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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

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske;

    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)....

  2. Bleomycin-induced pulmonary fibrosis after tumor lysis syndrome in a case of advanced yolk sac tumor treated with bleomycin, etoposide and cisplatin (BEP) chemotherapy.

    Science.gov (United States)

    Doi, Mihoko; Okamoto, Yohei; Yamauchi, Masami; Naitou, Hiroyuki; Shinozaki, Katsunori

    2012-10-01

    Ovarian yolk sac tumor (YST) is a highly aggressive malignancy arising in young women. Chemotherapy has dramatically improved the prognosis, and bleomycin, etoposide, and cisplatin (BEP) combination chemotherapy appears to be the most effective combination regimen. A 23-year-old woman was admitted to our hospital with worsening abdominal distention and a lower abdominal mass. She was diagnosed with a stage IIIc pure YST of the right ovary, and right salpingo-oophorectomy was performed; there were numerous disseminated peritoneal tumors within the abdominal cavity. A few days postoperatively, massive ascites developed, and right hydronephrosis occurred. Chemotherapy with BEP was started, and after 24 h of administration, oliguria and tumor lysis syndrome (TLS) developed. Continuous hemodiafiltration was started, and hemodialysis was initiated following full-dose standard cisplatin and etoposide on days 2-5 of the 1st cycle. After the electrolyte abnormalities and the elevation of creatinine became normal, the patient received an additional three cycles of BEP and achieved complete remission. However, she also suffered from severe non-hematological toxicities, including grade 3 left ventricular dysfunction and grade 4 pulmonary fibrosis. In the case of rapidly progressing and high-volume YST treated with BEP chemotherapy, special attention should be paid to bleomycin-induced pulmonary toxicity following TLS. Further study is required to optimize drug exposure to ensure efficacy and reduce the risk of side effects in this population. PMID:22127348

  3. Bleomycin cardiotoxicity during chemotherapy for an ovarian germ cell tumor

    OpenAIRE

    Didagelos, M; Boutis, A; Diamantopoulos, N; Sotiriadou, M; Fotiou, C

    2013-01-01

    Introduction: Platinum-based chemotherapeutic regimens, including BEP (bleomycin, etoposide, cisplatin) represent the standard of care, first line therapy in non-epithelial ovarian tumours. Cardiovascular toxicity is a rare adverse effect of bleomycin.

  4. Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

    OpenAIRE

    Ahitagni Biswas; Pramod Kumar Julka

    2016-01-01

    Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13 year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the...

  5. 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;

    2016-01-01

    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......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...... of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. PATIENTS AND METHODS: All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured...

  6. Beamed-Energy Propulsion (BEP) Study

    Science.gov (United States)

    George, Patrick; Beach, Raymond

    2012-01-01

    The scope of this study was to (1) review and analyze the state-of-art in beamed-energy propulsion (BEP) by identifying potential game-changing applications, (2) formulate a roadmap of technology development, and (3) identify key near-term technology demonstrations to rapidly advance elements of BEP technology to Technology Readiness Level (TRL) 6. The two major areas of interest were launching payloads and space propulsion. More generally, the study was requested and structured to address basic mission feasibility. The attraction of beamed-energy propulsion (BEP) is the potential for high specific impulse while removing the power-generation mass. The rapid advancements in high-energy beamed-power systems and optics over the past 20 years warranted a fresh look at the technology. For launching payloads, the study concluded that using BEP to propel vehicles into space is technically feasible if a commitment to develop new technologies and large investments can be made over long periods of time. From a commercial competitive standpoint, if an advantage of beamed energy for Earth-to-orbit (ETO) is to be found, it will rest with smaller, frequently launched payloads. For space propulsion, the study concluded that using beamed energy to propel vehicles from low Earth orbit to geosynchronous Earth orbit (LEO-GEO) and into deep space is definitely feasible and showed distinct advantages and greater potential over current propulsion technologies. However, this conclusion also assumes that upfront infrastructure investments and commitments to critical technologies will be made over long periods of time. The chief issue, similar to that for payloads, is high infrastructure costs.

  7. Impact of Bep or Carboplatin Chemotherapy on Testicular Function and Sperm Nucleus of Subjects with Testicular Germ Cell Tumor.

    Science.gov (United States)

    Ghezzi, Marco; Berretta, Massimiliano; Bottacin, Alberto; Palego, Pierfrancesco; Sartini, Barbara; Cosci, Ilaria; Finos, Livio; Selice, Riccardo; Foresta, Carlo; Garolla, Andrea

    2016-01-01

    Young males have testicular germ cells tumors (TGCT) as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO), the treatment of TGCT may include surveillance, radiotherapy, or chemotherapy (CT), basing on tumor histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis, and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide, and cisplatin (BEP), after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group), 54 with carboplatin (CARB group), and 58 were just surveilled (S-group). All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0) and after 12 (T1) and 24 months (T2) from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones, and testicular volume at baseline were not different between groups. At T1, we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S-group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S-group and Carb group. These alterations were persistent after 2 years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after 1 and 2 years from the end of treatment. Despite

  8. IMPACT OF BEP OR CARBOPLATIN CHEMOTHERAPY ON TESTICULAR FUNCTION AND SPERM NUCLEUS OF SUBJECTS WITH TESTICULAR GERM CELL TUMOR

    Directory of Open Access Journals (Sweden)

    Marco eGhezzi

    2016-05-01

    Full Text Available Young males have testicular germ cells tumours (TGCT as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO, the treatment of TGCT may include surveillance, radiotherapy or chemotherapy (CT, basing on tumour histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide and cisplatin (BEP, after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group, 54 with carboplatin (Carb group and 58 were just surveilled (S-group. All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0 and after 12 (T1 and 24 months (T2 from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones and testicular volume at baseline were not different between groups. At T1 we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S- group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S group and Carb group. These alterations were persistent after two years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after one and two years from the end of treatment

  9. 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; Aass, N;

    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-progno...

  10. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report.

    Science.gov (United States)

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María Del; Casero, Miguel Angel Racionero

    2016-01-01

    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A monitoring of pulmonary function is not routinely recommended for detecting BPT, although together with carefully assessment for symptoms or signs suggestive of pulmonary toxicity is the best way to reduce the risk of BPT. The frequency of pulmonary events in older patients makes us to think about the possibility of either reduce the dose of bleomycin or removing it from the BEP in ovarian GCT. PMID:27330950

  11. Protective effects of a bacterially expressed NIF-KGF fusion protein against bleomycin-induced acute lung injury in mice.

    Science.gov (United States)

    Li, Xinping; Li, Shengli; Zhang, Miaotao; Li, Xiukun; Zhang, Xiaoming; Zhang, Wenlong; Li, Chuanghong

    2010-08-01

    Current evidence suggests that the keratinocyte growth factor (KGF) and the polymorphonuclear leukocyte may play key roles in the development of lung fibrosis. Here we describe the construction, expression, purification, and identification of a novel NIF (neutrophil inhibitory factor)-KGF mutant fusion protein (NKM). The fusion gene was ligated via a flexible octapeptide hinge and expressed as an insoluble protein in Escherichia coli BL21 (DE3). The fusion protein retained the activities of KGF and NIF, as it inhibited both fibroblast proliferation and leukocyte adhesion. Next, the effects of NKM on bleomycin-induced lung fibrosis in mice were examined. The mice were divided into the following four groups: (i) saline group; (ii) bleomycin group (instilled with 5 mg/kg bleomycin intratracheally); (iii) bleomycin plus dexamethasone (Dex) group (Dex was given intraperitoneally (i.p.) at 1 mg/kg/day 2 days prior to bleomycin instillation and daily after bleomycin instillation until the end of the treatment); and (iv) bleomycin plus NKM group (NKM was given i.p. at 2 mg/kg/day using the same protocol as the Dex group). NKM significantly improved the survival rates of mice exposed to bleomycin. The marked morphological changes and increased hydroxyproline levels resulted from the instillation of bleomycin (on Day 17) in the lungs were significantly inhibited by NKM. These results revealed that NKM can attenuate bleomycin-induced lung fibrosis, suggesting that NKM could be used to prevent bleomycin-induced lung damage or other interstitial pulmonary fibrosis.

  12. 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 α-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

  13. 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.

  14. Nuclear Waste Disposal in Space: BEP's Best Hope?

    International Nuclear Information System (INIS)

    The best technology is worthless if it cannot find a market Beam energy propulsion (BEP) is a very promising technology, but faces major competition from less capable but fully developed conventional rockets. Rockets can easily handle projected markets for payloads into space. Without a new, huge demand for launch capability, BEP is unlikely to gain the resources it needs for development and application. Launching tens of thousands of tons of nuclear waste into space for safe and permanent disposal will provide that necessary demand while solving a major problem on earth. Several options exist to dispose of nuclear waste, including solar orbit, lunar orbit, soft lunar landing, launching outside the solar system, and launching into the sun

  15. Bleomycin clinical pharmacology by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Hall, S.W.; Strong, J.E.; Broughton, A.; Frazier, M.L.; Benjamin, R.S.

    1982-01-01

    Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m/sup 2/ and the volume of distribution was 13.2 l/m/sup 2/. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m/sup 2/ and the volume of distribution was 19.2 l/m/sup 2/. Bleomycin plasma clearance correlated well with serum creatinine (r/sup 2/=0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.

  16. Bleomycin-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Tomás Reinert

    2013-01-01

    Full Text Available Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

  17. 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.)

  18. 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......) direct injection into brain tissue or cysts. There were two main indications for the use of bleomycin directly into the brain: (i) cystic tumors in the form of craniopharyngiomas and (ii) solid brain tumors such as glioblastomas and astrocytomas. The most frequent adverse effects reported were transient...

  19. 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.

  20. Photochemical internalization of bleomycin for glioma treatment

    Science.gov (United States)

    Mathews, Marlon S.; Blickenstaff, Joseph W.; Shih, En-Chung; Zamora, Genesis; Vo, Van; Sun, Chung-Ho; Hirschberg, Henry; Madsen, Steen J.

    2012-05-01

    We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS2a-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS2a (PDT effect), bleomycin (chemotherapy effect), or AlPcS2a+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5 J/cm2 @ 5 mW/cm2) AlPcS2a-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1 μg/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5 J/cm2 together with 0.25 μg/ml bleomycin resulted in approximately 20% and 18% survival of F98 rat glioma cells and human glioma spheroids, respectively. These results show that AlPcS2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

  1. EXPRESSION PATTERN OF LUNG CANCER RELATED GENES IN MALIGNANT TRANSFORMATION OF BEP2D

    Institute of Scientific and Technical Information of China (English)

    范保星; 张开泰; 李刚; 谢玲; 马淑华; 葛世丽; 项小琼; 胡迎春; 王升启; 周平坤; 吴德昌

    2002-01-01

    Objective: To detect the expression difference of 60 lung cancer associated genes in human bronchial epithelial malignant transformation cell model (BEP2D) induced by alpha-particles. Methods: 60 lung cancer associated genes were collected and micro-arrayed onto the microscope slides using Cartesian PixSys5500 cDNA Microarray machine. Total RNA from BEP2D cells and passage 20 (Rl5H-20), passage 35 (R15H-35) cells derived from BEP2D following 1.5 Gy alpha-particles was extracted and labeled by fluorescent dye. The labeled probe was then hybridized with the cDNA. Results: 40, 47, 20 genes were detected in BEP2D, R15H-20 and R15H-35 respectively. The expression level of tumor suppressor genes decreased greatly in the transformed R15H-35. Most oncogenes decreased slightly in R15H-20. Most growth factors expressed only in R15H-20. Conclusion: In human bronchial epithelial malignant transformed cell model generated by alpha-particles, the loss-function of tumor suppressor genes at initiation stage was dominant, some related oncogenes and growth factors promoted the malignant transformation.

  2. Serial Analysis of Gene Expression in Immortalized BEP2D Cells and Malignant Transformed BEP2D Cells Induced by α-particle%SAGE方法分析永生化BEP2D细胞及α粒子诱发恶性转化BEP2D细胞的基因表达

    Institute of Scientific and Technical Information of China (English)

    葛世丽; 李刚; 陈伟; 楼铁柱; 吴德昌

    2001-01-01

    目的:采用基因表达系列分析(serialanalysisofgeneexpression,SAGE)方法,分析永生化BEP2D细胞及α粒子诱发恶性转化BEP2D细胞的基因表达。方法:细胞培养,收获永生化BEP2D细胞及α粒子诱发恶性转化BEP2D细胞;提取细胞总RNA,分离mRNA,合成生物素标记的双链cDNA;采用SAGE方法获取标签序列,结合UniGene文库分析标签代表的转录本,最终通过SAGE软件分析标签丰度,比较两组细胞基因表达差异。选取SAGE实验得到的在两组细胞中表达的已知基因Smad7和CCR11,以RTPCR方法制备探针,用两组细胞等量总RNA为样本,做Northernblot杂交。结果:建立了2个独立的SAGE文库。一个是1.5Gyα粒子照射诱发恶性转化BEP2D细胞的SAGE文库,一个是永生化BEP2D细胞SAGE文库。从2个文库中分别挑取克隆53个、50个,进行测序,测序一共得到总标签2331个,代表单一转录本252个,有70%的SAGE标签可找到与之一一对应的基因,有84个核糖体蛋白基因,约占33%;有12个转录本(4.8%)找不到与之理想匹配的已知基因;2个SAGE文库间,大多数基因表达丰度相近。对2个SAGE文库进行比较发现有在永生化细胞中高表达的基因,也有在恶转细胞中高表达的基因。Northernblot杂交证实SAGE方法得到的TGFβ诱导的Smad7基因在恶转BEP2D细胞中表达略高,化学激活物受体CCR11基因在永生化BEP2D细胞高表达。结论:(1)现有SAGE结果给出两组细胞基因表达丰度及表达差异的趋势。(2)SAGE方法结合Northernblot杂交,证实TGFβ诱导的Smad7基因在恶转BEP2D细胞中表达略高,化学激活物受体CCR11基因在永生化BEP2D细胞高表达。提示Smad7基因参与细胞恶转,CCR11基因对维持细胞正常生长有作用。(3)SAGE方法同时定量比较两组或两组以上mRNA间基因表达水平,简便、快捷,尤其适于筛查

  3. Functional characterization of "Bartonella" effector protein - BepE during "in vivo" and "in vitro" infection

    OpenAIRE

    Okujava, Rusudan

    2013-01-01

    The bartonellae is a family of gram-negative, fastidious, facultative intracellular, zoonotic bacteria. Most of the Bartonella species are highly adapted to establish asymptomatic bacteremia of their reservoir host within which the bacteria colonize erythrocytes as privileged host niche and develop long-lasting persistent infections. Bartonella uses a VirB type IV secretion system (T4SS) to translocate Bartonella effector proteins (Beps) into the infected cells. By using such a tool box it su...

  4. 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)

  5. Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; FENG Yu-lin; WEN Fu-qiang; HUANG Xiang-yang; XIAO Jun; WANG Ke; WANG Tao

    2008-01-01

    Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days.We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (Ⅰand Ⅲ) mRNA expression induced by bleomycin. Moreover,simvastatin down-regulated the increased expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-(] (TNF-a) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore,the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-βI and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

  6. BEP2D细胞受照前后蛋白质组学研究%PROTEOME ANALYSIS FOR EFFECTS OF RADIATION ON BEP2D CELL

    Institute of Scientific and Technical Information of China (English)

    薛振伟; 周小林; 谷娟娟; 蘧艳峰; 崔梅萍

    2009-01-01

    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 γ 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 γ-rays contracting with control image caused down-regulation of 104 kinds of cell proteins and up-regulation of 15 proteins. Irradiation with 3 Gy γ-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.%本研究利用蛋白质组学技术对受1.5Gy、3Gy γ射线照射的人支气管上皮(BEP2D)细胞和未经照射的人支气管上皮细胞蛋白差异表达谱进行了分析与鉴定.研究结果表明:2-D电泳后在分子量14.4~94kD,等电点3~10范围内分离出约1000多个不同蛋白质斑点.凝胶图象显示1.5Gy的γ射线照射后与对照组相比有15个蛋白点上调,104个下调;3Gy的γ射线照射后有26个蛋白点上调,144个下调;二个不同照射剂量共同表达的差异蛋白点有18个,其中上调的有3个,下调的有15个.通过对选取的10个蛋白点进行质谱分析,有2个蛋白点(样品D和样品660)经检索鉴定为肌球蛋白轻链(MLC).这些蛋白表达量的改变可能与辐射诱发肺部肿瘤的发生有关,为进一步研究肺癌的发病机理提供了一定的基础.

  7. Synthetic liposomes are protective from bleomycin-induced lung toxicity

    OpenAIRE

    Gwinn, William M.; Kapita, Mayanga C.; Wang, Ping M.; Cesta, Mark F.; Martin, William J.

    2011-01-01

    Idiopathic pulmonary fibrosis is a devastating disease characterized by a progressive, irreversible, and ultimately lethal form of lung fibrosis. Except for lung transplantation, no effective treatment options currently exist. The bleomycin animal model is one of the best studied models of lung injury and fibrosis. A previous study using mouse tumor models observed that liposome-encapsulated bleomycin exhibited reduced lung toxicity. Therefore, we hypothesized that airway delivery of syntheti...

  8. Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2010-01-01

    Single-dose intratracheal bleomycin has been instrumental for understanding fibrotic lung remodeling, but fails to recapitulate several features of idiopathic pulmonary fibrosis (IPF). Since IPF is thought to result from recurrent alveolar injury, we aimed to develop a repetitive bleomycin model that results in lung fibrosis with key characteristics of human disease, including alveolar epithelial cell (AEC) hyperplasia. Wild-type and cell fate reporter mice expressing β-galactosidase in cells...

  9. Cells containing factor XIIIa and pulmonary fibrosis induced by bleomycin.

    OpenAIRE

    Toida, M; Y. Okumura; Takami, T.

    1991-01-01

    To show the clinical importance of cells containing FXIIIa in pulmonary fibrosis induced by bleomycin, the distributions of FXIIIa and collagenous components were investigated immunohistochemically in both normal lung tissues and those affected by bleomycin. In the normal tissues FXIIIa-containing cells were sparse, but they were numerous in the pulmonary fibrotic tissues, especially in the subpleural area and around the blood vessels of alveolar septa, where slight to moderate fibrosis was s...

  10. Elastase modifies bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Trajano, Larissa Alexsandra Silva Neto; Trajano, Eduardo Tavares Lima; Lanzetti, Manuella; Mendonça, Morena Scopel Amorim; Guilherme, Rafael Freitas; Figueiredo, Rodrigo Tinoco; Benjamim, Cláudia Farias; Valenca, Samuel Santos; Costa, Andréa Monte Alto; Porto, Luís Cristóvão

    2016-04-01

    Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1U/mouse); elastase (using porcine pancreatic elastase (PPE)+bleomycin (3U/mouse 14 days before 0.1U/mouse of bleomycin; PPE+B); elastase (3U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE+B group. In the PPE+B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE+B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p<0.05), catalase (p<0.01) and glutathione peroxidase (p<0.01) parallel with an increase in nitrite (p<0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p<0.05, p<0.05 and p<0.01, respectively) and increased (p<0.01) in the PPE+B group at 21 days compared with the control group. Interleukin (IL)-1β expression was upregulated (p<0.01) whereas IL-6 was downregulated (p<0.05) in the PPE+B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group. PMID:26852294

  11. Induction of tumor necrosis factor-alpha as a cause of bleomycin-related toxicity

    NARCIS (Netherlands)

    Sleijfer, S; Vujaskovic, Z; Limburg, PC; Mulder, NH; Schraffordt Koops, H.

    1998-01-01

    BACKGROUND, The application of bleomycin is characterized by acute side effects, such as fever, chills, and sometimes hypotension and tachypnea. Furthermore, bleomycin is known to induce pneumonitis. There are several indications that the induction of cytokines by bleomycin is involved in the develo

  12. The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

    OpenAIRE

    Turgut, Nergiz H.; Kara, Haki; Elagoz, Sahende; Deveci, Koksal; Gungor, Huseyin; Arslanbas, Emre

    2016-01-01

    The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and...

  13. 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.

  14. Bleomycin effect on L5178Y cells

    International Nuclear Information System (INIS)

    We analyzed the effects of treatment with bleomycin (BLM) in 2 sublines of L5178Y (LY) murine lymphoma, LY-R, radioresistant, and LY-S, radiosensitive. LY-S cells were 2 times more sensitive to BLM than LY-R cells, similarly as in the case of X rays. Since there was no difference in the activity of drug transport system, this different susceptibility to BLM probably was due to the DNA repair defect in LY-S cells. Growth was impaired proportionally to the lethal effect and continued (days 3-6 after treatment with 50 microM BLM) until the elimination of dead cells from the cell population; 24 h after treatment cell cycle distributions indicated the presence of block in S phase (proportional to the dose of BLM). Contrarily to X or gamma-irradiation, BLM did not induce any block in the G2 phase. Initial DNA damage, estimated by the single cell gel electrophoresis, was linearly related to the dose of BLM in LY-S cells; in LY-R cells the damage level was significantly higher than in LY-S cells. In the higher (>10 microM BLM) dose range both dose - effect curves became identical. In gamma-irradiated LY-R and LY-S cells the dose - effect curves were identical. DNA damage distribution in BLM treated LY cells was much less uniform than in the gamma-irradiated ones; it indicated the presence of heavily damaged cells, a feature typical for BLM action. (author). 29 refs, 28 figs

  15. BEP Enhancement for Semi-Femtocell MIMO Systems Employing SC-QICs and OSTBCs

    Directory of Open Access Journals (Sweden)

    Ardavan Rahimian

    2013-01-01

    Full Text Available In mobile cellular networks, it is estimated that more than 60% of voice and data services occur indoors. Therefore, cellular network operators have shown an unprecedented interest in research on femtocell systems from various aspects to extend the indoor wireless coverage for providing high-quality and high data-rate wireless multimedia services contents. In an effort for reducing the bit-error probabilities (BEPs and also increasing bit/symbol capacity of bandwidth limited error-prone wireless channels in femtocell propagation areas, this paper presents the performance of a promising candidate technology designed based on the state-of-the-art techniques. The performance of powerful space-time turbo codes (STTCs based on serial concatenation of quadratic interleaved codes (SC-QICs with the optimal and also suboptimal decoding algorithms, in conjunction with orthogonal space-time block codes (OSTBCs have been presented in this contribution for wireless multiple-input single-output (MISO, and multiple-input multiple-output (MIMO semi-femtocells.

  16. 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...

  17. Elimination of multicopy plasmid R6K by bleomycin.

    OpenAIRE

    Attfield, P V; Pinney, R. J.

    1985-01-01

    Bleomycin eliminated multicopy plasmid R6K from growing cells of Escherichia coli AB1157 but failed to cure either of the low-copy plasmids R1 or R46. Measurements of R6K-encoded beta-lactamase and of covalently closed plasmid DNA indicated that the drug causes a progressive reduction in plasmid copy number.

  18. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

    OpenAIRE

    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

    2006-01-01

    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  19. Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; TIAN Qing; LIANG Zhi-xin; YANG Zhen; XU Shu-feng; SUN Ji-ping; CHEN Liang-an

    2010-01-01

    Background Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated.However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction.This study investigated the effect of gefitinib on lung fibrosis in mice.Methods We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib.C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline.Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.Results The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells.In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR).Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens Ⅰ and Ⅲ.Conclusions These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.

  20. 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

  1. Assessment of a high resolution annual WRF-BEP/CMAQ simulation for the urban area of Madrid (Spain)

    Science.gov (United States)

    de la Paz, David; Borge, Rafael; Martilli, Alberto

    2016-11-01

    Urban air quality has become one of the main environmental issues worldwide and there is an increasing need for modelling tools able to accurately reproduce the complex atmospheric phenomena that determine pollutant concentrations within cities. Eulerian 3D mesoscale models can consistently describe a wide range of spatial scales. However, urban areas present features that are usually missed by land-surface and PBL modules commonly implemented in such models. The Weather Research and Forecasting model (WRF) incorporates urban parameterizations to take into account changes in albedo, roughness length and thermal properties imposed by buildings. In this study, a model configuration based on the multi-layer Building Effect Parameterization (BEP) scheme is tested over the city of Madrid with the primarily aim of understanding the effect that the use of this urban canopy model may have on routinely (annual) air quality modelling activities in this urban area using the Community Multiscale Air Quality (CMAQ) model. To do so, the results for the main meteorological variables (temperature, planetary boundary layer height and wind fields) are compared with those from the WRF reference configuration (based on the BULK simple scheme) that has been used in the past for practical applications in this urban area. Both model outputs are compared with observations to assess changes in model performance. It was found that the BEP-based configuration improved significantly wind speed results over built areas, with an annual average bias of -0.3 m s-1 in comparison with the 1.6 m s-1 yielded by the reference WRF run. Meteorological outputs from the two alternative configurations were used to feed the CMAQ model to assess the influence of this urban parameterization on air quality predictions. The effect was a clear improvement of the model performance regarding the most relevant pollutants, reducing NO2 underestimation to only 1.6 μg m-3. Model skills to reproduce O3 and PM2

  2. [Consortium for detection and management of lung damage induced by bleomycin].

    Science.gov (United States)

    Biya, Josette; Stoclin, Annabelle; Dury, Sandra; Le Pavec, Jérôme; Mir, Olivier; Lazarovici, Julien; Fermé, Christophe; Annereau, Maxime; Ekpe, Kenneth; Massard, Christophe; Michot, Jean-Marie

    2016-01-01

    Bleomycin is a cytotoxic antibiotic and a component of chemotherapy regimens of germ cell tumors and lymphoma. Bleomycin lung injuries occur in 10% of patients, and lead to severe interstitial pneumonia in 3% of patients. Pulmonary toxicity is related to endothelial cells injury induce by free radicals and inflammatory cytokines. Diagnosis of bleomycin-induced lung toxicity is based on the combination of clinical and radiological features, and requires to rule out differential diagnoses including pneumocystis. "Bleomycin-induced pneumonitis" is the most frequent pattern; eosinophilic pneumonitis and organizing pneumonia are rarer. Occurrence of bleomycin lung toxicity requires an immediate and often permanent discontinuation. Treatment is based on steroid. Regular clinical and pulmonary function tests monitoring are mandatory for early detection of bleomycin-induced lung toxicity. PMID:27241272

  3. Pulmonary platelet trapping induced by bleomycin: correlation with fibrosis and involvement of the beta 2 integrins.

    OpenAIRE

    Piguet, P F; Vesin, C

    1994-01-01

    Platelet trapping was explored during the course of bleomycin induced pulmonary fibrosis by the injection of indium-111 labelled platelets and by light and electron microscopy (EM) of the alveolar capillaries. An i.v. injection of bleomycin markedly increased the localization of labelled platelets in the lung (but not in other organs) for about 3 weeks. On day 7 after bleomycin injection, a significant increase in the number of platelets in contact with the alveolar endothelium was seen with ...

  4. Genome-wide Screening Identifies Phosphotransferase System Permease BepA to Be Involved in Enterococcus faecium Endocarditis and Biofilm Formation.

    Science.gov (United States)

    Paganelli, Fernanda L; Huebner, Johannes; Singh, Kavindra V; Zhang, Xinglin; van Schaik, Willem; Wobser, Dominique; Braat, Johanna C; Murray, Barbara E; Bonten, Marc J M; Willems, Rob J L; Leavis, Helen L

    2016-07-15

    Enterococcus faecium is a common cause of nosocomial infections, of which infective endocarditis is associated with substantial mortality. In this study, we used a microarray-based transposon mapping (M-TraM) approach to evaluate a rat endocarditis model and identified a gene, originally annotated as "fruA" and renamed "bepA," putatively encoding a carbohydrate phosphotransferase system (PTS) permease (biofilm and endocarditis-associated permease A [BepA]), as important in infective endocarditis. This gene is highly enriched in E. faecium clinical isolates and absent in commensal isolates that are not associated with infection. Confirmation of the phenotype was established in a competition experiment of wild-type and a markerless bepA mutant in a rat endocarditis model. In addition, deletion of bepA impaired biofilm formation in vitro in the presence of 100% human serum and metabolism of β-methyl-D-glucoside. β-glucoside metabolism has been linked to the metabolism of glycosaminoglycans that are exposed on injured heart valves, where bacteria attach and form vegetations. Therefore, we propose that the PTS permease BepA is directly implicated in E. faecium pathogenesis. PMID:26984142

  5. Effects of bleomycin and antioxidants on the fatty acid profile of testicular cancer cell membranes.

    Science.gov (United States)

    Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A

    2016-02-01

    Bleomycin is used in chemotherapy regimens for the treatment of patients having testicular germ-cell tumor (TGCT). There is no study in the literature investigating the effects of bleomycin on membrane lipid profile in testicular cancer cells. We investigated membrane fatty acid (FA) profiles isolated, derivatized and analyzed by gas chromatography of NTera-2 testicular cancer cells incubated with bleomycin (Bleo) for 24 h in the absence and presence of N-Acetyl-L-Cysteine (NAC) and curcumin (Cur) as commonly used antioxidant adjuvants. At the same time the MAPK pathway and EGFR levels were followed up. Bleomycin treatment increased significantly saturated fatty acids (SFA) of phospholipids at the expense of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Bleomycin also led to a significant increase in the trans lipid isomers of oleic and arachidonic acids due to its free radical producing effect. Incubation with bleomycin increased the p38 MAPK and JNK levels and downregulated EGFR pathway. Coincubation of bleomycin with NAC reversed effects caused by bleomycin. Our results highlight the important role of membrane fatty acid remodeling occurring during the use of bleomycin and its concurrent use with antioxidants which can adjuvate the cytotoxic effects of the chemotherapeutic agents. PMID:26656160

  6. Carbon Monoxide Suppresses Bleomycin-Induced Lung Fibrosis

    OpenAIRE

    Zhou, Zhihong; Song, Ruiping; Fattman, Cheryl L.; Greenhill, Sara; Alber, Sean; Oury, Tim D.; Augustine M K Choi; Morse, Danielle

    2005-01-01

    Idiopathic pulmonary fibrosis is an incurable fibrosing disorder that progresses relentlessly to respiratory failure. We hypothesized that a product of heme oxygenase activity, carbon monoxide (CO), may have anti-fibrotic effects. To test this hypothesis, mice treated with intratracheal bleomycin were exposed to low-concentration inhaled CO or ambient air. Lungs of mice treated with CO had significantly lower hydroxyproline accumulation than controls. Fibroblast proliferation, thought to play...

  7. Bleomycin-associated Lung Toxicity in Childhood Cancer Survivors.

    Science.gov (United States)

    Zorzi, Alexandra P; Yang, Connie L; Dell, Sharon; Nathan, Paul C

    2015-11-01

    Pulmonary disease is a significant morbidity among childhood cancer survivors. The aim of this study was to characterize the pulmonary dysfunction experienced by childhood cancer survivors treated with bleomycin. A cross-sectional analysis of pulmonary function testing (PFT) in survivors treated with bleomycin was preformed. The most recent posttherapy PFT was assessed. Spirometry and lung volumes were categorized as normal, restrictive, obstructive, or mixed. Diffusing capacity of carbon monoxide (DLCO) was categorized as normal or abnormal. PFT data of 143 survivors was analyzed. PFTs were performed a median of 2.3 years (interquartile range, 1.4 to 4.9) from completion of therapy. Spirometry was abnormal in 58 (41%), only 5 (9%) had respiratory symptoms. Forty-two (70%) had obstructive, 11 (18%) restrictive, and 5 (9%) mixed ventilatory defects. The majority of abnormalities were mild (91%). DLCO was abnormal in 27. Reductions were mild in 96%. Patients with a history of relapse were more likely to develop abnormalities in spirometry and/or DLCO (odds ratio=5.02, 95% confidence interval: 1.3-19.4, P=0.01; odds ratio=3.47, 95% confidence interval: 1.01-11.9, P=0.03). Asymptomatic abnormalities of PFT are common among childhood cancer survivors treated with bleomycin and associated with a history of relapse. Research studying the risk for clinical progression of this dysfunction is warranted. PMID:26422284

  8. 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)

  9. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase.

    Science.gov (United States)

    Zimny, Jaroslaw; Sikora, Marta; Guranowski, Andrzej; Jakubowski, Hieronim

    2006-08-11

    Homocysteine (Hcy) editing by methionyl-tRNA synthetase results in the formation of Hcy-thiolactone and initiates a pathway that has been implicated in human disease. In addition to being cleared from the circulation by urinary excretion, Hcy-thiolactone is detoxified by the serum Hcy-thiolactonase/paraoxonase carried on high density lipoprotein. Whether Hcy-thiolactone is detoxified inside cells was unknown. Here we show that Hcy-thiolactone is hydrolyzed by an intracellular enzyme, which we have purified to homogeneity from human placenta and identified by proteomic analyses as human bleomycin hydrolase (hBLH). We have also purified an Hcy-thiolactonase from the yeast Saccharomyces cerevisiae and identified it as yeast bleomycin hydrolase (yBLH). BLH belongs to a family of evolutionarily conserved cysteine aminopeptidases, and its only known biologically relevant function was deamidation of the anticancer drug bleomycin. Recombinant hBLH or yBLH, expressed in Escherichia coli, exhibits Hcy-thiolactonase activity similar to that of the native enzymes. Active site mutations, C73A for hBLH and H369A for yBLH, inactivate Hcy-thiolactonase activities. Yeast blh1 mutants are deficient in Hcy-thiolactonase activity in vitro and in vivo, produce more Hcy-thiolactone, and exhibit greater sensitivity to Hcy toxicity than wild type yeast cells. Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone. PMID:16769724

  10. Vascular damage in testicular cancer patients : A study on endothelial activation by bleomycin and cisplatin in vitro

    NARCIS (Netherlands)

    Nuver, Janine; De Haas, Esther C.; Van Zweeden, Martine; Gietema, Jourik A.; Meijer, Coby

    2010-01-01

    Following treatment with bleomycin- and cisplatin-containing chemotherapy, testicular cancer patients frequently develop vascular complications, which may result from damage to endothelial cells. Understanding bleomycin- and cisplatin-induced endothelial alterations may help to develop strategies to

  11. Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity.

    Science.gov (United States)

    Burgy, Olivier; Wettstein, Guillaume; Bellaye, Pierre S; Decologne, Nathalie; Racoeur, Cindy; Goirand, Françoise; Beltramo, Guillaume; Hernandez, Jean-François; Kenani, Abderraouf; Camus, Philippe; Bettaieb, Ali; Garrido, Carmen; Bonniaud, Philippe

    2016-02-17

    Bleomycin (BLM) is a potent anticancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors, and melanomas. Unfortunately, BLM has major, dose-dependent, pulmonary toxicity that affects 20% of treated individuals. The most severe form of BLM-induced pulmonary toxicity is lung fibrosis. Deglyco-BLM is a molecule derived from BLM in which the sugar residue d-mannosyl-l-glucose disaccharide has been deleted. The objective of this study was to assess the anticancer activity and lung toxicity of deglyco-BLM. We compared the antitumor activity and pulmonary toxicity of intraperitoneally administrated deglyco-BLM and BLM in three rodent models. Pulmonary toxicity was examined in depth after intratracheal administration of both chemotherapeutic agents. The effect of both drugs was further studied in epithelial alveolar cells in vitro. We demonstrated in rodent cancer models, including a human Hodgkin's lymphoma xenograft and a syngeneic melanoma model, that intraperitoneal deglyco-BLM is as effective as BLM in inducing tumor regression. Whereas the antitumor effect of BLM was accompanied by a loss of body weight and the development of pulmonary toxicity, deglyco-BLM did not affect body weight and did not engender lung injury. Both molecules induced lung epithelial cell apoptosis after intratracheal administration, but deglyco-BLM lost the ability to induce caspase-1 activation and the production of ROS (reactive oxygen species), transforming growth factor-β1, and other profibrotic and inflammatory cytokines in the lungs of mice and in vitro. Deglyco-BLM should be considered for clinical testing as a less toxic alternative to BLM in cancer therapy. PMID:26888428

  12. N-acetyl-L-cysteine inhibits bleomycin induced apoptosis in malignant testicular germ cell tumors.

    Science.gov (United States)

    Kucuksayan, Ertan; Cort, Aysegul; Timur, Mujgan; Ozdemir, Evrim; Yucel, Suleyman Gultekin; Ozben, Tomris

    2013-07-01

    Antioxidants may prevent apoptosis of cancer cells via inhibiting reactive oxygen species (ROS). However, to date no study has been carried out to elucidate the effects of strong antioxidant N-acetylcysteine (NAC) on Bleomycin induced apoptosis in human testicular cancer (NTERA-2, NT2) cells. For this reason, we studied the effects of Bleomycin and NAC alone and in combination on apoptotic signaling pathways in NT2 cell line. We determined the cytotoxic effect of bleomycin on NT2 cells and measured apoptosis markers such as Caspase-3, -8, -9 activities and Bcl-2, Bax, Cyt-c, Annexin V-FTIC and PI levels in NT2 cells incubated with different agents for 24 h. Early apoptosis was determined using FACS assay. We found half of the lethal dose (LD50) of Bleomycin on NT2 cell viability as 400, 100, and 20 µg/ml after incubations for 24, 48, and 72 h, respectively. Incubation with bleomycin (LD50 ) and H2O2 for 24 h increased Caspase-3, -8, -9 activities, Cyt-c and Bax levels and decreased Bcl-2 levels. The concurrent incubation of NT2 cells with bleomycin/H2O2 and NAC (5 mM) for 24 h abolished bleomycin/H2O2-dependent increases in Caspase-3, -8, -9 activities, Bax and Cyt-c levels and bleomycin/H2O2-dependent decrease in Bcl-2 level. Our results indicate that bleomycin/H2O2 induce apoptosis in NT2 cells by activating mitochondrial pathway of apoptosis, while NAC diminishes bleomycin/H2O2 induced apoptosis. We conclude that NAC has antagonistic effects on Bleomycin-induced apoptosis in NT2 cells and causes resistance to apoptosis which is not a desired effect in eliminating cancer cells. PMID:23386420

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Li-Jun [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Ye, Hong [Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Zhang, Qian; Li, Feng-Zhi; Song, Lin-Jie; Yang, Jie; Mu, Qing [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Rao, Shan-Shan [Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Cai, Peng-Cheng [Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Xiang, Fei; Zhang, Jian-Chu [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Su, Yunchao [Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA (United States); Xin, Jian-Bao, E-mail: 814643835@qq.com [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China); Ma, Wan-Li, E-mail: whmawl@aliyun.com [Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Key Laboratory of Pulmonary Diseases, Ministry of Health of China, Wuhan, Hubei (China)

    2015-03-01

    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.

  15. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    Directory of Open Access Journals (Sweden)

    Stergios Boussios

    2015-01-01

    Full Text Available Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis.

  16. Bleomycin resistance : a new dominant selectable marker for plant cell transformation

    NARCIS (Netherlands)

    Hille, Jacques; Verheggen, Frank; Roelvink, Peter; Franssen, Henk; Kammen, Ab van; Zabel, Pim

    1986-01-01

    Plant cells are sensitive to the antibiotic bleomycin, a DNA damaging glycopeptide. A bleomycin resistance determinant, located on transposon Tn5 and functional in bacteria, has been cloned in a plant expression vector and introduced into Nicotiana plumbaginifolia using Agrobacterium tumefaciens. Th

  17. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor.

    Science.gov (United States)

    Boussios, Stergios; Moschetta, Michele; McLachlan, Jennifer; Banerjee, Susana

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis. PMID:26798532

  18. Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor

    OpenAIRE

    Stergios Boussios; Michele Moschetta; Jennifer McLachlan; Susana Banerjee

    2015-01-01

    Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis.

  19. DNA sequence and structure recognition by Fe(II)[center dot]bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Kane, S.A.

    1993-01-01

    The bleomycins (BLMs) are a family of clinically-important antitumor antibiotics whose chemotherapeutic effects are believed to be expressed at the level of DNA degradation. Bleomycin-mediated DNA strand scission is sequence-selective, resulting in cleavage predominantly at [sup 5[prime

  20. 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.

  1. 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

  2. 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.

  3. Increased and prolonged pulmonary fibrosis in surfactant protein C-deficient mice following intratracheal bleomycin.

    Science.gov (United States)

    Lawson, William E; Polosukhin, Vasiliy V; Stathopoulos, Georgios T; Zoia, Ornella; Han, Wei; 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

    2005-11-01

    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 during the first 2 weeks, and increased mortality. At 3 and 6 weeks after bleomycin, lungs from SFTPC-/- mice had increased fibroblast numbers, augmented collagen accumulation, and greater parenchymal distortion. Furthermore, resolution of fibrosis was delayed. Although remodeling was near complete in SFTPC+/+ mice by 6 weeks, SFTPC-/- mice did not return to baseline until 9 weeks after bleomycin. By terminal dUTP nick-end labeling staining, widespread cell injury was observed in SFTPC-/- and SFTPC+/+ mice 1 week after bleomycin; however, ongoing apoptosis of epithelial and interstitial cells occurred in lungs of SFTPC-/- mice, but not SFTPC+/+ mice, 6 weeks after bleomycin. Thus, SP-C functions to limit lung inflammation, inhibit collagen accumulation, and restore normal lung structure after bleomycin. PMID:16251411

  4. 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)

  5. 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)

  6. Pingyangmycin and Bleomycin Share the Same Cytotoxicity Pathway

    Directory of Open Access Journals (Sweden)

    Yanli He

    2016-06-01

    Full Text Available Pingyangmycin is an anticancer drug known as bleomycin A5 (A5, discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM is a mixture of mainly two compounds (A2 and B2, which is on the World Health Organization’s list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC50 of BLMs in different cancer cell lines varies from nM to μM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines.

  7. 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.

  8. The genome-wide DNA sequence specificity of the anti-tumour drug bleomycin in human cells.

    Science.gov (United States)

    Murray, Vincent; Chen, Jon K; Tanaka, Mark M

    2016-07-01

    The cancer chemotherapeutic agent, bleomycin, cleaves DNA at specific sites. For the first time, the genome-wide DNA sequence specificity of bleomycin breakage was determined in human cells. Utilising Illumina next-generation DNA sequencing techniques, over 200 million bleomycin cleavage sites were examined to elucidate the bleomycin genome-wide DNA selectivity. The genome-wide bleomycin cleavage data were analysed by four different methods to determine the cellular DNA sequence specificity of bleomycin strand breakage. For the most highly cleaved DNA sequences, the preferred site of bleomycin breakage was at 5'-GT* dinucleotide sequences (where the asterisk indicates the bleomycin cleavage site), with lesser cleavage at 5'-GC* dinucleotides. This investigation also determined longer bleomycin cleavage sequences, with preferred cleavage at 5'-GT*A and 5'- TGT* trinucleotide sequences, and 5'-TGT*A tetranucleotides. For cellular DNA, the hexanucleotide DNA sequence 5'-RTGT*AY (where R is a purine and Y is a pyrimidine) was the most highly cleaved DNA sequence. It was striking that alternating purine-pyrimidine sequences were highly cleaved by bleomycin. The highest intensity cleavage sites in cellular and purified DNA were very similar although there were some minor differences. Statistical nucleotide frequency analysis indicated a G nucleotide was present at the -3 position (relative to the cleavage site) in cellular DNA but was absent in purified DNA.

  9. Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin.

    Science.gov (United States)

    Motlagh, Najme Sadat Hosseini; Parvin, Parviz; Ghasemi, Fatemah; Atyabi, Fatemeh

    2016-06-01

    Several chemo-drugs act as the biocompatible fluorophores. Here, the laser induced fluorescence (LIF) properties of doxorubicin, paclitaxel and bleomycin are investigated. The absorption lines mostly lie over UV range according to the UV-VIS spectra. Therefore, a single XeCl laser provokes the desired transitions of the chemo-drugs of interest at 308 nm. It is shown that LIF spectra are strongly dependent on the fluorophore concentration giving rise to the sensible red shift. This happens when large overlapping area appears between absorption and emission spectra accordingly. The red shift is taken into account as a characteristic parameter of a certain chemo-drug. The fluorescence extinction (α) and self-quenching (k) coefficients are determined based on the best fitting of the adopted Lambert-Beer equation over experimental data. The quantum yield of each chemo-drug is also measured using the linearity of the absorption and emission rates. PMID:27375954

  10. Comparison of bleomycin-induced pulmonary apoptosis between NMRI mice and C57BL/6 mice

    OpenAIRE

    Safaeian, L.; Jafarian-Dehkordi, A.; Rabbani, M.; Sadeghi, H.M.; Afshar-Moghaddam, N.; Sarahroodi, S.

    2013-01-01

    Apoptosis has a critical role in the pathogenesis of bleomycin induced-pulmonary fibrosis. The severity of fibrosis varies among different strains of mice. Recent studies have indicated that expression of apoptotic regulatory genes may be specific in different cell types in various strains. In this study, bleomycin-induced pulmonary apoptosis in NMRI (Naval Medical Research Institute, USA) albino mice were compared with C57BL/6 black mice. Pulmonary fibrosis induced by single intratracheal ad...

  11. 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; Han, Wei; Kirk B. Lane; Li, Bo; Donnelly, Edwin F.; Holburn, George E.; Lewis, Kenneth G.; Collins, Robert D.; Hull, William M.; Glasser, Stephan W.; Jeffrey A Whitsett; 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...

  12. Extracellular superoxide dismutase attenuates release of pulmonary hyaluronan from the extracellular matrix following bleomycin exposure

    OpenAIRE

    Zelko, Igor N.; Folz, Rodney J

    2010-01-01

    The major pulmonary antioxidant enzyme involved in the protection of the lung interstitium from oxidative stress is extracellular superoxide dismutase (EC-SOD). It has been previously shown that EC-SOD knockout mice are more susceptible to bleomycin induced lung injury, however, the molecular mechanism(s) remains unclear. We report here that bleomycin-induced lung damage, in EC-SOD KO mice, is associated with increased hyaluronan release into alveolar fluid. Analysis of hyaluronan synthase ge...

  13. 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.

  14. [Local injection of bleomycin A 5 in children with hemangiomas. Analysis of 210 cases].

    Science.gov (United States)

    Zheng, Q T

    1991-05-01

    210 children with hemangiomas were treated by local injection of Bleomycin A5. Bleomycin A5 was effective in all patients with strawberry and mixed hemangiomas, 91.2% of patients with cavernous hemangiomas, 44.4% of patients with port-wine stain. There was no response in pampiniform hemangioma. The therapeutic mechanism, indications and complications of the new method for treatment of hemangioma are discussed. PMID:1717207

  15. Rat lung fibroblast collagen metabolism in bleomycin-induced pulmonary fibrosis.

    OpenAIRE

    Phan, S. H.; Varani, J.; Smith, D.

    1985-01-01

    Endotracheal bleomycin administration in rats and other animal species causes rapid development of pulmonary fibrosis, characterized by increased lung collagen synthesis and deposition. To clarify the mechanism, lung fibroblasts from bleomycin-treated rats (BRF) were isolated and maintained in tissue culture. They were then compared with those from normal untreated control animals, with respect to several key parameters of collagen metabolism. BRF synthesized collagen at a rate 35-82% above n...

  16. 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.

  17. The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats.

    Science.gov (United States)

    Turgut, Nergiz H; Kara, Haki; Elagoz, Sahende; Deveci, Koksal; Gungor, Huseyin; Arslanbas, Emre

    2016-01-01

    The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1β levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and 0.1% toluidine blue. TNF-α, IL-1β, and MDA levels and hydroxyproline content significantly increased (p Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1β activity, hydroxyproline content, and MDA level (p naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis. PMID:26977316

  18. Evaluation of Efficacy and Safety of BEP Regimen in the Treatment of High-risk Gestational Trophoblastic Tumor%BEP方案治疗高危型妊娠滋养细胞肿瘤的疗效及安全性评价

    Institute of Scientific and Technical Information of China (English)

    李淑兰

    2013-01-01

    Objective:To explore the clinical efficacy and safety of BEP regimen in the treatment of high-risk gestational trophoblastic tumor. Method:40 cases of patients with high-risk gestational trophoblastic tumor were treated with bleomycin+etoposide+cisplatin(BEP)from February 2005 to September 2012.Result:The course of treatment was(6.1±0.2)chemotherapy cycle.36 cases of patients achieved complete remission,accounted for 90%.4 cases of patients had drug resistance,accounted for 10%.The average time of drug resistance occured in(4.7±0.1)chemotherapy cycle,and then treated with cyclophosphamide+vincristine(CO)/etoposide+methotrexate+put red of actinomycin D(EMA).On basis of chemotherapy,1 case of patients was treated with operation,2 cases of patients were treated with radiotherapy,and 1 case died,3 cases of patients achieved complete remission. The main adverse reaction included hair loss,gastrointestinal discomfort and bone marrow suppression,secondary adverse reaction included liver function damage and peripheral neuritis,the differences were statistically significant(P<0.05).Conclusion:BEP regimen have good clinical efficacy and safety in the treatment of high-risk gestational trophoblastic tumor,and has very important application value.%  目的:探讨高危型妊娠滋养细胞肿瘤采用BEP方案治疗的临床效果及安全性。方法:本次研究选择的对象共40例,均为本院2005年2月-2012年9月收治的高危型妊娠滋养细胞肿瘤的患者,给予博来霉素+依托泊苷+顺铂(BEP)方案救治,并回顾分析其临床资料。结果:本组40例患者,平均接受BEP方案化疗(6.1±0.2)个疗程,其中完全缓解36例,占90%;耐药者4例,占10%。耐药患者平均进行(4.7±0.1)个疗程时出现耐药,均改用环磷酰胺+长春新碱(CO)/依托泊苷+甲氨蝶呤+放红菌素D(EMA)方案化疗,辅以手术治疗1例,辅以放疗治疗2例,后死亡1例,完全缓解3

  19. 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.

  20. Localization of bleomycin in a single living cell using three-photon excitation microscopy

    Science.gov (United States)

    Abraham, Anil T.; Brautigan, David L.; Hecht, Sidney M.; Periasamy, Ammasi

    2001-04-01

    Bleomycin has been used in the clinic as a chemotherapeutic agent for the treatment of several neoplasms, including non-Hodgkins lymphomas, squamous cell carcinomas, and testicular tumors. The effectiveness of bleomycin is believed to be derived from its ability to bind and oxidatively cleave DNA in the presence of a iron cofactor in vivo. A substantial amount of data on BLM has been collected, there is little information concerning the effects of bleomycin in living cells. In order to obtain data pertinent to the effects of BLM in intact cells, we have exploited the intrinsic fluorescence property of bleomycin to monitor the uptake of the drug in mammalian cells. We employed two light microscopy techniques, a wide-field and three-photon excitation (760 nm) fluorescence microscopy. Treatment of HeLa cells with bleomycin resulted in rapid to localization within the cells. In addition data collected from the wide field experiments, three-photon excitation of BLM which considerably reduced the phototoxic effect compared with UV light excitation in the wide-field microscopy indicated co-localization of the drug to regions of the cytoplasm occupied by the endoplasmic reticulum probe, DiOC5. The data clearly indicates that the cellular uptake of bleomycin after one minute includes the nucleus as well as in cytoplasm. Contrary to previous studies, which indicate chromosomal DNA as the target of bleomycin, the current findings suggest that the drug is distributed to many areas within the cell, including the endoplasmic reticulum, an organelle that is known to contain ribonucleic acids.

  1. The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nergiz H. Turgut

    2016-01-01

    Full Text Available The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80 were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula alone or followed by either naringin 40 mg/kg (orally or naringin 80 mg/kg (orally or water (1 mL, orally for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1β levels, hydroxyproline content, and malondialdehyde (MDA levels were assayed. Glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson’s trichrome, and 0.1% toluidine blue. TNF-α, IL-1β, and MDA levels and hydroxyproline content significantly increased (p<0.01 and GPx and SOD activities significantly decreased in bleomycin group (p<0.01. Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1β activity, hydroxyproline content, and MDA level (p<0.01 and increased GPx and SOD activities (p<0.05. Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.

  2. 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 μL or bleomycin (2 mg/Kg in 50 μL 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 (η, 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

  3. Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Satish K. Madala

    2011-01-01

    Full Text Available Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD and interstitial pulmonary fibrosis (IPF. Gene-targeted mice that lack SP-C (−/− develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of −/− mice. +/+ and −/− mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated +/+ and −/− mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated −/− mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF.

  4. Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice.

    Science.gov (United States)

    Madala, Satish K; Maxfield, Melissa D; Davidson, Cynthia R; Schmidt, Stephanie M; Garry, Daniel; Ikegami, Machiko; Hardie, William D; Glasser, Stephan W

    2011-01-01

    Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF). Gene-targeted mice that lack SP-C (Sftpc(-/-)) develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of Sftpc(-/-) mice. Sftpc(+/+) and -/- mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated Sftpc(+/+) and Sftpc(-/-) mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated Sftpc(-/-) mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF. PMID:21660239

  5. A Highly Sensitive Spectrophotometric Assay of Bleomycins Based on the Fading Reaction of Some Halofluorescein Dyes

    Institute of Scientific and Technical Information of China (English)

    LIU,Jiang-Tao; LIU,Zhong-Fang; HU,Xiao-Li; Kong,Ling; LIU,Shao-Pu

    2007-01-01

    In weak acidic medium, anticancer antibiotics bleomycin A5 (BLMA5) and bleomycin A2 (BLMA2) can react with halofluorescein dyes such as erythrosin (Ery), eosin Y (EY), eosin B (EB) and rose bengal (RB) by virtue of electrostatic attraction and hydrophobic force to form the ion-association complexes, which can result in the fading reactions of four halofluorescein dyes. The maximum fading wavelengths of these four dyes were located at 527 nm for Ery, 515 nm for EY, 517 nm for EB and 546 nm for RB, respectively. The decrements of absorbance (△A) were directly proportional to the concentrations of bleomycin in a certain range. A new method for the determination of bleomycins anticancer drugs based on fading reactions of halofluorescein dyes has been developed. The method was not only highly sensitive but also simple and rapid. The molar absorptivities (ε) ranged from 1.5 × 105 to 7.5 ×105 L·mol-1·cm-1. It was applied to determination of the bleomycins in human serum, urine and rabbit serum samples. In this work, the spectral properties and the optimum reaction conditions were investigated. The structure of ion-association complexes and the reaction mechanism were discussed.

  6. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Lili eGao

    2015-10-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  7. Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Minrui Liang

    2013-01-01

    Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

  8. Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer

    NARCIS (Netherlands)

    de Haas, Esther C; Zwart, Nynke; Meijer, Coby; Nuver, Janine; Suurmeijer, Albert J H; Hoekstra, Harald J; van der Steege, Gerrit; Sleijfer, Dirk Th; Gietema, Jourik A; Boezen, Hendrika

    2008-01-01

    PURPOSE: Response to chemotherapy may be determined by gene polymorphisms involved in metabolism of cytotoxic drugs. A plausible candidate is the gene for bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, an essential component of chemotherapy regimens for disseminated testicular ger

  9. 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.

  10. Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

    Science.gov (United States)

    Oliveira-Junior, Manoel Carneiro; Assumpção-Neto, Erasmo; Brandão-Rangel, Maysa Alves Rodrigues; Damaceno-Rodrigues, Nilsa Regina; Garcia Caldini, Elia; Velosa, Ana Paula Pereira; Teodoro, Walcy Rosolia; Ligeiro de Oliveira, Ana Paula; Dolhnikoff, Marisa; Eickelberg, Oliver; Vieira, Rodolfo Paula

    2016-01-01

    Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin-induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX); (n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1; p<0.01), (IL-1β; p<0.001), (IL-5; p<0.01), (IL-6; p<0.001), (IL-13; p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15–44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model. PMID:27677175

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

    Directory of Open Access Journals (Sweden)

    Tao Zhu

    2013-12-01

    Full Text Available 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-κB (NF-κB 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-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-α in bronchoalveolar lavage fluid (BALF were measured. HE staining and Masson’s trichrome (MT staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-β1 and α-SMA mRNA and protein were analyzed. Activation of NF-κB was determined by western blotting and electrophoretic mobility shift assay (EMSA. On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-α in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-β1 and α-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-κB p65/total NF-κB p65 and NF-κB p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-κB. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.

  12. Hypoxia-Induced Epithelial-Mesenchymal Transition Is Involved in Bleomycin-Induced Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Liang Guo

    2015-01-01

    Full Text Available Pulmonary fibrosis is a severe disease that contributes to the morbidity and mortality of a number of lung diseases. However, the molecular and cellular mechanisms leading to lung fibrosis are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT and the associated molecular mechanisms in bleomycin-induced lung fibrosis. The bleomycin-induced fibrosis animal model was established by intratracheal injection of a single dose of bleomycin. Protein expression was measured by Western blot, immunohistochemistry, and immunofluorescence. Typical lesions of lung fibrosis were observed 1 week after bleomycin injection. A progressive increase in MMP-2, S100A4, α-SMA, HIF-1α, ZEB1, CD44, phospho-p44/42 (p-p44/42, and phospho-p38 MAPK (p-p38 protein levels as well as activation of EMT was observed in the lung tissues of bleomycin mice. Hypoxia increased HIF-1α and ZEB1 expression and activated EMT in H358 cells. Also, continuous incubation of cells under mild hypoxic conditions increased CD44, p-p44/42, and p-p38 protein levels in H358 cells, which correlated with the increase in S100A4 expression. In conclusion, bleomycin induces progressive lung fibrosis, which may be associated with activation of EMT. The fibrosis-induced hypoxia may further activate EMT in distal alveoli through a hypoxia-HIF-1α-ZEB1 pathway and promote the differentiation of lung epithelial cells into fibroblasts through phosphorylation of p38 MAPK and Erk1/2 proteins.

  13. A windowless hydrogen gas target for the measurement of 7Be(p, γ)8B with the recoil separator ERNA

    International Nuclear Information System (INIS)

    A new measurement of the cross section of 7Be(p, γ)8B will be done in inverted kinematics with the recoil separator ERNA at the CIRCE laboratory in Caserta, Italy. The 8B recoils will be produced in a windowless hydrogen gas target. We report here on the construction and characterization of the gas cell. In detail we describe measurements for target density, the profile determination via the 7Li(p, p')7Li* reaction as well as the role and performance of a gaseous post-stripper. (orig.)

  14. Problems in the differentiation of lung infiltrates following bleomycin therapy from metastases

    Energy Technology Data Exchange (ETDEWEB)

    Mayr, B.; Bauer, W.M.; Clemm, C.; Hartenstein, R.

    1984-10-01

    Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest X-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases.

  15. Problems in the differentiation of lung infiltrates following bleomycin therapy from metastases

    International Nuclear Information System (INIS)

    Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest X-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases. (orig.)

  16. Hairpin DNA Sequences Bound Strongly by Bleomycin Exhibit Enhanced Double-Strand Cleavage

    OpenAIRE

    Roy, Basab; Hecht, Sidney M.

    2014-01-01

    Clinically used bleomycin A5 has been employed in a study of double-strand cleavage of a library of 10 hairpin DNAs originally selected on the basis of their strong binding to bleomycin. Each of the DNAs underwent double-strand cleavage at more than one site, and all of the cleavage sites were within, or in close proximity to, an eight-base-pair region of the duplex that had been randomized to create the original library. A total of 31 double-strand cleavage sites were identified on the 10 DN...

  17. Combined local and systemic bleomycin administration in electrochemotherapy to reduce the number of treatment sessions

    Directory of Open Access Journals (Sweden)

    Maglietti Felipe

    2016-03-01

    Full Text Available Electrochemotherapy (ECT, a medical treatment widely used in human patients for tumor treatment, increases bleomycin toxicity by 1000 fold in the treated area with an objective response rate of around 80%. Despite its high response rate, there are still 20% of cases in which the patients are not responding. This could be ascribed to the fact that bleomycin, when administered systemically, is not reaching the whole tumor mass properly because of the characteristics of tumor vascularization, in which case local administration could cover areas that are unreachable by systemic administration.

  18. A designer bleomycin with significantly improved DNA cleavage activity.

    Science.gov (United States)

    Huang, Sheng-Xiong; Feng, Zhiyang; Wang, Liyan; Galm, Ute; Wendt-Pienkowski, Evelyn; Yang, Dong; Tao, Meifeng; Coughlin, Jane M; Duan, Yanwen; Shen, Ben

    2012-08-15

    The bleomycins (BLMs) are used clinically in combination with a number of other agents for the treatment of several types of tumors, and the BLM, etoposide, and cisplatin treatment regimen cures 90-95% of metastatic testicular cancer patients. BLM-induced pneumonitis is the most feared, dose-limiting side effect of BLM in chemotherapy, which can progress into lung fibrosis and affect up to 46% of the total patient population. There have been continued efforts to develop new BLM analogues in the search for anticancer drugs with better clinical efficacy and lower lung toxicity. We have previously cloned and characterized the biosynthetic gene clusters for BLMs from Streptomyces verticillus ATCC15003, tallysomycins from Streptoalloteichus hindustanus E465-94 ATCC31158, and zorbamycin (ZBM) from Streptomyces flavoviridis SB9001. Comparative analysis of the three biosynthetic machineries provided the molecular basis for the formulation of hypotheses to engineer novel analogues. We now report engineered production of three new analogues, 6'-hydroxy-ZBM, BLM Z, and 6'-deoxy-BLM Z and the evaluation of their DNA cleavage activities as a measurement for their potential anticancer activity. Our findings unveiled: (i) the disaccharide moiety plays an important role in the DNA cleavage activity of BLMs and ZBMs, (ii) the ZBM disaccharide significantly enhances the potency of BLM, and (iii) 6'-deoxy-BLM Z represents the most potent BLM analogue known to date. The fact that 6'-deoxy-BLM Z can be produced in reasonable quantities by microbial fermentation should greatly facilitate follow-up mechanistic and preclinical studies to potentially advance this analogue into a clinical drug.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Lei Zhao

    Full Text Available 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.

  2. 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 radiolog...

  3. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie

    2015-04-01

    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. The Effect of Chemical Therapy with Bleomycin Sulfate on the Functional Parameters of the Endocrine Pancreas

    Directory of Open Access Journals (Sweden)

    Carlos Alberto da Silva

    2009-05-01

    Full Text Available Objective The objective of the present study was to evaluate the effect of bleomycin sulfate on parameters related to the functionality of pancreatic tissue, with emphasis on the glucose tolerance test, insulin tolerance test, insulinemia and static secretion of insulin as well as the insulin receptor, and PKA, PKC and GLUT2 concentrations in the pancreatic islets. Design Twenty-four male rats were divided into 2 groups: control and treated with bleomycin (2.5 mg/kg, intratracheal mode. After 7 days, the animals were euthanized and the analyses were carried out. Statistics The normality and the homoscedasticity of the data distribution were tested and ANOVA was applied. The Tukey post hoc test followed ANOVA for the comparison of the static insulin secretion test at different glucose concentrations. Results In the glucose tolerance test, the bleomycin group showed a larger area (17,306±539 mg/dLx60min than that of the control group (9,151±517 mg/dLx60min and in the insulin tolerance test, there was a greater percentage fall in glycemia (8.08±0.56% in the bleomycin than in the control group (3.87±1.14%. The bleomycin group also presented a reduction in insulin secretion and an increase in plasmatic insulin concentration in the static insulin secretion test. With respect to the concentrations of the insulin receptor, GLUT2, PKC and PKA in the pancreatic islets of the bleomycin group, there was an increase in GLUT2 (48.4% and PKC (70.8% and a reduction in PKA (38.5%. Conclusion During treatment with bleomycin, innumerable chemical-metabolic alterations were unleashed in the tissues which were not primary targets of the chemical therapy and which could compromise the homeostasis of the systems taking part in the glycemic adjustment, predisposing the organism to the development of a pre-diabetic pattern whose degree of incidence or reversibility is still unknown to the scientific community.

  6. Identification and quantification of bleomycin in serum and tumor tissue by liquid chromatography coupled to high resolution mass spectrometry.

    Science.gov (United States)

    Kosjek, Tina; Krajnc, Anja; Gornik, Tjasa; Zigon, Dusan; Groselj, Ales; Sersa, Gregor; Cemazar, Maja

    2016-11-01

    Bleomycin is a cytotoxic antibiotic available as a compost of structurally strongly related glycopeptides, which is in vivo found chelated with several metals. Its pharmacotherapy has merely been based on experimental dose - response data, whereas its biodistribution and pharmacokinetics remain fundamentally unknown. This is reasoned by an absence of a specific and sensitive mass spectrometry-based analytical method for its determination in biological tissues. We herein reveal the results of our study on the mass spectrometric behavior of two main bleomycin fractions A2 and B2, including their metal complexes, particularly the predominant copper chelates. In the electrospray ion source bleomycin forms double charged species, where for the metal-free fraction A2 and its copper complex m/z 707.76 and m/z 707.21 are seen, respectively. Hence, the second isotopic ion of the chelate (m/z 707.71) nearly coincides with the first isotopic ion of the metal-free fraction. This phenomenon can only be followed by high-resolution mass spectrometry, and is considered the plausible reason, why the attempts to determine bleomycin with mass spectrometry have been so scarce. The presented paper further describes a sensitive and selective liquid chromatography - mass spectrometry analytical method for determination of bleomycin in serum and tumor tissues. This newly developed method was employed for bleomycin pharmacokinetic studies in serum and tumors of laboratory animals. Additionally, the method was employed for determination of bleomycin pharmacokinetic parameters in elderly patients in order to determine the effective therapeutic window of electrochemotherapy with bleomycin. PMID:27591601

  7. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report

    OpenAIRE

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María del; Casero, Miguel Angel Racionero

    2016-01-01

    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A...

  8. FELD better not thinking of metastases only when liver lesions appear after bleomycin-based treatment for non-seminoma testis from metastases

    International Nuclear Information System (INIS)

    Bleomycin has become an integral part of chemotherapy in patients with germ-cell tumors. One of the most feared side effects is bleomycin-induced pneumonitis. In patients with mild or moderate BIP, radiological signs disappear almost completely within nine months after discontinuation of bleomycin treatment. We present a patient with a history of non seminoma of the testis and bleomycin-induced pneumonitis. During follow-up, regression of the hypothesis of eosinophilic migration to the liver after regression of bleomycin-induced pneumonitis is highly suspicious based on transient eosinophilia and focal eosinophilic liver disease. As follow up may consist of CT scanning in germ-line tumor patients, transient eosinophilic liver lesions reported during regressive bleomycin-induced pneumonitis should not be presumed automatically as metastatic tumor relapse and require further sequential imaging and pathological examination

  9. 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 (180μA 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.

  10. Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat.

    OpenAIRE

    Khalil, N.; Whitman, C.; Zuo, L; Danielpour, D; Greenberg, A

    1993-01-01

    In a model of pulmonary inflammation and fibrosis induced by the antineoplastic antibiotic, bleomycin, we previously demonstrated that TGF-beta was markedly elevated within 7 d of bleomycin administration. At the time of maximal TGF-beta production, TGF-beta 1 was localized by immunohistochemistry to be present almost exclusively in alveolar macrophages. In this study, we have demonstrated that alveolar macrophages stimulated by bleomycin-induced injury secrete large quantities of biologicall...

  11. 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

  12. Treatment of brain tumours with electroporation and bleomycin in an in vivo rat model

    OpenAIRE

    Ljungvall, Magnus; Salford, Leif; Persson, Bertil R

    2013-01-01

    The purpose of the study was to examine the possibilities of prolonging the life of rats with brain tumours using electroporation only while conducting impedance scans to evaluate the rate of electroporation. During the experiments, the treated rats in the first batch had tumors grow for 14 days and were then given electroporation with 8 + 8 exponential pulses at 800 v/cm, and 15 micro-F. Three of the animals given electroporation and bleomycin and one of the animals given e...

  13. CXC CHEMOKINE RECEPTOR 3 MODULATES BLEOMYCIN-INDUCED PULMONARY INJURY VIA INVOLVING INFLAMMATORY PROCESS

    Institute of Scientific and Technical Information of China (English)

    Jin-ming Gao; Bao Lu; Zi-jian Guo

    2006-01-01

    Objective To investigate the role of CXC chemokine receptor 3(CXCR3 ) in bleomycin-induced lung injury by using CXCR3 gene deficient mice.Methods Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea. Lung tissue was stained with HE method. Airway resistance was measured. Bronchoalveolar lavage (BAL) was performed using phosphate buffered saline twice, cell number and differentials were counted by Diff-Qnick staining. Interleukin(IL)-4, IL-5, IL-12p40, and interfon-γ in BAL fluid and lung homogenate were measured by enzyme-linked immunosorbent assay. Unpaired t test was explored to compare the difference between two groups.Results On day 7 after bleomycin injection via trachea, CXCR3 knockout mice were protected from bleomycininduced lung injury as evidenced by fewer accumulation of inflammatory cells in the airway and lung interstitium compared with their wild type littermates ( P<0.05 ). Airway resistance was also lower in CXCR3 knockout mice compared with wild type mice (P<0.01 ). Significantly lower level of inflammatory cytokines release, including the altered production of IL-4 and IL-5 both in BAL fluid and lung tissue was seen in CXCR3 knockout mice than in wild type mice (both P<0.05).Conclusion CXCR3 signaling promotes inflammatory cells recruiting and initiates inflammatory cytokines cascade following endotracheal bleomycin administration, indicating that CXCR3 might be a therapeutic target for pulmonary injury.

  14. Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats

    OpenAIRE

    Wan, Yun-Yan; Tian, Guang-Yan; Guo, Hai-Sheng; Kang, Yan-Meng; Yao, Zhou-Hong; Li, Xi-Li; Liu, Qing-Hua; Lin, Dian-Jie

    2013-01-01

    Background Recent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats. Methods The rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late ...

  15. Scanning electron microscopic study of capillary change in bleomycin-induced pulmonary fibrosis.

    OpenAIRE

    Kwon, K. Y.; Park, K K; Chang, E. S.

    1991-01-01

    The architectural changes which occur in the capillaries are difficult to illustrate without a three-dimensional tool, such as scanning electron microscopy. Therefore, a scanning electron microscopic study was occasionally undertaken to show the capillary changes of lung fibrosis. Fibrosis was induced in twenty rats by an intratracheal injection of bleomycin. After 30 days the rats were sacrificed, and light microscopy and scanning electron microscopy were performed. The vascular trees of bot...

  16. 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.

  17. Relationship between the time of doubling of pulmonary tumours and the uptake of labelled bleomycin

    International Nuclear Information System (INIS)

    The correlations between the uptake of cobalt 57 labelled bleomycin and, firstly, survival and, secondly, the time necessary for a primary bronchial carcinoma to double in volume were studied. Analysis of 22 cases showed significant correlations to p=0,001. The greater the fixation index, the shorter was the doubling time and the survival. One may consider that this finding permits measurement of the cellular proliferation of carcinomas, the clinical interest of which is obvious

  18. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  19. 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-κB (NF-κB) 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...

  20. Andrographolide plays an important role in bleomycin-induced pulmonary fibrosis treatment

    OpenAIRE

    Yin, Jia-ning; Li, Ya-Nan; Gao, Yang; Li, Shi-Bo; Li, Jian-Dong

    2015-01-01

    Pulmonary fibrosis (PF) leads to chronic inflammation and accumulation of macrophages, neutrophils, and lymphocytes in the alveoli. The factors involved in the development of PF include reactive oxygen species and tissue remodelling regulators. The present study demonstrates the effect of andrographolide on bleomycin (BLM)-induced PF in Sprague-Dawley rats. We investigated the total bronchoalveolar lavage fluid protein (BALF) and hydroxyproline (HYP) content along with the level of oxidative ...

  1. Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice

    Science.gov (United States)

    Trivedi, Ruchit; Redente, Elizabeth F.; Thakur, Ashish; Riches, David W. H.; Kompella, Uday B.

    2012-12-01

    Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation. Poly(lactide-co-glycolide) nanoparticles containing pirfenidone (NPs) were prepared and characterized. Biodistribution of NPs and solution was assessed using LC-MS after intratracheal administration in C57Bl/6 mice at 3 and 24 h and 1 week post-administration. Efficacy was tested in C57Bl/6 mice in a bleomycin-induced pulmonary fibrosis model. Mice received 10 μg pirfenidone intratracheally in solution or NPs, once a week, for 3 weeks after bleomycin administration. Drug effects were monitored on day 28. Lung hydroxyproline content, total number of cells, and numbers of macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage (BAL) were assessed. Numbers of macrophages, lymphocytes, and neutrophils were assessed in the lung as well. NPs sustained significantly higher levels of pirfenidone in the lungs and BAL at 24 h and 1 week, compared to the solution group. Pirfenidone solution and NPs significantly reduced hydroxyproline levels by 57 and 81%, respectively, compared to bleomycin alone. At the end of 4 weeks, BAL cellularity was reduced by 25.4% and 56% with solution and NP treatment, respectively. The numbers of lymphocytes and neutrophils in the BAL were also reduced by 58.9 and 82.4% for solution and 74.5% and 89.7% for NPs, respectively. The number of inflammatory macrophages in the lung was reduced by 62.8% and the number of neutrophils was reduced by 59.1% in the NP group and by 37.7% and 44.5%, respectively, in the solution group, compared to bleomycin alone. In conclusion, nanoparticles sustain lung pirfenidone delivery and enhance its anti-fibrotic efficacy.

  2. Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice

    International Nuclear Information System (INIS)

    Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation. Poly(lactide-co-glycolide) nanoparticles containing pirfenidone (NPs) were prepared and characterized. Biodistribution of NPs and solution was assessed using LC-MS after intratracheal administration in C57Bl/6 mice at 3 and 24 h and 1 week post-administration. Efficacy was tested in C57Bl/6 mice in a bleomycin-induced pulmonary fibrosis model. Mice received 10 μg pirfenidone intratracheally in solution or NPs, once a week, for 3 weeks after bleomycin administration. Drug effects were monitored on day 28. Lung hydroxyproline content, total number of cells, and numbers of macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage (BAL) were assessed. Numbers of macrophages, lymphocytes, and neutrophils were assessed in the lung as well. NPs sustained significantly higher levels of pirfenidone in the lungs and BAL at 24 h and 1 week, compared to the solution group. Pirfenidone solution and NPs significantly reduced hydroxyproline levels by 57 and 81%, respectively, compared to bleomycin alone. At the end of 4 weeks, BAL cellularity was reduced by 25.4% and 56% with solution and NP treatment, respectively. The numbers of lymphocytes and neutrophils in the BAL were also reduced by 58.9 and 82.4% for solution and 74.5% and 89.7% for NPs, respectively. The number of inflammatory macrophages in the lung was reduced by 62.8% and the number of neutrophils was reduced by 59.1% in the NP group and by 37.7% and 44.5%, respectively, in the solution group, compared to bleomycin alone. In conclusion, nanoparticles sustain lung pirfenidone delivery and enhance its anti-fibrotic efficacy. (paper)

  3. Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Zhou, Y; Zhu, W P; Cai, X J; Chen, M

    2016-01-01

    We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection. PMID:27173212

  4. Interspecies cytogenetic comparisons: Studies with x-radiation and bleomycin sulfate

    International Nuclear Information System (INIS)

    A series of in vitro experiments were conducted to determine if there are innate differences in the sensitivity of peripheral blood lymphocytes (PBLs) from different mammalian species to clastogens. Mouse, rat, and human whole blood samples were exposed to either 0, 0.38, 0.75, 1.5, or 3.0 Gy x-radiation or 0, 5, 10, 20, 40, or 80 μg/ml bleomycin for 4 hr. Bromodeoxyuridine-containing cultures were initiated and the PBLs stimulated to divide with phytohemagglutinin. All cultures were harvested following a 3-hr colcemid treatment. Slides were made and differentially stained, and first-division metaphases were scored for chromosome aberrations. In the x-radiation studies human PBLs were significantly more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs as measured by either the total percent aberrant cells or the number of dicentrics. Data from all three species could be fitted to a linear-quadratic model. Results with bleomycin suggest that the mouse and human PBLs are equally sensitive to the clastogenic effects of bleomycin. Both appeared to be more sensitive than the rat PBLs, but the variation between experiments was such that the results among species were not significantly different. These results indicate that there may be inherent differences in sensitivity among PBLs of mammalian species; however, more studies are needed to determine if the differences presented here hold for other agents. 39 refs., 2 figs., 4 tabs

  5. Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Zuojun Xu

    2012-07-01

    Full Text Available The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK, may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-β1 (TGF-β1, connective tissue growth factor (CTGF, alpha-smooth muscle actin (α-SMA, and plasminogen activator inhibitor-1 (PAI-1 mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.

  6. 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.)

  7. Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Zhang, Zongmei; Yu, Xiaoting; Fang, Xia; Liang, Aibin; Yu, Zhang; Gu, Pan; Zeng, Yu; He, Jian; Zhu, Hailong; Li, Shuai; Fan, Desheng; Han, Fei; Zhang, Lanjing; Yi, Xianghua

    2015-01-01

    Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis. PMID:26627341

  8. Periostin Deficiency Causes Severe and Lethal Lung Injury in Mice With Bleomycin Administration.

    Science.gov (United States)

    Kondoh, Hirofumi; Nishiyama, Takashi; Kikuchi, Yoshinao; Fukayama, Masashi; Saito, Mitsuru; Kii, Isao; Kudo, Akira

    2016-07-01

    Pulmonary capillary leakage followed by influx of blood fluid into the air space of lung alveoli is a crucial step in the progression of acute lung injury (ALI). This influx is due to increased permeability of the alveolar-capillary barrier. The extracellular matrix (ECM) between the capillary and the epithelium would be expected to be involved in prevention of the influx; however, the role of the ECM remains to be addressed. Here, we show that the ECM architecture organized by periostin, a matricellular protein, plays a pivotal role in the survival of bleomycin-exposed mice. Periostin was localized in the alveolar walls. Although periostin-null mice displayed no significant difference in lung histology and air-blood permeability, they exhibited early lethality in a model of bleomycin-induced lung injury, compared with their wild-type counterparts. This early lethality may have been due to increased pulmonary leakage of blood fluid into the air space in the bleomycin-exposed periostin-null mice. These results suggest that periostin in the ECM architecture prevents pulmonary leakage of blood fluid, thus increasing the survival rate in mice with ALI. Thus, this study provides an evidence for the protective role of the ECM architecture in the lung alveoli. PMID:27270966

  9. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    Science.gov (United States)

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A.

  10. 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.

  11. Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology.

    Directory of Open Access Journals (Sweden)

    Christine Egger

    Full Text Available Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR. In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.

  12. Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical

    International Nuclear Information System (INIS)

    Several radiolabeled bleomycin derivatives have been developed for imaging and/or therapy of neoplastic tissues. The most important imaging compounds contain indium-111, cobalt- 57, and rhodium-105. In our previous studies we have prepared radiolabeled bleomycin complexes such as gallium-67 as therapeutic and/or imaging agents. Our recent studies on the preparation and tumour imaging properties of [67Ga]bleomycin in normal and tumour-bearing mice showed a good tumour/blood and tumour/muscle ratio suggesting that it is an appropriate diagnostic agent. Due to the interesting properties and increasing importance of positron emission tomography, we investigated the possibility of incorporating 66Ga as a positron emitter with an antineoplastic compound, bleomycin, for use in tumour imaging. We optimized 66Ga complex formation conditions with bleomycin, to develop [66Ga]BLM. We hereby report the production of 66Ga, preparation, optimization, stability, and formulation studies of [66Ga]-bleomycin complex. Targetry: An electroplated 66Zn target on a copper backing plate was irradiated at an angle of 6 degrees toward the proton beam in order to achieve higher production yield. The target was cooled by a flow of 18 deg. C distilled water with a rate of 50 Lit/min. Chemical Separation: The irradiated target was dissolved by 10 N HCl (15 ml, H2O2 added) and the solution was passed through a cation exchange resin (Dowex 50 Wx8, H+ form) (h:10 cm, diameter:1 cm). The resulting high-purity [66Ga]GaCl3 solution was used directly in the labeling step. Labeling of bleomycin with [66Ga]GaCl3: [66Ga]GaCl3 (0.25-2.5 mCi) dissolved in acidic medium obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted to various pHs (1-7) using 1M HCl and/or 1M NaOH. 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 and was heated at different temperatures (25, 50, 80, and 100 deg. C) and was

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

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    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.

  14. Increased Cellular NAD+ Level through NQO1 Enzymatic Action Has Protective Effects on Bleomycin-Induced Lung Fibrosis in Mice

    Science.gov (United States)

    Oh, Gi-Su; Lee, Su-Bin; Karna, Anjani; Kim, Hyung-Jin; Shen, AiHua; Pandit, Arpana; Lee, SeungHoon

    2016-01-01

    Background Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to NAD+ by various quinones and thereby elevates the intracellular NAD+ levels. In this study, we examined the effect of increase in cellular NAD+ levels on bleomycin-induced lung fibrosis in mice. Methods C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with β-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor β1 (TGF-β1) and β-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1–induced ECM expression and EMT in A549 cells. Conclusion Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1–induced EMT in vitro, by elevating the NAD+/NADH ratio through NQO1 activation.

  15. Leukotriene B4 mediates macrophage influx and pulmonary hypertension in bleomycin-induced chronic neonatal lung injury.

    Science.gov (United States)

    Ee, Mong Tieng; Kantores, Crystal; Ivanovska, Julijana; Wong, Mathew J; Jain, Amish; Jankov, Robert P

    2016-08-01

    Systemically-administered bleomycin causes inflammation, arrested lung growth, and pulmonary hypertension (PHT) in the neonatal rat, similar to human infants with severe bronchopulmonary dysplasia (BPD). Leukotrienes (LTs) are inflammatory lipid mediators produced by multiple cell types in the lung. The major LTs, LTB4 and cysteinyl LTs, are suggested to contribute to BPD, but their specific roles remain largely unexplored in experimental models. We hypothesized that LTs are increased in bleomycin-induced BPD-like injury, and that inhibition of LT production would prevent inflammatory cell influx and thereby ameliorate lung injury. Rat pups were exposed to bleomycin (1 mg·kg(-1)·day(-1) ip) or vehicle (control) from postnatal days 1-14 and were treated with either zileuton (5-lipoxygenase inhibitor), montelukast (cysteinyl LT1 receptor antagonist), or SC57461A (LTA4 hydrolase inhibitor) 10 mg·kg(-1)·day(-1) ip. Bleomycin led to increased lung content of LTB4, but not cysteinyl LTs. Bleomycin-induced increases in tissue neutrophils and macrophages and lung contents of LTB4 and tumor necrosis factor-α were all prevented by treatment with zileuton. Treatment with zileuton or SC57461A also prevented the hemodynamic and structural markers of chronic PHT, including raised pulmonary vascular resistance, increased Fulton index, and arterial wall remodeling. However, neither treatment prevented impaired alveolarization or vascular hypoplasia secondary to bleomycin. Treatment with montelukast had no effect on macrophage influx, PHT, or on abnormal lung structure. We conclude that LTB4 plays a crucial role in lung inflammation and PHT in experimental BPD. Agents targeting LTB4 or LTB4-mediated signaling may have utility in infants at risk of developing BPD-associated PHT. PMID:27317685

  16. Brucella ovis PA mutants for outer membrane proteins Omp10, Omp19, SP41, and BepC are not altered in their virulence and outer membrane properties.

    Science.gov (United States)

    Sidhu-Muñoz, Rebeca S; Sancho, Pilar; Vizcaíno, Nieves

    2016-04-15

    Mutants in several genes have been obtained on the genetic background of virulent rough (lacking O-polysaccharide) Brucella ovis PA. The target genes encode outer membrane proteins previously associated with the virulence of smooth (bearing O-polysaccharide chains in the lipopolysaccharide) Brucella strains. Multiple attempts to delete omp16, coding for a homologue to peptidoglycan-associated lipoproteins, were unsuccessful, which suggests that Omp16 is probably essential for in vitro survival of B. ovis PA. Single deletion of omp10 or omp19-that encode two other outer membrane lipoproteins--was achieved, but the simultaneous removal of both genes failed, suggesting an essential complementary function between both proteins. Two other deletion mutants, defective in the Tol-C-homologue BepC or in the SP41 adhesin, were also obtained. Surprisingly when compared to previous results obtained with smooth Brucella, none of the B. ovis mutants showed attenuation in the virulence, either in the mouse model or in cellular models of professional and non-professional phagocytes. Additionally, and in contrast to the observations reported with smooth Brucella strains, several properties related to the outer membrane remained almost unaltered. These results evidence new distinctive traits between naturally rough B. ovis and smooth brucellae.

  17. Disruption of Calcium Signaling in Fibroblasts and Attenuation of Bleomycin-Induced Fibrosis by Nifedipine.

    Science.gov (United States)

    Mukherjee, Subhendu; Ayaub, Ehab A; Murphy, James; Lu, Chao; Kolb, Martin; Ask, Kjetil; Janssen, Luke J

    2015-10-01

    Fibrotic lung disease afflicts millions of people; the central problem is progressive lung destruction and remodeling. We have shown that external growth factors regulate fibroblast function not only through canonical signaling pathways but also through propagation of periodic oscillations in Ca(2+). In this study, we characterized the pharmacological sensitivity of the Ca(2+)oscillations and determined whether a blocker of those oscillations can prevent the progression of fibrosis in vivo. We found Ca(2+) oscillations evoked by exogenously applied transforming growth factor β in normal human fibroblasts were substantially reduced by 1 μM nifedipine or 1 μM verapamil (both L-type blockers), by 2.7 μM mibefradil (a mixed L-/T-type blocker), by 40 μM NiCl2 (selective at this concentration against T-type current), by 30 mM KCl (which partially depolarizes the membrane and thereby fully inactivates T-type current but leaves L-type current intact), or by 1 mM NiCl2 (blocks both L- and T-type currents). In our in vivo study in mice, nifedipine prevented bleomycin-induced fibrotic changes (increased lung stiffness, overexpression of smooth muscle actin, increased extracellular matrix deposition, and increased soluble collagen and hydroxyproline content). Nifedipine had little or no effect on lung inflammation, suggesting its protective effect on lung fibrosis was not due to an antiinflammatory effect but rather was due to altering the profibrotic response to bleomycin. Collectively, these data show that nifedipine disrupts Ca(2+) oscillations in fibroblasts and prevents the impairment of lung function in the bleomycin model of pulmonary fibrosis. Our results provide compelling proof-of-principle that interfering with Ca(2+) signaling may be beneficial against pulmonary fibrosis.

  18. Effects of 1,25( OH)2D3 on bleomycin-induced pulmonary fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    张宗梅

    2014-01-01

    Objective To observe the effects of 1,25(OH)2D3on bleomycin-induced pulmonary fibrosis in mice and to explore its mechanisms.Methods Ninety male C57BL/6mice,6 to 8 weeks old,were randomly divided into 3groups according to the table of random numbers:a control group,a model group and a treatment group(n=30each).Bleomycin was injected to the mice in the latter 2groups by single intratracheal injection to duplicate the pulmonary fibrosis model,while the control group was injected with

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

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    Yinghua Song

    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 μM. 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 α-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

  1. Serum bleomycin-detectable iron in patients with thalassemia major with normal range of serum iron.

    Directory of Open Access Journals (Sweden)

    Han,Khin Ei

    1995-06-01

    Full Text Available "Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma. The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females. High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl. Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl, normal serum iron does not preclude the presence of free iron in the serum.

  2. Human lung tumors: SPECT quantitation of differences in Co-57 bleomycin uptake

    International Nuclear Information System (INIS)

    A newly developed single photon emission computed tomography (SPECT) method was used to measure noninvasively the concentration of labeled drugs in human lung tumors. The validity of the method was established by the high correlation (r = .92) between in vivo SPECT measurement of the concentration of glucoheptonate labeled with technetium-99m and in vitro measurement of the concentration of the drug in specimens of nine of the same tumors obtained at surgery. The in vivo concentration of intravenously injected bleomycin labeled with cobalt-57 was measured over time in 14 human lung tumors. Significant differences were found in the uptake of bleomycin by the tumors, even those with the same histologic characteristics, when the concentration over time, the tumor/blood ratio at 30 minutes, and the tumor cumulative concentration were measured in vivo. Since the drug concentration in the blood was not related to the concentration in the tumor (r = .54), uptake of chemotherapeutic drugs should be measured in each patient individually

  3. CD4(+)CD25(hi)Foxp3(+) Cells Exacerbate Bleomycin-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Birjandi, Shirin Z; Palchevskiy, Vyacheslav; Xue, Ying Ying; Nunez, Stefanie; Kern, Rita; Weigt, S Sam; Lynch, Joseph P; Chatila, Talal A; Belperio, John A

    2016-08-01

    Idiopathic pulmonary fibrosis is a fatal lung disease with a median survival of 2 to 5 years. A decade of studies has downplayed inflammation contributing to its pathogenesis. However, these studies preceded the discovery of regulatory T cells (Tregs) and all of their functions. On the basis of human studies demonstrating Tregs can decrease graft-versus-host disease and vasculitides, there is consideration of their use to treat idiopathic pulmonary fibrosis. We hypothesized that Treg therapy would attenuate the fibroplasia involved in a preclinical murine model of pulmonary fibrosis. IL-2 complex was used in vivo to expand CD4(+)CD25(hi)Foxp3(+) cells in the lung during intratracheal bleomycin challenge; however, this unexpectedly led to an increase in lung fibrosis. More important, this increase in fibrosis was a lymphocyte-dependent process. We corroborated these results using a CD4(+)CD25(hi)Foxp3(+) cellular-based therapy. Mechanistically, we demonstrated that CD4(+)CD25(hi)Foxp3(+) cells undergo alterations during bleomycin challenge and the IL-2 complex had no effect on profibrotic (eg, transforming growth factor-β) or type 17 immune response cytokines; however, there was a marked down-regulation of the type 1 and augmentation of the type 2 immune response cytokines from the lungs. Collectively, our animal studies show that a specific lung injury can induce Treg alterations, which can augment pulmonary fibrosis. PMID:27317904

  4. Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Brewer, George J; Ullenbruch, Matthew R; Dick, Robert; Olivarez, Leovigildo; Phan, Sem H

    2003-03-01

    Tetrathiomolybdate (TM), a drug developed for the treatment of Wilson's disease, produces an antiangiogenic effect by reducing systemic copper levels. Several angiogenic cytokines appear to depend on normal levels of copper for activity. In both animal tumor models and in cancer patients, TM therapy has proved effective in inhibiting the growth of tumors. We have hypothesized that the activities of fibrotic and inflammatory cytokines are also subject to modulation by the availability of copper in a manner similar to angiogenic cytokines. As a first step in evaluating whether TM plays a therapeutic role in diseases of inflammation and fibrosis, we studied the effects of TM on a murine model of bleomycin-induced pulmonary fibrosis. Oral TM therapy resulted in dose-dependent reduction in serum ceruloplasmin, a surrogate marker of systemic copper levels. Significant decreases in systemic copper levels were associated with marked reduction in lung fibrosis as determined on the basis of histopathologic findings and a biochemical measure of fibrosis. The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit.

  5. Intralesional Bleomycin as an Adjunct Therapeutic Modality in Eyelid and Extraocular Malignancies and Tumors.

    Science.gov (United States)

    Meyer, David; Gooding, Caroline

    2015-01-01

    To present our recent experience with intralesional bleomycin (IBI) in nonmelanoma extraocular tumors, and present previous experience on periocular capillary hemangiomas and orbital lymphangiomas in a tertiary referral hospital. This was a retrospective descriptive study of patients with eyelid and extraocular malignancies where conventional therapies failed, or surgery was contraindicated or refused and were offered IBI as an alternate therapy. All patients were recruited from the Oculoplastics Clinic at Tygerberg Academic Hospital, Cape Town, South Africa. A solution containing 1 international unit of bleomycin per milliliter saline was injected intralesionally together with 2% lignocaine in a ratio of 4:1. The injected volume was calculated to be equivalent to the estimated volume of the lesion. A multipuncture technique with a 29-gauge needle was used. Patients requiring retreatment were injected every 4-8 weeks until satisfactory clinical endpoints were achieved. Our previous experience with IBI in extensive capillary hemangiomas and orbital lymphangiomas is reviewed. Cases are presented to illustrate that IBI induced significant regression and reduction in tumor size and marked clinical improvement of the eyelid and orbital basal cell carcinomas, Kaposi sarcoma, and mycosis fungoides. The improvements obviated the need for further surgical intervention in most cases. Based on clinical experience we propose that IBI should be considered a treatment modality in select cases of the malignant eyelid and ophthalmic vascular tumors where the conventional standard of care is not possible. IBI is a reasonable alternative or adjunct to consider in such cases. PMID:26692709

  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 μs 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. The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.

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    Abdulaleem Alnajar

    Full Text Available 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.

  8. 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

  9. Chemical activity of anticancer compounds : computational studies on the mechanism of bleomycin and the recognition of flavonoids

    NARCIS (Netherlands)

    Karawajczyk, Anna

    2007-01-01

    The thesis is focused on the DNA-cleaving antibiotic bleomycin that is successfully used in the chemotherapy against several types of cancer like head and neck cancer or certain lymphomas and testicular cancer. Although it has been in use for more than two decades, the mechanism of its action is not

  10. Comparative Analysis of the Biosynthetic Gene Clusters and Pathways for Three Structurally Related Antitumor Antibiotics Bleomycin, Tallysomycin and Zorbamycin†

    OpenAIRE

    Galm, Ute; Wendt-Pienkowski, Evelyn; Wang, Liyan; Huang, Sheng-Xiong; Unsin, Claudia; Tao, Meifeng; Coughlin, Jane M.; Shen, Ben

    2011-01-01

    The biosynthetic gene clusters for the glycopeptide antitumor antibiotics bleomycin (BLM), tallysomycin (TLM), and zorbamycin (ZBM) have been recently cloned and characterized from Streptomyces verticillus ATCC15003, Streptoalloteichus hindustanus E465-94 ATCC31158, and Streptomyces flavoviridis ATCC21892, respectively. The striking similarities and differences among the biosynthetic gene clusters for the three structurally related glycopeptide antitumor antibiotics prompted us to compare and...

  11. Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients

    International Nuclear Information System (INIS)

    Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer. Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference. The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach

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

    Directory of Open Access Journals (Sweden)

    Maria Cristina P. Araújo

    1999-09-01

    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.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 curcumina 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

  13. Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.

    Directory of Open Access Journals (Sweden)

    Orquidea Garcia

    Full Text Available The potential for amniotic fluid stem cell (AFSC treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF, is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0 or chronic (day 14 intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL, but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

  14. Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.

    Directory of Open Access Journals (Sweden)

    Evgenii Germanovich Skurikhin

    Full Text Available Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA. To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL. Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem /progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF-β, interleukin (IL-1β, tumor necrosis factor (TNF-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/ progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31‒ CD34‒ CD45‒ CD44+ CD73+ CD90+ CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan

  15. Cryptographic Protocols:

    DEFF Research Database (Denmark)

    Geisler, Martin Joakim Bittel

    cryptography was thus concerned with message confidentiality and integrity. Modern cryptography cover a much wider range of subjects including the area of secure multiparty computation, which will be the main topic of this dissertation. Our first contribution is a new protocol for secure comparison, presented...... framework. We call this framework VIFF, short for Virtual Ideal Functionality Framework. VIFF implements a UC functionality for general multiparty computation on asynchronous networks. We give a formal definition of the functionality in Chapter 3. There we also describe how we implemented the functionality...... 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 more theoretical subject...

  16. Rational Protocols

    Science.gov (United States)

    Cachin, Christian

    Security research continues to provide a plethora of new protocols and mechanisms; these solutions patch either existing vulnerabilities found in practical systems or solve hypothetical security problems in the sense that the problem is often conceived at the same time when the first solution is proposed. Yet only a very small fraction of this research is relevant to ordinary users in the sense that they are willing to actually deploy the technology.

  17. Bleomycin in octaarginine-modified fusogenic liposomes results in improved tumor growth inhibition.

    Science.gov (United States)

    Koshkaryev, Alexander; Piroyan, Aleksandr; Torchilin, Vladimir P

    2013-07-01

    Bleomycin (BLM) is an example of an anticancer drug that should be delivered into cytosol for its efficient therapeutic action. With this in mind, we developed octaarginine (R8)-modified fusogenic DOPE-liposomes (R8-DOPE-BLM). R8-modification dramatically increased (up to 50-fold) the cell-liposome interaction. R8-DOPE-liposomes were internalized via macropinocytosis and did not end up in the lysosomes. R8-DOPE-BLM led to a significantly stronger cell death and DNA damage in vitro relative to all controls. R8-DOPE-BLM demonstrated a prominent anticancer effect in the BALB/c mice bearing 4T1 tumors. Thus, R8-DOPE-BLM provided efficient intracellular delivery of BLM leading to strong tumor growth inhibition in vivo. PMID:22743614

  18. 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)

  19. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

    2015-04-01

    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression. PMID:25188360

  20. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

    2015-04-01

    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  1. 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); Parıldar, 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.

  2. Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

    Science.gov (United States)

    Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli

    2016-06-01

    Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression

  3. Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

    Science.gov (United States)

    Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli

    2016-06-01

    Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression

  4. Histology protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-06-01

    Full Text Available 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 what apparently are two separeted words: molecular biology and histology. Simply remembering to the youngest scientists.....

  5. BlmB and TlmB provide resistance to the bleomycin family of antitumor antibiotics by N-acetylating metal-free bleomycin, tallysomycin, phleomycin, and zorbamycin.

    Science.gov (United States)

    Coughlin, Jane M; Rudolf, Jeffrey D; Wendt-Pienkowski, Evelyn; Wang, Liyan; Unsin, Claudia; Galm, Ute; Yang, Dong; Tao, Meifeng; Shen, Ben

    2014-11-11

    The bleomycin (BLM) family of glycopeptide-derived antitumor antibiotics consists of BLMs, tallysomycins (TLMs), phleomycins (PLMs), and zorbamycin (ZBM). The self-resistant elements BlmB and TlmB, discovered from the BLM- and TLM-producing organisms Streptomyces verticillus ATCC15003 and Streptoalloteichus hindustanus E465-94 ATCC31158, respectively, are N-acetyltransferases that provide resistance to the producers by disrupting the metal-binding domain of the antibiotics required for activity. Although each member of the BLM family of antibiotics possesses a conserved metal-binding domain, the structural differences between each member, namely, the bithiazole moiety and C-terminal amine of BLMs, have been suggested to instill substrate specificity within BlmB. Here we report that BlmB and TlmB readily accept and acetylate BLMs, TLMs, PLMs, and ZBM in vitro but only in the metal-free forms. Kinetic analysis of BlmB and TlmB reveals there is no strong preference or rate enhancement for specific substrates, indicating that the structural differences between each member of the BLM family play a negligible role in substrate recognition, binding, or catalysis. Intriguingly, the zbm gene cluster from Streptomyces flavoviridis ATCC21892 does not contain an N-acetyltransferase, yet ZBM is readily acetylated by BlmB and TlmB. We subsequently established that S. flavoviridis lacks the homologue of BlmB and TlmB, and ZbmA, the ZBM-binding protein, alone is sufficient to provide ZBM resistance. We further confirmed that BlmB can indeed confer resistance to ZBM in vivo in S. flavoviridis, introduction of which into wild-type S. flavoviridis further increases the level of resistance.

  6. 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

  7. 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; Hojman, Pernille;

    2013-01-01

    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...

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

    OpenAIRE

    Srabani Kar; Surajlata Konsam; Garima Hore; Shinjini Mitra; Silpak Biswas; Aryabaran Sinha; Nikhil Ranjan Jana; Ena Ray Banerjee

    2015-01-01

    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 ...

  9. Inhibition of bleomycin-induced pulmonary fibrosis by nordihydroguaiaretic acid. The role of alveolar macrophage activation and mediator production.

    OpenAIRE

    Phan, S. H.; Kunkel, S L

    1986-01-01

    The role of alveolar macrophage activation and release of mediators remains unclear. In this study, this role is examined with respect to the effects of relatively selective inhibitors of arachidonate metabolism on the pathogenesis of pulmonary fibrosis. CBA/J mice were administered bleomycin (0.037 units) endotracheally to induce pulmonary fibrosis. Daily intraperitoneal injections of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) inhibited pulmonary fibrosis in a dose-dependent ...

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

    OpenAIRE

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

    1999-01-01

    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 ...

  11. Effect of polyunsaturated fatty acids and their metabolites on bleomycin-induced cytotoxic action on human neuroblastoma cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sailaja Polavarapu

    Full Text Available In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs tested on human neuroblastoma IMR-32 (0.5 × 10(4 cells/100 µl of IMR cells (EPA > DHA > ALA = GLA = AA > DGLA = LA: ∼ 60, 40, 30, 10-20% respectively at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2α, and PGI2 and leukotrienes (LTD4 and LTE4 tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4, 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA and 10(S,17(S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S,17(SDiHDoHE, metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions.

  12. Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments.

    Directory of Open Access Journals (Sweden)

    Wen-Jie Ji

    Full Text Available BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20 mg/kg/day by oral gavage revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson' trichrome staining in bleomycin treated (2.5 mg/kg, via oropharyngeal instillation male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+ of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c- remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.

  13. 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

  14. 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.

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

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    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.

  16. The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis.

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    Ajit A Kulkarni

    Full Text Available Pulmonary Fibrosis (PF is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11dien-28-oate, Bardoxolone methyl is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p≤0.01, inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p≤0.001, and excess production of the pro-fibrotic cytokine TGFβ by 50%. CDDO-Me also inhibited α-smooth muscle actin and fibronectin mRNA by 50% (p≤0.05. On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and αSMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation and by systemic autoimmune diseases.

  17. The experimental study of intra-bronchus embolization of bleomycin-lipiodol emulsion in dogs

    International Nuclear Information System (INIS)

    Objective: To investigate the possibility of using bleomycin-lipiodol emulsion (BLE) as an agent for functional pulmonary lobectomy. Methods: The bilateral lungs of sixteen healthy mongrel dogs were randomly divided into the Control group and the FPLT group. In FPLT group the target pulmonary, lobes were filled with BLE and then the target bronchi were occluded. In Control group the pulmonary lobes were done with nothing. The dogs were took X-ray films pre-procedure and post-procedure and then on 1st, 7th, 14th, 21st, and 28th day, respectively, some of them were sacrificed after procedure for histopathologieal examination. Results: Histopathologically in the early time the target pulmonary lobes were mainly inflammatory effusion. After seven days the alveoli collapsed, pulmonary interstitium widened and fibrous connective tissue proliferated. After twenty-eight days the target pulmonary lobes were atelectasis and entirely fibrosis. The fibrosis grade based on Ashcroft's semiquantitative grading system. The grade of pulmonary fibrosis was 0.66±0.06, 2.76±0.24, 4.70±0.22, 6.74±0.25 and 7.69±0.23 in FPLT group and 0.62±0.05, 0.63±0.10, 0.63±0.07, 0.62±011 and 0.63±0.10 in control group separately at 1st, 7th, 14th, 2lst and 28th day after procedure. There was significant difference in the corresponding period between the FPLT group and the control group (P<0.01) and between first day (0.66±0.06) and fourteenth day(4.70 ± 0.22) (P<0.01) and fourteenth day and twenty-eighth day (7.69±0.23) (P<0.01). Conclusion: Intra-bronchus embolization of bleomycin-lipiodol emulsion can result in atelectasis and fibrosis of the target pulmonary, lobes can achieve FPLT. (authors)

  18. 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)-β1 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

  19. 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

    2016-02-01

    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

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

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    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.).

  1. 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-1β 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-β1-induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1-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-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-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

  2. 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.)

  3. 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

  4. Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study

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    Yasmina M. Abd-Elhakim

    2014-01-01

    Full Text Available This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV and/or the chemotherapeutic agent bleomycin (BLM on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20 μg/mL respectively for 24 and 72 hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2. The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity.

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

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    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 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.

  6. Internal parameters monitored during intraarterial cytostatic therapy with methotrexate and bleomycin combined with radiotherapy

    International Nuclear Information System (INIS)

    Over a period of ten years, i.e., 1973 to 1983, the Vienna Clinic of Mandibular and Facial Surgery treated 109 patients with primary inoperable malignant tumors using regional chemotherapy, i.e., a combination of methotrexate and bleomycin. 95 patients in the groups were also irradiated. The aim of the internal examinations was to assess whether from the beginning of cytostatic therapy it would be possible to deduct from laboratory chemical examinations some prognostic factors, or whether changes in internal parameters during therapy correspond to the further development of the growth. The examination of chemical parameters showed that the permanently reduced levels of Fe and anemia are demonstrably adverse factors for prognosis. The drop in leukocyte and thrombocyte counts and the toxic damage of bone marrow also proved to be such an adverse factor. On the other hand the rise in serum levels of LDH, AST and ALT in the process of therapy may be assessed as favourable factors for the prognosis of the disease. (author). 1 fig., 12 refs

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

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    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.

  8. Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System

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    Yue Xu

    2013-01-01

    Full Text Available Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs coated with polyacrylic acid (PAA as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM, vibrating sample magnetometer (VSM, and Fourier transform infrared spectroscopy (FTIR. The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30 nm exhibit a saturation magnetization of 87 emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24 h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23 hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

  9. 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.

  10. 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.

  11. 烹调油烟冷凝物诱导永生化人支气管上皮细胞恶性转化的研究%Study for Malignant Transformation of Immortalized Human Bronchial Epithelial (BEP-2D)Cells Induced by Cooking Oil Fumes Condensation

    Institute of Scientific and Technical Information of China (English)

    张诚; 李强; 吴庆琛; 朱茂祥; 杨陟华; 陈丹; 张敏

    2011-01-01

    Objective To find a good method for chronic malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells induced by cooking oil fumes condensation (COFC ), establish a model of malignant tranformation of BEP-2D cells and discuss the harm of COFC. Methods Cells was divided into control group and experimental group. MTT was used to decide the chronic exposure doses of the COFC. The malignant tendency of transformed BEP-2D cells was identified by anti-blood serum experiment and the malignant features of transformed BEP-2D cells were identified by the method of semisolid agar culture. The capability of COFC inducing differentiation in anti-blood serum experiment and the colony forming frequency of BEP-2D cells in semisolid agar medium in each group were compared. Results The best method for malignant tranformation of BEP-2D cells induced by the COFC was that the BEP-2D cells were treated with COFC at doses of 50 μg/mL respectively. Inoculated to the 20 generations, the cells inoculative efficiency were obviously disparity in the comparison of control group (P < 0.01). Inoculated to the 35th generation, the anchorage independent growth was appeared in the P35 (P < 0.05). The P35 BEP-2DCOFC cells formed tumors in nude mice, and tumors were poorly differentiated to squamous cell carcinoma confirmed by histopathological examination. Conclusion The malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells could be successfully induced by the COFC at the dose of 50 μg/mL, and the prompt cooking lampblack had the carcinogenicity to the human body.%目的 用烹调油烟冷凝物(COFC)诱导正常永生化人支气管上皮细胞(BEP-2D)慢性恶性转化,构建恶性转化的细胞模型,以探讨COFC的危害.方法 通过MTT法确定诱导物的染毒剂量,以COFC处理细胞,用血清抗性实验和锚着独立生长实验鉴定细胞恶性转化的倾向和恶性特征,比较对照组和实验组抗血清促分化的能力

  12. Expression of PEPT2 mRNA in the lung of rat with bleomycin-induced pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li Li; Dianhua Wang; Xuan Zhang; Xing Song

    2013-01-01

    Objective:Pulmonary fibrosis is a common pathological phenomena in lung cancer patients after chemotherapy or radiotherapy, which is a key factor hindering to transport ion of high concentrated drug to the lung tissue, peptide trans-porter has become targets of the rational design of peptides and peptide drug. The purpose of the study is to investigate the expression of PEPT2 mRNA in the lung of rats with bleomycin (BLM)-induced pulmonary fibrosis. Methods:Fifty healthy adult Spragne-Dawley rats were randomized into five groups, the rats in BLM 7d, 14d and 28d groups were treated with a single instil ation of 5 mg/kg of BLM, to induced pulmonary fibrosis models. On days 7, 14 and 28, the animals were kil ed by exsan-guination respectively. Normal saline (NS) group were treated by NS, on days 14, the animals were kil ed by exsanguinations. Control group were untreated. The lung samples were processed for light microscopy and determined the hydroxyproline (HYP) concentration. The expression of PEPT2 mRNA were measured by RT-PCR. PEPT2 cDNA fragments were tested by dideoxy chain termination. Results:Compared with control and NS group, HYP levels increased on day 7 of BLM group, but there was no statistical significant dif erence (P>0.05). HYP levels markedly increased on days 14 and 28 of BLM group, there was statistical significant dif erence (P0.05). Conclusion:The pulmonary fibrosis models of SD rats can be induced by a single instil ation of 5 mg/kg of bleomycin on 28d. There were no significant changes of PEPT2 mRNA expression in the lung of rats with bleomycin-induced pulmonary fibrosis.

  13. 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

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

    Science.gov (United States)

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

    2016-07-01

    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 mg/ml bleomycin for 3 hours, cells were fixed for immunofluorescence assays and for RNA preparation. Extents of DNA damages were quantified by focus pattern and focus number counting of phosphorylated histone protein H2AX (γg-H2AX). The cells on the ISS showed modestly increased average focus 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 profiles 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 γg-H2AX focus counts between flight and ground was due to the higher percentage of proliferating cells in space, but spaceflight did not

  15. Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    LONG Xiang; XIONG Sheng-dao; XIONG Wei-ning; XU Yong-jian

    2007-01-01

    Background So far, there is no efficient treatment for pulmonary fibrosis. The objective of this study was to determine whether intramuscular injection of the hepatocyte growth factor (HGF) plasmid DNA by in vivo electroporation could prevent bleomycin-induced pulmonary fibrosis in rats, and to investigate the possible mechanisms.Methods Twenty male Wistar rats were randomly divided into four groups: control group(group C), model group (group M), early intervention group (group Ⅰ ) and late intervention group (groupⅡ). Groups M, Ⅰ and Ⅱ were intratracheally infused with bleomycin, then injected the plasmid pcDNA3.1-hHGF to group Ⅰ on day 7, 14 and 21. Group Ⅱ received the same treatment like Group Ⅰ on day 14 and 21. All the rats were killed on day 28 after bleomycin injection. We detected Homo HGF expression in the rats with ELISA method and estimated the pathological fibrosis score of lung tissue using hematoxylin eosin (HE) and Massion staining. The mRNA expression of transforming growth factor-β1 (TGF-β1),cycloxygenase-2 (COX-2), and rat HGF in rat pulmonary parenchyma were evaluated by RT-PCR.Immunohistochemistry and Western blotting were performed to determine the protein expression of transforming TGF-β1 and COX-2 in lung parenchyma.Results The plasmid pcDNA3.1-hHGF could express hHGF in NIH3T3 cells and the hHGF protein is secreted into the culture medium. The expression of hHGF protein could be monitored in quadriceps muscle, plasma and lung in Groups Ⅰ and Ⅱ. Pulmonary fibrosis levels of Groups Ⅰ and Ⅱ were obviously lower than that of group M (P<0.05).Expression of TGF-β1 protein and mRNA in lung tissue was markedly decreased in Groups Ⅰ and Ⅱ compared with Group M (P<0.05). The level of expression of HGF and COX-2 mRNA was higher in Groups Ⅰ and Ⅱ than in Group M (P<0.05).Conclusions Injection of the plasmid pcDNA3.1-hHGF into skeletal muscle with electroporation has a potential role in the treatment of bleomycin

  16. Niche nanoparticle-based FRET assay for bleomycin detection via DNA scission.

    Science.gov (United States)

    Pei, Haimeng; Zheng, Yiqun; Kong, Rongmei; Xia, Lian; Qu, Fengli

    2016-11-15

    We describe a highly sensitive nanoparticle-based fluorescence resonance energy transfer (FRET) probe developed without using molecular fluorophores as donors and acceptors. The success of this work relies on the strategy that DNA scission was designed to occur to the probe when target presented, which enabled the fluorescence signal "turn-on" of graphene quantum dots (GQDs) and thus quantitative analysis. In particular, amino-modified SiO2 NPs were initially coated by GQDs to form highly emitting SiO2/GQDs, followed by conjunction with DNA functionalized gold nanoparticles (Au NPs-DNA) to form SiO2/GQDs-DNA-Au NPs composite. Owing to the FRET interactions between the GQDs and Au NPs, the fluorescence of GQDs was effectively quenched by Au NPs. When bleomycin (BLM), a model analyte, was mixed with the probe, the fluorescence signal of GQDs would be restored due to the removal of Au NPs from the SiO2/GQDs surface by DNA scission treatment with BLM in the presence of Fe (II). The current FRET probe shows a good linear relationship between the fluorescence intensity and the concentration of BLM in the range from 0.5nM to 1μM with a detection limit of 0.2nM. The probe also shows satisfactory results for the analysis of clinical serum samples. This method provides versatility to the application of GQDs in FRET biosensing and could be potentially extended to other similar systems by replacing the linker between the GQDs and Au NPs. PMID:27155119

  17. 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-β1, IFN-γ and TNF-α 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.

  18. 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-PGF2α (8-iso-PGF2α. 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-PGF2α. 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.

  19. Degradation of DNA by iron-bleomycin: mechanistic implications of product 18O incorporation

    International Nuclear Information System (INIS)

    Interaction of d(CGCGCG) with Bleomycin (BLM), activated either with Fe(III) and H2O2 or Fe(II), O2 and one electron, results in production of cytosine and a modified oligonucleotide strand (1). Reduction of 1 with NaBD4 followed by enzymatic digestion, derivatization, and GC-MS permits the identification of 2-deoxypentitols-1,4-d2 as their tetra-trimethylsilyl (TMS) derivatives. Similar products have also been isolated from calf thymus DNA and poly(dG-dC). These results provide unequivocal evidence for the intermediacy of a 4' ketone, 1' aldehyde modified carbohydrate. An alternate mode of DNA degradation requires additional O2 and leads to formation of 3' phosphoglycolate termini and base propenals. Glycolate (GA), released from calf thymus DNA, poly(dA-dT) or d(CGCGCG) by enzymatic digestion, can be isolated by chromatography on DEAE Sephadex, silylated and analyzed by GC-MS. This analysis, after incubation with Fe(II) x 18O2 x BLM or Fe(III) x H216O2 x BLM plus 18O2, reveals the incorporation of a single atom of 18O at the C-1 position. Pulse-chase experiments demonstrate that it is the excess molecular oxygen and not the O2 required for drug activation that is incorporated into the carboxylate group of 3' phosphoglycolate and provide evidence for the proposed addition of O2 to a C4' carbon radical. Isotopic enrichments of the other products of DNA oxidation, formed in the presence of 18O2 are also being determined

  20. 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

  1. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

    Science.gov (United States)

    Xiang, Juan; Cheng, Si; Feng, Tianlong; Wu, Yan; Xie, Weina; Zhang, Mian; Xu, Xianghong; Zhang, Chaofeng

    2016-07-01

    Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages. PMID:27144994

  2. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

    Science.gov (United States)

    Xiang, Juan; Cheng, Si; Feng, Tianlong; Wu, Yan; Xie, Weina; Zhang, Mian; Xu, Xianghong; Zhang, Chaofeng

    2016-07-01

    Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.

  3. Mobile internet protocol analysis

    OpenAIRE

    Brachfeld, Lawrence J.

    1999-01-01

    Mobile Internet Protocol (IP) is a proposed standard that builds on the current Internet Protocol by making the fact that a user is mobile transparent to applications and higher level protocols such as Transmission Control Protocol (TCP) and User Datagram Protocol (UDP). Mobile IP allows mobile computers to send and receive packets addressed with their home network IP address, regardless of the IP address of their current point of attachment on the Internet while maintaining any current conne...

  4. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... 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. Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury

    Directory of Open Access Journals (Sweden)

    Ferguson Mark WJ

    2007-09-01

    Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFβ1 as a key effector cytokine in the development of lung fibrosis. Methods In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18 of transgenic mice (Tr+ that overexpressed active TGFβ1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. Results The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFβ1 associated pulmonary fibrosis. Conclusion This data emphasises the importance of a host predisposition in the form of endogenous TGFβ1, in the development of pulmonary fibrosis in response to an exogenous injury.

  6. The resonance Rayleigh scattering of the interaction of copper(Ⅱ)-bleomycinA2 with DNA and its analytical application

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The forming of bleomycinA2-Cu(Ⅱ) cationic chelate and the interaction of the chelate with DNA have been investigated by using resonance Rayleigh scattering(RRS),molecular absorption and fluorescence spectra.The result shows that in aqueous solution,bleomycinA2(BLMA2) can react with Cu(Ⅱ) to form 1:1 cationic chelate which contributes to the changes of the absorption spectra and the quenched fluorescence of BLMA2.When the cationic chelate further bound with DNA to form ternary ion-association complexes,the remarkable enhancement of the RRS intensity was observed.In this work,the optimum conditions for the coordination reaction of BLMA2 with Cu(Ⅱ) and some influencing factors have been investigated.The reaction mechanism of BLMA2-Cu(Ⅱ) binding with DNA was suggested and a binding model was proposed.In addition,the fluorescence quenching type of BLMA2 was investigated.A highly sensitive,simple and rapid new method for the determination of DNA by using BLMA2-Cu(Ⅱ) as RRS probe has been developed.The detection limits(3σ) are 7.2 ng/mL for ctDNA,7.1 ng/mL for sDNA and 18 ng/mL for hsDNA.The method can be applied to the determination of trace amounts of DNA.

  7. Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Behnam Motlagh, P. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Henriksson, R. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Grankvist, K. [Dept. of Clinical Chemistry, Umeaa Univ. Hospital (Sweden)

    1995-12-31

    At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, so far as we know, not been studied in this respect. In the present study, the effects of the 5-HT{sub 3} receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10{sup -5} mol/l) had no effect on the survival of irradiated cells. Granisetron (10{sup -5} mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10{sup -7} mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT{sub 3} receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment. (orig.).

  8. The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing.

    Science.gov (United States)

    Zampetti-Bosseler, F; Scott, D

    1985-08-01

    In agreement with our earlier observation (Scott and Zampetti-Bosseler, 1982) on X-irradiated normal and ataxia-telangiectasia (A-T) fibroblasts, we now report that after bleomycin or neocarzinostatin treatment also, A-T cells exhibit less G2 delay than normal cells. We confirm that A-T cells sustain more chromosome damage and lethality than normal cells after bleomycin. These observations support the hypothesis (Painter and Young, 1980) that A-T cells are defective in the recognition of certain lesions which normally lead to delays in progression through the cell cycle, during which they are repaired, and which, if unrepaired, lead to cell-lethal chromosome damage. However, we find that after bleomycin, as opposed to X-rays, the contribution of this type of lesion to cell death is minimal. The predominant lesions leading to cell death after bleomycin are not manifested at chromosome aberrations and do not lead to G2 delay or DNA-synthesis inhibition. A-T cells are defective in the recognition and/or repair of both types of lesion.

  9. The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin

    NARCIS (Netherlands)

    Korteland, J.; Dekker, B.G.; Ligny, C.L. de

    1980-01-01

    The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin was determined by titration of 99TcO4− with Sn(II) in the presence of these complexing agents. Both direct titration, and addition of an excess of Sn(II) and back-titrat

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    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.

  12. LOW DOSE PIRFENIDONE SUPPRESSES TRANSFORMING GROWTH FACTOR BETA-1 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1,AND PROTECTS RATS FROM LUNG FIBROSIS INDUCED BY BLEOMYCIN

    Institute of Scientific and Technical Information of China (English)

    Xin-lun Tian; Wei Yao; Zi-jian Guo; Li Gu; Yuan-jue Zhu

    2006-01-01

    Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-13 (MMP-13) in lung tissue.Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-800 mg·kg-1·d-1), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg·kg -1·d-1 at 7 days or 14 days after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in lung tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of proteins of TGF-β, TIMP-1, and MMP-13 were detected by Western blotting.Results At doses of 25, 50, and 100 mg·kg-1·d-1, pirfenidone had significant anti-fibrofic effects for bleomycin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50mg·kg-1 1d-1 (HE: P<0.01, P<0.01, and P =0.064; sirius red: P<0.05, P<0.01, and P<0. 05; hydroxyproline: P=0.595, P<0.01, and P=0.976). Pirfenidone at a dosage of 50 mg·kg -1·d-1 inhibited protein expression of TGF-β1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13.Conclusion Low dose pirfenidone, especially at dosage of 50 mg·kg-1·d-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-β1 and TIMP-1 in lung tissue.

  13. Prostaglandin Transporter (PGT/SLCO2A1 Protects the Lung from Bleomycin-Induced Fibrosis.

    Directory of Open Access Journals (Sweden)

    Takeo Nakanishi

    Full Text Available Prostaglandin (PG E2 exhibits an anti-fibrotic effect in the lung in response to inflammatory reactions and is a high-affinity substrate of PG transporter (SLCO2A1. The present study aimed to evaluate the pathophysiological relevance of SLCO2A1 to bleomycin (BLM-induced pulmonary fibrosis in mice. Immunohistochemical analysis indicated that Slco2a1 protein was expressed in airway and alveolar type I (ATI and II (ATII epithelial cells, and electron-microscopic immunohistochemistry further demonstrated cell surface expression of Slco2a1 in ATI cells in wild type (WT C57BL/6 mice. PGE2 uptake activity was abrogated in ATI-like cells from Slco2a1-deficient (Slco2a1-/- mice, which was clearly observed in the cells from WT mice. Furthermore, the PGE2 concentrations in lung tissues were lower in Slco2a1-/- than in WT mice. The pathological relevance of SLCO2A1 was further studied in mouse BLM-induced pulmonary fibrosis models. BLM (1 mg/kg or vehicle (phosphate buffered saline was intratracheally injected into WT and Slco2a1-/- mice, and BLM-induced fibrosis was evaluated on day 14. BLM induced more severe fibrosis in Slco2a1-/- than in WT mice, as indicated by thickened interstitial connective tissue and enhanced collagen deposition. PGE2 levels were higher in bronchoalveolar lavage fluid, but lower in lung tissues of Slco2a1-/- mice. Transcriptional upregulation of TGF-β1 was associated with enhanced gene transcriptions of downstream targets including plasminogen activator inhitor-1. Furthermore, Western blot analysis demonstrated a significant activation of protein kinase C (PKC δ along with a modest activation of Smad3 in lung from Slco2a1-/- mice, suggesting a role of PKCδ associated with TGF-β signaling in aggravated fibrosis in BLM-treated Slco2a1-/- mice. In conclusion, pulmonary PGE2 disposition is largely regulated by SLCO2A1, demonstrating that SLCO2A1 plays a critical role in protecting the lung from BLM-induced fibrosis.

  14. Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats

    Science.gov (United States)

    Zhang, Ke; Si, Xiao-Ping; Huang, Jian; Han, Jian; Liang, Xu; Xu, Xiao-Bo; Wang, Yi-Ting; Li, Guo-Yu; Wang, Hang-Yu; Wang, Jin-Hui

    2016-01-01

    Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague–Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T-SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-β1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-β1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play

  15. Dysregulated macrophages are present in bleomycin-induced murine laryngotracheal stenosis

    Science.gov (United States)

    Hillel, Alexander T.; Samad, Idris; Ma, Garret; Ding, Dacheng; Sadler, Kaitlyn; Powell, Jonathan D.; Lane, Andrew P.; Horton, Maureen R.

    2015-01-01

    Objective To define the inflammatory cell infiltrate preceding fibrosis in a laryngotracheal stenosis (LTS) murine model. Study Design Prospective controlled murine study. Setting Tertiary care hospital in a research university. Subjects and Methods Chemomechanical injury mice (n=44) sustained bleomycin-coated wire-brush injury to the laryngotracheal complex while mechanical injury controls (n=42) underwent PBS-coated wire-brush injury. Mock surgery controls (n=34) underwent anterior transcervical tracheal exposure only. Inflammatory and fibrosis protein and gene expression was assessed in each condition. Immunohistochemistry served as a secondary outcome. Results In chemomechanical injury mice, there was an up-regulation of: Collagen I (p<0.0001, p<0.0001), Tgf-β (p=0.0023, p=0.0008), and elastin (p<0.0001, p<0.0001) on Day 7, acute inflammatory gene: Il1β (p=0.0027, p=0.0008) on Day 1, and macrophage gene: CD11b (p=0.0026, p=0.0033) on Day 1 versus mechanical and mock controls respectively. M1 marker iNOS expression decreased (p=0.0014) while M2 marker arg1 (p=0.0002) increased on Day 7 compared to mechanical controls. Flow cytometry demonstrated increased macrophages (p=0.0058, day 4) and M1 macrophages (p=0.0148, day 4, p=0.0343, day 7, p=0.0229, day 10) compared to mock controls. There were similarities between chemomechanical and mechanical injury mice with an increase in M2 macrophages at day 10 (p=0.0196). Conclusions The mouse model demonstrated increased macrophages involved with the development of LTS. Macrophage immunophenotype suggested that dysregulated M2 macrophages have a role in abnormal laryngotracheal wound healing in both species. These results support this animal model as a representation for human disease. Furthermore, this data delineates inflammatory cells and signaling pathways in LTS that may potentially be modulated to lessen fibroblast proliferation and collagen deposition. PMID:26084828

  16. Biosynthesis of collagen crosslinks. III. In vivo labeling and stability of lung collagen in rats with bleomycin-induced pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Last, J.A.; Reiser, K.M. (Univ. of California, Davis (USA))

    1989-08-01

    Rats were injected intraperitoneally with 1 mCi (each) of (3H)lysine at Day 11 of neonatal life to label their lung collagen. Five weeks later, half of the animals were given an intratracheal injection of 1.5 U of bleomycin sulfate via a tracheostomy; control animals received saline intratracheally by the same technique. Age-matched groups of control and bleomycin-treated rats were killed, and their lung collagen was analyzed at zero (control animals only), 1, 2, 4, 6, and 10 wk after bleomycin administration, a time course appropriate for development of pulmonary fibrosis in this animal model. We measured radioactivity in hydroxylysine and in the difunctional collagen crosslinks hydroxylysinonorleucine and dihydroxylysinonorleucine at each time point. No evidence of breakdown of this pool of mature, preformed collagen was observed in lungs of either the control or the bleomycin-treated rats. We also measured the total lung content of hydroxypyridinium, a trifunctional collagen crosslink, by its intrinsic fluorescence. There was no evidence of collagen degradation in lungs of either group of rats by this criterion either. We conclude that there is no biochemically detectable turnover of mature lung collagen, defined as that pool of lung collagen that is obligatorily extracellular (i.e., crosslinked and containing labeled hydroxylysine from an injection of precursor 5 to 15 wk earlier), in either normal rat lungs or lungs of rats made fibrotic with bleomycin. Statistical analysis of the data suggests that our methodology was sensitive and precise enough to have detected turnover of less than 0.5% of lung collagen per day, some 20-fold less than estimates of lung collagen turnover that have been suggested to be occurring in vivo by others using different techniques and presumably studying different pools of lung collagen.

  17. Research on Protocol Migration

    Institute of Scientific and Technical Information of China (English)

    汪芸; 顾冠群; 等

    1996-01-01

    This paper elaborates the concept and model of protocol migration in network interconnection.Migration strategies and principles are discussed and several cases are studied in detail which show the basic procedure and techniques used in protocol migration.

  18. 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...

  19. Gene Expression Profile Changes and Cellular Responses to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Rohde, Larry; Wu, Honglu

    2016-01-01

    Living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. In addition, DNA in space can be damaged by toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage affects the accuracy of the radiation risk assessment for astronauts and the mutation rate in microorganisms. Although possible synergistic effects of space radiation and microgravity 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 cellular responses to DNA damage, confluent human fibroblast cells (AG1522) flown on 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). Damages in the DNA were quantified by immunofluorescence staining for ?-H2AX, which showed similar percentages of different types of stained cells between flight and ground. However, there was a slight shift in the distribution of the ?-H2AX foci number in the flown cells with countable foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. A microarray analysis of gene expressions in response to bleomycin treatment was also performed. Comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. Similar responses at the RNA level between different gravity conditions were also observed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly

  20. 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.

  1. Blind Collective Signature Protocol

    Directory of Open Access Journals (Sweden)

    Nikolay A. Moldovyan

    2011-06-01

    Full Text Available Using the digital signature (DS scheme specified by Belarusian DS standard there are designed the collective and blind collective DS protocols. Signature formation is performed simultaneously by all of the assigned signers, therefore the proposed protocols can be used also as protocols for simultaneous signing a contract. The proposed blind collective DS protocol represents a particular implementation of the blind multisignature schemes that is a novel type of the signature schemes. The proposed protocols are the first implementations of the multisignature schemes based on Belarusian signature standard.

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

    Institute of Scientific and Technical Information of China (English)

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

    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.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  3. 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 ...

  4. 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.

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

    International Nuclear Information System (INIS)

    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, α-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

  6. Treatment Outcomes of AIDS-Associated Kaposi's Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin/Vincristine Compared to Vincristine Monotherapy

    OpenAIRE

    Mwafongo, Albert A.; ROSENBERG, Nora E.; Wingston Ng'ambi; Werner, Alexandra B.; Garneau, William M.; Joe Gumulira; Sam Phiri; Mina C Hosseinipour

    2014-01-01

    Purpose Despite Kaposi's sarcoma (KS) being the most prevalent AIDS-associated cancer in resource limited settings, optimal treatment options remain unknown. We assessed whether bleomycin/vincristine compared to vincristine monotherapy was associated with improved treatment outcomes for AIDS-associated KS among patients initiating combination antiretroviral therapy (cART) in Malawi. Methods All patients initiating cART and chemotherapy for AIDS-related KS were identified from an electronic da...

  7. 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, α-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.

  8. Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

    Directory of Open Access Journals (Sweden)

    Qi Wang

    Full Text Available BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines. RESULTS: Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352% in BLM-resistant sub-clones (p<0.05 for both. Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05. Significantly reduced DNA damage (COMET and γ-H2AX assays, G2/M arrest, and apoptosis (p<0.05 for each set of comparison following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05. CONCLUSION: Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.

  9. Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response

    Directory of Open Access Journals (Sweden)

    Pazit Y. Cohen

    2015-01-01

    Full Text Available Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1− myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days, as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+ lymphocytes and Thy1− myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

  10. 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.

  11. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    . 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...

  12. 基于遥感-过程耦合模型的地表蒸散量应用研究%Research of land surface evapotranspiration based on remote sensing process coupling model BEPS

    Institute of Scientific and Technical Information of China (English)

    吴荣军; 葛琴; 詹习武; 关福来; 姚树然

    2013-01-01

    As an important processes of the land and atmosphere interaction in land surface process, evapotranspiration (ET) plays an key role in the biosphere, atmosphere and hydrosphere. In this paper, the remote sensing process coupling model BEPS was used. The main inputs were the Moderate Resolution Imaging Spectroradiometer (MODIS) data and the NCEP/NCAR reanalysis datas. We simulated and analyzed land surface evapotranspiration of the United States from 2007 to 2009. Meanwhile, the flux observation data of AmeriFlux was used to verify the reliability and applicability of the model in evapotranspiration simulation The results show that:the correlation coefficient of the land surface evapotranspiration between the BEPS model and the measured data was 0.729 7 (P<0.05), which mean that BEPS model could be well used in simulating the evapotranspiration in America. ET showed a single peak trend obviously within a year, which value was high from May to Septembe and more than 60 mm·mon-1. The minimum value was 8.39 mm·mon-1 in January, while maximum value was 18.04 mm·mon-1 in July. And the annual evapotranspiration was 505 mm·a-1. Influenced by topography, climate and evapotranspiration, the southern region mainly covered by grassland and farmland had the highest value, where annual evapotranspiration was generally above 600 mm·a-1 and the highest value was 1 667 mm·a-1. Annual evapotranspiration was 400-600 mm·a-1 in north-central area and Eastern area. The value of evapotranspiration in the western area where vegetation types were woodland and mixed forest., presented to be lowest among all area in America, which annual evapotranspiration was less than 400 mm·a-1. What's more, the value of precipitation minus ET showed a decreasing trend from eastern area to western area, which minimum value was mainly distributed in the western desert. The ratio of ET and precipitation was 0.72 increased from east to west, and reached the maximum value in western and north

  13. Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue

    Institute of Scientific and Technical Information of China (English)

    Jin Xiaoguang; Dai Huaping; Ding Ke; Xu Xuefeng; Pang Baosen; Wang Chen

    2014-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic.There is no effective therapy except for lung transplantation.Rapamycin is an immunosuppressive drug with potent antifibrotic activity.The purpose of this study was to examine the effects of rapamycin on bleomycininduced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1).Methods Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model.Rapamycin was given at a dose of 0.5 mg/kg per gavage,beginning one day before bleomycin instillation and once daily until animal sacrifice.Ten rats in each group were sacrificed at 3,7,14,28 and 56 days after bleomycin administration.Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System.Type Ⅰ and Ⅲ collagen fibers were identified by Picro-sirius-polarization.Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay,MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin.Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days.The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P <0.05).It was also demonstrated that rapamycin treatment reduced the expression of MMP-9 and TIMP-1 in lung tissue that was increased by bleomycin.Conclusion These results highlight the significance of rapamycin in alleviating

  14. STAT1 Antisense Oligonucleotides Attenuate the Proinflammatory Cytokine Release of Alveolar Macrophages in Bleomycin-Induced Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Xianming Fan; Zengli Wang

    2005-01-01

    To investigate the effect of signal transducers and activators of transcription 1 (STAT1) antisense oligonucleotides (ASON) on concentrations of TNF-α, IL-8, NO secreted by alveolar macrophages (AMs) in bleomycin-induced rat pulmonary fibrosis, five adult female Wistar rats were intratracheally instilled with bleomycin. After 7 days, the rats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia and bronchoalveolar lavage (BAL) was performed to obtain AMs. AMs were divided into four groups, treated with STAT1 ASON, STAT1 sense oligonucleotides (SON), dexamethasone (DEX) and medium alone (control), respectively. AMs and media were collected after culture for 36 h. The mRNA and protein expressions of STAT1 and ICAM-1 in AMs were detected by RT-PCR and ELISA, respectively. The concentrations of TNF-α, IL-8, NO in cultured medium were detected.The STAT1 mRNA expression by AMs in the STAT1 ASON group was lower than those of AMs in the STAT1 SON group, the DEX group and the control group (p < 0.05). Moreover, the STAT1 mRNA expression by AMs in the DEX group was also lower than those of AMs in the STAT1 SON group and the control group (p < 0.05), but the STAT1 mRNA expression by AMs in the STAT1 SON group was not different from that of the control group (p >0.05). The protein expressions of STAT1 and ICAM-1 and the mRNA expression of ICAM-1 showed similar changes to the STAT1 mRNA expression by AMs. The concentrations of TNF-α, IL-8, NO in cultured medium from STAT1 ASON group were lower than those from STAT1 SON, DEX and the control groups (p < 0.05). Moreover,the concentrations of TNF-α, IL-8, NO in cultured medium from DEX group were also lower than those from the control and STAT1 SON group (p < 0.05), but no difference between STAT1 SON group and the control (p > 0.05).The results suggest that STAT1 ASON could inhibit the secretion of TNF-α, IL-8, NO in AMs, and STAT1 could become a target of treating pulmonary fibrosis.

  15. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhang Dongwei

    2011-11-01

    Full Text Available Abstract Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1 on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-β1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-β1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-β1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39% and K (41%-76% and a 30% decrease in TGF-β1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-β1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that

  16. IPv6 Protocol Analyzer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    With the emerging of next generation Intemet protocol (IPv6), it is expected to replace the current version of Internet protocol (IPv4) that will be exhausted in the near future. Besides providing adequate address space, some other new features are included into the new 128 bits of IP such as IP auto configuration, quality of service, simple routing capability, security, mobility and multicasting. The current protocol analyzer will not be able to handle IPv6 packets. This paper will focus on developing protocol analyzer that decodes IPv6 packet. IPv6 protocol analyzer is an application module,which is able to decode the IPv6 packet and provide detail breakdown of the construction of the packet. It has to understand the detail construction of the IPv6, and provide a high level abstraction of bits and bytes of the IPv6 packet.Thus it increases network administrators' understanding of a network protocol,helps he/she in solving protocol related problem in a IPv6 network environment.

  17. 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.

  18. 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

  19. 1996 : Track Count Protocol

    Data.gov (United States)

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

  20. 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.

  1. Biochemical evaluation of a 108-member deglycobleomycin library: viability of a selection strategy for identifying bleomycin analogues with altered properties.

    Science.gov (United States)

    Ma, Qian; Xu, Zhidong; Schroeder, Benjamin R; Sun, Wenyue; Wei, Fang; Hashimoto, Shigeki; Konishi, Kazuhide; Leitheiser, Christopher J; Hecht, Sidney M

    2007-10-17

    The bleomycins (BLMs) are clinically used glycopeptide antitumor antibiotics that have been shown to mediate the sequence-selective oxidative damage of both DNA and RNA. Previously, we described the solid-phase synthesis of a library of 108 unique analogues of deglycoBLM A6, a congener that cleaves DNA analogously to BLM itself. Each member of the library was assayed for its ability to effect single- and double-strand nicking of duplex DNA, sequence-selective DNA cleavage, and RNA cleavage in the presence and absence of a metal ion cofactor. All of the analogues tested were found to mediate concentration-dependent plasmid DNA relaxation to some extent, and a number exhibited double-strand cleavage with an efficiency comparable to or greater than deglycoBLM A6. Further, some analogues having altered linker and metal-binding domains mediated altered sequence-selective cleavage, and a few were found to cleave a tRNA3Lys transcript both in the presence and in the absence of a metal cofactor. The results provide insights into structural elements within BLM that control DNA and RNA cleavage. The present study also permits inferences to be drawn regarding the practicality of a selection strategy for the solid-phase construction and evaluation of large libraries of BLM analogues having altered properties.

  2. Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice.

    Science.gov (United States)

    Guo, Huizhen; Zhang, Zhenbiao; Su, Zuqing; Sun, Chaoyue; Zhang, Xie; Zhao, Xiaoning; Lai, Xiaoping; Su, Ziren; Li, Yucui; Zhan, Janis Yaxian

    2016-04-01

    Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL-1β, TNF- α, IL-6 and TGF-β1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-β, α-SMA, p-Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM. PMID:26874212

  3. Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

    Directory of Open Access Journals (Sweden)

    Chantal Viart-Ferber

    2013-01-01

    Full Text Available The first aim of the study is to determine whether combined lung diffusing capacities of nitric oxide (TLNO and of carbon monoxide (TLCO are accurate in the followup of patients receiving either methotrexate (MTX or bleomycin (BLM. The second objective is to determine whether TLCO, TLNO, KCO, and TLCO/VI% (inspiratory volume expressed as percentage of predicted value correlate better with the diffusing capacity of the membrane (Dm and/or capillary lung volume (Vc. TLNO and TLCO were measured in three groups: 22 “normal” subjects (N group, 17 patients receiving MTX, and 12 patients treated with BLM. TLCO, TLNO, Dm, and Vc were much lower in the MTX and BLM groups compared to those of the N one. The ratio TLNO/TLCO was higher in the BLM group compared to that of the N group and compared to that of the MTX group. KCO correlated neither with Dc nor with Vc, whereas TLCO/VI% correlated significantly with both Dm and Vc. Combined measurement of TLCO and TLNO seems to be useful in the followup of patients receiving agents inducing lung toxicity and gives a good idea of the alveolar membrane and the capillary volume.

  4. Topics in free radical-mediated DNA damage: purines and damage amplification - superoxic reactions - bleomycin, the incomplete radiomimetic

    International Nuclear Information System (INIS)

    Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reactions (radical transfer reactions) may contribute to these clustered lesions, and examples of such damage amplification reactions are given. In one example a purine is involved. With 2'-deoxy adenosine and 2'-deoxy guanosine it is shown that these purine nucleosides undergo unexpected radical reactions. Evidence for the radical transfer from the purine to the sugar moiety is provided by the formation of the 5'-aldehydes. These products have been assayed with 2-thiobarbituric acid (TBA), a reagent commonly applied to the detection of malonaldehyde. TBA-reactive material has also been assayed in γ-irradiated DNA, about one-third of this is free malonaldehyde, while the major part of the TBA-reactive material remains bound to the DNA. In contrast, bleomycin-treated DNA yields practically no free malonaldehyde, and the major TBA-reactive products are identified as the thymine and adenine base propenals. (Author)

  5. Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro.

    Science.gov (United States)

    Yilmaz, Dilek; Teksoy, Ozgun; Bilaloglu, Rahmi; Çinkilic, Nilufer

    2016-01-01

    Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3 µg/mL) and a single dose of BLM (20 µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20 µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3 µg/mL. Combined treatments of BLM and naringin (2 and 3 µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20 µg/mL)-induced genotoxicity. PMID:25941869

  6. Cytoskeleton - Methods and Protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-03-01

    Full Text Available Cytoskeleton - Methods and ProtocolsSecond edition, 2010; Ray H. Gavin (Ed; Springer Protocols methods in molecular biology, vol. 586 Humana press, Totowa, New Jersey (USA; Pages: 390; €95.44; ISBN: 978-1-60761-375-6Ray H. Gavin, from the Brooklyn College of The City University of New York, Brooklyn, NY, USA, wrote a few line as preface of this book. This is quite understandable: there is not a great need of words when there are facts that sustain and favour the dissemination of a cultural product. This is the case of the second edition of Cytoskeleton - Methods and Protocols, which appears just ten years after the first edition...

  7. 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...

  8. Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis.

    Science.gov (United States)

    Conte, Enrico; Fagone, Evelina; Gili, Elisa; Fruciano, Mary; Iemmolo, Maria; Pistorio, Maria Provvidenza; Impellizzeri, Daniela; Cordaro, Marika; Cuzzocrea, Salvatore; Vancheri, Carlo

    2016-06-01

    In this study, the bleomycin model of pulmonary fibrosis was utilized to investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate therapeutic effects in a subset of mice, Ac-SDKP was administered one week after BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks later. Measurement of fluid and collagen content in the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and molecular analysis were performed. Compared to BLEO-treated mice, animals that received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality, weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage (histological evidence of lung injury), and fibrosis (collagen histological staining and soluble collagen content in the lung) at up to 21 days. Moreover, IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO-induced IL-17 and TGF-β expression in lung tissue. Importantly, α-SMA expression, the hallmark of myofibroblast differentiation, was also decreased. This is the first report showing not only a preventive protective role of Ac-SDKP but also its significant therapeutic effects in the bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.

  9. Apoptosis - Methods and Protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-03-01

    Full Text Available Apoptosis - Methods and ProtocolsSecond edition, 2009; Peter Erhardt and Ambrus Toth (Eds; Springer Protocols - Methods in molecular biology, vol. 559; Humana press, Totowa, New Jersey (USA; Pages: 400; €88.35; ISBN: 978-1-60327-016-8The editors rightly begin the preface telling us that: “The ability to detect and quantify apoptosis, to understand its biochemistry and to identify its regulatory genes and proteins is crucial to biomedical research”. Nowadays this is a grounding concept of biology and medicine. What is particularly remarkable...

  10. Security Protocols in a Nutshell

    OpenAIRE

    Toorani, Mohsen

    2016-01-01

    Security protocols are building blocks in secure communications. They deploy some security mechanisms to provide certain security services. Security protocols are considered abstract when analyzed, but they can have extra vulnerabilities when implemented. This manuscript provides a holistic study on security protocols. It reviews foundations of security protocols, taxonomy of attacks on security protocols and their implementations, and different methods and models for security analysis of pro...

  11. Business protocol in integrated Europe

    OpenAIRE

    Pavelová, Nina

    2009-01-01

    The first chapter devotes to definitions of basic terms such as protocol or business protocol, to differences between protocol and etiquette, and between social etiquette and business etiquette. The second chapter focuses on the factors influencing the European business protocol. The third chapter is devoted to the etiquette of business protocol in the European countries. It touches the topics such as punctuality and planning of business appointment, greeting, business cards, dress and appear...

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

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Larraza, Daniel M. [IMBICE, C.C. 403, 1900 La Plata (Argentina)]. E-mail: danielop@imbice.org.ar; Padron, Juan [IMBICE, C.C. 403, 1900 La Plata (Argentina); Ronci, Natalia E. [IMBICE, C.C. 403, 1900 La Plata (Argentina); Vidal Rioja, Lidia A. [IMBICE, C.C. 403, 1900 La Plata (Argentina)

    2006-08-30

    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 {sup o}C. 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.

  13. VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension

    Institute of Scientific and Technical Information of China (English)

    龚方戚; 林幼敏; 汤宏峰; 顾伟忠; 汪伟; 康曼丽

    2004-01-01

    Objective: To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonary arteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with intratracheal bleomycin (BLM). Methods: Immature rabbits were divided into control and BLM group. Two and four weeks after intratracheal normal saline or BLM injection, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter; the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization.Results: Two and four weeks after intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52%in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the cavity in middle and small pulmonary arteries became narrow; the Thickness Index (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4 weeks; the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and 43%, 51% in 4 weeks.There was no significant difference between 2 weeks and 4 weeks BLM groups. Conclusion: The pulmonary artery pressure was elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks and 4 weeks of intratracheal 4 U/kg BLM injection.

  14. 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.

  15. 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)

  16. 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.

  17. 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 β1 (TGF-β1), we observed upregulation of HSP27 along with that of α-smooth muscle actin (α-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-β1-treated MRC-5 cells. In lung tissues of bleomycin-treated mice, HSP27 was strongly upregulated and substantially co-localized with α-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 α-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

  18. 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

  19. Phototherapy Modalities and Protocols

    Directory of Open Access Journals (Sweden)

    Ayten Ferahbaş

    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.

  20. 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..... 

  1. Dysphonia risk screening protocol

    Directory of Open Access Journals (Sweden)

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  2. Automatic Validation of Protocol Narration

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo;

    2003-01-01

    We perform a systematic expansion of protocol narrations into terms of a process algebra in order to make precise some of the detailed checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we...... demonstrate that these techniques suffice for identifying a number of authentication flaws in symmetric key protocols such as Needham-Schroeder, Otway-Rees, Yahalom and Andrew Secure RPC....

  3. An automatic protocol composition checker

    OpenAIRE

    Kojovic, Ivana

    2012-01-01

    Formal analysis is widely used to prove security properties of the protocols. There are tools to check protocols in isolation, but in fact we use many protocols in parallel or even vertically stacked, e.g. running an application protocol (like login) over a secure channel (like TLS) and in general it is unclear if that is safe. There are several works that give sufficient conditions for parallel and vertical composition, but there exists no program to check whether these conditions are actual...

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Yan Cai

    Full Text Available 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.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.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 TGFβ 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.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

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Cheng-Fan, E-mail: zhouchengfan@sohu.com [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Zhou, Deng-Chuan [Department of Emergency Medicine and Critical Care Medicine, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng [Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Wu, Chang-Hao [Department of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey (United Kingdom); Zhu, Qi-Xing, E-mail: zqxing@yeah.net [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China)

    2014-06-15

    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

  7. Static Validation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.;

    2005-01-01

    We methodically expand protocol narrations into terms of a process algebra in order to specify some of the checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demonstrate that these techniques...

  8. Transfusion protocol in trauma

    Directory of Open Access Journals (Sweden)

    Kaur Paramjit

    2011-01-01

    Full Text Available Blood and blood components are considered drugs because they are used in the treatment of diseases. As with any drug, adverse effects may occur, necessitating careful consideration of therapy. Like any other therapeutic decision, the need for transfusion should be considered on the basis of risks and benefits and alternative treatments available to avoid over- and under-transfusion. This review is focused on the blood transfusion protocol in trauma patients with hemorrhagic shock. Besides, issues related to emergency and massive transfusion have also been elaborated. We conducted a comprehensive MEDLINE search and reviewed the relevant literature, with particular reference to emergency medical care in trauma.

  9. 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.

  10. 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

  11. Provenance Query Protocol

    OpenAIRE

    Miles, S.; Moreau, L; Groth, P; Tan, V.; Munroe, S; Jiang, Sheng

    2006-01-01

    A related document defines schemas to be used for documentation about the execution of a process. It also defines the provenance of a data item as the process that led to that item. A provenance query is a query for the provenance of a data item and the results of such a query is documentation of the process that led to the item. In this document, we specify a protocol by which a querying actor and provenance store can communicate in performing a provenance query. This primarily takes the for...

  12. 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.

  13. 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)

  14. MAP3K19 Is a Novel Regulator of TGF-β Signaling That Impacts Bleomycin-Induced Lung Injury and Pulmonary Fibrosis.

    Directory of Open Access Journals (Sweden)

    Stefen A Boehme

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive, debilitating disease for which two medications, pirfenidone and nintedanib, have only recently been approved for treatment. The cytokine TGF-β has been shown to be a central mediator in the disease process. We investigated the role of a novel kinase, MAP3K19, upregulated in IPF tissue, in TGF-β-induced signal transduction and in bleomycin-induced pulmonary fibrosis. MAP3K19 has a very limited tissue expression, restricted primarily to the lungs and trachea. In pulmonary tissue, expression was predominantly localized to alveolar and interstitial macrophages, bronchial epithelial cells and type II pneumocytes of the epithelium. MAP3K19 was also found to be overexpressed in bronchoalveolar lavage macrophages from IPF patients compared to normal patients. Treatment of A549 or THP-1 cells with either MAP3K19 siRNA or a highly potent and specific inhibitor reduced phospho-Smad2 & 3 nuclear translocation following TGF-β stimulation. TGF-β-induced gene transcription was also strongly inhibited by both the MAP3K19 inhibitor and nintedanib, whereas pirfenidone had a much less pronounced effect. In combination, the MAP3K19 inhibitor appeared to act synergistically with either pirfenidone or nintedanib, at the level of target gene transcription or protein production. Finally, in an animal model of IPF, inhibition of MAP3K19 strongly attenuated bleomycin-induced pulmonary fibrosis when administered either prophylactically ortherapeutically. In summary, these results strongly suggest that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease.

  15. Knock out of S1P3 receptor signaling attenuates inflammation and fibrosis in bleomycin-induced lung injury mice model.

    Directory of Open Access Journals (Sweden)

    Ken Murakami

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein-coupled receptors (S1P1-5. Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1 or transforming growth factor β1 (TGF-β1 levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis.

  16. 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.

  17. 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...

  18. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    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......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, and how....... 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...

  19. A PROGRAMMED LABOUR - PROTOCOL

    Directory of Open Access Journals (Sweden)

    Savita

    2014-12-01

    Full Text Available A Prospective randomized Clinical study of outcome of labour following. “A Programmed labour. Protocol” was done at Department of OBG, MRMC Gulbarga. The Protocol was aimed with dual. Objective of Providing Pain relief during labour and teaching the goal of safe motherhood by optimizing objective outcome. AIMS AND OBJECTIVES: Shortening of duration of labour. Effect of labour analgesia. Monitoring of the events during labour. Lowering the incidence of operative deliveries. METHODS: 100 cases primi pregnant women admitted in labour room are randomly selected. It is designed to apply to low risk primi parous, singleton cephalic presentation without evidence of CPD and spontaneous onset of labour. RESULTS: Shortened duration of all the stages of Labour, especially significant reduction in duration of active phase of labour. CONCLUSION: The programmed labour is simple easy and effective method for painless and safe delivery.

  20. Protocols for Robotic Telescope Networks

    Directory of Open Access Journals (Sweden)

    Alain Klotz

    2010-01-01

    This paper is addressed to astronomers who are not specialists in computer science. We give explanations of some basic and advanced protocols to receive events and how to implement them in a robotic observatory software. We describe messages such as GCN notices, VOEvents or RTML, and protocols such as CGI, HTTP, SOAP, RSS, and XMPP.

  1. 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.

  2. 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

  3. Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma. The EORTC Lymphoma Cooperative Group.

    Science.gov (United States)

    Meerwaldt, J H; Carde, P; Somers, R; Thomas, J; Kluin-Nelemans, J C; Bron, D; Noordijk, E M; Cosset, J M; Bijnens, L; Teodorovic, I; Hagenbeek, A

    1997-01-01

    CHOP has been and still is regarded by many as the 'standard' treatment of advanced non-Hodgkin's lymphoma. In 1980 the EORTC Lymphoma Cooperative Group started a study to evaluate the addition of vincristine and bleomycin to its standard four-drug combination chemotherapy, CHVmP (cyclophosphamide, hydroxorubicin, Vm-26, prednisone). Eligible patients were stage III or IV, intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation E-I). One-hundred-eighty-nine patients were entered, of whom 140 were eligible and evaluable. A previous report showed an improved response rate and failure-free survival (FFS) and overall survival for the combination CHVmP-VB. At ten years, the outcome still favors the addition of vincristine and bleomycin. The FFS was 34% vs. 23% and the overall survival 34% vs 22%. This difference was mainly due to a difference in CR rate (74% vs. 49%), Relapse-free survival for patients reaching a CR was the same in both arms. When the patients were grouped according to the International Prognostic Factor Index, no statistically significant difference could be observed in favor of one treatment within either group. This trial clearly demonstrates the benefit gained by the addition of vincristine and bleomycin to 'standard' chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma.

  4. AN IMPROVED AUTHENTICATED KEY AGREEMENT PROTOCOL

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In 1999, Seo and Sweeney proposed a simple authenticated key agreement protocol that was designed to act as a Diffie-Hellman key agreement protocol with user authentication.Various attacks on this protocol are described and enhanced in the literature. Recently, Ku and Wang proposed an improved authenticated key agreement protocol, where they asserted the protocol could withstand the existing attacks. This paper shows that Ku and Wang's protocol is still vulnerable to the modification attack and presents an improved authenticated key agreement protocol to enhance the security of Ku and Wang's protocol. The protocol has more efficient performance by replacing exponentiation operations with message authentication code operations.

  5. SIP protocol model for OMNET++

    Directory of Open Access Journals (Sweden)

    Jan Kucerak

    2016-01-01

    Full Text Available The article describes our new SIP protocol implementation for the OMNeT++ simulation framework. OMNeT++ simulation framework provides an extensive support of IP related protocols, nevertheless a working SIP protocol implementation is missing. Real measurements were also done using a SIPp traffic generator and the results are compared to those obtained by our new SIP model. Since this work is a part of bigger project concerned strictly on measuring "first response times" over networks with a faulty transmission links, the actually collected statistics are focused only this way.

  6. 博莱霉素涂层支架对胆管良性狭窄的影响%Effects of bleomycin eluting stent on benign biliary stricture

    Institute of Scientific and Technical Information of China (English)

    张庆普; 张晓; 黄涛; 赵付生; 贾廷印; 延学军

    2014-01-01

    Objective To investigate the effects of bleomycin eluting stent on benign biliary stricture.Methods Twenty-four New Zeal white rabbits with bile duct injury were randomly assigned into group A (n =12) and group B (n =12),subject to the implantation of the extrahepatic bile duct bleomycin-coated stents and ordinary stents.After 0 d and 4 weeks,the ear vein blood was taken for determination of total bilirubin,then the rabbits were sacrifaced,the papaffin-embedded sections were prepared by the implanted stents,and stained with hematoxylin and eosin (HE).The computer image detection system was used to examine the changes of gallbladder lumen areas in two groups.Fas,transforming growth factor-β1 (TGF-β1),and α-smooth muscle actin (α-SMA) antibodies were employed for immunostaining in two groups.Results Fas gene expression level in bile duct tissue of group A was significantly higher than in group B (P < 0.05).TGF-β1 and α-SMA expression levels in group A were significantly lower than in group B (P < 0.05).The extrahepatic bile duct stenosis was significantly alleviated,and liver function improved significantly in group A as compared with group B (P < 0.05).Conclusion Bleomycin enhances the expression of Fas gene in rabbit smooth muscle cells,promotes apoptosis,inhibits fibroblast activity,and decreases the deposit of collagen,resulting in the suppression of bile duct stricture,and the recovery of liver function.%目的 观察博莱霉素涂层支架对兔胆管良性狭窄的影响.方法 24只新西兰白兔行胆管损伤后平均分入A、B组,分别将博莱霉素涂层支架和普通支架植入两组兔的肝外胆管内.0d、4周后,取耳缘静脉血,检测总胆红素变化,随后处死兔,取植入支架行石蜡切片,行苏木素-伊红(HE)染色,并采用计算机图像检测系统检测两组胆管腔面积变化,同时各组切片行Fas、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)抗体进行免疫

  7. Characterization of Quin-C1 for its anti-inflammatory property in a mouse model of bleomycin-induced lung injury

    Institute of Scientific and Technical Information of China (English)

    Min HE; Ni CHENG; Wei-wei GAO; Meng ZHANG; Yue-yun ZHANG; Richard D YE; Ming-wei WANG

    2011-01-01

    Aim: To study the in vivo effects of Quin-C1, a highly specific agonist for formyl peptide receptor 2 (FPR2/ALX), in a mouse model of bleomycin (BLM)-induced lung injury.Methods: Male ICR mice were injected intratracheally with BLM (d O), and intraperitoneally with Quin-C1 (0.2 mg/d) or vehicle between d 1 and d 28, during which pulmonary inflammation was monitored. A similar regimen was carried out between d 5 and d 28 to dif-ferentiate anti-inflammatory from anti-fibrotic effects. During the treatment, leukocyte numbers in bronchoalveolar lavage fluid (BALF)were counted, and FPR2/ALX transcripts, tumor necrosis factor а (TNF-а), interleukin-1β (IL-1β), the mouse keratinocyte-derived chemokine (KC), transforming growth factor 1β (TGF-1β) and C-X-C motif chemokine 10 (CXCL10) expression levels in the lung tissue were also measured. Both hydroxyprollne content and histological changes were examined on d 28 to assess the severity of lung fibro-sis.Results: BLM caused a significant increase in expression levels of all the selected cytokines and chemokines, as well as a thickening of the alveolar wall. Treatment with Quin-C1 significantly reduced the neutrophil and lymphocyte counts in BALF, diminished expres-sion of TNF-а, IL-1β, KC, and TGF-1β, and decreased collagen deposition in lung tissue. The treatment also lowered the content of lung hydroxyproline. Quin-C1 did not ameliorate lung fibrosis when the treatment was started 5 d after the BLM challenge, suggesting that the protection may be attributed to its anti-inflammatory effects. Exposure to BLM or BLM plus Quin-C1 did not change the level of FPR2/ALX transcripts (mFprl, mFpr2, and Lxa4r) in the lung tissue.Conclusion: The results demonstrate an anti-inflammatory role for Quin-C1 in bleomycin-induced lung injury, which may be further explored for therapeutic applications.

  8. Dynamic random channel reservation protocol

    Institute of Scientific and Technical Information of China (English)

    Ren Yanying; Zhang Wenjun; Yu Songyu

    2005-01-01

    Demand assignment MAC protocols have been used widely in wireless networks. It can effectively utilize wireless bandwidth. Some strategies can be used by demand assignment MAC protocols to further improve their efficiency. The concept of transmit probability is introduced. This concept allows a request slot to be assigned to many different traffic classes at the same time. Based on it, the dynamic random channel reservation (DRCR) protocol is proposed. The DRCR protocol operates dynamically by observing the traffic conditions. It uses information about the recent traffic conditions to assign transmit probability with which an mobile station can select request slots with lower traffic. The performance of DRCR is evaluated and compared with RSCA. The results show that DRCR is more stable than RSCA, it offers shorter delays of requests than RSCA and can relieve heavily stressed traffic classes faster than RSCA.

  9. National Elk Refuge vaccination protocol

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Proposal by the State of Wyoming, Wyoming Game and Fish Department, to vaccinate elk on the National Elk Refuge. The proposal provides a protocol for vaccinating...

  10. 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.

  11. Improved Authenticated Multi-Key Agreement Protocol

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hua; YUAN Zheng; WEN Qiaoyan

    2006-01-01

    Zhou et al give an attack on Harn's modified authenticated multi-key agreement protocol, and give a protocol that can prevent the unknown key-share attack. The paper points out that the protocol is vulnerable to a concatenation attack. This paper proposes an improved authenticated multi-key agreement protocol which shows how to make Harn's protocol more secure by modifying the signature and verification. And this protocol can escape the concatenation attack.

  12. Self-Healing Protocol Implementations

    OpenAIRE

    Tschudin, Christian; Yamamoto, Lidia

    2005-01-01

    Current studies on self-configuring and adaptive networks aim at developing specific and fixed protocols which are able to optimize their configuration in a variable network environment. In this talk we study the problem where the protocols need to cope with a defective execution, including the lossy execution or the injection of foreign code. One guiding question will be the creation of robust execution circuits which can distribute over a network and which continue their service despite par...

  13. 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.

  14. Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Tada, Hitoshi

    2016-03-01

    Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy.

  15. Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Tada, Hitoshi

    2016-03-01

    Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy. PMID:26886341

  16. Bleomycin, adiamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin`s lymphoma. Long-term survival rate and complications

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Kouichi; Yasuda, Shigeo; Itami, Jun [Chiba Univ. (Japan). School of Medicine] [and others

    1998-06-01

    This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin`s lymphoma. Seventy patients with non-Hodgkin`s lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival. (author)

  17. Dose evaluation of therapeutic radiolabeled bleomycin complexes based on biodistribution data in wild-type rats:Effect of radionuclides in absorbed dose of different organs

    Institute of Scientific and Technical Information of China (English)

    Hassan Yousefnia; Samaneh Zolghadri; Amir Reza Jalilian; Mohammad Ghannadi-Maragheh

    2015-01-01

    Bleomycins (BLMs), as tumor-seeking antibiotics, have been used for over 20 years in treatment of several types of cancers. Several radioisotopes are used in radiolabeling of BLMs for therapeutic and diagnostic purpos-es. An important points in developing new radiopharmaceuticals, especially therapeutic agents, is the absorbed dose delivered in critical organs. In this work, absorbed dose to organs after injection of 153Sm-, 177Lu-and 166Ho-labeled BLM was investigated by radiation dose assessment resource (RADAR) method based on biodis-tribution data in wild-type rats. The absorbed dose effect of the radionuclides was evaluated. The maximum absorbed dose for the complexes was observed in the kidneys, liver and lungs. For all the radiolabeled BLMs, bone and red marrow received considerable absorbed dose. Due to the high energy beta particles emitted by 166Ho, higher absorbed dose is observed for 166Ho-BLM in the most organs. The reported data can be useful for the determination of the maximum permissible injected activity of the radiolabeled BLMs in the treatment planning programs.

  18. Regeneration of alveolar type I and II cells from Scgb1a1-expressing cells following severe pulmonary damage induced by bleomycin and influenza.

    Directory of Open Access Journals (Sweden)

    Dahai Zheng

    Full Text Available The lung comprises an extensive surface of epithelia constantly exposed to environmental insults. Maintaining the integrity of the alveolar epithelia is critical for lung function and gaseous exchange. However, following severe pulmonary damage, what progenitor cells give rise to alveolar type I and II cells during the regeneration of alveolar epithelia has not been fully determined. In this study, we have investigated this issue by using transgenic mice in which Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP. We show that following severe alveolar damage induced either by bleomycin or by infection with influenza virus, the majority of the newly generated alveolar type II cells in the damaged parenchyma were labeled with EGFP. A large proportion of EGFP-expressing type I cells were also observed among the type II cells. These findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells, are a major cell type that gives rise to alveolar type I and II cells during the regeneration of alveolar epithelia in response to severe pulmonary damage in mice.

  19. Bleomycin, adiamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma. Long-term survival rate and complications

    International Nuclear Information System (INIS)

    This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival. (author)

  20. Pretreatment with UV light renders the chromatin in human fibroblasts more susceptible to the DNA-damaging agents bleomycin, gamma radiation and 8-methoxypsoralen

    International Nuclear Information System (INIS)

    Confluent human fibroblast cultures were pretreated with either 254 nm UV light (UV) or methyl methanesulphonate (MMS), incubated at 370C and subsequently challenged on ice with bleomycin (BLM), gamma-radiation or 8-methoxy-psoralen (MOP). The resulting number of challenge-induced DNA damages (measured as DNA strand breaks or cross-links) were compared with the numbers induced in similarly challenged but non-pretreated control cells. It was found that the timing of the subsequent challenge of cells pretreated with UV did significantly affect the amount of induced DNA damage. When the challenging agents were administered after a 10-20 min incubation period following UV pretreatment, the amount of induced DNA damage was increased 50% over control cells. In contrast, the timing of the subsequent challenge of cells pretreated with MMS has no influence on the level of challenge-induced damage. It is hypothesized that UV-irradiated chromatin undergoes a time-dependent decondensation that renders it more susceptible to the induction of strand breaks and cross-links by BLM, gamma-radiation and MOP. A possible role for chromatin decondensation in UV-induced excision repair is discussed. (author)

  1. Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

    International Nuclear Information System (INIS)

    A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications, possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity

  2. Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Bin Liao; Chen Zhu; Wenjun Wang; Xiaoqin Zhan; Xianming Fan

    2008-01-01

    It has been demonstrated that alveolar macrophages (AMs) play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. In addition, abnormal signal transducer and activator of transcription-1 (STAT1) activation in AMs may play a pivotal role in the process of alveolitis and pulmonary fibrosis. In this study, we transfected STAT1 antisense oligodeoxynucleotide (ASON) into rats by aerosolization, and then investigated the effect of STAT1 ASON on inflammatory mediators such as TGF-β, PDGF and TNF-α in bronchoalveolar lavage fluid (BALF) from rats with bleomycin (BLM)-induced rat pulmonary fibrosis. Our results showed that STAT1 ASON by aerosolization could enter into lung tissues and AMs. STAT1 ASON could inhibit mRNA and protein expressions of STATI and ICAM-1 in AMs of rat with pulmonary fibrosis, and had no toxic side effect on liver and kidney. Aerosolized STAT1 ASON could ameliorate the alveolitis through inhibiting the secretion of inflammatory mediators in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis. Cellular & Molecular Immunology. 2008;5(3):219-224.

  3. Protocols.io: Virtual Communities for Protocol Development and Discussion

    Science.gov (United States)

    Stoliartchouk, Alexei; Kindler, Lori; Hurwitz, Bonnie L.

    2016-01-01

    The detailed know-how to implement research protocols frequently remains restricted to the research group that developed the method or technology. This knowledge often exists at a level that is too detailed for inclusion in the methods section of scientific articles. Consequently, methods are not easily reproduced, leading to a loss of time and effort by other researchers. The challenge is to develop a method-centered collaborative platform to connect with fellow researchers and discover state-of-the-art knowledge. Protocols.io is an open-access platform for detailing, sharing, and discussing molecular and computational protocols that can be useful before, during, and after publication of research results. PMID:27547938

  4. Protocols.io: Virtual Communities for Protocol Development and Discussion.

    Science.gov (United States)

    Teytelman, Leonid; Stoliartchouk, Alexei; Kindler, Lori; Hurwitz, Bonnie L

    2016-08-01

    The detailed know-how to implement research protocols frequently remains restricted to the research group that developed the method or technology. This knowledge often exists at a level that is too detailed for inclusion in the methods section of scientific articles. Consequently, methods are not easily reproduced, leading to a loss of time and effort by other researchers. The challenge is to develop a method-centered collaborative platform to connect with fellow researchers and discover state-of-the-art knowledge. Protocols.io is an open-access platform for detailing, sharing, and discussing molecular and computational protocols that can be useful before, during, and after publication of research results. PMID:27547938

  5. 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.

  6. Superposition Attacks on Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Funder, Jakob Løvstad; Nielsen, Jesper Buus;

    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...... 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...... 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...

  7. Symbolic Analysis of Cryptographic Protocols

    DEFF Research Database (Denmark)

    Dahl, Morten

    a concrete protocol by Blumberg et al. using one-way functions and commitments for providing various location based vehicle services, and report on our ndings and experience of carrying out its analysis using the ProVerif tool. Third, we make an abstract model of the powerful simulation-based Universally...... 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...... to implement several interesting two-party functionalities. As a case study we use the ProVerif tool to analyse an oblivious transfer protocol by Damgard et al. under static corruption...

  8. Lightweight Distance Bounding Protocol against Relay Attacks

    Science.gov (United States)

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  9. 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.)

  10. Additional protocol experience in Romania

    International Nuclear Information System (INIS)

    Full text: National Commission for Nuclear Activities Control (CNCAN) is the national regulatory body with regulation, authorization and control responsibilities. CNCAN has the right and obligation to ensure that safeguards are applied, in accordance with the terms of the safeguards agreement, on all source or special fissionable material in all peaceful nuclear activities within the State, under its jurisdiction or carried out under its control anywhere, for the exclusive purpose of verifying that such material is not diverted to nuclear weapons or other nuclear explosive devices. CNCAN has built a strong primary and secondary legislation in order to have a strong legal framework to fulfill the NPT, Safeguards Agreement and Additional Protocol requirements. In respect of the non-proliferation issues CNCAN has as a major goal to strengthen the effectiveness and to improve the efficiency of the safeguards system. Also closer co-operation between the IAEA and CNCAN as coordinator of the national system of accounting for and control of nuclear material has been developed by organizing international and national seminars on the implementation of safeguards and the additional protocol. After the entry into force of the Additional Protocol, CNCAN prepared appropriate declarations and answers to the relevant IAEA questions in order to obtain a drawn conclusion of the absence of undeclared nuclear material and nuclear activities within Romania territory. The IAEA evaluated in Romania not only the results of its nuclear material related activities under the Safeguards Agreement but also the results of its broader, more qualitative, evaluation and verification activities under the Additional Protocol. CNCAN assured that the IAEA inspectors have complementary access according to the Additional Protocol as requested in accordance with the provisions of the Safeguards Agreement and the Additional Protocol and cooperated in resolving in a timely manner, any questions or

  11. The Simplest Protocol for Oblivious Transfer

    DEFF Research Database (Denmark)

    Chou, Tung; Orlandi, Claudio

    2015-01-01

    Oblivious Transfer (OT) is the fundamental building block of cryptographic protocols. In this paper we describe the simplest and most efficient protocol for 1-out-of-n OT to date, which is obtained by tweaking the Diffie-Hellman key-exchange protocol. The protocol achieves UC-security against...... optimizations) is at least one order of magnitude faster than previous work. Category / Keywords: cryptographic protocols / Oblivious Transfer, UC Security, Elliptic Curves, Efficient Implementation...

  12. Analysis of the Transport Layer Security protocol

    OpenAIRE

    Firing, Tia Helene

    2010-01-01

    In this master thesis we have presented a security analysis of the TLS protocol with particular emphasis on the recently discovered renegotiation attack. From our security proof we get that the Handshake protocol with renegotiation, including the fix from IETF, is secure, and hence not vulnerable to the renegotiation attack anymore. We have also analysed the Handshake protocol with session resumption, and the Application data protocol together with the Record protocol. Both of these prot...

  13. Developing security protocols in χ-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 effo......-Spaces aids several steps in the development of a security protocolprotocol executions can be simulated in hostile environments, a security protocol can be implemented, and security properties of implementations can be formally verified....

  14. 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)

  15. Protocol biopsies for renal transplantation

    Directory of Open Access Journals (Sweden)

    Rush David

    2010-01-01

    Full Text Available Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.

  16. Kyoto protocol on climate change

    International Nuclear Information System (INIS)

    This article reports a short overview of main points of Kyoto protocol to United Nations Framework Convention on climate Change and of some options still to be defined, evolutions of Italian emissions with respect to other European countries, check of decree by inter ministerial committee on economic planning on national plan to reduce emissions

  17. Performance Evaluation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele;

    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...... of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  18. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...

  19. From protocol to published report

    DEFF Research Database (Denmark)

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs;

    2016-01-01

    %) of the sample, and 87% (95% CI: 80 to 94%) of the trials were hospital based. CONCLUSIONS: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives....

  20. Improving the DGK comparison protocol

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2012-01-01

    When processing signals in the encrypted domain, homomorphic encryption can be used to enable linear operations on encrypted data. Comparison of encrypted data however requires an additional protocol between the parties and will be relatively expensive. A well-known and frequently used comparison pr

  1. The Kyoto Protocol and China

    Institute of Scientific and Technical Information of China (English)

    佘巧云

    2005-01-01

    The kyoto Protocol is an agreement to the United Nations Framework Convention on CLimate Change (UNFCCC)2,an international treaty on global warming .It is a legally binding agreement under which industrialized countries will reduce their collective emissions of greenhouse gases by an average of 5.2% compared to the level of 1990 during the 2008-12 period.

  2. Recursive Ping-Pong Protocols

    DEFF Research Database (Denmark)

    Huttel, Hans; Srba, Jiri

    2004-01-01

    This paper introduces a process calculus with recursion which allows us to express an unbounded number of runs of the ping-pong protocols introduced by Dolev and Yao. We study the decidability issues associated with two common approaches to checking security properties, namely reachability analysis...

  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. Automata-theoretic protocol programming

    NARCIS (Netherlands)

    Jongmans, Sung-Shik Theodorus Quirinus

    2016-01-01

    Parallel programming has become essential for writing scalable programs on general hardware. Conceptually, every parallel program consists of workers, which implement primary units of sequential computation, and protocols, which implement the rules of interaction that workers must abide by. As progr

  5. 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…

  6. 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- α) 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

  7. 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 π-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 μM 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.

  8. Aliskiren attenuates bleomycin-induced pulmonary fibrosis in rats: focus on oxidative stress, advanced glycation end products, and matrix metalloproteinase-9.

    Science.gov (United States)

    Abuelezz, Sally A; Hendawy, Nevien; Osman, Wesam M

    2016-08-01

    Pulmonary fibrosis is a progressive lung disorder with high mortality rate and limited successful treatment. This study was designed to assess the potential anti-oxidant and anti-fibrotic effects of aliskiren (Alsk) during bleomycin (BLM)-induced pulmonary fibrosis. Male Wistar rats were used as control untreated or treated with the following: a single dose of 2.5 mg/kg of BLM endotracheally and BLM and Alsk (either low dose 30 mg/kg/day or high dose 60 mg/kg/day), and another group was given Alsk 60 mg/kg/day alone. Alsk was given by gavage. Alsk anti-oxidant and anti-fibrotic effects were assessed. BLM significantly increased relative lung weight and the levels of lactate dehydrogenase and total and differential leucocytic count in bronchoalveolar lavage that was significantly ameliorated by high-dose Alsk treatment. As markers of oxidative stress, BLM caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease of superoxide dismutase and glutathione transferase enzymes. High-dose Alsk treatment restored these markers toward normal values. Alsk counteracted the overexpression of advanced glycation end products, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 in lung tissue induced by BLM. Fibrosis assessed by measuring hydroxyproline content, which markedly increased in the BLM group, was also significantly reduced by Alsk. These were confirmed by histopathological and immunohistochemical examination which revealed that Alsk attenuates signs of pulmonary fibrosis and decreased the overexpressed MMP-9 and transforming growth factor β1. Collectively, these findings indicate that Alsk has a potential anti-fibrotic effect beside its anti-oxidant activity. PMID:27154762

  9. Improvement In MAODV Protocol Using Location Based Routing Protocol

    Directory of Open Access Journals (Sweden)

    Kaur Sharnjeet

    2016-01-01

    Full Text Available Energy saving is difficult in wireless sensor network (WSN due to limited resources. Each node in WSN is constrained by their limited battery power for their energy. The energy is reduced as the time goes off due to the packet transmission and reception. Energy management techniques are necessary to minimize the total power consumption of all the nodes in the network in order to maximize its life span. Our proposed protocol Location based routing (LBR aimed to find a path which utilizes the minimum energy to transmit the packets between the source and the destination. The required energy for the transmission and reception of data is evaluated in MATLAB. LBR is implemented on Multicast Ad hoc On Demand Distance Vector Routing Protocol (MAODV to manage the energy consumption in the transmission and reception of data. Simulation results of LBR show the energy consumption has been reduced.

  10. 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.

  11. How to write a protocol: part 2.

    Science.gov (United States)

    Thomas, Kathy; Farrell, Mary Beth

    2015-03-01

    Clinical protocols play an important role in the provision of high-quality care in nuclear medicine. Properly written protocols help to ensure that nuclear medicine procedures are performed in a standardized, reproducible manner so that patients receive high-quality care. The following article is the second in a 2-part series on how to write a protocol. A framework for composing protocols and the components of clinical imaging protocols were detailed in the first article. This article details the framework and components of protocols for cardiac stress testing, therapy, and quality control. PMID:25655345

  12. Novel analysis and improvement of Yahalom protocol

    Institute of Scientific and Technical Information of China (English)

    CHEN Chun-ling; YU Han; L(U) Heng-shan; WANG Ru-chuan

    2009-01-01

    The modified version of Yahalom protocol improved by Burrows, Abradi, and Needham (BAN) still has security drawbacks. This study analyzed such flaws in a detailed way from the point of strand spaces, which is a novel method of analyzing protocol's security. First, a mathematical model of BAN-Yahalom protocol is constructed. Second, penetrators' abilities are restricted with a rigorous and formalized definition. Moreover, to increase the security of this protocol against potential attackers in practice, a further improvement is made to the protocol. Future application of this re-improved protocol is also discussed.

  13. Implementation and evaluation of a protocol management system for automated review of CT protocols.

    Science.gov (United States)

    Grimes, Joshua; Leng, Shuai; Zhang, Yi; Vrieze, Thomas; McCollough, Cynthia

    2016-09-08

    Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol-monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency.

  14. Implementation and evaluation of a protocol management system for automated review of CT protocols.

    Science.gov (United States)

    Grimes, Joshua; Leng, Shuai; Zhang, Yi; Vrieze, Thomas; McCollough, Cynthia

    2016-01-01

    Protocol review is important to decrease the risk of patient injury and increase the consistency of CT image quality. A large volume of CT protocols makes manual review labor-intensive, error-prone, and costly. To address these challenges, we have developed a software system for automatically managing and monitoring CT proto-cols on a frequent basis. This article describes our experiences in the implementation and evaluation of this protocol monitoring system. In particular, we discuss various strategies for addressing each of the steps in our protocol-monitoring workflow, which are: maintaining an accurate set of master protocols, retrieving protocols from the scanners, comparing scanner protocols to master protocols, reviewing flagged differences between the scanner and master protocols, and updating the scanner and/or master protocols. In our initial evaluation focusing only on abdo-men and pelvis protocols, we detected 309 modified protocols in a 24-week trial period. About one-quarter of these modified protocols were determined to contain inappropriate (i.e., erroneous) protocol parameter modifications that needed to be corrected on the scanner. The most frequently affected parameter was the series description, which was inappropriately modified 47 times. Two inappropriate modifications were made to the tube current, which is particularly important to flag as this parameter impacts both radiation dose and image quality. The CT protocol changes detected in this work provide strong motivation for the use of an automated CT protocol quality control system to ensure protocol accuracy and consistency. PMID:27685112

  15. Kyoto: protocol on climate protection

    International Nuclear Information System (INIS)

    At the 3rd Conference of the Signatory States to the United Nations Climate Framework Convention held in Kyoto, the so-called Kyoto Protocol on the UN Climate Framework Convention was adopted unanimously, after two years of difficult and complex negotiations, on December 11, 1997. The protocol for the first time includes legally binding obligations for the industrialized countries requiring them to reduce their greenhouse gas emissions between 2008 and 2012 by a total of 5.2% relative to the 1990 level. In meeting this obligation, the industrialized countries assumed different levels of reduction and limitation, respectively. Thus, e.g., the EU countries accepted a Communitywide reduction by 8%, while the USA is obliged to reduce by 7% and Japan by 6%. (orig.)

  16. 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

  17. 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).

  18. 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.

  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. A student teamwork induction protocol

    OpenAIRE

    Kamau, Caroline; Spong, A.

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in HE. 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 contract) designed to minimize social loafing, optimize coordination (by boosting good information sampling) and orient group dynamics towards the task. In the absen...

  1. Heuristic Methods for Security Protocols

    OpenAIRE

    Qurat ul Ain Nizamani; Emilio Tuosto

    2009-01-01

    Model checking is an automatic verification technique to verify hardware and software systems. However it suffers from state-space explosion problem. In this paper we address this problem in the context of cryptographic protocols by proposing a security property-dependent heuristic. The heuristic weights the state space by exploiting the security formulae; the weights may then be used to explore the state space when searching for attacks.

  2. Analysing Protocol Stacks for Services

    DEFF Research Database (Denmark)

    Gao, Han; Nielson, Flemming; Nielson, Hanne Riis

    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 standa...... 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....

  3. 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.

  4. Automatic analysis of distance bounding protocols

    CERN Document Server

    Malladi, Sreekanth; Kothapalli, Kishore

    2010-01-01

    Distance bounding protocols are used by nodes in wireless networks to calculate upper bounds on their distances to other nodes. However, dishonest nodes in the network can turn the calculations both illegitimate and inaccurate when they participate in protocol executions. It is important to analyze protocols for the possibility of such violations. Past efforts to analyze distance bounding protocols have only been manual. However, automated approaches are important since they are quite likely to find flaws that manual approaches cannot, as witnessed in literature for analysis pertaining to key establishment protocols. In this paper, we use the constraint solver tool to automatically analyze distance bounding protocols. We first formulate a new trace property called Secure Distance Bounding (SDB) that protocol executions must satisfy. We then classify the scenarios in which these protocols can operate considering the (dis)honesty of nodes and location of the attacker in the network. Finally, we extend the const...

  5. How to write a protocol: part 1.

    Science.gov (United States)

    Thomas, Kathy; Farrell, Mary Beth

    2015-03-01

    Clinical imaging protocols play an important role in the provision of high-quality care in nuclear medicine. It is imperative that all nuclear medicine facilities have protocols for every procedure performed. However, creating protocols that are detailed, unambiguous, and consistent is often easier said than done. Properly written protocols help to ensure that nuclear medicine procedures are performed in a standardized, reproducible manner so that patients receive high-quality care. This 2-part article provides technologists with a framework for composing comprehensive protocols. Part 1 discusses the secrets to successfully composing protocols ensuring they are detailed and step-by-step along with the importance of basing protocols on evidence from published guidelines and peer-reviewed literature. The components and important aspects of clinical imaging protocols are detailed. PMID:25613336

  6. 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 classical communica...

  7. Static Validation of a Voting Protocol

    DEFF Research Database (Denmark)

    Nielsen, Christoffer Rosenkilde; Andersen, Esben Heltoft; Nielson, Hanne Riis

    2005-01-01

    The desired security properties of electronic voting protocols include verifiability, accuracy, democracy and fairness. In this paper we use a static program analysis tool to validate these properties for one of the classical voting protocols under appropriate assumptions. The protocol...... is formalised in an extension of the LySa process calculus with blinding signatures. The analysis, which is fully automatic, pinpoints previously undiscovered flaws related to verifiability and accuracy and we suggest modifications of the protocol needed for validating these properties....

  8. ACSEPP On-Line Electronic Payment Protocol

    Institute of Scientific and Technical Information of China (English)

    WANG Shao-bin; ZHU Xian; HONG Fan

    2004-01-01

    With analyzing the existing on-line electronic payment protocols, this paper presents a new on-line electronic payment protocol named ACSEPP: Anonymous, Convenient and Secure Electronic Payment Protocol.Its aim is to design a practical electronic payment protocol which is both secure and convenient.Without using PKI_CA frame, it realized the anonymity of consumer and merchant, the convenient of handling, the low cost of maintenance and the security.

  9. Component versioning for protocol configuration management

    Institute of Scientific and Technical Information of China (English)

    CHEN Tian-zhou; HE Zhen-jie; HUANG Jiang-wei; DAI Hong-jun

    2005-01-01

    Classical software configuration management which deals with source code versioning becomes insufficient when most components are distributed in binary form. As an important aspect of software configuration, protocol configuration also encounters those problems. This paper focuses on solving protocol component versioning issues for protocol configuration management on embedded system, incorporating the following versioning issues: version identification, version description and protocol component archiving and retrieving based on the version library.

  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. Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.

    Science.gov (United States)

    Xu, Jianguo; Gonzalez, Edilson T; Iyer, Smita S; Mac, Valerie; Mora, Ana L; Sutliff, Roy L; Reed, Alana; Brigham, Kenneth L; Kelly, Patricia; Rojas, Mauricio

    2009-07-01

    The incidence of pulmonary fibrosis increases with age. Studies from our group have implicated circulating progenitor cells, termed fibrocytes, in lung fibrosis. In this study, we investigate whether the preceding determinants of inflammation and fibrosis were augmented with aging. We compared responses to intratracheal bleomycin in senescence-accelerated prone mice (SAMP), with responses in age-matched control senescence-accelerated resistant mice (SAMR). SAMP mice demonstrated an exaggerated inflammatory response as evidenced by lung histology. Bleomycin-induced fibrosis was significantly higher in SAMP mice compared with SAMR controls. Consistent with fibrotic changes in the lung, SAMP mice expressed higher levels of transforming growth factor-beta1 in the lung. Furthermore, SAMP mice showed higher numbers of fibrocytes and higher levels of stromal cell-derived factor-1 in the peripheral blood. This study provides the novel observation that apart from increases in inflammatory and fibrotic factors in response to injury, the increased mobilization of fibrocytes may be involved in age-related susceptibility to lung fibrosis. PMID:19359440

  12. Multidrug chemotherapy (vincristine-bleomycin-methotrexate) followed by radiotherapy in inoperable carcinomas of the head and neck: preliminary report of a pilot study of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    This is a preliminary report on the Radiation Therapy Oncology Group (RTOG) pilot study 77-08, of a combination of chemotherapy with vincristine-bleomycin-methotrexate, followed by radiotherapy, for inoperable carcinomas of the head and neck. The main objectives of the study were to determine toxicity and tumor control. Patients who were included had untreated carcinomas, with no distant metastases, and with adequate pulmonary, renal, and liver function. Forty patients were registered for the study. Chemotherapy started with vincristine--1.5 mgs/m2 (maximum of 2 mgs) by I.V. injection, followed by bleomycin drip for 48 hours (15 units/day), and then methotrexate (200 mgs/m2 divided in equal doses 6 hours apart) with folinic acid rescue. Eleven patients received one course of the stated chemotherapy; 28 were given two courses with one week rest period between them. Radical curative radiotherapy was started usually two weeks after chemotherapy. A surgical procedure was considered if the patient was found operable after receiving a dose of 5000 rad with continuous therapy or at 3000 rad with split-course therapy. The level of toxicity that resulted from this combined therapy was considered acceptable. The percentage of complete response of the primary tumor was 6% with chemotherapy; this increased to 46% after irradiation, and to 65% when surgery was added

  13. Second-line chemotherapy with bleomycin, methotrexate, and vinorelbine (BMV) for patients with squamous cell carcinoma of the head, neck and esophagus (SCC-HN&E) pretreated with a cisplatin-containing regimen: a phase II study.

    Science.gov (United States)

    Moroni, M; Giannetta, L; Gelosa, G; Secondino, S; Chillura, G; Colombo, E; Siena, S

    2003-08-01

    We evaluated the toxicity and activity of bleomycin, methotrexate and vinorelbine (BMV) combination chemotherapy in cisplatin-pretreated patients with squamous cell carcinoma of the head, neck and esophagus (SCC-HN&E) with the aim of identifying a second-line therapy combination and schedule that might offer an improved therapeutic index. BMV (bleomycin 15 I.U., total dose, methotrexate 30 mg/m2, and vinorelbine 30 mg/m2) was administered intravenously every 2 weeks until disease progression, to 26 consecutive patients. Clinical and CT-scan evaluations revealed 7 partial responses (PR) 127%, 95% confidence interval: 9.6%-44.4%], and 13 patients with stable disease (SD) [50%]. The mean progression-free survival for patients who achieved a PR or SD was 6.47 months (range 4-13 months), with 75% of these patients experiencing partial relief of symptoms, mainly pain and dysphagia. BMV, administered second-line in an outpatient setting, has activity similar to that of the taxanes, but with a more acceptable toxicity profile including an absence of alopecia.

  14. Bioinspired Security Analysis of Wireless Protocols

    DEFF Research Database (Denmark)

    Petrocchi, Marinella; Spognardi, Angelo; Santi, Paolo

    2016-01-01

    work, this paper investigates feasibility of adopting fraglets as model for specifying security protocols and analysing their properties. In particular, we give concrete sample analyses over a secure RFID protocol, showing evolution of the protocol run as chemical dynamics and simulating an adversary...

  15. Cryptanalysis on Cheng et al. protocol

    Science.gov (United States)

    Thakur, Tejeshwari

    2016-06-01

    Deployment of new node in any wireless sensor network is a sensitive task. This is the reason why, an Access Control Protocol is required in WSN. In this paper, we demonstrate that Access Control Protocol proposed by Cheng et al.[1] for Wireless Sensor Network is insecure. The reason is that this protocol fails to resist the active attack.

  16. Epidemic Protocols for Pervasive Computing Systems - Moving Focus from Architecture to Protocol

    DEFF Research Database (Denmark)

    Mogensen, Martin

    2009-01-01

    epidemic protocols as distribution mechanism for pervasive systems. The nature of epidemic protocols make them easy to implement, easy to deploy, and resilient to failures. By using epidemic protocols, it is possible to mitigate a wide range of the potential issues on the protocol layer. The result...

  17. Optimizing One Fair Document Exchange Protocol

    CERN Document Server

    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 incorporates the concept of enforcing the honesty of one party. The proposed protocol consists of only three messages and is more efficient than related protocols.

  18. Vulnerabilities in Quantum Key Distribution Protocols

    CERN Document Server

    Kuhn, D R

    2003-01-01

    Recently proposed quantum key distribution protocols are shown to be vulnerable to a classic man-in-the-middle attack using entangled pairs created by Eve. It appears that the attack could be applied to any protocol that relies on manipulation and return of entangled qubits to create a shared key. The protocols that are cryptanalyzed in this paper were proven secure with respect to some eavesdropping approaches, and results reported here do not invalidate these proofs. Rather, they suggest that quantum cryptographic protocols, like conventional protocols, may be vulnerable to methods of attack that were not envisaged by their designers.

  19. Reactive broadcasting protocol for video on demand

    Science.gov (United States)

    Paris, Jehan-Francois; Carter, Steven W.; Long, Darrell D. E.

    1999-12-01

    We propose a reactive broadcasting protocol that addresses the problem of distributing moderately popular videos in a more efficient fashion. Like all efficient broadcasting protocols, reactive broadcasting assumes that the customer set-top box has enough local storage to store at least one half of each video being watched. Unlike other broadcasting protocols, reactive broadcasting only broadcasts the later portions of each video. the initial segment of each video is distributed on demand using a stream tapping protocol. Our simulations show that reactive broadcasting outperforms both conventional broadcasting protocols and pure stream tapping for a wide range of video request rates.

  20. Sequence Patterns of Identity Authentication Protocols

    Institute of Scientific and Technical Information of China (English)

    Tao Hongcai; He Dake

    2006-01-01

    From the viewpoint of protocol sequence, analyses are made of the sequence patterns of possible identity authentication protocol under two cases: with or without the trusted third party (TTP). Ten feasible sequence patterns of authentication protocol with TTP and 5 sequence patterns without TTP are gained. These gained sequence patterns meet the requirements for identity authentication,and basically cover almost all the authentication protocols with TTP and without TTP at present. All of the sequence patterns gained are classified into unilateral or bilateral authentication. Then , according to the sequence symmetry, several good sequence patterns with TTP are evaluated. The accompolished results can provide a reference to design of new identity authentication protocols.

  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. Novel Ω-protocols for NP

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Ω-protocols, introduced by Garay, Mackenzie and Yang, is a variant of S-protocols with online extractor which is a useful tool to overcome the nest effect in concurrent scenario. In this work, we construct an Ω-protocol for Hamiltonian cycle problem, and therefore, it allows us to present Ω-protocol for any NP relation. For most general NP relations, our construction of Ω-protocols is much more efficient than the informal one described by Garay et al. and we believe that the method for our construction may be of independent interest.

  3. 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.;

    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 ...

  4. Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients during and after chemotherapy

    NARCIS (Netherlands)

    Lubberts, S; Boer, H; Altena, R; Meijer, C; van Roon, A M; Zwart, N; Oosting, S F; Kamphuisen, P W; Nuver, J; Smit, A J; Mulder, A B; Lefrandt, J D; Gietema, J A

    2016-01-01

    BACKGROUND: Metastatic testicular cancer (TC) can be cured with bleomycin, etoposide and cisplatin (BEP) chemotherapy. This comes at the price of an increased cardiovascular disease risk, not only years afterwards, but also during and shortly after chemotherapy. To prevent cardiovascular events, hig

  5. Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients during and after chemotherapy

    NARCIS (Netherlands)

    Lubberts, S.; Boer, H.; Altena, R.; Meijer, C.; van Roon, A. M.; Zwart, N.; Oosting, S. F.; Kamphuisen, P. W.; Nuver, J.; Smit, A. J.; Mulder, A. B.; Lefrandt, J. D.; Gietema, J. A.

    2016-01-01

    Background: Metastatic testicular cancer (TC) can be cured with bleomycin, etoposide and cisplatin (BEP) chemotherapy. This comes at the price of an increased cardiovascular disease risk, not only years afterwards, but also during and shortly after chemotherapy. To prevent cardiovascular events, hig

  6. Chemotherapy-related vascular toxicity : studies in germ cell tumour patients

    NARCIS (Netherlands)

    Nuver, Janine

    2005-01-01

    Testicular cancer is a highly curable disease that mainly affects men between 20 and 40 years of age. Nowadays, over 80% of patients become long-term survivors following treatment with chemotherapy that consists of a combination of bleomycin, etoposide, and cisplatin (BEP-regimen). Unfortunately, va

  7. Authenticating Tripartite Key Agreement Protocol with Pairings

    Institute of Scientific and Technical Information of China (English)

    Sheng-Li Liu; Fang-Guo Zhang; Ke-Fei Chen

    2004-01-01

    In this paper, an authenticated tripartite key agreement protocol is proposed, which is an ID-based one with pairings. This protocol involves only one round. The authenticity of the protocol is assured by a special signature scheme, so that messages carrying the information of two ephemeral keys can be broadcasted authentically by an entity. Consequently, one instance of the protocol results in eight session keys for three entities. In other word, one instance of the protocol generates a session key, which is eight times longer than those obtained from traditional key agreement protocols. Security attributes of the protocol are presented, and the computational overhead and bandwidth of the broadcast messages are analyzed as well.

  8. 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.

  9. Security Protocols: Specification, Verification, Implementation, and Composition

    DEFF Research Database (Denmark)

    Almousa, Omar

    An important aspect of Internet security is the security of cryptographic protocols that it deploys. We need to make sure that such protocols achieve their goals, whether in isolation or in composition, i.e., security protocols must not suffer from any aw that enables hostile intruders to break...... their security. Among others, tools like OFMC [MV09b] and Proverif [Bla01] are quite efficient for the automatic formal verification of a large class of protocols. These tools use different approaches such as symbolic model checking or static analysis. Either approach has its own pros and cons, and therefore, we...... called SPS (Security Protocol Specification) language, that enables users, without requiring deep expertise in formal models from them, to specify a wide range of real-world protocols in a simple and intuitive way. Thus, SPS allows users to verify their protocols using different tools, and generate...

  10. Language, Semantics, and Methods for Security Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico

    Security protocols help in establishing secure channels between communicating systems. Great care needs therefore to be taken in developing and implementing robust protocols. The complexity of security-protocol interactions can hide, however, security weaknesses that only a formal analysis can...... reveal. The last few years have seen the emergence of successful intensional, event-based, formal approaches to reasoning about security protocols. The methods are concerned with reasoning about the events that a security protocol can perform, and make use of a causal dependency that exists between...... 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...

  11. A Secure Short Message Communication Protocol

    Institute of Scientific and Technical Information of China (English)

    Chao-Wen Chang; Heng Pan; Hong-Yong Jia

    2008-01-01

    According to the security requirement of the short message service (SMS) industry application, a secure short message communication protocol is proposed. This is an application level protocol constructed on the standard SMS communication protocol using public key authentication and key agreement without the need of wireless public key infrastructure (WPKI). Secure short message transmission and dynamic key agreement between mobile terminals and the accessing gateway are realized. The security of the proposed protocol is validated through the BAN logic. Compared with the standard SMS protocol, the effective payload rate of our protocol can reach 91.4%, and subscriber identity module (SIM) tool kit (STK) applications based on our protocol suit well for all kinds of mobile terminals in practical application.

  12. 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.

  13. Protocols for calibrating multibeam sonar

    OpenAIRE

    Foote, Kenneth G.; Chu, Dezhang; Hammar, Terence R.; Baldwin, Kenneth C.; Mayer, Larry A.; Hufnagle, Lawrence C. jr.; Jech, J. Michael

    2005-01-01

    Development of protocols for calibrating multibeam sonar by means of the standard-target method is documented. Particular systems used in the development work included three that provide the water-column signals, namely the SIMRAD SM2000/90- and 200-kHz sonars and RESON SeaBat 8101 sonar, with operating frequency of 240 kHz. Two facilities were instrumented specifically for the work: a sea well at the Woods Hole Oceanographic Institution and a large, indoor freshwater tank at the University o...

  14. Research on Container Behaviors Protocol

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    With the development of middleware technology, there are some new features to be adopted on demand in middleware platform based on container component. Aiming at the adaptation of middleware platform, from the nature of component container, this paper begins with behaviors features of EJB (Enterprise Java Bean) container, extracts general behaviors protocol of container, and defines its formal behaviors specification. In the end, the interactive relationship of components is described by WRIGHT language, and the configuration of whole system is shown. The method proposed in this paper mines the hidden features of framework of component container, and applies to refactor middleware platform in reflection and aspect-oriented programming technology.

  15. 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

  16. Protocolized Resuscitation of Burn Patients.

    Science.gov (United States)

    Cancio, Leopoldo C; Salinas, Jose; Kramer, George C

    2016-10-01

    Fluid resuscitation of burn patients is commonly initiated using modified Brooke or Parkland formula. The fluid infusion rate is titrated up or down hourly to maintain adequate urine output and other endpoints. Over-resuscitation leads to morbid complications. Adherence to paper-based protocols, flow sheets, and clinical practice guidelines is associated with decreased fluid resuscitation volumes and complications. Computerized tools assist providers. Although completely autonomous closed-loop control of resuscitation has been demonstrated in animal models of burn shock, the major advantages of open-loop and decision-support systems are identifying trends, enhancing situational awareness, and encouraging burn team communication. PMID:27600131

  17. Trust relationships in exchange protocols

    OpenAIRE

    González-Deleito Collell, Nicolás

    2005-01-01

    Les protocoles d'échange d'informations représentent un des grands domaines actuels de recherche en sécurité informatique, et sont entre autres à la base des mécanismes de commerce électronique. Ils sont par exemple nécessaires à la réalisation d'un achat en ligne, à la signature d'un contrat électronique et au courrier électronique recommandé. Dans ces exemples, les échanges d'informations consistent à échanger respectivement un objet électronique contre un paiement, des signatures digitales...

  18. 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

  19. Analyzing the effect of routing protocols on media access control protocols in radio networks

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, C. L. (Christopher L.); Drozda, M. (Martin); Marathe, A. (Achla); Marathe, M. V. (Madhav V.)

    2002-01-01

    We study the effect of routing protocols on the performance of media access control (MAC) protocols in wireless radio networks. Three well known MAC protocols: 802.11, CSMA, and MACA are considered. Similarly three recently proposed routing protocols: AODV, DSR and LAR scheme 1 are considered. The experimental analysis was carried out using GloMoSim: a tool for simulating wireless networks. The main focus of our experiments was to study how the routing protocols affect the performance of the MAC protocols when the underlying network and traffic parameters are varied. The performance of the protocols was measured w.r.t. five important parameters: (i) number of received packets, (ii) average latency of each packet, (iii) throughput (iv) long term fairness and (v) number of control packets at the MAC layer level. Our results show that combinations of routing and MAC protocols yield varying performance under varying network topology and traffic situations. The result has an important implication; no combination of routing protocol and MAC protocol is the best over all situations. Also, the performance analysis of protocols at a given level in the protocol stack needs to be studied not locally in isolation but as a part of the complete protocol stack. A novel aspect of our work is the use of statistical technique, ANOVA (Analysis of Variance) to characterize the effect of routing protocols on MAC protocols. This technique is of independent interest and can be utilized in several other simulation and empirical studies.

  20. Latest approaches of Kyoto protocol

    International Nuclear Information System (INIS)

    Recently EURELECTRIC welcome the proposal of new EC Directive concerning the inclusion in the EU Emissions Trading Scheme (ETS) of credits from the project mechanisms - Joint Implementation (JI) and Clean Development Mechanism (CDM). The proposed Directive is an amendment to the EU Emissions Trading Directive adopted in June 2003. EURELECTRIC calls for unlimited use of credits in ETS. The draft Directive provides for the application of these mechanisms to begin as of 2008, on condition that the Kyoto Protocol does actually enter into force, an event which is still dependent on Russia's ratification. Such ratification has been subject to contradictory statements from the Russian Government, and the question of whether their signature to the Protocol is forthcoming is still fraught with uncertainty. Although it is not anticipated that significant quantities of JI or CDM certified credits will be available in the period 2005-2007, those that do become available would provide some additional liquidity in the emissions trading market. There is a direct relation between the coming ETS and electricity pricing: environmental policy is the driver, based on the need to switch to a low-carbon future and manage the necessary investments in a rational manner - and emissions trading is the best solution available. Romania has good opportunities to be involved in the greenhouse gases market, both in ETS and JI mechanisms. Some JI projects between Romanian and The Netherlands are already done or underway. (author)

  1. 抗KL-6抗体减弱博莱霉素诱导的肺纤维化%Bleomycin-induced pulmonary fibrosis is attenuated by anti-KL-6 antibody

    Institute of Scientific and Technical Information of China (English)

    徐凌; 杨丹榕; 朱松雷; 顾杰; 丁凤鸣; 边巍; 容朝晖; 沈策

    2013-01-01

    目的 探讨抗KL-6抗体对博莱霉素诱导的肺纤维化的预防作用及可能机制.方法 用气管内滴注博莱霉素的方法制作小鼠肺纤维化模型,于滴注博莱霉素前2天开始雾化抗KL-6抗体,至滴注博莱霉素后第21天.通过支气管肺泡灌洗液细胞计数及分类评价肺部炎症情况,通过肺组织病理评分、羟脯氨酸含量评价肺纤维化情况.通过肺组织中KL-6、转化生长因子p1(TGF-β1)、肝细胞生长因子(HGF)水平、Ⅰ型和Ⅲ型胶原的表达及上皮细胞凋亡情况探讨其可能机制.结果 预防性应用抗KL6抗体可显著降低第21天支气管肺泡灌洗液中的细胞总数及巨噬细胞、淋巴细胞数(P<0.05);降低第14、21天时的肺组织病理评分、羟脯氨酸含量及Ⅰ型、Ⅲ型胶原的表达(P<0.05);降低各时间点上肺组织中KL-6、TGF-β1水平(P<0.05);升高第14、21天时HGF水平(P<0.05);减少各个时间点上的上皮细胞凋亡数(P<0.05).结论 预防性应用抗KL-6抗体可减弱博莱霉素诱导的炎症和纤维化反应,其治疗效应可能是通过降低Ⅰ型和Ⅲ型胶原的表达、增加HGF的产生、减少KL 6和TGF-β1的产生、降低肺上皮细胞的凋亡而发挥作用.%Objective To assess the effect and mechanisms of anti-KL-6 antibody on bleomycininduced pulmonary fibrosis in mice.Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal instillation of bleomycin.Anti-KL-6 antibody was given from two days before bleomycin instillation to the 21st day after bleomycin instillation.Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count.Changes in tissue remodeling were evaluated by quantified pathological examination,measurement of hydroxyproline content.Collagen type Ⅰ and type Ⅲ were detected by qRT-PCR,KL-6,transforming growth factor-β1 (TGF-β1),and hepatocyte growth factor (HGF) in lung tissues were detected by ELISA,and epithelial

  2. Research on Routing Protocol of Mobile Ad Hoc Network

    OpenAIRE

    Tuo Ming Fu; Che Min

    2016-01-01

    Routing protocol is an important content of mobile Ad Hoc. The typical mobile Ad Hoc network routing protocols is introduced. The advantages and disadvantages of these routing protocols are analyzed. A hybrid routing protocol is put forward based on this.

  3. 博莱霉素联合局部热疗治疗恶性胸腔积液的临床观察%Clinical observation of bleomycin combined with local thermotherapy in the treatment of malignant pleural effusion

    Institute of Scientific and Technical Information of China (English)

    周洋; 黄河; 张家洪; 龚建化

    2014-01-01

    Objective To observe the clinical effect of bleomycin combined with local thermotherapy in the treatment of NSCLC patients with malignant pleural effusion. Methods 50 NSCLC patients with malignant pleural effusion were randomly divided into two groups. All patients were treated with thoracentesis and inserted central ve-nous catheter to drainage pleural effusion. After exhaustion of pleural effusion, the control group was treated with ble-omycin by pleural perfusion, and the experiment group was treated with local thermotherapy on the base of the control group. The treatment, side effect and quality of life were compared. Results After the treatment, the KPS scores of living quality and the total effective rate of controlling pleural effusion were better in the experiment group than in the control group (P<0. 05), and the side effect was significant lower in the experiment group than in the control group (P<0. 05). Conclusion Bleomycin combined with local thermotherapy has a synergistic effect in the treatment of NSCLC with malignant pleural effusion.%目的:观察博莱霉素联合局部热疗治疗非小细胞肺癌( NSCLC)恶性胸腔积液的临床疗效。方法将50例NSCLC恶性胸腔积液的患者随机分为两组,采用胸腔穿刺术置入中心静脉导管引流胸腔积液,待排尽胸腔积液后,对照组给予胸腔灌注博莱霉素,实验组在对照组的基础上给予患者局部热疗,比较两组治疗情况、毒副反应及生活质量改善情况。结果两组患者治疗后,实验组患者的生活质量KPS评分及控制胸水的总有效率均明显高于对照组(P<0.05),且不良反应明显少于对照组(P<0.05)。结论博莱霉素联合局部热疗治疗NSCLC恶性胸腔积液具有协同作用,值得临床推广。

  4. Symmetric cryptographic protocols for extended millionaires' problem

    Institute of Scientific and Technical Information of China (English)

    LI ShunDong; WANG DaoShun; DAI YiQi

    2009-01-01

    Yao's millionaires' problem is a fundamental problem in secure multiparty computation, and its solutions have become building blocks of many secure multiparty computation solutions. Unfortunately,most protocols for millionaires' problem are constructed based on public cryptography, and thus are inefficient. Furthermore, all protocols are designed to solve the basic millionaires' problem, that is,to privately determine which of two natural numbers is greater. If the numbers are real, existing solutions do not directly work. These features limit the extensive application of the existing protocols. This study introduces and refines the first symmetric cryptographic protocol for the basic millionaires' problem, and then extends the symmetric cryptographic protocol to privately determining which of two real numbers is greater, which are called the extended millionaires' problem, and proposes corresponding Constructed based on symmetric cryptography, these protocols are very efficient.

  5. 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.

  6. Novel construction of Secure RFID Authentication Protocol

    Directory of Open Access Journals (Sweden)

    Shafiqul Abidin

    2014-10-01

    Full Text Available This article proposes an efficient and secure authentication protocol for secure and low-cost RFID systems in random oracles. Security is one of the prime concerns of RFID system. Proposed protocol relies on Elliptic Curve Discrete Logarithm Problem (ECDLP to achieve security. The protocol achieves the most important security goals scalability, anonymity and anti-cloning for RFID system. A password based protocol has vulnerability on fixed password. This can be exploited by threats. In the proposed protocol, there is a provision to change the password of the Tags. Hence the vulnerability can be reduced in an acceptable level. Computation cost is very less as compare to the other protocols.

  7. 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.

  8. 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.)

  9. [The research protocol. Part I].

    Science.gov (United States)

    Miranda-Novales, María Guadalupe; Villasís-Keever, Miguel Ángel

    2015-01-01

    One of the principal aims in research is the publication of the study in scientific journals. This implies two challenges: the first one, the election of an adequate research design, and the second one, the concrete and simple wording of the results for the study to be accepted in the most appropriate journal according to the scope. Despite numerous supporting documents are available for both issues, the publication process is long, tiresome, and can discourage the most enthusiastic researcher. This is the first of a series of articles with the objective to describe the steps from the research question to the publication of the study. First of all, the importance of the research design will be addressed. The structure of the protocol is essential to achieve the objectives, and provides a way to organize the investigation in a logic, comprehensible and efficient manner.

  10. The comparative cost analysis of EAP Re-authentication Protocol and EAP TLS Protocol

    Directory of Open Access Journals (Sweden)

    Seema Mehla

    2010-05-01

    Full Text Available the Extensible Authentication Protocol (EAP is a generic framework supporting multiple types of authentication methods. In systems where EAP is used for authentication, it is desirable to not repeat the entire EAP exchange with another authenticator. The EAP reauthentication Protocol provides a consistent, methodindependentand low-latency re-authentication. It is extension to current EAP mechanism to support intradomain handoff authentication. This paper analyzed the performance of the EAP re-authentication protocol, andcompared it with that of the EAP-TLS protocol. The result shows that the authentication delay of EAP reauthentication protocol is only twentieth of that in the EAPTLS protocol.

  11. An Identity- Based Key- Exchange Protocol

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ya-juan; ZHU Yue-fei; HUANG Qiu-sheng

    2005-01-01

    An identity-based key-exchange protocol using a bilinear map is proposed and it is proved SK-secure(session key secure) in the AM (authenticated links adversarial model)provided the BDDH (bilinear Diffie-Hellmen) assumption is correct. Then we apply the signature-based authenticator to our protocol and obtain an identity-Based key-exchange protocol that is SK-secure in the UM (unauthenticated links adversarial model) provided the BDDH assumption is correct.

  12. Vulnerabilities in Quantum Key Distribution Protocols

    OpenAIRE

    Kuhn, D. Richard

    2003-01-01

    Recently proposed quantum key distribution protocols are shown to be vulnerable to a classic man-in-the-middle attack using entangled pairs created by Eve. It appears that the attack could be applied to any protocol that relies on manipulation and return of entangled qubits to create a shared key. The protocols that are cryptanalyzed in this paper were proven secure with respect to some eavesdropping approaches, and results reported here do not invalidate these proofs. Rather, they suggest th...

  13. 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...

  14. 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 system...

  15. Security in network environment-network protocols

    OpenAIRE

    Fessl, Jaromír

    2011-01-01

    Work is focused on network protocols features and security characteristics. Overview of protocols is made through all layers of OSI model and by this design structured. For each layer is made summary of interesting facts. Separate chapter is dedicated for VPN and for implementation possibilities of VPN. In chapter Practical problems are reflected most important problems of actual security (from network protocol point of view) concerned on SSL/TLS, SMTP and DNS. Together with security charact...

  16. Security analysis of session initiation protocol

    OpenAIRE

    Dobson, Lucas E.

    2010-01-01

    Approved for public release; distribution is unlimited The goal of this thesis is to investigate the security of the Session Initiation Protocol (SIP). This was accomplished by researching previously discovered protocol and implementation vulnerabilities, evaluating the current state of security tools and using those tools to discover new vulnerabilities in SIP software. The CVSS v2 system was used to score protocol and implementation vulnerabilities to give them a meaning that was us...

  17. VULNERABILITIES OF THE SSL/TLS PROTOCOL

    OpenAIRE

    Jelena Ćurguz

    2016-01-01

    This paper analyzes vulnerabilities of the SSL/TLS Handshake protocol, which is responsible for authentication of the parties in the communication and negotiation of security parameters that will be used to protect confidentiality and integrity of the data. It will be analyzed the attacks against the implementation of Handshake protocol, as well as the attacks against the other elements necessary to SSL/TLS protocol to discover security flaws that were exploited, modes of attac...

  18. Rewriting-Based Verification of Authentication Protocols

    OpenAIRE

    Ogata, Kazuhiro; Futatsugi, Kokichi

    2004-01-01

    We propose a method of formally analysing security protocols based on rewriting. The method is roughly as follows. A security protocol is modeled as an observational transition system, which is described in CafeOBJ. Proof scores showing that the protocol has safety (security) properties are then written in CafeOBJ and the proof scores are executed (rewritten) by the CafeOBJ system.

  19. Bitcoin-NG: A Scalable Blockchain Protocol

    OpenAIRE

    Eyal, Ittay; Gencer, Adem Efe; Sirer, Emin Gun; van Renesse, Robbert

    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...

  20. 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...

  1. 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].

  2. CIMS Network Protocol and Its Net Models

    Institute of Scientific and Technical Information of China (English)

    罗军舟; 顾冠群

    1997-01-01

    Computer communication network architectures for cims are based on the OSI Reference Model.In this paper,CIMS network protocol model is set up on the basis of the corresqonding service model.Then the authors present a formal specification of transport protocols by using an extended Predicate/Transition net system that is briefly introduced in the third part.Finally,the general methods for the Petri nets based formal specification of CIMS network protocols are outlined.

  3. Universal protocol for alopecia areata clinical studies.

    Science.gov (United States)

    Mesinkovska, Natasha A; Bergfeld, Wilma F

    2013-12-01

    Within the area of alopecia areata research, there is an obvious need for well-designed clinical trials of therapeutic agents. The National Alopecia Areata Foundation (NAAF) has created an initiative for the development of a unified protocol with guidelines for clinical studies. The NAAF universal protocol represents a joint effort of clinicians and investigators with experience in treating alopecia areata. This protocol will serve as a tremendous resource to facilitate future clinical studies. PMID:24326554

  4. A Formal Approach to Protocol Performance Testing

    Institute of Scientific and Technical Information of China (English)

    XU Mingwei; WU Jianping

    1999-01-01

    This paper proposes a formal approach to protocol performance testing based on the extended concurrent TTCN. To meet the needs of protocol performance testing, concurrent TTCN is extended, and the extended concurrent TTCN's operational semantics is defined in terms of Input-Output Labeled Transition System. An architecture design of protocol performance test system is described, and an example of test cases and its test resultare given.

  5. Quantum three-pass cryptography protocol

    Science.gov (United States)

    Yang, Li; Wu, Ling-An; Liu, Songhao

    2002-09-01

    We present a new kind of quantum cryptography protocol based on Shamir's three-pass protocol of classical cryptography, which allows the transmission of qubits directly and secretly via the aid of an unjammable classical channel. In this protocol we implement the encryption and decryption transformations via rotations on the Poincare sphere of the photons polarization parameters. The key technique is that Bob's encryption rotation must be commutative with Alice s decryption rotation; this means that the axes of these two rotations must be parallel. We also present a security analysis of the protocol under a man-in-the-middle attack.

  6. Network Coding Protocols for Smart Grid Communications

    DEFF Research Database (Denmark)

    Prior, Rui; Roetter, Daniel Enrique Lucani; Phulpin, Yannick;

    2014-01-01

    We propose a robust network coding protocol for enhancing the reliability and speed of data gathering in smart grids. At the heart of our protocol lies the idea of tunable sparse network coding, which adopts the transmission of sparsely coded packets at the beginning of the transmission process...... but then switches to a denser coding structure towards the end. Our systematic mechanism maintains the sparse structure during the recombination of packets at the intermediate nodes. The performance of our protocol is compared by means of simulations of IEEE reference grids against standard master-slave protocols...

  7. A formal model of fair exchange protocols

    Institute of Scientific and Technical Information of China (English)

    QING Sihan; LI Gaicheng

    2005-01-01

    Based on the study of existing fair exchange protocols, this paper sets up an accurate formal model by stepwise refinement. In the process of refinement an unreliable channel is employed to simulate an attack behavior. The model provides a novel formal definition of exchanged items, and presents the formal goals for fairness, accountability,etc., reflecting the inherent requirements for fair exchange protocols across-the-board. In order to check, prove, and design fair exchange protocols effectively and efficiently, the model puts forward a novel property of abuse-freeness which applies to all fair exchange protocols, gives a formal definition for trust strand of the third party, and presents general criteria of designing a secure and effective fair exchange protocol. Taking a typical fair exchange protocol as an example, this paper presents the analysis steps of fair exchange protocols appealing to our model. An unknown attack is uncovered. The analysis reveals the process of a complete attack, discovering deeper reasons for causing an attack.Finally, we modify the flawed protocol and the revised protocol ensures the desirable properties.

  8. A New Watermarking Protocol against Conspiracy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun; KOU Weidong; FAN Kai; CAO Xuefei

    2006-01-01

    A trusted third party introduced in watermarking protocols would decrease the security and affect the implementation of the protocols. In this paper, a new watermarking protocol with an un-trusted third party (UTTP) was proposed. Based on the idea of all-or-nothing disclosure of secret (ANDOS), all of the buyer, the seller and the third party didn't know the exact watermark, which was embedded in a digital content for tracing piracy. The proposed protocol provided mechanisms to trace piracy and protect customer's right. In addition, the problem that a seller colluded with UTTP to frame the buyer, namely, the conspiracy problem, could be avoided.

  9. Tool Supported Analysis of Web Services Protocols

    DEFF Research Database (Denmark)

    Marques, Abinoam P.; Ravn, Anders Peter; Srba, Jiri;

    2011-01-01

    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...

  10. 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.

  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. 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

  14. Equilibria of Generalized Cut and Choose Protocols

    DEFF Research Database (Denmark)

    Branzei, Simina; Caragiannis, Ioannis; Kurokawa, David;

    Classic cake cutting protocols — which fairly allocate a divisible good among agents with heterogeneous preferences — are susceptible to manipulation. Do their strategic outcomes still guarantee fairness? To answer this question we adopt a novel algo rithmic approach, proposing a concrete...... 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...

  15. Experimental Study on Effect of Compound Biejia Ruangan Prescription(复方鳖甲软肝方) on High-Resolution Computerized Tomographic Images in Bleomycin Induced Pulmonary Fibrosis Rats

    Institute of Scientific and Technical Information of China (English)

    张东伟; 王继峰; 牛建昭; 高宝华; 李贡宇

    2003-01-01

    Objective: To study the therapeutic effect of Compound Biejia Ruangan prescription (CBRP) on rat model with pulmonary fibrosis induced by bleomycin. Methods: Fifty-four male Sprague-Dawley rats were randomly divided into 6 groups (9 rats in each group). From the first day to the 28th day of the experiment, except to those in the sham-model control group that were treated with normal saline, the same amount of bleomycin injection as the normal saline given to the control group was given through endotracheal instillation to all the rats in all the other groups. From the 29th day of the modeling, CBRP solution of different dosages was respectively injected into the rats in the high, moderate and low CBRP dose group, while equal volume of normal saline was given to those in the sham-model control group and the model control group, and an equal volume of prednisone solution was given to rats in the prednisone group. On the 80th day, the high-resolution computerized tomographic (HRCT) images were observed on an equal footing, and HRCT-pathology was correlatively studied. Results: Different HRCT pathological changes were shown in the rats with pulmonary fibrosis, such as lung consolidation, thickening of interlobular septum and interlobular mesenchyma as well as lobular deformation, nodule shadow, abnormal brochiovascular tract, thickened pleura with irregular junction and polished glass-like dense shadows. Honeycomb lung was observed in some cases. Pathological sections showed fibrotic proliferation of lung tissues and noticeable pulmonary interstitial fibrosis. CBRP could improve HRCT images of rats with pulmonary fibrosis, and lower fibrotic proliferation of the lung tissue.Conclusion: CBRP plays its therapeutic role possibly through its effect on the structure of the lung in rats with pulmonary fibrosis.

  16. Analysis of a security protocol in ?CRL

    NARCIS (Netherlands)

    Pang, J.

    2002-01-01

    Needham-Schroeder public-key protocol; With the growth and commercialization of the Internet, the security of communication between computers becomes a crucial point. A variety of security protocols based on cryptographic primitives are used to establish secure communication over insecure open netwo

  17. Diagrammatization of the Transmission Control Protocol

    Directory of Open Access Journals (Sweden)

    Sabah Al-Fedaghi

    2012-09-01

    Full Text Available With the wide spread of Internet services, developers and users need a greater understanding of the technology of networking. Acquiring a clear understanding of communication protocols is an important step in understanding how a network functions; however, many protocols are complicated, and explaining them can be demanding. In addition, protocols are often explained in terms of traffic analysis and oriented toward technical staff and those already familiar with network protocols. This paper aims at proposing a diagrammatic methodology to represent protocols in general, with a focus on the Transmission Control Protocol and Secure Sockets Layer in particular. The purpose is to facilitate understanding of protocols for learning and communication purposes. The methodology is based on the notion of flow of primitive things in a system with six stages: creation, release, transfer, arrival, acceptance, and processing. Though the method presents a basic description of protocols without in-depth analysis of all aspects and mechanisms, the resultant conceptual description is a systematic specification that utilizes a few basic notions that assist in illustrating functionality and support comprehension.

  18. Climate Change And The Kyoto Protocol

    International Nuclear Information System (INIS)

    The problem of global warming is addressed. Changes in earth surface temperature, emission of CO2 and other four major green house gases are presented. Effect of global warming on weather, ocean, and ecosystem is discussed. A brief history of the Kyoto protocol starting from the 151 Earth Summit in 1972 is outlined. An overview of the protocol and a brief summary are given

  19. Kyoto Protocol: trade versus the environment

    International Nuclear Information System (INIS)

    Could the signatories to the Kyoto Protocol find themselves up against the WTO? This paper examines how the climate change agreement could conflict with trade rules, and shows that there are potentially serious conflicts in the interface between the WTO and the Kyoto Protocol. It argues for dialogue and debate before it is too late. (author)

  20. Performance of a connectionless protocol over ATM

    NARCIS (Netherlands)

    Heijenk, Geert J.; Moorsel, van Aad P.A.; Niemegeers, Ignas G.

    1992-01-01

    Recent studies show the existence of a demand for a connectionless broadband service. In order to cope with this demand, a connectionless protocol for the B-ISDN needs to be designed. Such a protocol should make use of ATM and the ATM Adaptation Layer. It needs to specify destination and bandwidth o

  1. Summary Report on Rational Cryptographic Protocols

    DEFF Research Database (Denmark)

    Alwen, Joël; Cachin, Christian; Pereira, Olivier;

    This report gives an overview of some of the models and techniques in rational cryptography, an emerging research area which in particular uses the methodologies and techniques of game theory to analyze cryptographic protocols and which uses cryptographic protocol theory to implement game theoretic...

  2. Welfare monitroing system : assessment protocol for horses

    NARCIS (Netherlands)

    Livestock Research,

    2012-01-01

    This document describes the protocol for horses in more detail. For the development of the protocol the Welfare Quality® framework was used. For each measure there is a description how to assess the measure including the method of classification.

  3. 40 CFR 161.70 - Acceptable protocols.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Acceptable protocols. 161.70 Section 161.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA... Development (OECD) Protocols. Tests conducted in accordance with the requirements and recommendations of...

  4. The Formal Specifications for Protocols of Decoders

    Institute of Scientific and Technical Information of China (English)

    YUAN Meng-ting; WU Guo-qing; SHU Feng-di

    2004-01-01

    This paper presents a formal approach, FSPD (Formal Specifications for Protocols of Decoders), to specify decoder communication protocols. Based on axiomatic, FSPD is a precise language with which programmers could use only one suitable driver to handle various types of decoders. FSPD is helpful for programmers to get high adaptability and reusability of decoder-driver software.

  5. Secure Geographic Routing Protocols: Issues and Approaches

    CERN Document Server

    sookhak, Mehdi; Haghparast, Mahboobeh; ISnin, Ismail Fauzi

    2011-01-01

    In the years, routing protocols in wireless sensor networks (WSN) have been substantially investigated by researches. Most state-of-the-art surveys have focused on reviewing of wireless sensor network .In this paper we review the existing secure geographic routing protocols for wireless sensor network (WSN) and also provide a qualitative comparison of them.

  6. Secure Geographic Routing Protocols: Issues and Approaches

    Directory of Open Access Journals (Sweden)

    Mehdi sookhak

    2011-09-01

    Full Text Available In the years, routing protocols in wireless sensor networks (WSN have been substantially investigated by researches Most state-of-the-art surveys have focused on reviewing of wireless sensor network .In this paper we review the existing secure geographic routing protocols for wireless sensor network (WSN and also provide a qualitative comparison of them.

  7. Forests and the Kyoto Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Goetze, D.C. [Environment Canada, Ottawa, ON (Canada)

    2001-07-01

    This PowerPoint presentation referred to carbon sinks in the Clean Development Mechanism (CDM) as specified in the Kyoto Protocol. Policy issues, opportunities and challenges were discussed. The slides summarized the environmental potential of carbon sink projects, the current status of carbon sinks in the CDM, and strategies towards a CDM carbon sink. The Nyakach, Kenya biomass enhancement case study was presented, along with the Colombian Andean biodiversity corridor reforestation project. Potential sink projects were described as those resulting in direct reduction of emissions. These include reducing deforestation by protecting forests from being converted to agriculture, by protecting forests from the impacts of human activities, and by substituting biomass energy sources for fossil fuels. Indirect reduction of emissions via sequestration involves restoring natural forests in deforested or degraded areas and expanding agroforests and plantations. The co-benefits of carbon sink projects are biodiversity and socio-economic benefits. Under the Bonn Agreement, afforestation and reforestation projects are eligible under the CDM. Credits are limited to 1 per cent of Annex 1 party's base year emissions per year. The important elements of the Marrakech Accord are the prompt start of the CDM, as well as modalities and procedures.

  8. Treatment protocols for cervical cancer

    Directory of Open Access Journals (Sweden)

    Vujkov Tamara

    2002-01-01

    Full Text Available Introduction Cervical cancer is the second most common cancer in women worldwide and the second cause of cancer death among women. About 95% (90% in developed countries of invasive carcinomas are of sqamous types, and 5% (10% in developed countries are adenocarcinomas. FIGO classification of cervical carcinomas, based on clinical staging and prognostic factor dictate therapeutic procedures and help in designing treatment protocols. Therapeutic modalities Surgical therapy includes conization, radical hysterectomy with pelvic lymphadenectomy and palliative operation urinary diversion and colostomy. Radiotherapy, brachytherapy and teletherapy are most recently combined with chemotherapy as concurrent chemoradiation. Discussion and conclusion No change in therapeutic modalities will ever decrease mortality rate of cervical carcinoma as much as education, prevention and early screening. The 5-year survival for locally advanced disease has not improved during the last 40 years as a result of failure to deliver therapy to the paraaortic region. Paraaortic lymph nodes should be evaluated before therapy planning by different imaging procedures, or more exactly by surgical staging: laparoscopy or laparotomy. Radical operations of cervical carcinoma should be performed by experienced surgeons, educated for this type of operation, with sufficient number of cases.

  9. Quantum Communication Complexity of Quantum Authentication Protocols

    CERN Document Server

    Guedes, Elloá B

    2011-01-01

    In order to perform Quantum Cryptography procedures it is often essencial to ensure that the parties of the communication are authentic. Such task is accomplished by quantum authentication protocols which are distributed algorithms based on the intrinsic properties of Quantum Mechanics. The choice of an authentication protocol must consider that quantum states are very delicate and that the channel is subject to eavesdropping. However, even in face of the various existing definitions of quantum authentication protocols in the literature, little is known about them in this perspective, and this lack of knowledge may unfavor comparisons and wise choices. In the attempt to overcome this limitation, in the present work we aim at showing an approach to evaluate quantum authentication protocols based on the determination of their quantum communication complexity. Based on our investigation, no similar methods to analyze quantum authentication protocols were found in the literature. Pursuing this further, our approa...

  10. Security Weaknesses in Arbitrated Quantum Signature Protocols

    Science.gov (United States)

    Liu, Feng; Zhang, Kejia; Cao, Tianqing

    2014-01-01

    Arbitrated quantum signature (AQS) is a cryptographic scenario in which the sender (signer), Alice, generates the signature of a message and then a receiver (verifier), Bob, can verify the signature with the help of a trusted arbitrator, Trent. In this paper, we point out there exist some security weaknesses in two AQS protocols. Our analysis shows Alice can successfully disavow any of her signatures by a simple attack in the first protocol. Furthermore, we study the security weaknesses of the second protocol from the aspects of forgery and disavowal. Some potential improvements of this kind of protocols are given. We also design a new method to authenticate a signature or a message, which makes AQS protocols immune to Alice's disavowal attack and Bob's forgery attack effectively.

  11. Cryptanalysis of the arbitrated quantum signature protocols

    Science.gov (United States)

    Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo; Wen, Qiao-Yan

    2011-08-01

    As a new model for signing quantum messages, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver, Bob, can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender, Alice, can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics on AQS protocols that can be studied in future.

  12. Cryptanalysis of the arbitrated quantum signature protocols

    CERN Document Server

    Gao, Fei; Guo, Fen-Zhuo; Wen, Qiao-Yan

    2011-01-01

    As a new model for signing quantum message, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver Bob can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender Alice can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics in future study on AQS protocols.

  13. VULNERABILITIES OF THE SSL/TLS PROTOCOL

    Directory of Open Access Journals (Sweden)

    Jelena Ćurguz

    2016-05-01

    Full Text Available This paper analyzes vulnerabilities of the SSL/TLS Handshake protocol, which is responsible for authentication of the parties in the communication and negotiation of security parameters that will be used to protect confidentiality and integrity of the data. It will be analyzed the attacks against the implementation of Handshake protocol, as well as the attacks against the other elements necessary to SSL/TLS protocol to discover security flaws that were exploited, modes of attack, the potential consequences, but also studying methods of defense. All versions of the protocol are going to be the subject of the research but emphasis will be placed on the critical attack that the most endanger the safety of data. The goal of the research is to point out the danger of existence of at least vulnerability in the SSL/TLS protocol, which can be exploited and endanger the safety of the data that should be protected.

  14. Multicast Protocol for Uni-Directional Networks

    Institute of Scientific and Technical Information of China (English)

    黄皓; 陈贵海; 谢立; 孙钟秀

    2000-01-01

    A very inexpensive receive-only satellite receiver can receive high bandwidth traffic from a feeder. Therefore the connection between the feeder and the receiver is uni-directional. The existing routing protocols, such as Link-State and Distance-Vector, are designed on the premise that any links are bidirectional and they cannot handle the uni-directional links. In this paper, a dynamic multicast routing protocol is proposed, which can handle uni-directional networks. This protocol can also adapt to the dynamic change of the topology of the network and has good scalability. A formal description of the protocol by Petri net is given. Liveness,deadlock free and other properties of the protocol are proved.

  15. A fully efficient secure quantum cryptography protocol

    CERN Document Server

    Xiang Bin Wang

    2001-01-01

    Since Bennett and Brassard suggested their quantum key distribution protocol(BB84 protocol) in 1984, the subject has been extensively studied both theoretically and experimentally. The protocol allows two remote parties Alice and Bob to create and share a secret key using a quantum channel and public authenticated communications. The quantum key created in this way is in principle secure because eavesdroppers have no way to tap the quantum channel without disturb it. In the protocol, two level quantum bits are measured in two basis, $X$ and $Z$ randomly by Bob. So at least half of the measurement results will be discarded because Bob has a half probability taking the measurement in a wrong basis. On the other hand, the security is not the maximum in BB84 protocol. To increase the security, one may straightforwardly increase the number of basis used in the protocol. For example, six state protocol was proposed recently for two level system. However, in this way, it seems to be the case that the higher the secu...

  16. Efficient Privacy Preserving Protocols for Similarity Join

    Directory of Open Access Journals (Sweden)

    Bilal Hawashin

    2012-04-01

    Full Text Available During the similarity join process, one or more sources may not allow sharing its data with other sources. In this case, a privacy preserving similarity join is required. We showed in our previous work [4] that using long attributes, such as paper abstracts, movie summaries, product descriptions, and user feedbacks, could improve the similarity join accuracy using supervised learning. However, the existing secure protocols for similarity join methods can not be used to join sources using these long attributes. Moreover, the majority of the existing privacy‐preserving protocols do not consider the semantic similarities during the similarity join process. In this paper, we introduce a secure efficient protocol to semantically join sources when the join attributes are long attributes. We provide two secure protocols for both scenarios when a training set exists and when there is no available training set. Furthermore, we introduced the multi‐label supervised secure protocol and the expandable supervised secure protocol. Results show that our protocols can efficiently join sources using the long attributes by considering the semantic relationships among the long string values. Therefore, it improves the overall secure similarity join performance.

  17. Snakebite management in Iran: Devising a protocol

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Monzavi

    2014-01-01

    Full Text Available Background: Snakebite in Iran has been a health concern. However, management of snakebite is not standardized and varies from center to center. This study is aimed at devising an evidence-based comprehensive protocol for snakebite management in Iran, to reduce unnecessary variations in practice. Materials and Methods: A narrative search in electronic databases was performed. Fifty peer-reviewed articles, guidelines, and textbooks were reviewed and practical details were extracted. Our currently used protocol in the Mashhad Toxicology Center was supplemented with this information. Consequently an improved wide-range protocol was developed. The protocol was then discussed and amended within a focus group comprised of medical toxicologists and internal medicine specialists. The amended version was finally discussed with expert physicians specialized in different areas of medicine, to be optimized by supplementing other specific considerations. Results: During a one-year process, the protocol was finalized. The final version of the protocol, which was designed in six steps, comprised of three components: A schematic algorithm, a severity grading scale, and instructions for supportive and adjunctive treatments. The algorithm pertains to both Viperidae and Elapidae snakebite envenomations and consists of a planned course of action and dosing of antivenom, based on the severity of the envenomation. Conclusion: Snakebite envenomation is a clinical toxicologic emergency, which needs to be treated in a timely and organized manner. Hence, a multi-aspect protocol was designed to improve the clinical outcomes, reduce unnecessary administration of antivenom, and help physicians make more proper clinical judgments.

  18. Energy Efficient Routing Protocol for MANET

    Directory of Open Access Journals (Sweden)

    S.Gopinath

    2012-03-01

    Full Text Available In recent years, many energy-efficient routing protocols have been proposed. However, very little efforts have been taken in studying the energy consumption of individual node, overhead and route maintaining issues. While not considering the design of energy efficient routing protocol, it may perform very worst than the normal routing protocol. Here, we have proposed On Demand Based Energy Efficient Routing Protocol (ODBEERP. The main aim of proposed protocol is to discover the minimum power-limitation route. The power limitation of a route is decided by the node which has the minimum energy in that route. So compared with the minimum node energy in any other route, the minimum node energy in the minimum power-limitation route has more energy. We have also proposed a more accurate analysis to track the energy consumptions due to various factors, and improve the performance during path discovery and in mobility scenarios. The proposed protocol is evaluated with object oriented discrete event simulator environment. Simulation results shows that the ODBEERP achieves good throughput, less delay, high packet delivery ratio and good energy efficiency than the existing protocol PEER.

  19. ANALYSIS OF THE PROTECTED EXTENSIBLE AUTHENTICATION PROTOCOL

    Directory of Open Access Journals (Sweden)

    Amit Rana

    2012-09-01

    Full Text Available 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 Client identity protection andkey generation thus preventing unauthorized user accessand protecting or encrypting the data against maliciousactivities.

  20. Advanced Internet Protocols, Services, and Applications

    CERN Document Server

    Oki, Eiji; Tatipamula, Mallikarjun; Vogt, Christian

    2012-01-01

    Today, the internet and computer networking are essential parts of business, learning, and personal communications and entertainment. Virtually all messages or transactions sent over the internet are carried using internet infrastructure- based on advanced internet protocols. Advanced internet protocols ensure that both public and private networks operate with maximum performance, security, and flexibility. This book is intended to provide a comprehensive technical overview and survey of advanced internet protocols, first providing a solid introduction and going on to discu

  1. Demand Priority Protocol Simulation and Evaluation

    Institute of Scientific and Technical Information of China (English)

    ZHAN Yongzhao; SONG Shunlin; XIE Li

    1999-01-01

    A new network protocol (DemandPriority Protocol) environment can provide more satisfying service fordifferent urgent transmission requests. In this paper, in order toprovide guidance for the selection of environment of multimedia datatransmission in Computer Supported Cooperative Work better, anobject-oriented protocol specification language based on C++ is used todesign a virtual environment of multiworkstation of computer cooperativework and to simulate exe-cution of demand priority network protocoland then the performances of various transmission requests are analyzed.Finally, an evaluation of the demand priority LAN is given.

  2. The Russian Federation and the Kyoto Protocol

    OpenAIRE

    Douma, Wybe; Ratsiborinskaya, Daria

    2007-01-01

    textabstractThis book brings together the results of two conferences: 'The Kyoto Protocol and beyond: A legal perspective', organised by the University of Siena on 10-11 June 2006, and 'Tackling Climate Change: An appraisal of the Kyoto Protocol and options for the future', held at the T.M.C. Asser Institute in The Hague on 30-31 March 2007. These conferences focused on the legal aspects of the Kyoto Protocol implementation and the post-2012 regime. Experts in European and international envir...

  3. Security-Preserving Asymmetric Protocol Encapsulation

    OpenAIRE

    Vaudenay, Serge; Phan, Raphael C-W

    2007-01-01

    Query-response based protocols between a client and a server such as SSL, TLS, SSH are asymmetric in the sense that the querying client and the responding server play different roles, and for which there is a need for two-way linkability between queries and responses within the protocol. We are motivated by the observation that though results exist in other related contexts, no provably secure scheme has been applied to the setting of client-server protocols, which differ from conventional co...

  4. Performance evaluation of TCP over ABT protocols

    Science.gov (United States)

    Ata, Shingo; Murata, Masayuki; Miyahara, Hideo

    1998-10-01

    ABT is promising for effectively transferring a highly bursty data traffic in ATM networks. Most of past studies focused on the data transfer capability of ABT within the ATM layer. In actual, however, we need to consider the upper layer transport protocol since the transport layer protocol also supports a network congestion control mechanism. One such example is TCP, which is now widely used in the Internet. In this paper, we evaluate the performance of TCP over ABT protocols. Simulation results show that the retransmission mechanism of ABT can effectively overlay the TCP congestion control mechanism so that TCP operates in a stable fashion and works well only as an error recovery mechanism.

  5. Overview of the InterGroup protocols

    Energy Technology Data Exchange (ETDEWEB)

    Berket, Karlo [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Agarwal, Deborah A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Melliar-Smith, P. Michael [Univ. of California, Santa Barbara, CA (United States); Moser, Louise E. [Univ. of California, Santa Barbara, CA (United States)

    2001-03-01

    Existing reliable ordered group communication protocols have been developed for local-area networks and do not, in general, scale well to large numbers of nodes and wide-area networks. The InterGroup suite of protocols is a scalable group communication system that introduces a novel approach to handling group membership, and supports a receiver-oriented selection of service. The protocols are intended for a wide-area network, with a large number of nodes, that has highly variable delays and a high message loss rate, such as the Internet. The levels of the message delivery service range from unreliable unordered to reliable group timestamp ordered.

  6. Analysis of Enhanced Associativity Based Routing Protocol

    Directory of Open Access Journals (Sweden)

    Said A. Shaar

    2006-01-01

    Full Text Available This study introduces an analysis to the performance of the Enhanced Associativity Based Routing protocol (EABR based on two factors; Operation complexity (OC and Communication Complexity (CC. OC can be defined as the number of steps required in performing a protocol operation, while CC can be defined as the number of messages exchanged in performing a protocol operation[1]. The values represent the worst-case analysis. The EABR has been analyzed based on CC and OC and the results have been compared with another routing technique called ABR. The results have shown that EABR can perform better than ABR in many circumstances during the route reconstruction.

  7. Analyzing security protocols in hierarchical networks

    DEFF Research Database (Denmark)

    Zhang, Ye; Nielson, Hanne Riis

    2006-01-01

    Validating security protocols is a well-known hard problem even in a simple setting of a single global network. But a real network often consists of, besides the public-accessed part, several sub-networks and thereby forms a hierarchical structure. In this paper we first present a process calculus...... capturing the characteristics of hierarchical networks and describe the behavior of protocols on such networks. We then develop a static analysis to automate the validation. Finally we demonstrate how the technique can benefit the protocol development and the design of network systems by presenting a series...

  8. Comparison of on Demand Routing Protocols

    Directory of Open Access Journals (Sweden)

    Bharat Bhushan

    2013-02-01

    Full Text Available 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 requirements. On the other hand on demand routing strategy creates routes when required and hence is very much suitable for ad hoc network. This paper therefore examines the performance of three on demand routing protocols at application layer using QualNet-5.01 simulator.

  9. Implementation of the Additional Protocol in Japan

    International Nuclear Information System (INIS)

    The Additional Protocol between Japan and the IAEA entered into force in December 1999. To come into force a series of implementation trials of Additional Protocol was carried out at two Japanese representative nuclear research centers, i.e. Tokai Research Establishment of Japan Atomic Energy Research Institute (JAERI) and Oarai Engineering Center of Japan Nuclear Fuel Cycle Development Institute (JNC). These trials were proposed by Japan and were conducted in cooperation with the IAEA Secretariat. In addition, Japan amended 'the Law for the Regulation of Reactors etc.', to collect adequate information to submit to the IAEA, to arrange the surrounding for the complementary access, etc. In addition, Japan Submitted the Initial Declaration of the Additional Protocol within 180 days of the entry into force of the Protocol, in the middle of June, 2000

  10. Saudi Arabia and CERN sign protocol

    CERN Multimedia

    2008-01-01

    On 9 May 2008, Mohammed I. Al Suwaiyel, President of the King Abdulaziz City of Science and Technology, representing the Government of Saudi Arabia, and CERN Director-General, Robert Aymar, signed a protocol to the 2006 cooperation agreement between CERN and Saudi Arabia. Members of the Saudi Arabian Government visit ATLAS.The purpose of the protocol is to define the operational framework needed to carry out various specific tasks provided for in the cooperation agreement in order to promote the development of a high energy particle physics community in Saudi Arabia and its ultimate visible participation as a member of the global CERN community. Signing the protocol, Mohammed I. Al-Suwaiyel said: "The Saudi Arabian Government has taken a number of initiatives to promote R&D in the interests of our country’s development and the advancement of science. Thanks to this protocol, Saudi scientists will be able to work towards this go...

  11. Standardized North American Marsh Bird Monitoring Protocol

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document describes monitoring protocols for marshbirds in North America. Monitoring parameters, field procedures, survey methods, timing of surveys, recording...

  12. Privacy-Preserving Protocols for Eigenvector Computation

    CERN Document Server

    Pathak, Manas A

    2010-01-01

    In this paper, we present a protocol for computing the dominant eigenvector of a collection of private data distributed across multiple parties, with the individual parties unwilling to share their data. Our proposed protocol is based on secure multiparty computation with a trusted third-party arbitrator who deals with data encrypted by the other parties using an additive homomorphic cryptosystem. We also augment the protocol with randomization to make it difficult, with a high probability, for any party to estimate properties of the data belonging to other parties from the intermediate steps. The previous approaches towards this problem were based on expensive QR decomposition of correlation matrices, we present an efficient algorithm using the power iteration method. We present an analysis of the correctness, security, efficiency of protocol and experiments over a prototype implementation.

  13. Multicast Routing Protocols in Adhoc Mobile networks

    Directory of Open Access Journals (Sweden)

    S.Nagaprasad,

    2010-11-01

    Full Text Available The majority of applications are in areas where rapid deployment and dynamic reconfiguration are necessary and a wire line network is not available. These include military battlefields, emergency search and rescue sites, classrooms, and conventions where participants share information dynamically using their mobile devices. Well established routing protocols do exist to offer efficient multicasting service in conventional wired networks. These protocols, having been designed for fixed networks, may fails to keep up with node movements and frequent topology changes in a MANET. Therefore, adapting existing wired multicast protocols as such to a MANET, which completely lacks infrastructure, appear less promising. Providing efficient multicasting over MANET faces many challenges, includes scalability,quality of service, reliable service, security, Address configuration, Applications for multicast over MANET. The existing multicast routing protocol do not addresses these issues effectively over Mobile Adhoc Networks (MANET.

  14. Protocol to Exploit Waiting Resources for UASNs

    Directory of Open Access Journals (Sweden)

    Li-Ling Hung

    2016-03-01

    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  15. Protocol to Exploit Waiting Resources for UASNs.

    Science.gov (United States)

    Hung, Li-Ling; Luo, Yung-Jeng

    2016-01-01

    The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN) is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  16. National Wildlife Refuge System Survey Protocol Template

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This template was developed for drafting National Wildlife Refuge System (NWRS) Survey Protocols. The template is arranged in the same order as the eight basic...

  17. ARC Code TI: Geometry Manipulation Protocol (GMP)

    Data.gov (United States)

    National Aeronautics and Space Administration — The Geometry Manipulation Protocol (GMP) is a library which serializes datatypes between XML and ANSI C data structures to support CFD applications. This library...

  18. Compiling symbolic attacks to protocol implementation tests

    Directory of Open Access Journals (Sweden)

    Michael Rusinowitch

    2013-07-01

    Full Text Available Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically generating abstract attacks and converting them to concrete tests on protocol implementations. In particular we aim to improve previously proposed blackbox testing methods in order to discover automatically new attacks and vulnerabilities. As a proof of concept we have experimented our proposed architecture to detect a renegotiation vulnerability on some implementations of SSL/TLS, a protocol widely used for securing electronic transactions.

  19. Protocol to Exploit Waiting Resources for UASNs.

    Science.gov (United States)

    Hung, Li-Ling; Luo, Yung-Jeng

    2016-01-01

    The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN) is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols. PMID:27005624

  20. Identity-based authentication protocol for grid

    Institute of Scientific and Technical Information of China (English)

    Li Hon; Sun Shixin; Yang Homiao

    2008-01-01

    Current grid authentication frameworks are achieved by applying the standard SSL authentication protocol(SAP).The authentication process is very complicated,and therefore,the grid user is in a heavily loaded point both in computation and in communication.Based on identity-based architecture for grid(IBAG)and corre-sponding encryption and signature schemes,an identity-based authentication protocol for grid is proposed.Being certificate-free,the authentication protocol aligns well with the demands of grid computing.Through simulation testing,it is seen that the authentication protocol is more lightweight and efficient than SAP,especially the more lightweight user side.This contributes to the larger grid scalability.

  1. How To Develop Survey Protocols: A Handbook

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This handbook provides a standard and guidance for developing and reviewing survey protocols used in the National Wildlife Refuge System. In the handbook, survey...

  2. Rethinking low extra delay background transport protocols

    CERN Document Server

    Carofiglio, Giovanna; Rossi, Dario; Testa, Claudio; Valenti, Silvio

    2010-01-01

    BitTorrent has recently introduced LEDBAT, a novel application-layer congestion control protocol for data exchange. The protocol design starts from the assumption that network bottlenecks are at the access of the network, and that thus user traffic competes creating self-inducing congestion. To relieve from this phenomenon, LEDBAT is designed to quickly infer that self-induced congestion is approaching (by detecting relative changes of the one-way delay in the transmission path), and to react by reducing the sending rate prior that congestion occurs. Prior work has however shown LEDBAT to be affected by a latecomer advantage, where newly arriving connections can starve already existing flows. In this work, we propose modifications to the congestion window update mechanism of the LEDBAT protocol that aim at solving this issue, guaranteeing thus intra-protocol fairness and efficiency. Closed-form expressions for the stationary throughput and queue occupancy are provided via a fluid model, whose accuracy is conf...

  3. Reparable Key Distribution Protocols for Internet Environments

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    It has claimed that any practical way to achieve perfect reparability for key distribution protocol (KDP) could only be futile. Fortunately, this paper presents reparable KDPs for internet environments with the use of the concept of timestamps.

  4. Secure Key Management Protocol in WIMAX

    OpenAIRE

    Noudjoud Kahya; Nacira Ghoualmi; Pascal Lafourcade

    2012-01-01

    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. ...

  5. OAuth protocol for CERN Web Applications

    OpenAIRE

    Kleszcz, Emil; Rodriguez Fernandez, Luis; Marescaux, Nicolas Bernard

    2016-01-01

    Project Specification The CERN Authentication service has recently increased his offer of SSO protocols/frameworks with OAuth2 standard. The purpose of the work is to explain the need for an authorization standard and explain how does OAuth2 protocol addresses our requirements. OAuth is an open standard for authorization which provides a secure access to server resources that belongs to a user. As a wide known and relatively new standard (2012) is used by big players in the industry a...

  6. The Kyoto Protocol: Can We Meet?

    OpenAIRE

    Boromisa, Ana-Maria; Tišma, Sanja

    2008-01-01

    Integration into the EU is one of strategic foreign policy goals of Croatia. Before accession, Croatia has to align with the EU policies and legislation. The European Commission in its Croatia 2007 Progress report identified ratification of the Kyoto Protocol as progress regarding environmental chapter of accession negotiations. By ratifying the Kyoto Protocol in May 2007 Croatia pledged to reduce greenhouse gases by 5% in the first commitment period, 2008-2012, from the amount released into ...

  7. The obscure future of the Kyoto protocol

    OpenAIRE

    Tsayem Demaze, Moise

    2013-01-01

    Since it came into effect in 2005 followed by its first period of application from 2008 to 2012, the Kyoto protocol has been subject to debates and international negotiations about its post-2012 future. Many grey areas persist, even though the Durban conference, held in December 2011, and the Doha conference, held in December 2012, ratified the principle of a second period of application of the protocol and started negotiations for a new international treaty supposed to come into effect in 2020.

  8. The Kyoto Protocol : a Review and Perspectives

    OpenAIRE

    Böhringer, Christoph

    2003-01-01

    International concern about climate change has led to the Kyoto Protocol, negotiated in 1997, which contains legally binding emission targets for industrialized countries to be achieved during the commitment period 2008-2012. While proponents of the Protocol celebrate it as a breakthrough in international climate policy, opponents criticize that its approach, namely setting targets and timetables for emission reductions, is seriously flawed. This paper provides a critical assessment of the Pr...

  9. Mutual Authentication Protocols for RFID Systems

    Institute of Scientific and Technical Information of China (English)

    Ashrar A. Omer; Johnson P. Thomas; Ling Zhu

    2008-01-01

    With the availability of low-cost radio frequency identification (RFID) tags, security becomes an increasing concern.However, such tags do not permit complex eryptographic functions due to their computational, communications, and storage limitations.In this paper, we investigate the security issues and requirements of RFID systems, and propose ultra-light weight and light weight protocols for low-cost RFID tags. The proposed protocols has been applied to a supply chain management system.

  10. Quantum Key Distribution Protocol with User Authentication

    CERN Document Server

    Lee, H; Lee, D; Lim, J; Yang, H J; Lee, Hwayean; Lee, Sangjin; Lee, Donghoon; Lim, Jongin; Yang, HyungJin

    2005-01-01

    We propose a quantum key distribution protocol with quantum based user authentication. User authentication is executed by validating the correlation of GHZ states. Alice and Bob can distribute a secure key using the remaining GHZ states after authentication. This secret key does not leak even to the arbitrator by the properties of the entanglement. We will show that our protocol is secure against the cloning attack.

  11. Protocol for communications in potentially noisy environments

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, Gerlad M.; Farrow, Jeffrey

    2016-02-09

    A communications protocol that is designed for transmission of data in networks that are subjected to harsh conditions is described herein. A network includes a plurality of devices, where the devices comprise respective nodes. The nodes are in communication with one another by way of a central network hub. The protocol causes the nodes to transmit data over a network bus at different data rates depending upon whether the nodes are operating normally or an arbitration procedure has been invoked.

  12. Voice over Internet Protocol (VOIP): Future Potential

    OpenAIRE

    Ms. Deepti

    2014-01-01

    VoIP (voice over IP) delivers standard voice over telephone services over Internet Protocol (IP). VoIP is the technology of digitizing sound, compressing it, breaking it up into data packets, and sending it over an IP (internet protocol) network where it is reassembled, decompressed, and converted back into an analog wave form. Gateways are the key component required to facilitate IP Telephony. A gateway is used to bridge the traditional circuit switched PSTN with the packet switched Internet...

  13. Compiling symbolic attacks to protocol implementation tests

    OpenAIRE

    Michael Rusinowitch; Ghazi Maatoug; Hatem Ghabri

    2013-01-01

    Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically g...

  14. Trust Authentication Protocol on the Web

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    It is unsuitable to use traditional identity-based authentication on the Web where entities are not foreknown to each other. Trust relationship must be established between strangers before authentication. To achieve trust authentication, the resource-constrained trust negotiation is addressed, and traditional authentication key exchange protocol is extended. Owing to avoiding the heavy computational demands the public key cryptography operations bring about, the authentication protocol is well-suited for security authentication on the Web.

  15. Dose protocols of acetylcholine test in Chinese

    Institute of Scientific and Technical Information of China (English)

    向定成; 龚志华; 何建新; 洪长江; 邱建; 马骏

    2004-01-01

    @@ Acetylcholine test has been widely used clinically in several countries as a practical test provoking coronary artery spasm.1-3 Although it has also been launched recently in a few hospitals in China, the dose protocol for acetylcholine test used in these hospitals were from abroad.4,5 This study was aimed at developing a dose protocol for acetylcholine test suitable for Chinese people.

  16. Analyzing the exhaustiveness of the synapse protocol

    OpenAIRE

    Marinkovic, Bojan; Ciancaglini, Vincenzo; Ognjanovic, Zoran; Glavan, Paola; Liquori, Luigi; Maksimovic, Petar

    2015-01-01

    International audience The Synapse protocol is a scalable protocol designed for information retrieval over inter-connected heterogeneous overlay networks. In this paper, we give a formal description of Synapse using the Abstract State Machines framework. The formal description pertains to Synapse actions that manipulate distributed keys. Based on this formal description, we present results concerning the expected exhaustiveness for a number of scenarios and systems maintained by the Synaps...

  17. Hybrid Long-Distance Entanglement Distribution Protocol

    DEFF Research Database (Denmark)

    Brask, J.B.; Rigas, I.; Polzik, E.S.;

    2010-01-01

    We propose a hybrid (continuous-discrete variable) quantum repeater protocol for long-distance entanglement distribution. Starting from states created by single-photon detection, we show how entangled coherent state superpositions can be generated by means of homodyne detection. We show that near......-deterministic entanglement swapping with such states is possible using only linear optics and homodyne detectors, and we evaluate the performance of our protocol combining these elements....

  18. Field Monitoring Protocol. Heat Pump Water Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Sparn, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Earle, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Christensen, D. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Maguire, J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wilson, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hancock, C. E. [Mountain Energy Partnership, Longmont, CO (United States)

    2013-02-01

    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  19. Variable TDMA MAC Protocol For WDM EPON

    Institute of Scientific and Technical Information of China (English)

    Minsuk; Jung; Yongseok; Chang; Jonghoon; Eom; Sungho; Kim

    2003-01-01

    A MAC(Media Access Control) protocol, one of the most important technologies for an EPON(Ethernet Passive Optical Network), contains a scheduling algorithm to avoid collisions in shared links and assigns an effective bandwidth when ONUs (Optical Network Units) transfer signals upward. The current paper proposes a MAC Protocol that operates a TDMA(Time method with a variable slot assignment to overcome short of bandwidth using by the number of n wavelength., the next generation access network. To verify ...

  20. Field Monitoring Protocol: Heat Pump Water Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Sparn, B.; Earle, L.; Christensen, D.; Maguire, J.; Wilson, E.; Hancock, E.

    2013-02-01

    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  1. Optimistic protocol for partitioned distributed database systems

    International Nuclear Information System (INIS)

    A protocol for transaction processing during partition failures is presented which guarantees mutual consistency between copies of data-items after repair is completed. The protocol is optimistic in that transactions are processed without restrictions during the failure; conflicts are detected at repair time using a precedence graph and are resolved by backing out transactions according to some backout strategy. The protocol is then evaluated using simulation and probabilistic modeling. In the simulation, several parameters are varied such as the number of transactions processed in a group, the type of transactions processed, the number of data-items present in the database, and the distribution of references to data-items. The simulation also uses different backout strategies. From these results we note conditions under which the protocol performs well, i.e., conditions under which the protocol backs out a small percentage of the transaction run. A probabilistic model is developed to estimate the expected number of transactions backed out using most of the above database and transaction parameters, and is shown to agree with simulation results. Suggestions are then made on how to improve the performance of the protocol. Insights gained from the simulation and probabilistic modeling are used to develop a backout strategy which takes into account individual transaction costs and attempts to minimize total backout cost. Although the problem of choosing transactions to minimize total backout cost is, in general, NP-complete, the backout strategy is efficient and produces very good results

  2. Network-topology-adaptive quantum conference protocols

    Institute of Scientific and Technical Information of China (English)

    Zhang Sheng; Wang Jian; Tang Chao-Jing; Zhang Quan

    2011-01-01

    As an important application of the quantum network communication,quantum multiparty conference has made multiparty secret communication possible.Previous quantum multiparty conference schemes based on quantum data encryption are insensitive to network topology.However,the topology of the quantum network significantly affects the communication efficiency,e.g.,parallel transmission in a channel with limited bandwidth.We have proposed two distinctive protocols,which work in two basic network topologies with efficiency higher than the existing ones.We first present a protocol which works in the reticulate network using Greeberger-Horne-Zeilinger states and entanglement swapping.Another protocol,based on quantum multicasting with quantum data compression,which can improve the efficiency of the network,works in the star-like network.The security of our protocols is guaranteed by quantum key distribution and one-time-pad encryption.In general,the two protocols can be applied to any quantum network where the topology can be equivalently transformed to one of the two structures we propose in our protocols.

  3. Performance of coopMAC Protocols over CSMA/CA 802.11 protocols

    Directory of Open Access Journals (Sweden)

    H.Srikanth.Kamath

    2013-06-01

    Full Text Available Wireless communication is very fast becoming the most frequently used form of communication. Ad-Hoc networks can be easily set up anywhere without any infrastructure cost and its mobility adds to its advantage. Hence with increase in its demand the quality of the setup comes under scrutiny, hence calling for its development. This paper presents the concept of Cooperative MAC protocols. Cooperative MAC protocols are found to be more efficient over 802.11 MAC protocols and improve the network performance substantially. Comparison of 802.11 MAC protocols and CoopMAC protocols on NS2 platform is carried out and successfully proved that cooperative MAC protocols offer much higher throughput.

  4. EAR Protocol-Towards Fair Optimistic Non-Repudiation Exchange

    Institute of Scientific and Technical Information of China (English)

    WANG Hai-yan; WANG Ru-chuan

    2005-01-01

    Fairness is of crucial importance for the exchange protocols via Internet. Non-repudiation therefore becomes one of the vital premises, which are essential in the exchange of sensitive and important messages. This paper is to propose a new exchange protocol, termed "EAR" Exchange Protocol as it consists of three sub-protocols: Exchange sub-protocol, Abort sub-protocol and Recovery sub-protocol. It is to be argued that the incorporation of these three sub-protocols may effectively enables EAR to assure non-repudiation, strong fairness, timeliness, confidentiality and the minimized involvement of the Trusted Third Party (TTP).

  5. Security Analysis of Broadcaster Group Key Exchange Protocols

    Institute of Scientific and Technical Information of China (English)

    LI Li; ZHANG Huanguo

    2006-01-01

    Group key exchange protocols are basic protocols to provide privacy and integrity in secure group communication. This paper discusses the security of one type of group key exchange protocols and defines the kind of protocols as broadcaster group protocols. It points out two attacks on this kind of protocols. The first attack can be avoided by using fresh values in each action during one session of the group protocol. The second attack should be related with concrete application. It also proposes a dynamic key agreement protocol as an example of solutions at the last part of the paper.

  6. Chain-Chain Based Routing Protocol

    Directory of Open Access Journals (Sweden)

    Samia A Ali

    2011-05-01

    Full Text Available Wireless sensor network (WSN is an emerging technology for monitoring physical world. WSNs consist of large numbers of sensor nodes operated by battery mostly in harsh environment. Thus energy conservation is a primary issue for organization of these sensor nodes. Another crucial issue is the data delivery time by sensor nodes to the sink node, especially in Military, medical fields, and security monitoring systems where minimum delay is desirable. Number of protocols has been proposed in the literature for routing. One of such protocols is the cluster based routing protocol LEACH (low energy adaptive clustering hierarchy. LEACH protocol organizes WSN into a set of clusters and a periodic voting for cluster head is performed in order to be evenly distributed among all the sensors of the WSN. This periodical cluster head voting in LEACH, however, consumes an amount of non-negligible energy and other resources. For energy conservation, PEGASIS (power efficient gathering in sensor information systems a near optimal chain-based protocol has been proposed, however, it is faced with the challenge of long delay for the transmitted data. Another routing protocol called CCM (Chain-Cluster based Mixed routing, which is mainly a hybrid of LEACH and PEGASIS is proposed, the consumed energy increases as network size increases. In this paper, we propose an efficient routing protocol called CCBRP (Chain-Chain based routing protocol, it achieves both minimum energy consumption and minimum delay. The CCBRP protocol mainly divides a WSN into a number of chains (Greedy algorithm is used to form each chain as in PEGSIS protocol and runs in two phases. In the first phase, sensor nodes in each chain transmit data to their chain leader nodes in parallel. In the second phase, all chain leader nodes form a chain (also, using Greedy algorithm and choose randomly a leader node then all chain leader nodes send their data to this chosen leader node. This chosen leader node

  7. Protocol Independent Multicast Based States Allocation

    Directory of Open Access Journals (Sweden)

    G Hemalatha

    2012-02-01

    Full Text Available In this paper the Protocol Independent Multicast (PIM protocol is being used. The PIM protocol avoids the packet drop and diverting problem. The PIM protocol is not dependent on any specific unicast routing protocol. It is IP routing independent protocol. The PIM uses the unicast and multicast information to create a distribution tree along the reverse path from the receivers towards the source. The PIM protocol consists of three modes such as sparse mode, dense mode and bidirectional mode. The sparse mode is used to sends the file from router to a receiver. The dense mode is used to sends the file from router to multiple receivers. The bidirectional mode is used to sends the message from router to sender and then continue the other process depending on the sender requirements. The client sends the file from sender to destination via the router. First the sender selects the file name and receiver name for transmission. Then the state is assigned automatically depend upon the user selection. The state can be defined by the number of destination selected to transmit the file from the source. If the sender selects single destination, it will assign “Without forwarding state router” for transmission. Otherwise it will assign “Forwarding state router” for transmission. If the receiver is not available, the router sends a message to sender such that “the requested receiver is not available”. Then the client will decide the file is transfer or not, it will reply with transfer the file, then the file will be transferred until the file will be discarded at client side. If the sender tries the same process after two times, the router will display the warning message as “the requested receiver is not available, this file will be discarded at client side”. Then it continues the other process.

  8. Performance Evaluation of Routing Protocols in MANET

    Directory of Open Access Journals (Sweden)

    Smitha Sunny

    2015-01-01

    Full Text Available Mobile Ad-Hoc Network (MANET is an autonomous system that is composed of the mobile nodes which communicates through wireless links without any preexisting infrastructure. MANET is a collection of mobile nodes which can self-organize freely and dynamically into arbitrary and temporary network topologies. Mobile nodes in ad-hoc networks function as a router and can dynamically establish routes among themselves by means of a routing protocol. Routing protocols in mobile ad-hoc network helps node to send and receive packets. Therefore, selection of an appropriate routing protocol is an integral part of establishing a MANET. A suitable and effective routing mechanism helps to extend the successful deployment of mobile ad-hoc networks. An attempt has been made to compare the performance between on-demand reactive routing protocols namely AODV, DSR and proactive routing protocol namely DSDV for Constant Bit Rate (CBR traffic by varying network scope i.e. number of participating nodes as well as by varying the speed. The parameters used for evaluation are Packet delivery ratio (PDR, Normalized routing overhead, Average end to end delay (Delay, Throughput and Average Energy consumption. The simulations are carried out using Network Simulator NS2:34.

  9. A Lightweight Buyer-Seller Watermarking Protocol

    Directory of Open Access Journals (Sweden)

    Yongdong Wu

    2008-01-01

    Full Text Available The buyer-seller watermarking protocol enables a seller to successfully identify a traitor from a pirated copy, while preventing the seller from framing an innocent buyer. Based on finite field theory and the homomorphic property of public key cryptosystems such as RSA, several buyer-seller watermarking protocols (N. Memon and P. W. Wong (2001 and C.-L. Lei et al. (2004 have been proposed previously. However, those protocols require not only large computational power but also substantial network bandwidth. In this paper, we introduce a new buyer-seller protocol that overcomes those weaknesses by managing the watermarks. Compared with the earlier protocols, ours is n times faster in terms of computation, where n is the number of watermark elements, while incurring only O(1/lN times communication overhead given the finite field parameter lN. In addition, the quality of the watermarked image generated with our method is better, using the same watermark strength.

  10. WDM Network and Multicasting Protocol Strategies

    Directory of Open Access Journals (Sweden)

    Pinar Kirci

    2014-01-01

    Full Text Available Optical technology gains extensive attention and ever increasing improvement because of the huge amount of network traffic caused by the growing number of internet users and their rising demands. However, with wavelength division multiplexing (WDM, it is easier to take the advantage of optical networks and optical burst switching (OBS and to construct WDM networks with low delay rates and better data transparency these technologies are the best choices. Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive applications. In the paper, a new multicasting protocol with OBS is proposed. The protocol depends on a leaf initiated structure. The network is composed of source, ingress switches, intermediate switches, edge switches, and client nodes. The performance of the protocol is examined with Just Enough Time (JET and Just In Time (JIT reservation protocols. Also, the paper involves most of the recent advances about WDM multicasting in optical networks. WDM multicasting in optical networks is given as three common subtitles: Broadcast and-select networks, wavelength-routed networks, and OBS networks. Also, in the paper, multicast routing protocols are briefly summarized and optical burst switched WDM networks are investigated with the proposed multicast schemes.

  11. Manet Load Balancing Parallel Routing Protocol

    Directory of Open Access Journals (Sweden)

    Hesham Arafat Ali

    2012-07-01

    Full Text Available In recent years, multi-path routing protocols have attained more attention in mobile ad hoc networks as compared to other routing schemes due to their abilities and efficiency in improving bandwidth of communication, increasing delivery reliability, responding to congestion and heavy traffic. Several protocols have been developed to address multi path routing, but it always has a problem that the discovered paths may be not 100% disjoint and sending data is done in only one path until it's broken; the discovery of multiple paths also generates more overhead on the network. Load Balancing Parallel Routing Protocol [LBPRP] tried to solve previous multi path problems, distributing traffic among multiple paths sending data in parallel form as it uses all paths in the same time. We employed a simple test scenario to be sure of proposed model efficiency and to validate the proposed Load Balancing Parallel Routing Protocol. [LBPRP] will achieve load balancing in sending data, decreasing the end-to-end delay and increasing the packet delivery ratio and throughput, thus the performance of multi-path routing protocols can be improved consequently.

  12. Economics of the Kyoto Protocol for Russia

    Energy Technology Data Exchange (ETDEWEB)

    Golub, D.D.; Strukova, E. [Environmental Defense, Washington, DC (United States)

    2004-07-01

    The authors propose a careful analysis of the economic consequences of the Kyoto Protocol for Russian economic recovery. They review a different GHG forecasts for Russia and develop a new forecast for uncertain GDP growth and the changing elasticity of GHG emissions per GDP. As the rate of growth remains uncertain, elasticity could change over time, as well as the fuel mix. They apply the Monte-Carlo method to simulate these uncertainties and to produce a reasonable interval for CO{sub 2} emissions in 2010. The probability of Russia exceedings its Kyoto emissions budget is essentially zero. They also discuss the benefits for Russia from the Kyoto Protocol, and more generally from the implementation of GHG mitigation policy. Ancillary benefits from Kyoto Protocol implementation will bring essential reductions in risk to human health. On the other hand, potential negative changes in the fuel mix and GDP structure, as well as a slowing of the innovation process, could exacerbate the existing health problems. Alternatives to the Kyoto Protocol may bring much tougher commitments to Russia. In conclusion the Kyoto Protocol is the best possible deal for Russia. 24 refs., 4 figs., 5 tabs.

  13. Controlled Delegation Protocol in Mobile RFID Networks

    Directory of Open Access Journals (Sweden)

    Yang MingHour

    2010-01-01

    Full Text Available To achieve off-line delegation for mobile readers, we propose a delegation protocol for mobile RFID allowing its readers access to specific tags through back-end server. That is to say, reader-tag mutual authentication can be performed without readers being connected to back-end server. Readers are also allowed off-line access to tags' data. Compared with other delegation protocols, our scheme uniquely enables back-end server to limit each reader's reading times during delegation. Even in a multireader situation, our protocol can limit reading times and reading time periods for each of them and therefore makes back-end server's delegation more flexible. Besides, our protocol can prevent authorized readers from transferring their authority to the unauthorized, declining invalid access to tags. Our scheme is proved viable and secure with GNY logic; it is against certain security threats, such as replay attacks, denial of service (DoS attacks, Man-in-the-Middle attacks, counterfeit tags, and breaches of location and data privacy. Also, the performance analysis of our protocol proves that current tags can afford the computation load required in this scheme.

  14. Semen cryopreservation protocols of Mangalarga Marchador stallions

    Directory of Open Access Journals (Sweden)

    Marcela Leite Candeias

    2012-09-01

    Full Text Available The effect of the utilization of three semen protocols (Inra 82®, Merck Gema and Botu-crio® and two filling techniques (0.25 and 0.50 mL straws in Mangalarga Marchador stallions were studied in this experiment. Sperm parameters were assessed during processing and post-freezing. No interactions between the protocols and type of filling were observed, so they were assessed separately. Sperm parameters were not altered when the extender was added to the centrifugation; however, there was reduction of motility and strength when freezing extenders were added. The Botu-crio® protocol preserved the parameters of total and progressive sperm motility, smoothed path velocity (µm/s, straight line velocity (µm/s, track velocity (µm/s and the average and fast spermatozoa percentage better than the others. No difference between the extenders for the percentage of sperm integrity was observed. There was no difference in the responses studied on the filling techniques. The stallions presented better freezing with the use of the Botu-crio® protocol. The best post-freezing viability results were found for semen frozen using the Botu-crio® protocol and there were no differences concerning the sperm quality comparing 0.25 and 0.50 mL straws.

  15. Eccentricity in Zone Routing Protocol for MANET

    Directory of Open Access Journals (Sweden)

    Mrs Komal Nair

    2012-06-01

    Full Text Available A Mobile Ad-Hoc Network (MANET is a decentralized network of autonomous mobile nodes, able to communicate with each other over wireless links. Due to the mobility of the nodes, the topology ofthe network changes spontaneously, therefore use of conventional routing tables maintained at fixed points (routers is not suggested. Such a network may operate in a standalone fashion. There are variousrouting protocols available for MANETs. The most popular ones are DSR, DSDV and ZRP .The zone routing protocol (ZRP is a hybrid routing protocol that proactively maintains routes within a localregion of the network. ZRP can be configured for a particular network through adjustment of a single parameter, the routing zone radius. In this paper, we address the issue of configuring the ZRP to providethe best performance for a particular network at any time with the concept of eccentricity. The results illustrate the important characteristics of different protocols based on their performance and thus suggest some improvements in the respective protocol. The tools used for the simulation are NS2 which is the main simulator, NAM (Network Animator and Tracegraph which is used for preparing the graphs from the trace files.

  16. Welfare Quality assessment protocol for laying hens = Welfare Quality assessment protocol voor leghennen

    OpenAIRE

    Niekerk, van, M.; H. Gunnink; Reenen, van, A Alexander

    2012-01-01

    Results of a study on the Welfare Quality® assessment protocol for laying hens. It reports the development of the integration of welfare assessment as scores per criteria as well as simplification of the Welfare Quality® assessment protocol. Results are given from assessment of 122 farms.

  17. Animation of Natural Language Specifications of Authentication Protocols

    Directory of Open Access Journals (Sweden)

    Mabroka A. Mayouf

    2008-01-01

    Full Text Available Problem Statement: A few visualization tools have been created for protocol design and analysis. Although these tools provide an environment for designing security protocols, each one has its own protocol definition language (its also called informal specification language. The problem is that the user should understand the language which related to the used tool in order to define an exist protocol or design a new one. For specification, a language needs to be intuitive as well as easily usable and understandable by the security protocol engineer. It must be able to precisely and unambiguously specify the behavior of security protocol. Approach: In this study, we propose an approach for protocol specification based on the Natural language definitions of protocol semantics. By using programmatic semantics together with animations, representational flexibility of different protocol demonstration is retained for as long as it is needed. Result: This study provides an environment that can be used by protocols designers to develop and investigate different scenarios of security protocols especially authentication protocols. Natural Language Protocol Specifications (NLPS approach is used to define the protocol. The environment accepts the natural language text of protocol specifications and converts it to animations of protocol behavior. Conclusions/Recommendations: NLPS environment can really help protocol designer to consider and investigate the behavior of security protocols. It can also be used for teaching-learning security protocol concepts. In further, we will consider the possibility of analyzing security protocols using our NLPS environment and animation techniques in order to improve the correctness; that is determining whether or not the intended security properties of a protocol do hold.

  18. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

    Science.gov (United States)

    Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

    2016-01-01

    A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID:26811365

  19. A Review: Multi Protocol Label Switching (Mpls

    Directory of Open Access Journals (Sweden)

    Rashed Qayoom Shawl,

    2014-01-01

    Full Text Available The demand for technology called MPLS is increasing day by day in most internet service provider networks. Majority of the carriers are deploying MPLS in their backbone networks to facilitate a number of services and applications such as virtual private networks, quality of service (QoS and traffic engineering. MPLS is a scalable, protocol-independent protocol. MPLS allows for creating end-to-end circuits across any type of transport medium using any protocol. The primary benefit of MPLS is to eliminate the dependence on a particular OSI model data-link layer technology such as asynchronous transfer mode (ATM, Frame Relay or Ethernet and eliminates the need for multiple layer-2 networks to satisfy different types of traffic. This paper reflects a detailed overview on MPLS with its architectural terminology, working and the services that it offers.

  20. MILITARY MULTI-HOP ROUTING PROTOCOL

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Military tactical network is one of the most important applications of ad hoc network. Currently the existing routing protocols are put forward based on the simple and universal network model which has the ability of multi-hop routing but cannot work efficiently in the special military applications. The narrow bandwidth and limited energy of the wireless network make general routing protocols seem to be more redundant.In order to satisfy military needs properly, this letter makes a detailed analysis of physical nodes and traffic distribution in military network, uses cross-layer design concept for reference, combines traffic characteristic of application layer with routing protocol design. It categorized routing problem as crucial routes and non-crucial routes which adopted separate maintenance methods. It not only realizes basic transmission function but also works efficiently. It is quite fit for military application.