diagnostic value of thermography and sup(99m)Tc bleomycin scintigraphy for nodules of the thyroid

    International Nuclear Information System (INIS)

    The combined interest of thermography and sup(99m)Tc bleomycin scintigraphy in the differential diagnosis of a cold thyroid nodule was evaluated in 86 patients. In all cases a histological examination was performed. Of the 30 malignant nodules (clinically suspect and solitary nodules) 21 (70%) showed concentrations of sup(99m)Tc bleomycin while only 7 of the 12 solitary malignant nodules did so. Among the 54 benign nodules the false positive rate was 54%. Thermography was positive in 26 (87%) of the 30 malignant nodules and in only 8 (67%) of the 12 solitary malignant nodules. For the 54 benign nodules the false positive rate was 72%. The combined results of the study do not provide any improvement in diagnostic accuracy. Thus it can be said that applications of sup(99m)Tc bleomycin and thermography in the diagnosis of solitary hypofixiant nodules are of limited value

  10. Bleomycin-induced DNA synthesis in a cell-free system using a permeable mouse sarcoma cell Extract.

    Directory of Open Access Journals (Sweden)

    Seki,Shuji

    1987-10-01

    Full Text Available To investigate factors involved in excision repair DNA synthesis, a soluble extract was prepared from permeable mouse sarcoma (SR-C3H/He cells by homogenization and ultracentrifugation. DNA synthesis measured by using native calf thymus DNA as the template-primer and the extract as the polymerase source showed low activity. The DNA synthesis was enhanced more than ten-fold by the addition of an appropriate concentration of bleomycin, a radiomimetic DNA-damaging drug. Using selective inhibitors of DNA polymerases, it was shown that the DNA polymerase involved in the bleomycin-induced DNA synthesis was DNA polymerase beta. In addition to DNA polymerase beta, an exonuclease which converts bleomycin-damaged DNA into suitable template-primers for repair DNA synthesis appeared to be present in the permeable cell extract.

  11. Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair.

    Science.gov (United States)

    MacKenzie, BreAnne; Henneke, Ingrid; Hezel, Stefanie; Al Alam, Denise; El Agha, Elie; Chao, Cho-Ming; Quantius, Jennifer; Wilhelm, Jochen; Jones, Matthew; Goth, Kerstin; Li, Xiaokun; Seeger, Werner; Königshoff, Melanie; Herold, Susanne; Rizvanov, Albert A; Günther, Andreas; Bellusci, Saverio

    2015-05-15

    Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26(rtTA/+);tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0-11; days 0-28) or during later stages (days 6-28 and 14-28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice. PMID:25820524

  12. Tissue uptakes of 67 Ga-bleomycin and carrier free 67 Ga in fibrosarcoma-bearing mic

    International Nuclear Information System (INIS)

    67Gallium-bleomycin complex was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radio peaks with Rf at 0.7 and 0.4 respectively with a purity of above % 95. Tissue uptake of 67 Gallium-bleomycin complex and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content, bladder and the total body were counted by well counter at 1,2,4,24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67 Gallium-bleomycin complex was 1.75 - 1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67 Gallium-bleomycin complex were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67 Gallium-bleomycin complex was lower than 67GaCl3 in all time intervals. Colon content uptake of 67 Gallium-bleomycin complex was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratios of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67 Gallium-bleomycin complex and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67 Gallium-bleomycin complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga (67GaCl3) has two main advantages: 1) high tumor to soft tissue uptake ratio that make it suitable for tumor imaging. 2) faster excretion specially at first three hours post injection.In addition complex is stable in vitro and in vivo

  13. Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

    OpenAIRE

    Marlise Ladvocat Bartholomei-Santos; Edmundo José de Lucca

    1997-01-01

    Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS...

  14. Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

    Scientific Electronic Library Online (English)

    Yinghua, Song; Lubing, Zhu; Ming, Li.

    2013-10-01

    Full Text Available OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 ?M). Cell proliferation [...] was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of ?-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.

  15. Bleomycin enhances the efficacy of sonodynamic therapy using aluminum phthalocyanine disulfonate.

    Science.gov (United States)

    Osaki, Tomohiro; Yokoe, Inoru; Uto, Yoshihiro; Ishizuka, Masahiro; Tanaka, Toru; Yamanaka, Nobuyasu; Kurahashi, Tsukasa; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu

    2016-01-01

    Sonodynamic therapy (SDT), or ultrasound combined with sonosensitization, is a promising approach because it is noninvasive and penetrates deeper than light does in photodynamic therapy. We examined whether bleomycin (BLM) could improve the efficacy of SDT. We performed an in vitro study using Colon-26 cells, which are derived from mouse colon cancer. SDT with BLM was significantly more cytotoxic than SDT alone both in vitro and in vivo. We also observed an ultrasound intensity-dependent cytotoxic effect of SDT with BLM. These findings suggest that SDT with BLM might provide a novel noninvasive treatment for deep-seated tumors. PMID:26384895

  16. 57Co-bleomycin scintigraphy for the preoperative detection and staging of lung tumors

    International Nuclear Information System (INIS)

    Twenty-five consecutive patients with lung tumors were classified according to the presence of metastases by the use of 57Co-Bleomycin scintigraphy. Twenty-two of the tumors visualized but metastatic spread to hilar lymph nodes was not detected. Reliable separation of central tumors with and without growth into neighbouring organs was not possible. Mediastinal uptake was found in eight cases but only a part of these could be verified by operation. The method can contribute to the evaluation of lung tumors and can be helpful to avoid some unnecessary thoracotomies. (orig.)

  17. Catalytic Mechanism of Bleomycin N-Acetyltransferase Proposed on the Basis of Its Crystal Structure*

    OpenAIRE

    Oda, Kosuke; MATOBA, Yasuyuki; Noda, Masafumi; Kumagai, Takanori; Sugiyama, Masanori

    2009-01-01

    Bleomycin (Bm) N-acetyltransferase, BAT, is a self-resistance determinant in Bm-producing Streptomyces verticillus ATCC15003. In our present study, we crystallized BAT under both a terrestrial and a microgravity environment in the International Space Station. In addition to substrate-free BAT, the crystal structures of BAT in a binary complex with CoA and in a ternary complex with Bm and CoA were determined. BAT forms a dimer structure via interaction of its C-terminal domains in the monomers...

  18. Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs

    OpenAIRE

    Reed, Scott D; Fulmer, Amanda; Buckholz, Julia; Zhang, Boyu; CUTRERA, JEFFRY; Shiomitsu, Kiejiro; LI, SHULIN

    2010-01-01

    Based on superior outcomes from electrochemogene therapy (ECGT) compared to electrochemotherapy (ECT)in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA (fIL-12 DNA) injection combined with trans-lesional electroporation resulted in complete cure of two recurrent World Health Organization (WHO) stageT2bN0M0 oral squamous cell carcinomas (SCCs)and one T2N0M0acanthomatous ameloblastoma. Three remaining ...

  19. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    LENUS (Irish Health Repository)

    Quintyne, Keith Ian

    2011-09-01

    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  20. Consolidation electrochemotherapy with bleomycin in metastatic melanoma during treatment with dabrafenib

    International Nuclear Information System (INIS)

    Small molecules that inhibit V600 mutated BRAF protein, such as vemurafenib and dabrafenib, are effective in treatment of metastatic melanoma. We here describe the clinical course of a V600E BRAF mutated metastatic melanoma patient with systemic disease, who developed tumor progression on superficial soft-tissue metastases during treatment with dabrafenib. Bleomycin electrochemotherapy during dabrafenib treatment was administered to control the soft-tissue progressing metastases and ensured sustained local control without significant toxicity. The new combined approach maintained the patient quality of life and allowed for the prosecution of the target therapy, which proved to be still effective on systemic disease, up to 17 months

  1. Cross section measurement of the reaction 7Be(p,?)8B at low energy and its applications to the solar neutrino problem

    International Nuclear Information System (INIS)

    The 8B production through the 7Be(p,?)8B reaction is the main sources of high energy solar electron neutrinos. The cross section of this reaction at energies of the order of 20 KeV is essential to the solar models. We have measured this cross section between 0.4 MeV and 1.5 MeV by means of a Van de Graaff accelerator, using a radioactive 7Be target. The alpha particle production due to 8Be radioactive decay is used in order to deduce the reaction cross section. The total cross section has a total uncertainty lower than 10%. The results are given. These are in agreement and disagreement with Filiponne and Kavannagh, respectively. The data analysis leads to an astrophysical factor corresponding to this reaction, S17(0), within the interval 16.6 ± 1.0 to 20.1 ± 1 eV barn. The uncertainty comes essentially from the implied different energy depending quantities, as predicted by different models

  2. Astrophysical Impact of the Updated 9Be(p,?)6Li and 10B(p,?)7Be Reaction Rates As Deduced By THM

    Science.gov (United States)

    Lamia, L.; Spitaleri, C.; Tognelli, E.; Degl'Innocenti, S.; Pizzone, R. G.; Prada Moroni, P. G.

    2015-10-01

    The complete understanding of the stellar abundances of lithium, beryllium, and boron represents one of the most interesting open problems in astrophysics. These elements are largely used to probe stellar structure and mixing phenomena in different astrophysical scenarios, such as pre-main-sequence or main-sequence stars. Their different fragility against (p,?) burning reactions allows one to investigate different depths of the stellar interior. Such fusion mechanisms are triggered at temperatures between T ? (2-5) × {10}6 K, thus defining a corresponding Gamow energy between ? 3-10 keV, where S(E)-factor measurements need to be performed to get reliable reaction rate evaluations. The Trojan Horse Method is a well defined procedure to measure cross sections at Gamow energies overcoming the uncertainties due to low-energy S(E)-factor extrapolation as well as electron screening effects. Taking advantage of the {\\mathtt{THM}} measure of the 9Be(p,?)6Li and 10B(p,?)7Be cross sections, the corresponding reaction rates have been calculated and compared with the evaluations by the NACRE collaboration, widely used in the literature. The impact on surface abundances of the updated 9Be and 10B (p,?) burning rates is discussed for pre-MS stars.

  3. The LIM-Only Protein FHL2 Attenuates Lung Inflammation during Bleomycin-Induced Fibrosis

    Science.gov (United States)

    Schied, Tanja; Chiquet-Ehrismann, Ruth; Loser, Karin; Vogl, Thomas; Ludwig, Stephan; Wixler, Viktor

    2013-01-01

    Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2) is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages. PMID:24260575

  4. A CLINICAL STUDY IN MANAGEMENT OF HYPERTROPHIC SCARS A ND KELOIDS WITH INTRALESIONAL INJECTION OF BLEOMYCIN

    Directory of Open Access Journals (Sweden)

    Rajshekar

    2015-08-01

    Full Text Available Keloids and hypertrophic scars remain a nagging problem even with the emergence of multiple modalities in their treatment. The wide range of modalities used for their treatment also point out that no single treatment is definitively superior. AIMS: The aim of this study was to define the role of Bleomycin and to confirm its effectiveness in the management of keloids and hypertrophic scars. SETTINGS AND DESIGN: This was a prospective clinical trial involving 40 patients with hypertrophic scars and keloids. METHODS AND MATERIAL: Patients were followed for 1year in department of general surgery VIMS Bellary , treated with four monthly intralesional injections of Bl eomycin. Assessment of the size of keloids and hypertrophic scars was done at the beginning, at the time of stopping the therapy and during the follow - up. EXCLUSION CRITERIA: patients under 18 years were not considered suitable for this treatment; pregnant and women likely to become pregnant women were not enrolled in the study. STATISTICAL ANALYSIS USED: The response to treatment was divided into the following categories: 75 percent flattening = excellent response. RESULTS: Of the forty patients, 27(67.5% showed excellent response, 6(15% showed good response, 4(10% showed fair response and 3(7.5% showed poor response. There was comp lete resolution of symptoms in 24 patients (60% and improvement in the other 16(40%. CONCLUSIONS: In the treatment of hypertrophic scars and keloids, the intralesional injection of Bleomycin is very effective and safe.

  5. Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Zhou, Xian-Mei; Cao, Zhen-Dong; Xiao, Na; Shen, Qi; Li, Jian-Xin

    2016-02-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4-methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-?1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin?induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF. PMID:26675886

  6. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

    Directory of Open Access Journals (Sweden)

    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 ?s each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  7. Radio-isotope scanning using labelled bleomycin in positive and differential diagnosis of primary and secondary malignant pulmonary lesions

    International Nuclear Information System (INIS)

    A lung scan using bleomycin labelled with cobalt 57 was carried out in 308 patients representing 191 primary malignant tumours, 48 pulmonary metastases and 69 benign lesions. The primary and secondary malignant lesions always gave rise to a hyperactive focus except in 8 cases of primary lung tumour. The negative examination may be explained, either by the small size of the lesion or by radiotherapy in progress. Among the benign lesions, only advanced tuberculosis and very inflammatory lung diseases frequently took up labelled bleomycin (15 hyperactive foci out of 69 benign lesions). Quantitative measurements, i.e. ratio of the lesional activity/activity of healthy lung tissue, were carried out in all patients. The malignant lesions were usually more active than the benign lesions. There was no definite correlation between the uptake of labelled bleomycin and the histological nature of the lesion. However, undifferentiated and anaplastic carcinomas were often more active. One should emphasize that these results show that a hyperactive focus has a 94% chance of being a carcinoma. The absence of bleomycin uptake means that there is a 92% chance of a benign lesion

  8. Intraoperative respiratory failure in a patient after treatment with bleomycin: previous and current intraoperative exposure to 50% oxygen.

    Science.gov (United States)

    Luis, M; Ayuso, A; Martinez, G; Souto, M; Ortells, J

    1999-01-01

    Patients treated with bleomycin (BLM) are at risk of developing acute respiratory distress syndrome (ARDS) post-operatively, and this has been associated with high intraoperative concentrations of oxygen. We report progressive arterial desaturation noticeable 2 h after the start of a 4-h radical neck dissection for which the anaesthesia included 50% O2 in N2O. The patient had received two courses of bleomycin within the previous 2 months and had undergone an uneventful right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks previously. His pulmonary function tests before the second procedure showed a slight depression of diffusing capacity (DLco) to 80% of predicted and minimal airway obstruction consistent with his history of smoking. The pulse oximetric reading during his second procedure reached 75%, but rose to 95% after treatment with methylprednisolone salbutamol and inspired O2 concentrations between 80% and 100%. By the end of the procedure, he satisfied the criteria for ARDS and was transferred to the ICU, where he developed bilateral pneumonia, deteriorated and died of multiple organ failure. This case suggests that the risk of hyperoxic pulmonary damage in patients exposed to bleomycin may increase not only with the degree and duration of hyperoxia in a given exposure, but also with the latent effects of recent previous exposure. Near normality of pulmonary function tests cannot be taken as reassurance, and small changes may have more adverse prognostic significance than in patients who have not been exposed to bleomycin. PMID:10084104

  9. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    OpenAIRE

    Zheng, Min-hua; Feng, Bo; Li, Jian-Wen; Lu, Ai-Guo; Wang, Ming-Liang; Hu, Wei-guo; Sun, Ji-Yuan; Hu, Yan-Yan; Ma, Jun-Jun; Yu, Bao-Ming

    2005-01-01

    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.

  10. Association of the emerging carbapenemase NDM-1 with a bleomycin resistance protein in Enterobacteriaceae and Acinetobacter baumannii.

    Science.gov (United States)

    Dortet, Laurent; Nordmann, Patrice; Poirel, Laurent

    2012-04-01

    The carbapenemase NDM-1 has been identified recently in Enterobacteriaceae and Acinetobacter baumannii as a source of multidrug resistance, including resistance to carbapenems. By analyzing the immediate genetic environment of the bla(NDM-1) carbapenemase gene among a series of NDM-1-producing enterobacterial isolates, a novel gene (ble(MBL), for ble gene associated with the metallo-?-lactamase NDM-1) was identified. The ble(MBL) gene encodes a novel bleomycin resistance protein (BRP), named BRP(MBL), that shares weak similarities with known BRPs (less than 60% amino acid identity). The expression of BRP(MBL) conferred resistance to bleomycin and to bleomycin-like molecules in Enterobacteriaceae and A. baumannii. The bla(NDM-1) and ble(MBL) genes were coexpressed under the control of the same promoter, located upstream of the bla(NDM-1) gene and at the extremity of the insertion sequence ISAba125. Most of the NDM producers possessed the ble(MBL) gene. Although BRP(MBL) did not modify the growth or death rates of Escherichia coli under experimental conditions, it suppressed the mutation rate of hypermutable E. coli and therefore may stabilize the plasmid-borne bla(NDM-1) gene. This study suggests that the emerging carbapenemase NDM-1 is selected by bleomycin-like molecules, and that BRP(MBL) producers (and consequently NDM producers) are better suited to various environments. PMID:22290943

  11. Effect of continuous infusion of bleomycin on the time for completion of repair of sublethal radiation damage in mouse lip mucosa during fractionated irradiation

    International Nuclear Information System (INIS)

    The influence of a simultaneous continuous infusion of bleomycin on the time necessary for repair of sublethal radiation damage during fractionated irradiation of mouse ip mucosa was studied. Although there are strong indications that bleomycin interferes with the accumulation and repair of sublethal radiation damage, no significant change in the time course of these repair processes could be demonstrated following various analyses of the experimental results. An interval of at most 4 h between successive irradiations was sufficient to allow for a similar amount of repair of sublethal damage as compared with either 24 h (2 fractions) or 6 h (10 fractions), whether or not radiation was combined with bleomycin infusion

  12. Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

    Scientific Electronic Library Online (English)

    Maria Cristina P., Araújo; Francisca da Luz, Dias; Sergio N., Kronka; Catarina S., Takahashi.

    1999-09-01

    Full Text Available Antioxidantes de ocorrência natural têm sido exaustivamente estudados quanto a sua capacidade de proteger organimos e células contra danos oxidativos. Muitos constituintes das plantas, incluindo cúrcuma e curcumina, parecem ser potentes antimutágenos e antioxidantes. Os efeitos de cúrcuma e curcumin [...] a na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). Três concentrações de cada droga, cúrcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em células CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem cúrcuma nem curcumina evitaram o dano cromossômico induzido pela BLM em fase alguma do ciclo celular. Ao contrário, a potenciação da clastogenicidade da BLM pelo curcumina foi nitidamente observada em células tratadas durante as fases S e G2/S. A curcumina também se mostrou clastogênica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogênicos permanece desconhecido. Abstract in english Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberr [...] ation frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 and 500 mg/ml) and curcumin (2.5, 5 and 10 mg/ml), were combined with BLM (10 mg/ml) in CHO cells treated during the G1/S, S or G2/S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G2/S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.

  13. In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors

    International Nuclear Information System (INIS)

    Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue

  14. Lysophosphatidic acid receptor-2 deficiency confers protection against bleomycin-induced lung injury and fibrosis in mice.

    Science.gov (United States)

    Huang, Long Shuang; Fu, Panfeng; Patel, Priya; Harijith, Anantha; Sun, Tianjiao; Zhao, Yutong; Garcia, Joe G N; Chun, Jerold; Natarajan, Viswanathan

    2013-12-01

    Idiopathic pulmonary fibrosis is a devastating disease characterized by alveolar epithelial cell injury, the accumulation of fibroblasts/myofibroblasts, and the deposition of extracellular matrix proteins. Lysophosphatidic acid (LPA) signaling through its G protein-coupled receptors is critical for its various biological functions. Recently, LPA and LPA receptor 1 were implicated in lung fibrogenesis. However, the role of other LPA receptors in fibrosis remains unclear. Here, we use a bleomycin-induced pulmonary fibrosis model to investigate the roles of LPA2 in pulmonary fibrogenesis. In the present study, we found that LPA2 knockout (Lpar2(-/-)) mice were protected against bleomycin-induced lung injury, fibrosis, and mortality, compared with wild-type control mice. Furthermore, LPA2 deficiency attenuated the bleomycin-induced expression of fibronectin (FN), ?-smooth muscle actin (?-SMA), and collagen in lung tissue, as well as levels of IL-6, transforming growth factor-? (TGF-?), and total protein in bronchoalveolar lavage fluid. In human lung fibroblasts, the knockdown of LPA2 attenuated the LPA-induced expression of TGF-?1 and the differentiation of lung fibroblasts to myofibroblasts, resulting in the decreased expression of FN, ?-SMA, and collagen, as well as decreased activation of extracellular regulated kinase 1/2, Akt, Smad3, and p38 mitogen-activated protein kinase. Moreover, the knockdown of LPA2 with small interfering RNA also mitigated the TGF-?1-induced differentiation of lung fibroblasts. In addition, LPA2 deficiency significantly attenuated the bleomycin-induced apoptosis of alveolar and bronchial epithelial cells in the mouse lung. Together, our data indicate that the knockdown of LPA2 attenuated bleomycin-induced lung injury and pulmonary fibrosis, and this may be related to an inhibition of the LPA-induced expression of TGF-? and the activation and differentiation of fibroblasts. PMID:23808384

  15. Histology protocols

    OpenAIRE

    CarloAlberto Redi

    2010-01-01

    Tim D. Hewitson & Ian A. Darby (Eds) Humana press, Totowa, New Jersey (USA) Series: Springer Protocols Methods in Molecular Biology, Volume 611, 2010 Pages: 230; € 83.15 ISBN: 978-1-60327-344-2 Impressive as it can sounds in the era that Biology see a clear dominance of reductionism with the idea that complexity can be disentagled more and more thanks to the use of molecular tools, the reader will remain fascinated by this slim and agile volume devoted to bring together wha...

  16. Cryptographic Protocols:

    DEFF Research Database (Denmark)

    Geisler, Martin Joakim Bittel

    terminate, in which no information is released. The communication complexity of this protocol is the same as that of a passively secure solution up to a constant factor. It is secure against an adaptive and active adversary corrupting less than n=3 players. Following the presentation of VIFF, we turn to a...... the number of inputs. We round off this dissertation with Chapter 6. There we return to the practical side of things and consider how users of online collaboration tools and network storage services place considerable trust in their providers. We presents a novel approach for protecting data integrity...... in revision control systems hosted by an untrusted provider. It guarantees atomic read and write operations on the shared data when the service is correct and preserves fork-linearizability when the service is faulty. A prototype has been implemented on top of the Subversion revision control system...

  17. Cell adhesion molecules regulate fibrotic process via Th1/Th2/Th17 cell balance in a bleomycin-induced scleroderma model

    OpenAIRE

    Yoshizaki, Ayumi; Yanaba, Koichi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Asako; Akiyama, Yuichiro; Muroi, Eiji; Hara, Toshihide; Ogawa, Fumihide; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Tedder, Thomas F; Sato, Shinichi

    2010-01-01

    Mice subcutaneously injected with bleomycin, an experimental model for human systemic sclerosis, develop skin and lung fibrosis, which is mediated by inflammatory cell infiltration. This process is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules in this pathogenetic process, the bleomycin-induced fibrosis was examined in mice lacking adhesion molecules. In addition, this model does not require antigen sensitization. Therefore, we can exclude the possi...

  18. Bleomycin-induced lung injury in the rat: effects of the platelet-activating factor (PAF) receptor antagonist BN 52021 and platelet depletion.

    OpenAIRE

    EVANS, T. W.; McAnulty, R. J.; Rogers, D F; CHUNG, K. F.; BARNES, P. J.; Laurent, G. J.

    1990-01-01

    Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug. Platelets and platelet-activating factor (PAF), a membrane-derived phospholipid, have been implicated in the mechanisms that can mediate pulmonary microvascular injury. We sought to investigate the role of PAF in bleomycin-induced lung injury in the rat, using the PAF receptor antagonist BN 52021; and the role...

  19. Chromosome aberrations by a new /sup 111/In-Bleomycin complex

    International Nuclear Information System (INIS)

    A new /sup 111/In-Bleomycin Complex (/sup 111/In-BLMC) was prepared and was effective for tumor imaging and therapy in mouse glioma and for killing human small cell lung cancer (SCLC) cells. Human SCLC cells (N417 or H526, NCI) were exposed to 0.9% NaCl, BLM (10-20 ?g/ml) or /sup 111/In-BLMC (24-50 ?Ci carried by 10-20 ?g BLM/ml) at 370C for 60 min. Cells were washed with fresh medium, treated with colcemid, hypotonic solution and fixer. Slides were stained with Giemsa solution and Q-binding stain. The karyotpe of the cells was analyzed. Experimental data is given. The results indicate that the /sup 111/In-BLMC causes chromosome damage which contributes to the tumor cell killing. The radiation dose from Auger electrons is small but concentrated and greatly increased chromosomal effects over that caused by BLM alone

  20. Labelling of bleomycin with technetium-99m for diagnosis in nuclear medicine

    International Nuclear Information System (INIS)

    A study about the behavior of the labelling yield of an antineoplastic drug (bleomycin) with a short-leved radionuclide (99 sup(m) Tc), using An(II) as a reductor agent, is presented. Parameters like the pH in the labelling, influence of the reaction time and mass of tin on the labelling yield were analysed. To simplify the labelling,, a lyofilized kit of Sn(II)/BLM in evacuated vials was prepared. The quality control involving paper chromatography, sterility and 'in vivo' test was made. The 'in vivo' tests were made both in healthy rats and in those with tumorous tissues, under barbituric action. The biological distribution, the concentration time of the products in tumors, the excretion time and excretion via were studied by means of scintigraphy and scintiphotos. (Author)

  1. Cyclotron production of carrier-free cobalt-55, a new positron-emitting label for bleomycin

    International Nuclear Information System (INIS)

    A method for producing carrier-free 55Co (18.5 h) by proton bombardment of natural iron targets is presented. 55Co is formed primarily by means of the 56Fe (p, 2n)55Co reaction. Thin-target and thick-target yields as well as cross-section calculations are given in the 15-MeV to 40-MeV proton-energy range. Half-life measurements indicate a value of 18.5 h for 55Co. Chemical purification of the 55Co from the iron target is described 56Co, 52Mn, and 54Mn were found as radionuclidic impurities in the final preparation. The 55Co solution contains less than 0.5 ?g/ml of iron contamination. Synthesis of 55Co-bleomycin results in better than 99% labelling yield. (author)

  2. Scintigraphy with 67Ga-citrate and 3In-bleomycin in rectal cancer

    International Nuclear Information System (INIS)

    Scintigraphy with 67Cs-citrate and 111In-bleomycin was performed in 26 patients with primary rectal cancer, 176 patients with suspected tumors, and in 34 patients without clinicoroentgenological signs of cancer recurrence. A focus of higher accumulation of these radionuclides in the rectal area was recorded in all 26 patients. Of 176 patients with symptoms of recurrence tumors were detected by means of ultrasonic and computed tomography of the small pelvis in 158 patients. False-positive results were marked in 18 (10.2%) patients with chronic infalmmatory processes at the site of the resected rectum, in anastomositis, and prostatic adenoma. In the control group of 34 patients false-positive results were marked in 8.8%. Positive scintigraphy used in combined diagnosis of rectal cancer recurrence holds promise

  3. Lung cancer detection using a miniature sodium iodide detector and cobalt-57 bleomycin

    International Nuclear Information System (INIS)

    A small sodium iodide scintillation detector was designed for insertion through a fiberoptic bronchoscope to detect and localize sites of deposition of cobalt-57 bleomycin in lung cancer. The detector was used in 40 diagnostic studies of 34 patients; 21 of the patients had tumors. We compared the sensitivity, specificity, accuracy, and predictive value of the detector to those of plain chest x-ray films and bronchoscopy in detecting tumors. Sensitivity and specificity for the detector were 68 percent and 80 percent, respectively; for bronchoscopy, 72 percent and 100 percent; and for roentgenograms, 80 percent and 53 percent. Sensitivity for the detector and bronchoscopy combined was 92 percent. The detector succeeded in locating nonvisible submucosal and extraluminal tumors, and may contribute to early diagnosis and more accurate staging of lung cancer

  4. Minimally Invasive Treatment of Giant Haemangiomas of the Liver: Embolisation With Bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Bozkaya, Halil, E-mail: halilbozkaya@yahoo.com; Cinar, Celal, E-mail: celalcinar@hotmail.com [Ege University, Division of Interventional Radiology, Department of Radiology, School of Medicine (Turkey); Besir, Fahri Halit, E-mail: drfhbesir@gmail.com [Duzce University, Department of Radiology, School of Medicine (Turkey); Par?ldar, Mustafa, E-mail: mparildar@yahoo.com; Oran, Ismail, E-mail: ismailoran@gmail.com [Ege University, Division of Interventional Radiology, Department of Radiology, School of Medicine (Turkey)

    2013-04-12

    PurposeThe management of patients with giant haemangioma of the liver remains controversial. Although the usual treatment method for symptomatic giant haemangioma is surgery, the classical paradigm of operative resection remains. In this study, we evaluated the symptomatic improvement and size-reduction effect of embolisation with bleomycin mixed with lipiodol for the treatment of symptomatic giant hepatic haemangioma.MethodsThis study included 26 patients [21 female, five male; age 41–65 years (mean 49.83 ± 1.53)] with symptomatic giant haemangioma unfit for surgery and treated with selective embolisation by bleomycin mixed with lipiodol. The patients were followed-up (mean 7.4 ± 0.81 months) clinically and using imaging methods. Statistical analysis was performed using SPSS version 16.0, and p < 0.05 was considered to indicate statistical significance.ResultsEmbolisation of 32 lesions in 26 patients was performed. The mean volume of the haemangiomas was 446.28 ± 88 cm{sup 3} (range 3.39–1559 cm{sup 3}) before intervention and 244.43 ± 54.38 cm{sup 3} (range 94–967 cm{sup 3}) after intervention. No mortality or morbidity related to the treatment was identified. Symptomatic improvement was observed in all patients, and significant volume reduction was achieved (p = 0.001).ConclusionThe morbidity of surgical treatment in patients with giant liver hemangioma were similar to those obtained in patients followed-up without treatment. Therefore, follow-up without treatment is preferred in most patients. Thus, minimally invasive embolisation is an alternative and effective treatment for giant symptomatic haemangioma of the liver.

  5. Curcumin effect on Bleomycin-induced pulmonary fibrosis in Mus musculus

    Directory of Open Access Journals (Sweden)

    Annisa Rahmi

    2015-06-01

    Full Text Available Curcumin, a curcuminoid compound of turmeric has been demonstrated to have anti-oxidant and anti-inflammatory properties. Bleomycin (BLM is an anti-cancer drug induced pulmonary fibrosis in human and animals. This study was aimed to investigate biological effects of curcumin on bleomycin-induced pulmonary fibrosis in mice (Mus musculus through pathomorphological assessment. In this study, 16 mice ddy strain were divided into four groups, namely (i control, mice were subcutaneously (SC injected with 100 µl sterilized aquadest in dorsal skin, (ii BLM group, injected SC with 100 µl of 1 mg/ml BLM in dorsal skin, (iii Curcumin (CMN group, mice were intraperitoneally (IP injected with 100 mg/kg body weight (BW curcumin dissolved in 0,5% carboxy methyl cellulose (CMC and injected with 100 µl sterilized aquadest SC, (iv BLM+CMN group, injected SC with 100 µl of BLM 1 mg/ml and injected IP with 100 mg/kg BW CMN in 0,5% CMC. All treatments were performed daily for four weeks period. The lung samples were collected and fixed in buffered neutral formalin (BNF 10%. Histopathological evaluation was performed with hematoxylin-eosin (HE and Masson’s trichrome (MT stains. The results showed that BLM treatment significantly increased fibrosis area and alveolar wall area fraction as compared to control. OIn the other hand, CMN treatment significantly reduced fibrosis area and alveolar wall area fraction in mice treated with BLM. In conclusion, our study showed that CMN treatment may inhibit lung fibrogenesis in BLM-induced pulmonary fibrosis.

  6. Pulmonary epithelial permeability in patients treated with bleomycin containing chemotherapy detected by technetium-99m diethylene triamine penta-acetic acid aerosol (99mTc-DTPA) scintigraphy

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate pulmonary epithelial permeability using 99mTc-DTPA scintigraphy in patients treated with bleomycin-containing regimens. Twelve non-smoking chemotherapy-naive patients with no clinical or radiological evidence of pulmonary disease and treated with bleomycin-containing chemotherapy were tested with 99mTc-DTPA scintigraphy before the first cycle and every 3 weeks until the third month after the end of chemotherapy (total cumulative dose of bleomycin 347.9 mg). Pretreatment values (T1/2 74.93 minutes) of 99mTc-DTPA scintigraphy were significantly higher than those obtained after the total dose of bleomycin (T1/2 51.00 minutes) (p99mTc-DTPA values decreased as the bleomycin dose increased. We conclude that cumulative bleomycin doses are related to increased pulmonary epithelial permeability at a dose of 256.5 mg. However, whether this is related to clinical toxicity is uncertain and large, multi-center prospective studies are needed. (author)

  7. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-? signaling in lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Inagaki Hirofumi

    2006-01-01

    Full Text Available Abstract Background Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL fluid and for induction of messenger RNA (mRNA of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT-polymerase chainreaction (PCR on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3 protein assay by western blotting in MLg2908. Results Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-?. The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-?, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-?. Conclusion These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-? signaling in lung fibroblasts.

  8. Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven (9)Be(p, n) boron neutron capture therapy neutron source.

    Science.gov (United States)

    Hashimoto, Y; Hiraga, F; Kiyanagi, Y

    2015-12-01

    We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8MeV to 30MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. PMID:26272165

  9. Discovery in PET/CT of an acute pulmonary toxicity with rapidly fatal bleomycin; Decouverte en TEP/TDM d'une toxicite pulmonaire aigue a la bleomycine rapidement fatale

    Energy Technology Data Exchange (ETDEWEB)

    Le Dortz, L.; Ben Fredj, M.; Lenoir, L.; Bahri, H.; Devillers, A.; Garin, E. [Centre Eugene-Marquis, Service de medecine nucleaire, 35 - Rennes (France)

    2010-07-01

    Purpose: we report the case of a patient treated by chemotherapy for a Hodgkin disease showing after treatment an important pulmonary uptake that appears bilateral and symmetric on PET in connection with an acute toxicity at the preclinical stage. Conclusions: an intense and diffuse pulmonary uptake of the {sup 18}F.D.G. during the chemotherapy, including particularly the bleomycin, can reveal an acute serious pulmonary toxicity and potentially deadly at the pre-symptomatic stage. (N.C.)

  10. Imaging and staging of head and neck cancer using a low pH In-111-bleomycin complex

    International Nuclear Information System (INIS)

    Bleomycin (BLM), a natural antibiotic toxic to dividing cells has been used for treatment of several forms of cancer. BLM has been labelled with various cations but most have turned out to be unstable in vivo. In-BLM has demonstrated high bone marrow uptake, but by using an In-111-bleomycin complex (BLMC) formed at low pH, the low in vivo stability and high bone marrow uptake can be avoided. Our premise is to combine radiotherapy and chemotherapy by using radionuclide-BLMC. In this study we used In-111-A2a-c'-BLMC in 28 head and neck cancer patients. Scintigraphic findings were compared to those of surgery, pre-operative radiology and proliferation markers. The injected patient activity was approximately 85 MBq, 100 MBq/mg. (Author)

  11. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin

    International Nuclear Information System (INIS)

    Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy. Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics

  12. Therapeutic use of fisetin, curcumin, and mesoporous carbaon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Srabani Kar

    2015-04-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients responds to such a therapy. IPF is a progressive, ultimately fatal disorder for which substantive medical therapy is desperately needed. Fisetin is a flavonol which inhibits the activity of several pro-inflammatory cytokines. The polyphenol curcumin is used to treat inflammatory diseases, abdominal disorders, and a variety of other ailments. The aim of this study was to evaluate the beneficial effect of fistine, curcumin and mesoporous carbaon nanoparticle (MCN loaded fisetin as an anti-inflammatory agents against bleomycin-induced changes in mice with IPF. In our study, flavonoids showed their anti fibrotic action. The inflammatory cell count was greatly increased for bleo treated individuals and effectiveness of fisein was increased after addition of MCN particles with it, curcumin also showed anti- inflammatory effects. In another experiment, bleomycin effectively inhibits the cellular recruitment to the spleen and treatment with fisetin, and curcumin increases the cellular recruitment in spleen. Colony count was also increased in MCN+fisetin treated groups, and it was statistically significant. We also observed the increased level of cytokines with fisetin treatment, with curcumin treatment and with MCN +fisetin treatment as compared to the bleo treated sample. In conclusion, the present research suggests that fisetin and curcumin and MCN loaded fisetin may be a promising therapeutic agent for bleomycin-induced changes in mice with IPF. This will open up new perspectives for a potential role of these drugs as a molecular target in Idiopathic pulmonary fibrosis. [Biomed Res Ther 2015; 2(4.000: 250-262

  13. Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor-? (PPAR?) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR? agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

  14. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne

    2013-01-01

    Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy.

  15. Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Gong Yong; Bok, Se Mi; Han, Young Min [Department of Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Chung, Myung Ja [Department of Pathology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Yoon, Kwon-Ha [Department of Radiology, Iksan Hospital, Iksan (Korea, Republic of); Kim, So Ri [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Yong Chul, E-mail: leeyc@jbnu.ac.kr [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2012-08-15

    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR{gamma} agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

  16. Effects of Spaceflight on Molecular and Cellular Responses to Bleomycin-Induced DNA Damages in Confluent Human Fibroblasts

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2016-01-01

    Spaceflights expose human beings to various risk factors. Among them are microgravity related physiological stresses in immune, cytoskeletal, and cardiovascular systems, and space radiation related elevation of cancer risk. Cosmic radiation consists of energetic protons and other heavier charged particles that induce DNA damages. Effective DNA damage response and repair mechanism is important to maintain genomic integrity and reduce cancer risk. There were studies on effects of spaceflight and microgravity on DNA damage response in cell and animal models, but the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on molecular and cellular responses to DNA damages, bleomycin, an anti-cancer drug and radiomimetic reagent, was used to induce DNA damages in confluent human fibroblasts flown to the International Space Station (ISS) and on ground. After exposure to 1.0 µg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by foci and pattern counting of phosphorylated histone protein H2AX (?-H2AX). The cells on the ISS showed modestly increased average foci counts per nucleus while the distribution of patterns was similar to that on the ground. PCR array analysis showed that expressions of several genes, including CDKN1A and PCNA, were significantly changed in response to DNA damages induced by bleomycin in both flight and ground control cells. However, there were no significant differences in the overall expression profile of DNA damage response genes between the flight and ground samples. Analysis of cellular proliferation status with Ki-67 staining showed a slightly higher proliferating population in cells on the ISS than those on ground. Our results suggested that the difference in ?-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not significantly affect initial transcriptional responses to bleomycin treatment in the selected genes in the DNA damage signaling pathways

  17. Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo

    Directory of Open Access Journals (Sweden)

    Farahnaz Fatemi

    2005-01-01

    Full Text Available Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients was treated with bleomycin tattoo and the group B with cryotherapy and triamcinolone injection. There were four therapeutic sessions one month apart. All patients were followedup for three month after the end of treatment .The therapeutic response was determined as reduction of lesion size or flattening relative to initial size. Therapeutic response was 88.3±14% in group A and 67.4 ±22.5% in group B (p<0.001. In group A 69%, but in group B only 49% of patients were asymptomatic after the end of treatment. In group A there was no relation between therapeutic response and lesion size (p=0.58 but in group B lesions those were smaller (<100mm2 had better therapeutic response than larger ones (p=0.007. It was concluded that bleomycin tattoo is more effective in treatment of hypertrophic scar and keloid than traditional treatment, cryotherapy plus triamcinolone injection especially in larger ones.

  18. Serial micro-CT assessment of the therapeutic effects of rosiglitazone in a bleomycin-induced lung fibrosis mouse model

    International Nuclear Information System (INIS)

    The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 ± 1.4 at 3 weeks to 0.9 ± 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.

  19. Serial micro-CT assessment of the therapeutic effects of rosiglitazone in a bleomycin-induced lung fibrosis mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Jung; Jin, Gong Yong; Bok, Se Mi; Han, Young Min; Lee, Young Sun; Jung, Myung Ja; Kwon, Keun Sang [Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Institute for Medical Sciences, Jeonju (Korea, Republic of)

    2014-08-15

    The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 ± 1.4 at 3 weeks to 0.9 ± 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.

  20. Protocol Implementation Generator

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.

    2010-01-01

    Users expect communication systems to guarantee, amongst others, privacy and integrity of their data. These can be ensured by using well-established protocols; the best protocol, however, is useless if not all parties involved in a communication have a correct implementation of the protocol and all necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implemen...

  1. Fair Certified Email Protocol

    Directory of Open Access Journals (Sweden)

    Abdullah Mohammed Alaraj

    2013-07-01

    Full Text Available In this paper, a new fair certified email protocol is proposed. The proposed protocol uses offline trusted third party (TTP that will only be involved if a party misbehaves, otherwise the TTP is inactive. The protocol is based on the verifiable and recoverable encryption of keys. In this regard, the recipient of an email will be able to verify if the encrypted key used to encrypt the email is correct. The protocol comprises of only three messages in the exchange sub-protocol and three messages in the recovery sub-protocol. The proposed protocol is more efficient compared with related protocols.

  2. Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice

    Directory of Open Access Journals (Sweden)

    Ghofrani Hossein A

    2010-05-01

    Full Text Available Abstract Background Pulmonary fibrosis (PF is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well. Results PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7. Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF-? mRNA level and increased mRNA level of interleukin (IL-6 but did not influence IL-1?. At later stage (days 14 and 24 cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF-?1 and collagen type Ia1 (COL(I?1. However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival. Conclusions Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.

  3. Radiotherapy and bleomycin-containing chemotherapy in the treatment of advanced head and neck cancer: report of six patients and review of the literature

    International Nuclear Information System (INIS)

    In an effort to improve the complete remission rate achievable with bleomycin and cisplatin, administered prior to radiotherapy in previously untreated patients with unresectable epidermoid carcinoma of the head and neck, we initiated a pilot study employing simultaneous chemotherapy and radiotherapy. Six patients were treated with bleomycin (B) 15 mg i.m. t.i.w. 30-60 minutes prior to radiotherapy (RT) treatment with conventional fractionation, 180-200 rad/fx, 5 fx/week. During interruptions in B + RT for healing of mucocutaneous reactions, patients received cisplatin 40 mg/mg m2 once weekly. Toxicity included severe mucositis within the radiation port in all patients, three episodes of infection, and significant myelosuppression in one patient. Transient mild serum creatinine elevation occurred in four patients. Three patients did not complete treatment because of severity of toxicity. Response was: primary--4/6CR, 1/6 PR; regional nodes--1/5 CR, 4/5 PR. Review of the literature of concurrent bleomycin and radiotherapy trials in head and neck cancer indicates that other investigators have encountered severe toxicity using bleomycin dose and radiation fractionation schedules similar to ours. Toxicity may be reduced when lower doses of concurrent bleomycin and/or alternative radiation fractionation schedules are employed. Although results of uncontrolled trials suggest a possible therapeutic advantage to treatment with the combination compared to radiotherapy alone, this has not clearly been established in the four randomized trials reviewed

  4. Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil.

    Science.gov (United States)

    Boussen, H; Cvitkovic, E; Wendling, J L; Azli, N; Bachouchi, M; Mahjoubi, R; Kalifa, C; Wibault, P; Schwaab, G; Armand, J P

    1991-09-01

    Undifferentiated nasopharyngeal carcinoma (UCNT) is known to be radiosensitive and chemosensitive, but the latter has never been studied prospectively with phase II methodology. After an intensive work-up, 49 patients with recurrent (REC) and/or metastatic (MTS) UCNT were treated with three monthly cycles of cisplatin (CDDP) 100 mg/m2 day 1; bleomycin 15 mg intravenously (IV) day 1, and 16 mg/m2/d continuous infusion (CI) days 1 to 5; and fluorouracil (5FU) 650 mg/m2/d CI days 1 to 5 (PBF). Of the 49 patients, 33 were North African. The sex ratio was three males:one female, and the median World Health Organization (WHO) performance status was 1.6. In the 48 patients assessable for response, we observed nine (19%) complete responses (CRs) and 29 (60%) partial responses (PRs) (60%), for a 79% overall response rate (95% confidence interval, 68% to 90%) in the assessable group and a 78% global rate. There were eight CRs (24%) observed in the group without previous chemotherapy (33 patients) compared with one CR in the chemotherapy pretreated group (16 patients). Four patients are still alive without evidence of disease after 52+, 54+, 58+, and 58+ months, respectively. All of them had less than three bone MTS sites, and received radiation therapy in these sites. The results confirm the chemosensitivity of UCNT, and the observation of unmaintained long-term responders makes curability a possible consideration. PMID:1714951

  5. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

    Science.gov (United States)

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-01-01

    Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 ?L/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 ?g/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

  6. Effective treatment of Kaposi's sarcoma by electrochemotherapy and intravenous bleomycin administration.

    Science.gov (United States)

    Latini, A; Bonadies, A; Trento, E; Bultrini, S; Cota, C; Solivetti, F M; Ferraro, C; Ardigò, M; Amorosi, B; Palamara, G; Bucher, S; Giuliani, M; Cordiali-Fei, P; Ensoli, F; Di Carlo, A

    2012-01-01

    The present prospective study was aimed at evaluating the long-term efficacy of local electrochemotherapy (ECT) with the intravenous administration of bleomycin, on disease progression and viral activity in classic Kaposi's sarcoma (cKS), a vascular tumor related to human herpes virus-8 infection. Eighteen patients affected by isolate or multiple cutaneous lesions, refractory to conventional treatments, although in the absence of visceral involvement, were enrolled in a study. Follow-up visits were performed after 4 weeks and every 6 months for up to 48 months. A more extensive exploration of the immunologic status as well as of virological parameters was performed in nine patients. The results showed a significant clinical improvement in all patients after 4 weeks. A complete regression was observed in 12 patients after the first ECT, while four patients required a second treatment on the residual lesions after 4 weeks from the first intervention. The positive outcome persisted during the subsequent clinical control visits. Two patients, that showed rapidly evolving did not improve and relapsed despite a second round of ECT treatment. Effective treatment was associated with the reduction of viral load to undetectable levels. These data support the conduct of larger studies directed at validating the efficacy of ECT as a first-line therapy for cKS. PMID:22741941

  7. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Yoon Hee Cho

    2016-02-01

    Full Text Available Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM, a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 ?L/mL, the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 ?g/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  8. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

    International Nuclear Information System (INIS)

    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (∼0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM

  9. Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Benkhaled, L.; Xuncla, M.; Caballin, M.R. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain); Barrios, L. [Universitat Autonoma de Barcelona, Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia (Spain); Barquinero, J.F. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain)], E-mail: Francesc.Barquinero@uab.es

    2008-01-01

    Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation ({approx}0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

  10. Development of an in vivo radionuclide generator by labeling bleomycin with 191Os

    International Nuclear Information System (INIS)

    Bleomycin (BLM) has been labeled with various radioisotopes and widely used in therapy and diagnosis. 191Os is a parent radionuclide with 15.4 day half-life and decays by beta emission to 191mIr, which is a radionuclide with 4.96 s half-life. BLM was labeled with 191Os-hexachloro-osmate and its distribution and stability in wild-type mice was determined. The complex was obtained at the pH 2 in normal saline at 90 deg C in 48 h. Radio-TLC showed an overall radiochemical yield of 93-97%, radio-chemical purity > 97%. The biodistribution study for 191Os-hexachloro-osmate and 191Os-BLM were carried in wild type-mice up to 14 days. Lungs, liver and spleen uptake increased 24-72 h after administration of 1910s-BLM. 24 h after administration, the radioactivity of the kidney increased and remained constant. (author)

  11. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Science.gov (United States)

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-01-01

    Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

  12. Involvement of Kruppel-like factor 9 in bleomycin-induced pulmonary toxicity.

    Science.gov (United States)

    Gu, Yue; Wu, Yan-Bing; Wang, Li-Hui; Yin, Jia-Ning

    2015-10-01

    Oxidative stress or the production of reactive oxygen species (ROS) has been implicated as an important factor in the development of bleomycin (BLM)-induced pulmonary toxicity; however, the mechanism behind the toxicity remains to be elucidated. The present study aimed to investigate the key factor involved in BLM?induced toxicity. The study was conducted in human pulmonary fibroblast (HPF) cells and in a mouse model. The ROS level, cell death assay, protein and gene expression levels of Kruppel?like factor 9 (Klf9) and other associated factors were assessed. A dose?dependent increase in ROS, lipid peroxidation, cell death, and protein and mRNA expression levels of NF?E2?related transcription factor 2 (Nrf2) and Klf9 were observed in BLM?treated cells. However, the expression levels of the other antioxidant proteins assessed, including catalase, super oxide dismutase, glutathione reductase and thioredoxin reductase 2, were decreased. The expression levels of Nrf2 were decreased in cells treated with a higher concentration (>200 µM) of BLM. These results suggested that in response to increased intracellular levels of ROS, above a critical threshold, Nrf2 stimulates the expression of Klf9, resulting in a further increase in Klf9?mediated ROS production and subsequent cell death. Furthermore, the data suggested that Klf9 may be considered as an adjunctive therapeutic target for BLM-induced pulmonary toxicity. PMID:26133229

  13. The effects of combined treatment with radiation and bleomycin on the oral carcinoma involving the mandible

    International Nuclear Information System (INIS)

    The effect of concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin on oral carcinoma involving the mandible was examined histologically. In 14 of 18 patients who had mandibles resected after this combined treatment, bone invasion by carcinoma was observed histologically. According to Shimosato's classification of histological effects, 3 belonged to Grade III/IV, 4 to IIb, 3 to IIa and 4 to I. The formation of new bone that was considered to be reparable was observed in the marked effective patients. In 4 patients the Grade IIb, residual surviving cancer cells were observed in the mandible. Accordingly, excision was needed in the area of radiologic features of mandibular infiltration. But it is considered that although the excision scope for the patient who has received the preoperative treatment is the same as that for the patient who has not, it is advantageous for the former patient that a wider safety region is obtained. (author)

  14. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    International Nuclear Information System (INIS)

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.)

  15. Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer - dosimetric and biokinetic aspects

    International Nuclear Information System (INIS)

    Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (111In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45±0.24x10-3% ID/g in primary tumours and 0.52±0.20x10-3% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm-3. The radioactivity half-lives in the tumours were 30±7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that 111In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using 114mIn-labelled BLMC. (orig.)

  16. Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice

    Directory of Open Access Journals (Sweden)

    Tagami Atsuro

    2008-05-01

    Full Text Available Abstract Background The role of angiotensin II type 2 receptor (AT2 in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1 and AT2 antagonists in a mouse model of bleomycin (BLM-induced pulmonary fibrosis. Methods We examined effects of the AT1 antagonist (AT1A olmesartan medoxomil (olmesartan and the AT2 antagonist (AT2A PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF. Results With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF-? levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF-?1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-? and monocyte chemoattractant protein (MCP-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP-2 level but not TGF-?1. Conclusion Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.

  17. Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Liu Dai-Shun

    2009-06-01

    Full Text Available Abstract Background Advanced glycation end products (AGEs have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM-stimulated rat model treated with aminoguanidine (AG, a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg and orally administered with AG (40, 80, 120 mg/kg once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47, a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGF?1 and its downstream Smad proteins were analyzed by Western blot. Results AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p Conclusion These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGF?/Smads signaling.

  18. Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

    Science.gov (United States)

    De Palo, G; Zambetti, M; Pilotti, S; Rottoli, L; Spatti, G; Fontanelli, R; Musumeci, R; Kenda, R; Bombardieri, E; Stefanon, B

    1992-11-01

    Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens. PMID:1281804

  19. Electrochemotherapy with intravenous bleomycin injection: an observational study in superficial squamous cell carcinoma in cats.

    Science.gov (United States)

    Tozon, Natasa; Pavlin, Darja; Sersa, Gregor; Dolinsek, Tanja; Cemazar, Maja

    2014-04-01

    The aim of this study was to evaluate the efficacy and safety of electrochemotherapy (ECT) with bleomycin for treatment of squamous cell carcinoma (SCC) in cats. Between March 2008 and October 2011, 11 cats with 17 superficial SCC nodules in different clinical stages (ranging from Tis to T4), located on nasal planum (6/11), pinnae (3/11) and both locations (2/11), were included in a prospective non-randomised study. Sixteen of 17 SCC nodules were treated with ECT (15/16 with single session and in one case with two sessions); one nodule was surgically removed. Altogether, complete response (CR) was achieved for 81.8% (9/11) cats and 87.5% (14/16) nodules, lasting from 2 months up to longer than 3 years. Only 2/9 cats in which CR was initially observed, had recurrence 2 and 8 months after the ECT procedure. In the remaining two cats with highly infiltrative spread into adjacent tissues, progression of the disease was observed, despite ECT, and both were euthanased 4 and 5 months after the procedure. ECT in cats was well tolerated and no evident local or systemic side effects were observed. The results of this study suggest that ECT is a highly effective and safe method of local tumour control of feline cutaneous SCCs. It should be considered as an alternative treatment option, especially when other treatment approaches are not acceptable by the owners, owing to their invasiveness, mutilation or high cost. PMID:24127456

  20. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo

    Science.gov (United States)

    Huang, Tsung-Teng; Lai, Hsin-Chih; Ko, Yun-Fei; Ojcius, David M.; Lan, Ying-Wei; Martel, Jan; Young, John D.; Chong, Kowit-Yu

    2015-01-01

    Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1? and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-?1–induced expression of fibronectin and ?-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-?1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-?1 in lung tissues, and this effect is accompanied by decreased collagen 3?1 and ?-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis. PMID:26497260

  1. Malformaciones linfáticas: tratamiento percutáneo con bleomicina / Lymphatic malformations: percutaneus treatment with bleomycin

    Scientific Electronic Library Online (English)

    José Luis, Cuervo; Eduardo, Galli; Guillermo, Eisele; Erica, Johannes; Alejandro, Fainboim; Silvia, Tonini; Walter, Joaquin; Bettina, Viola; Miguel, Nazar.

    2011-10-01

    Full Text Available Las malformaciones linfáticas son anomalías del desarrollo del sistema linfático que tienden a sufrir complicaciones en su evolución. En la última década, la terapia con agentes esclerosantes ha ido ganando popularidad sobre la cirugía, por su eficacia, sus menores complicaciones y sus excelentes re [...] sultados estéticos. Presentamos una serie de 24 pacientes tratados mediante esclerosis percutánea con bleomicina. Los resultados fueron excelentes (reducción de volumen ? 95% y asintomáticos) en 12 pacientes, buenos (reducción de volumen entre 50% y 95% y asintomáticos) en 5 pacientes, regulares (reducción de volumen Abstract in english Lymphatic malformations are developmental abnormalities of the lymphatic system, which tend to complicate during their evolution. In the last decade, therapy with sclerosing agents has gained popularity over surgery due to its effectiveness, fewer complications, and excellent cosmetic results. We pr [...] esent a series of 24 patients treated with percutaneous bleomycin injection. Results were excellent (volume reduction ? 95%, without symptoms) in 12 patients, good (volume reduction between 50% and 95%, without symptoms) in 5 patients, fair (volume reduction

  2. Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.

    Science.gov (United States)

    Huang, Tsung-Teng; Lai, Hsin-Chih; Ko, Yun-Fei; Ojcius, David M; Lan, Ying-Wei; Martel, Jan; Young, John D; Chong, Kowit-Yu

    2015-01-01

    Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1? and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-?1-induced expression of fibronectin and ?-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-?1-treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin-induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-?1 in lung tissues, and this effect is accompanied by decreased collagen 3?1 and ?-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis. PMID:26497260

  3. Airway epithelial progenitors are region specific and show differential responses to bleomycin-induced lung injury.

    Science.gov (United States)

    Chen, Huaiyong; Matsumoto, Keitaro; Brockway, Brian L; Rackley, Craig R; Liang, Jiurong; Lee, Joo-Hyeon; Jiang, Dianhua; Noble, Paul W; Randell, Scott H; Kim, Carla F; Stripp, Barry R

    2012-09-01

    Mechanisms that regulate regional epithelial cell diversity and pathologic remodeling in airways are poorly understood. We hypothesized that regional differences in cell composition and injury-related tissue remodeling result from the type and composition of local progenitors. We used surface markers and the spatial expression pattern of an SFTPC-GFP transgene to subset epithelial progenitors by airway region. Green fluorescent protein (GFP) expression ranged from undetectable to high in a proximal-to-distal gradient. GFP(hi) cells were subdivided by CD24 staining into alveolar (CD24(neg)) and conducting airway (CD24(low)) populations. This allowed for the segregation of three types of progenitors displaying distinct clonal behavior in vitro. GFP(neg) and GFP(low) progenitors both yielded lumen containing colonies but displayed transcriptomes reflective of pseudostratified and distal conducting airways, respectively. CD24(low)GFP(hi) progenitors were present in an overlapping distribution with GFP(low) progenitors in distal airways, yet expressed lower levels of Sox2 and expanded in culture to yield undifferentiated self-renewing progeny. Colony-forming ability was reduced for each progenitor cell type after in vivo bleomycin exposure, but only CD24(low) GFP(hi) progenitors showed robust expansion during tissue remodeling. These data reveal intrinsic differences in the properties of regional progenitors and suggest that their unique responses to tissue damage drive local tissue remodeling. PMID:22696116

  4. Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin

    Directory of Open Access Journals (Sweden)

    Ghada M. Suddek

    2014-01-01

    Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

  5. Clinical evaluation of tumor scintigraphy with sup(99m)Tc-bleomycin, (1)

    International Nuclear Information System (INIS)

    Fundamental studies on the labeling techniques for sup(99m) Tc-bleomycin (sup(99m) Tc-BLM) were performed. Among them, Sn-resin kit method was found to be the best method, which could produce the most chemically stable sup(99m) Tc-BLM, requiring minimum amount of tin without ascorbic acid. Clinical evaluation of the kit labeled sup(99m) Tc-BLM was performed in various malignant and benign diseases. A comparative study with 67Ga citrate (67Ga) scintigraphy was also performed. sup(99m) Tc-BLM was revealed to have superior sensitivity and specificity of 73% and 72% for malignant tumors over those with 67Ga of 64% and 41%, respectively. Though sup(99m) Tc-BLM scintigraphy had a disadvantage in detecting lesions in the trunk comparing to 67Ga scintigraphy due to the high back ground radioactivity from 30 min. to 1 hr. after intravenous injection, it provides a excellent means in detecting malignant tumors in the limbs, head and neck. (author)

  6. Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Wang, Lei; Song, Yimin; Li, Xiankui; Guo, Haizhou; Zhang, Guojun

    2016-01-01

    Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate-buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF. PMID:26372067

  7. Autoradiographic and histological findings in vulva carcinomas with local bleomycin therapy

    International Nuclear Information System (INIS)

    Bleomycin was administered to 25 female patients with vulva carcinoma with problematic location of high operation risk. Macroscopically, in 75% of the cases, there was a tumour reduction of more than 50%. In addition to an immediate effect, at a later date (tau- = 21 days) the tumour was observed to have diminished. Histologically, in the well-reacting tumours a higher differentiation, foreign body granulomas, tumour decomposition, tumour-giant cells, and proliferation of the connective tissue. The histological changes were accompanied by a significant restriction of the proliferation which could be proven autoradiographically. The reaction of the carcinomas depended on the stage of the tumour, the degree of differentiation of the tumours, on the initial proliferation activity, and the age of the patients, however not on the sort of pre-treatment and the extent of the carcinoma. The local application of BLM should be reserved exclusively for cases with problematic location and high operation risk. The application of BLM in connection with a radiotherapy or poly-chemotherapy is discussed for these cases. (orig.) 891 MG/orig. 892 RDG

  8. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Scheistroeen, M. (Norwegian Radium Hospital, Oslo (Norway)); Trope, C. (Norwegian Radium Hospital, Oslo (Norway))

    1993-01-01

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.).

  9. The Wireless Application Protocol

    OpenAIRE

    Dave Singelee; Bart Preneel

    2005-01-01

    The Wireless Application Protocol WAP is a protocol stack for wireless communication networks. WAP uses WTLS, a wireless variant of the SSL/TLS protocol, to secure the communication between the mobile phone and other parts of the WAP architecture. This paper describes the security architecture of WAP and some important properties of the WTLS protocol. There are however some security problems with WAP and the WTLS protocol. Privacy, data protection and integrity are not always provided. Users ...

  10. The combined effect of bleomycin and irradiation on mouse lip mucosa. 2. Influence on the accumulation and repair of sublethal damage during fractionated irradiation

    International Nuclear Information System (INIS)

    The effect on the mouse lip mucosa of different fractionated irradiation schedules with and without bleomycin was investigated. Lowering the fraction size resulted in a progressive increase of both the dose modification factors (DMF) and the absolute dose reduction (ADR), i.e. from 1.19 and 2.8 Gy respectively for single doses to 1.86 and 21.5 Gy respectively for 20 fractions. The mechanisms involved are most probably a direct cell kill by bleomycin, together with a reduced capacity to accumulate and/or to repair sublethal damage, although the influence of redistribution in the cell cycle during bleomycin infusion can not be excluded. Such large differences in the interaction between chemotherapy and irradiation as a function of the fractionation schedule could lead to a significant underestimate of response if data from single dose or 2-fraction experiments are extrapolated to regimens used in clinical practice. (Auth.)

  11. Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

    International Nuclear Information System (INIS)

    Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also counteracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF-?B inhibition.

  12. Antifibrotic effect of lysophosphatidic acid receptors LPA1 and LPA3 antagonist on experimental murine scleroderma induced by bleomycin.

    Science.gov (United States)

    Ohashi, Takenobu; Yamamoto, Toshiyuki

    2015-09-01

    The study of lysophosphatidic acid (LPA) receptor has recently focused on its involvement in the pathogenesis of systemic sclerosis (SSc). We examined the inhibitory effects of the antagonist for the LPA receptor, a selective LPA1 and LPA3 antagonist (Ki16425), on dermal and lung fibrosis in a mouse model of SSc. Ki16425 was administered intra-dermally after 6 h on the same sites as bleomycin injection. Histopathological examination showed that skin lesions were markedly attenuated by treatment with Ki16425 at doses of 1 and 10 mg/kg, along with reduced dermal thickness. Hydroxyproline contents in the Ki16425-treated skin showed a decrease of 35% (1 mg/kg) and 45% (10 mg/kg) compared with those in the oil-injected skin of the controls. The number of mast cells and phospho-Smad2/3-positive spindle cells of the Ki16425-treated skin was significantly decreased compared with that in the controls. Additionally, RT-PCR analysis showed that the mRNA levels of TGF-?1, CTGF, MIP-1?, IFN-? and collagen ?1(I) were significantly decreased in both the 1-mg/kg and 10-mg/kg groups of the Ki16425-treated mice compared with those in the controls. Furthermore, treatment with bleomycin and Ki16425 showed reduction in lung fibrosis, and the hydroxyproline contents in the lungs of the Ki16425-treated mice showed a decrease of 25% (1 mg/kg) and 32% (10 mg/kg) compared with those in the lungs of the controls. Taken together, Ki16425 was found to improve dermal and lung fibrosis in a mouse model of bleomycin-induced murine scleroderma. These results suggest that Ki16425 has the potential to be an effective new treatment for scleroderma. PMID:25959255

  13. Investigation of the interacorporcal decay, elimination rate and diagnostic confidence of 57Co-bleomycine in patients with the uterine cervix cancer

    International Nuclear Information System (INIS)

    In 20 women with diagnosed squamous carcinoma of the uterine cervix the 57Co-Bleomycine was used for the estimation of the intracorporeal decay, elimination rate and neoplasmic tissue storage of the complex. Whole body scanner ''Scan modus'' type and gamma chamber were used. A rapid elimination of the examined complex with urine was noted, the blood concentration was significantly higher (p57Co-Bleomycine) can be applied as diagnostic means in cases of uterine squamous carcinoma and in its metastases. (author)

  14. Comparative study of fixation of Co57 labelled bleomycin, labelled gallium citrate and Hg197 labelled mercury chloride, benign or malignant pulmonary lesions

    International Nuclear Information System (INIS)

    Over the last ten years, numerous labelled molecules have been used in lung diseases, in order to attempt definite localisation of primary or secondary carcinoma. Three of these substances are now used: cobalt 57-labelled bleomycin, Hg197Cl2 and Ga67 citrate. A study of 34 patient with malignant or tuberculous lung disease with definite diagnosis, permitted demonstration of the fact that the highest uptake, or the best images, were obtained with labelled bleomycin. However, the long period of Co57 limits its indications in young subjects and, in these cases, HgCl2 is indicated

  15. Experimental studies on the radiation-modifying effect of bleomycin in malignant and normal mouse tissue in vivo

    DEFF Research Database (Denmark)

    Molin, J; Søgaard, P E; Overgaard, Jens

    1981-01-01

    The interaction between bleomycin (BLM) and radiation was studied in a C3H mammary carcinoma and its surrounding normal skin. In the skin, single and fractionated doses of sequential treatment with BLM (25 mg/kg) 24 hours prior to radiation therapy did not influence the response to irradiation, whereas simultaneous treatment with BLM given 15 minutes before radiation therapy enhanced the reaction to irradiation by a factor of 1.2 or 1.4 following treatment with one fraction or five fractions, re...

  16. Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation

    OpenAIRE

    Xie, TING; LIANG, JIURONG; Guo, Rishu; Liu, Ningshan; Noble, Paul W.; Jiang, Dianhua

    2011-01-01

    The molecular mechanisms of lung injury and fibrosis are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiological processes. To gain insight into miRNAs in the regulation of lung fibrosis, total RNA was isolated from mouse lungs harvested at different days after bleomycin treatment, and miRNA array with 1,810 miRNA probes was performed thereafter. MiRNAs expressed in lungs with ...

  17. Radiotherapy, combined with simultaneous chemotherapy with mitomycin C and bleomycin for inoperable head and neck cancer--preliminary report

    International Nuclear Information System (INIS)

    Purpose: Prospectively designed randomized clinical study was undertaken to assess the efficacy of simultaneous application of irradiation, Mitomycin C, and Bleomycin in treatment of patients with inoperable head and neck carcinoma. Methods and Materials: Between March 1991 and October 1993, 49 patients with inoperable head and neck carcinoma were randomly assigned to receive either radiation therapy alone (group A) or radiotherapy combined with simultaneous application of Mitomycin C and Bleomycin (group B). Patients in both groups were irradiated five times weekly with 2 Gy to the total dose of 66-70 Gy. Chemotherapy regimen included intramuscular application of Bleomycin 5 units twice a week, with the planned dose being 70 units and Mitomycin C 15 mg/m2 applied intravenously after delivery of 9-10 Gy of irradiation. The application of Mitomycin C was planned to be repeated on last day of radiotherapy in the dose of 10 mg/m2. In attempt to enhance the effect of chemotherapeutic drugs, patients in group B received also Nicotinamide, Chlorpromazine, and Dicoumarol. Results: The difference in complete response rate between both treatment groups (24% in group A and 63% in group B) was statistically significant (p = 0.015). The difference in response rate was much more pronounced in patients with oropharyngeal carcinoma only (18% in group A compared to 81% in group B; p = 0.0003), while for all other subgroups added together, there was observed no benefit of multidrug therapy. Median follow-up was 18 months. Disease-free survival of patients in group A (9%) was significantly lower then in group B (48%) (p 0.001). The difference between both treatment groups was even greater in patients with oropharyngeal carcinoma only: disease-free survival of these patients in group B was 66%, while in group A, all recurred (p = 0.00001). Conclusion: From results of our prospective randomized study it seems that the group of patients that received multidrug treatment with Mytomycin C, Bleomycin, Nicotinamide, Chlorpromazine, and Dicoumarol as enhancers of radiotherpy fared better than patients treated by radiotherapy alone

  18. Bleomycin-resistance gene derived from the transposon Tn5 confers selective advantage to Escherichia coli K-12.

    OpenAIRE

    Blot, M.; Meyer, J.; Arber, W

    1991-01-01

    The plasmid pRAB2 contains a silent operon derived from the transposon Tn5 and carrying the gene neo for neomycin-kanamycin resistance and a truncated ble gene (ble333) for bleomycin resistance. Spontaneous mutants that express the two resistances provide Escherichia coli cells an improved fitness during the phase of decline in the absence of the antibiotics. It is shown that the ble333 gene product is responsible for this better fitness. These results can explain a previously described selec...

  19. Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

    Directory of Open Access Journals (Sweden)

    Magaly M. Sales

    1999-03-01

    Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP vs. 10 normal individuals (P = 0.67. Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando comparados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP usou-se o radiomimético bleomicina (BLM. Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e feminino. Entretanto, a distribuição de quebras induzidas por bleomicina em cada grupo cromossômico não foi similar nos pacientes do sexo feminino e controles normais. É possível que a sensibilidade cromossômica à BLM encontrada nos pacientes com FAP esteja relacionada a deficiência de reparo de DNA.

  20. Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

    Directory of Open Access Journals (Sweden)

    Flower Roderick J

    2011-10-01

    Full Text Available Abstract Background The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1 is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. Results Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i the degree of inflammation at day 7; and ii indexes of fibrosis (assessed by deposition of hydroxyproline in the lung at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-?1, IFN-? and TNF-? generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21 or therapeutically (from day 14 onward, ameliorated both signs of inflammation and fibrosis. Conclusion Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.

  1. Ultrastructural changes of human esophageal carcinoma induced by preoperative treatments with bleomycin and/or radiation

    International Nuclear Information System (INIS)

    In the present study, 44 cases of esophageal carcinoma were electron-microscopically examined. Nuclear bodies of various types observed in carcinoma cells or in normal mucosa of the esophagus treated by bleomycin and radiation, single or combined (BLM/R), were classified into seven types. Types A and B were observed in carcinoma cells of both conditions of untreated or treated with BLM/R. Types C, D and E were specific findings in squamous carcinoma cells after BLM/R treatment. Types F and G were considered to be far advanced in terms of other nuclear bodies and were observed in strongly affected carcinoma cells. These nucleolar changes were considered to be specific alterations induced by BLM in esophageal carcinoma cells. The appearance of various nuclear bodies and a series of nucleolar segregation after BLM/R treatments were confirmed as well in metastatic lesions of abdominal lymph nodes that may be affected only with minimal or disregardable scattered radiation, if any, giving no sifnificant influence to cell activity. This fact has suggested that types C, D and E nuclear bodies and nucleolar segregation are changes specific to BLM/R treatments, some solely to BLM. Other nuclear changes consisted in the appearance of fibrillar structures of three different types that were considered to have been produced by disturbed ribosomal activity in the nuclei. On the basis of results in the present study, BLM apparently showed serious evidence of remarkable influences or effects, although not constantly and generally available, on certain squamous carcinoma cells of the esophagus. Some of the evidence was represented by nucleolar segregation and characteristic nuclear bodies of different types, particularly of types C, D and E. (J.P.N.)

  2. The effects of combined treatment with radiation and bleomycin on the primary oral carcinoma

    International Nuclear Information System (INIS)

    Eighty-two previously untreated patients with squamous cell carcinoma arising from the oral mucosa were treated by concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin at our department from 1976 to 1985. Therapeutic effects were examined clinically and histologically, and the role as a preoperative treatment was discussed. Moreover, a statistical analysis was performed to determine the factors related to the histological effects. 1. The ratio of complete response was 42.7 % and the ratio of partial response was 89.0 %. 2. 59 patients had subsequent treatment with surgery. Step sections were prepared from surgically resected specimens and examined microscopically. 1) According to Shimosato's classification of histological effects, 19 belonged to Grade III/IV, 15 to IIb, 13 to IIa and 12 to I/0. 2) In 7 of 15 Grade IIb patients, residual survival cancer cells were not observed at the margin of the area previously occupied by tumor at the beginning of treatment. Accordingly, 44.1 % (7 with IIb and 19 with III/IV) of 59 patients may be controlled by the more conservative surgery. 3. 18 patients with CR received additional combined therapy alone without any further treatment. Local control rate of these patients was 66.7 %. Therefore, 31 patients (these 12 patients and 19 of Grade III/IV) could be controlled by this therapy alone. 4. The histological effects significantly depended on the following factors of tumors; size, growth pattern, and degree of histologic differentiation. 82.2 % of 73 patients could be classified into good effective group or poor group accurately by the quantification theory Type II of Hayashi. It is considered that this method is useful for predicting the effects of this combined treatment. (author) 57 refs

  3. Effect of early treatment with transcutaneous electrical diaphragmatic stimulation (TEDS on pulmonary inflammation induced by bleomycin

    Directory of Open Access Journals (Sweden)

    Laisa A. Santos

    2013-12-01

    Full Text Available BACKGROUND : Bleomycin (B is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. OBJECTIVE: The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS. METHOD : Wistar rats were divided into 4 groups (n=5: a control group (C; a stimulated group (TEDS; a group treated with a single dose of B (intratracheally, 2.5 mg/kg (B; and a group treated with B and electric stimulation (B + TEDS. After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE and 8-isoprostane-PGF2? (8-iso-PGF2?. The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2?. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p?0.05. RESULTS : The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. CONCLUSION : B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage.

  4. Bleomycin-induced alterations in DNA replication: relationship to DNA damage.

    Science.gov (United States)

    Dziegielewski, J; Melendy, T; Beerman, T A

    2001-01-23

    Bleomycin (BLM), a well-known DNA scission agent, is assumed to inhibit intracellular DNA replication by damaging the DNA template (cis-acting mechanism), although other DNA damaging compounds can alter DNA replication through modulation of crucial replication factor(s) (trans-acting mechanism). The present study examines the relationship between DNA damage and inhibition of replication caused by BLM in the well-defined simian virus 40 (SV40) intracellular and cell-free in vitro systems. Treatment of SV40-infected BSC-1 cells for 2 h with BLM at 50 microg/mL, induced 0.3 break/viral genome. Under the same treatment conditions, analysis of replication intermediates on two-dimensional gels showed a decrease in both mass of SV40 replication intermediates and replication activity. The mass of SV40 intermediates was decreased to about 30%, whereas replication activity was reduced to less than 5%. These results suggest that BLM inhibits both initiation and elongation phases of SV40 replication. In a cell-free DNA replication system, extracts from BLM-treated cells (50 micro/mL) were able to support SV40 DNA replication by only 50%. In this study, non-drug-treated DNA template was used, implying that BLM can induce a trans-acting effect. Finally, the drug-induced effects on SV40 DNA replication in cell-free and intracellular viral systems were compared to the effects on genomic DNA replication in BSC-1 cells. Overall, the results support the concept that BLM-induced inhibition of DNA replication occurs by both trans- (inhibition of replication of nondamaged template) and cis-acting mechanisms (template damage). PMID:11170387

  5. T regulatory cells and attenuated bleomycin-induced fibrosis in lungs of CCR7-/- mice

    Directory of Open Access Journals (Sweden)

    Trujillo Glenda

    2010-09-01

    Full Text Available Abstract Background C-C chemokine receptor (CCR7 is a regulator of dendritic cell and T cell migration, and its role in tissue wound healing has been investigated in various disease models. We have previously demonstrated that CCR7 and its ligand, chemokine (C-C motif ligand (CCL21, modulates wound repair in pulmonary fibrosis (PF but the mechanism of this is unknown. The objective of this study was to investigate whether the absence of CCR7 protects against bleomycin (BLM-induced PF. CCR7-/- mice failed to mount a fibrotic pulmonary response as assessed by histologic collagen staining and quantification by hydroxyproline. We hypothesized that the prominent characteristics of CCR7-/- mice, including elevated levels of cytokine and chemokine mediators and the presence of bronchus-associated lymphoid tissue (BALT might be relevant to the protective phenotype. Results Pulmonary fibrosis was induced in CCR7+/+ and CCR7-/- mice via a single intratracheal injection of BLM. We found that the lung cytokine/chemokine milieu associated with the absence of CCR7 correlated with an increase in BALT, and might be attributable to regulatory T cell (Treg homeostasis and trafficking within the lungs and lymph nodes. In response to BLM challenge, CCR7-/- mice exhibited an early, steady increase in lung CD4+ T cells and increased CD4+ CD25+ FoxP3+ Tregs in the lungs 21 days after challenge. These findings are consistent with increased lung expression of interleukin-2 and indoleamine 2,3-dioxygenase in CCR7-/- mice, which promote Treg expansion. Conclusions Our study demonstrates that the protective phenotype associated with BLM-treated CCR7-/- mice correlates with the presence of BALT and the anchoring of Tregs in the lungs of CCR7-/- mice. These data provide novel evidence to support the further investigation of CCR7-mediated Treg trafficking in the modulation of BLM-induced PF.

  6. SPECT quantitation of cobalt-57 bleomycin delivery to human brain tumors

    International Nuclear Information System (INIS)

    A newly developed and validated noninvasive quantitative SPECT method was used to measure the in vivo uptake of [57Co]bleomycin (Co-bleo) in 13 human brain tumors and the uptake of [/sup 99m/Tc]glucoheptonate (GH) in 23 brain tumors. Significant differences in tumor uptake were found. The tumor concentration over time, the tumor to blood radioactivity at 30 min and the tumor cumulative concentration of radioactivity showed marked differences even between tumors with the same histology. Only a weak correlation was found between tumor concentration of Co-bleo and of GH. Therefore, a simple imaging agent such as GH cannot, at the present time, serve as an indicator of individual tumor uptake and further experience with other agents is still necessary. Contrary to the generally held view, no correlation was found between the concentration of drug in the blood and its tumor concentration. It is suggested, therefore, that the level of a drug in the blood cannot be used as a criterion of the amount that will penetrate the tumor. Direct SPECT measurement of the concentration of the drug in the tumor itself should be performed. The bioavailability of a drug is critical in order for it to exert it tumoricidal effect. The results, showing marked differences in uptake between brain tumors, suggest that before chemotherapy is administered, uptake of the chemotherapeutic drug in the individual tumor to be treated should be assessed and comparisons should be made between the uptake of a series of drugs to determine which drug would be most efficacious on the basis of its uptake as well as its tumor cell killing potential

  7. A young male with shortness of breath

    Directory of Open Access Journals (Sweden)

    Khan Fahmi

    2008-01-01

    Full Text Available We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum; the patient received four cycles of chemotherapy. After 8 months, the patient was seen in the clinic; he was well.

  8. Rational exchange protocols

    OpenAIRE

    Alcaide Raya, Almudena

    2008-01-01

    An exchange protocol describes a sequence of steps by which several entities are capable of exchanging certain pieces of information in a particular context. Rational{exchange protocols serve that core purpose with several important advantages over the existing exchange paradigms, those referred to as fair{exchange solutions. Traditional fair{exchange protocols impose strong restrictions on the protocol exe- cution context. They ensure fairness to participants but at the expense of entities s...

  9. The Sprague Dawley rats as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin

    Directory of Open Access Journals (Sweden)

    Daniel Francisco Arencibia Arrebola

    2010-04-01

    Full Text Available The micronuclei assay in bone marrow is easily to reproduce and its offer clear information on the cellular proliferation in bone marrow. This system allow registering in vivo the capacity of the chemical substances to induce chromosomics ruptures to interfere or the chromosomes metaphases migration during the mitosis of the somatic cells. In this article wedecide to evaluate the Sprague Dawley rats in both sexes as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin. Which were formed 5 experimental groups per sex, the first administered with NaCl 0,9 % by intraperitoneal (i.p route, the second and third groups were administered with cyclophosphamide by i.p route,with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience obtained higher results of the micronucleis inductions with the use of cyclophosphamide was administered 48 and 24 hours beforesacrifice in SD rats of both sexes. That which constitutes in our experimental conditions the best experimental design to induce the micronucleis formation in bone marrow cells of rodents, increasing considerably the spontaneous frequency to present in this species of rat, useful in evaluation studies on in vivo antigenotoxic drugs effects.

  10. Low-magnification image analysis of Giemsa stained, electroporation and bleomycin treated endothelial monolayers provides reliable monolayer integrity data.

    Science.gov (United States)

    Meulenberg, Cécil J W; Cemazar, Maja

    2014-06-01

    The aim of this study was to develop an in vitro cell model for studying the in vivo observed vascular effect, induced by exposing blood vessels to changing electric field strengths. Human microvascular endothelial cells (HMEC-1) were cultured as monolayers on 8 chamber glass slides as a model of capillary wall. Exposed to electric pulses alone, or in the presence of bleomycin (electrochemotherapy), monolayers were incubated with culture medium, fixed with methanol, stained with Giemsa, and photographed. Images of high-contrast low-magnification monolayers made under identical optimal light exposure were converted to greyscale, and the use of a threshold tool yielded a binary distribution, from which we determined two parameters of monolayer integrity: the covered surface area and the number of cells. We show that this low-magnification image analysis method for attached endothelial cells provides reliable control parameters of monolayer integrity, representing capillary wall. Besides, already within 2h post-treatment the data show distinct effects in the monolayer integrity parameters for electric pulses alone, or in the presence of bleomycin. The present method can be readily introduced to short and long-term toxicity assays with a variety of treatment conditions. PMID:24412537

  11. Scintigraphy with 57Co-bleomycin in the detection of lung cancer. A review of 268 well-documented patients

    International Nuclear Information System (INIS)

    Over a 5-year period 57Co-bleomycin scintigraphy for tumor detection was performed with a large-field-of-view gamma camera. The scintigrams of 268 patients with lung cancer, with a benign lesion, or with no abnormality in the chest, were reviewed. A sensitivity of 96% was found. In a group of 193 patients in whom a preoperative pathologic diagnosis could not be obtained sensitivity was 95%, specificity was 87%. Correlation between tumor size and tumor-to-non-tumor ratio was established for squamous cell carcinoma, adenocarcinoma, and small cell anaplastic carcinoma. Adenocarcinomas were smaller and showed lower tumor-to-non-tumor ratios than other histologic types. In squamous cell carcinoma a possible correlation between tumor-to-non-tumor ratio and histologic differentiation was investigated, but could not be established. It is concluded that 57Co-bleomycin scintigraphy is helpful in the evaluation of patients with possible lung cancer in whom a preoperative pathologic diagnosis cannot be obtained

  12. Adaptation of TURN protocol to SIP protocol

    CERN Document Server

    Guezouri, Mustapha; Keche, Mokhtar

    2010-01-01

    Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On the other, it is caused by the dynamic allocation of UDP ports for emission and reception of packets RTP/RTCP. The TURN Protocol may face this weakness. However, its use requires a certain number of exchanges between the clients and a TURN server before establishing the multimedia sessions and this increase the latent time. In this article, we propose to adapt TURN protocol for applications based on SIP protocol such as telephony over Internet, conference video, etc. This adaptation optimises the establishment of multimedia sessions by integrating a manager of TCP connections and multimedia flow controller into SIP Proxy server.

  13. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  14. Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2/ERK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Bo Zhu

    2013-12-01

    Full Text Available Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS in lung tissues and, thus, prevented nitric oxide (NO release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2 and phosphorylation extracellular regulated protein kinases (p-ERK expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

  15. Biochemical and histological impact of direct renin inhibition by aliskiren on myofibroblasts activation and differentiation in bleomycin induced pulmonary fibrosis in adult mice.

    Science.gov (United States)

    Asker, Samar A; Mazroa, Shireen A; Boshra, Vivian; Hassan, Ahmed M

    2015-08-01

    Aliskiren is a drug classified as a direct renin inhibitor. The renin-angiotensin system plays an important role in pulmonary fibrogeneses. This study aimed to investigate the impact of aliskiren on pulmonary fibrosis induced by bleomycin. Forty adult mice were divided into group I (control), group II (aliskiren 25mg/kg/day IP), group III (bleomycin 0.035U/g intraperitoneally twice weekly for 4 weeks) and group IV (aliskiren+bleomycin). Plasma renin activity (PRA), lung content of hydroxyproline and transforming growth factor-?1 (TGF-?1) were assayed. Lung paraffin sections were prepared for histological study and immunohistochemical detection of alpha smooth muscle actin (?SMA) as a marker for myofibroblasts activation and differentiation. Bleomycin induced a significant elevation of PRA with a significant increase in hydroxyproline and TGF-?1 in group III. Microscopically, pulmonary fibrosis was evident in the form of areas of collapsed alveoli, intense inflammatory cells infiltrations, excess accumulation of collagen, and excessively encountered ?SMA positively immune-stained myofibroblasts, compared to a negative immune-reaction in groups I and II. In group IV, aliskiren resulted in a significant decrease in PRA, TGF-?1 and hydroxyproline, with an attenuation of pulmonary fibrosis and a decrease in ?SMA positively immune-stained myofibroblasts. In conclusion, renin inhibition by aliskiren attenuated pulmonary fibrosis through decreasing TGF-?1 and myofibroblasts activation and differentiation. PMID:26002989

  16. Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

    Scientific Electronic Library Online (English)

    Magaly M., Sales; Edmundo J. de, Lucca; Seizo, Yamashita; Luis Henrique Cury, Saad.

    1999-03-01

    Full Text Available Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP) e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando compar [...] ados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP) usou-se o radiomimético bleomicina (BLM). Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e feminino. Entretanto, a distribuição de quebras induzidas por bleomicina em cada grupo cromossômico não foi similar nos pacientes do sexo feminino e controles normais. É possível que a sensibilidade cromossômica à BLM encontrada nos pacientes com FAP esteja relacionada a deficiência de reparo de DNA. Abstract in english Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleo [...] mycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

  17. Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report

    International Nuclear Information System (INIS)

    Purpose: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone. Methods and materials: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66-70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week IM, total dose 70 units, mitomycin C 15 mg/m2 IV after delivery of 10 Gy, and 10 mg/m2 IV on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol. Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients. Results: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%-80%). DFS at the median follow-up of 14 months was 60% (95% CI 43-77%) and OS 58% (95% CI 42-74%). Conclusion: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone

  18. Evaluación de implantes de norgestomet reutilizados en protocolos de sincronización del estro en vacas Brahman / Evaluation of reused norgestomet implants in estrus synchronization protocols in Brahman cows

    Scientific Electronic Library Online (English)

    Luis, Uribe-Velásquez; Adriana, Correa-Orozco; Lina, Cuartas-Betancurth; Diego, Villamizar-Ramirez; Santiago, Ángel-Botero.

    2013-01-01

    Full Text Available Objetivo. Evaluar las concentraciones de progesterona, la manifestación de estro y las tasas de preñez en vacas Bos indicus sometidas a varios protocolos de sincronización del estro con un implante de norgestomet usado previamente. Materiales y métodos. Sesenta vacas recibieron un implante auricular [...] de norgestomet reutilizado y fueron distribuidas en uno de cuatro protocolos: (1) benzoato de estradiol (BE) + progesterona (P4) + prostaglandina F2? (PG) (BE+P4+PG); (2) valerato de estradiol (VE) + norgestomet (NG) (VE+NG); (3) el mismo protocolo BE+P4+PG, asociado con 400 UI de gonadotropina coriónica equina (eCG) (BE+P4+PG+eCG); (4) el mismo protocolo VE+NG, asociado con 400 UI de eCG (VE+NG+eCG). El implante fue removido el día 9, con inseminación artificial (IA) 12 horas después de la detección del estro. La preñez fue diagnosticada 45 días después de la IA. Las muestras de sangre fueron tomadas los días 0, 4 y 9 (después de colocar el implante) para el análisis de progesterona por RIA. Resultados. En el día 4, las concentraciones de progesterona fueron menores en vacas tratadas con BE+P4+PG (0.90 ± 0.73 ng/ml; p0.05). Conclusiones. Los implantes de norgestomet reutilizados fueron eficaces para sincronizar el estro y alcanzar tasas de preñez adecuadas en vacas Brahman. Abstract in english Objective. To evaluate progesterone concentrations, occurrence of estrus and pregnancy rates in Bos indicus cows submitted to several estrous synchronization protocols with previously used Norgestomet implants. Materials and methods. Sixty cows were given a reused Norgestomet ear implant on Day 0 an [...] d were assigned to receive one of four protocols: (PROT 1) estradiol benzoate (EB) + progesterone (P4) + prostaglandin F2? (PG) (EB+P4+PG); (PROT 2) estradiol valerate (EV) + norgestomet (NG) (EV+NG); (PROT 3) same as EB+P4+PG protocol, plus a 400 UI equine chorionic gonadotropin (eCG) (EB+P4+PG+eCG); (PROT 4) same as EV+NG protocol, plus a 400 UI eCG (EV+NG+eCG). The implant was removed on Day 9, with artificial insemination (AI) 12 h after detection of estrus. Pregnancy was diagnosed 45 d after AI. Blood samples were collected on Day 0, 4 and 9 (after ear implant was placed), for progesterone analysis by RIA. Results. On day 4, progesterone concentrations were lower in cows treated with EB+P4+PG (0.90 ± 0.73 ng/ml; p0.05). Conclusions. Reusing Norgestomet implants was effective for synchronizing estrus and promote satisfactory pregnancy rates in Brahman cows.

  19. Block Advertisement Protocol

    OpenAIRE

    Nemirovsky, Danil

    2015-01-01

    Bitcoin, a decentralized cryptocurrency, has attracted a lot of attention from academia, financial service industry and enthusiasts. The trade-off between transaction confirmation throughput and centralization of hash power do not allow Bitcoin to perform at the same level as modern payment systems. Block Advertisement Protocol is proposed as a step to resolve this issue. The protocol allows block mining and block relaying to happen in parallel. The protocol dictates a miner to advertise the ...

  20. Vertical Protocol Composition

    DEFF Research Database (Denmark)

    Groß, Thomas; Mödersheim, Sebastian Alexander

    2011-01-01

    The security of key exchange and secure channel protocols, such as TLS, has been studied intensively. However, only few works have considered what happens when the established keys are actually used—to run some protocol securely over the established “channel”. We call this a vertical protocol composition, and it is truly commonplace in today’s communication with the diversity of VPNs and secure browser sessions. In fact, it is normal that we have several layers of secure channels: For instance, ...

  1. Kinetics of 111In-labeled bleomycin in patients with brain tumors. Compartmental vs. non-compartmental models

    International Nuclear Information System (INIS)

    The kinetics of an indium-111 labeled bleomycin complex (111In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of 111In-BLMC in the plasma pool was 14±7 min without and 1.8±0.6 h when accounting for recirculation, and 13±4 h in the total body pool. The mean plasma clearance of 111In-BLMC was 0.3±0.1 ml blood/min and the mean half-life in urine was 3.5±0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma=0.02±0.01, from depot to plasma=(12±9) * 10-4, from plasma to depot=0.01±0.01, from tumor to plasma=0.39±0.19 and from plasma to tumor=1.11±0.57, all in units minute-1. The mean turnover time from the tumor was 4.5±2.7 min and from the depot 20±8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing the in vivo behaviors of 111In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor. (author)

  2. Distribution of 67Ga-Bleomycin complex in normal rats and comparison with 67Ga-Cl3

    International Nuclear Information System (INIS)

    67Ga- chloride was prepared in Cyclotron Department of Nuclear Research Center of Agriculture and Medicine, then Bleomycin was labeled with 67Ga-Chloride according to the general procedure, but some factors were modified. Distribution of 67 Ca-Bleomycin and 67 Ga-Chloride in 12 tissue of normal rats was studied 1,2, 4, 24 and 48 hours after injection, percent of injection dose per gram of tissue (%ID/g. tissue) in all of 12 normal rats for 67 Ga-Cl3 was lesser than 67Ga-Bl 1,2 and 4 hours after injection, About 67Ga-Bl %ID/g, tissues for bladder was high, because it goes out of body by urine, and there was a high %ID/g, tissue in lung after 1, 2 and 4 hours. About 67GaCl3 likes 67Ga-Bl there was a high %ID/g tissue for bladder, after that was high %ID/g tissue in lung and kidney, too. Also 48 hours after injection, clearance of 67Ga-Bl from blood was 2.64 times that of 67Ga-Cl3 in normal rats and the clearance of 607Ga-Bl in blood from 1 hour till 48 hours after injection to the clearance of 67GaCl3 in blood for above times is about 7 times. They can be reasons that 67Ga does not isolated from 67Ga-Bl complex and not attach to plasma proteins

  3. Transport Protocol Throughput Fairness

    Directory of Open Access Journals (Sweden)

    Saleem Bhatti

    2009-11-01

    Full Text Available Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP. These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants, and protocols that provide congestion control without reliability. For the former category, along with the deployed base of ‘vanilla’ TCP – TCP NewReno – the TCP variants BIC and CUBIC are widely used within Linux: for the latter category, the Datagram Congestion Control Protocol (DCCP is currently on the IETF Standards Track. It is clear that future traffic patterns will consist of a mix of flows from these protocols (and others. So, it is important for users and network operators to be aware of the impact that these protocols may have on users. We show the measurement of fairness in throughput performance of DCCP Congestion Control ID 2 (CCID2 relative to TCP NewReno, and variants Binary Increase Congestion control (BIC, CUBIC and Compound, all in “out-of-the box” configurations. We use a testbed and endto- end measurements to assess overall throughput, and also to assess fairness – how well these protocols might respond to each other when operating over the same end-to-end network path. We find that, in our testbed, DCCP CCID2 shows good fairness with NewReno, while BIC, CUBIC and Compound show unfairness above round-trip times of 25ms.

  4. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early as...... possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity....

  5. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Tolver, Anders; Jørgensen, L W; Andersen, J.L.; Adamsen, L; Højman, P.; Nielsen, R. H.; Rørth, Mikkel; Daugaard, Gedske

    2014-01-01

    Abstract Background: Bleomycin–etoposid–cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and...

  6. Renal impairment and late toxicity in germ-cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J.; Mortensen, M. S.; Kier, M. G. G.; Christensen, I. J.; Agerbaek, M.; Gupta, Ramneek; Daugaard, G.

    2015-01-01

    Background Treatment with bleomycin–etoposide–cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. Patients and methods BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. ...

  7. Renal impairment and late toxicity in germ-cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J; Mortensen, M S; Kier, M G G; Christensen, I J; Agerbaek, M; Gupta, R; Daugaard, Gedske

    2015-01-01

    BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity...

  8. Renal impairment and late toxicity in germ cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J; Mortensen, M S; Kier, M G G; Christensen, I J; Agerbaek, M; Gupta, R; Daugaard, G

    2015-01-01

    BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N=1,206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity....

  9. Changes in sensitivity to radiation and to bleomycin occurring during the life history of monolayer cultures of a mouse tumour cell line

    International Nuclear Information System (INIS)

    The response to X-radiation and to bleomycin has been measured at a number of times during the life of monolayer cultures of EMT6 mouse tumour cells. Little change in radiation sensitivity was seen at any time and no loss of the shoulder to the survival curve occurred. Cultures in early plateau phase (where a considerable amount of cell proliferation is balanced by cell loss) showed a reduced sensitivity to bleomycin when compared with cells in exponential growth. However, after a longer period in plateau phase, when proliferation had virtually ceased, the sensitivity became greater than that of exponential phase cells. These findings are discussed with reference to the conflicting results of other workers. (author)

  10. High cathepsin B activity in alveolar macrophages occurs with elastase-induced emphysema but not with bleomycin-induced pulmonary fibrosis in hamsters.

    Science.gov (United States)

    Padilla, M L; Galicki, N I; Kleinerman, J; Orlowski, M; Lesser, M

    1988-04-01

    Cathepsin B activity was quantitated in alveolar macrophages obtained from hamsters 10, 21, and 105 days after the intratracheal instillation of porcine pancreatic elastase, bleomycin, or normal saline. Alveolar macrophages lavaged from animals receiving elastase contained significantly higher enzyme levels at 21 and 105 days (16,200 and 17,000 U/mg protein/hr, respectively) as compared with saline-treated animals (12,300 units). In contrast, cells from animals receiving bleomycin showed a decrease in activity at 21 and 105 days (9700 and 9900 units, respectively). At 10 days enzyme levels did not differ significantly. The results suggest that cathepsin B levels in alveolar macrophages reflect differences in lung destruction and connective tissue repair in vivo. In addition, the finding of high cathepsin B activity in animals with emphysema suggests the possibility that cysteine proteases contribute to progressive lung destruction initiated by the intratracheal instillation of elastase. PMID:2451429

  11. Determination of hidden chromosome instability in persons suffered from the action of factors of the Chernobyl accident by the modified 'G2 bleomycin sensitivity assay'

    International Nuclear Information System (INIS)

    With the help of the modified 'G2-bleomycin sensitivity assay' the voluntary investigation of hidden chromosome instability in 53 persons with different radiation exposures had been fulfilled. In all examined groups, the individual levels of chromosome injuries under identical bleomycin exposure varied in a wide range and didn't depend on their initial values in intact cultures. Among control donors and individuals with low radiation exposure, ? 33 % hypertensive persons had been identified that can be considered as a genetically caused phenomenon. In patients recovered from acute radiation, 57.9 % persons expressed the hidden chromosome instability. The data obtained allow us to assume that high doses of ionizing radiation can modify the inherited susceptibility of human chromosomes to a mutagen exposure.

  12. Protocol Fuel Mix reporting

    International Nuclear Information System (INIS)

    The protocol in this document describes a method for an Electricity Distribution Company (EDC) to account for the fuel mix of electricity that it delivers to its customers, based on the best available information. Own production, purchase and sale of electricity, and certificates trading are taken into account. In chapter 2 the actual protocol is outlined. In the appendixes additional (supporting) information is given: (A) Dutch Standard Fuel Mix, 2000; (B) Calculation of the Dutch Standard fuel mix; (C) Procedures to estimate and benchmark the fuel mix; (D) Quality management; (E) External verification; (F) Recommendation for further development of the protocol; (G) Reporting examples

  13. Playing With Population Protocols

    Directory of Open Access Journals (Sweden)

    Xavier Koegler

    2009-06-01

    Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

  14. ATM and Internet protocol

    CERN Document Server

    Bentall, M; Turton, B

    1998-01-01

    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  15. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification. In response, we promote linear logic as a high-level language for both specifying and implementing voting protocols. Our linear logical specifications of the single-winner first-past-the-post (SW- FPTP) and single transferable vote (STV) protocols demonstrate that this approach leads to concise implementations that closely correspond to their legal specification, thereby increasing trust.

  16. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    Energy Technology Data Exchange (ETDEWEB)

    Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

    2013-09-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, ?-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  17. Direct Thrombin Inhibition Reduces Lung Collagen, Accumulation, and Connective Tissue Growth Factor mRNA Levels in Bleomycin-Induced Pulmonary Fibrosis

    OpenAIRE

    Howell, David C.J.; Goldsack, Neil R.; Richard P. Marshall; McAnulty, Robin J; Starke, Richard; Purdy, Gordon; Laurent, Geoffrey J.; Chambers, Rachel C

    2001-01-01

    Dramatic activation of the coagulation cascade has been extensively documented for pulmonary fibrosis associated with acute and chronic lung injury. In addition to its role in hemostasis, thrombin exerts profibrotic effects via activation of the major thrombin receptor, protease-activated receptor-1. In this study, we examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast responses in vitro and on bleomycin-induced pulmonary fibrosis in rats. UK-156406 significantly inh...

  18. Essential Roles of the CC Chemokine Ligand 3-CC Chemokine Receptor 5 Axis in Bleomycin-Induced Pulmonary Fibrosis through Regulation of Macrophage and Fibrocyte Infiltration

    OpenAIRE

    Ishida, Yuko; Kimura, Akihiko; Kondo, Toshikazu; HAYASHI, Takahito; Ueno, Masaya; Takakura, Nobuyuki; Matsushima, Kouji; Mukaida, Naofumi

    2007-01-01

    We investigated the pathogenic roles of CC chemokine ligand (CCL)3 and its receptors, CC chemokine receptor (CCR)1 and CCR5, in bleomycin (BLM)-induced pulmonary fibrosis (PF). An intratracheal injection of BLM into wild-type (WT) mice caused a massive infiltration of granulocytes and macrophages, followed by the development of diffuse PF with fibrocyte accumulation. Intrapulmonary CCL3 expression was enhanced rapidly and remained at elevated levels until PF developed. Moreover, CCL3 protein ...

  19. Adenosine A2A Receptor Blockade or Deletion Diminishes Fibrocyte Accumulation in the Skin in a Murine Model of Scleroderma, Bleomycin-induced Fibrosis

    OpenAIRE

    Katebi, Majid; Fernandez, Patricia; Chan, Edwin S. L.; Cronstein, Bruce N.

    2008-01-01

    Peripheral blood fibrocytes are a newly identified circulating leukocyte subpopulation that migrates into injured tissue where it may display fibroblast-like properties and participate in wound healing and fibrosis of skin and other organs. Previous studies in our lab demonstrated that A2A receptor-deficient and A2A antagonist-treated mice were protected from developing bleomycin-induced dermal fibrosis, thus the aim of this study was to determine whether the adenosine A2A receptor regulates ...

  20. Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review

    Directory of Open Access Journals (Sweden)

    F. Lobo Bailón

    2012-12-01

    Full Text Available Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo del tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo.Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with intralesional bleomycin injection is an effective and safe treatment for low-flow vascular malformations.

  1. Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema / Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review

    Scientific Electronic Library Online (English)

    F., Lobo Bailón; B., Berenguer Fröhner; B., González Meli; C., Marín Molina; E., De Tomás y Palacios; C., Alonso Bañuelos.

    2012-12-01

    Full Text Available Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo de [...] l tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo. Abstract in english Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of [...] the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with intralesional bleomycin injection is an effective and safe treatment for low-flow vascular malformations.

  2. Effect of apurinic/apyrimidinic endonucleases and polyamines on DNA treated with bleomycin and neocarzinostatin: specific formation and cleavage of closely opposed lesions in complementary strands

    International Nuclear Information System (INIS)

    Bleomycin and neocarzinostatin induce modified apurinic/apyrimidinic (AP) sites by oxidation of the sugar moiety in DNA. In order to quantitatively assess the susceptibility of these lesions to repair endonucleases, drug-treated 3H-labeled colE1 DNA was mixed with 14C-labeled heat-depurinated DNA, and endonuclease-susceptible sites in the mixture were titrated with various AP endonucleases or with polyamines. Single- and double-strand breaks were quantitated by determining the fractions of supercoiled, nicked circular, and linear molecules. Exonuclease III and endonucleases III and IV of Escherichia coli, indicating cleavage of drug-induced AP sites. Bleomycin-induced AP sites were much more sensitive to cleavage by putrescine than heat-induced sites. Treatment with putrescine or very high concentrations of endonuclease III also increased the number of double-strand breaks in bleomycin-treated DNA, suggesting a minor class of lesion consisting of an AP site accompanied by a closely opposed break in the complementary strand. These complex lesions were resistant to cleavage by endonuclease IV. These results suggest that virtually all neocarzinostatin-induced AP sites are accompanied by a closely opposed strand break. Several characteristics of the putative AP site/strand break lesions induced by neocarzinostatin suggest that they may correspond to certain AP-like lesions which were previously detected on DNA sequencing gels as endonuclease IV susceptible sites and which have been strongly implicated in neocarzinostatin-induced mutagenesis

  3. 1996 : Track Count Protocol

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The goal of St. Vincent National Wildlife Refuges Track Count Protocol is to provide an index to the population size of game animals inhabiting St. Vincent Island.

  4. Authenticated file broadcast protocol

    OpenAIRE

    Reis, Simão; Zúquete, André; Faneca, Carlos; Vieira, José

    2015-01-01

    The File Broadcast Protocol (FBP) was developed as a part of the DETIboot system. DETIboot allows a host to broadcast an operating system image through an 802.11 wireless network to an arbitrary number of receivers. Receivers can load the image and immediately boot a Linux live session. The initial version of FBP had no security mechanisms. In this paper we present an authentication protocol developed for FBP that ensures a correct file distribution from the intended source to the receivers. ...

  5. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification. In response, we promote linear logic as a high-level language for both specifying and implementing voting protocols. Our linear logical specifications of the single-winner first-past-the-post (SW- FPTP) and ...

  6. USA-USSR protocol

    CERN Multimedia

    1970-01-01

    On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

  7. A case-control study of nonrandom distribution of bleomycin-induced chromatid breaks in lymphocytes of lung cancer cases.

    Science.gov (United States)

    Wu, X; Hsu, T C; Annegers, J F; Amos, C I; Fueger, J J; Spitz, M R

    1995-02-01

    We used a case-control study design to determine the association between bleomycin-induced chromatid breaks and the risk of lung cancer in general and by specific histopathological types. Lymphocytes from primary blood cultures of 78 controls and 75 cases with 4 histopathological types of lung cancer were treated with 0.03 unit/ml bleomycin for 5 h, and the frequency of induced chromatid breakage and the locations of the breaks were determined in Q-banded preparations. After adjustment for their length, the larger chromosomes had more breaks than the smaller chromosomes in both cases and controls. The cases had significantly more breaks on chromosomes 4 and 5 than the controls did, with odds ratios (ORs) of 4.9 [95% confidence limits (CL), 2.0, 11.7] and 3.9 (95% CL, 1.6, 9.3), respectively. When the lung cancers were classified by histopathological type, adenocarcinomas had significantly more breaks on chromosomes 4 and 5, with ORs of 3.0 (95% CL, 1.0, 8.7) and 3.5 (95% CL, 1.2, 10.7), respectively. For squamous cell carcinoma, the ORs were significantly elevated for breaks on chromosomes 2, 4, and 5 with ORs of 3.5 (95% CL, 1.0, 11.7), 10.2 (95% CL, 2.5, 41.9), and 7.9 (95% CL, 1.9, 32.8). For small cell carcinoma, breaks on chromosomes 2 and 4 showed significantly increased ORs of 33.2 (95% CL, 2.2, 513.3) and 20.4 (95% CL, 1.7, 250.1), respectively. However, no specific chromatid breaks were detected in cases with large cell carcinoma. When the frequency of chromatid breaks at specific regions was calculated, breaks at 4p14, 4q27, 4q31, 5q21-q22, 5q31, and 5q33 were significantly more common in lung cancer cases than in controls. Lung cancer risk had a dose-response relationship with breaks on chromosomes 4 and 5. Cigarette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5. The findings suggest that the susceptibility of particular chromosome loci to mutagenic damage may be a risk factor for specific types of lung cancer. PMID:7530597

  8. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    2013-01-01

    This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS (covered in Chapter 3 and 4), and how they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small O(1) internal memory to store N pieces of data on a server while revealing nothing more than the size of the memory N, and the number of accesses. This specifically includes hiding the access pattern. We construct an oblivious RAM that hides the client’s access pattern with information theoretic security with an amortized log3 N query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to log2 N, while also avoiding the bottleneck of sorting networks. And we show how to utilize this construction for four-playerMPC. Another line of work (covered in Chapter 2) has results about the power of correlated randomness; meaning in a preprocessing phase the participants in a MPC protocol receive samples from some joint distribution to aid them implement the secure computation. Especially we look at the communication complexity of protocols in this model, and perfectly secure protocols. We show general protocols for any finite functionality with statistical security and optimal communication complexity (but exponential amount of preprocessing). And for two-player functionalities where only one player receives output (sender-receiver functionalities) with perfect security. We also show protocols for some specific sender-receiver tasks with both optimal communication and small preprocessing. We show lower bounds on the amount of communication and show the impossibility of general perfect protocols when both parties receive output. Also we show how to use the sender-receiver protocols with perfect security given correlated randomness to construct secure protocols in the plain model with perfect correctness.

  9. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern....... We construct an oblivious RAM that hides the client's access pattern with information theoretic security with an amortized $\\log^3 N$ query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to $\\log^2 N$, while also avoiding the...... the secure computation. Especially we look at the communication complexity of protocols in this model, and perfectly secure protocols. We show general protocols for any finite functionality with statistical security and optimal communication complexity (but exponential amount of preprocessing). And...

  10. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult...... including recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  11. Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? Part 2. Challenge with bleomycin

    International Nuclear Information System (INIS)

    The present study concerns the possible adaptive response, induced in vivo by a continuous exposure to ionizing radiations, to a challenge treatment with the radiomimetic glycopeptide bleomycin (BLM). Lymphocytes from children contaminated as a consequence of Chernobyl accident were treated for the last 5 h of culture with 2.5 ?g/ml BLM. The induced chromosome damage was significantly lower than that found with the same treatment in lymphocytes from control children. This hyposensitivity to BLM was still present if, 1 h after the addition of the drug, inhibitors of the enzymes involved in DNA repair, such as 3-aminobenzamide (2 mM), or aphidicolin (0.4 ?M) or 3-dideoxythymidine (5 mM) were added to the cultures. The resistance to BLM in lymphocytes from contaminated children seems to be related to a mechanism upstream in respect to the activities of enzymes involved in the DNA repair and specifically linked to the action of this drug. This is consistent with the different response found when the cells were challenged with ionizing radiation in vitro, as reported in the accompanying paper (L. Padovani, L. et al. (1995) Mutation Res., this issue)

  12. RecN and RecG are required for Escherichia coli survival of Bleomycin-induced damage.

    Science.gov (United States)

    Kosa, Jessica L; Zdraveski, Zoran Z; Currier, Sophie; Marinus, Martin G; Essigmann, John M

    2004-10-01

    The sensitivity of a panel of DNA repair-defective bacterial strains to BLM was investigated. Escherichia coli recA cells were far more sensitive than were uvrA, dam-3, and mutM mutY strains, underscoring the importance of RecA to survival. Strains recBCD and recN, which lack proteins required for double strand break (DSB) repair, were highly sensitive to BLM, while recF cells were not. The requirement for DSB-specific enzymes supports the hypothesis that DSBs are the primary cause of bleomycin cytotoxicity. The acute sensitivity of recN cells was comparable to that of recA, implying a central role for the RecN protein in BLM lesion repair. The Holliday junction processing enzymes RecG and RuvC were both required for BLM survival. The recG ruvC double mutant was no more sensitive than either mutation alone, suggesting that both enzymes participate in the same pathway. Surprisingly, ruvAB cells were no more sensitive than wildtype, implying that RuvC is able to perform its role without RuvAB. This observation contrasts with current models of recombination in which RuvA, B, and C function as a single complex. The most straightforward explanation of these results is that DSB repair involves a structure that serves as a good substrate for RecG, and not RuvAB. PMID:15450413

  13. Experimental studies on the radiation-modifying effect of bleomycin in malignant and normal mouse tissue in vivo

    International Nuclear Information System (INIS)

    The interaction between bleomycin (BLM) and radiation was studied in a C3H mammary carcinoma and its surrounding normal skin. In the skin, single and fractionated doses of sequential treatment with BLM (25 mg/kg) 24 hours prior to radiation therapy did not influence the response to irradiation, whereas simultaneous treatment with BLM given 15 minutes before radiation therapy enhanced the reaction to irradiation by a factor of 1.2 or 1.4 following treatment with one fraction or five fractions, respectively. The tumor response to irradiation was not influenced by a single sequential treatment, but five daily fractions of radiation therapy following five daily dose fractions of BLM increased the radiation dose needed to control 50% of the tumors, probably because the tumors continued to grow during the BLM treatment. Simultaneous treatment enhanced the response to irradiation by a factor of 1.2 after both single-dose and fractionated therapy. Based on these data it was concluded that none of the combined treatment schedules were able to produce a better therapeutic effect than radiation therapy alone. Furthermore, mortality due to lung fibrosis in mice treated with BLM indicated the marked toxicity of the drug. This toxicity was most pronounced after fractionated treatment and when radiation therapy and BLM were given simultaneously

  14. Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina

    International Nuclear Information System (INIS)

    Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals

  15. In vivo biodistribution of 131I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models

    International Nuclear Information System (INIS)

    Bleomycins (BLMs; BLM, A2, and B2) were labeled with 131I and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM (127I-BLM). Five peaks were detected for BLM and three peaks for 127I-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zealand rabbits. The biodistribution results of 131I-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers (131I-A2 and 131I-B2) are similarly found with that of 131I-BLM. (author)

  16. Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? Part 2. Challenge with bleomycin

    International Nuclear Information System (INIS)

    The present study concerns the possible adaptive response, induced in vivo by a continuous exposure to ionizing radiations, to a challenge treatment with the radiomimetic glycopeptide bleomycin (BLM). Lymphocytes from children contaminated as a consequence of Chernobyl accident were treated for the last 5 h of culture with 2.5 ?g/ml BLM. The induced chromosome damage was significantly lower than that found with the same treatment in lymphocytes from control children. This hyposensitivity to BLM was still present if, 1 h after the addition of the drug, inhibitors of the enzymes involved in DNA repair, such as 3-aminobenzamide (2 mM), or aphidicolin (0.4 ?M) or 3-dideoxythymidine (5 mM) were added to the cultures. The resistance to BLM in lymphocytes from contaminated children seems to be related to a mechanism upstream in respect to the activities of enzymes involved in the DNA repair and specifically linked to the action of this drug. This is consistent with the different response found when the cells were challenged with ionizing radiation in vitro, as reported in another accompanying paper in this issue

  17. Symmetric cryptographic protocols

    CERN Document Server

    Ramkumar, Mahalingam

    2014-01-01

    This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

  18. Developing security protocols in ?-Spaces

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Milicia, Giuseppe

    2002-01-01

    It is of paramount importance that a security protocol effectively enforces the desired security requirements. The apparent simplicity of informal protocol descriptions hides the inherent complexity of their interactions which, often, invalidate informal correctness arguments and justify the effort of formal protocol verification. Verification, however, is usually carried out on an abstract model not at all related with a protocol’s implementation. Experience shows that security breaches introdu...

  19. Stream Control Transmission Protocol Steganography

    OpenAIRE

    Fraczek, Wojciech; Mazurczyk, Wojciech; Szczypiorski, Krzysztof

    2010-01-01

    Stream Control Transmission Protocol (SCTP) is a new transport layer protocol that is due to replace TCP (Transmission Control Protocol) and UDP (User Datagram Protocol) protocols in future IP networks. Currently, it is implemented in such operating systems like BSD, Linux, HP-UX or Sun Solaris. It is also supported in Cisco network devices operating system (Cisco IOS) and may be used in Windows. This paper describes potential steganographic methods that may be applied to SC...

  20. Security Protocol Design: A Case Study Using Key Distribution Protocols

    Directory of Open Access Journals (Sweden)

    Reiner Dojen

    2009-10-01

    Full Text Available Nowadays security protocols are a key component in providing security services for fixed and mobile networks. These services include data confidentiality, radio link encryption, message integrity, mobile subscriber authentication, electronic payment, certified e-mail, contract signing and nonrepudiation. This paper is concerned with design of effective security protocols. Security protocols are introduced and some common attacks against security protocols are discussed. The vulnerabilities that lead to theattacks are analyzed and guidelines for effective security protocol design are proposed. The presented guidelines are applied to the Andrew Secure RPC protocol and its adapted versions. It is demonstrated that compliance with the guidelines successfully avoidsfreshness and parallel session attacks.

  1. Radioisotopic generators: work protocol

    International Nuclear Information System (INIS)

    This work proposes the valuation of radioisotope generator behaviour from the users. Such as in Molybdenum 99 and Technetium 99 the present protocol treat three methodology aspects:(1) Leaching profile of 99mTc determination;(2) chemical purity controls, and radiochemical and radionuclides in Tc99 leaching;(3)99mTc leaching efficiency determination

  2. Model Additional Protocol

    International Nuclear Information System (INIS)

    Since the end of the cold war a series of events has changed the circumstances and requirements of the safeguards system. The discovery of a clandestine nuclear weapons program in Iraq, the continuing difficulty in verifying the initial report of Democratic People's Republic of Korea upon entry into force of their safeguards agreement, and the decision of the South African Government to give up its nuclear weapons program and join the Treaty on the Non-Proliferation of Nuclear Weapons have all played a role in an ambitious effort by IAEA Member States and the Secretariat to strengthen the safeguards system. A major milestone in this effort was reached in May 1997 when the IAEA Board of Governors approved a Model Protocol Additional to Safeguards Agreements. The Model Additional Protocol was negotiated over a period of less than a year by an open-ended committee of the Board involving some 70 Member States and two regional inspectorates. The IAEA is now in the process of negotiating additional protocols, State by State, and implementing them. These additional protocols will provide the IAEA with rights of access to information about all activities related to the use of nuclear material in States with comprehensive safeguards agreements and greatly expanded physical access for IAEA inspectors to confirm or verify this information. In conjunction with this, the IAEA is working on the integration of these measures with those provided for in comprehensive safeguards agreements, with a view to maximizing the effectiveness and efficiency, within available resources, the implementation of safeguards. Details concerning the Model Additional Protocol are given. (author)

  3. A family of quantum protocols

    CERN Document Server

    Devetak, I; Winter, A

    2003-01-01

    We introduce two dual, purely quantum protocols: for entanglement distillation assisted by quantum communication (``mother'' protocol) and for entanglement assisted quantum communication (``father'' protocol). We show how a large class of ``children'' protocols (including many previously known ones) can be derived from the two by direct application of teleportation or super-dense coding. Furthermore, the parent may be recovered from most of the children protocols by making them ``coherent''. We also summarize the various resource trade-offs these protocols give rise to.

  4. Security Protocol Design: A Case Study Using Key Distribution Protocols

    OpenAIRE

    Reiner Dojen; Tom Coffey; Anca Jurcut; Robert Gyorodi

    2009-01-01

    Nowadays security protocols are a key component in providing security services for fixed and mobile networks. These services include data confidentiality, radio link encryption, message integrity, mobile subscriber authentication, electronic payment, certified e-mail, contract signing and nonrepudiation. This paper is concerned with design of effective security protocols. Security protocols are introduced and some common attacks against security protocols are discussed. The vulnerabilities th...

  5. Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit

    International Nuclear Information System (INIS)

    Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (57Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity

  6. Phototherapy Modalities and Protocols

    Directory of Open Access Journals (Sweden)

    Ayten Ferahba?

    2010-12-01

    Full Text Available Over the past few years, the development of irradiation devices with new emission spectra has led to an expanded role for phototherapy in the treatment of skin diseases. This development is best illustrated by the increasing frequency with which 311 nm UVB phototherapy is used for the treatment of psoriasis and vitiligo, especially. Another example is UVA1 340-400 nm. UVA1 was first used to treat patients with atopic dermatitis, but it has been found to be efficacious in several other skin diseases. This is overview of the protocols for phototherapy with UV in the treatment of skin diseases as currently used according to recent literature review. There are, of course, other protocols in use that are effective.

  7. Mitosis Methods & Protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-06-01

    Full Text Available Mitosis Methods & Protocols Andrew D. McAinsh (Edt Humana press, Totowa, New Jersey (USA Series: Springer Protocols Methods in Molecular Biology, Volume 545, 2009 ISBN: 978-1-60327-992-5   It is quite clear from the contents of this book that the remarkably fascinating phenomenon of mitosis (that captured, and still is capturing, the attention of entire generations of scientists is still open to research. This is mainly due to our lack of knowledge of so many multifaced events of this extraordinarly complex process. The reader giving a glace through the Contents and Contributors sections is speechless: All of the first-class models (i.e., budding yeast, Caenorabditis, Drosophila, Xenopus and Human are presented..... 

  8. Blind Cognitive MAC Protocols

    OpenAIRE

    Mehanna, Omar; Sultan, Ahmed; Gamal, Hesham El

    2008-01-01

    We consider the design of cognitive Medium Access Control (MAC) protocols enabling an unlicensed (secondary) transmitter-receiver pair to communicate over the idle periods of a set of licensed channels, i.e., the primary network. The objective is to maximize data throughput while maintaining the synchronization between secondary users and avoiding interference with licensed (primary) users. No statistical information about the primary traffic is assumed to be available a-priori to the seconda...

  9. Specifying agent interaction protocols

    OpenAIRE

    Rueda, Sonia Vivian; Martínez, María Vanina; Simari, Guillermo Ricardo

    2005-01-01

    Argumentation-based negotiation is an adequate alternative for modelling situations in which agents have limited information and bounded capacities. In this research line, each agent elaborates arguments as part of its own planning process and also to justify its proposals, counter-proposals and rejections during the negotiation process. Our proposal analyzes and compares three tools for the specification of interaction protocols: finite state machines, UML, and dialogues games.

  10. Adaptive Latency Insensitive Protocols

    OpenAIRE

    Casu, Mario Roberto; Macchiarulo, Luca

    2007-01-01

    Latency-insensitive design copes with excessive delays typical of global wires in current and future IC technologies. It achieves its goal via encapsulation of synchronous logic blocks in wrappers that communicate through a latency-insensitive protocol (LIP) and pipelined interconnects. Previously proposed solutions suffer from an excessive performance penalty in terms of throughput or from a lack of generality. This article presents an adaptive LIP that outperforms previous static implementa...

  11. 111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

    International Nuclear Information System (INIS)

    Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis

  12. Protective effects of 1-[(aminopropyl)amino] ethanethiol against bleomycin and nitrogen mustard-induced mutagenicity in V79 cells

    International Nuclear Information System (INIS)

    The effects of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) on bleomycin (BLM) and nitrogen mustard- (HN2) induced cytotoxicity, DNA damage, and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster cells were examined. The antimutagenic effect of WR1065 on cis-diamminedichloroplatinum (cis-DDP) and radiation- (XRT) induced HGPRT mutations was also evaluated for comparative purposes. Cell survival and mutagenesis were assayed after a 30-min exposure of WR1065 (4 mM) to the cells and a subsequent 30-min exposure to therapy agents. WR1065 effectively protected against both effects. The induction of mutants corrected for background by BLM, HN2, cis-DDP or XRT was linear in all cases. Mutation frequencies without WR1065 were 78 x 10-6 per unit BLM; 66 x 10-7 per ?g HN2; 25 x 10-7 per ?g cis-DDP; and 87 10-7 per Gy of XRT. With WR1065 these frequencies were reduced to 37 x 10-6 per unit BLM; 40 x 10-7 per ?g HN2; 1 x 10-7 per ?g cis-DDP; and 44 x 10-7 per Gy of XRT. Mutation protection factors (MPF), a ratio of the corresponding slopes of the mutation induction curves, with and without WR1065, were BLM, MPF = 2.8; HN2, MPF = 3.4; cis-DDP, MPF = 7.1; and XRT, MPF = 5.1. WR1065 protected against the formation of single-strand-breaks (SSB) in DNA by BLM or HN2, as assayed by the method of alkaline elution. WR1065 did not induce SSB in control cells. The ability of radioprotectors to reduce the mutagenic effects of agents used in radiation and chemotherapy may be an important additional benefit for consideration in their use in the treatment of human cancer. 18 refs., 6 figs., 1 tab

  13. Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

    International Nuclear Information System (INIS)

    Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 oC. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

  14. Study on combined effects of radiation and bleomycin on carcinoma of tongue iduced by DMBA in hamster

    International Nuclear Information System (INIS)

    Carcinoma of the tongue (Mostly squamous cell carcinoma) was induced in hamsters by 9,10-dimethyl-1, 2-benzanthracene (DMBA). The amount of various kinds of free radicals, which increased due to radioactive radiation and administration of bleomycin (BLM) in tongue and liver tissues, was determined by an electron spin resonance method. The hamsters were separated into seven groups: BLM administration only (group A1), 60Co-?-ray irradiation only (A2), 60Co-?-ray irradiation 30 min after BLM administration (A3), BLM administration 30 min after 60Co-?-ray irradiation (A4), 60Co-?-ray irradiation 24 h after BLM administration (A5), BLM administration 24 h after 60Co-?-ray irradiation (A6), and the control (A7). Mean free radicals in the groups were compared, using samples fixed 5 min after treatment. The ratio of mean free radicals of carcinoma of the tongue were 2.6, 2.9, 3.7, 3.9, 3.0, 3.2, and 1 in A1, A2, A3, A4, A5, A6, and A7. The ratio of mean free radicals of the liver under the same condition were 1.5, 1.6, 3.3, 3.8, 2.2, 2.6, and 1. A combination of BLM and radioactive radiation increased the amount of free radicals in carcinoma of the tongue and in the liver. Especially BLM administration 30 min after 60Co-?-ray irradiation showed a synergistic effect. Judging from the amount of free radicals determined, the effect of radioactive irradiation increased when combined with BLM administration. BLM was most effective when it was administered 5 min after radioactive irradiation. (Tsunoda, M.)

  15. Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast

    International Nuclear Information System (INIS)

    The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions

  16. Communication protocols; Protocolos de comunicacao

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Augusto Passos [SMAR, Rio de Janeiro, RJ (Brazil)

    1998-07-01

    This paper analyses the various digital communication protocols connecting field and control room. The document describes the main characteristics of some protocols and their applicability to the automation of various industrial processes connected to the petroleum industry.

  17. Satellite Communications Using Commercial Protocols

    Science.gov (United States)

    Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

    2000-01-01

    NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

  18. Composite Protocols and Networking Services

    OpenAIRE

    Minden, Gary

    2005-01-01

    Active Networking is concerned with the rapid definition and deployment of innovative, but reliable and robust, networking services. Towards this end we have developed a composite protocol and networking services architecture that encourages re-use of protocol functions, is well defined, and facilitates automatic checking of interfaces and protocol component properties. The architecture has been used to implement common Internet protocols and services. We will report on this work at the works...

  19. Synchronizing internet protocol security (SIPSec)

    CERN Document Server

    Shoniregun, Charles A

    2007-01-01

    Synchronizing Internet Protocol Security (SIPSec) focuses on the combination of theoretical investigation and practical implementation, which provides an in-depth understanding of the Internet Protocol Security (IPSec) framework. The standard internet protocol is completely unprotected, allowing hosts to inspect or modify data in transit. This volume identifies the security problems facing internet communication protocols along with the risks associated with internet connections. It also includes an investigative case study regarding the vulnerabilities that impair IPSec and proposes a SIPSec

  20. Validation of survivability validation protocols

    Energy Technology Data Exchange (ETDEWEB)

    Stringer, T.A. [Kaman Sciences Corp., Colorado Springs, CO (United States)

    1993-05-01

    Issues associated with the validation of survivability protocols are discussed. Both empirical and analytical approaches to protocol validation are included. The use of hybrid simulations (hardware-in-the-loop, scene generators, software generators, man-in-the-loop, etc.) for the validation of survivability protocols is discussed.

  1. Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis

    Science.gov (United States)

    Park, Ah-Mee; Kanai, Kyosuke; Itoh, Tatsuki; Sato, Takao; Tsukui, Tatsuya; Inagaki, Yutaka; Selman, Moises; Matsushima, Kouji; Yoshie, Osamu

    2016-01-01

    Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor ?1 (TGF-?1), we observed upregulation of HSP27 along with that of ?-smooth muscle actin (?-SMA), a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN) and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-?1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with ?-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells), E-cadherin (a marker of epithelial cells) or F4/80 (a marker of macrophages). A similar co-localization of HSP27 and ?-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin-induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases. PMID:26859835

  2. Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Park, Ah-Mee; Kanai, Kyosuke; Itoh, Tatsuki; Sato, Takao; Tsukui, Tatsuya; Inagaki, Yutaka; Selman, Moises; Matsushima, Kouji; Yoshie, Osamu

    2016-01-01

    Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor ?1 (TGF-?1), we observed upregulation of HSP27 along with that of ?-smooth muscle actin (?-SMA), a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN) and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-?1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with ?-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells), E-cadherin (a marker of epithelial cells) or F4/80 (a marker of macrophages). A similar co-localization of HSP27 and ?-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin-induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases. PMID:26859835

  3. Analysis of the dose-response relationships of chromosomal aberrations after irradiation and bleomycin exposure of different human lymphocyte fractions in vitro

    International Nuclear Information System (INIS)

    Cytogenetic analyses could be carried out on whole blood and pure T-cell cultures and also on cells of the 'buffy-coat'. In pure B-cell cultures even after 96 hours no mitogenic stimulation could be achieved. Parameters of radiosensitivity and bleomycin sensitivity were dicentric chromosomes, for which the dose-response relationships were calculated. Chromosomal investigations on the 'buffy-coat' cells did not provide indications referring to a varying radiosensitivity compared to whole blood cultures. In pure T-cell cultures T-lymphocytes, which had been separated after whole blood irradiation exposure, showed lower aberration rates than lymphocytes, which had been cultured after whole blood irradiation without previous separation. In the case of bleomycin exposure the treatment of previously separated leucocytes and T-lymphocytes respectively, led to lower aberration rates than the treatment before separation. Therefore it is apparently not necessary for a cytogenetic dosimetry or mutagenicity to depart from the whole blood culture method. (orig./MG)

  4. A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer

    International Nuclear Information System (INIS)

    Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor

  5. Deletions at short direct repeats and base substitutions are characteristic mutations for bleomycin-induced double- and single-strand breaks, respectively, in a human shuttle vector system

    Science.gov (United States)

    Dar, M. E.; Jorgensen, T. J.

    1995-01-01

    Using the radiomimetic drug, bleomycin, we have determined the mutagenic potential of DNA strand breaks in the shuttle vector pZ189 in human fibroblasts. The bleomycin treatment conditions used produce strand breaks with 3'-phosphoglycolate termini as > 95% of the detectable dose-dependent lesions. Breaks with this end group represent 50% of the strand break damage produced by ionizing radiation. We report that such strand breaks are mutagenic lesions. The type of mutation produced is largely determined by the type of strand break on the plasmid (i.e. single versus double). Mutagenesis studies with purified DNA forms showed that nicked plasmids (i.e. those containing single-strand breaks) predominantly produce base substitutions, the majority of which are multiples, which presumably originate from error-prone polymerase activity at strand break sites. In contrast, repair of linear plasmids (i.e. those containing double-strand breaks) mainly results in deletions at short direct repeat sequences, indicating the involvement of illegitimate recombination. The data characterize the nature of mutations produced by single- and double-strand breaks in human cells, and suggests that deletions at direct repeats may be a 'signature' mutation for the processing of DNA double-strand breaks.

  6. Impersonation Attack on EKE Protocol

    Directory of Open Access Journals (Sweden)

    Shirisha Tallapally

    2010-04-01

    Full Text Available The key exchange protocol is one of the most elegant ways of establishing secure communication between pair of users by using a session key. The passwords are of low entropy, hence the protocol should resist all types of password guessing attacks. Recently ECC-3PEKE protocol has been proposed by Chang and Chang. They claimed the protocol is secure, efficient and practical. Unless their claims Yoon and Yoo presented an Undetectable online password guessing attack on the above protocol. A key recovery attack was proved on ECC-3PEKE protocol using the Undetectable online password guessing attack proposed by Yoon and Yon. In the present paper an Impersonation attack on ECC-3PEKE protocol using the Undetectable online password guessing attack proposed by Yoon and Yon is demonstrated

  7. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Division des Ressources Humaines; Human Resources Division; Tel. 74683-79494

    2000-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

  8. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Division du Personnel

    1999-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

  9. Sincalide - the final protocol

    International Nuclear Information System (INIS)

    Full text: HIDA biliary studies examine the gallbladder (GB) to give a percentage ejection fraction (EF). Porcine CCK was an accepted agent for stimulating the GB prior to being withdrawn in the UK from 1998. Sincalide (a synthetic CCK) was the suggested replacement. We have tried many administration regimes in an attempt to get results comparable with our established CCK protocols. Dose concentration and length of infusion times have been studied. Initially a dose of 10 ngm/kg/min given over 2 minutes (manufacturer's recommended dose) was used. This gave falsely low ejection fractions. The dose was reduced to 3 ngm/kg/min over 3 minutes as it was felt the higher dose may be causing constriction of the sphincter of Oddi. This gave a slight improvement with 22 % of patients having normal EF (>35 %). The length of infusion was extended to 15 minutes and the dose concentration reduced again to 0.6 ngm/kg/min. 62 % of patients had a normal EF. However, on many of the curves the gallbladder was still contracting on completion of the 15 minute infusion and began to refill immediately after stopping Sincalide. A further change of protocol was indicated. The infusion time was extended to 30 minutes and the dose concentration per minute kept the same. Imaging began at 30 minutes post HIDA injection and continued for a total of 50 minutes. Sincalide infusion began at 35 minutes if a GB was visualized. This protocol has been performed on 17 patients. 53 % of these had a normal result (comparable with a normal rate of 40 % previously established with CCK) with a mean EF of 60 %. The mean EF of patients with abnormal studies was 15 %. Curves showed a plateau by 30 minutes in 94 % of patients indicating that gallbladder contraction was complete. No normal range is available so results were compared with ultrasound (US). All patients who had an abnormal US scan also had abnormal HIDA results. Three patients had a normal US scan and abnormal HIDA study. These are currently undergoing further investigations. We conclude that 0.6 ngm/kg/minute Sincalide infused over 30 minutes is a satisfactory replacement for CCK and is the protocol we recommend for HIDA studies. (author)

  10. Address Resolution Protocol Optimization

    Directory of Open Access Journals (Sweden)

    Nor Adnan Yahaya

    2009-09-01

    Full Text Available This paper proposes an improved Address Resolution Protocol (ARP for Ethernet-based networks. Inthe proposed alternative method, the ARP request packets are not broadcasted but instead unicastedto an ARP server which will have all the mappings of all the hosts connected to the network.This significantly reduces ARP signaling and processing overhead. The ARP server obtains the mappingsthrough a novel passive method that does not introduce additional overhead in the network. Furthermore,the use of the ARP server makes it much easier to secure the network against certain attacks like ARPpoisoning.

  11. Security and SCADA protocols

    International Nuclear Information System (INIS)

    Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

  12. Protocol Architecture Model Report

    Science.gov (United States)

    Dhas, Chris

    2000-01-01

    NASA's Glenn Research Center (GRC) defines and develops advanced technology for high priority national needs in communications technologies for application to aeronautics and space. GRC tasked Computer Networks and Software Inc. (CNS) to examine protocols and architectures for an In-Space Internet Node. CNS has developed a methodology for network reference models to support NASA's four mission areas: Earth Science, Space Science, Human Exploration and Development of Space (REDS), Aerospace Technology. This report applies the methodology to three space Internet-based communications scenarios for future missions. CNS has conceptualized, designed, and developed space Internet-based communications protocols and architectures for each of the independent scenarios. The scenarios are: Scenario 1: Unicast communications between a Low-Earth-Orbit (LEO) spacecraft inspace Internet node and a ground terminal Internet node via a Tracking and Data Rela Satellite (TDRS) transfer; Scenario 2: Unicast communications between a Low-Earth-Orbit (LEO) International Space Station and a ground terminal Internet node via a TDRS transfer; Scenario 3: Multicast Communications (or "Multicasting"), 1 Spacecraft to N Ground Receivers, N Ground Transmitters to 1 Ground Receiver via a Spacecraft.

  13. Secretoglobin 3A2 Exhibits Anti-Fibrotic Activity in Bleomycin-Induced Pulmonary Fibrosis Model Mice

    Science.gov (United States)

    Cai, Yan; Kimura, Shioko

    2015-01-01

    Objective Secretoglobin (SCGB) 3A2 is a novel lung-enriched cytokine, previously shown to exhibit anti-inflammatory, growth factor, and anti-fibrotic activities. The latter activity was demonstrated using exogenously-administered recombinant SCGB3A2 in the bleomycin (BLM)-induced pulmonary fibrosis model. Whether SCGB3A2 exhibits anti-fibrotic activity in vivo is not known. Methods Mice null for the Scgb3a2 gene were subjected to the BLM-induced pulmonary fibrosis model, and the severity of pulmonary fibrosis determined using histological and biochemical methods. Results BLM treatment caused weight loss of both Scgb3a2-null and wild-type mice, however, the loss was far more pronounced in BLM-treated Scgb3a2-null than wild-type mice, and the weight of day 21 of BLM-treated Scgb3a2-null mice was about half of that of BLM-treated wild-type mice. Hematoxylin & Eosin, Masson Trichrome, and Sirius Red staining of lung sections, Ashcroft fibrosis scores, hydroxyproline contents, and the levels of mRNAs encoding various collagens demonstrated that BLM-treated Scgb3a2-null mouse lungs had more severe fibrosis than those of wild-type mouse lungs. Total and differential inflammatory cell numbers in bronchoalveolar lavage fluids, and levels of lung mRNAs including those encoding Th2 cytokines such as IL-4 and profibrotic cytokines such as TGF? were higher in BLM-treated Scgb3a2-null mouse lungs as compared to those of wild-type mouse lungs. In contrast, mRNAs encoding surfactant proteins A, B, C, and D, and SCGB1A1 did not differ between BLM-treated Scgb3a2-null and wild-type mouse lungs. Conclusion The role of SCGB3A2 in fibrosis was revisited using Scgb3a2-null mice and littermate controls in the BLM-induced pulmonary fibrosis model. The pulmonary fibrosis in the Scgb3a2-null mice was more severe than the wild-type controls, thus establishing that SCGB3A2 has anti-fibrotic activity in vivo. Importantly, surfactant proteins and SCGB1A1 appear not to be involved in the susceptibility of Scgb3a2-null mice to BLM-induced pulmonary fibrosis. PMID:26559674

  14. Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

    International Nuclear Information System (INIS)

    Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated with BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent EMT in BLM-induced skin fibrosis. • NAC attenuated EMT induction in the process of BLM-induced skin fibrosis. • NAC didn't significantly inhibit TGF-β expression in BLM-induced skin fibrosis

  15. Licklider Transmission Protocol Implementation

    Science.gov (United States)

    Burleigh, Scott C.; Krupiarz, Chris

    2011-01-01

    This software is an implementation of the Licklider Transmission Protocol (LTP), a communications protocol intended to support the Bundle Protocol in Delay-Tolerant Network (DTN) operations. LTP is designed to provide retransmission-based reliability over links characterized by extremely long message round-trip times and/or frequent interruptions in connectivity. Communication in interplanetary space is the most prominent example of this sort of environment, and LTP is principally aimed at supporting long-haul reliable transmission over deep-space RF links. Like any reliable transport service employing ARQ (Automatic Repeat re-Quests), LTP is stateful. In order to assure the reception of a block of data it has sent, LTP must retain for possible retransmission all portions of that block which might not have been received yet. In order to do so, it must keep track of which portions of the block are known to have been received so far, and which are not, together with any additional information needed for purposes of retransmitting part, or all, of the block. Long round-trip times mean substantial delay between the transmission of a block of data and the reception of an acknowledgement from the block s destination, signaling arrival of the block. If LTP postponed transmission of additional blocks of data until it received acknowledgement of the arrival of all prior blocks, valuable opportunities to use what little deep space transmission bandwidth is available would be forever lost. For this reason, LTP is based in part on a notion of massive state retention. Any number of requested transmission conversations (sessions) may be concurrently in flight at various displacements along the link between two LTP engines, and the LTP engines must necessarily retain transmission status and retransmission resources for all of them. Moreover, if any of the data of a given block are lost en route, it will be necessary to retain the state of that transmission during an additional round trip while the lost data are retransmitted; even multiple retransmission cycles may be necessary. LTP's possible multiplicity of sessions per association makes it necessary for each segment of application data to include an additional demultiplexing token: a session ID that uniquely identifies the session in which the segment was issued and, implicitly, the block of data being conveyed by this session. This software comprises a prototype implementation developed by Johns Hopkins University APL in cooperation with JPL, together with adaptations that improve the robustness, correctness, and operability of that implementation.

  16. Formal Verification of Quantum Protocols

    CERN Document Server

    Nagarajan, R; Nagarajan, Rajagopal; Gay, Simon

    2002-01-01

    We propose to analyse quantum protocols by applying formal verification techniques developed in classical computing for the analysis of communicating concurrent systems. One area of successful application of these techniques is that of classical security protocols, exemplified by Lowe's discovery and fix of a flaw in the well-known Needham-Schroeder authentication protocol. Secure quantum cryptographic protocols are also notoriously difficult to design. Quantum cryptography is therefore an interesting target for formal verification, and provides our first example; we expect the approach to be transferable to more general quantum information processing scenarios. The example we use is the quantum key distribution protocol proposed by Bennett and Brassard, commonly referred to as BB84. We present a model of the protocol in the process calculus CCS and the results of some initial analyses using the Concurrency Workbench of the New Century (CWB-NC).

  17. Stream Control Transmission Protocol Steganography

    CERN Document Server

    Fraczek, Wojciech; Szczypiorski, Krzysztof

    2010-01-01

    Stream Control Transmission Protocol (SCTP) is a new transport layer protocol that is due to replace TCP (Transmission Control Protocol) and UDP (User Datagram Protocol) protocols in future IP networks. Currently, it is implemented in such operating systems like BSD, Linux, HP-UX or Sun Solaris. It is also supported in Cisco network devices operating system (Cisco IOS) and may be used in Windows. This paper describes potential steganographic methods that may be applied to SCTP and may pose a threat to network security. Proposed methods utilize new, characteristic SCTP features like multi-homing and multistreaming. Identified new threats and suggested countermeasures may be used as a supplement to RFC 5062, which describes security attacks in SCTP protocol and can induce further standard modifications.

  18. Protocols for Scholarly Communication

    CERN Document Server

    Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

    2007-01-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...

  19. Mobile Multilayer IPsec protocol

    Directory of Open Access Journals (Sweden)

    T.Gayathri

    2009-08-01

    Full Text Available A mobile user moves around and switches between wireless cells, subnets and domains, it needs to maintain the session continuity. At the same time security of signaling and transport media should not be compromised. A multi-layer security framework involving user authentication, packet based encryption and access control mechanism can provide the desired level of security to the mobile users. Supporting streaming traffic in a mobile wireless Internet is faced with several challenges due to continuous handoff experienced by a mobile user. These challenges include dynamic binding, location management, quality of service and end-to-end security for signaling and transport. Mobile users will use heterogeneous radio access networking technologies. Mobile multilayer IPsec protocol (MML IPSec extends ML-IPSec to deal with mobility and make it suitable for wireless networks. MML-IPSec is integration of ML-IPSec and mobile IP.

  20. Impersonation with the Echo Protocol

    CERN Document Server

    Chung, Y; Chung, Yoo; Lee, Dongman

    2005-01-01

    The Echo protocol tries to do secure location verification using physical limits imposed by the speeds of light and sound. While the protocol is able to guarantee that a certain object is within a certain region, it cannot ensure the authenticity of further messages from the object without using cryptography. This paper describes an impersonation attack against the protocol based on this weakness. It also describes a couple of approaches which can be used to defend against the attack.

  1. Meiotic and Mitotic Phenotypes Conferred by the blm1-1 Mutation in Saccharomyces cerevisiae and MSH4 Suppression of the Bleomycin Hypersusceptibility

    Directory of Open Access Journals (Sweden)

    Carol Wood Moore

    2003-01-01

    Full Text Available Abstract: Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores produced during meiosis by homozygous normal BLM1/BLM1, heterozygous BLM1/blm1-1, and homozygous mutant blm1-1/blm1-1 diploid strains was studied and compared. Approximately 88% of the tetrads derived from homozygous blm1-1/blm1-1 mutant diploid cells only produced one or two viable spores. In contrast, just one tetrad among all BLM1/BLM1 and BLM1/blm1-1 tetrads only produced one or two viable spores. Rather, 94% of BLM1/BLM1 tetrads and 100% of BLM1/blm1-1 tetrads produced asci with four or three viable spores. Thus, at least one copy of the BLM1 gene is essential for the production of four viable spores after meiosis. During mitotic growth, mutant blm1-1 strains grew at reduced rates and produced cells with high frequencies of unusual morphologies compared to wild-type strains. These results indicated BLM1 is also essential for normal mitotic growth. We also investigated the suppression by the MSH4 gene, a meiosis-specific MutS homolog, of the bleomycin hypersusceptibility of blm1-1 mutant cells, and the relationship of MSH4 to BLM1. We screened a genomic library, and isolated the MSH4 gene on the basis of its ability to suppress lethal effects of bleomycin in blm1-1 cells. However, genetic mapping studies indicated that BLM1 and MSH4 are not the same gene. The possibility that chromosomal nondisjunction could be the basis for the inability of blm1-1/blm1-1 mutant cells to produce four viable spores after meiosis is discussed.

  2. Protocol Composition Frameworks, A Header Driven Model

    OpenAIRE

    Bünzli, Daniel C.; Mena, Sergio; Nestmann, Uwe

    2005-01-01

    Protocol composition frameworks provide off-the-shelf composable protocols to simplify the development of custom protocol stacks. All recent protocol frameworks use a general-purpose event-driven model to manage the interactions between protocols. In complex compositions, where protocols offer their service to more than one other protocol, the one-to-many interaction scheme of the event-driven model introduces composition problems by mixing up the targets to which data (list of headers) shoul...

  3. Message Broadcasting Protocols in VANET

    OpenAIRE

    Ghassan Samara; Wafaa A.H. Ali Alsalihy

    2012-01-01

    Vehicular Ad hoc Networks (VANET) is one of the most challenging research areas in the field of mobile ad hoc networks. In this research, we propose a comparison between the emergency message broadcasting protocols and identifying the Pros and cons of each protocol.

  4. Message Broadcasting Protocols in VANET

    Directory of Open Access Journals (Sweden)

    Ghassan Samara

    2012-01-01

    Full Text Available Vehicular Ad hoc Networks (VANET is one of the most challenging research areas in the field of mobile ad hoc networks. In this research, we propose a comparison between the emergency message broadcasting protocols and identifying the Pros and cons of each protocol.

  5. A Streaming Protocol for Memcached

    Directory of Open Access Journals (Sweden)

    W. Li

    2012-01-01

    Full Text Available Memcached is a general-purpose distributed memory caching system that was originally developed by Danga Interactive for Live Journal but is now used by many other sites and It is thought to be one of the most effective solutions to speed up dynamic database-driven websites by caching data and objects in RAM to reduce the number of times that an external data source must be read. Memcached system uses a client-server architecture, it provides its standard memcached protocol to support any types of programming languages. The memcached protocol is simple and very efficient, while it doesn’t support big data objects very well. In this study, the memcached systems were firstly illustrated and then a detailed introduction was provided for the memcached protocol and then the issues of the stock protocol were specified. After that, a new streaming protocol was illustrated which was well designed for big data objects and could be easily integrated into original memcached protocols. Finally, some experiments were done to evaluate the new streaming protocol and finally the new protocol was proved to be very efficient for big data objects storage and it explored new application fields for memcached.

  6. Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide

    International Nuclear Information System (INIS)

    The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% (±9%) and the overall 3-year survival 78% (±9%). (author)

  7. Effect of vincristine or bleomycin on radiation-induced cell killing of mice spermatogonial stem cells: The importance of sequence and time interval

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, P.V.; Sorensen, D. (Danish Cancer Society, Aarhus (Denmark))

    1991-02-01

    The effect of single doses of vincristine (VCR) or bleomycin (BLM) on mice spermatogonia was investigated, and the influence of either of these drugs on the radiation response of murine spermatogonial stem cells was examined. When assessed by flow cytometry, VCR (1.0 mg/kg) or BLM (100 mg/kg) reduced the survival in the differentiated spermatogonia to 4% and 37% of controls, respectively (p less than 0.05). VCR reduced the stem cells to 79% of controls (p less than 0.05), whereas BLM had no apparent effect on the stem cells (p greater than 0.05). Drugs were administered intraperitoneally up to 28 days before or after local irradiation with 9 Gy. VCR produced significant enhancement of radiation-induced damage to spermatogonial stem cells, which was most prominent when administered 6 or 12 hr after irradiation. BLM administered before irradiation or 1 hr after radiotherapy produced significant enhancement.

  8. Effect of vincristine or bleomycin on radiation-induced cell killing of mice spermatogonial stem cells: The importance of sequence and time interval

    International Nuclear Information System (INIS)

    The effect of single doses of vincristine (VCR) or bleomycin (BLM) on mice spermatogonia was investigated, and the influence of either of these drugs on the radiation response of murine spermatogonial stem cells was examined. When assessed by flow cytometry, VCR (1.0 mg/kg) or BLM (100 mg/kg) reduced the survival in the differentiated spermatogonia to 4% and 37% of controls, respectively (p less than 0.05). VCR reduced the stem cells to 79% of controls (p less than 0.05), whereas BLM had no apparent effect on the stem cells (p greater than 0.05). Drugs were administered intraperitoneally up to 28 days before or after local irradiation with 9 Gy. VCR produced significant enhancement of radiation-induced damage to spermatogonial stem cells, which was most prominent when administered 6 or 12 hr after irradiation. BLM administered before irradiation or 1 hr after radiotherapy produced significant enhancement

  9. Single strand breaks in DNA of Ehrlich ascites tumour cells irradiated by thermal neutrons, and effect of bleomycin on the repair kinetics

    International Nuclear Information System (INIS)

    The induction of single strand break (SSB) and the effect of bleomycin (BLM) on the repair kinetics in Ehrlich ascites tumour (EAT) cells after thermal neutron irradiation were examined using alkaline sucrose gradient method, and also a comparison was made between those induced by neutron irradiation and those by ?-irradiation. Thermal neutron produced 5.6 x 10-10 SSB per cell per fluence and 60Co-?-ray, 9.0 x 102 SSB per cell per Gy. Both the radiations exhibited linear dose effect relationships over the dose range examined. The concentration of BLM required to inhibit the repair of SSB after thermal neutron irradiation was less than that after ?-ray by a factor of about 100. (author)

  10. An Improved Resource Reservation Protocol

    Directory of Open Access Journals (Sweden)

    Desire Oulai

    2007-01-01

    Full Text Available The classical resource reservation protocol (RSVP is a ?ow-based signaling protocol used for reserving resources in the network for a given session. RSVP maintains state information for each reservation at every router along the path. Even though this protocol is very popular, he has some weaknesses. Indeed, RSVP does not include a bidirectional reservation process and it requires refresh messages to maintain the soft states in the routers for each session. In this paper, we propose a sender-oriented version of RSVP that can reserve the resources in both directions with only one message, thus reducing the delay for establishing the reservations. We also suggest a refreshment mechanism without any refresh message which could be applied to any soft states protocol. Simulation results show that the proposed protocol is approximately twice faster than RSVPv2 for establishing bidirectional reservations with almost no control overhead during the session.

  11. Internet Protocol Television (IPTV

    Directory of Open Access Journals (Sweden)

    Lokesh Mittal

    2012-09-01

    Full Text Available IPTV is one of the mostly used technology of Internet and IP application. IPTV is a service for the delivery of broadcast TV, movies on demand and other interactive multimedia services over a secure, end-to-end operator managed broadband IP data network with desired QoS to the public with a broadband Internet connection. IPTV system may also include Internet services such as Web access and VoIP where it may be called Triple Play and is typically supplied by a broadband operator using the same infrastructure. IPTV is not the Internet Video that simply allows users to watch videos, like movie previews and web-cams, over the Internet in a best effort fashion. IPTV technology offers revenue-generating opportunities for the telecom and cable service providers. For traditional telephone service providers, Triple Play is delivered using a combination of optical fiber and Digital Subscriber Line (DSL technologies to its residential base. IPTV is a system where a digital television service is delivered by using Internet Protocol over a network infrastructure, which may include delivery by a broadband connection. A general definition of IPTV is television content that, instead of being delivered through traditional broadcast and cable formats, is received by the viewer through the technologies used for computer networks. In this paper I am trying to discuss this topic as my knowledge, including what is IPTV, how it works, its advantages and its applications

  12. Protocols for Scholarly Communication

    Science.gov (United States)

    Pepe, A.; Yeomans, J.

    2007-10-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should guide authors naturally towards OA publication, and CERN wants to help reach a full open access publishing environment for the particle physics community and related sciences in the next few years.

  13. Fluorofenidone attenuates bleomycin-induced pulmonary fibrosis by inhibiting eukaryotic translation initiation factor 3a (eIF3a) in rats.

    Science.gov (United States)

    Wu, Yue-Han; Li, Xian-Wei; Li, Wen-Qun; Li, Xiao-Hui; Li, Yuan-Jian; Hu, Gao-Yun; Liu, Zhao-Qian; Li, Dai

    2016-02-15

    Fluorofenidone is a novel derivative of l-mimosine. It has remarkable anti-fibrotic properties. In this study, we established that fluorofenidone ameliorates pulmonary fibrosis (PF) both in vivo and in vitro by specifically inhibiting the expression of eukaryotic translation initiation factor 3a (eIF3a). eIF3a plays an important role in the development and progression of PF. An animal model of PF was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Rats were orally administered with fluorofenidone (250, 500mg/kg/d·[i.g.]) and pirfenidone (500mg/kg/d·[i.g.]) for 28 days. Primary pulmonary fibroblasts were cultured to determine the effect of fluorofenidone on TGF-?1-induced (5ng/ml) proliferation and differentiation of fibroblasts. The expression/level of eIF3a, TGF-?1, ?-SMA, collagen I, and collagen III were analyzed by ELISA, real-time PCR, and western blot. The cell proliferation rate was determined by MTS assay. The results indicate that fluorofenidone significantly improves the pathological changes in lung tissues and reduces the deposition of collagen by inhibiting eIF3a in rats with bleomycin-induced PF. Moreover, in a culture of pulmonary fibroblasts, fluorofenidone decreased the up-regulation of TGF-?1-induced eIF3a by inhibiting the proliferation of cells and reducing the expression of ?-SMA, collagen I, and collagen III. These findings suggest that eIF3a is a new and special target of fluorofenidone, which could be potentially used in the development of a drug that treats PF. PMID:26821114

  14. Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    Lee, Changkyu; Seo, Jisoo; Hwang, Ha Shin; Thao, Le Quang; Lee, Seunghyun; Lee, Eun Seong; Lee, Eun Hee; Choi, Han-Gon; Youn, Yu Seok

    2016-03-01

    Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA-NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+13.6mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs (-28.3mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180?g/mouse) twice a week produced marked anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300?g/mouse) on the basis of hematoxylin/eosin and Masson's trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects. PMID:26898446

  15. Preventive effects of Citrus reticulata essential oil on bleomycin-induced pulmonary fibrosis in rats and the mechanism

    Directory of Open Access Journals (Sweden)

    Xian-mei Zhou

    2012-02-01

    Full Text Available OBJECTIVE: To investigate the effects of essential oil of Citrus reticulata (EOCR on proliferation of human embryonic lung fibroblasts (HELFs, and to explore its protective effects on bleomycin (BLM-induced lung fibrosis in rats.METHODS: Routinely cultured HELFs during the logarithmic phase of growth were divided into control and treated groups, and applied for evaluation of inhibitory activity using methylthiazol tetrazolium (MTT assay. A rat model of BLM-induced pulmonary fibrosis was used for the evaluation of antifibrotic effect of EOCR. Forty-two Sprague-Dawley rats were randomly divided into normal group, model group, prednisone group and different doses of EOCR groups. BLM was intratracheally instilled into all the rats except those in the normal group, and EOCR was orally given to BLM-treated rats at doses of 25, 50, 100 and 200 mg/kg once per day for four weeks. The rats in the normal group were intratracheally administered the same volume of saline. On the 28th day, rats were sacrificed under anesthesia, and the serum and lung tissues were collected. Superoxide dismutase (SOD activities and malondialdehyde (MDA contents in serum and lung tissues were analyzed with corresponding kits; type Ⅰ collagen (Col Ⅰ content in lung tissues was evaluated with enzyme-linked immunosorbent assay; pulmonary fibrosis was assessed by lung histology; protein and mRNA expressions of connective tissue growth factor (CTGF in lung tissues were measured with immunohistochemical and in situ hybridization semiquantitative image analyses, respectively.RESULTS: The EOCR at different concentrations displayed inhibitory activity on proliferation of HELFs. In in vivo experiment, the weight gain of the rats in groups treated with EOCR at doses of 50, 100 and 200 mg/kg per day was significantly higher than those in the model group at the 7th, 14th, 21st and 28th day (P<0.05 or P<0.01. The scores of alveolitis and pulmonary fibrosis in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were significantly lower than those in the model group (P<0.01; the SOD levels in serum and pulmonary tissues of the EOCR (50, 100 and 200 mg/kg groups were markedly increased compared with the model group (P<0.01 , while the MDA levels in both serum and pulmonary tissues were markedly reduced (P<0.05; the Col Ⅰ level in pulmonary tissues of the EOCR (100 and 200 mg/kg per day groups were markedly lower than that of the model group (P<0.01; the protein and mRNA expressions of CTGF in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were down-regulated compared with the model group (P<0.01.CONCLUSION: The results indicate that EOCR has preventive effects on BLM-induced pulmonary fibrosis in rats. The mechanism may be via adjusting the unbalance of oxidation and antioxidation, down-regulating CTGF protein and mRNA expressions, and reducing collagen deposition and fibrosis.

  16. Data Link Layer Protocol Simulator User Guide

    OpenAIRE

    Nataf, Emmanuel

    2008-01-01

    The data link layer protocol simulator allows to write protocol and to see them in execution. This guide describes a step by step approach from simple information communication without any control to windows protocols. A protocol oriented java API is defined to write protocol algorithms.

  17. Symbolic Analysis of Cryptographic Protocols

    DEFF Research Database (Denmark)

    Dahl, Morten

    Compos- able framework by Canetti for specifying and analysing protocols, and show that our model is sound with respect to its standard computational interpretation. Our model supports powerful primitives such as homomorphic encryption and non-interactive zero-knowledge proofs, which we show may be used......We present our work on using abstract models for formally analysing cryptographic protocols: First, we present an ecient method for verifying trace-based authenticity properties of protocols using nonces, symmetric encryption, and asymmetric encryption. The method is based on a type system of...

  18. A Framework for the Development of Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Milicia, Giuseppe

    We present the ?-Spaces framework, a tool designed to support every step of a security protocol’s life cycle. Its Integrated Development Environment (IDE) eases the task of protocol design, debugging and simulation....

  19. Automatic Sequencing for Experimental Protocols

    Science.gov (United States)

    Hsieh, Paul F.; Stern, Ivan

    We present a paradigm and implementation of a system for the specification of the experimental protocols to be used for the calibration of AXAF mirrors. For the mirror calibration, several thousand individual measurements need to be defined. For each measurement, over one hundred parameters need to be tabulated for the facility test conductor and several hundred instrument parameters need to be set. We provide a high level protocol language which allows for a tractable representation of the measurement protocol. We present a procedure dispatcher which automatically sequences a protocol more accurately and more rapidly than is possible by an unassisted human operator. We also present back-end tools to generate printed procedure manuals and database tables required for review by the AXAF program. This paradigm has been tested and refined in the calibration of detectors to be used in mirror calibration.

  20. Assessment of Established Survey Protocols

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — A form and instructions for quickly and briefly assessing a previously prior to 2013 reviewed or approved survey protocol for use as a National or Regional survey...

  1. Analysis of Two Types Deniable Authentication Protocols

    OpenAIRE

    Haibo Tian; Xiaofeng Chen; Yong Ding

    2009-01-01

    Deniability enables protocol participants to deny their involvement after they have taken part in a particular protocol run. In this paper, we present the security analysis of a class of interactive deniable authentication protocols and a noninteractive one. For interactive protocols, we focus on a serial of pairings based protocols proposed by Chou et al and repaired by Lim et al. We point out that their repaired protocols are still not secure under Key Compromise Impersonation (KCI) attack ...

  2. Multilevel Security Protocol using RFID

    OpenAIRE

    Syed Faiazuddin; S.Venkat Rao; S.C.V. Ramana Rao; M.V.Sainatha Rao; P. Sathish Kumar

    2011-01-01

    Though RFID provides automatic object identification, yet it is vulnerable to various security threats that put consumer and organization privacy at stake. In this work, we have considered some existing security protocols of RFID system and analyzed the possible security threats at each level. We have modified those parts of protocol that have security loopholes and thus finally proposed a modified four-level security model that has the potential to provide fortification against security threats

  3. The Groningen protocol: another perspective

    OpenAIRE

    Jotkowitz, A B; Glick, S.

    2006-01-01

    The Groningen protocol allows for the euthanasia of severely ill newborns with a hopeless prognosis and unbearable suffering. We understand the impetus for such a protocol but have moral and ethical concerns with it. Advocates for euthanasia in adults have relied on the concept of human autonomy, which is lacking in the case of infants. In addition, biases can potentially influence the decision making of both parents and physicians. It is also very difficult to weigh the element of quality of...

  4. Secure E-payment Protocol

    Directory of Open Access Journals (Sweden)

    Sattar J Aboud

    2009-11-01

    Full Text Available The vast spreading of information in the last decade has led to greatdevelopment in e-commerce. For instance, e-trade and e-bank are two mainInternet services that implement e-transaction from anyplace in the world. Thishelps merchant and bank to ease the financial transaction process and to giveuser friendly services at any time. However, the cost of workers andcommunications falls down considerably while the cost of trusted authority andprotecting information is increased. E-payment is now one of the most centralresearch areas in e-commerce, mainly regarding online and offline paymentscenarios. In this paper, we will discuss an important e-payment protocol namelyKim and Lee scheme examine its advantages and delimitations, whichencourages the author to develop more efficient scheme that keeping allcharacteristics intact without concession of the security robustness of theprotocol. The suggest protocol employs the idea of public key encryption schemeusing the thought of hash chain. We will compare the proposed protocol with Kimand Lee protocol and demonstrate that the proposed protocol offers moresecurity and efficiency, which makes the protocol workable for real worldservices.

  5. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x107 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x107 spleen cells to 1x106 myeloma cells (ratio 10:1). Centrifuge the mixture of cells at 300g for 10 minutes. While the cells are centrifuging, set aside 30 ml of serum-free RPMI 1640 in another 50-ml tube. Prepare the 50% PEG and place the timer in the hood. 6. Remove all the supernatant from the cell pellet. Overlay the pellet of cells with 0.5 ml of 50% PEG with a Pasteur pipet during 1 minute. Then add 5 ml of serum-free RPMI 1640 during 3 minutes. At the end of 3 minutes, add during a minute 15 ml of the same medium. 7. Centrifuge at 250g for 10 minutes. Gently resuspend the fused cells at a concentration of 5 x104 cells/ml, in a RPMI medium containing serum at 20%, HAT (selective growth) and antibiotics. 8. Distribute the cell suspension into 96-well-flat-bottom-tissue-culture plates add 0.2 ml per well. Incubate the plates at 37 deg. C in 5% CO2. Three to 4 days in HAT medium is sufficient for arresting the proliferation of unfused myeloma cells. Screening and establishing a Hybridorna line. The screening could be perform using different immunoassay alternatives (ELISA, RIA, etc). The principal requisite is have been developed a reproducible method before to make the fusion. These method could be improve using the serum of mice immunized as sample. Approximately 1 week after the fusion, colonies of hybrid cells will be ready to screen. During the screening, samples of tissue culture media are removed from wells that have growing hybridomas and are tested for the presence of the desired antibodies. Successful fusions will produce between 2000 and 5000 hybridomas colonies. Depending on the fusion, individual wells will become ready to screening over 2 to 6 day period. Typically, the first wells could be ready to screen in day 7 or 8, and most of the wells will need to be screened within the next 4 or 5 days. When you detected a possible positive clone, you could transfer hybrids of interest to 24-plates adding 1 ml of HAT medium (RPMI 1640) supplemented with serum at 20%. Cryopreserve each culture of cells when they have reached at least 3/4 confluency, 2 ampules/cell culture. Save the supernatants for further studies. Regarding to separate the interested cells of irrelevant cells, you must been do a limited diluted procedures. Ascitis production. To produce ascitis the number of cells depend of the every particular clone. Usually we inoculated ip between 1 to 2 x106 cells/ml/mice in PBS buffer. The animals must be inoculated intraperitonealy with Pristan (Sigma) or mineral oil using 0.5 ml per mice. The inoculation could be occurred 7 to 10 days before to inoculated the clone. The weight of the animals must be controlled in order to obtain better yield. The bioreactors are an alternative method to produce AcMs without it have not used animals models. IgG purification process on protein A columns. Mouse antibodies of the IgG1 subclass do not have a high affinity for protein A. Every subclass could be eluted at different peaks using a gradient pH. Usually we use 3M NaCl/1.5 M Gly pH 8.9 as a coupling buffer. For eluting IgGs we use 0.1M Citric Acid in a gradient pH (6 to IgG1, 5 to IgG2a or IgG2b, 4 IgG3). 1. Adjust a Sepharose Protein A (Pharmacia) beads using NaCl/1.5 M Gly pH 8.9 (coupling buffer). 2. Diluted the ascitis 1:10 in coupling buffer using a filter paper for remove the aggregations. 3. Pass the solution trough a Protein A bead column at a standarized flow according your equipment. The capacity of the Protein A beads for IgGl is approximately 5 mg/ml of wet beads. Ascitis contain between 1-10 mg/ml. 4. Wash the colums with 10 volumes of coupling buffer. 5. Elute the column with 0.1 M Citric Acid in a gradient pH starting at 6 to 4. Collect the eluate in appropriate tube, and identify the immunoglobulin-containing fractions by absorbance a 280 nm (1 DO = 0.8 mg/ml)

  6. Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina / Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury

    Scientific Electronic Library Online (English)

    Adriana Ignacio de, Padua; Célio Lopes, Silva; Simone Gusmão, Ramos; Lúcia Helena, Faccioli; José Antônio Baddini, Martinez.

    2008-11-01

    Full Text Available OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo) e injetados com salina intratraqueal (IT); grupo SB, [...] tratados com salina (placebo) e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%). A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente) em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente). Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%).O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão). CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina. Abstract in english OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB [...] , injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

  7. Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury

    Directory of Open Access Journals (Sweden)

    Adriana Ignacio de Padua

    2008-11-01

    Full Text Available OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo e injetados com salina intratraqueal (IT; grupo SB, tratados com salina (placebo e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%. A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente. Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%.O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão. CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina.OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo and then receiving intratracheal (IT instillation of saline; SB, injected with saline (placebo and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure was higher in the SB group than in the SS group (57.7% vs. 11.1%. The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively. The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%. The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung. CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

  8. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Tolver, Anders; Jørgensen, L W; Andersen, J.L.; Adamsen, L; Højman, P.; Nielsen, R. H.; Rørth, Mikkel; Daugaard, Gedske

    2014-01-01

    Abstract Background: Bleomycin–etoposid–cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. Methods: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9...

  9. Superselection rules and quantum protocols

    Science.gov (United States)

    Kitaev, Alexei; Mayers, Dominic; Preskill, John

    2004-05-01

    We show that superselection rules do not enhance the information-theoretic security of quantum cryptographic protocols. Our analysis employs two quite different methods. The first method uses the concept of a reference system—in a world subject to a superselection rule, unrestricted operations can be simulated by parties who share access to a reference system with suitable properties. By this method, we prove that if an n -party protocol is secure in a world subject to a superselection rule, then the security is maintained even if the superselection rule is relaxed. However, the proof applies only to a limited class of superselection rules, those in which the superselection sectors are labeled by unitary irreducible representations of a compact symmetry group. The second method uses the concept of the format of a message sent between parties—by verifying the format, the recipient of a message can check whether the message could have been sent by a party who performed charge-conserving operations. By this method, we prove that protocols subject to general superselection rules (including those pertaining to non-Abelian anyons in two dimensions) are no more secure than protocols in the unrestricted world. However, the proof applies only to two-party protocols. Our results show in particular that, if no assumptions are made about the computational power of the cheater, then secure quantum bit commitment and strong quantum coin flipping with arbitrarily small bias are impossible in a world subject to superselection rules.

  10. Biomodelos para la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina / Biomodels for micronucleis induction on bone marrow cells by cyclophosphamide and bleomycin

    Scientific Electronic Library Online (English)

    Daniel Francisco, Arencibia; Alexis, Vidal; Luis Alfredo, Rosario; Yolanda Emilia, Suárez; Livan, Delgado.

    2011-04-01

    Full Text Available En este trabajo se evaluó la línea de ratones Balb/c, de ambos sexos, como biomodelo en la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina. Se formaron cinco grupos experimentales/sexo: al primero se le administró NaCl al 0,9%, al segundo y al tercero ciclofosf [...] amida y al cuarto y quinto bleomicina. Todos los medicamentos fueron suministrados por vía intraperitoneal, con diseños de tratamientos diferentes y dosis de 50 mg/kg en los tres primeros grupos y de 20 mg/kg en los dos últimos. Se obtuvo como resultado una mayor inducción de micronúcleos en eritrocitos policromáticos y un mayor índice de citotoxicidad por el uso de la ciclofosfamida, administrada en dos ocasiones antes del sacrificio, con intervalos de 24 horas entre ambas administraciones. Esto constituyó, bajo nuestras condiciones experimentales, el mejor diseño para inducir un número considerable de micronúcleos en células de la médula ósea de ratones, siendo estos resultados útiles para evaluar drogas con efecto antigenotóxico y pudiera servir también como control positivo en estudios de mutagénesis o genotoxicidad. Abstract in english Balb/c mice of both sexes were evaluated as biomodel in the induction of micronucleis in bone marrow cells by cyclophosphamide and bleomycin. They were divided into five experimental groups per sex. The first one was administered with NaCl 0.9% by intraperitoneal (i.p) route, the second and third gr [...] oups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at 20 mg/kg doses. This resulted in a higher micronucleis induction of polychromatic erythrocytes and in a higher citotoxicity index with the use of cyclophosphamide administered twice before the sacrifice, with a 24-hours interval between administrations. According to our experimental conditions, this is the best design to induce a considerable number of micronucleis in bone marrow cells of mice, being useful in experimental designs to evaluate drugs with antigenotoxic effect. In addition, it implies its use according to the best found experimental design as positive control in mutagenesis and genotoxicity studies.

  11. Effects of Herba Ephedra Sinicae and Fructus Schisandrae Chinensis on pathology of rats with bleomycin A5-induced idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Hua-qiang Zhai

    2011-05-01

    Full Text Available Objective: To observe the different effects between Mahuang (Herba Ephedra Sinicae and Wuweizi (Fructus Schisandrae Chinensis on the pathological changes of rats with bleomycin A5-induced pulmonary fibrosis.Methods: Ninety Wistar rats were randomly divided into sham operation group, model group, hydrocortisone group, Herba Ephedra Sinicae group, Fructus Schisandrae Chinensis group and Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group. There were 16 rats in each group except the sham operation group (10 rats. Pulmonary fibrosis was induced by a single intratracheal injection of bleomycin A5. Hematoxylin and eosin straining and immunohistochecical method were used after 7- and 28-day treatment to observe the pathology of lung injury, measure the inner diameter of pulmonary arterioles and the density of nuclear membrane.Results: Compared with the sham operation group at 7 and 28 d, alveolar inflammation level was significantly increased in the model group (P?0.01. Alveolar inflammation level was decreased obviously in the hydrocortisone group (P?0.05 after 7- and 28-day treatment as compared with the model group, and that in Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group was also decreased obviously (P?0.05 at 28 d. Compared with the sham operation group, nuclear density of the model group was increased, while its inner diameter was decreased (P?0.05. In the Fructus Schisandrae Chinensis group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group, the nuclear density was decreased (P?0.05 as compared with the model group. Inner diameter in the Herba Ephedra Sinicae group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group was higher than that in the model group (P?0.05. Microvessel density of the model group was obviously higher than that of the sham operation group (P?0.05. Compared with the model group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group had lower microvessel density (P?0.05.Conclusion: Herba Ephedra Sinicae combined with Fructus Schisandrae Chinensis can restrain pulmonary artery injury. The nuclear density and microvessel density can be reduced by Fructus Schisandrae Chinensis, while Herba Ephedra Sinicae can increase the inner diameter.

  12. More Robust Multiparty Protocols with Oblivious Transfer

    CERN Document Server

    Müller-Quade, J

    2001-01-01

    With oblivious transfer multiparty protocols become possible even in the presence of a faulty majority. But all known protocols can be aborted by just one disruptor. This paper presents more robust solutions for multiparty protocols with oblivious transfer. This additional robustness against disruptors weakens the security of the protocol such that we can observe a trade off between robustness and security. We give an application to quantum multiparty protocols. These allow the implementation of oblivious transfer and the protocols of this paper relative to temporary assumptions, i.e., the security increases after the termination of the protocol.

  13. Sequential Rationality in Cryptographic Protocols

    CERN Document Server

    Gradwohl, Ronen; Rosen, Alon

    2010-01-01

    Much of the literature on rational cryptography focuses on analyzing the strategic properties of cryptographic protocols. However, due to the presence of computationally-bounded players and the asymptotic nature of cryptographic security, a definition of sequential rationality for this setting has thus far eluded researchers. We propose a new framework for overcoming these obstacles, and provide the first definitions of computational solution concepts that guarantee sequential rationality. We argue that natural computational variants of subgame perfection are too strong for cryptographic protocols. As an alternative, we introduce a weakening called threat-free Nash equilibrium that is more permissive but still eliminates the undesirable ``empty threats'' of non-sequential solution concepts. To demonstrate the applicability of our framework, we revisit the problem of implementing a mediator for correlated equilibria (Dodis-Halevi-Rabin, Crypto'00), and propose a variant of their protocol that is sequentially r...

  14. Cryptographic Protocols under Quantum Attacks

    CERN Document Server

    Lunemann, Carolin

    2011-01-01

    The realm of this thesis is cryptographic protocol theory in the quantum world. We study the security of quantum and classical protocols against adversaries that are assumed to exploit quantum effects to their advantage. Security in the quantum world means that quantum computation does not jeopardize the assumption, underlying the protocol construction. But moreover, we encounter additional setbacks in the security proofs, which are mostly due to the fact that some well-known classical proof techniques are forbidden by certain properties of a quantum environment. Interestingly, we can exploit some of the very same properties to the benefit of quantum cryptography. Thus, this work lies right at the heart of the conflict between highly potential effects but likewise rather demanding conditions in the quantum world.

  15. The Geneva Protocol of 1925

    International Nuclear Information System (INIS)

    This paper reports that when President Gerald Ford signed the instruments of ratification for the Geneva Protocol of 1925 on January 22, 1975, a tortured, half-century-long chapter in U.S. arms control policy was brought to a close. Fifty years earlier, at the Geneva Conference for the Control of the International Trade in Arms, Munitions and Implements of War, the United States had played a key role in drafting and reaching agreement on the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare. The protocol, signed by thirty nations, including the United States, on June 17, 1925, prohibits the use in war of asphyxiating, poisonous or other gases, and of all analogous liquids, materials or devices as well as the use of bacteriological methods of warfare

  16. The Kyoto protocol development; La viabilite du protocole de Kyoto

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)

    2002-04-01

    From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

  17. A protocol's life after attacks

    OpenAIRE

    Bistarelli, Stefano

    2003-01-01

    In the analysis of security protocols, it is customary to stop as soon as we find and attack. Tons of ink can be spilled on whether an "attack" is really an attack, but it goes without saying that there is no life after that, hence no interest in continuing the analysis. If the protocol is broken, then we ought to fix it. Yet, fixing things is expensive and other measures may be more effective. In the physical world, most ATM safes would not resist heavy shelling with anti-tank bazookas, but ...

  18. Analyzing security of Authenticated Routing Protocol (ARAN)

    OpenAIRE

    Seema Mehla; Bhawna Gupta; Preeti Nagrath

    2010-01-01

    Ad hoc network allow nodes to communicate beyond their direct wireless transmission range by introducing cooperation in mobile computer (nodes). Many proposed routing protocol for ad hoc network operate in an ad hoc fashion, as on demand routing protocol often have low overhead and faster reaction time than other type of routingbased on periodic protocol. However variety of attacks targeting routing protocol have been identified. By attacking the routing protocol attacker can absorb network t...

  19. SILC-A Secured Internet Chat Protocol

    OpenAIRE

    ANINDITA SINHA; SAUGATA SINHA

    2013-01-01

    The Secure Internet Live Conferencing (SILC) protocol, a new generation chat protocol provides full featured conferencing services, compared to any other chat protocol. Its main interesting point is security which has been described all through the paper. We have studied how encryption and authentication of the messages in the network achieves security. The security has been the primary goal of the SILC protocol and the protocol has been designed from the day one security in mind. In this pap...

  20. Preparation, distribution, stability and tumour imaging properties of [62Zn] bleomycin complex in normal and tumour-bearing mice as a molecular pet generator

    International Nuclear Information System (INIS)

    PET is a powerful imaging technique with many advantages over single photon imaging. Nowadays, several positron emitter radioisotopes and their radio-labeled complexes have been developed for imaging. 62Zn/62Cu positron generator system has been widely proposed as a source of perfusion tracers (Green, 1987 and Green et al, 1988). In this study we have developed a 62Zn/62Cu-bleomycin tracer system as a biological generator for PET. The radiochemical separation of the 62Zinc (Neirinckx 1977) from natural copper target (electroplated over Ni layer) was carried out with a method described by (Green et al, 1990 and Okazawa et al, 1994) with slight modification. After dissolving of the irradiated target, solution was heated under a flow of nitrogen to dry up until a precipitate was formed. The precipitate was rinsed 2 times by distilled water (10 ml) and a portion of 2N HCl was added and mixed gently. The solution was pumped through a column 10x100mm filled with BioRad AG-1X8 resin and preconditioned with 2N HCl. For the elution of 62Zn in anion exchange resin, 0.005 N HCl was adopted instead of water used by (Green et al, 1990, Qaim 2001), because [62Zn] chloride form is suitable for the BLM labeling The samples were taken for the gamma spectroscopy analysis, using HPGe Canberra detector, in each steps. [62Zn]Zinc chloride (0.25-2.5 mCi) dissolved in acidic media obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted using HCl 1M and/or NaOH 1M (pH=1-7). The mixture was evaporated by slight warming, under a nitrogen flow. A mixture of BLM (0.25-2.5 mg,) in normal saline (0.1 mL) was then added. This mixture was heated at different temperatures (25, 50, 80 and 100 deg. C). The mixture was cooled in an ice bath and rapidly sent for use. The active solution was checked for radiochemical purity by polymer-backed silica gel layer using a mixture of ammonium acetate 10%-methanol as the mobile phase. These analyses were carried out every 30 min after labeling step. The final solution was then passed through a 0.22 m filter and pH adjusted to 5-7 by the addition of sodium acetate (1M) buffer. Pyrogen test was performed using a commercial LAL kit. Stability of [62Zn]BLM complex in final product and human/mice serum in vitro. A sample of [62Zn]BLM (0.5 mCi) was kept at room temperature for 48 hrs while checked by RTLC at various time intervals (2, 4, 8, 12 and 24). A micropipette sample (50 mL) was taken from the shaking mixture and the ratio of free radiozinc to [62Zn]BLM was checked by radio thin layer chromatography (eluent: 10% NH4OAc and methanol 1:1). The patterns for [62Zn]ZnCl2 and [62Zn]BLM were not changed in 24 hrs. Animal studies: Fibrosarcoma cells (about 104) of were injected SC to the dorsal area of Balb C mice weighing 20-25 g. After 14 days the tumour weighed 0.7 g and was not grossly necrotic. The distribution of [62Zn]-ZnCl2 and [62Zn]-BLM among tissues were determined for untreated mice and for mice with fibrosarcoma. A volume (0.1 ml) of final [62Zn]-BLM solution containing 20-40 uCi radioactivity (6 mg bleomycin in 50 mL) was injected into the dorsal tail vein. The total amout of radioactivity injected into each mouse was measured by counting the 1-ml syringe before and after injection in a radiometer with a fixed geometry. The animals were sacrificed by ether asyxphycation at selected times after injection, the tissues weighed and their specific activities determined with a gamma-ray scintillation as percentage of injected dose per gram of tissues (data not shown here) No unlabelled and/or labeled by-products were observed upon RTLC analysis of the final preparations. In contrast to other labeled bleomycins, [62Zn]bleomycin, has a lower half life causing less undesirable irradiation and it also benefits from PET radiopharmacutical advantages. Its rather higher half-life in contrast to other PET radioisotopes and high chemical stability of radiopharmaceutical form makes it a suitable possible PET tracer for use in neighborhood PET centers. [62Zn]-BLM can be used in PET oncology studies due to

  1. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  2. Performance Evaluation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael

    2005-01-01

    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools.

  3. Bundle Security Protocol for ION

    Science.gov (United States)

    Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

    2011-01-01

    This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

  4. IMPROVED SECURE ADDRESS RESOLUTION PROTOCOL

    Directory of Open Access Journals (Sweden)

    Abhishek Samvedi

    2014-05-01

    Full Text Available In this paper, an improved secure address resolution protocol is presented where ARP spoofing attack is prevented. The proposed methodology is a centralised methodology for preventing ARP spoofing attack. In the proposed model there is a central server on a network or subnet which prevents ARP spoofing attack.

  5. Superposition Attacks on Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Funder, Jakob LØvstad

    2011-01-01

    Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security of several primitives in this model. We show that a secret-sharing scheme that is secure with threshold $t$ in the standard model is secure against superposition attacks if and only if the threshold is lowered to $t/2$. We use this result to give zero-knowledge proofs for all of NP in the common reference string model. While our protocol is classical, it is sound against a cheating unbounded quantum prover and computational zero-knowledge even if the verifier is allowed a superposition attack. Finally, we consider multiparty computation and show that for the most general type of attack, simulation based security is not possible. However, putting a natural constraint on the adversary, we show a non-trivial example of a protocol that can indeed be simulated.

  6. Modified oral metronidazole desensitization protocol.

    Science.gov (United States)

    Gendelman, Samantha R; Pien, Lily C; Gutta, Ravi C; Abouhassan, Susan R

    2014-03-01

    The Center for Disease Control guidelines recommend desensitization to metronidazole in patients with trichomoniasis and hypersensitivity to metronidazole. There is only one published oral metronidazole desensitization protocol. The purpose of this study was to design a new, more gradual oral desensitization protocol to decrease systemic reactions that may occur when using the previously published protocol. We present two patients with presumed IgE-mediated allergy to metronidazole who underwent oral desensitization using our modified protocol. Case 1 was a 65-year-old woman with trichomoniasis who presented for metronidazole desensitization with a history of intraoperative anaphylaxis and positive skin tests to metronidazole. The patient tolerated six doses of the modified desensitization but developed systemic symptoms of nasal congestion and diffuse pruritus after the 25- and 100-mg doses. Both reactions were treated with intravenous (i.v.) antihistamines. Because of gastrointestinal irritation, the desensitization was completed at a dose of 250 mg orally every 6 hours. Case 2 was a 42-year-old woman with trichomoniasis and a history of hives immediately after administration of i.v. metronidazole who presented for desensitization. The patient had negative skin-prick and intradermal testing to metronidazole. She developed lip tingling and pruritus on her arms 15 minutes after the 10-mg dose. Fexofenadine at 180 mg was given orally and symptoms resolved. She tolerated the rest of the protocol without reaction and received a total dose of 2 g of metronidazole. Our oral metronidazole desensitization for presumed IgE-mediated reactions offers a second option for physicians wishing to use a more gradual escalation in dose. PMID:24612959

  7. A Comparison of Effects of ABVD and ChlVPP Chemotherapeutic Protocols for Hodgkin's Disease on Rats’ Epididiymal and Testicular Tissues

    Directory of Open Access Journals (Sweden)

    S. Zare

    2010-01-01

    Full Text Available The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone group and two control groups one for each treatment group. One half of the lethal dose for 50% of population (LD50 was used for treatment of animals in each protocol. Testes and epididymis tissues were examined for structural changes and serum testosterone level was measured by Lission (chemiluminescence method. Body weight, testis and epididymis weights, in treated rats were significantly less than their control groups specifically in ABVD group was less than ChlVPP group. Decreasing of mean diameter of seminiferous tubules, height of spermatogenic cells and diameter of epididymis in caput, corpus and cauda in ABVD group were significantly more than ChlVPP and control group. The serum testosterone level in ABVD group was significantly less than ChlVPP and control group. According to this study results, the ChlVPP had fewer impairment effects than ABVD on testis and epididymis tissue in tolerance doses on male rats' reproductive system. More clinical trial studies are suggested on Hodgkin's patients. With equal treatment effectiveness, it will be better to use the most reliable and safe treatment especially in young patients.

  8. Performance Evaluation of MANET Routing Protocols Based on Internet Protocols

    Directory of Open Access Journals (Sweden)

    Hilal Bello Said,

    2015-11-01

    Full Text Available The topology of mobile ad hoc network (MANET changes rapidly and unpredictably due to nodes mobility. This makes routing protocols very important to analyze so as to communicate efficiently between the wireless nodes. Another important issue in the MANET is the internet protocols IPv4 and IPV6. The former which have been conventionally in use for long and the latter which is seen as the future standard for network architecture is studied due to its improved protection and huge address space support. In this paper, performance of AODV, DYMO, OLSRv2 and OLSR are analyzed under the IPv4 and IPv6 standards using the Qualnet simulator. Distinct performance metrics viz. Packet delivery ratio, Throughput, Average End-to-End Delay, and Average jitter are selected for the experiment. The results are then analyzed and scrutinized to provide qualitative assessment of their performances.

  9. Session Initiation Protocol Attacks and Challenges

    CERN Document Server

    Keshavarz, Hassan; Noor, Rafidah Md

    2012-01-01

    In recent years, Session Initiation Protocol (SIP) has become widely used in current internet protocols. It is a text-based protocol much like Hyper Text Transport Protocol (HTTP) and Simple Mail Transport Protocol (SMTP). SIP is a strong enough signaling protocol on the internet for establishing, maintaining, and terminating session. In this paper the areas of security and attacks in SIP are discussed. We consider attacks from diverse related perspectives. The authentication schemes are compared, the representative existing solutions are highlighted, and several remaining research challenges are identified. Finally, the taxonomy of SIP threat will be presented.

  10. Using Ovsynch protocol versus Cosynch protocol in dairy cows

    Directory of Open Access Journals (Sweden)

    Ion Valeriu Caraba

    2013-10-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 As a research on the reproductive physiology and endocrinology surrounding the estrous cycle in dairy cattle has been compiled, several estrous synchronization programs have been developed for use with dairy cows. These include several programs that facilitate the mass breeding of all animals at a predetermined time (timed-AI rather than the detection of estrus. We studied on 15 dary cows which were synchronized by Ovsynch and Cosynch programs. The estrus response for cows in Ovsynch protocol was of 63%. Pregnancy per insemination at 60 days was of 25%. Estrus response for cow in Cosynch protocol was of 57%. Pregnancy per insemination at 60 days was of 57%. Synchronization of ovulation using Ovsynch protocols can provide an effective way to manage reproduction in lactating dairy cows by eliminating the need for estrus detection. These are really efficient management programs for TAI of dairy cows that are able to reduce both the labour costs and the extra handling to daily estrus detection and AI. 

  11. On using Mobile IP Protocols

    Directory of Open Access Journals (Sweden)

    Fayza A. Nada

    2006-01-01

    Full Text Available The recent advances in wireless communication technology and the unprecedented growth of the Internet have paved the way for wireless networking and IP mobility. Mobile Internet protocol has been designed within the IETF to support the mobility of users who wish to connect to the Internet and maintain communications as they move from place to place. This study describes and summarizes the current Internet draft for mobile IP (MIPv4 with its major components: agent discovery, registration and tunneling. In addition, we outline the available encapsulation techniques and route optimization procedure. In the end, we describe the design of the new protocol for transparent routing of IPv6 packets to mobile IPv6 nodes operating in the Internet.

  12. Neonatal euthanasia: The Groningen Protocol*

    Science.gov (United States)

    Vizcarrondo, Felipe E.

    2014-01-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  13. Neonatal euthanasia: The Groningen Protocol.

    Science.gov (United States)

    Vizcarrondo, Felipe E

    2014-11-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  14. CDTP Chain Distributed Transfer Protocol

    CERN Document Server

    Vagner, S

    2004-01-01

    The rapid growth of the internet in general and of bandwidth capacity at internet clients in particular poses increasing computation and bandwidth demands on internet servers. Internet access technologies like ADSL [DSL], Cable Modem and Wireless modem allow internet clients to access the internet with orders of magnitude more bandwidth than using traditional modems. We present CDTP a distributed transfer protocol that allows clients to cooperate and therefore remove the strain from the internet server thus achieving much better performance than traditional transfer protocols (e.g. FTP [FTP]). The CDTP server and client tools are presented also as well as results of experiments. Finally a bandwidth measurement technique is presented. CDTP tools use this technique to differentiate between slow and fast clients.

  15. Chapter 14: Chiller Evaluation Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Tiessen, A.

    2014-09-01

    This protocol defines a chiller measure as a project that directly impacts equipment within the boundary of a chiller plant. A chiller plant encompasses a chiller--or multiple chillers--and associated auxiliary equipment. This protocol primarily covers electric-driven chillers and chiller plants. It does not include thermal energy storage and absorption chillers fired by natural gas or steam, although a similar methodology may be applicable to these chilled water system components. Chillers provide mechanical cooling for commercial, institutional, multiunit residential, and industrial facilities. Cooling may be required for facility heating, ventilation, and air conditioning systems or for process cooling loads (e.g., data centers, manufacturing process cooling). The vapor compression cycle, or refrigeration cycle, cools water in the chilled water loop by absorbing heat and rejecting it to either a condensing water loop (water cooled chillers) or to the ambient air (air-cooled chillers).

  16. Power Control Protocols in VANET

    OpenAIRE

    Samara, Ghassan; Salem, Amer O. Abu; Alhmiedat, Tareq

    2013-01-01

    Vehicular Ad hoc Networks (VANET) is one of the most challenging research area in the field of the Mobile Ad hoc Network (MANET), Power control is a critical issue in VANETwhere is should be managed carefully to help the channel to have high performance. In this paper a comparative study in the published protocols in the field of safety message dynamic power control will be presented and evaluated.

  17. New protocol supporting collaborative simulation

    OpenAIRE

    Nguyen Trong, Khanh; Marilleau, Nicolas; Ho, Tuong Vinh; Fallah-Seghrouchni, Amal El

    2011-01-01

    Major researches in the domain of complex systems are interdisciplinary, collaborative and geographically distributed. The purpose of our work is to explore a new methodology that facilitates scientist's interactions during the simulation process. Through the analysis of the collaboration and pluridisciplinary in a simulation project, we have identified the needs of a common representation about models and simulators. Then, we provide an extension of ODD protocol including new features dedica...

  18. On using Mobile IP Protocols

    OpenAIRE

    Fayza A. Nada

    2006-01-01

    The recent advances in wireless communication technology and the unprecedented growth of the Internet have paved the way for wireless networking and IP mobility. Mobile Internet protocol has been designed within the IETF to support the mobility of users who wish to connect to the Internet and maintain communications as they move from place to place. This study describes and summarizes the current Internet draft for mobile IP (MIPv4) with its major components: agent discovery, registration and...

  19. Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Hendron, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht, Cheryn [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2010-09-01

    The House Simulation Protocol document was developed to track and manage progress toward Building America's multi-year, average whole-building energy reduction research goals for new construction and existing homes, using a consistent analytical reference point. This report summarizes the guidelines for developing and reporting these analytical results in a consistent and meaningful manner for all home energy uses using standard operating conditions.

  20. Implicit Simulations using Messaging Protocols

    OpenAIRE

    Kohring, G.A.

    2002-01-01

    A novel algorithm for performing parallel, distributed computer simulations on the Internet using IP control messages is introduced. The algorithm employs carefully constructed ICMP packets which enable the required computations to be completed as part of the standard IP communication protocol. After providing a detailed description of the algorithm, experimental applications in the areas of stochastic neural networks and deterministic cellular automata are discussed. As an ...

  1. Cost estimation of Kyoto Protocol

    International Nuclear Information System (INIS)

    This article proposes a reflection on important aspects in the costs determination performance of Kyoto Protocol. The evaluation of the main models evidence possible impacts on the economies. A key role in the determination of the cost is represented by the relative hypothesis to emission trading and the projects CDM-JI and from the political capacity at the cost negative or equal to zero

  2. Active Virtual Network Management Protocol

    OpenAIRE

    Bush, Stephen F.

    1999-01-01

    This paper introduces a novel algorithm, the Active Virtual Network Management Protocol (AVNMP), for predictive network management. It explains how the AVNMP facilitates the management of an active network by allowing future predicted state information within an active network to be available to network management algorithms. This is accomplished by coupling ideas from optimistic discrete event simulation with active networking. The optimistic discrete event simulation method used is a form o...

  3. Secure Multi-Player Protocols

    DEFF Research Database (Denmark)

    Fehr, Serge

    2003-01-01

    While classically cryptography is concerned with the problem of private communication among two entities, say players, in modern cryptography multi-player protocols play an important role. And among these, it is probably fair to say that secret sharing, and its stronger version verifiable secret sharing (VSS), as well as multi-party computation (MPC) belong to the most appealing and/or useful ones. The former two are basic tools to achieve better robustness of cryptographic schemes against malfu...

  4. DSTC Layering Protocols in Wireless Cooperative Networks

    CERN Document Server

    Elamvazhuthi, P S; Dey, B K

    2008-01-01

    In adhoc wireless relay networks, layers of relays are used to communicate from a source to a destination to achieve better reliability. In this paper, we consider five protocols derived from an earlier proposed protocol, where the relays do a simple processing before transmitting and as a result achieve distributed space-time code. Four of the protocols discussed utilize more complicated relaying schemes than simple layered protocols proposed in earlier literature. We have analyzed the effectiveness of these protocols in various power loss configurations among the paths. Optimum power allocation of the total power among various transmissions have been found by reasonable fine search for all the protocols. Bit error rate plots are compared under optimum power allocation for these protocols. From the simulation results, we draw some guidelines as to which protocol is good for what kind of environment.

  5. A New Evaluation Model for Security Protocols

    Directory of Open Access Journals (Sweden)

    Xuewen DONG

    2011-09-01

    Full Text Available Till today, the study of performance of security protocols of WLAN has been one of research focuses. Whereas, owing to enormous complexity and low efficiency of modeling security protocols, there has been by now no uniform method or technology that can be used generally to simulate and evaluate security protocols, and no simulation system available that can well support research on performance of security protocols. So in view of the status quo, we, in this paper, mainly propose a novel security protocol simulation architecture and a simulation extending method for simulating security protocols of WLAN, and then set up a simulation platform for modeling such protocols based on OPNET, a famous simulation software. Finally, with an instance of extending and simulating a security protocol of WLAN, the validity and the universality of the simulation architecture and the extending method as well as the feasibility and correctness of the simulation platform are demonstrated.

  6. High-dose-rate brachytherapy with local injection of bleomycin for N0 oral tongue cancer. Possibilities of the control of tumor implant by inserting applicators and the decrease in tumor dose

    International Nuclear Information System (INIS)

    Twenty-eight patients with N0 oral tongue cancer were treated with high-dose-rate (HDR) interstitial brachytherapy combined with local injection of bleomycin between December 1997 and June 2001 at the Department of Radiology, National Kyushu Medical Center Hospital. A median dose of 5 mg of bleomycin was injected locally, and 16-20 Gy was delivered to the area surrounding applicators for control of the tumor implant during the initial two days. The two-year local recurrence-free survival rate was 96% [T1, 2: 100% (8/8, 15/15), T3: 80% (4/5)]. The two-year secondary neck node metastasis rate was 7.1% [T1: 12.5% (1/8), T2: 6.7% (1/15), T3: 0% (0/5)]. There were no tumor implants in any patients. We tried to decrease the minimal tumor dose step by step. The groups with median minimal tumor doses of 60 Gy, 50 Gy, and 40 Gy had local recurrence rates of 12.5% (1/8), 0% (0/14), and 0% (0/6), respectively. Local recurrence rates were not increased by decreasing the minimal tumor dose. Two patients (7%) had secondary neck node metastasis. Late adverse effects were tongue ulcer: 11% (3/28), oral floor ulcer: 4% (1/28), and osteonecrosis: 4% (1/28). These results suggest that control of the tumor implant and the decrease in minimal tumor dose below 60 Gy may be possible with the local injection of bleomycin and delivery of doses to the area surrounding the applicators when N0 tongue cancer is treated using 192Ir-HDR brachytherapy. (author)

  7. Entangled and sequential quantum protocols with dephasing

    OpenAIRE

    Boixo, Sergio; Heunen, Chris

    2011-01-01

    Sequences of commuting quantum operators can be parallelized using entanglement. This transformation is behind some optimal quantum metrology protocols and recent results on quantum circuit complexity. We show that dephasing quantum maps in arbitrary dimension can also be parallelized. This implies that for general dephasing noise the protocol with entanglement is not more fragile than the corresponding sequential protocol and, conversely, the sequential protocol is not less...

  8. Adaptation Process for Ad hoc Routing Protocol

    OpenAIRE

    Yawut, Cholatip; Paillassa, Beatrice; Dhaou, Riadh

    2010-01-01

    Because of several constraints in ad hoc networks, an adaptive ad hoc routing protocol is increasingly required. In this paper, we propose a synopsis of an adaptation process for an adaptive ad hoc routing protocol. Next, we put into practice the analysis of the process of adaptation to mobility by realizing an adaptive routing protocol: CSR (Cluster Source Routing) which is an extension of a widely used ad hoc routing protocol: DSR (Dynamic source Routing). Mobility and density metrics are c...

  9. Quantum bit commitment protocol without quantum memory

    OpenAIRE

    Ramos, Rubens Viana; Mendonca, Fabio Alencar

    2008-01-01

    Quantum protocols for bit commitment have been proposed and it is largely accepted that unconditionally secure quantum bit commitment is not possible; however, it can be more secure than classical bit commitment. In despite of its usefulness, quantum bit commitment protocols have not been experimentally implemented. The main reason is the fact that all proposed quantum bit commitment protocols require quantum memory. In this work, we show a quantum bit commitment protocol th...

  10. A father protocol for quantum broadcast channels

    CERN Document Server

    Dupuis, F; Dupuis, Fr\\'ed\\'eric; Hayden, Patrick

    2006-01-01

    We present a new protocol for quantum broadcast channels based on the fully quantum Slepian-Wolf protocol. The protocol yields an achievable rate region for entanglement-assisted transmission of quantum information through a quantum broadcast channel that can be considered the quantum analogue of Marton's region for classical broadcast channels. The protocol can be adapted to yield achievable rate regions for unassisted quantum communication and for entanglement-assisted classical communication. Regularized versions of all three rate regions are provably optimal.

  11. Cryptanalysis of an Authentication Key Exchange Protocol

    OpenAIRE

    Chou-Chan Yang; Ya-Wen Yang; Ting-Yi Chang

    2005-01-01

    An authenticated multiple-key agreement protocol uses a digital signature to sign the Diffie-Hellman public keys which can generate multiple session key in a single round of message exchange and achieve mutual authentication. Recently, Hwang et al. proposed an authentication key exchange protocol which takes less computation time than Harn and Lin;s protocol. However, this study, shows that Hwang et al.`s protocol is vulnerable to forgery attacks. An attacker can fool one communication part i...

  12. An Analysis on Implementation of Leach Protocol

    OpenAIRE

    Ms. Mondakini Dihingia; Mr. Santosh Ranadev; A. Shobha Rani

    2014-01-01

    Wireless sensor network consists of set of sensor nodes which is widely used in monitoring purposes. In order to increase the wireless sensor network life time various protocol was developed. In this paper presents a comparative analysis among various protocols to reduce energy consumption within the wireless sensor network. Here we typically analysis leach protocol and is various drawback and how these drawback are used to implement V-LEACH protocol

  13. A father protocol for quantum broadcast channels

    OpenAIRE

    Dupuis, Frédéric; Hayden, Patrick; Li, Ke

    2006-01-01

    A new protocol for quantum broadcast channels based on the fully quantum Slepian-Wolf protocol is presented. The protocol yields an achievable rate region for entanglement-assisted transmission of quantum information through a quantum broadcast channel that can be considered the quantum analogue of Marton's region for classical broadcast channels. The protocol can be adapted to yield achievable rate regions for unassisted quantum communication and for entanglement-assisted c...

  14. A New Evaluation Model for Security Protocols

    OpenAIRE

    Xuewen DONG; Ma, Jianfeng; Yang, Chao

    2011-01-01

    Till today, the study of performance of security protocols of WLAN has been one of research focuses. Whereas, owing to enormous complexity and low efficiency of modeling security protocols, there has been by now no uniform method or technology that can be used generally to simulate and evaluate security protocols, and no simulation system available that can well support research on performance of security protocols. So in view of the status quo, we, in this paper, mainly propose a novel secur...

  15. Asymptotic adaptive bipartite entanglement distillation protocol

    OpenAIRE

    Hostens, Erik; Dehaene, Jeroen; De Moor, Bart

    2006-01-01

    We present a new asymptotic bipartite entanglement distillation protocol that outperforms all existing asymptotic schemes. This protocol is based on the breeding protocol with the incorporation of two-way classical communication. Like breeding, the protocol starts with an infinite number of copies of a Bell-diagonal mixed state. Breeding can be carried out as successive stages of partial information extraction, yielding the same result: one bit of information is gained at the cost (measuremen...

  16. Automatic Verification of Security Protocols Using Approximations

    OpenAIRE

    Boichut, Yohan; Héam, Pierre-Cyrille; Kouchnarenko, Olga

    2005-01-01

    Security protocols are widely used in open modern networks to ensure safe communications. It is now recognized that formal analysis can provide the level of assurance required by both developers and users of the protocols. Unfortunately it is generally undecidable to certify whether a protocol is safe or not. However the automatic verification of security protocols can be attempted using abstraction-based approximation. For this purpose, tree automata approximations were introduced by Genet a...

  17. Real Study of Host Identity Protocol

    Directory of Open Access Journals (Sweden)

    Gaurav Malik

    2014-05-01

    Full Text Available Host Identity Protocol(HIP[22,25] is a proposed protocol for providing security,mobility and multihoping to the current internet architecture. HIP establishes a new name space of Host identities(HI for representing hosts independent of their locations in the network. By contrast, the current architecture uses internet protocol(IP addresses to identify hosts.

  18. Response of S180 murine tumor to bleomycin in combination with radiation and hyperthermia using micronucleus assay: a multimodality approach for therapeutic augmentation

    International Nuclear Information System (INIS)

    Response of a transplantable tumor, S180, grown intradermally in inbred Balb/c mice, was assessed by using micronucleus assay after treating the solid tumors with bleomycin (BLM), radiation (RT) and hyperthermia (HT) vis-a-vis multimodality approach. The frequency of micronuclei (MN) though did not vary greatly during the one week of observation in untreated tumors, it significantly increased in the drug and RT groups at 24 hr post-treatment. However, MN frequency was non-significant in the HT group from the control. A drug dose dependent linear increase in the frequency of MN induction was evident in 10, 15 and 20 mg/kg body weight BLM alone treated groups. Combination of radiation with BLM or HT further increased the MN counts in the bimodality groups. But, MN induction at 24 hr post-treatment in the tri- modality group (BLM+RT+HT) was non-significant from that of the bimodality treatments. However, the tumors treated with trimodality treatment presented severe tumor necrosis, indicating increased cell loss, and resulting in immediate tumor regression. In all the bi-modality groups MN counts though declined 3 or 5 days post-treatment, the values remained significantly higher than the control, on day 7 post-treatment. Micronucleus assay could be used as a predictive parameter for the assessment of post-irradiation tumor regression response. However, the tumor response assessment with MN assay alone may not be sufficient and the role of other parameters, such as apoptosis and necrosis, in immediate tumor regression, especially radiosensitive/thermosensitive tumors can not be ignored while taking multi modality approach into consideration for cancer therapy. (author)

  19. Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in other bacteria

    Directory of Open Access Journals (Sweden)

    Itzen Aymelt

    2011-08-01

    Full Text Available Abstract Background The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity. Whereas it is believed that phenazine-producing pseudomonads possess highly active superoxide dismutases and catalases, it has recently been found that the plant-colonizing bacterium Enterobacter agglomerans expresses a small gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the phenazine antibiotic produced by this strain. Results To understand the resistance mechanism installed by EhpR we have determined its crystal structure in the apo form at 2.15 Å resolution and in complex with griseoluteic acid at 1.01 Å, respectively. While EhpR shares a common fold with glyoxalase-I/bleomycin resistance proteins, the ligand binding site does not contain residues that some related proteins employ to chemically alter their substrates. Binding of the antibiotic is mediated by ?-stacking interactions of the aromatic moiety with the side chains of aromatic amino acids and by a few polar interactions. The dissociation constant KD between EhpR and griseoluteic acid was quantified as 244 ± 45 ?M by microscale thermophoresis measurements. Conclusions The data accumulated here suggest that EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. It is tempting to speculate that EhpR acts in concert with EhpJ, a transport protein of the major facilitator superfamily that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The low affinity of EhpR for griseoluteic acid may be required for its physiological function.

  20. Celastrol enhances Nrf2 mediated antioxidant enzymes and exhibits anti-fibrotic effect through regulation of collagen production against bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Divya, Thomas; Dineshbabu, Vadivel; Soumyakrishnan, Syamala; Sureshkumar, Anandasadagopan; Sudhandiran, Ganapasam

    2016-02-25

    Pulmonary fibrosis (PF) is characterized by excessive accumulation of extracellular matrix components in the alveolar region which distorts the normal lung architecture and impairs the respiratory function. The aim of this study is to evaluate the anti-fibrotic effect of celastrol, a quinine-methide tri-terpenoid mainly found in Thunder God Vine root extracts against bleomycin (BLM)-induced PF through the enhancement of antioxidant defense system. A single intratracheal instillation of BLM (3 U/kg.bw) was administered in rats to induce PF. Celastrol (5 mg/kg) was given intraperitoneally, twice a week for a period of 28 days. BLM-induced rats exhibits declined activities of enzymatic and non-enzymatic antioxidants which were restored upon treatment with celastrol. BLM-induced rats show increased total and differential cell counts as compared to control and celastrol treated rats. Histopathological analysis shows increased inflammation and alveolar damage; while assay of hydroxyproline and Masson's trichrome staining shows an increased collagen deposition in BLM-challenged rats that were decreased upon celastrol treatment. Celastrol also reduces inflammation in BLM-induced rats as evidenced by decrease in the expressions of mast cells, Tumor necrosis factor-alpha (TNF- ?) and matrix metalloproteinases (MMPs) 2 and 9. Further, Western blot analysis shows that celastrol is a potent inducer of NF-E2-related factor 2 (Nrf2) and it restores the activities of Phase II enzymes such as hemoxygenase-1 (HO-1), glutathione-S-transferase (GSTs) and NADP(H): quinine oxidoreductase (NQO1) which were declined upon BLM administration. The results of this study show evidence on the protective effect of celastrol against BLM-induced PF through its antioxidant and anti-fibrotic effects. PMID:26768587

  1. Simple and Efficient Contract Signing Protocol

    CERN Document Server

    Alaraj, Abdullah M

    2012-01-01

    In this paper, a new contract signing protocol is proposed based on the RSA signature scheme. The protocol will allow two parties to sign the same contract and then exchange their digital signatures. The protocol ensures fairness in that it offers parties greater security: either both parties receive each other's signatures or neither does. The protocol is based on offline Trusted Third Party (TTP) that will be brought into play only if one party fails to sign the contract. Otherwise, the TTP remains inactive. The protocol consists of only three messages that are exchanged between the two parties.

  2. Analysing ZigBee Key Establishment Protocols

    CERN Document Server

    Yüksel, Ender

    2012-01-01

    In this report, we present our approach for protocol analysis together with a real example where we find an important flow in a contemporary wireless sensor network security protocol. We start by modelling protocols using a specific process algebraic formalism called LySa process calculus. We then apply an analysis based on a special program analysis technique called control flow analysis. We apply this technique to the ZigBee-2007 End-to-End Application Key Establishment Protocol and with the help of the analysis discover an unknown flaw. Finally we suggest a fix for the protocol, and verify that the fix works by using the same technique.

  3. Generalized quarantine disinfestation research protocol

    International Nuclear Information System (INIS)

    The purpose of a quarantine disinfestation treatment is to prevent the establishment of a pest associated with a commodity to be imported into a country or region where it does not already occur or where its presence is restricted. Irradiation is particularly suited to this purpose with applications over a wide range of commodities and pests. It meets the current consumer requirement of freedom from chemical residues that are associated with fumigation and insecticide treatments. Disinfestation treatments may need to gain the specific approval of quarantine authorities in each importing country. Therefore the supporting data required may differ from country to country. Such differences are usually minor and this generalised protocol will provide most of the information required by most importing countries. This protocol is intended to meet the broad quarantine treatment requirements of the following countries: Japan, USA, Australia and New Zealand. At present irradiation is likely to prove acceptable only to USA. This can be expected to change as public perception of irradiation matures and confidence develops. Additional countries for which the methodology should prove generally acceptable include the other ASEAN countries, China, Korea, Taiwan, India, South Africa and most South American and Central American countries. Signatories to GATT have agreed to abide by the principle of equivalence so there should be some flexibility in how the work is done including existing data obtained in an equivalent manner. This protocol applies particularly to pests of fresh horticultural produce that can be maintained in laboratory cultures (e.g. fruit flies and mites), but it can be adapted for use with field-collected insects provided that adequate numbers of known stages can be obtained

  4. INEEL AIR MODELING PROTOCOL ext

    Energy Technology Data Exchange (ETDEWEB)

    C. S. Staley; M. L. Abbott; P. D. Ritter

    2004-12-01

    Various laws stemming from the Clean Air Act of 1970 and the Clean Air Act amendments of 1990 require air emissions modeling. Modeling is used to ensure that air emissions from new projects and from modifications to existing facilities do not exceed certain standards. For radionuclides, any new airborne release must be modeled to show that downwind receptors do not receive exposures exceeding the dose limits and to determine the requirements for emissions monitoring. For criteria and toxic pollutants, emissions usually must first exceed threshold values before modeling of downwind concentrations is required. This document was prepared to provide guidance for performing environmental compliance-driven air modeling of emissions from Idaho National Engineering and Environmental Laboratory facilities. This document assumes that the user has experience in air modeling and dose and risk assessment. It is not intended to be a "cookbook," nor should all recommendations herein be construed as requirements. However, there are certain procedures that are required by law, and these are pointed out. It is also important to understand that air emissions modeling is a constantly evolving process. This document should, therefore, be reviewed periodically and revised as needed. The document is divided into two parts. Part A is the protocol for radiological assessments, and Part B is for nonradiological assessments. This document is an update of and supersedes document INEEL/INT-98-00236, Rev. 0, INEEL Air Modeling Protocol. This updated document incorporates changes in some of the rules, procedures, and air modeling codes that have occurred since the protocol was first published in 1998.

  5. Generalized routing protocols for multihop relay networks

    KAUST Repository

    Khan, Fahd Ahmed

    2011-07-01

    Performance of multihop cooperative networks depends on the routing protocols employed. In this paper we propose the last-n-hop selection protocol, the dual path protocol, the forward-backward last-n-hop selection protocol and the forward-backward dual path protocol for the routing of data through multihop relay networks. The average symbol error probability performance of the schemes is analysed by simulations. It is shown that close to optimal performance can be achieved by using the last-n-hop selection protocol and its forward-backward variant. Furthermore we also compute the complexity of the protocols in terms of number of channel state information required and the number of comparisons required for routing the signal through the network. © 2011 IEEE.

  6. Tool Supported Analysis of Web Services Protocols

    DEFF Research Database (Denmark)

    Marques, Abinoam P.; Ravn, Anders Peter; Srba, Jiri; Vighio, Saleem

    We describe an abstract protocol model suitable for modelling of web services and other protocols communicating via unreliable, asynchronous communication channels. The model is supported by a tool chain where the first step translates tables with state/transition protocol descriptions, often used...... e.g. in the design of web services protocols, into an intermediate XML format. We further translate this format into a network of communicating state machines directly suitable for verification in the model checking tool UPPAAL. We introduce two types of communication media abstractions in order to...... ensure the finiteness of the protocol state-spaces while still being able to verify interesting protocol properties. The translations for different kinds of communication media have been implemented and successfully tested, among others, on agreement protocols from WS-Business Activity....

  7. Desynchronization Attacks on RFID Security Protocols

    Directory of Open Access Journals (Sweden)

    Miaolei Deng

    2013-02-01

    Full Text Available The characteristics of radio frequency identification (RFID systems introduce growing security and privacy concerns. RFID systems need security protocols to provide confidentiality, user privacy, mutual authentication and etc. Many security protocols for the RFID system have been presented. This paper analyze several of the newest RFID security protocols which proposed by Niu et al., Fu et al. and Habibi et al. respectively form the security viewpoint of data desynchronization attack. These lightweight protocols were expected to proposed security protections for the RFID system and safeguard against almost all major attacks. However, we found that these RFID security protocols were vulnerable to the attack of data desynchronization. Based on strand spaces model, data desynchronization attacks on these protocols were analyzed and described. Furthermore, improvements to overcome the security vulnerabilities of two protocols presented by Niu et al. and Fu et al. were given.

  8. Language, Semantics, and Methods for Security Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico

    representation and do not address how to build up protocol representations in a compositional fashion. This dissertation presents a new, event-based approach to reasoning about security protocols. We seek a broader class of models to show how event-based models can be structured in a compositional way and so...... used to give a formal semantics to security protocols which supports proofs of their correctness. More precisely, we give a compositional event-based semantics to an economical, but expressive, language for describing security protocols (SPL); so the events and dependency of a wide range of protocols...... related to a transition semantics which can easily be implemented. (An existing SPL implementation bridges the gap that often exists between abstract protocol models on which verification of security properties is carried out and the implemented protocol.) SPL-nets are a particular kind of contextual...

  9. Asymptotic adaptive bipartite entanglement distillation protocol

    CERN Document Server

    Hostens, E; Dehaene, J; Dehaene, Jeroen; Hostens, Erik; Moor, Bart De

    2006-01-01

    We present a new asymptotic bipartite entanglement distillation protocol that outperforms all existing asymptotic schemes. This protocol is based on the breeding protocol with the incorporation of two-way classical communication. Like breeding, the protocol starts with an infinite number of copies of a Bell-diagonal mixed state. Breeding can be carried out as successive stages of partial information extraction, yielding the same result: one bit of information is gained at the cost (measurement) of one pure Bell state pair (ebit). The basic principle of our protocol is at every stage to replace measurements on ebits by measurements on a finite number of copies, whenever there are two equiprobable outcomes. In that case, the entropy of the global state is reduced by more than one bit. Therefore, every such replacement results in an improvement of the protocol. We explain how our protocol is organized as to have as many replacements as possible. The yield is then calculated for Werner states.

  10. Effective Protocols for Mobile Communications and Networking

    Energy Technology Data Exchange (ETDEWEB)

    Espinoza, J.; Sholander, P.; Van Leeuwen, B,

    1998-12-01

    This report examines methods of mobile communications with an emphasis on mobile computing and wireless communications. Many of the advances in communications involve the use of Internet Protocol (IP), Asynchronous Transfer Mode (ATM), and ad hoc network protocols. However, many of the advances in these protocols have been focused on wired communications. Recently much focus has been directed at advancing communication technology in the area of mobile wireless networks. This report discusses various protocols used in mobile communications and proposes a number of extensions to existing protocols. A detailed discussion is also included on desirable protocol characteristics and evaluation criteria. In addition, the report includes a discussion on several network simulation tools that maybe used to evaluate network protocols.

  11. Performance Comparison of Mobile Ad Hoc Network Routing Protocol and Transmission Control Protocol

    OpenAIRE

    Akinwole A.K.; Emuoyibofarhe O. J.

    2012-01-01

    In this work the Performance Comparison of Mobile Ad Hoc Network (MANET) Routing Protocols and Transmission Control Protocol (TCP) was investigated in order to evaluate the performance of Routing Protocols (AODV, DSR and TORA) and TCP (Tahoe, Reno and New Reno). The Model that represented the hypothetical network was developed and simulated using OMNet++ 4.1. The three Routing protocols were tested upon each of the three variants of Transmission Control Protocol. End to end throughput was the...

  12. A Streaming Protocol for Memcached

    OpenAIRE

    Li, W.; Zhou, B.; Wang, X.

    2012-01-01

    Memcached is a general-purpose distributed memory caching system that was originally developed by Danga Interactive for Live Journal but is now used by many other sites and It is thought to be one of the most effective solutions to speed up dynamic database-driven websites by caching data and objects in RAM to reduce the number of times that an external data source must be read. Memcached system uses a client-server architecture, it provides its standard memcached protocol to support any type...

  13. New Models for Population Protocols

    CERN Document Server

    Michail, Othon

    2010-01-01

    Wireless sensor networks are about to be part of everyday life. Homes and workplaces capable of self-controlling and adapting air-conditioning for different temperature and humidity levels, sleepless forests ready to detect and react in case of a fire, vehicles able to avoid sudden obstacles or possibly able to self-organize routes to avoid congestion, and so on, will probably be commonplace in the very near future. Mobility plays a central role in such systems and so does passive mobility, that is, mobility of the network stemming from the environment itself. The population protocol model was

  14. Design of Open Core Protocol

    OpenAIRE

    NayabRasool Shaik; Srikanth Pothula

    2011-01-01

    As more and more IP cores are integrated intoan SOC design, the communication flow between IP cores has increased drastically and the efficiency of the on-chip bus has become a dominant factor for the performance of a system. The on-chip bus design can be divided into two parts, namely the interface and the internal architecture of the bus. In this work we adopt the well-defined interface standard, the Open Core Protocol and focus on the design of the internal bus architecture. We develop an ...

  15. Trypanosoma spp. ring test protocol

    International Nuclear Information System (INIS)

    Test material will be chosen by the coordinating lab for incorporation into a proficiency panel after repeated testing by more than one analyst on multiple PCR runs on different days. Test material: suitable test material will be provided. Protocol and laboratory procedures: Each laboratory is allowed to use their own 'in-house' test procedure (SOPs will nevertheless be provided by the respective laboratories for comparison and evaluation). Each PCR should be executed on two separate occasions. Test material used will be coded and sent as a blind panel to the participants. Each participating laboratory will be given a unique set of codes

  16. Superselection rules and quantum protocols

    CERN Document Server

    Kitaev, A; Preskill, J; Kitaev, Alexei; Mayers, Dominic; Preskill, John

    2004-01-01

    We show that superselection rules do not enhance the information-theoretic security of quantum cryptographic protocols. Our analysis employs two quite different methods. The first method uses the concept of a reference system -- in a world subject to a superselection rule, unrestricted operations can be simulated by parties who share access to a reference system with suitable properties. By this method, we prove that if an n-party protocol is secure in a world subject to a superselection rule, then the security is maintained even if the superselection rule is relaxed. However, the proof applies only to a limited class of superselection rules, those in which the superselection sectors are labeled by unitary irreducible representations of a compact symmetry group. The second method uses the concept of the format of a message sent between parties -- by verifying the format, the recipient of a message can check whether the message could have been sent by a party who performed charge-conserving operations. By this...

  17. Optimization of Collection Tree Protocol

    Directory of Open Access Journals (Sweden)

    Harleen Kaur

    2013-06-01

    Full Text Available Collection tree protocol is a tree based protocol which is mainly used for aggregation. It is minimum cost routing tree which selects the path having minimum cost routing gradient. It will generate one or more trees to root which is called base station. When any node has data it sends data up the tree which is forwarded to root.CTP will provide link quality estimation among nearby neighbours. It will indicate number of transmissions from a node to send a packet to destination and whose acknowledgment is successfully received. It sends data to root by choosing a next hop. CTP is having a problem of fast energy depletion which is caused by congestion in the network. Also energy level of the network is not highly scalable. Whenever a node in a network is failed it is not able to do the function and it should not effect on overall network. When more number of nodes are added in the network, congestion will take place and so it does not have an additional energy to choose an optimal path. In revised CTP, to enhance the energy level of a network RSSI is used in broadcast fault tolerant algorithm. RSSI means power received by antenna. CTP suffers a problem by disseminating data statically in network. So in revised CTP line mobility model is integrated which will send data dynamically to sink node.

  18. Design of Open Core Protocol

    Directory of Open Access Journals (Sweden)

    NayabRasool Shaik

    2011-11-01

    Full Text Available As more and more IP cores are integrated intoan SOC design, the communication flow between IP cores has increased drastically and the efficiency of the on-chip bus has become a dominant factor for the performance of a system. The on-chip bus design can be divided into two parts, namely the interface and the internal architecture of the bus. In this work we adopt the well-defined interface standard, the Open Core Protocol and focus on the design of the internal bus architecture. We develop an efficient bus architecture to support most advanced bus functionalities defined in open core protocol , including burst transactions, lock transactions, pipelined transactions, and out-of-order transactions. We first model and design the on-chip bus with transaction level modeling for the consideration of design flexibility and fast simulation speed. We then implement the RTL models of the bus for synthesis and gate-level simulation. Experimental results show that the proposed TLM model is quite efficient for the whole system simulation and the real implementation can significantly save the communication time.

  19. Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars / Resultados de uma combinacao de bleomicina e triamcinolone acetonide no tratamento de queloides e cicatrizes hipertroficas

    Scientific Electronic Library Online (English)

    Francisco Miguel, Camacho-Martinez; Elena Rodriguez, Rey; Francisco Camacho, Serrano; Adriana, Wagner.

    2013-06-01

    Full Text Available Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de [...] bleomicina e acetonido de triancinolona por cm2 (BAT). Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29%) amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores). O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados. Abstract in english While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per [...] cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

  20. Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars Resultados de uma combinação de bleomicina e triamcinolone acetonide no tratamento de quelóides e cicatrizes hipertróficas

    Directory of Open Access Journals (Sweden)

    Francisco Miguel Camacho-Martínez

    2013-06-01

    Full Text Available While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA. In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29% softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids. The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de bleomicina e acetonido de triancinolona por cm2 (BAT. Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29% amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores. O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados.

  1. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.; Rørth, Mikkel; Daugaard, Gedske; Hojman, Pernille

    2014-01-01

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective of...

  2. VANET Routing Protocols: Pros and Cons

    CERN Document Server

    Paul, Bijan; Bikas, Md Abu Naser

    2012-01-01

    VANET (Vehicular Ad-hoc Network) is a new technology which has taken enormous attention in the recent years. Due to rapid topology changing and frequent disconnection makes it difficult to design an efficient routing protocol for routing data among vehicles, called V2V or vehicle to vehicle communication and vehicle to road side infrastructure, called V2I. The existing routing protocols for VANET are not efficient to meet every traffic scenarios. Thus design of an efficient routing protocol has taken significant attention. So, it is very necessary to identify the pros and cons of routing protocols which can be used for further improvement or development of any new routing protocol. This paper presents the pros and cons of VANET routing protocols for inter vehicle communication.

  3. Merging Multiparty Protocols in Multiparty Choreographies

    Directory of Open Access Journals (Sweden)

    Fabrizio Montesi

    2013-02-01

    Full Text Available Choreography-based programming is a powerful paradigm for defining communication-based systems from a global viewpoint. A choreography can be checked against multiparty protocol specifications, given as behavioural types, that may be instantiated indefinitely at runtime. Each protocol instance is started with a synchronisation among the involved peers. We analyse a simple transformation from a choreography with a possibly unbounded number of protocol instantiations to a choreography instantiating a single protocol, which is the merge of the original ones. This gives an effective methodology for obtaining new protocols by composing existing ones. Moreover, by removing all synchronisations required for starting protocol instances, our transformation reduces the number of communications and resources needed to execute a choreography.

  4. Test order effects in simultaneous protocols.

    Science.gov (United States)

    Imam, Abdulrazaq A; Warner, Timothy A

    2014-03-01

    Simultaneous protocols typically yield poorer stimulus equivalence outcomes than do other protocols commonly used in equivalence research. Two independent groups of three 3-member equivalence sets of stimuli were used in conditional discrimination procedures in two conditions, one using the standard simultaneous protocol and the other using a hybrid simultaneous training and simple-to-complex testing. Participants completed the two conditions in one long session in Experiment 1, but in separate sessions in Experiment 2. The same stimulus sets used in Experiment 1 were randomized for the two conditions in Experiment 2. Overall, accuracy was better with the hybrid than with the standard protocol in both experiments. The equivalence yield was also better under the hybrid than under the standard protocol in each experiment. The results suggest that the order of testing for emergent relations may account for the difficulty often encountered with the standard simultaneous protocol. PMID:24272620

  5. DAQ architecture and read-out protocole

    CERN Document Server

    Harris, F; Jost, B; Mato, P; Mato, Pere

    1998-01-01

    The proposed LHCb readout architecture is overviewed, followed by discussion and comparison of two candidate readout protocols, namely the 'Full Readout' and'Phased Readout' protocols.The philosophy of the Full Readout protocol is to send all of the event data to a processor before commencing the high level trigger algorithms.This results in simplicity in the protocol at the cost of the bandwidth requirement for the readout network. This is our preferred approach if the network costs are not prohibitive. Using the Phased Readout protocol the event data is sent in portions according to the demands of the trigger algorithms. This results in a more complex protocol, but in a reduction on the readout network bandwidth requirement.The effect of transmission errors on the behaviour of the system, and the implementation of system partitioning, are also discussed.1

  6. Software for simulating IMRT protocol

    International Nuclear Information System (INIS)

    The Intensity Modulated Radiation Therapy - IMRT is an advanced technique to cancer treatment widely used on oncology around the world. The present paper describes the SOFT-RT software which is a tool for simulating IMRT protocol. Also, it will be present a cerebral tumor case of studied in which three irradiation windows with distinct orientation were applied. The SOFT-RT collect and export data to MCNP code. This code simulates the photon transport on the voxel model. Later, a out-module from SOFT-RT import the results and express the dose-response superimposing dose and voxel model in a tree-dimensional graphic representation. The present paper address the IMRT software and its function as well a cerebral tumor case of studied is showed. The graphic interface of the SOFT-RT illustrates the example case. (author)

  7. Fetal MRI: techniques and protocols

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Neuroradiology, University Clinics of Radiodiagnostics, Medical University Vienna, Waehringerguertel 18-10, 1090, Vienna (Austria); Brugger, Peter Christian [Department of Anatomy, Integrative Morphology Group, Medical University Vienna (Austria); Prayer, Lucas [Diagnosezentrum Urania, Vienna (Austria)

    2004-09-01

    The development of ultrafast sequences has led to a significant improvement in fetal MRI. Imaging protocols have to be adjusted to the rapidly developing fetal central nervous system (CNS) and to the clinical question. Sequence parameters must be changed to cope with the respective developmental stage, to produce images free from motion artefacts and to provide optimum visualization of the region and focus of interest. In contrast to postnatal studies, every suspect fetal CNS abnormality requires examination of the whole fetus and the extrafetal intrauterine structures including the uterus. This approach covers both aspects of fetal CNS disorders: isolated and complex malformations and cerebral lesions arising from the impaired integrity of the feto-placental unit. (orig.)

  8. Fetal MRI: techniques and protocols

    International Nuclear Information System (INIS)

    The development of ultrafast sequences has led to a significant improvement in fetal MRI. Imaging protocols have to be adjusted to the rapidly developing fetal central nervous system (CNS) and to the clinical question. Sequence parameters must be changed to cope with the respective developmental stage, to produce images free from motion artefacts and to provide optimum visualization of the region and focus of interest. In contrast to postnatal studies, every suspect fetal CNS abnormality requires examination of the whole fetus and the extrafetal intrauterine structures including the uterus. This approach covers both aspects of fetal CNS disorders: isolated and complex malformations and cerebral lesions arising from the impaired integrity of the feto-placental unit. (orig.)

  9. E-Cash Payment Protocols

    Directory of Open Access Journals (Sweden)

    Shweta Srivastava

    2012-09-01

    Full Text Available E-cash is a payment system designed and implemented for making purchases over open networks such as the Internet. Need of a payment system which enables the electronic transactions are growing at the same time that the use of Internet is growing in our daily life. Present days electronic payment systems have a major problem, they cannot handle the security and the users anonymity and at the same time these systems are secure on the cost of their users anonymity. This paper shows the payment protocols for digital cash and discusses how a digital cash system can be formed by presenting a few of the present days digital cash systems in details. We also provide a comparison and determine them together to see which one of them fulfils the properties for digital cash and the required security level.

  10. Automation of Network Protocol Analysis

    Directory of Open Access Journals (Sweden)

    keerthi Manchikanti, J Shiva Prashanth, Vishnu Murthy G

    2012-06-01

    Full Text Available This paper “Automation of Network Protocol Analysis” is mainly aimed to automate the entire process. Starting from sniffing the network packets till the validation of it has been taken care. Here we have automated the logging part through a C program. Whenever packets will be transmitted from a system, Ethereal/Wireshark will be automatically invoked and start capturing the network packets. That will be stored in .pcap format automatically. To validate the contents the logic has been implemented to check particular pattern of packets or any specific string. The .pcap format will be converted into a text format so that the validation can be accomplished through parsing the entire Ethereal/Wireshark log. Based upon the parsing logic, pass/fail verdict will be indicated to user. The logic can always be extended depending upon the project requirements. The performance of the network is also calculated.

  11. [Climate change and Kyoto protocol].

    Science.gov (United States)

    Ergasti, G; Pippia, V; Murzilli, G; De Luca D'Alessandro, E

    2009-01-01

    Due to industrial revolution and the heavy use of fossil fuels, the concentration of greenhouse gases in the atmosphere has increased dramatically during the last hundred years, and this has lead to an increase in mean global temperature. The environmental consequences of this are: the melting of the ice caps, an increase in mean sea-levels, catastrophic events such as floodings, hurricanes and earthquakes, changes to the animal and vegetable kingdoms, a growth in vectors and bacteria in water thus increasing the risk of infectious diseases and damage to agriculture. The toxic effects of the pollution on human health are both acute and chronic. The Kyoto Protocol is an important step in the campaign against climatic changes but it is not sufficient. A possible solution might be for the States which produce the most of pollution to adopt a better political stance for the environment and to use renewable resources for the production of energy. PMID:19798904

  12. Analysing Protocol Stacks for Services

    DEFF Research Database (Denmark)

    Gao, Han; Nielson, Flemming

    2011-01-01

    We show an approach, CaPiTo, to model service-oriented applications using process algebras such that, on the one hand, we can achieve a certain level of abstraction without being overwhelmed by the underlying implementation details and, on the other hand, we respect the concrete industrial standards used for implementing the service-oriented applications. By doing so, we will be able to not only reason about applications at different levels of abstractions, but also to build a bridge between the views of researchers on formal methods and developers in industry. We apply our approach to the financial case study taken from Chapter 0-3. Finally, we develop a static analysis to analyse the security properties as they emerge at the level of concrete industrial protocols.

  13. Desynchronization Attacks on RFID Security Protocols

    OpenAIRE

    Miaolei Deng; Weijun Zhu

    2013-01-01

    The characteristics of radio frequency identification (RFID) systems introduce growing security and privacy concerns. RFID systems need security protocols to provide confidentiality, user privacy, mutual authentication and etc. Many security protocols for the RFID system have been presented. This paper analyze several of the newest RFID security protocols which proposed by Niu et al., Fu et al. and Habibi et al. respectively form the security viewpoint of data desynchronization attack. These ...

  14. VANET Routing Protocols: Pros and Cons

    OpenAIRE

    Paul, Bijan; IBRAHIM, MD.; Bikas, Md. Abu Naser

    2012-01-01

    VANET (Vehicular Ad-hoc Network) is a new technology which has taken enormous attention in the recent years. Due to rapid topology changing and frequent disconnection makes it difficult to design an efficient routing protocol for routing data among vehicles, called V2V or vehicle to vehicle communication and vehicle to road side infrastructure, called V2I. The existing routing protocols for VANET are not efficient to meet every traffic scenarios. Thus design of an efficient routing protocol h...

  15. SCRUTINY OF BROADCASTING PROTOCOLS IN VANET

    OpenAIRE

    Rohini Nere; Uma Nagaraj

    2015-01-01

    Definitive broadcasting in vehicular ad hoc networks is the key to success for various services and applications on an intelligent transportation system. Many trusted broadcasting protocols have been proposed but none of them has been evaluated in realistic scenario. In this paper, we discuss these reliable broadcasting protocols on VANET. Basic mechanism in broadcasting, and also we are providing collective research of Broadcasting protocols in vanet in that some real time protoc...

  16. Failure of Kak quantum key distribution protocol

    Indian Academy of Sciences (India)

    Ching-Nung Yang; Su-Hsuan Chu; Bing-Ling Lu

    2005-01-01

    Kak's quantum key distribution (QKD) protocol provides not only the distribution but also the integrity of secret key simultaneously in quantum channel. Consequently the additional exchange of information, used to check whether an eavesdropper exists, is unnecessary. In this comment, we will point out the failure of Kak's protocol and show that Kak's protocol does not have the joint distribution and integration that the author declares in [1].

  17. Emission trading under the Kyoto Protocol

    OpenAIRE

    Holtsmark, Bjart; Hagem, Cathrine

    2003-01-01

    On 11 December 1997, delegates to the third conference of the Parties to the UN Framework Convention on Climate Change agreed upon the Kyoto Protocol. The protocol sets binding emission targets for developed nations (Annex B countries). The Protocol states that Annex B countries may participate in emission trading. The rules for emission trading are to be discussed at the fourth Conference of the Parties in November 1998. differentiation of targets among countries, but not in any systematic...

  18. Analysing ZigBee Key Establishment Protocols

    OpenAIRE

    Yüksel, Ender

    2012-01-01

    In this report, we present our approach for protocol analysis together with a real example where we find an important flow in a contemporary wireless sensor network security protocol. We start by modelling protocols using a specific process algebraic formalism called LySa process calculus. We then apply an analysis based on a special program analysis technique called control flow analysis. We apply this technique to the ZigBee-2007 End-to-End Application Key Establishment Pr...

  19. Medium Access Control Protocols for Wireless ATM

    Directory of Open Access Journals (Sweden)

    A. Cizmar

    1999-06-01

    Full Text Available The most crucial issues in the conception of an efficient wireless ATM network are the design of the physical layer, data link layer. Medium Access Control (MAC protocol and mobility management functions. In this article we focus on MAC protocols, namely on requirements for MAC protocols and on basic concepts of TDMA and CDMA based one. For illustration we consider with Time Division Duplex (TDD as well as Frequency Division Duplex (FDD.

  20. Control protocols for the UNK control system

    Energy Technology Data Exchange (ETDEWEB)

    Elin, A. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Kopylov, L. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Matyushin, A. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Mikheev, M. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Scherbakov, E. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Trofimov, N. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Yourpalov, V. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation)); Zelepoukin, S. (Institute for High Energy Physics, 142284 Protvino, Moscow region (Russian Federation))

    1994-12-15

    Conceptual studies on control protocols have been carried out for a few years in the framework of the CERN-IHEP collaboration on accelerator control. Generalized equipment models were used for the control protocol definition for the UNK control system. The paper presents a general approach to the implementation of the protocol adopted for the UNK control system and first results of prototyping on the UNK beam transfer line equipment. ((orig.))

  1. ANALYSIS OF THE PROTECTED EXTENSIBLE AUTHENTICATION PROTOCOL

    OpenAIRE

    Amit Rana; Dr. Rajender Singh Chhillar

    2012-01-01

    The Internet Engineering Task Force (IETF) has proposednew protocols for highly secured wireless networking. Thepurpose of this paper is to implement one such proposedsecurity protocol - PEAP (Protected ExtensibleAuthentication Protocol) [1]. PEAP was jointly developedby Microsoft, Cisco and RSA security. The protocolimplementation is done on the server end of a Client/Servernetwork model on a RADIUS server (RemoteAuthentication Dial-in User Service). The proposedprotocol - PEAP provides for ...

  2. Hybrid Technique For Secure Sum Protocol

    OpenAIRE

    Priyanka Jangde; Gajendra Singh Chandel; Durgesh Kumar Mishra

    2011-01-01

    Secure Multiparty Computation (SMC) allows parties to compute the combine result of their individual data without revealing their data to others. Secure sum computation is one of the important tool of the SMC. On SMC many eminent researchers give their protocols especially in secure sum computation, researchers show their interest. In this paper we provide unique hybrid protocol for secure sum computation which is the combination of Ideal and Real Model. This protocol provides zero data leaka...

  3. Wireless sensors networks MAC protocols analysis

    OpenAIRE

    Lamia CHAARI; Lotfi KAMOUN

    2010-01-01

    Wireless sensors networks performance are strictly related to the medium access mechanism. An effective one, require non-conventional paradigms for protocol design due to several constraints. An adequate equilibrium between communication improvement and data processing capabilities must be accomplished. To achieve low power operation, several MAC protocols already proposed for WSN. The aim of this paper is to survey and to analyze the most energy efficient MAC protocol in or...

  4. Verifiable Protocol Design for Agent Argumentation Dialogues

    OpenAIRE

    Moschoyiannis, S.; Krause, P; Bryant, D; McBurney, P.

    2009-01-01

    We describe a formal approach to protocol design for dialogues between autonomous agents in a digital ecosystem that involve the exchange of arguments between the participants. We introduce a vector language-based representation of argumentation protocols, which captures the interplay between different agentspsila moves in a dialogue in a way that (a) determines the legal moves that are available to each participant, in each step, and (b) records the dialogue history. We use UML protocol stat...

  5. Reactive Networking using Dynamic Link Exchange Protocol

    OpenAIRE

    Nilsson, Kim

    2014-01-01

    This master thesis studies the possibilities of using a radio-router protocol in order to increase the quality of service in dynamic tactical network environments. We cover three radio-router protocols with emphasis on Dynamic Link Exchange Protocol (DLEP). Many applications, such as voice and video communication, have bandwidth and latency requirements which need to be fulfilled in order to provide a sufficient level of quality. This poses a problem in tactical network environments where lin...

  6. Optimizing One Fair Document Exchange Protocol

    OpenAIRE

    Alaraj, Abdullah M.

    2012-01-01

    This paper presents an efficient fair document exchange protocol. The exchange of the documents will be between two parties. The protocol is based on the verifiable and recoverable encryption of a document's key. This verifiable and recoverable encryption of the document's key will allow one party to verify the encrypted key. It will also ensure this party that the Semi Trusted Third Party will be able to recover the key if the other party misbehaves. The protocol also incor...

  7. Bitcoin-NG: A Scalable Blockchain Protocol

    OpenAIRE

    Eyal, Ittay; Gencer, Adem Efe; Sirer, Emin Gun; Renesse, Robbert van

    2015-01-01

    Cryptocurrencies, based on and led by Bitcoin, have shown promise as infrastructure for pseudonymous online payments, cheap remittance, trustless digital asset exchange, and smart contracts. However, Bitcoin-derived blockchain protocols have inherent scalability limits that trade-off between throughput and latency and withhold the realization of this potential. This paper presents Bitcoin-NG, a new blockchain protocol designed to scale. Based on Bitcoin's blockchain protocol, Bitcoin-NG is By...

  8. Using Image Attributes for Human Identification Protocols

    OpenAIRE

    Jameel, Hassan; Lee, Heejo; Lee, Sungyoung

    2007-01-01

    A secure human identification protocol aims at authenticating human users to a remote server when even the users' inputs are not hidden from an adversary. Recently, the authors proposed a human identification protocol in the RSA Conference 2007, which is loosely based on the ability of humans to efficiently process an image. The advantage being that an automated adversary is not effective in attacking the protocol without human assistance. This paper extends that work by trying to solve some ...

  9. Comparison of on Demand Routing Protocols

    OpenAIRE

    Bharat Bhushan; Shailender Gupta; C.K.Nagpal

    2013-01-01

    A routing protocol is used to facilitate communication in ad hoc network. The primary goal of such a routing protocol is to provide an efficient and reliable path between a pair of nodes. The routing protocols for ad hoc network can be categorized into three categories: table driven, on demand and hybrid routing. The table driven and hybrid routing strategies require periodic exchange of hello messages between nodes of the ad hoc network and thus have high processing and bandwidth requirement...

  10. Security Attacks On MANET Routing Protocols

    Directory of Open Access Journals (Sweden)

    Chiragkumar V. Patel

    2013-10-01

    Full Text Available The paper gives idea about various routing protocols for Mobile Ad-Hoc Network against security issues. MANET is vulnerable to various security attacks due to its dynamically changing topology, self configurable nature and lack of centralized control. Malicious node can significantly degrade the performance and reliability of Ad-hoc Network routing protocols. From the survey it has been made quite clear that basic MANET protocols are vulnerable to various routing attacks. While Secure AODV (SAODV routing protocol performs quite well to improve performance in presence of security attack in MANET.

  11. Mac protocols for cyber-physical systems

    CERN Document Server

    Xia, Feng

    2015-01-01

    This book provides a literature review of various wireless MAC protocols and techniques for achieving real-time and reliable communications in the context of cyber-physical systems (CPS). The evaluation analysis of IEEE 802.15.4 for CPS therein will give insights into configuration and optimization of critical design parameters of MAC protocols. In addition, this book also presents the design and evaluation of an adaptive MAC protocol for medical CPS, which exemplifies how to facilitate real-time and reliable communications in CPS by exploiting IEEE 802.15.4 based MAC protocols. This book wil

  12. Secure Key Management Protocol in WIMAX

    Directory of Open Access Journals (Sweden)

    Noudjoud Kahya

    2012-12-01

    Full Text Available The Worldwide Interoperability for Microwave Access (WIMAX /IEEE 802.16, is new technology basedon wireless metropolitan area network. Security of connections access in WIMAX /IEEE 802.16 iscomplete with respect to the Privacy Key Management (PKM protocol. The protocol is responsible forproviding the secure distribution of keying data from Base Station (BS to Subscriber Station (SS. In thispaper we provide the formal analysis of PKMv2 using Scyther tool to verify the security properties. Wefound that PKMv2 is vulnerable to replay, DoS, Man-in-the middle attacks. At last we have proposed asecure protocol (SPKM to prevent the authorization protocol from such attacks.

  13. Traffic Performance Analysis of Manet Routing Protocol

    CERN Document Server

    Rajeswari, S; 10.5121/ijdps.2011.2306

    2011-01-01

    The primary objective of this research work is to study and investigate the performance measures of Gossip Routing protocol and Energy Efficient and Reliable Adaptive Gossip routing protocols. We use TCP and CBR based traffic models to analyze the performance of above mentioned protocols based on the parameters of Packet Delivery Ratio, Average End-to-End Delay and Throughput. We will investigate the effect of change in the simulation time and Number of nodes for the MANET routing protocols. For Simulation, we have used ns-2 simulator.

  14. Equilibria of Generalized Cut and Choose Protocols

    DEFF Research Database (Denmark)

    Branzei, Simina; Caragiannis, Ioannis; Kurokawa, David; Procaccia, Ariel

    computational model and reasoning about the game-theoretic properties of algorithms that operate in this model. Specifically, we show that each protocol in the class of generalized cut and choose (GCC) protocols — which includes the most important discrete cake cutting protocols — is guaranteed to have...... stronger fairness notion of envy-freeness. Finally, we show that under an obliviousness restriction, which still allows the computation of approximately envy-free allocations, GCC protocols are guaranteed to have exact subgame perfect Nash equilibria...

  15. Entangled and sequential quantum protocols with dephasing

    CERN Document Server

    Boixo, Sergio

    2011-01-01

    Sequences of commuting quantum operators can be parallelized using entanglement. This transformation is behind some optimal quantum metrology protocols and recent results on quantum circuit complexity. We show that dephasing quantum maps in arbitrary dimension can also be parallelized. This implies that for general dephasing noise the protocol with entanglement is not more fragile than the corresponding sequential protocol and, conversely, the sequential protocol is not less effective than the entangled one. We derive this result diagrammatically, in the language of string diagrams in dagger compact closed categories. Therefore, it applies verbatim to other theories.

  16. Wireless sensors networks MAC protocols analysis

    CERN Document Server

    Chaari, Lamia

    2010-01-01

    Wireless sensors networks performance are strictly related to the medium access mechanism. An effective one, require non-conventional paradigms for protocol design due to several constraints. An adequate equilibrium between communication improvement and data processing capabilities must be accomplished. To achieve low power operation, several MAC protocols already proposed for WSN. The aim of this paper is to survey and to analyze the most energy efficient MAC protocol in order to categorize them and to compare their performances. Furthermore we have implemented some of WSN MAC protocol under OMNET++ with the purpose to evaluate their performances.

  17. Cryptanalysis of an Authentication Key Exchange Protocol

    Directory of Open Access Journals (Sweden)

    Chou-Chan Yang

    2005-01-01

    Full Text Available An authenticated multiple-key agreement protocol uses a digital signature to sign the Diffie-Hellman public keys which can generate multiple session key in a single round of message exchange and achieve mutual authentication. Recently, Hwang et al. proposed an authentication key exchange protocol which takes less computation time than Harn and Lin;s protocol. However, this study, shows that Hwang et al.`s protocol is vulnerable to forgery attacks. An attacker can fool one communication part into believing the forged short-term public keys and share session keys with him.

  18. Multimode Communication Protocols Enabling Reconfigurable Radios

    Directory of Open Access Journals (Sweden)

    Berlemann Lars

    2005-01-01

    Full Text Available This paper focuses on the realization and application of a generic protocol stack for reconfigurable wireless communication systems. This focus extends the field of software-defined radios which usually concentrates on the physical layer. The generic protocol stack comprises common protocol functionality and behavior which are extended through specific parts of the targeted radio access technology. This paper considers parameterizable modules of basic protocol functions residing in the data link layer of the ISO/OSI model. System-specific functionality of the protocol software is realized through adequate parameterization and composition of the generic modules. The generic protocol stack allows an efficient realization of reconfigurable protocol software and enables a completely reconfigurable wireless communication system. It is a first step from side-by-side realized, preinstalled modes in a terminal towards a dynamic reconfigurable anymode terminal. The presented modules of the generic protocol stack can also be regarded as a toolbox for the accelerated and cost-efficient development of future communication protocols.

  19. Efficient secure two-party protocols

    CERN Document Server

    Hazay, Carmit

    2010-01-01

    The authors present a comprehensive study of efficient protocols and techniques for secure two-party computation -- both general constructions that can be used to securely compute any functionality, and protocols for specific problems of interest. The book focuses on techniques for constructing efficient protocols and proving them secure. In addition, the authors study different definitional paradigms and compare the efficiency of protocols achieved under these different definitions.The book opens with a general introduction to secure computation and then presents definitions of security for a

  20. Wind power agreement protocol; Protocole d'accord eolien

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-10-01

    The aim of this protocol of agreement is to propose to wind turbine fitters some models of contracts allowing the setting up of wind turbines on agricultural lots. These documents, which make an indissociable ensemble, apply to both phases of development of a wind power project: the feasibility study phase, for a duration comprised between 2 and 5 years (studies, administrative procedures, precise definition of the project), and the construction, exploitation and dismantling phase. These documents will serve as common guidelines for both the farmers and the wind turbine designers. Both parties agree to meet together in the future to propose some modifications of these texts if necessary. The four models of contracts are attached to the document: contract for the feasibility study phase, first contract between the landlord and the farmer for the cancellation of the rural lease, second contract between the landlord and the wind power exploitation company for the common right lease, and the third contract between the farmer and the wind power company for the indemnification convention. (J.S.)