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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

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

    2012-01-01

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

  2. 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)

    Daugaard, G; Skoneczna, I; Aass, N; De Wit, R; De Santis, M; Dumez, H; Marreaud, S; Collette, L; Lluch, J R G; Bokemeyer, C; Schmoll, H J

    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...

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

    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 preliminary, these data demonstrate that in selected patients with TGCTs CT with carboplatin represents a therapeutic option that that seems to not affect sex hormones, spermatogenesis, and sperm nucleus.

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

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

    2016-01-01

    significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence...... PFT. CONCLUSION: After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group.......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...

  5. Bleomycin-induced flagellate dermatitis

    Guilherme Devidé Mota

    2014-07-01

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

  6. Progress of Bep Treatments on Nb at JLAB

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

    2010-05-01

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

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

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

    2016-04-01

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

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

    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.

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

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

    2015-01-01

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

  10. Labeled bleomycin as a tumor localizing agent

    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.)

  11. Vincristine, bleomycin, mitomycin C, cisplatin combination

    During the past five years the EORTC Gynecological Cancer Cooperative Group (G.C.C.G.) performed several studies in patients with disseminated squamous cell carcinoma of the uterine cervix (SCCUC). The first trial protocol (55802) studies the efficacy and toxicity of a bleomycin-mitomycin C based regimen to which vincristine and cisplatin were added (VBMP). The overall response rate in 50 evaluable patients was 40% and median time to progression was 48 weeks and 32 weeks for patients with complete response (16%) and partial response respectively. Of interest was that the complete remission rate in patients with only distant metastases was 30% (for patients with only lung and/or lymph nodes metastases 40%) and some of these patients had long term disease-free survival. The toxicity of the VBMP regimen was acceptable to the patients

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

    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

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

    Coopersmith, Jonathan

    2006-05-01

    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.

  14. Bleomycin lung: a case report

    Rashid, Rabia Sofia

    2009-01-01

    A 69-year-old gentleman with non-Hodgkin’s lymphoma (stage I), with baseline fibrotic lung changes on CT, received six cycles of R-PMitCebo chemotherapy containing bleomycin. Three months later he presented to the Accident and Emergency Department with progressive dyspnoea, dry cough, pyrexia and generalised lethargy. Chest radiographs showed bilateral lower zone opacities. Clinically, all signs initially pointed to community-acquired penumonia, but he failed to respond to standard treatment ...

  15. Bleomycin treatment of brain tumors: an evaluation

    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...... fairly well tolerated at doses much higher than that used in electrochemotherapy....

  16. BEPS redesign of 168 commercial buildings: summary report

    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.

  17. Different iron(II) complexes of bleomycin A2

    By 13C-nmr on iron-bleomycin preparations, an iron-bleomycin-CO complex is found that loses its CO upon standing, as demonstrated using 14CO. Iron-bleomycin, prepared without rigorous exclusion of oxygen, reacts with CO to a stable diamagnetic iron-bleomycin-CO complex

  18. Scintigraphy of ORL tumours with cobalt bleomycin

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

  19. Assessment of BEP of MIMO-OFDMA systems

    Manohar Naik Ramavath#1 B.A.Sarath Manohar Babu

    2013-09-01

    Full Text Available MIMO antenna systems with OFDMA are used for high data rate systems for 4th generation wireless networks. Multi cell systems developed based on wireless standards such as WiMAX and 3GPP LTE. In this paper we are calculating average BEP (bit error probability of MIMO-OFDMA systems. Multiuser access scenarios are two types those are co-ordination and randomization. For interference mitigation in co-ordinated scenario we arrange ULA (uniform linear array with closely spaced antennas and beamforming process and in randomization we arrange OSTBC (orthogonal space time block coding with antennas sufficiently spaced apart. Numerical results of analytical frame work is used for different applications and wide range system configurations.

  20. 57Co-bleomycin and *I-bleomycin in Ehrlich's carcinoma model of the mouse

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

  1. Tumor-specific radiopharmaceuticals: radiolabeled bleomycin

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

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

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

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

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

  4. Ultraviolet enhancement of DNA base release by bleomycin

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

  5. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance

    Schwartz, Donald R.; Homanics, Gregg E.; Hoyt, Dale G.; Klein, Ed; Abernethy, John; Lazo, John S.

    1999-01-01

    The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent, is deaminated in vitro by Blmh. We used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is the sole enzyme required for BLM deamination. Although some Blmh null mice were viable and reproduced, only about 65% of the expected number survived the neonatal period, reveali...

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

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

    2011-01-01

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

  7. El plan de acción BEPS de la OCDE: pasado, presente y futuro

    Pedrosa López, José Carlos

    2015-01-01

    Este trabajo ofrece una visión general del denominado Plan de Acción BEPS de la OCDE. El estudio se divide en tres grandes bloques. En primer lugar se explica el origen del proyecto haciendo referencia a informes previos de Organizaciones Internacionales e Instituciones Europeas. En segundo lugar, explica su situación actual y los siete informes de las acciones publicados. En tercer lugar, se exponen los próximos pasos del Plan de Acción BEPS antes de que finalice en diciembre 2015. Finalment...

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

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

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

    Abbasi, Fatemeh; Abadi, Akram Ghahghai Nezam

    2009-01-01

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

  10. Consecutive radiation-bleomycin therapy of cancer

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

  11. An effective implementation scheme of just-in-time protocol for optical burst switching networks

    Wu, Guiling; Li, Xinwan; Chen, Jian-Ping; Wang, Hui

    2005-02-01

    Optical burst switching (OBS) has been emerging as a promising technology that can effectively support the next generation IP-oriented transportation networks. JIT signaling protocol for OBS is relatively simple and easy to be implemented by hardware. This paper presented an effective scheme to implement the JIT protocol, which not only can effectively implement reservation and release of optical channels based on JIT, but also can process the failure of channel reservation and release due to loss of burst control packets. The scheme includes: (1) a BHP (burst head packet) path table is designed and built at each OBS node. It is used to guarantee the corresponding burst control packet, i.e. BHP, BEP (burst end packet) and BEP_ACK (BEP acknowledgement), to be transmitted in the same path. (2) The timed retransmission of BEP and the reversed deletion of the item in BHP path tables triggered by the corresponding BEP_ACK are combined to solve the problems caused by the loss of the signaling messages in channel reservation and release process. (3) Burst head packets and BEP_ACK are transmitted using "best-effort" method. Related signaling messages and their formats for the proposed scheme are also given.

  12. Bleomycin Containing Chemotherapeutic Regimen Induced Acquired Partial Lipodystrophy

    Tandon, Vishal R; Gupte, Novy; Mahajan, Vivek; Sharma, Rahul; Langer, Cheena; Khajuria, Vijay; Mahajan, Annil

    2016-01-01

    Bleomycin toxicity predominantly affects the skin and lungs. Cutaneous toxicity classically known to present with bleomycin are flagellate erythema and drug rash. We hereby report an isolated case of (bleomyicn)-induced acquired partial (lipodytrophy) having potential cosmetic implications in a young women prescribed postoperatively following a case of germ cell carcinoma of ovary (endodermal sinus tumor). PMID:26955139

  13. Alteration of bleomycin cytotoxicity by glutathione depletion or elevation

    In part, some of the cytotoxicity of bleomycin may be lessened or enhanced by modulation of glutathione (GSH) concentrations. Enhancement of bleomycin cytotoxicity was observed when GSH levels were low and protection was observed when GSH levels were elevated. Since H2O2 is one of the reactive species produced by bleomycin catalyzed oxygen activation, the authors studied the effects of H2O2 exposure after GSH depletion. H2O2, like bleomycin, shows enhanced cytotoxicity in GSH depleted cells. It has been proposed that bleomycin cytotoxicity requires reducing equivalents from non-protein bound thiols (such as GSH) to activate the bleomycin-metal complex, which in turn reacts with oxygen to generate free radicals and peroxides. The data suggest that either GSH is not required to cycle reducing equivalents to the oxidized bleomycin-metal complex, or the low levels of depleted GSH attained (less than 5% of control) were still sufficient to effect reduction. Further, the data shows that GSH in fact provides a means of protection and detoxification from the cytotoxic effects of bleomycin

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

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

  15. Tumor scanning with 57Co-bleomycin

    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)

  16. The effects of Bleomycin A5 on infantile maxillofacial haemangioma

    Zhao Fu-yun

    2011-07-01

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

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

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

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

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

  19. Scintigraphic studies of malignant tumors using 111In-bleomycin

    A study was made of the potentialities of 111In-bleomycin in the diagnosis of lung cancer, malignant lymphomas, breast, nasopharyngeal and colonic cancer, lung metastases of synovial sarcoma. There were examined patients operated on for lung cancer to detect metastases to mediastinal lymph nodes. A group of patients with benign tumors and chronic inflammatory lung processes was examined for differential diagnosis of malignant and benign tumors. A total of 135 patients were examined using 111In-bleomycin. The results of radioisotope studies were verified by operative, morphological, X-ray and endoscopic findings. A high sensitivity has been shown for 111In-bleomycin in the diagnosis of lung and colonic cancer, malignant lymphomas. No correlation has been shown between the accumulation of 111In-bleomycin and the histologic structure of malignant tumors

  20. Stress Linearization and Strength Evaluation of the BEP's Flow Plates for a Dual Cooled Fuel Assembly

    Kim, Jae Yong; Yoon, Kyung Ho; Kang, Heung Seok; Lee, Young Ho; Lee, Kang Hee; Kim, Hyung Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-10-15

    A fuel assembly is composed of 5 major components, such as a top end piece (TEP), a bottom end piece (BEP), spacer grids (SGs), guide tubes (GTs) and an instrumentation tube (IT) and fuel rods (FRs). There are no ASME criteria about all components except for a TEP/BEP. The TEP/BEP should satisfy stress intensity limits in case of condition A and B of ASME, Section III, Division 1 . Subsection NB. In a dual cooled fuel assembly, the array and position of fuels are changed from those of a conventional PWR fuel assembly to achieve a power uprating. The flow plates of top/bottom end pieces (TEP/BEP) have to be modified into proper shape to provide flow holes to direct the heated coolant into/out of the fuel assembly but structural intensity of these plates within a 22.241 kN axial loading should satisfy Tresca stress limits in ASME code. In this paper, stress linearization procedure and strength evaluation of a newly designed BEP for the dual cooled fuel assembly are described.

  1. Pulmonary toxicity after radiation and bleomycin: a review

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

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

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

  3. Proteome analysis for effects of radiation on BEP2D cell

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

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

    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

  5. Bleomycin: revival of an old drug.

    Mir, L M; Tounekti, O; Orlowski, S

    1996-07-01

    1. Bleomycin (BLM) is a cytotoxic drug currently used in anticancer chemotherapy. We present here a summary of the well established "old" knowledge concerning BLM structure, properties and activity at the molecular level, as well as its current clinical uses. 2. Then, we introduce "new" recent facts concerning BLM interaction with animal cells, that demonstrate the peculiar characteristics of that drug and its potentialities. Indeed, BLM has an high intrinsic cytotoxicity (i.e. it is a very potent drug once inside the cell). However, BLM cytotoxicity is limited because BLM is unable to diffuse through the plasma membrane. The very low amounts of BLM that can reach the cell interior enter the cells by a mechanism that requires BLM interaction with a plasma membrane protein. 3. Finally, we present and discuss a new possible use of BLM in an antitumor approach that we term electrochemotherapy. This new treatment, still under development, is based on the increased BLM delivery into tumor cells after cell permeabilization by electric pulses administered locally at the solid tumor site. This results in a huge local potentiation of BLM activity, in the absence of systemic adverse effects. Clinical trials are in progress. PMID:8842674

  6. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance.

    Schwartz, D R; Homanics, G E; Hoyt, D G; Klein, E; Abernethy, J; Lazo, J S

    1999-04-13

    The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent, is deaminated in vitro by Blmh. We used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is the sole enzyme required for BLM deamination. Although some Blmh null mice were viable and reproduced, only about 65% of the expected number survived the neonatal period, revealing an important role for Blmh in neonatal survival. Mice lacking Blmh exhibited variably penetrant tail dermatitis that resembled rodent ringtail. The histopathology of the tail dermatitis was similar to skin lesions in humans with pellagra, necrolytic migratory erythema, and acrodermatitis enteropathica. Compared with controls, Blmh null mice were more sensitive to acute BLM lethality and developed pulmonary fibrosis more readily following BLM treatment. Thus, we have established that Blmh is an essential protectant against BLM-induced death and has an important role in neonatal survival and in maintaining epidermal integrity. PMID:10200322

  7. Bleomycin and radiation-induced lung damage in mice

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

  8. Bleomycin sclerotherapy for severe symptomatic and persistent pelvic lymphocele.

    Fernandes, Ana Sofia; Costa, Antónia; Mota, Raquel; Paiva, Vera

    2014-01-01

    Background. Pelvic lymphoceles are frequently described as a complication of pelvic lymphadenectomy performed for surgical staging of gynaecologic malignancies. Case Report. A 72-year-old woman presented with severe symptomatic and refractory lymphocele associated with persistent lower limb lymphedema and recurrent erysipelas. After four CT fluoroscopy scan guided percutaneous catheter drainages, the lymphocele complicated with infection finally resolved with two sessions of bleomycin sclerotherapy. Conclusion. Symptomatic persistent lymphoceles require treatment and nowadays the first option is interventional radiologic procedures. Bleomycin is a safe and effective sclerosing agent and therefore should be regarded as a first-line treatment choice. PMID:25105040

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

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

  10. Bleomycin effect on L5178Y cells

    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

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

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

  12. Acute respiratory failure induced by bleomycin and hyperoxia

    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

  13. The production and imaging of 55Co labelled bleomycin

    The production of 55Co was embarked for the labelling of bleomycin. This radiopharmaceutical in combination with a high resolution, high sensitive positron camera is a valuable tool in the detection and staging of lung cancer. The production method and the positron camera are described

  14. Elimination of multicopy plasmid R6K by bleomycin.

    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.

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

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

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

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

    2013-01-01

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

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

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

    2009-11-01

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

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

    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...

  19. Preventive effect of erythromycin on experimental bleomycin-induced acute lung injury in rats

    Azuma, A; Furuta, T.; Enomoto, T.; Hashimoto, Y.; Uematsu, K.; Nukariya, N.; Murata, A.; Kudoh, S.

    1998-01-01

    BACKGROUND—Erythromycin has been reported to have an inhibitory effect on chronic inflammatory airway disease and chronic infiltration of neutrophils into the airway. Bleomycin (BLM) often induces interstitial lung fibrosis following acute lung injury. A study was undertaken to investigate the effects of erythromycin (EM) on experimental bleomycin-induced acute lung injury in rats.
METHODS—Bleomycin-induced lung injury was assessed by light microscopic examination, measurement ...

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

    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 ...

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

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

    2014-08-01

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

  2. 89Strontium-induced bone marrow depression suppresses the early inflammatory response and fibrosis caused by intratracheal bleomycin

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

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

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

  4. Re-186-bleomycine: Radiopharmaceutic for diagnosis and therapy

    Bleomycine is an antibiotic used for chemotherapy of several neoplasms. Earlier studies with labelling of bleomycine (BLM) with different radionuclide were done. It was tested for different kind of tumours imaging. Due to previous encouraging imaging results with BLM-Tc-99m , BLM-Co-57 and BLM-In-111 authors decided to check the possibility and methods of labelling BLM with Re-186 to obtain radiopharmaceuticals potentially suitable for diagnosis and treatment of some neoplastic tumours. Different methods of labelling were investigated. The best one are electrolytic and with use of cationic-Sn complex modified by using of gentisic acid and incubation of the reaction mixture at 100 deg. C for 10 min. (author)

  5. Bleomycin Sclerotherapy for Severe Symptomatic and Persistent Pelvic Lymphocele

    Ana Sofia Fernandes; Antónia Costa; Raquel Mota; Vera Paiva

    2014-01-01

    Background. Pelvic lymphoceles are frequently described as a complication of pelvic lymphadenectomy performed for surgical staging of gynaecologic malignancies. Case Report. A 72-year-old woman presented with severe symptomatic and refractory lymphocele associated with persistent lower limb lymphedema and recurrent erysipelas. After four CT fluoroscopy scan guided percutaneous catheter drainages, the lymphocele complicated with infection finally resolved with two sessions of bleomycin sclerot...

  6. Production of [103Pd]Bleomycin complex for targeted therapy

    Due to the anticancer properties of bleomycin (BLM) complexes, production of [103Pd]bleomycin ([103Pd]BLM) was targeted. Palladium-103 (T1/2 16.96 d) was produced via the 103Rh(p,n)103Pd nuclear reaction using a natural rhodium target. Proton energy was 18 MeV with 200 μA irradiation for 15 h (final activity 25.9 GBq of 103Pd2+, RCP > 95%, radionuclidic purity > 99%). 103Pd was separated from the irradiated target by anion exchange using a Dowex 1z8 (Cl-)/100-200 mesh resin in the form of Pd(NH3)2Cl2 in order to react with bleomycin to yield [103Pd]BLM. Chemical purity of the final product was in accordance to the accepted limits. [103Pd]BLM was prepared with a radiochemical yield of more than 98% at 80oC in 30 min. The labeling reaction was optimized for time, temperature and ligand concentration. Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 370 MBq/mmol. The stability of the tracer was checked in the final product and presence of human serum at up to 3 h. The complex was stable in human serum at 37 oC up to 2 h of incubation. Biodistribution studies using a SPECT system performed in normal rats in the first 2-3 h. (author)

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

    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)

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

    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

  9. Cationic lipid:DNA complexes allow bleomycin uptake by melanoma cells.

    Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Glikin, Gerardo C; Finocchiaro, Liliana M E

    2013-05-01

    Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli β-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8°C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy. PMID:23453489

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

    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.

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

    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

  12. Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours.

    Simpson, A. B.; Paul, J.; Graham, J; Kaye, S.B.

    1998-01-01

    We conducted a retrospective review of fatal bleomycin pulmonary toxicity in patients treated for germ cell tumours during 1991-95 at the Beatson Oncology Centre, Glasgow. Case notes of patients treated with bleomycin were reviewed with respect to cumulative bleomycin dose, renal impairment, exposure to supplemental oxygen, thoracic radiotherapy and age. A total of 194 patients underwent chemotherapy, of whom 180 received bleomycin-containing regimens. Five fatal cases of pulmonary toxicity w...

  13. Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy

    Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication. (orig.)

  14. Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy

    Jain, Tarun P.; Thulkar, Sanjay; Saha, Sanchita [All India Institute of Medical Sciences, Department of Radiology, New Delhi (India); Bakhshi, Sameer; Dominic, Joseph [All India Institute of Medical Sciences, Department of Medical Oncology, New Delhi (India)

    2005-12-01

    Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication. (orig.)

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

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

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

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

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

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

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

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

  19. Intralesional bleomycin for the treatment of periocular capillary hemangiomas

    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.

  20. Cytogenetic analysis of malignant transformants of human bronchial epithelial cells BEP2D generated by α-particles exposure

    Objective: To analyze the cytogenetic changes in malignant transformants of human bronchial epithelial cell line (BEP2D) generated by α-particles exposure. Methods: Tumor cell lines were derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of 1.5 Gy α-particles-irradiated BEP2D cells. G-banding patterns of chromosomes was used to analyze the karyotypes. Results: Five individual malignant transformed cell lines were analyzed. Deletions of one copy of chr13 and chrY, and an unidentified fragment attached to the long arms of chr2 and chr12 respectively (chr2q+, chr12q+) were observed in all the malignant transformed cell lines. The proportion of polyploid of BERP35T-2 and BERP35T-4 cells was about 40% and was higher than that of PEB2D cells (5%). Conclusions: The process of cellular malignant transformation induced by α-particles exposure could involve some characteristic cytogenetic changes

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

    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.

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

    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

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

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

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

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

    2016-03-01

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

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

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

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

    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)

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

    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)

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

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

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

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

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

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

    2014-01-01

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

  11. The sup 9 Be(p, gamma) sup 1 sup 0 B cross section at low energies

    Barker, F C

    2002-01-01

    Data for the sup 9 Be(p, gamma) sup 1 sup 0 B reaction with proton energies up to 1800 keV are fitted using R-matrix formulae that include channel contributions where appropriate. The data include values of the astrophysical S factor, the branching ratios for gamma-transitions to the four lowest states of sup 1 sup 0 B, angular distributions and analysing powers. Use is made of experimental values of asymptotic normalization constants obtained from sup 9 Be( sup 1 sup 0 B, sup 9 Be) sup 1 sup 0 B. A good fit is obtained with two 1 sup - levels, two 2 sup - levels, one 0 sup + level and one 2 sup + level.

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

    Manning, Robert M.

    2015-01-01

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

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

    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. Hemagiomas and vascular malformation on face and neck - with intralesional bleomycin injection

    Tatulescu, D; Secheli, I; Secheli, M

    2006-01-01

    Bleomycin, an antineoplasic polipeptidic antibiotic, has been recently used in treatment of vascular anomalies, as a sclerosing agent if it is injected intralesional. We report a study of 4 patients with ages between 3 weeks and 12 years, admitted in "Maria Sklodowska Curie" Children Hospital Bucharest in Surgery Department, and treated with Bleomycin intralesional injections, for vascular anomalies inoperable because of the large surfaces involved or volume of the lesions and special locati...

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

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

    1999-01-01

    Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid ...

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

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

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

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

    2012-08-15

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

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

    Lawson, William E.; Polosukhin, Vasiliy V.; Georgios T. Stathopoulos; 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.

    2005-01-01

    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...

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

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

    2002-01-01

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

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

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

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

    Dhar S

    2009-01-01

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

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

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

    2013-05-01

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

  3. Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice.

    Zhou, Yong; Sun, Guo-Ying; Liu, Tian; Duan, Jia-Xi; Zhou, Hui-Fang; Lee, Kin Sing; Hammock, Bruce D; Fang, Xiang; Jiang, Jian-Xin; Guan, Cha-Xiang

    2016-02-01

    Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-β1-induced α-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model. PMID:26310139

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

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

    2013-07-15

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

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

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

    2013-01-01

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

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

    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 forced oscillations at detecting inflammation and fibrosis.

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

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

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

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

  9. Bleomycin as carrier substance for sup(99m)technetium in tumour diagnosis

    sup(99m)Tc-Bleomycin is a promising tool for scintigraphic imaging of some types of malignant tumours. The rapid decay of sup(99m)Tc, together with a high affinity of bleomycin for certain histologically-defined tumours recommends its use in humans. Moreover, by using high specific activities of bleomycin, no toxic effects are to be expected. At 00C, the chelate of sup(99m)Tc and bleomycin is stable and its storage or transport are recommended at this temperature. Following the i.v. injection of rats with sup(99m)Tc-bleomycin, a high specific activity is found in the liver, spleen, lungs and skin. In view of its excretion by the kidneys an extremely high activity is found in the urogenial system. Scintigraphic imaging of lymph nodes in a case of Hodgkin's disease, of an embryonal carcinoma, of a thyroid carcinoma, of an astrocytoma and of a solid carcinoma was obtained in patients investigated by this method. (author)

  10. 111In-bleomycin breast and axilla imaging

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

  11. Biological basis of combination therapy with radiation and bleomycin

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C2W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C2W cells were irradiated, incubated at 370C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

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

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

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

    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.

  14. Study of Low Temperature Baking Effect on Field Emission on Nb Samples Treated by BEP, EP, and BCP

    Field emission is still one of the major obstacles facing Nb superconducting radio frequency (SRF) community for allowing Nb SRF cavities to reach routinely accelerating gradient of 35 MV/m that is required for the international linear collider. Nowadays, the well know low temperature baking at 120 C for 48 hours is a common procedure used in the SRF community to improve the high field Q slope. However, some cavity production data have showed that the low temperature baking may induce field emission for cavities treated by EP. On the other hand, an earlier study of field emission on Nb flat samples treated by BCP showed an opposite conclusion. In this presentation, the preliminary measurements of Nb flat samples treated by BEP, EP, and BCP via our unique home-made scanning field emission microscope before and after the low temperature baking are reported. Some correlations between surface smoothness and the number of the observed field emitters were found. The observed experimental results can be understood, at least partially, by a simple model that involves the change of the thickness of the pent-oxide layer on Nb surfaces.

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

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

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

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

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

    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.

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

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

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

    Crimi Nunzio

    2006-11-01

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

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

    Saify B

    2004-01-01

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

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

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

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

    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.

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

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

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

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

    2012-01-01

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

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

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

    2006-01-01

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

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

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

    2010-01-01

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

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

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

    2012-06-01

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

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

    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

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

    Bartholomei-Santos Marlise Ladvocat

    1997-01-01

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

  10. The role of bleomycin combination in radiation therapy for squamous cell carcinoma in the oral cavity

    In an effort to improve tumor control by radiation therapy, a treatment regimen consisting of concurrent combination of bleomycin (90 mg/3 weeks) and radiation (30 Gy/3 weeks) was applied. Between 1972 and 1981, 287 patients with squamous cell carcinoma in the oral cavity were subjected to this bleomycin-radiation combination regimen. All except 4 patients experienced marked response after treatment using the bleomycin-radiation combination alone. One hundred thirty-four patients (47 %) obtained CR and 149 (53 %) PR. Higher CR rates were obtained in patients with carcinoma of the lower gum (62 %), of the upper gum (68 %), and of the cheek mucosa (43 %), compared to patients with carcinoma of the floor of the mouth (21 %), and of the tongue (15 %). In each of the tumor sites, small lesions (T1, T2) obtained higher CR rates, compared with large lesions (T3, T4). Of the 134 patients who experienced CR, 83 were observed without any further treatment after bleomycin-radiation combination alone. Local recurrence-free rates of these patients were 72 % for T1, T2 lesions and 48 % for T3, T4 lesions. Local control rates were increased to 85 % and 78 %, respectively, with successful salvage treatment involving surgery or interstitial radiotherapy for post-irradiation failures. (author)

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

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

  12. Macrophage metalloelastase (MMP-12 deficiency does not alter bleomycin-induced pulmonary fibrosis in mice

    Boichot Elisabeth

    2006-02-01

    Full Text Available Abstract Background Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix in the interstitium resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs and their inhibitors (TIMPs in the fibrogenic process remains misunderstood. In particular, macrophage metalloelastase, also identified as MMP-12, is known to be involved in remodeling processes under pathological conditions. However, MMP-12 involvement in pulmonary fibrosis is unknown. Here we investigated fibrotic response to bleomycin in MMP-12 deficient mice. Materials and methods C57BL/6 mice, Balb/c mice and MMP-12 -/- mice with a C57BL/6 background received 0.3 mg bleomycin by intranasal administration. 14 days after, mice were anesthetized and underwent either bronchoalveolear lavage (BAL or lung removal. Collagen deposition in lung tissue was determined by Sircol™ collagen assay, MMP activity in BAL fluid was analyzed by zymography, and other mediators were quantified in BAL fluid by ELISA. Real time PCR was performed to assess gene expression in lung removed one or 14 days after bleomycin administration. Student t test or Mann & Whitney tests were used when appropriate for statistical analysis. Results The development of pulmonary fibrosis in "fibrosis prone" (C57BL/6 mice was associated with prominent MMP-12 expression in lung, whereas MMP-12 expression was weak in lung tissue of "fibrosis resistant" (Balb/c mice. MMP-12 mRNA was not detected in MMP-12 -/- mice, in conformity with their genotype. Bleomycin elicited macrophage accumulation in BAL of MMP-12 -/- and wild type (WT mice, and MMP-12 deficiency had no significant effect on BAL cells composition. Collagen content of lung was increased similarly in MMP-12 -/- and WT mice 14 days after bleomycin administration. Bleomycin elicit a raise of TGF-β protein, MMP-2 and TIMP-1 protein and mRNA in BAL fluids and lung respectively, and no significant difference was observed between MMP-12 -/- and WT mice considering those parameters. Conclusion The present study shows that MMP-12 deficiency has no significant effect on bleomycin-induced fibrosis.

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

    Yonggang WEI

    2009-03-01

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

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

    Sergei P. Atamas

    2013-06-01

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

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

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

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

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

  17. The Antioxidative Effect of Chamomile, Anthocyanoside and their Combination on Bleomycin-induced Pulmonary Fibrosis in Rat

    Javadi, Iraj; Emami, SeyedAlireza

    2015-01-01

    Introduction: Bleomycin is a small peptide with 1500Daltun of molecular weight which has two junction areas in two molecule’s opposite sides, one of them to relate to the DNA and the other to relate to the iron. Iron is a crucially important factor in free radical production and cytotoxic activity of bleomycin. Material and methods: The study attempts to study, and compare, the effect of using Chamomile, Anthocyanoside and their combination, as anti-inflammatory agent to ameliorates, to preve...

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

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille; Eriksen, Jens; Gehl, Julie

    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...... 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...

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

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

    2006-01-01

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

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

    [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.

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

    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

  2. Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin

    Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to gamma-rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohemagglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to gamma-rays or bleomycin in G0, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after gamma-ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (gamma-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age

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

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

    1983-01-01

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

  4. Folk medicine Terminalia catappa and its major tannin component, punicalagin, are effective against bleomycin-induced genotoxicity in Chinese hamster ovary cells.

    Chen, P S; Li, J H; Liu, T Y; Lin, T C

    2000-05-01

    Terminalia catappa L. is a popular folk medicine for preventing hepatoma and treating hepatitis in Taiwan. In this paper, we examined the protective effects of T. catappa leaf water extract (TCE) and its major tannin component, punicalagin, on bleomycin-induced genotoxicity in cultured Chinese hamster ovary cells. Pre-treatment with TCE or punicalagin prevented bleomycin-induced hgprt gene mutations and DNA strand breaks. TCE and punicalagin suppressed the generation of bleomycin-induced intracellular free radicals, identified as superoxides and hydrogen peroxides. The effectiveness of TCE and punicalagin against bleomycin-induced genotoxicity could be, at least in part, due to their antioxidative potentials. PMID:10773401

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

    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

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

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

    1983-01-01

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

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

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

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

    NIKOS KATSAROS

    2003-05-01

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

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

    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......In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or...... radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S-ACE was...

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

    Han,Khin Ei; Okada,Shigeru

    1995-01-01

    "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 ...

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

    Prasoon Soni

    2011-01-01

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

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

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

    1983-10-01

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

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

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

  14. Colloidal Gold-Mediated Delivery of Bleomycin for Improved Outcome in Chemotherapy

    Celina Yang; Jamie Uertz; Devika B. Chithrani

    2016-01-01

    Nanoparticles (NPs) can be used to overcome the side effects of poor distribution of anticancer drugs. Among other NPs, colloidal gold nanoparticles (GNPs) offer the possibility of transporting major quantities of drugs due to their large surface-to-volume ratio. This is while confining these anticancer drugs as closely as possible to their biological targets through passive and active targeting, thus ensuring limited harmful systemic distribution. In this study, we chose to use bleomycin (BL...

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

    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. PMID:7505240

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

    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

  17. Combination therapy for advanced oral squamous cell carcinoma with radiation and bleomycin, 1

    Twenty-five patients of advanced oral cancers (squamous cell carcinoma) were treated with combination of radiation and bleomycin in the first course of treatment, and then treated with either Ra needle or 198Au grain implantation, 2 to 3 weeks after the first course of treatment for severe mucositis. The treatments were performed during 1975 to 1977. In the combination therapy, external irradiation (daily 250 rad) of Telecobalt γ-ray or Betatron electron beam was given by 4 fractionations per week during 2.5 to 3 weeks (2,500 to 3,000 rad). Bleomycin (5 mg) was injected intramuscularly about 30 min before the irradiation, giving a total of 50 to 60 mg during therapy. In the second course of therapy, Ra needle or 198Au grain implants were employed in 14 cases and further external irradiation was given for the remaining cases except one which had two primary origins of cancer in the tongue and liver. As a result of the combination therapy, 12 primary tumors out of 25 cases markedly regressed (more than 50% regression) and by subsequent radiotherapy, 11 primary tumors out of 24 were completely controlled during more than 14 months of follow-up observation. The tongue cancer in one exceptional case was controlled by the combination of radiation (3,000 rad) and bleomycin (60 mg) alone. Fifteen of 25 patients are still alive, while 10 patients died of cancer. This therapy of combined irradiation and bleomycin seems to be effective on advanced oral cancers because the local tumor control rate increased markedly. (author)

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

    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.

  19. Potentiation of Bleomycin Lethality in HeLa and V79 Cells by Bee Venom

    Oršolić, Nada

    2009-01-01

    This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that s...

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

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

    2013-01-01

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

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

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

    2011-01-01

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

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

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

    2010-01-01

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

  3. Telomerase activity is required for bleomycin-induced pulmonary fibrosis in mice

    Liu, Tianju; Chung, Myoung Ja; Ullenbruch, Matthew; Yu, Hongfeng; Jin, Hong; Hu, Biao; Choi, Yoon Young; Ishikawa, Fuyuki; Phan, Sem H

    2007-01-01

    In addition to its well-known expression in the germline and in cells of certain cancers, telomerase activity is induced in lung fibrosis, although its role in this process is unknown. To identify the pathogenetic importance of telomerase in lung fibrosis, we examined the effects of telomerase reverse transcriptase (TERT) deficiency in a murine model of pulmonary injury. TERT-deficient mice showed significantly reduced lung fibrosis following bleomycin (BLM) insult. This was accompanied by a ...

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

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

    2007-01-01

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

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

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

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

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

  7. A young male with shortness of breath

    Khan Fahmi; Al Ani Ahmed; Allaithy Mustafa; Al-Bozom Issam

    2008-01-01

    We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum); ...

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

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

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

    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.

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

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

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

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

  12. Monitoring of 57Co-bleomycin delivery to brain metastases and their tumors of origin

    The concentration of cobalt-57 (57Co)-labeled bleomycin delivered to three brain metastases and to their tumors of origin in the lungs was measured using a single-photon emission computerized tomography technique. In two brain metastases the 57Co-bleomycin concentration measured at different times after the intravenous injection was significantly lower than that in the originating lung tumors (p less than 0.01 and p less than 0.001). In these two patients, the tumor cumulative concentration (TCC) of drug in the brain neoplasm compared to the lung carcinoma was 12.92 versus 15.12 and 10.30 versus 19.74 micrograms/cc/min. In the third patient there was no significant difference in drug concentration between the tumor in the brain and in the lung (TCC 16.02 vs. 15.09 micrograms/cc/min). There was a significant difference in the drug TCC between the three brain metastases: the difference between the lowest and highest concentrations was more than 50% (10.3 vs. 16.02 micrograms/cc/min). When the concentration in the tumor over time (CT(t)) of the 57Co-bleomycin was compared in the brain and lung tumors, a good correlation was found in each of the three cases (r = 0.93, 0.99, and 0.97). This suggests that the difference in drug uptake between brain metastases and their originating lung tumor is a quantitative rather than a qualitative phenomenon. The results show that the amount of drug to which brain metastases are exposed varies and may be very low in some tumors; therefore, effectiveness of drug delivery may play a role in the nonresponsiveness of brain metastases to treatment

  13. Sensitivity to genotoxic effects of bleomycin of blood lymphocytes of people residing in villages of ChNPP exclusion zone

    On purpose of comparative determination of cell repair system activity of people residing without permission in the villages of ChNPP exclusion zone and of Yahotyn district, Kiev region (control group) the chromosome sensitivity of peripheral blood lymphocytes to genotoxic effect of bleomycin in vitro was studied. Chromatid break frequency per cell was a criterium for the estimation. It was found a significantly higher sensitivity to bleomycin in ChNPP exclusion zone self-settlers' group due to cell reaction of people younger than 60. For the elderly people there was revealed no significant difference

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

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

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

    Marlise Ladvocat Bartholomei-Santos; Edmundo José de Lucca

    1997-01-01

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

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

    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.

  17. 57Co-bleomycin scintigraphy for the preoperative detection and staging of lung tumors

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

  18. Changes of global terrestrial carbon budget and major drivers in recent 30 years simulated using the remote sensing driven BEPS model

    Ju, W.; Chen, J.; Liu, R.; Liu, Y.

    2013-12-01

    The process-based Boreal Ecosystem Productivity Simulator (BEPS) model was employed in conjunction with spatially distributed leaf area index (LAI), land cover, soil, and climate data to simulate the carbon budget of global terrestrial ecosystems during the period from 1981 to 2008. The BEPS model was first calibrated and validated using gross primary productivity (GPP), net primary productivity (NPP), and net ecosystem productivity (NEP) measured in different ecosystems across the word. Then, four global simulations were conducted at daily time steps and a spatial resolution of 8 km to quantify the global terrestrial carbon budget and to identify the relative contributions of changes in climate, atmospheric CO2 concentration, and LAI to the global terrestrial carbon sink. The long term LAI data used to drive the model was generated through fusing Moderate Resolution Imaging Spectroradiometer (MODIS) and historical Advanced Very High Resolution Radiometer (AVHRR) data pixel by pixel. The meteorological fields were interpolated from the 0.5° global daily meteorological dataset produced by the land surface hydrological research group at Princeton University. The results show that the BEPS model was able to simulate carbon fluxes in different ecosystems. Simulated GPP, NPP, and NEP values and their temporal trends exhibited distinguishable spatial patterns. During the period from 1981 to 2008, global terrestrial ecosystems acted as a carbon sink. The averaged global totals of GPP NPP, and NEP were 122.70 Pg C yr-1, 56.89 Pg C yr-1, and 2.76 Pg C yr-1, respectively. The global totals of GPP and NPP increased greatly, at rates of 0.43 Pg C yr-2 (R2=0.728) and 0.26 Pg C yr-2 (R2=0.709), respectively. Global total NEP did not show an apparent increasing trend (R2= 0.036), averaged 2.26 Pg C yr-1, 3.21 Pg C yr-1, and 2.72 Pg C yr-1 for the periods from 1981 to 1989, from 1990 to 1999, and from 2000 to 2008, respectively. The magnitude and temporal trend of global terrestrial carbon budget were similar to the values recently reported by the Global Carbon Project. The obvious increases in global GPP and NPP were mainly driven by the enhancement of atmospheric CO2 fertilization. The change of LAI played the secondary role. Climate had a small negative impact on global terrestrial carbon sequestration. The relative importance of changes in climate, atmospheric CO2 concentration, and LAI in altering the temporal trend of carbon sequestration differed spatially. During the period from 2000 to 2008, terrestrial carbon sinks mainly existed in the northern region of South America, the western region of middle Africa, Southeast Asia, Southeast China, Southeast United States, and some regions of Eurasia.

  19. Cryptographic Protocols:

    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...... in Chapter 2. Comparisons play a key role in many systems such as online auctions and benchmarks — it is not unreasonable to say that when parties come together for a multiparty computation, it is because they want to make decisions that depend on private information. Decisions depend on comparisons....... We have implemented the comparison protocol in Java and benchmarks show that is it highly competitive and practical. The biggest contribution of this dissertation is a general framework for secure multiparty computation. Instead of making new ad hoc implementations for each protocol, we want a single...

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

    Evans, T.W.; McAnulty, R.J.; Rogers, D.F.; Chung, K.F.; Barnes, P.J.; Laurent, G.J. (Brompton Hospital, London (England))

    1990-04-01

    Bleomycin is a highly effective antitumor agent, but pulmonary toxicity, characterized by an acute inflammatory reaction and associated pulmonary edema, limits clinical use of the drug. Platelets and platelet-activating factor (PAF), a membrane-derived phospholipid, have been implicated in the mechanisms that can mediate pulmonary microvascular injury. The authors sought to investigate the role of PAF in bleomycin-induce lung injury in the rat, using the PAF receptor antagonist BN 52021; and the role of platelets though the use of an anti-platelet antibody. Lung injury was induced by intratracheal bleomycin (1.5 mg) and assessed by measurements of lung wet weight and total pulmonary extravascular albumin space (TPEAS). Bleomycin caused a significant increase in both indices after 48 hr, compared with control animals. A single dose of BN 52021 significantly reduced the bleomycin-induced increase in lung weight, but not the rise in TPEAS. Increasing the dose of BN 52021 had no additional effect. Reducing circulating platelet numbers by approximately 75% had no effect on either the increase in lung weight or TPEAS, observed 48 hr after bleomycin. PAF may partially contribute to the acute inflammatory reaction seen after intratracheal bleomycin in rats.

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

    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.

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

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

    2013-01-01

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

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

    Spugnini, Enrico P; Dotsinsky, Ivan; Mudrov, Nikolay; Citro, Gennaro; D'Avino, Alfredo; Baldi, Alfonso

    2008-01-01

    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 mus 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. PMID:18980687

  4. Symptomatic Abdominal Simple Cysts: Is Percutaneous Sclerotherapy with Hypertonic Saline and Bleomycin a Treatment Option?

    Souftas, V. D.; Kosmidou, M.; Karanikas, M.; Souftas, D.; Menexes, G.; Prassopoulos, P.

    2015-01-01

    Aim. To evaluate the feasibility of percutaneous sclerotherapy of symptomatic simple abdominal cysts, using hypertonic saline and bleomycin, as an alternative to surgery. Materials and Methods. This study involved fourteen consecutive patients (ten women, four men, mean age: 59.2 y) with nineteen symptomatic simple cysts (liver n = 14, kidney n = 3, and adrenal n = 2) treated percutaneously using a modified method. Initially CT-guided drainage was performed; the next day the integrity of the cyst/exclusion of extravasation or communications was evaluated under fluoroscopy, followed by two injections/reabsorptions of the same quantity of hypertonic NaCl 15% solution and three-time repetition of the same procedure with the addition of bleomycin. The catheter was then removed; the patients were hospitalized for 12 hours and underwent follow-ups on 1st, 3rd, 6th, and 12th months. Cyst's volumes and the reduction rate (%) were calculated in each evaluation. Results. No pain or complications were noted. A significant cyst's volume reduction was documented over time (P < 0.001). On the 12th month 17 cysts disappeared and two displayed a 98.7% and 68.9% reduction, respectively. Conclusion. This percutaneous approach constitutes a very promising nonsurgical alternative for patients with symptomatic simple cyst, without complications under proper precautions, leading to eliminating the majority of cysts. PMID:25878660

  5. Povidone-iodine and bleomycin in the management of malignant pleural effusion.

    Alavi, Ali Asghar; Eshraghi, Mohsen; Rahim, Mohammad Bagher; Meysami, Ali Pasha; Morteza, Afsaneh; Hajian, Hanieh

    2011-01-01

    Malignant pleural effusion is a common complication in certain malignancies. Pleurodesis is the best option most of the time. The purpose of this study was to compare the choice of belomycin with povidone-iodine, which is not only determined by the efficacy of the agent but also by its cost, accessibility, safety, ease of administration and the number of administrations to achieve a complete response. We performed a randomized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion. Patients were selected and randomly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine. Primary characteristics of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. A complete response was obtained in 79% of belomycin group and 75% of povidone-iodine group which was not statistically significant. Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up. This was significant after controlling for age, pain score and dyspnea score after drainage, using general linear model. Due to similar effect and significant cost advantage between bleomycin and povidone-iodine, we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions. PMID:22052141

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

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

    2016-02-01

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

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

    Rajshekar

    2015-08-01

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

  8. Contribution to the scintigraphic diagnosis of malignant endothoracic tumors by 57Co labeled bleomycin

    The results of the exploration by 57Co bleomycin scintigraphy in 97 thoracic tumors are reported. The Bleo-57Co scintigraphy detects primary and secondary malignant tumors underevaluated by classical tests. In the thorax, the radioactive focus are easily detected on account of the light physiological uptake of the Bleo-57Co. It is particularly interesting in the mediastinal tumors where the picture is not covered by cardiovascular interference. Mediastinal, pleural and costal tumors have been explored. Pulmonary tumors give the best results, they fixe in 93% of the case. All the mediastinal tumors have capted the bleomycin but the uptake was very light even when the tumor was a large one. The exploration of pleural and costal tumors was less interesting. In conclusion, the Bleo-57Co scintigraphy, gives indications about the volume of the tumor and its spread in the organism. By this method, malignancy in a tumor can be diagnosed. It can be used to survey cancer patients which have been treated. Nevertheless the long half-life (270 days) and the lack of specificity of the Bleo-57Co for the malignant tumors, justify discussion about indications and the results of such an exploration

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

    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

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

    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

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

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

    1999-01-01

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

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

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

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

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

  14. The Antioxidative Effect of Chamomile, Anthocyanoside and their Combination on Bleomycin-induced Pulmonary Fibrosis in Rat

    Javadi, Iraj; Emami, SeyedAlireza

    2015-01-01

    Introduction: Bleomycin is a small peptide with 1500Daltun of molecular weight which has two junction areas in two molecule’s opposite sides, one of them to relate to the DNA and the other to relate to the iron. Iron is a crucially important factor in free radical production and cytotoxic activity of bleomycin. Material and methods: The study attempts to study, and compare, the effect of using Chamomile, Anthocyanoside and their combination, as anti-inflammatory agent to ameliorates, to prevent or control the development of fibrosis due to Bleomycin (BLM). to prepare pulmonary fibrosis model, male Wistar rats weighting 180-220g were assigned to specific groups Rats of each group received intratracheally 1U/100 g of BLM. 20 rats were divided to five comparable groups, as(1) BLM group, (2) saline group, (3) Chamomile group, (4) Anthocyanoside group, (5) combination of Anthocyanoside and Chamomile group. Antioxidative combinations were given as pretreatment and treatment after the rats received Bleomycine. Results: After 3 week, Malondialdehyde (MDA)was measured for each rat’s lung. After three weeks, MDA was reduced, compared to BLM group, to 44.27%, 37.80% and 46.07% in Anthocyanoside, Chamomiland combination group, respectively. It was concluded from the present study that administration of combination of Chamomile and Anthocyanoside lead to a significant reduction in Bleomycin-induced MDA. Conclusion: The mechanism of the effect of these combinations is possibly the result of phenolic combinations as antioxidant and oxy free radical scavenger and inhibitor of lipid peroxidation. PMID:26543307

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

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

    2013-12-01

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

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

    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)

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

    Annisa Rahmi

    2015-06-01

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

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

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

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

    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 following lung injury. However, these changes do not prevent the development of lung fibrosis. Overall, these data suggest that the absence of Slpi does not markedly modify the development of lung fibrosis following bleomycin-induced lung injury. PMID:26974397

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

    Inagaki Hirofumi

    2006-01-01

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

  1. Histology protocols

    CarloAlberto Redi

    2010-01-01

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

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

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

    2010-07-01

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

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

    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

  4. Chemical composition of the Lippia origanoides essential oils and their antigenotoxicity against bleomycin-induced DNA damage.

    Vicuña, Gloria Carolina; Stashenko, Elena E; Fuentes, Jorge Luis

    2010-07-01

    The present work evaluated the chemical composition of the essential oils (EO) obtained from Lippia origanoides and their DNA protective effect against bleomycin-induced genotoxicity. L. origanoides EO chemical composition was determined by gas chromatography-mass spectrometry (GC-MS). The major compounds of the L. origanoides EOs were thymol (34-58%) and carvacrol (26%). The antigenotoxic effects of the EOs, major compounds and standard compound (epigallocatechin gallate) were assayed in co-incubation procedures using the SOS chromotest in Escherichia coli. Both EOs and their major compounds protected bacterial cells against bleomycin-induced genotoxicity indicating that these two compounds were principally responsible for the antigenotoxicity detected in the oils. Thymol and carvacrol antigenotoxicity was lower than those observed with epigallocatechin gallate. The results were discussed in relation to the chemopreventive potential of L. origanoides EOs and their major components, carvacrol and thymol. PMID:19874875

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

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

  6. Nucleobase-based barbiturates: their protective effect against DNA damage induced by bleomycin-iron, antioxidant, and lymphocyte transformation assay.

    Dhorajiya, Bhaveshkumar D; Dholakiya, Bharatkumar Z; Ibrahim, Ahmed S; Badria, Farid A

    2014-01-01

    A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, (1)H NMR, (13)C NMR, HMBC, and UV spectroscopy) and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3 -TBA manifested the best protective effect against DNA damage induced by bleomycin. PMID:24900997

  7. Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus

    Survival and swallowing were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radio -therapy was given to 51 patients, while 46 patients had 2 courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 year in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p=0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy. (author). 16 refs.; 1 fig.; 1 tab

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

    Srabani Kar

    2015-04-01

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

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

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

    2016-01-01

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

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

    Zhang Dongwei; Huang Chuangfang; Yang Changfu; Liu Renzuo J; Wang Jifeng; Niu Jianzhao; Brömme Dieter

    2011-01-01

    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 ...

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

    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 known. Thus the harmful side effects are difficult to eliminate. On the other hand the process of design or improvement of pharmaceuticals is extremely complex and expensive. Therefore a new trend...

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

    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.

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

    Ghofrani Hossein A

    2010-05-01

    Full Text Available Abstract Background Pulmonary fibrosis (PF is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well. Results PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7. Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF-α mRNA level and increased mRNA level of interleukin (IL-6 but did not influence IL-1β. At later stage (days 14 and 24 cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF-β1 and collagen type Ia1 (COL(Iα1. However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival. Conclusions Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.

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

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

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

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

    2015-01-01

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

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

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

    1991-09-01

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

  17. Colloidal Gold-Mediated Delivery of Bleomycin for Improved Outcome in Chemotherapy

    Celina Yang

    2016-03-01

    Full Text Available Nanoparticles (NPs can be used to overcome the side effects of poor distribution of anticancer drugs. Among other NPs, colloidal gold nanoparticles (GNPs offer the possibility of transporting major quantities of drugs due to their large surface-to-volume ratio. This is while confining these anticancer drugs as closely as possible to their biological targets through passive and active targeting, thus ensuring limited harmful systemic distribution. In this study, we chose to use bleomycin (BLM as the anticancer drug due to its limited therapeutic efficiency (harmful side effects. BLM was conjugated onto GNPs through a thiol bond. The effectiveness of the chemotherapeutic drug, BLM, is observed by visualizing DNA double strand breaks and by calculating the survival fraction. The action of the drug (where the drug takes effect is known to be in the nucleus, and our experiments have shown that some of the GNPs carrying BLM were present in the nucleus. The use of GNPs to deliver BLM increased the delivery and therapeutic efficacy of the drug. Having a better control over delivery of anticancer drugs using GNPs will establish a more successful NP-based platform for a combined therapeutic approach. This is due to the fact that GNPs can also be used as radiation dose enhancers in cancer research.

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

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

    2016-01-01

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

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

    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.

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

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

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

    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.

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

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

    2016-01-01

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

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

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

    2011-10-01

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

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

    Liu Dai-Shun

    2009-06-01

    Full Text Available Abstract Background Advanced glycation end products (AGEs have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM-stimulated rat model treated with aminoguanidine (AG, a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg and orally administered with AG (40, 80, 120 mg/kg once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47, a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGFβ1 and its downstream Smad proteins were analyzed by Western blot. Results AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p Conclusion These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGFβ/Smads signaling.

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

    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.

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

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

  7. Treatment of orbital venous malformations with intralesional injection of bleomycin lipiodol emulsion

    Objective: To evaluate the efficacy and safety of intralesional injection with bleomycin lipiodol emulsion (BLE) for the treatment of orbital venous malformation (OVM). Methods: There were 15 cases with left- sided OVM (n=9 ) and right- sided OVM (n=6). All patients had proptosis. The pr optosis was less than 5 mm in 11 cases, >5 mm and ≤8 mm in 4 cases. The mean value was 4.2 mm. Four patients noticed reduction in their vision and two had diplopia. Those patients were examined by CT or MR. Direct venography was performed in each patient. After the diagnosis of OVM was confirmed, intralesional injection of BLE was performed. The efficacy of the treatment and complications were observed during the following 8 to 42 months (mean 23 months). Results: The BLE were successfully injected in all the patients. All patients had resolution of proptosis and diplopia. Three patients gained improvement of visual acuity. The periorbital swelling occurred in all patients after operation and resolved within 1 week without special treatment. Other complications, such as orbital hemorrhage and periorbital scar, were not observed during following-up. Conclusion: Intralesional injection with BLE is convenient, safe and efficient for the treatment of OVM. (authors)

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

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

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

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

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

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

    2016-01-01

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

  11. 57Co-bleomycin imaging study of tumors of the head and neck

    57Co-Bleomycin (57Co-BLM) was used to visualize malignancies of the head and neck because it does not present the disadvantages of many other radiopharmaceuticals. In a series of 21 patients with 9 control subjects and 12 cases of tumors, 57Co-BLM showed a high and rapid uptake in primary site and metastases of malignant tumors of various histologic types, but not in benign tumors such as angiofibromas. Compared to 67Ga-citrate, 57Co-BLM has many advantages for tumor imaging in the areas of nose, pharynx and larynx: No background activity due to the concentration of 57Co-BLM in normal structures of the head and neck has ever been observed, as opposed to what happens with 67Ga-citrate. Furthermore, the blood clearance of 57Co-BLM is much more rapid than that of 67Ga-citrate, so that an early study may be performed in a 6 to 24 hr interval instead of 48 to 72 hr with 67Ga-citrate. 57Co-BLM scintigraphy is an easy, non-invasive and sensible diagnostic technique in determining the extent of malignant tumors in ORL patients

  12. Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production.

    Yao, Yingying; Wang, Yi; Zhang, Zhijun; He, Long; Zhu, Jianghui; Zhang, Meng; He, Xiaoyu; Cheng, Zhenshun; Ao, Qilin; Cao, Yong; Yang, Ping; Su, Yunchao; Zhao, Jianping; Zhang, Shu; Yu, Qilin; Ning, Qin; Xiang, Xudong; Xiong, Weining; Wang, Cong-Yi; Xu, Yongjian

    2016-05-01

    C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop(-/-) mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor β (TGF-β) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-β secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages. PMID:26883801

  13. Fair Certified Email Protocol

    Abdullah Mohammed Alaraj

    2013-07-01

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

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

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

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

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

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

    Ohashi, Takenobu; Yamamoto, Toshiyuki

    2015-09-01

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

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

    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

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

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

  19. Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells

    von der Maase, H

    1984-01-01

    The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost...... which interval the D0 surprisingly increased by a factor of 1.4. Administration of MM-C from 24 h before to 24 h after irradiation enhanced the radiation response. The effect peaked on administration 6 h before irradiation (DEF = 1.21) and diminished by application after irradiation. Cis-DDP enhanced...

  20. Interest of Co57 labelled bleomycin in assessment of local and regional dissemination carcinoma of the lung

    165 cases of lung carcinoma were studied with signs on radio-isotope scanning, either of local or regional spread (81 cases) or relapse after treatment (13 cases), or metastases (90 cases). A scan using Co57 labelled bleomycin permitted the discovery: in almost 50% of cases, of mediastinal spread, and in 33% of cases, spread to the clavicular lymph nodes, unnoticed on clinical examination; in 7 cases out of 13, relapse after surgery; in 3 cases, in the presence of clinical metastases, primary lung tumour; 67 metastatic lesions

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

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

  2. Distinct Roles of Ape1 Protein in the Repair of DNA Damage Induced by Ionizing Radiation or Bleomycin*

    Fung, Hua; Demple, Bruce

    2010-01-01

    Ionizing radiation (IR) and bleomycin (BLM) are used to treat various types of cancers. Both agents generate cytotoxic double strand breaks (DSB) and abasic (apurinic/apyrimidinic (AP)) sites in DNA. The human AP endonuclease Ape1 acts on abasic or 3′-blocking DNA lesions such as those generated by IR or BLM. We examined the effect of siRNA-mediated Ape1 suppression on DNA repair and cellular resistance to IR or BLM in human B-lymphoblastoid TK6 cells and HCT116 colon tumor cells. Partial Ape...

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

    Magaly M. Sales

    1999-03-01

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

  4. Response of mouse tongue epithelium to single doses of bleomycin and radiation

    Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED50) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

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

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

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

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

  7. Histopathologic observation of anti-tumor effect of bleomycin and irradiation on cancers of tongue

    Nine cases of squamous cell carcinoma of the tongue were treated by either intramuscular or local injections of total 60 to 200 mg of Bleomycin (BLM), and 7 cases by total doses of 1,200 to 5,320 rads of irradiation, followed by surgical removal of primary neoplasm. The histologic examination was do ne focussing on the antitumor effect of both treatments. In the cases with keratinizing component more than 25 % in the biopsy specimens, the earliest change due to BLM was vacuolar degeneration of proliferating cells either at the base of superficial cancer epithelia or at the periphery of invading cancer foci. When the proliferating cancer cells disappeared, an appearance of invading cancer foci resembled to that of ectopic islands of normal squamous epithelium. These foci of differentiated squamous cell carcinoma gradually underwent morphological change into the so-called cancer pearls. Finally, the cancer pearls degenerated, leaving foreign bodies consisting of concreted keratin. The stromal reaction was characterized by the formation of granulation tissues accompanying significant numbers of foreign body giant cells. In the cases of lingual carcinoma with poor squamous differentiation, these processes were indistinct. Instead, the proliferating anaplastic cancer cells were markedly reduced and the remaining cancer cells transformed into large bizarre cells, probably at degenerative stage. On the histologic level, irradiation showed essentially similar antitumor effect to BLM, except for the rapid formation of concreted keratin bodies accompanying more abundant foreign body giant cells and the presence of irregular granulation tissues at different stages. We concluded that both BLM and irradiation had a powerful antitumor action on squamous cell carcinoma of the tongue. (J.P.N.)

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

    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.

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

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

    2001-01-23

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

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

    Flower Roderick J

    2011-10-01

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

  11. Safely composing security protocols

    Cortier, Véronique; Delaitre, Jérémie; Delaune, Stéphanie

    2007-01-01

    Security protocols are small programs that are executed in hostile environments. Many results and tools have been developed to formally analyze the security of a protocol in the presence of active attackers that may block, intercept and send new messages. However even when a protocol has been proved secure, there is absolutely no guarantee if the protocol is executed in an environment where other protocols, possibly sharing some common identities and keys like public keys or long-term symmetr...

  12. Mobile internet protocol analysis

    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...

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

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

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

    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-HT3 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 (10-5 mol/l) had no effect on the survival of irradiated cells. Granisetron (10-5 mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10-7 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-HT3 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.)

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

    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.).

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

    Daniel Francisco Arencibia Arrebola

    2010-04-01

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

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

    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.

  18. A young male with shortness of breath

    Khan Fahmi

    2008-01-01

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

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

    Bo Zhu

    2013-12-01

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

  20. Assessment of preferential cleavage of an actively transcribed retroviral hybrid gene in murine cells by deoxyribonuclease I, bleomycin, neocarzinostatin, or ionizing radiation

    Preferential cleavage induced by bleomycin, neocarzinostatin, or ionizing radiation in a transcribed cellular gene was evaluated through comparisons with deoxyribonuclease I. The glucocorticoid-inducible LTL gene previously described served as the specific DNA target. A Southern blot analysis was used to specifically assess cleavage of the LTL gene in nuclei isolated from cells either treated or untreated with the synthetic glucocorticoid dexamethasone. Hypersensitivity of the gene to bleomycin or neocarzinostatin, which paralleled deoxyribonuclease I hypersensitivity, was evident only in nuclei isolated from dexamethasone-treated cells. Like deoxyribonuclease I, sites of dexamethasone-inducible drug hypersensitivity were coincident with the binding region for the glucocorticoid receptor found within the regulatory sequences of the LTL gene. In contrast, no hypersensitivity to ionizing radiation was evident. Although bleomycin and neocarzinostatin showed qualitatively similar preferences for the threshold LTL gene, quantitative evaluations of damage to total cellular DNA by filter elution showed that the relative specificity of bleomycin for the hypersensitive region was much less than that of either deoxyribonuclease I or neocarzinostatin

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

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

    2015-08-01

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

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

    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.

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

    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

  4. Rational exchange protocols

    Alcaide Raya, Almudena

    2008-01-01

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

  5. Synthesizing secure protocols

    Cortier, Véronique; Warinschi, Bogdan; Zalinescu, Eugen

    2007-01-01

    We propose a general transformation that maps a protocol secure in an extremely weak sense (essentially in a model where no adversary is present) into a protocol that is secure against a fully active adversary which interacts with an unbounded number of protocol sessions, and has absolute control over the network. The transformation works for arbitrary protocols with any number of participants, written with usual cryptographic primitives. Our transformation provably preserves a large class of...

  6. Protocol Implementation Generator

    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 a...

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

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

  8. Adaptation of TURN protocol to SIP protocol

    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.

  9. Efficient decentralized consensus protocols

    Lakshman, T. V.; Agrawala, A. K.

    1986-01-01

    Decentralized consensus protocols are characterized by successive rounds of message interchanges. Protocols which achieve a consensus in one round of message interchange require O(N-squared) messages, where N is the number of participants. In this paper, a communication scheme, based on finite projective planes, which requires only O(N sq rt N) messages for each round is presented. Using this communication scheme, decentralized consensus protocols which achieve a consensus within two rounds of message interchange are developed. The protocols are symmetric, and the communication scheme does not impose any hierarchical structure. The scheme is illustrated using blocking and nonblocking commit protocols, decentralized extrema finding, and computation of the sum function.

  10. Bleomycin, methotrexate and vincristine before irradiation of stage III and IV laryngeal and pharyngeal squamous cell carcinoma

    Primary treatment with bleomycin, methotrexate and vincristine for two weeks followed by curatively intended 60Co irradiation was administered to 153 patients consecutively referred to the three main treatment centres in Denmark over more than a two-year period. Seventy-one laryngeal and 82 pharyngeal squamous cell carcinomas were evaluated. According to the TNM classification (UICC) 76 patients had stage III and 77 patients stage IV disease. The immediate response (complete + partial) to chemotherapy was 20%. Judging from frequency of local recurrence, metastases as well as survival the treatment results were not obviously improved. A high frequency of complications was observed after this combination of chemotherapy and irradiation, and it was often impossible to fulfil the irradiation to the planned dose in appropriate time. (orig.)

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

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

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

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

  13. Security of RFID protocols

    Van Deursen, Ton

    2011-01-01

    Radio-frequency identification (RFID) is a technology that uses radio waves to exchange data between RFID readers and tags. The low manufacturing costs and small size and the lack of need of a power source make RFID tags useful in many applications, but also impose a strong need for secure RFID protocols. The first part of this thesis considers the analysis of untraceability of RFID protocols. We start by designing a formal syntax and semantics for security protocols. We define untraceab...

  14. Block Advertisement Protocol

    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 ...

  15. Multiparty Quantum Cryptographic Protocol

    We propose a multiparty quantum cryptographic protocol. Unitary operators applied by Bob and Charlie, on their respective qubits of a tripartite entangled state encoding a classical symbol that can be decoded at Alice's end with the help of a decoding matrix. Eve's presence can be detected by the disturbance of the decoding matrix. Our protocol is secure against intercept-resend attacks. Furthermore, it is efficient and deterministic in the sense that two classical bits can be transferred per entangled pair of qubits. It is worth mentioning that in this protocol, the same symbol can be used for key distribution and Eve's detection that enhances the efficiency of the protocol

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

    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.

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

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

    1988-04-01

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

  18. Salvage therapy with mitoxantrone, etoposide, bleomycin and dexamethasone for refractory or relapsed aggressive non-Hodgkin’s lymphoma patients with a poor performance status or comorbidity

    Lin, Xuede; Shi, Xi; ZENG, WUCHA; Min ZHENG; HUANG, LIMING

    2014-01-01

    The treatment of refractory or relapsed aggressive non-Hodgkin’s lymphoma (NHL) in patients in a state of poor health is difficult due to their ineligibility to receive intensive salvage chemotherapy. In the present study, 16 refractory or relapsed aggressive NHL patients with a poor performance status or comorbidities were treated with mitoxantrone, etoposide, bleomycin and dexamethasone (MEBD) therapy. The treatment consisted of 10 mg/m2 intravenous (IV) mitoxantrone on day 1, 75 mg/m2 IV e...

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

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

    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...

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

    Bo Zhu; Ai-Qun Ma; Lan Yang; Xiao-Min Dang

    2013-01-01

    Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-ind...

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

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

    2001-01-01

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

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

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

    2007-01-01

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

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

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

    2008-01-01

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

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

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

    2013-09-01

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

  5. Transport Protocol Throughput Fairness

    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.

  6. Linear Logical Voting Protocols

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    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...

  7. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496.

    Evens, Andrew M; Hong, Fangxin; Gordon, Leo I; Fisher, Richard I; Bartlett, Nancy L; Connors, Joseph M; Gascoyne, Randy D; Wagner, Henry; Gospodarowicz, Mary; Cheson, Bruce D; Stiff, Patrick J; Advani, Ranjana; Miller, Thomas P; Hoppe, Richard T; Kahl, Brad S; Horning, Sandra J

    2013-04-01

    There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0·3% for patients aged <60 years (P < 0·001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P = 0·002; 5-year overall survival: 58% and 90%, respectively, P < 0·0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P = 0·37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, P = 0·30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P < 0·0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events. PMID:23356491

  8. Coded Splitting Tree Protocols

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

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

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

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

    1995-02-01

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

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

    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 curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior such as proliferation, migration and apoptosis rates and on the expression of TGF-β1 in mouse lung and HFL-1 cells. These results suggest that cathepsin-inducing drugs such as curcumin may be beneficial in the treatment of lung fibrosis.

  11. Protocol Fuel Mix reporting

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

  12. ATM and Internet protocol

    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

  13. Playing With Population Protocols

    Xavier Koegler

    2009-06-01

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

  14. Timed analysis of security protocols

    Corin, R.; Etalle, S.; Hartel, P.H.; Mader, A

    2007-01-01

    We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols using UPPAAL. Further, a taxonomy is obtained by studying and categorising protocols from the well known Clark Jacob library and the Security Protocol Open Repository (SPORE) library. Finally, we ...

  15. 1996 : Track Count Protocol

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

  16. Authenticated file broadcast protocol

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

    2015-01-01

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

  17. USA-USSR protocol

    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.

  18. Principles of Protocol Design

    Sharp, Robin

    This is a new and updated edition of a book first published in 1994. The book introduces the reader to the principles used in the construction of a large range of modern data communication protocols, as used in distributed computer systems of all kinds. The approach taken is rather a formal one......, primarily based on descriptions of the protocols in the notation of CSP (Communicating Sequential Processes)....

  19. Outcomes of Bleomycin-based electrochemotherapy in patients with repeated loco-regional recurrences of vulvar cancer.

    Pellegrino, Antonio; Damiani, Gianluca Raffaello; Mangioni, Costantino; Strippoli, Davide; Loverro, Giuseppe; Cappello, Antonio; Turoli Scd, Daniela; Corso, Silvia; Tartagni, Massimo; Pezzotta, Maria Grazia

    2016-05-01

    Objective To evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments. Methods Ten patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires. Results Diagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD ± 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10-20) min. After a median follow-up of 12 (3-22) months, six patients (60%) were alive. Conclusions Objective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3-22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting. PMID:26882959

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

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

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

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

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

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

    2004-10-01

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

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

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

  4. Bleomycin - induced DNA damage and DNA repair in chicken embryo cells as compared to X-irradiation

    Following in vitro- and in ovo-exposure of chicken embryo cells, the level of bleomycin (BM) - induced damage was evaluated by using DNA synthesis, nucleoid sedimentation (SED), and viscometry of alkaline cell lysates (VISC). This damage was compared to X-irradiation, using 5.9-378 nM BM in vitro, 1.5-116 μg BM/egg in ovo, and 2-32 Gy, respectively, in vitro as well as in ovo. With respect to BM, the most notable result is the increase in DNA synthesis and VISC at the lowest concentrations of the drug. A decrease in both parameters was observed at high BM concentrations and following exposure to X-rays, concomitantly with an increase in SED. Regarding the radiomimetic drug BM and X-rays, different modes of DNA damage and DNA repair are suggested by previous investigations and the present results. Therefore, further evidence is presented, that the chicken embryo can act as a simple, rapid and inexpensive test system to characterize the biological effects of many nucleo- and/or cytotoxic agents. (orig.)

  5. Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma

    Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. The incidence of measurable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes has been correlated. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases

  6. X-ray-sensitive mutants of mouse mammary carcinoma cells are hypersensitive to bleomycin and hydrogen peroxide

    Radiation-sensitive mutants, SX9 and SX10, were isolated from mouse mammary carcinoma FM3A cells. The mutant SX9 complemented another radiation-sensitive strain M10 of mouse leukemia L5178Y cells, but SX10 did not. SX9 and SX10 cells were more sensitive than the wild-type cells to the lethal effects of bleomycin. The frequency of X-ray-induced mutations to 6-thioguanine resistance was much higher in SX9 cells than in the wild-type cells in the dose range up to 1 Gy, although the induced mutant frequencies were not very different between these two cell strains when compared at equivalent survival. SX9, SX10 and M10 cells were found to be far more sensitive than the respective wild-type cells to hydrogen peroxide inactivation, but the levels of catalase activity were similar among these cell strains. These mutants should be useful for cloning and identifying the human genes responsible for radiation sensitivity. (author)

  7. On the AAGL Protocol

    Chowdhury, M M

    2007-01-01

    Recently theAAGL(Anshel-Anshel-Goldfeld-Lemieux) hasbeenproposed which canbe usedforRFIDtags. We give algorithms for the problem (we call the MSCSPv) on which the security of theAAGL protocol is based upon. Hence we give various attacks for general parameters on the recent AAGLprotocol proposed. One ofour attacks is a deterministic algorithm which has space complexity and time complexityboth atleast exponentialin the worst case. In abetter case using a probabilistic algorithm the time complexity canbe O(|XSS(ui')^L5*(n^(1+e)) and the space complexity can be O(|XSS(ui')|^L6), where the element ui' is part of a public key, n is the index of braid group, XSS is a summit type set and e is a constant in a limit. The above shows the AAGL protocol is potentially not significantly more secure as using key agreement protocols based on the conjugacy problem such as the AAG (Anshel-Anshel-Goldfeld) protocol because both protocols can be broken with complexity which do not significantly differ. We think our attacks can b...

  8. DNA repair protocols

    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...

  9. Vertical Protocol Composition

    Groß, Thomas; Mödersheim, Sebastian Alexander

    2011-01-01

    composition, and it is truly commonplace in today’s communication with the diversity of VPNs and secure browser sessions. In fact, it is normal that we have several layers of secure channels: For instance, on top of a VPN-connection, a browser may establish another secure channel (possibly with a different...... end point). Even using the same protocol several times in such a stack of channels is not unusual: An application may very well establish another TLS channel over an established one. We call this selfcomposition. In fact, there is nothing that tells us that all these compositions are sound, i.e., that...... the combination cannot introduce attacks that the individual protocols in isolation do not have. In this work, we prove a composability result in the symbolic model that allows for arbitrary vertical composition (including self-composition). It holds for protocols from any suite of channel and...

  10. Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways.

    Alshatwi, Ali A; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Elango, Ramesh

    2016-03-01

    Bleomycin is a chemotherapeutic agent that is frequently used in the treatment of various cancers. Bleomycin causes serious adverse effects via antioxidant defense abnormalities against reactive oxygen species (ROS). However, the current cervical cancer monodrug therapy strategy has failed to produce the expected outcomes; hence, combinational therapies are gaining great interest. Tea polyphenols are also effective antioxidative and chemo-preventive agents. However, the combined effect of tea polyphenol (TPP) and bleomycin (BLM) against cervical cancer remains unknown. In this study, we focused on the potential of TPP on BLM anticancer activity against cervical cancer cells. Cervical cancer cells (SiHa) were treated with various concentrations of TPP, BLM and TPP combined with BLM (TPP-BLM), and their effects on cell growth, intracellular reactive oxygen species, poly-caspase activity, early apoptosis and the expression of caspase-3, caspase-8 and caspase-9, Bcl-2 and p53 were assessed. The MTT assay revealed that the SiHa cells were less sensitive to growth inhibition by TPP treatment compared with both BLM and the combination therapy. Nuclear staining indicated that exposure to TPP-BLM increased the percentage of apoptotic nuclei compared with a mono-agent treatment. Caspase activation assay demonstrated that proportion of early and late apoptotic/secondary necrotic cells was higher in the cells treated with the combination therapy than in those treated with either TPP or BLM alone. The TPP-BLM treatment synergistically induced apoptosis through caspase-3, caspase-8 and caspase-9 activation, Bcl-2 upregulation and p53 overexpression. This study suggests that TPP-BLM may be used as an efficient antioxidant-based combination therapy for cervical cancer. PMID:26800624

  11. Stream Control Transmission Protocol Steganography

    Fraczek, Wojciech; Mazurczyk, Wojciech; Szczypiorski, Krzysztof

    2010-01-01

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

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

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

  13. Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor β1 level

    Asghari, Mohammad Hossein; Hobbenaghi, Rahim; Nazarizadeh, Ali; Mikaili, Peyman

    2015-01-01

    Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-β1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into...

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

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

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

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

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

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

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

    Haslett, C.; Shen, A.S.; Feldsien, D.C.; Allen, D.; Henson, P.M.; Cherniack, R.M. (National Jewish Center for Immunology and Respiratory Medicine, Denver, CO (USA))

    1989-09-01

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

  18. 111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

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

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

    Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)], E-mail: ghoffmann@holycross.edu; Gessner, Gabrielle S.; Hughes, Jennifer F.; Ronan, Matthew V.; Sylvia, Katelyn E.; Willett, Christine J. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)

    2007-10-01

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

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

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

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

    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.

  2. Simple wavelength assignment protocol

    Suryaputra, Stephen; Touch, Joseph D.; Bannister, Joseph A.

    2000-10-01

    IP routers can be coupled with wavelength-selective optical cross- connects to support existing Internet infrastructure in a wavelength division multiplexing (WDM) optical network. Because optical wavelength routing is transparent to IP, packets can bypass traditional forwarding and pass directly through the optical cross-connect, resulting in very high throughput and low delay routing. This approach shares features with label switching, but wavelengths are much more scarce resource than labels. Because optical switches have larger switching times than electronic switches, and wavelength conversions are expensive, wavelength label swapping is not easily done. Wavelength label assignments must consider these limitations to be practical in an optical environment. The performance of an instance of this approach, called Packet over Wavelengths (POW) has been simulated and studied. A new signaling protocol, Simple Wavelength Assignment Protocol (SWAP) is devised to be POW signaling protocol. SWAP takes into account the optical device limitations, and is designed to minimize wavelength conversion, utilize wavelengths with the merging of flows, and reduce the reconfiguration of optical switches. SWAP, to our knowledge, is the first approach to combine signaling and wavelength assignment in an on- line protocol. This paper describes high level SWAP design challenges, decision, and overhead.

  3. Model Additional Protocol

    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)

  4. A family of quantum protocols

    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.

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

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

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

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

    2016-01-01

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

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

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

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

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

    2016-01-01

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

  9. Symmetric cryptographic protocols

    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

  10. Mitosis Methods & Protocols

    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..... 

  11. Phototherapy Modalities and Protocols

    Ayten Ferahba?

    2010-12-01

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

  12. Communication protocols; Protocolos de comunicacao

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

    1998-07-01

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

  13. Satellite Communications Using Commercial Protocols

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

    2000-01-01

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

  14. Specifying agent interaction protocols

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

    2005-01-01

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

  15. Blind Cognitive MAC Protocols

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

    2008-01-01

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

  16. Seismic protocol urges sensitivity

    This paper is a preliminary summary of a protocol manual for conducting seismic surveys in various topographic and geographic situations to minimize environmental impacts. The manual aims at addressing unique issues for six different types of ecological environments in such a way as to enhance contractors' overall awareness of the types of environmental issues they may encounter, along with some common sense methods of dealing with them. Those six environments are marine, coastal, rain forest, arctic, semi-level terrains, and mountainous

  17. Dysphonia risk screening protocol

    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.

  18. Synchronizing internet protocol security (SIPSec)

    Shoniregun, Charles A

    2007-01-01

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

  19. Publishing Protocols for Partnered Research

    Hysong, Sylvia J.; Woodard, LeChauncy; Garvin, Jennifer H.; Murawsky, Jeffrey; Petersen, Laura A.

    2014-01-01

    Published scientific protocols are advocated as a means of controlling bias in research reporting. Indeed, many journals require a study protocol with manuscript submission. However, publishing protocols of partnered research (PPR) can be challenging in light of the research model’s dynamic nature, especially as no current reporting standards exist. Nevertheless, as these protocols become more prevalent, a priori documentation of methods in partnered research studies becomes increasingly impo...

  20. Static Validation of Security Protocols

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.; Nielson, Hanne Riis; Nielson, Flemming

    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...

  1. Automatic Validation of Protocol Narration

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo; Nielson, Flemming; Nielson, Hanne Riis

    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...

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

    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 EMT in BLM-induced skin fibrosis. • NAC attenuated EMT induction in the process of BLM-induced skin fibrosis. • NAC didn't significantly inhibit TGF-β expression in BLM-induced skin fibrosis.

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

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

  4. A protected password change protocol

    Wang, R C; Mo, K R; Wang, Ren-Chiun; Yang, Chou-Chen; Mo, Kun-Ru

    2005-01-01

    Some protected password change protocols were proposed. However, the previous protocols were easily vulnerable to several attacks such as denial of service, password guessing, stolen-verifier and impersonation atacks etc. Recently, Chang et al. proposed a simple authenticated key agreement and protected password change protocol for enhancing the security and efficiency. In this paper, authors shall show that password guessing, denial of service and known-key attacks can work in their password change protocol. At the same time, authors shall propose a new password change protocol to withstand all the threats of security.

  5. Impersonation Attack on EKE Protocol

    Shirisha Tallapally

    2010-04-01

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

  6. INTRODUCTION TO ROUTING PROTOCOLS

    Nikhil Kumar

    2014-06-01

    Full Text Available In this era of communication network, we can access any website or contact any person with the help of internet or telephone anywhere in the world without knowing where the website is hosted and without knowing where the person is located. This all is done within a few seconds very efficiently. But the question comes out how it is done? And the answer is that, it is only done with the help of network routing. In this paper we review the IP routing and its protocols.

  7. Address Resolution Protocol Optimization

    Nor Adnan Yahaya

    2009-09-01

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

  8. Sincalide - the final protocol

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

  9. FRENCH PROTOCOL CARDS

    Human Resources Division

    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

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

    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.

  12. Security and SCADA protocols

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

  13. Protocol Architecture Model Report

    Dhas, Chris

    2000-01-01

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

  14. Licklider Transmission Protocol Implementation

    Burleigh, Scott C.; Krupiarz, Chris

    2011-01-01

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

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

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

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

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

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

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

    1991-02-01

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

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

    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)

  19. Formal Verification of Quantum Protocols

    Nagarajan, R; Nagarajan, Rajagopal; Gay, Simon

    2002-01-01

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

  20. Stream Control Transmission Protocol Steganography

    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.

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

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

    2016-02-15

    Fluorofenidone is a novel derivative of l-mimosine. It has remarkable anti-fibrotic properties. In this study, we established that fluorofenidone ameliorates pulmonary fibrosis (PF) both in vivo and in vitro by specifically inhibiting the expression of eukaryotic translation initiation factor 3a (eIF3a). eIF3a plays an important role in the development and progression of PF. An animal model of PF was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Rats were orally administered with fluorofenidone (250, 500mg/kg/d·[i.g.]) and pirfenidone (500mg/kg/d·[i.g.]) for 28 days. Primary pulmonary fibroblasts were cultured to determine the effect of fluorofenidone on TGF-β1-induced (5ng/ml) proliferation and differentiation of fibroblasts. The expression/level of eIF3a, TGF-β1, α-SMA, collagen I, and collagen III were analyzed by ELISA, real-time PCR, and western blot. The cell proliferation rate was determined by MTS assay. The results indicate that fluorofenidone significantly improves the pathological changes in lung tissues and reduces the deposition of collagen by inhibiting eIF3a in rats with bleomycin-induced PF. Moreover, in a culture of pulmonary fibroblasts, fluorofenidone decreased the up-regulation of TGF-β1-induced eIF3a by inhibiting the proliferation of cells and reducing the expression of α-SMA, collagen I, and collagen III. These findings suggest that eIF3a is a new and special target of fluorofenidone, which could be potentially used in the development of a drug that treats PF. PMID:26821114

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

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

    2016-03-01

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

  3. Salvage therapy with mitoxantrone, etoposide, bleomycin and dexamethasone for refractory or relapsed aggressive non-Hodgkin's lymphoma patients with a poor performance status or comorbidity.

    Lin, Xuede; Shi, Xi; Zeng, Wucha; Zheng, Min; Huang, Liming

    2014-11-01

    The treatment of refractory or relapsed aggressive non-Hodgkin's lymphoma (NHL) in patients in a state of poor health is difficult due to their ineligibility to receive intensive salvage chemotherapy. In the present study, 16 refractory or relapsed aggressive NHL patients with a poor performance status or comorbidities were treated with mitoxantrone, etoposide, bleomycin and dexamethasone (MEBD) therapy. The treatment consisted of 10 mg/m(2) intravenous (IV) mitoxantrone on day 1, 75 mg/m(2) IV etoposide on days 1-3, 20 mg IV dexamethasone on days 1-4 and 15 mg intramuscular bleomycin on days 1, 4, 8 and 12, every 21 days. The efficacy and toxicity of the regimen were evaluated. The overall response rate was 68.8%, with a complete response rate of 18.8% and a partial response rate of 50.0%. The efficacy of the treatment for B-cell lymphoma was greater than that for T-cell lymphoma. The median progression-free survival time for the patients was 16.7 months and the median overall survival time was 22.4 months. The one-year overall survival rate was 62.5% and the two-year overall survival rate was 43.8%. The most common toxicity symptom was myelosuppression. In conclusion, refractory or relapsed aggressive NHL patients with a poor performance status or comorbidity are eligible for chemotherapy. MEBD therapy is an effective and feasible salvage regimen for NHL patients in a state of poor health. PMID:25295084

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

    Franz-Bacon, Karin; DiTirro, Danielle N.; Ly, Tai Wei; Bacon, Kevin B.

    2016-01-01

    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. PMID:27144281

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

    Xian-mei Zhou

    2012-02-01

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

  6. Protocols for Scholarly Communication

    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...

  7. Unconditionally Secure Protocols

    Meldgaard, Sigurd Torkel

    used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern......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 they are....... We construct an oblivious RAM that hides the client's access pattern with information theoretic security with an amortized $\\log^3 N$ query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to $\\log^2 N$, while also avoiding the...

  8. A PROGRAMMED LABOUR - PROTOCOL

    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.

  9. Symbolic Analysis of Cryptographic Protocols

    Böhl, Florian

    2014-01-01

    We rely on the security properties of cryptographic protocols every day while browsing the Internet or withdrawing money from an ATM. However, many of the protocols we use today were standardized without a proof of security. Serious flaws in protocols restrict the level of security we can reach for applications. This thesis motivates why we should strive for proofs of security and provides a framework that makes using automated tools to conduct such proofs more feasible.

  10. Dynamic Tags for Security Protocols

    Arapinis, Myrto; Delaune, Stéphanie; Kremer, Steve

    2014-01-01

    The design and verification of cryptographic protocols is a notoriously difficult task, even in symbolic models which take an abstract view of cryptography. This is mainly due to the fact that protocols may interact with an arbitrary attacker which yields a verification problem that has several sources of unboundedness (size of messages, number of sessions, etc. In this paper, we characterize a class of protocols for which deciding security for an unbounded number of sessions is decidable. Mo...

  11. Simulatable security for quantum protocols

    Unruh, Dominique

    2004-01-01

    The notion of simulatable security (reactive simulatability, universal composability) is a powerful tool for allowing the modular design of cryptographic protocols (composition of protocols) and showing the security of a given protocol embedded in a larger one. Recently, these methods have received much attention in the quantum cryptographic community. We give a short introduction to simulatable security in general and proceed by sketching the many different definitional choices together with...

  12. A protected password change protocol

    Wang, Ren-Chiun; Yang, Chou-Chen; Mo, Kun-Ru

    2005-01-01

    Some protected password change protocols were proposed. However, the previous protocols were easily vulnerable to several attacks such as denial of service, password guessing, stolen-verifier and impersonation atacks etc. Recently, Chang et al. proposed a simple authenticated key agreement and protected password change protocol for enhancing the security and efficiency. In this paper, authors shall show that password guessing, denial of service and known-key attacks can work in their password...

  13. Compiling and securing cryptographic protocols

    Chevalier, Yannick

    2009-01-01

    Protocol narrations are widely used in security as semi-formal notations to specify conversations between roles. We define a translation from a protocol narration to the sequences of operations to be performed by each role. Unlike previous works, we reduce this compilation process to well-known decision problems in formal protocol analysis. This allows one to define a natural notion of prudent translation and to reuse many known results from the literature in order to cover more crypto-primitives. In particular this work is the first one to show how to compile protocols parameterised by the properties of the available operations.

  14. Message Broadcasting Protocols in VANET

    Ghassan Samara; Wafaa A.H. Ali Alsalihy

    2012-01-01

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

  15. Message Broadcasting Protocols in VANET

    Ghassan Samara

    2012-01-01

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

  16. A Streaming Protocol for Memcached

    W. Li

    2012-01-01

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

  17. An Improved Resource Reservation Protocol

    Desire Oulai

    2007-01-01

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

  18. Internet Protocol Television (IPTV

    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

  19. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly.

    Stamatoullas, Aspasia; Brice, Pauline; Bouabdallah, Reda; Mareschal, Sylvain; Camus, Vincent; Rahal, Ilhem; Franchi, Patricia; Lanic, Hélène; Tilly, Hervé

    2015-07-01

    There is no standard of care in elderly classical Hodgkin lymphoma (cHL) patients. ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), the standard chemotherapy for younger patients, is also used in elderly patients but little is known about toxicity and efficacy. We retrospectively analysed 147 patients aged 60 years and over treated with ABVD in three French haematological centres. Treatment regimen modification was applied in 56 patients for toxicity or HL progression. Bleomycin was removed or reduced in 53 patients, mainly for pulmonary toxicity. Neither initial characteristics nor treatment characteristics were found to correlate with lung toxicity. One hundred and seventeen patients achieved a complete remission, 6 a partial remission, 16 had refractory disease and 8 were non-evaluable. Five-year overall survival was estimated at 67%. With a median follow-up of 58 months, 51 patients died and 14% of deaths were related to lung toxicity. Our study confirms the efficacy of ABVD in elderly patients even if results are inferior to those obtained in younger patients with the same regimen. ABVD can be proposed as front-line chemotherapy in selected elderly cHL patients. The frequency of pulmonary events leads us to propose to either reduce the dose of bleomycin or to remove it from the regimen. PMID:25891777

  20. Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury

    Adriana Ignacio de Padua

    2008-11-01

    Full Text Available OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo e injetados com salina intratraqueal (IT; grupo SB, tratados com salina (placebo e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%. A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente. Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%.O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão. CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina.OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo and then receiving intratracheal (IT instillation of saline; SB, injected with saline (placebo and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure was higher in the SB group than in the SS group (57.7% vs. 11.1%. The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively. The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%. The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung. CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

  1. Performance Evaluation of Security Protocols

    Genge, Bela

    2009-01-01

    We propose a comparative performance evaluation of security protocols. The novelty of our approach lies in the use of a polynomial mathematical model that captures the performance of classes of cryptographic algorithms instead of capturing the performance of each algorithm separately, approach that is used in other papers. A major advantage of using such a model is that it does not require implementation-specific information, because the decision is based on comparing the estimated performances of protocols instead of actually evaluating them. The approach is validated by comparatively evaluating the performances of 1000 automatically generated security protocols against the performances of their actual implementations.

  2. Assessment of Established Survey Protocols

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

  3. Automatic Sequencing for Experimental Protocols

    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.

  4. Effects of Herba Ephedra Sinicae and Fructus Schisandrae Chinensis on pathology of rats with bleomycin A5-induced idiopathic pulmonary fibrosis

    Hua-qiang Zhai

    2011-05-01

    Full Text Available Objective: To observe the different effects between Mahuang (Herba Ephedra Sinicae and Wuweizi (Fructus Schisandrae Chinensis on the pathological changes of rats with bleomycin A5-induced pulmonary fibrosis.Methods: Ninety Wistar rats were randomly divided into sham operation group, model group, hydrocortisone group, Herba Ephedra Sinicae group, Fructus Schisandrae Chinensis group and Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group. There were 16 rats in each group except the sham operation group (10 rats. Pulmonary fibrosis was induced by a single intratracheal injection of bleomycin A5. Hematoxylin and eosin straining and immunohistochecical method were used after 7- and 28-day treatment to observe the pathology of lung injury, measure the inner diameter of pulmonary arterioles and the density of nuclear membrane.Results: Compared with the sham operation group at 7 and 28 d, alveolar inflammation level was significantly increased in the model group (P?0.01. Alveolar inflammation level was decreased obviously in the hydrocortisone group (P?0.05 after 7- and 28-day treatment as compared with the model group, and that in Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group was also decreased obviously (P?0.05 at 28 d. Compared with the sham operation group, nuclear density of the model group was increased, while its inner diameter was decreased (P?0.05. In the Fructus Schisandrae Chinensis group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group, the nuclear density was decreased (P?0.05 as compared with the model group. Inner diameter in the Herba Ephedra Sinicae group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group was higher than that in the model group (P?0.05. Microvessel density of the model group was obviously higher than that of the sham operation group (P?0.05. Compared with the model group, Herba Ephedra Sinicae plus Fructus Schisandrae Chinensis group and hydrocortisone group had lower microvessel density (P?0.05.Conclusion: Herba Ephedra Sinicae combined with Fructus Schisandrae Chinensis can restrain pulmonary artery injury. The nuclear density and microvessel density can be reduced by Fructus Schisandrae Chinensis, while Herba Ephedra Sinicae can increase the inner diameter.

  5. Neonatal euthanasia: The Groningen Protocol*

    Vizcarrondo, Felipe E.

    2014-01-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criter...

  6. Automated Setup of Display Protocols

    Bergström, Patrik

    2015-01-01

    Radiologists' workload has been steadily increasing for decades. As digital technology matures it improves the workflow for radiology departments and decreases the time necessary to examine patients. Computer systems are widely used in health care and are for example used to view radiology images. To simplify this, display protocols based on examination data are used to automatically create a layout and hang images for the user. To cover a wide variety of examinations hundreds of protocols mu...

  7. Kyoto Protocol one step closer

    Showstack, Randy

    The European Union (EU) could soon decide to ratify the Kyoto Protocol on climate change, following a 4 March meeting of the European Commissions environment council to approve the treaty.European Commission President Romani Prodi said the council's move enables the 15 EU member states to take the steps toward simultaneous ratification together with the commission before 1 June."I urge our partners both in the developed and in the developing countries to also ratify the Kyoto Protocol soon," he said.

  8. Superposition Attacks on Cryptographic Protocols

    Damgård, Ivan; Funder, Jakob; Nielsen, Jesper Buus; Salvail, Louis

    2013-01-01

    Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum s...

  9. Domain-specific scheduling protocols

    Tilgner, Christian

    2012-01-01

    A database scheduler takes requests from transactions and generates a request order that fulfills the constraints of a scheduling protocol, e.g., correctness criteria. The goal of this thesis is to provide a new method for the development of domain-specific protocols for scheduling database requests.Scheduling concurrent requests is an ubiquitous problem in modern server systems based on, e.g., Web Services that handle large numbers of concurrent requests. These systems require user scalabili...

  10. LISP: a southbound SDN protocol?

    Rodríguez Natal, Alberto; Portoles Comeras, Marc; Ermagan, Vina; Lewis, Darrel; Farinacci, Dino; Maino, Fabio; Cabellos Aparicio, Alberto

    2015-01-01

    The Locator/ID Separation Protocol (LISP) splits current IP addresses overlapping semantics of identity and location into two separate namespaces. Since its inception the protocol has gained considerable attention from both industry and academia, motivating several new use cases to be proposed. Despite its inherent control-data decoupling and the abstraction and flexibility it introduces into the network, little has been said about the role of LISP on the SDN paradigm. In this article we try ...

  11. Multilevel Security Protocol using RFID

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

    2011-01-01

    Though RFID provides automatic object identification, yet it is vulnerable to various security threats that put consumer and organization privacy at stake. In this work, we have considered some existing security protocols of RFID system and analyzed the possible security threats at each level. We have modified those parts of protocol that have security loopholes and thus finally proposed a modified four-level security model that has the potential to provide fortification against security threats

  12. Self-Healing Protocol Implementations

    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

    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. Monoclonal antibodies technology. Protocols

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x107 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x107 spleen cells to 1x106 myeloma cells (ratio 10:1). Centrifuge the mixture of cells at 300g for 10 minutes. While the cells are centrifuging, set aside 30 ml of serum-free RPMI 1640 in another 50-ml tube. Prepare the 50% PEG and place the timer in the hood. 6. Remove all the supernatant from the cell pellet. Overlay the pellet of cells with 0.5 ml of 50% PEG with a Pasteur pipet during 1 minute. Then add 5 ml of serum-free RPMI 1640 during 3 minutes. At the end of 3 minutes, add during a minute 15 ml of the same medium. 7. Centrifuge at 250g for 10 minutes. Gently resuspend the fused cells at a concentration of 5 x104 cells/ml, in a RPMI medium containing serum at 20%, HAT (selective growth) and antibiotics. 8. Distribute the cell suspension into 96-well-flat-bottom-tissue-culture plates add 0.2 ml per well. Incubate the plates at 37 deg. C in 5% CO2. Three to 4 days in HAT medium is sufficient for arresting the proliferation of unfused myeloma cells. Screening and establishing a Hybridorna line. The screening could be perform using different immunoassay alternatives (ELISA, RIA, etc). The principal requisite is have been developed a reproducible method before to make the fusion. These method could be improve using the serum of mice immunized as sample. Approximately 1 week after the fusion, colonies of hybrid cells will be ready to screen. During the screening, samples of tissue culture media are removed from wells that have growing hybridomas and are tested for the presence of the desired antibodies. Successful fusions will produce between 2000 and 5000 hybridomas colonies. Depending on the fusion, individual wells will become ready to screening over 2 to 6 day period. Typically, the first wells could be ready to screen in day 7 or 8, and most of the wells will need to be screened within the next 4 or 5 days. When you detected a possible positive clone, you could transfer hybrids of interest to 24-plates adding 1 ml of HAT medium (RPMI 1640) supplemented with serum at 20%. Cryopreserve each culture of cells when they have reached at least 3/4 confluency, 2 ampules/cell culture. Save the supernatants for further studies. Regarding to separate the interested cells of irrelevant cells, you must been do a limited diluted procedures. Ascitis production. To produce ascitis the number of cells depend of the every particular clone. Usually we inoculated ip between 1 to 2 x106 cells/ml/mice in PBS buffer. The animals must be inoculated intraperitonealy with Pristan (Sigma) or mineral oil using 0.5 ml per mice. The inoculation could be occurred 7 to 10 days before to inoculated the clone. The weight of the animals must be controlled in order to obtain better yield. The bioreactors are an alternative method to produce AcMs without it have not used animals models. IgG purification process on protein A columns. Mouse antibodies of the IgG1 subclass do not have a high affinity for protein A. Every subclass could be eluted at different peaks using a gradient pH. Usually we use 3M NaCl/1.5 M Gly pH 8.9 as a coupling buffer. For eluting IgGs we use 0.1M Citric Acid in a gradient pH (6 to IgG1, 5 to IgG2a or IgG2b, 4 IgG3). 1. Adjust a Sepharose Protein A (Pharmacia) beads using NaCl/1.5 M Gly pH 8.9 (coupling buffer). 2. Diluted the ascitis 1:10 in coupling buffer using a filter paper for remove the aggregations. 3. Pass the solution trough a Protein A bead column at a standarized flow according your equipment. The capacity of the Protein A beads for IgGl is approximately 5 mg/ml of wet beads. Ascitis contain between 1-10 mg/ml. 4. Wash the colums with 10 volumes of coupling buffer. 5. Elute the column with 0.1 M Citric Acid in a gradient pH starting at 6 to 4. Collect the eluate in appropriate tube, and identify the immunoglobulin-containing fractions by absorbance a 280 nm (1 DO = 0.8 mg/ml)

  15. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice

    Chow, Leola N.; Schreiner, Petra; Ng, Betina Y. Y.; Lo, Bernard; Hughes, Michael R.; Scott, R. Wilder; Gusti, Vionarica; Lecour, Samantha; Simonson, Eric; Manisali, Irina; Barta, Ingrid; McNagny, Kelly M.; Crawford, Jason; Webb, Murray; Underhill, T. Michael

    2016-01-01

    Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID:26998906

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

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

    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)

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

    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)

  19. Preparation, distribution, stability and tumour imaging properties of [62Zn] bleomycin complex in normal and tumour-bearing mice as a molecular pet generator

    PET is a powerful imaging technique with many advantages over single photon imaging. Nowadays, several positron emitter radioisotopes and their radio-labeled complexes have been developed for imaging. 62Zn/62Cu positron generator system has been widely proposed as a source of perfusion tracers (Green, 1987 and Green et al, 1988). In this study we have developed a 62Zn/62Cu-bleomycin tracer system as a biological generator for PET. The radiochemical separation of the 62Zinc (Neirinckx 1977) from natural copper target (electroplated over Ni layer) was carried out with a method described by (Green et al, 1990 and Okazawa et al, 1994) with slight modification. After dissolving of the irradiated target, solution was heated under a flow of nitrogen to dry up until a precipitate was formed. The precipitate was rinsed 2 times by distilled water (10 ml) and a portion of 2N HCl was added and mixed gently. The solution was pumped through a column 10x100mm filled with BioRad AG-1X8 resin and preconditioned with 2N HCl. For the elution of 62Zn in anion exchange resin, 0.005 N HCl was adopted instead of water used by (Green et al, 1990, Qaim 2001), because [62Zn] chloride form is suitable for the BLM labeling The samples were taken for the gamma spectroscopy analysis, using HPGe Canberra detector, in each steps. [62Zn]Zinc chloride (0.25-2.5 mCi) dissolved in acidic media obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted using HCl 1M and/or NaOH 1M (pH=1-7). The mixture was evaporated by slight warming, under a nitrogen flow. A mixture of BLM (0.25-2.5 mg,) in normal saline (0.1 mL) was then added. This mixture was heated at different temperatures (25, 50, 80 and 100 deg. C). The mixture was cooled in an ice bath and rapidly sent for use. The active solution was checked for radiochemical purity by polymer-backed silica gel layer using a mixture of ammonium acetate 10%-methanol as the mobile phase. These analyses were carried out every 30 min after labeling step. The final solution was then passed through a 0.22 m filter and pH adjusted to 5-7 by the addition of sodium acetate (1M) buffer. Pyrogen test was performed using a commercial LAL kit. Stability of [62Zn]BLM complex in final product and human/mice serum in vitro. A sample of [62Zn]BLM (0.5 mCi) was kept at room temperature for 48 hrs while checked by RTLC at various time intervals (2, 4, 8, 12 and 24). A micropipette sample (50 mL) was taken from the shaking mixture and the ratio of free radiozinc to [62Zn]BLM was checked by radio thin layer chromatography (eluent: 10% NH4OAc and methanol 1:1). The patterns for [62Zn]ZnCl2 and [62Zn]BLM were not changed in 24 hrs. Animal studies: Fibrosarcoma cells (about 104) of were injected SC to the dorsal area of Balb C mice weighing 20-25 g. After 14 days the tumour weighed 0.7 g and was not grossly necrotic. The distribution of [62Zn]-ZnCl2 and [62Zn]-BLM among tissues were determined for untreated mice and for mice with fibrosarcoma. A volume (0.1 ml) of final [62Zn]-BLM solution containing 20-40 uCi radioactivity (6 mg bleomycin in 50 mL) was injected into the dorsal tail vein. The total amout of radioactivity injected into each mouse was measured by counting the 1-ml syringe before and after injection in a radiometer with a fixed geometry. The animals were sacrificed by ether asyxphycation at selected times after injection, the tissues weighed and their specific activities determined with a gamma-ray scintillation as percentage of injected dose per gram of tissues (data not shown here) No unlabelled and/or labeled by-products were observed upon RTLC analysis of the final preparations. In contrast to other labeled bleomycins, [62Zn]bleomycin, has a lower half life causing less undesirable irradiation and it also benefits from PET radiopharmacutical advantages. Its rather higher half-life in contrast to other PET radioisotopes and high chemical stability of radiopharmaceutical form makes it a suitable possible PET tracer for use in neighborhood PET centers. [62Zn]-BLM can be used in PET oncology studies due to its suitable physical and chemical properties as a PET radiopharmaceutical

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

    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

  1. Superselection rules and quantum protocols

    We show that superselection rules do not enhance the information-theoretic security of quantum cryptographic protocols. Our analysis employs two quite different methods. The first method uses the concept of a reference system--in a world subject to a superselection rule, unrestricted operations can be simulated by parties who share access to a reference system with suitable properties. By this method, we prove that if an n-party protocol is secure in a world subject to a superselection rule, then the security is maintained even if the superselection rule is relaxed. However, the proof applies only to a limited class of superselection rules, those in which the superselection sectors are labeled by unitary irreducible representations of a compact symmetry group. The second method uses the concept of the format of a message sent between parties--by verifying the format, the recipient of a message can check whether the message could have been sent by a party who performed charge-conserving operations. By this method, we prove that protocols subject to general superselection rules (including those pertaining to non-Abelian anyons in two dimensions) are no more secure than protocols in the unrestricted world. However, the proof applies only to two-party protocols. Our results show in particular that, if no assumptions are made about the computational power of the cheater, then secure quantum bit commitment and strong quantum coin flipping with arbitrarily small bias are impossible in a world subject to superselection rules

  2. GDB: Group Distance Bounding Protocols

    Defrawy, Karim El; Tsudik, Gene

    2010-01-01

    Secure distance bounding (DB) protocols allow one entity, the verifier, to securely obtain an upper-bound on the distance to another entity, the prover. Thus far, DB was considered mostly in the context of a single prover and a single verifier. There has been no substantial prior work on secure DB in group settings, where a set of provers interact with a set of verifiers. The need for group distance bounding (GDB) is motivated by many practical scenarios, including: group device pairing, location-based access control and secure distributed localization. GDB is also useful in mission-critical networks and automotive computer systems. This paper addresses, for the first time, GDB protocols by utilizing the new passive DB primitive and the novel mutual multi-party GDB protocol. We show how they can be used to construct secure and efficient GDB protocols for various settings. We analyze security and performance of our protocols and compare them with existing DB techniques when applied to group settings.

  3. Lightweight Distance Bounding Protocol against Relay Attacks

    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.

  4. Sequential Rationality in Cryptographic Protocols

    Gradwohl, Ronen; Rosen, Alon

    2010-01-01

    Much of the literature on rational cryptography focuses on analyzing the strategic properties of cryptographic protocols. However, due to the presence of computationally-bounded players and the asymptotic nature of cryptographic security, a definition of sequential rationality for this setting has thus far eluded researchers. We propose a new framework for overcoming these obstacles, and provide the first definitions of computational solution concepts that guarantee sequential rationality. We argue that natural computational variants of subgame perfection are too strong for cryptographic protocols. As an alternative, we introduce a weakening called threat-free Nash equilibrium that is more permissive but still eliminates the undesirable ``empty threats'' of non-sequential solution concepts. To demonstrate the applicability of our framework, we revisit the problem of implementing a mediator for correlated equilibria (Dodis-Halevi-Rabin, Crypto'00), and propose a variant of their protocol that is sequentially r...

  5. Emergency department radiation accident protocol.

    Leonard, R B; Ricks, R C

    1980-09-01

    Every emergency department faces the potential problem of handling one or more victims of a radiation accident. While emergency departments near nuclear power plants or isotope production laboratories probably have a detailed protocol for such emergencies, a similar protocol is needed for the emergency department that may have to handle an isolated event, such as a vehicular accident that spills radioactive material and contaminates passengers or bystanders. This communication attempts to answer that need, presenting a step-by-step protocol for decontamination of a radiation victim, the rationale on which each step is based, a list of needed supplies, and a short summary of decorporation procedures that should be started in the emergency department. PMID:7425419

  6. Superposition Attacks on Cryptographic Protocols

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

    2011-01-01

    Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece of...... information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security of...... security is not possible. However, putting a natural constraint on the adversary, we show a non-trivial example of a protocol that can indeed be simulated....

  7. The Geneva Protocol of 1925

    This paper reports that when President Gerald Ford signed the instruments of ratification for the Geneva Protocol of 1925 on January 22, 1975, a tortured, half-century-long chapter in U.S. arms control policy was brought to a close. Fifty years earlier, at the Geneva Conference for the Control of the International Trade in Arms, Munitions and Implements of War, the United States had played a key role in drafting and reaching agreement on the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare. The protocol, signed by thirty nations, including the United States, on June 17, 1925, prohibits the use in war of asphyxiating, poisonous or other gases, and of all analogous liquids, materials or devices as well as the use of bacteriological methods of warfare

  8. Analyzing security of Authenticated Routing Protocol (ARAN)

    Seema Mehla; Bhawna Gupta; Preeti Nagrath

    2010-01-01

    Ad hoc network allow nodes to communicate beyond their direct wireless transmission range by introducing cooperation in mobile computer (nodes). Many proposed routing protocol for ad hoc network operate in an ad hoc fashion, as on demand routing protocol often have low overhead and faster reaction time than other type of routingbased on periodic protocol. However variety of attacks targeting routing protocol have been identified. By attacking the routing protocol attacker can absorb network t...

  9. Group Covariant Protocols for Quantum String Commitment

    Tsurumaru, Toyohiro

    2006-01-01

    We study the security of quantum string commitment (QSC) protocols with group covariant encoding scheme. First we consider a class of QSC protocol, which is general enough to incorporate all the QSC protocols given in the preceding literatures. Then among those protocols, we consider group covariant protocols and show that the exact upperbound on the binding condition can be calculated. Next using this result, we prove that for every irreducible representation of a finite group, there always ...

  10. Authentication and Key Agreement Protocols Preserving Anonymity

    Kumar V. Mangipudi; Katti, Rajendra S.; Huirong Fu

    2006-01-01

    Anonymity is a very important security feature in addition to authentication and key agreement features in communication protocols. In this paper, we propose two authentication and key agreement (AKA) protocols: the AKA protocol with user anonymity (UAP) and the AKA protocol with user and server anonymity (USAP). The proposed protocols have the following advantages: first of all, they preserve anonymity, which is a security feature that was ignored in most of the previously proposed AKA proto...

  11. SILC-A Secured Internet Chat Protocol

    ANINDITA SINHA; SAUGATA SINHA

    2013-01-01

    The Secure Internet Live Conferencing (SILC) protocol, a new generation chat protocol provides full featured conferencing services, compared to any other chat protocol. Its main interesting point is security which has been described all through the paper. We have studied how encryption and authentication of the messages in the network achieves security. The security has been the primary goal of the SILC protocol and the protocol has been designed from the day one security in mind. In this pap...

  12. The Kyoto protocol development; La viabilite du protocole de Kyoto

    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.)

  13. A protocol's life after attacks

    Bistarelli, Stefano

    2003-01-01

    In the analysis of security protocols, it is customary to stop as soon as we find and attack. Tons of ink can be spilled on whether an "attack" is really an attack, but it goes without saying that there is no life after that, hence no interest in continuing the analysis. If the protocol is broken, then we ought to fix it. Yet, fixing things is expensive and other measures may be more effective. In the physical world, most ATM safes would not resist heavy shelling with anti-tank bazookas, but ...

  14. Protocol biopsies for renal transplantation

    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.

  15. A Student Teamwork Induction Protocol

    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…

  16. Performance Evaluation of Security Protocols

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele; Degano, Pierpablo; Nielson, Flemming; Nielson, Hanne Riis; Priami, Corrado

    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use of...... possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  17. Bundle Security Protocol for ION

    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.

  18. IMPROVED SECURE ADDRESS RESOLUTION PROTOCOL

    Abhishek Samvedi

    2014-05-01

    Full Text Available In this paper, an improved secure address resolution protocol is presented where ARP spoofing attack is prevented. The proposed methodology is a centralised methodology for preventing ARP spoofing attack. In the proposed model there is a central server on a network or subnet which prevents ARP spoofing attack.

  19. A Student Teamwork Induction Protocol

    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…

  20. 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

    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)

  1. Modified oral metronidazole desensitization protocol.

    Gendelman, Samantha R; Pien, Lily C; Gutta, Ravi C; Abouhassan, Susan R

    2014-03-01

    The Center for Disease Control guidelines recommend desensitization to metronidazole in patients with trichomoniasis and hypersensitivity to metronidazole. There is only one published oral metronidazole desensitization protocol. The purpose of this study was to design a new, more gradual oral desensitization protocol to decrease systemic reactions that may occur when using the previously published protocol. We present two patients with presumed IgE-mediated allergy to metronidazole who underwent oral desensitization using our modified protocol. Case 1 was a 65-year-old woman with trichomoniasis who presented for metronidazole desensitization with a history of intraoperative anaphylaxis and positive skin tests to metronidazole. The patient tolerated six doses of the modified desensitization but developed systemic symptoms of nasal congestion and diffuse pruritus after the 25- and 100-mg doses. Both reactions were treated with intravenous (i.v.) antihistamines. Because of gastrointestinal irritation, the desensitization was completed at a dose of 250 mg orally every 6 hours. Case 2 was a 42-year-old woman with trichomoniasis and a history of hives immediately after administration of i.v. metronidazole who presented for desensitization. The patient had negative skin-prick and intradermal testing to metronidazole. She developed lip tingling and pruritus on her arms 15 minutes after the 10-mg dose. Fexofenadine at 180 mg was given orally and symptoms resolved. She tolerated the rest of the protocol without reaction and received a total dose of 2 g of metronidazole. Our oral metronidazole desensitization for presumed IgE-mediated reactions offers a second option for physicians wishing to use a more gradual escalation in dose. PMID:24612959

  2. Response of S180 murine tumor to bleomycin in combination with radiation and hyperthermia using micronucleus assay: a multimodality approach for therapeutic augmentation

    Response of a transplantable tumor, S180, grown intradermally in inbred Balb/c mice, was assessed by using micronucleus assay after treating the solid tumors with bleomycin (BLM), radiation (RT) and hyperthermia (HT) vis-a-vis multimodality approach. The frequency of micronuclei (MN) though did not vary greatly during the one week of observation in untreated tumors, it significantly increased in the drug and RT groups at 24 hr post-treatment. However, MN frequency was non-significant in the HT group from the control. A drug dose dependent linear increase in the frequency of MN induction was evident in 10, 15 and 20 mg/kg body weight BLM alone treated groups. Combination of radiation with BLM or HT further increased the MN counts in the bimodality groups. But, MN induction at 24 hr post-treatment in the tri- modality group (BLM+RT+HT) was non-significant from that of the bimodality treatments. However, the tumors treated with trimodality treatment presented severe tumor necrosis, indicating increased cell loss, and resulting in immediate tumor regression. In all the bi-modality groups MN counts though declined 3 or 5 days post-treatment, the values remained significantly higher than the control, on day 7 post-treatment. Micronucleus assay could be used as a predictive parameter for the assessment of post-irradiation tumor regression response. However, the tumor response assessment with MN assay alone may not be sufficient and the role of other parameters, such as apoptosis and necrosis, in immediate tumor regression, especially radiosensitive/thermosensitive tumors can not be ignored while taking multi modality approach into consideration for cancer therapy. (author)

  3. Celastrol enhances Nrf2 mediated antioxidant enzymes and exhibits anti-fibrotic effect through regulation of collagen production against bleomycin-induced pulmonary fibrosis.

    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

  4. Atomic resolution structure of EhpR: phenazine resistance in Enterobacter agglomerans Eh1087 follows principles of bleomycin/mitomycin C resistance in other bacteria

    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.

  5. Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor β1 level.

    Asghari, Mohammad Hossein; Hobbenaghi, Rahim; Nazarizadeh, Ali; Mikaili, Peyman

    2015-01-01

    Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-β1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into six groups, including: (I) positive (BLM) control group, (II) negative (normal saline) control group, (III) sham group (R. sativus extract 150 mg/kg), and (IV-VI) treatment groups. In order to induce pulmonary fibrosis, four groups were treated with a single dose of BLM sulfate (7.5 U/kg) through intratracheal instillation. Treatment groups (IV-VI) received RSN extract (75, 150, and 300 mg/kg) orally a week before and two weeks after the administration of BLM. At the end of the treatment course, blood and lung tissue samples were taken and the measurement of TGF-β1 and histopathological examination of the lung tissues performed. The results showed that RSN, at 300 mg/kg dose, could significantly decrease the serum level of TGF-β1 and severity of the histological lesions as compared to the positive control group. The results of the current study indicate that the components present in the extract can remarkably prevent the aggravation of pulmonary fibrosis via decreasing TGF-β1 level. PMID:26752991

  6. Improvement In MAODV Protocol Using Location Based Routing Protocol

    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.

  7. Session Initiation Protocol Attacks and Challenges

    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.

  8. Using Ovsynch protocol versus Cosynch protocol in dairy cows

    Ion Valeriu Caraba

    2013-10-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 As a research on the reproductive physiology and endocrinology surrounding the estrous cycle in dairy cattle has been compiled, several estrous synchronization programs have been developed for use with dairy cows. These include several programs that facilitate the mass breeding of all animals at a predetermined time (timed-AI rather than the detection of estrus. We studied on 15 dary cows which were synchronized by Ovsynch and Cosynch programs. The estrus response for cows in Ovsynch protocol was of 63%. Pregnancy per insemination at 60 days was of 25%. Estrus response for cow in Cosynch protocol was of 57%. Pregnancy per insemination at 60 days was of 57%. Synchronization of ovulation using Ovsynch protocols can provide an effective way to manage reproduction in lactating dairy cows by eliminating the need for estrus detection. These are really efficient management programs for TAI of dairy cows that are able to reduce both the labour costs and the extra handling to daily estrus detection and AI. 

  9. Chapter 14: Chiller Evaluation Protocol

    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).

  10. Neonatal euthanasia: The Groningen Protocol*

    Vizcarrondo, Felipe E.

    2014-01-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  11. Neonatal euthanasia: The Groningen Protocol.

    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

  12. On using Mobile IP Protocols

    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.

  13. CDTP Chain Distributed Transfer Protocol

    Vagner, S

    2004-01-01

    The rapid growth of the internet in general and of bandwidth capacity at internet clients in particular poses increasing computation and bandwidth demands on internet servers. Internet access technologies like ADSL [DSL], Cable Modem and Wireless modem allow internet clients to access the internet with orders of magnitude more bandwidth than using traditional modems. We present CDTP a distributed transfer protocol that allows clients to cooperate and therefore remove the strain from the internet server thus achieving much better performance than traditional transfer protocols (e.g. FTP [FTP]). The CDTP server and client tools are presented also as well as results of experiments. Finally a bandwidth measurement technique is presented. CDTP tools use this technique to differentiate between slow and fast clients.

  14. From protocol to published report

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

    2016-01-01

    published reports of academic clinical drug trials. METHODS: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory...... 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39 % of the trials (95 % CI: 29 to 49 %). Randomized controlled trials (RCTs) constituted 72 % (95 % CI: 63 to...... 81 %) 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....

  15. Kioto protocol; Protocolo de Kioto

    Romero, A.

    2005-07-01

    Atmospheric contamination by greenhouse gases is a global problem, and thus its solution requires global measures. Although the consequences of climate change are questioned and the foreseeable effects are not excessively serious, there are plenty of scientific reasons for all countries to make the necessary efforts to meet the objectives established by the Kyoto Protocol of reducing the six greenhouse gases over the period 2008-2012. Therefore, it seems essential that we understand the nature of the transformation that are occurring in the different systems, what changes they are causing and what costs they incur. Independently of its effectiveness and realism, the Kyoto Protocol is the first regulatory step in the direction of globalization in the environmental field. (Author)

  16. DSTC Layering Protocols in Wireless Cooperative Networks

    Elamvazhuthi, P S; Dey, B K

    2008-01-01

    In adhoc wireless relay networks, layers of relays are used to communicate from a source to a destination to achieve better reliability. In this paper, we consider five protocols derived from an earlier proposed protocol, where the relays do a simple processing before transmitting and as a result achieve distributed space-time code. Four of the protocols discussed utilize more complicated relaying schemes than simple layered protocols proposed in earlier literature. We have analyzed the effectiveness of these protocols in various power loss configurations among the paths. Optimum power allocation of the total power among various transmissions have been found by reasonable fine search for all the protocols. Bit error rate plots are compared under optimum power allocation for these protocols. From the simulation results, we draw some guidelines as to which protocol is good for what kind of environment.

  17. Database communication protocol analyses and security detection

    In this paper we introduced the analysis of TDS protocol in the communication application between Client and Server about SYBASE and MICROSOFT SQL SERVER and do some test for some bugs existed in the protocol. (authors)

  18. Analysing Protocol Stacks for Services

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

    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...... 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....

  19. Cost estimation of Kyoto Protocol

    This article proposes a reflection on important aspects in the costs determination performance of Kyoto Protocol. The evaluation of the main models evidence possible impacts on the economies. A key role in the determination of the cost is represented by the relative hypothesis to emission trading and the projects CDM-JI and from the political capacity at the cost negative or equal to zero

  20. Bounding Component Behavior via Protocols

    Plášil, František; Višňovský, Stanislav; Besta, Miloslav

    Los Alamitos : IEEE Computer Society, 1999 - (Firesmith, D.; Riehle, R.; Pour, G.; Meyer, B.), s. 387-398 ISBN 0-7695-0278-4. [TOOLS /30./. Santa Barbara (US), 01.08.1999-05.08.1999] R&D Projects: GA AV ČR IAA2030902; GA ČR GA201/99/0244 Institutional research plan: AV0Z1030915 Keywords : software components * behavior protocols * software architecture Subject RIV: JC - Computer Hardware ; Software

  1. Power Control Protocols in VANET

    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.

  2. Building America House Simulation Protocols

    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.

  3. Performance Evaluation of Security Protocols

    Genge, Bela; Haller, Piroska

    2009-01-01

    We propose a comparative performance evaluation of security protocols. The novelty of our approach lies in the use of a polynomial mathematical model that captures the performance of classes of cryptographic algorithms instead of capturing the performance of each algorithm separately, approach that is used in other papers. A major advantage of using such a model is that it does not require implementation-specific information, because the decision is based on comparing the estimated performanc...

  4. Petri Nets in Cryptographic Protocols

    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...... how the Petri-net semantics can be used to prove security properties....

  5. Heuristic Methods for Security Protocols

    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.

  6. Heuristic Methods for Security Protocols

    Qurat ul Ain Nizamani

    2009-10-01

    Full Text Available 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.

  7. Privacy Protection for Authentication Protocols

    Poettering, Bertram

    2012-01-01

    In our highly computerized and networked society, privacy of individuals is precious and becomes increasingly important. Problems particularly arise in the context of authentication protocols where, as a general rule, entities actively reveal their respective identities to each other. To encounter this issue, different privacy-preserving authentication methods have been developed in the last decades. The list of these techniques comprises, apart from identity escrow, ring authenticat...

  8. Active Virtual Network Management Protocol

    Bush, Stephen F.

    1999-01-01

    This paper introduces a novel algorithm, the Active Virtual Network Management Protocol (AVNMP), for predictive network management. It explains how the AVNMP facilitates the management of an active network by allowing future predicted state information within an active network to be available to network management algorithms. This is accomplished by coupling ideas from optimistic discrete event simulation with active networking. The optimistic discrete event simulation method used is a form o...

  9. Cryptanalysis of an Authentication Key Exchange Protocol

    Chou-Chan Yang; Ya-Wen Yang; Ting-Yi Chang

    2005-01-01

    An authenticated multiple-key agreement protocol uses a digital signature to sign the Diffie-Hellman public keys which can generate multiple session key in a single round of message exchange and achieve mutual authentication. Recently, Hwang et al. proposed an authentication key exchange protocol which takes less computation time than Harn and Lin;s protocol. However, this study, shows that Hwang et al.`s protocol is vulnerable to forgery attacks. An attacker can fool one communication part i...

  10. An Analysis on Implementation of Leach Protocol

    Ms. Mondakini Dihingia; Mr. Santosh Ranadev; A. Shobha Rani

    2014-01-01

    Wireless sensor network consists of set of sensor nodes which is widely used in monitoring purposes. In order to increase the wireless sensor network life time various protocol was developed. In this paper presents a comparative analysis among various protocols to reduce energy consumption within the wireless sensor network. Here we typically analysis leach protocol and is various drawback and how these drawback are used to implement V-LEACH protocol

  11. Automatic Verification of Security Protocols Using Approximations

    Boichut, Yohan; Héam, Pierre-Cyrille; Kouchnarenko, Olga

    2005-01-01

    Security protocols are widely used in open modern networks to ensure safe communications. It is now recognized that formal analysis can provide the level of assurance required by both developers and users of the protocols. Unfortunately it is generally undecidable to certify whether a protocol is safe or not. However the automatic verification of security protocols can be attempted using abstraction-based approximation. For this purpose, tree automata approximations were introduced by Genet a...

  12. Analysis of Security Protocols as Open Systems

    MARTINELLI, Fabio

    2001-01-01

    We propose a methodology for the formal analysis of security protocols. This originates from the observation that the verification of security protocols can be conveniently treated as the verification of {em open} systems, i.e. systems which may have unspecified components. These might be used to represent a hostile environment wherein the protocol runs and whose behavior cannot be predicted a priori. We define a language for the description of security protocols, namely Crypto-CCS, and a log...

  13. More Robust Multiparty Protocols with Oblivious Transfer

    Mueller-Quade, J.; Imai, H

    2001-01-01

    With oblivious transfer multiparty protocols become possible even in the presence of a faulty majority. But all known protocols can be aborted by just one disruptor. This paper presents more robust solutions for multiparty protocols with oblivious transfer. This additional robustness against disruptors weakens the security of the protocol and the guarantee that the result is correct. We can observe a trade off between robustness against disruption and security and correctness. We give an appl...

  14. Approaches to Formal Verification of Security Protocols

    Lal, Suvansh; Jain, Mohit; Chaplot, Vikrant

    2011-01-01

    In recent times, many protocols have been proposed to provide security for various information and communication systems. Such protocols must be tested for their functional correctness before they are used in practice. Application of formal methods for verification of security protocols would enhance their reliability thereby, increasing the usability of systems that employ them. Thus, formal verification of security protocols has become a key issue in computer and communications security. In...

  15. A New Evaluation Model for Security Protocols

    Xuewen DONG; Ma, Jianfeng; Yang, Chao

    2011-01-01

    Till today, the study of performance of security protocols of WLAN has been one of research focuses. Whereas, owing to enormous complexity and low efficiency of modeling security protocols, there has been by now no uniform method or technology that can be used generally to simulate and evaluate security protocols, and no simulation system available that can well support research on performance of security protocols. So in view of the status quo, we, in this paper, mainly propose a novel secur...

  16. SECURITY PROTOCOL COMPOSITION FOR WEB SERVICES

    Genge Bela; Haller Piroska

    2009-01-01

    The composition method, security protocol specification and middleware, developed in our previous work, are used in the process of composing Web services that use heterogeneous security protocols. Existing solutions rely on using standard security protocols that must be implemented by all Web services for the composition to be successful. This way, services implementing new protocols can not be composed with existing ones. This is why, the main contribution of the paper is the integration of ...

  17. Automated Unbounded Verification of Security Protocols

    Chevalier, Yannick; Vigneron, Laurent

    2002-01-01

    We present a new model for automated verification of security protocols, permitting the use of an unbounded number of protocol runs. We prove its correctness, completeness and also that it terminates. It has been implemented and its efficiency is clearly shown by the number of protocols successfully studied. In particular, we present an attack previously unreporte- d on the Denning-Sacco symmetric key protocol.

  18. Authenticated Key Agreement Protocols: A Comparative Study

    Areej Omar Baalghusun; Olfa Fahad Abusalem; Zahra Abbas Al Abbas; Jayaprakash Kar

    2014-01-01

    One of the most important and challenging cryptographic primitives in Public Key Cryptography is Key Agreement Protocol where two or more parties share secret values and establish the session key. Many authors have proposed key agreement protocols. In this article, we have viewed some authenticated Key Agreement Protocols and presented a comparative study. We have also described the design principle, security requirement and various attacks on Key Agreement Protocol.

  19. Crypto-Verifying Protocol Implementations in ML

    Bhargavan, K.; Corin, R.J.; Fournet, C.

    2007-01-01

    We intend to narrow the gap between concrete implementations and verified models of cryptographic protocols. We consider protocols implemented in F#, a variant of ML, and verified using CryptoVerif, Blanchet's protocol verifier for computational cryptography. We experiment with compilers from F# code to CryptoVerif processes, and from CryptoVerif declarations to F# code. We present two case studies: an implementation of the Otway-Rees protocol, and an implementation of a simplified password-b...

  20. A father protocol for quantum broadcast channels

    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.

  1. 07421 Executive Summary -- Formal Protocol Verification Applied

    Chen, Liqun; Kremer, Steve; Ryan, Mark D.

    2008-01-01

    Security protocols are a core part of distributed computing systems, and are part of our everyday life since they are used in web servers, email, mobile phones, bank transactions, etc. However, security protocols are notoriously difficult to get right. There are many cases of protocols which are proposed and considered secure for many years, but later found to have security flaws. Formal methods offer a promising way for automated security analysis of protocols. While the...

  2. Asymptotic adaptive bipartite entanglement distillation protocol

    Hostens, Erik; Dehaene, Jeroen; De Moor, Bart

    2006-01-01

    We present a new asymptotic bipartite entanglement distillation protocol that outperforms all existing asymptotic schemes. This protocol is based on the breeding protocol with the incorporation of two-way classical communication. Like breeding, the protocol starts with an infinite number of copies of a Bell-diagonal mixed state. Breeding can be carried out as successive stages of partial information extraction, yielding the same result: one bit of information is gained at the cost (measuremen...

  3. Instability Free Routing: Beyond One Protocol Instance

    Le, F.; Zhang, H; Xie, Geoffrey

    2008-01-01

    Today, a large body of research exists regarding the correctness of routing protocols. However, many reported global diisruptions of Internet connectivity, e.g., inter-AD persistent loops, cannot be explained by looking at a eingle routing protocol at a time. In fact, these anomalies have long been suspected in the operator community to be caused by the interactions between routing protocols. The interactions between protocol instances are governed by two proceduress at the boeder routers:...

  4. A father protocol for quantum broadcast channels

    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...

  5. Bioinspired Security Analysis of Wireless Protocols

    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...

  6. Static Validation of a Voting Protocol

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

    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...

  7. Real Study of Host Identity Protocol

    Gaurav Malik

    2014-05-01

    Full Text Available Host Identity Protocol(HIP[22,25] is a proposed protocol for providing security,mobility and multihoping to the current internet architecture. HIP establishes a new name space of Host identities(HI for representing hosts independent of their locations in the network. By contrast, the current architecture uses internet protocol(IP addresses to identify hosts.

  8. 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

    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

  9. Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars Resultados de uma combinação de bleomicina e triamcinolone acetonide no tratamento de quelóides e cicatrizes hipertróficas

    Francisco Miguel Camacho-Martínez

    2013-06-01

    Full Text Available While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA. In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29% softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids. The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de bleomicina e acetonido de triancinolona por cm2 (BAT. Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29% amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores. O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados.

  10. Password-Based Key Agreement Protocol

    Chunbo Ma

    2007-01-01

    Full Text Available In this study, we will review Kim et al.’s protocol and Lee et al.’s protocol respectively and show that their protocols are not secure as they have claimed. Then, we firstly present our improved password-based key agreement protocol based on Kim et al.’s scheme and show that it withstands password guessing attack and illegal modification. Then we propose an improved Verifier-based key agreement protocol based on Lee et al.’s scheme and demonstrate that it is secure against Stolen-verifier attack and password guessing attack.

  11. Password-Based Key Agreement Protocol

    Chunbo Ma; Jun Ao; Jianhua Li

    2007-01-01

    In this study, we will review Kim et al.’s protocol and Lee et al.’s protocol respectively and show that their protocols are not secure as they have claimed. Then, we firstly present our improved password-based key agreement protocol based on Kim et al.’s scheme and show that it withstands password guessing attack and illegal modification. Then we propose an improved Verifier-based key agreement protocol based on Lee et al.’s scheme and demonstrate that it is secure against Stolen-verifier at...

  12. Simple and Efficient Contract Signing Protocol

    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.

  13. Tool Supported Analysis of Web Services Protocols

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

    We describe an abstract protocol model suitable for modelling of web services and other protocols communicating via unreliable, asynchronous communication channels. The model is supported by a tool chain where the first step translates tables with state/transition protocol descriptions, often used...... e.g. in the design of web services protocols, into an intermediate XML format. We further translate this format into a network of communicating state machines directly suitable for verification in the model checking tool UPPAAL. We introduce two types of communication media abstractions in order to...... ensure the finiteness of the protocol state-spaces while still being able to verify interesting protocol properties. The translations for different kinds of communication media have been implemented and successfully tested, among others, on agreement protocols from WS-Business Activity....

  14. The Simplest Protocol for Oblivious Transfer

    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...... elements), and 2mn ciphertexts. We also report on an implementation of the protocol using elliptic curves, and on a number of mechanisms we employ to ensure that our software is secure against active attacks too. Experimental results show that our protocol (thanks to both algorithmic and implementation...... optimizations) is at least one order of magnitude faster than previous work. Category / Keywords: cryptographic protocols / Oblivious Transfer, UC Security, Elliptic Curves, Efficient Implementation...

  15. Desynchronization Attacks on RFID Security Protocols

    Miaolei Deng

    2013-02-01

    Full Text Available The characteristics of radio frequency identification (RFID systems introduce growing security and privacy concerns. RFID systems need security protocols to provide confidentiality, user privacy, mutual authentication and etc. Many security protocols for the RFID system have been presented. This paper analyze several of the newest RFID security protocols which proposed by Niu et al., Fu et al. and Habibi et al. respectively form the security viewpoint of data desynchronization attack. These lightweight protocols were expected to proposed security protections for the RFID system and safeguard against almost all major attacks. However, we found that these RFID security protocols were vulnerable to the attack of data desynchronization. Based on strand spaces model, data desynchronization attacks on these protocols were analyzed and described. Furthermore, improvements to overcome the security vulnerabilities of two protocols presented by Niu et al. and Fu et al. were given.

  16. Effective Protocols for Mobile Communications and Networking

    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.

  17. Developing security protocols in χ-Spaces

    Crazzolara, Federico; Milicia, Giuseppe

    It is of paramount importance that a security protocol effectively enforces the desired security requirements. The apparent simplicity of informal protocol descriptions hides the inherent complexity of their interactions which, often, invalidate informal correctness arguments and justify the effort...... of formal protocol verification. Verification, however, is usually carried out on an abstract model not at all related with a protocol’s implementation. Experience shows that security breaches introduced in implementations of successfully verified models are rather common. The χ-Spaces framework is...... an implementation of SPL (Security Protocol Language), a formal model for studying security protocols. In this paper we discuss the use of χ-Spaces as a tool for developing robust security protocol implementations. To make the case, we take a family of key-translation protocols due to Woo and Lam and...

  18. Language, Semantics, and Methods for Security Protocols

    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...... events. Methods like strand spaces and the inductive method of Paulson have been designed to support an intensional, event-based, style of reasoning. These methods have successfully tackled a number of protocols though in an ad hoc fashion. They make an informal spring from a protocol to its...

  19. Asymptotic adaptive bipartite entanglement distillation protocol

    Hostens, E; Dehaene, J; Dehaene, Jeroen; Hostens, Erik; Moor, Bart De

    2006-01-01

    We present a new asymptotic bipartite entanglement distillation protocol that outperforms all existing asymptotic schemes. This protocol is based on the breeding protocol with the incorporation of two-way classical communication. Like breeding, the protocol starts with an infinite number of copies of a Bell-diagonal mixed state. Breeding can be carried out as successive stages of partial information extraction, yielding the same result: one bit of information is gained at the cost (measurement) of one pure Bell state pair (ebit). The basic principle of our protocol is at every stage to replace measurements on ebits by measurements on a finite number of copies, whenever there are two equiprobable outcomes. In that case, the entropy of the global state is reduced by more than one bit. Therefore, every such replacement results in an improvement of the protocol. We explain how our protocol is organized as to have as many replacements as possible. The yield is then calculated for Werner states.

  20. Generalized routing protocols for multihop relay networks

    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.

  1. Efficient ID-based authentication and key agreement protocols for the session initiation protocol

    KILINÇ, Hacı Hakan; ALLABERDİYEV, Yolguly; YANIK, Tuğrul

    2015-01-01

    In a widely deployed VoIP system tens of thousands of clients compete for the SIP proxy server's authentication service. SIP protocol implementations have to meet certain QoS and security requirements. In this study new ID-based protocols are proposed for the SIP authentication and key agreement protocols. These protocols minimize the use of expensive pairing functions but still resist notable attacks. The security of the proposed protocols are analyzed and demonstrated with security pro...

  2. INEEL AIR MODELING PROTOCOL ext

    C. S. Staley; M. L. Abbott; P. D. Ritter

    2004-12-01

    Various laws stemming from the Clean Air Act of 1970 and the Clean Air Act amendments of 1990 require air emissions modeling. Modeling is used to ensure that air emissions from new projects and from modifications to existing facilities do not exceed certain standards. For radionuclides, any new airborne release must be modeled to show that downwind receptors do not receive exposures exceeding the dose limits and to determine the requirements for emissions monitoring. For criteria and toxic pollutants, emissions usually must first exceed threshold values before modeling of downwind concentrations is required. This document was prepared to provide guidance for performing environmental compliance-driven air modeling of emissions from Idaho National Engineering and Environmental Laboratory facilities. This document assumes that the user has experience in air modeling and dose and risk assessment. It is not intended to be a "cookbook," nor should all recommendations herein be construed as requirements. However, there are certain procedures that are required by law, and these are pointed out. It is also important to understand that air emissions modeling is a constantly evolving process. This document should, therefore, be reviewed periodically and revised as needed. The document is divided into two parts. Part A is the protocol for radiological assessments, and Part B is for nonradiological assessments. This document is an update of and supersedes document INEEL/INT-98-00236, Rev. 0, INEEL Air Modeling Protocol. This updated document incorporates changes in some of the rules, procedures, and air modeling codes that have occurred since the protocol was first published in 1998.

  3. Planetary Protection Alternate Protocol Certification

    Baker, Amy; Barengoltz, Jack; Tisdale, David

    The talk presents a standardized approach for new method certification or alterative testing protocol (ATP) certification against the existing U.S. Planetary Protection Standards. In consideration of new method certification there are two phases of activities that are relevant to the certification process. The first is sample acquisition which typically incorporates swab or wipes sampling on relevant hardware, associated facilities and ground support equipment. The sampling methods introduce considerations of field sampling efficiency as it relates to spore distribution on the spacecraft, spacecraft material influences on the ability of the swab or wipe to remove spores from the hardware, the types of swabs and wipes used (polyester, cotton, macrofoam), and human sampling influences. The second portion of a new protocol certification looks specifically at the lab work-up or analysis of the samples provided to the laboratory. Variables in this process include selection of appropriate biomarkers, extraction efficiencies (removal of spores or constituents of interest from the sampling device), and a method's ability to accurately determine the number of spores present in the sample with a statistically valid level of confidence as described by parameters such as precision, accuracy, robustness, specificity and sensitivity. Considerations for alternative testing protocols such as those which utilize bioburden reduction techniques include selection of appropriate biomarkers for testing, test materials and a defined statistical approach that provides sufficient scientific data to support the modification of an existing NASA specification or the generation of a new NASA specification. Synergies between the U.S. and European Space Agency approaches will also be discussed.

  4. New Models for Population Protocols

    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

  5. Internet protocol television (IPTV) services

    Nuuri, Aminullah

    2011-01-01

    The purpose of this thesis is to know what IPTV is and how the IPTV network architectures work. The role of IPTV is to deliver video, audio and data commonly called triple play services over an IP network. This thesis describes how video on demand (VOD) shows its relation to the IPTV and introduces unicast and multicast services, IPTV protocols such as RTP and RSTP, IPTV set-top box and some other common ways of this particular technology. It also demonstrates how the Sonera IPTV system deliv...

  6. Recursive Ping-Pong Protocols

    Huttel, Hans; Srba, Jiri

    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...... and bisimulation checking. Our main result is that our channel-free and memory-less calculus is Turing powerful, assuming that at least three principals are involved. We also investigate the expressive power of the calculus in the case of two participants. Here, our main results are that reachability...

  7. Trypanosoma spp. ring test protocol

    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

  8. Optical protocols for terabit networks

    Chua, P. L.; Lambert, J. L.; Morookian, J. M.; Bergman, L. A.

    1991-01-01

    This paper describes a new fiber-optic local area network technology providing 100X improvement over current technology, has full crossbar funtionality, and inherent data security. Based on optical code-division multiple access (CDMA), using spectral phase encoding/decoding of optical pulses, networking protocols are implemented entirely in the optical domain and thus conventional networking bottlenecks are avoided. Component and system issues for a proof-of-concept demonstration are discussed, as well as issues for a more practical and commercially exploitable system. Possible terrestrial and aerospace applications of this technology, and its impact on other technologies are explored. Some initial results toward realization of this concept are also included.

  9. A Streaming Protocol for Memcached

    Li, W.; Zhou, B.; Wang, X.

    2012-01-01

    Memcached is a general-purpose distributed memory caching system that was originally developed by Danga Interactive for Live Journal but is now used by many other sites and It is thought to be one of the most effective solutions to speed up dynamic database-driven websites by caching data and objects in RAM to reduce the number of times that an external data source must be read. Memcached system uses a client-server architecture, it provides its standard memcached protocol to support any type...

  10. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.; Rørth, Mikkel; Daugaard, Gedske; Hojman, Pernille

    2014-01-01

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective of...

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

    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.

  12. Optimization of Collection Tree Protocol

    Harleen Kaur

    2013-06-01

    Full Text Available Collection tree protocol is a tree based protocol which is mainly used for aggregation. It is minimum cost routing tree which selects the path having minimum cost routing gradient. It will generate one or more trees to root which is called base station. When any node has data it sends data up the tree which is forwarded to root.CTP will provide link quality estimation among nearby neighbours. It will indicate number of transmissions from a node to send a packet to destination and whose acknowledgment is successfully received. It sends data to root by choosing a next hop. CTP is having a problem of fast energy depletion which is caused by congestion in the network. Also energy level of the network is not highly scalable. Whenever a node in a network is failed it is not able to do the function and it should not effect on overall network. When more number of nodes are added in the network, congestion will take place and so it does not have an additional energy to choose an optimal path. In revised CTP, to enhance the energy level of a network RSSI is used in broadcast fault tolerant algorithm. RSSI means power received by antenna. CTP suffers a problem by disseminating data statically in network. So in revised CTP line mobility model is integrated which will send data dynamically to sink node.

  13. Implementation of the Kyoto protocol

    The Rio Earth summit in 1992 has been the starting point of an international awareness about the global risk of climatic change. At this occasion, the richest countries committed themselves to stabilize their greenhouse gas emissions and to reach by the year 2000 an emissions level equivalent to the one of 1990. The Kyoto protocol in 1997 has permitted to convert this will into juridically constraining quantitative commitments. In 2005, Russia ratified the protocol while in 2001 the USA refused to do so. Because the commitments signed are ambitious, flexibility mechanisms have been implemented: 'emission permits' (emissions trading), 'joint implementation' allowing the investments abroad for greenhouse gases abatement in another developed country, and 'clean development mechanisms' when investments are made in a developing country. The Marrakech conference of December 2001 has permitted to fix up the eligibility criteria of projects belonging to the joint implementation and clean development mechanisms. The effective implementation of these mechanisms still raises technical difficulties to evaluate and measure the effective abatement of greenhouse gas emissions. (J.S.)

  14. Latest approaches of Kyoto protocol

    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)

  15. Telomerase Repeated Amplification Protocol (TRAP)

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al., 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC- counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al., 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is analyzed by electrophoresis. TSNT is, an internal standard control, amplified by TS primer. NT is its own reverse primer, which is not a substrate for telomerase. These primers are used to identify false-negative results by if the gel lacks internal control bands.

  16. VANET Routing Protocols: Pros and Cons

    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.

  17. Automation of Network Protocol Analysis

    keerthi Manchikanti, J Shiva Prashanth, Vishnu Murthy G

    2012-06-01

    Full Text Available This paper “Automation of Network Protocol Analysis” is mainly aimed to automate the entire process. Starting from sniffing the network packets till the validation of it has been taken care. Here we have automated the logging part through a C program. Whenever packets will be transmitted from a system, Ethereal/Wireshark will be automatically invoked and start capturing the network packets. That will be stored in .pcap format automatically. To validate the contents the logic has been implemented to check particular pattern of packets or any specific string. The .pcap format will be converted into a text format so that the validation can be accomplished through parsing the entire Ethereal/Wireshark log. Based upon the parsing logic, pass/fail verdict will be indicated to user. The logic can always be extended depending upon the project requirements. The performance of the network is also calculated.

  18. Secure Multi-Player Protocols

    Fehr, Serge

    While classically cryptography is concerned with the problem of private communication among two entities, say players, in modern cryptography multi-player protocols play an important role. And among these, it is probably fair to say that secret sharing, and its stronger version verifiable secret...... (captured by the term threshold cryptography). The latter allows—at least in principle—to execute any collaboration among a group of players in a secure way that guarantees the correctness of the outcome but simultaneously respects the privacy of the participants. In this work, we study three aspects of...... the (mathematical) representation of the task that needs to be securely executed. (3) We propose a unified treatment of perfectly secure linear VSS and distributed commitments (a weaker version of the former), and we show that the security of such a scheme can be reduced to a linear algebra condition...

  19. Fetal MRI: techniques and protocols

    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.)

  20. Fetal MRI: techniques and protocols

    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.)