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

Scientific Electronic Library Online (English)

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

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

2006-11-01

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[A case of pneumomediastinum during BEP (bleomycin, etoposide, cisplatin) chemotherapy for testicular cancer].  

Science.gov (United States)

We report a case of drug-induced pneumomediastinum by bleomycin in testicular cancer, which is extremely rare ; to our knowledge, only 3 cases have been reported. A 28-year-old man presented with a left testicular mass. He underwent radical left inguinal orchiectomy that demonstrated a seminoma, pT3N0M0. Ten months after surgery, para-aortic lymph node metastasis appeared, and he received three cycles of bleomycin, etoposide and cisplatin (BEP) chemotherapy. On day 13 of the fourth course of BEP, he complained of snowball crepitation of the neck and computed tomography revealed subcutaneous emphysema, extensive mediastinal air, and intraspinal air accumulation without pneumothorax. The pneumomediastinum and subcutaneous emphysema tended to deteriorate until 15 days after the onset of pneumomediastinum, but fortunately he had no signs or symptoms of infection. These findings resolved spontaneously after 1 month. PMID:23995535

Noguchi, Go; Ota, Junichi; Ishigaki, Hanako; Onuki, Tatsuaki; Kato, Yoshitake; Moriyama, Masatoshi

2013-08-01

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Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis.  

Science.gov (United States)

Cytotoxic anticancer chemotherapy affects pituitary-testicular hormonal axis in humans and in animals. This study investigated the effects on Leydig cells of three cycles of bleomycin, etoposide and cisplatin (0.75, 7.5, and 1.5mg/kg, respectively; BEP) chemotherapy in rat testis. The chemotherapy has induced hyperplasia of and degenerative changes in Leydig cells at the end of BEP exposure, which remained so even after a recovery time of 63 days. The increased testicular oxidative stress at the end of the chemotherapy returned to normal level after the recovery time. The chemotherapy has stimulated the transcription of scavenger receptor class type-B1 (SCARB1), steroidogenic acute-regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), CYP17A1, and inhibited that of 17?-hydroxysteroid dehydrogenase (HSD17B6) and CYP19A1 in association with increased cholesterol and decreased testosterone levels. Even after the recovery time, the chemotherapy still had inhibitory effects on the transcription of all of the above genes in addition to luteinizing hormone receptor and HSD3B1, but not on the StAR gene. The cholesterol and testosterone levels also did not show any significant differences with the control group. The decreased testosterone level at the end of chemotherapy was probably due to inhibition of HSD3B1 and HSD17B6 genes. In conclusion, clinically relevant dose-levels and treatment protocols of BEP chemotherapy adversely affect Leydig cell function. The BEP chemotherapy inhibits the transcription of steroidogenic enzymes and that these effects sustain over an extended period of time without returning to normal levels. PMID:25523482

Al-Bader, Maie; Kilarkaje, Narayana

2015-01-15

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Basic Education and Policy Support (BEPS) Activity.  

Science.gov (United States)

The Basic Education and Policy Support (BEPS) Activity is a multi-year, worldwide, indefinite quantity contract by which the U.S. Agency for International Development (USAID) Global Bureau Center for Human Capacity (G/HCD) can work to achieve four objectives: (1) improve the quality, efficiency, access, and equity of education, particularly basic…

Creative Associates International, Inc., Washington, DC.

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Status of 174 MHz RF system for BEP  

International Nuclear Information System (INIS)

The new RF system for the BEP storage ring (which is an injector of VEPP-2000 accelerating complex) will increase the particles energy in the BEP from 0.9 to 1 GeV. RF system operates at a frequency of 174 MHz and consists of an accelerating cavity, RF power generator and control system.

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Bleomycin-induced flagellate dermatitis  

Scientific Electronic Library Online (English)

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

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

2014-07-01

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Effect of bleomycin-radiotherapy combination in management of head and neck squamous cell carcinoma  

International Nuclear Information System (INIS)

Twenty-five patients with head and neck squamous cell carcinoma were treated with bleomycin-radiotherapy protocol, 15 mg bleomycin I.V. on alternate days followed by radiation within half an hour. The average total dose of bleomycin was 150 mg. Radiotherapy was given daily. Two patients were lost to follow-up very early in the course of the treatment and were removed from the study for statistical purposes. Thirty-six patients with head and neck squamous cell carcinoma who were treated with radiotherapy alone during the same period were used as controls. The patients were followed for two years. The incidence of response rate did not differ significantly between regimens; however, the incidence of side effects with bleomycin-radiotherapy, 82.61%, is significantly more than that of radiotherapy alone (52.78%). Median survial time (MST) of those responding to bleomycin-radiotherapy protocol was seven months and 12 days and for radiotherapy responders was six months. Neither the response rate nor the MST improve significantly after pretreatment with bleomycin. On the contrary, the incidence of side effects increased significantly

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Labeled bleomycin as a tumor localizing agent  

International Nuclear Information System (INIS)

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

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Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells.  

Science.gov (United States)

Testicular cancer is the most common cancer among young men of reproductive age. Bleomycin is a frequently used drug for the treatment of several malignancies and is part of the chemotherapy protocols used for testicular cancer; however, side-effects are common. Bleomycin causes an increase in oxidative stress which has been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an active component of the spice turmeric, has been demonstrated to induce apoptosis in a number of malignancies. However, to date no study has been carried out to elucidate its anticancer activity and interaction with bleomycin in testicular cancer cells. In this study, we investigated and compared the effects of curcumin, bleomycin and hydrogen peroxide (H2O2) on apoptotic signaling pathways. Curcumin (20 µM), bleomycin (400 µg/ml) and H2O2 (400 µM) incubation for 24 h decreased the viability of NTera-2 cells, and increased caspase-3, -8 and -9 activities, Bax and cytoplasmic cytochrome c levels and decreased Bcl-2 levels. The concurrent use of curcumin with bleomycin induced caspase-3, -8 and -9 activities to a greater extent in NTera-2 cells than the use of each drug alone. Our observations suggest that the effects of curcumin and bleomycin on apoptotic signaling pathways are synergistic. Therefore, we propose to use curcumin together with bleomycin to decrease its therapeutic dose and, therefore, its side-effects. PMID:22469952

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

2012-06-01

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Det svenska CFC-regelverkets ändamålsenlighet samt dess förhållande till BEPS  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Syftet med uppsatsen är att analysera ändamålsenligheten med de svenska CFC-reglerna samt att problematisera det nuvarande CFC-regelverket utifrån de åtgärder och nyckel-överväganden som lyfts fram ur OECDs två rapporter om BEPS. BEPS är ett omfattande problem, vilket har presenterats i två rapporter framförda av OECD. Syftet med rapporterna är att de ska mynna ut i åtgärder på det mellanstatliga beskattningsområdet för att motverka BEPS. Många länder har inkorporerat CFC-...

Providakis, Johan

2014-01-01

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Further studies of transport and distribution of bleomycin in EAT cells using 57Co-bleomycin  

International Nuclear Information System (INIS)

Synergistic action of bleomycin and X-rays has been observed on rates of DNA synthesis of EAT cells in predominantly plateau phase suspensions where the drug dose (20?g/ml) is split into two halves, one delivered 30 mins before exposure to X-rays (2.5krad) and one immediately afterwards. An improved response to the split drug dose radiation schedule (2x1?g/ml) compared to bleomycin given as a single dose plus radiation (200rad) has been observed in the depression of growth rates of EAT cells in the exponential phase in culture. These findings are considered in relation to values obtained for the biological half-life of bleomycin incubated with cells and to the transport kinetics, intracellular distribution and dialysibility of 57Co-bleomycin within the cell. The results suggest that only a small proportion of intracellular bleomycin is bound to DNA and decreases after reaching a maximum, irrespective of the steady levels of 57Co-bleomycin in the cell as a whole. Most of the intracellular bleomycin appears to be associated with proteins, forming a non-dialysable complex which does not influence cell growth and will be unable to potentiate radiation damage. Bleomycin is believed to be transported into the cells by facilitated diffusion. Some evidence is presented to suggest that extracellular bleomycin may stimulate increased carrier availability. (author)

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Bleomycin  

Science.gov (United States)

... throat, tonsils, and sinuses) and cancer of the penis, testicles, cervix, and vulva (the outer part of ... IMPORTANT WARNING section, call your doctor immediately: sudden numbness or weakness of face, arm, or leg on ...

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Assessment of BEP of MIMO-OFDMA systems  

Directory of Open Access Journals (Sweden)

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.

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

2013-09-01

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Vascular changes in bleomycin-induced scleroderma.  

Science.gov (United States)

Systemic sclerosis (SSc) is characterized by vascular injury, immunological abnormalities, and fibrosis of the skin as well as various internal organs. Vascular impairment is the early manifestation and plays a fundamental role in the pathogenesis of SSc. Recent studies suggest that complex interactions among the endothelial cells, pericytes, smooth muscle cells, and fibroblasts are involved in the systemic vasculopathy in SSc, and histological feature of proliferation of vascular wall is seen in the lesional scleroderma skin at the late stage of disease. One of the most representative mouse models for scleroderma is the bleomycin-induced scleroderma; however, aspects of vascular alteration have not been described in detail so far. A number of studies have shown that bleomycin stimulates endothelial cells and fibroblasts to induce proinflammatory and fibrogenic cytokines, apoptosis, reactive oxygen species, and so on. This paper makes a focus on the vascular involvement in the bleomycin-induced murine scleroderma. PMID:22028717

Yamamoto, Toshiyuki; Katayama, Ichiro

2011-01-01

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BLEOMYCIN EFFECTS ON MOUSE MEIOTIC CHROMOSOMES  

Science.gov (United States)

The effects of a radiomimetic chemical, bleomycin (BLM), on meiotic chromosomes was evaluated in mice. hromosome aberrations were analyzed at meiotic metaphase I, and damage to the synaptonemal complex was analyzed in meiotic prophase cells. n the metaphase aberration studies, an...

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Energy dependence of the 7Be(p,?)8B S factor, and charge symmetry in the 7Li+n and 7Be+p systems  

International Nuclear Information System (INIS)

The measured energy dependence of the 7Be(p,?)8B S factor is fitted better by the cluster-model calculation of Descouvemont and Baye than by other models. It is suggested here that this may be connected with the cluster model predicting too high an absolute value of the S factor. Evidence for a breakdown of charge symmetry between the 7Li+n and 7Be+p systems is discussed and found not to be convincing. R-matrix formulae are used

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Excretion and organic distribution of 57Co-bleomycin emulsions  

International Nuclear Information System (INIS)

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

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A reaction of cobalt bleomycin with dissolved oxygen  

International Nuclear Information System (INIS)

Metal binding is essential for the diagnostic use of bleomycins, as they are used as a vehicle to carry the radioactive metal to tumour tissues. The stability of the metal bleomycin is therefore important. The reaction of a solution of cobalt bleomycin with air has been investigated spectroscopically. The visible spectrum of the cobalt bleomycin changed with the passage of air. Further changes occurred in the spectrum over 24 hours. The spectra showed that at least three forms of cobalt bleomycin exist in a solution containing stoichiometric amounts of cobalt and bleomycin. Oxygenation was rapid but conversion of the intermediate to the final compound took place with a time scale of hours. (U.K.)

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Metal complexes of bleomycin: evaluation of [Rh-105]-bleomycin for use in targeted radiotherapy  

International Nuclear Information System (INIS)

Bleomycin has been used as a carrier for several radioisotopes; however, its potential for clinical use has been limited either by the in vivo stability of the complexes or the half-life of the isotope used. The chemical, biological, and radiological properties of 105Rhodium appear to make it an ideal choice for targeted radiotherapy. The synthesis and purification of a hereto unreported 105Rhodium-bleomycin (105Rh-BLM) complex is described. The stability of this complex in plasma is sufficient to allow targeted delivery of the radioisotope. 57Cobalt-bleomycin was studied under identical conditions for comparative purposes. The suitability of 105Rh-BLM for targeted therapy, which appears to be limited by the renal clearance of this agent, is discussed

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Intrapleural bleomycin in the treatment of chylothorax.  

Science.gov (United States)

Chylothorax is an accumulation of thoracic lymph or chyle in the pleural cavity. It is a rare condition and is usually caused by trauma or malignant disease. We present three cases with chylothorax due to malignant non-Hodgkin's lymphoma [high grade malignant (1 case) and low grade malignant (2 cases)] treated with pleurodesis with bleomycin and systemic chemotherapy (CHOP, CNOP, trofosfamide). Complete remissions (CR) were achieved in all three cases. Two patients had a recurrent chylothorax 3 and 12 months after initial treatment. They were treated with a second intrapleural installation of bleomycin and continuing systemic chemotherapy (CNOP, trofosfamide) and are still alive in CR with a follow-up period of 28 and 30 months respectively. One patient died of relapsing non-Hodgkin's lymphoma after 23 months of follow-up. There was no sign of recurrent chylothorax. We conclude that chylothorax caused by lymphoma can be satisfactorily controlled by pleurodesis with bleomycin combined with systemic chemotherapy. Immediate action is necessary to prevent great loss of lipids and proteins. The underlying malignancy must be controlled to achieve a good prognosis. PMID:7535348

Norum, J; Aasebø, U

1994-12-01

 
 
 
 
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BEP-relations for N2 dissociation over stepped transition metal and alloy surfaces  

DEFF Research Database (Denmark)

We present density functional theory (DFT) calculations for N(2) dissociation on stepped face-centred cubic (211) surface slabs. By using the same crystal structure, the same adsorption site for atomic nitrogen, and the same transition-state bond length of N(2) over a range of pure metal surfaces, a perfectly linear Bronsted-Evans-Polanyi (BEP) relation between the transition-state potential energy and the dissociative chemisorption energy is obtained. The perfect BEP relation, which extends over 12 eV in chemisorption energy, suggests that the manifestation of BEP relations for surface reactions is a general electronic structure effect, and that geometric effects are responsible for the scatter which is normally observed around the BEP line. The BEP relation is also shown to be valid for both surface and bulk alloys. The scatter is, however, larger than for the pure elements. This can be understood as a larger geometrical variance. To analyze the accuracy of the DFT calculations a detailed convergence study is performed for several adsorbates on stepped hexagonal close-packed and face-centred cubic Ru slabs.

Fronczek-Munter, Ture RØnved; Bligaard, Thomas

2008-01-01

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Bleomycin induced flagellate erythema: Revisiting a unique complication.  

Science.gov (United States)

Bleomycin induced flagellate dermatitis is a rare and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in common clinical practice. We herein describe a case of a 22-year-old Indian male with Hodgkin's lymphoma, Ann Arbor stage IIBEX developing flagellate dermatitis following 1(st) cycle of chemotherapy with ABVD regimen. The diagnostic dilemma in the illustrative case underscores the importance of awareness and prompt identification and treatment of this dermatological toxicity in limiting morbidity in patients undergoing bleomycin based combination chemotherapy. In patients having severe rash, bleomycin should be expeditiously discontinued. Omission of bleomycin does not compromise the treatment outcome in the majority of patients with Hodgkin's lymphoma. PMID:24125992

Biswas, Ahitagni; Chaudhari, Pritee B; Sharma, Punit; Singh, Lavleen; Julka, Pramod Kumar; Sethuraman, Gomathy

2013-01-01

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The 7Be(p, ?)8B astrophysical S-factor  

International Nuclear Information System (INIS)

We present the results of the recent precise S17(0) determination by the Seattle-TRIUMF 7Be(p, ?)8B collaboration. We discuss new investigations of the robustness of our estimated extrapolation uncertainty. We comment on the comparison of direct and Coulomb dissociation determinations of S17(E), and on neutrino physics and the Standard Solar Model

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Identification of differentially expressed genes in different malignant transformation phases of BEP2D cell line  

International Nuclear Information System (INIS)

Objective: To screen and identify differentially expressed genes in different malignant transformation phased of BEP2D cell line induced by alpha-particles. Methods: Suppression subtractive hybridization (SSH) and cDNA microarray were performed. Results: Three suppression subtractive cDNA libraries were constructed. BEP2D cDNA library contained 416 clones, R15H20 cDNA library contained 301 clones, and R15H35 cDNA library contained 586 clones. After confirmed by cDNA microarray, the positive rates in BEP2D cDNA microarray were 90.4%, 21.6% and 19.7%; in R15H20 cDNA microarray, 8.6%, 93.8% and 31.6%; and in R15H35 cDNA microarray, 23.5%, 18.2%, 90.7% when hybridized with probes coming from BEP2D, R15H20 and R15H35 cells, respectively. Conclusions: The combination of SSH and cDNA microarray is a rapid and effective method for high throughout screening and identification of differentially expressed genes in different samples. The cDNAs confirmed by cDNA microarray may be the relative genes that associate with malignant transformation of bronchial epithelial cells induced by alpha-particles

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GUM Analysis for TIMS Isotopic Ratios in BEP0 Graphite Qualification Samples, Round 2  

Energy Technology Data Exchange (ETDEWEB)

In May 2007, one set of three samples from NBL were addressed to Steve Petersen for TIMS analysis, and included BEP0 samples numbered 27008, 30986, and 50846. All cores were trimmed by tooling, and lightly cleaned by CO2 pellet blasting. Small discs were cut from the second set of samples for SIMS analysis, with the remainder of each used for TIMS preparation.

Gerlach, David C.; Heasler, Patrick G.; Reid, Bruce D.

2009-01-01

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

Science.gov (United States)

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.

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

2005-02-01

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The effects of Bleomycin A5 on infantile maxillofacial haemangioma  

Directory of Open Access Journals (Sweden)

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.

Zhao Fu-yun

2011-07-01

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Labelling and pharmacokinetics of 131I-bleomycin with regard to tumor affinity and in comparison with 57Co- and 111In-bleomycin  

International Nuclear Information System (INIS)

Bleomycin was labelled with 131I and checked electrophoretically and chromatographically as to its activity. The pharmacokinetics of 131I-bleomycin were tested in mice bearing different tumors. Its whole-body retention and organ distribution were determined in comparison to 57Co- and 111In-bleomycin, resp

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

International Nuclear Information System (INIS)

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

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Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2010-01-01

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New determination of the 7Be(p,?)8B S-factor  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from E-bar cm=116 to 2460 keV. Our new measurements lead to S17(0)=22.1+/-0.6(expt)+/-0.6(theor)eV-bar b based on data from E-bar cm=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. We compare our results to other S17(0) values extracted from both direct (7Be(p,?)8B) and indirect (Coulomb dissociation and heavy-ion reaction) measurements, and show that the results of these 3 types of experiments are not mutually compatible. We recommend a 'best' value, S17(0)=21.4+/-0.5(expt)+/-0.6(theor)eV-bar b, based on the mean of all modern direct measurements below the 1+ resonance

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New charge exchange model of GEANT4 for $^{9}$Be(p, n)$^{9}$B reaction  

CERN Document Server

Taking ENDF/B-VII.1 differential cross section data as input, a new data-based charge exchange model of GEANT4 dedicated to the $^{9}$Be(p, n)$^{9}$B reaction is developed. The resulting model turns out to be in good agreement with the experimental data for the neutron yield spectrum, making significant improvement compared to other GEANT4 hadronic models.

Shin, Jae Won

2014-01-01

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Study of the Be(p, n) and Be(d, n) source reactions  

International Nuclear Information System (INIS)

We have developed lithium glass detector arrays to measure the energy spectra of neutrons below 1 MeV. The use of a calibrated neutron source spectrum allows measurement of neutron spectra from 0.070 to 14 MeV. The angular distribution and the neutron energy spectra are reported for the Be(d, n) and Be(p, n) neutron source reactions. The applications of these reactions to Boron Neutron Capture Therapy (BNCT) and neutron radiography are discussed. (author)

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Oxidative damage of BEP2D cells irradiated 60Co ?-rays  

International Nuclear Information System (INIS)

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

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Amino acid analysis and cell cycle dependent phosphorylation of an H1-like, butyrate-enhanced protein (BEP; H10; IP25) from Chinese hamster cells  

International Nuclear Information System (INIS)

A fraction enriched in the butyrate-enhanced protein (BEP) has been isolated from Chinese hamster (line CHO) cells by perchloric acid extraction and Bio-Rex 70 chromatography. Amino acid analyses indicate that the composition of BEP resembles that of CHO H1; however, BEP contains 11% less alanine than H1, and, in contrast to H1, BEP contains methionine. Treatment of BEP with cyanogen bromide results in the cleavage of a small fragment of approx. 20 amino acids so that the large fragment seen in sodium dodecyl sulfate-acrylamide gels has a molecular weight of approx. 20,000. Radiolabeling and electrophoresis indicate that BEP is phosphorylated in a cell cycle dependent fashion. These data suggest that (1) BEP is a specialized histone of the H1 class and (2) BEP is the species equivalent of calf lung histone H10, rat H10, and IP25, a protein enhanced in differentiated Friend erythroleukemia cells. The data also indicate that putative HMG1 and HMG2 proteins do not undergo the extensive cell cycle dependent phosphorylations measured for histone H1 and BEP

36

HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era.  

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PURPOSE: The prognosis of HIV-infected patients with non-Hodgkin lymphoma in the highly active antiretroviral therapy (HAART) era approaches that of the general population when they are treated with the same protocols. We analyzed the outcome of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the HAART era according to HIV serostatus to establish whether this also holds true for HL. PATIENTS AND METHODS: From 1997 to 2010, 224 pa...

Montoto, S.; Shaw, K.; Okosun, J.; Gandhi, S.; Fields, P.; Wilson, A.; Shanyinde, M.; Cwynarski, K.; Marcus, R.; Vos, J.; Young, Am; Tenant-flowers, M.; Orkin, C.; Johnson, M.; Chilton, D.

2012-01-01

37

Combined bleomycin and radiotherapy in oral cancer  

International Nuclear Information System (INIS)

A clinical trial comparing bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using to opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8 and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis. (author)

38

Bleomycin and radiation-induced lung damage in mice  

International Nuclear Information System (INIS)

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

39

51Cr-bleomycin in the diagnosis of ocular melanoma  

International Nuclear Information System (INIS)

51Cr-bleomycin was administered to 18 patients suspected of having an ocular melanoma with varying degree of development. The diagnosis was verified prior to surgical removal of the eye-ball by fluorescent angiography and computerized axial tomography. In operated patients histological diagnosis was also available. Scintigraphy after 51Cr-bleomycin administration appeared to be an effective diagnostic measure: sensitivity and specificity reached 90 and 87%, respectively. It is concluded that the method is useful in the preoperative diagnosis of ocular melanoma. (orig.)

40

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

International Nuclear Information System (INIS)

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

 
 
 
 
41

The 9Be(p, ?)10B cross section at low energies  

International Nuclear Information System (INIS)

Data for the 9Be(p, ?)10B 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 ?-transitions to the four lowest states of 10B, angular distributions and analysing powers. Use is made of experimental values of asymptotic normalization constants obtained from 9Be(10B, 9Be) 10B. A good fit is obtained with two 1- levels, two 2- levels, one 0+ level and one 2+ level

42

The new Seattle-TRIUMF 7Be(p,?)8B S-factor determination  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from E-bar cm=116 to 2460 keV. Our new measurements lead to S17(0) = 22.1 +/- 0.6(expt) +/- 0.6(theor) eV b, where the central value is based on the theory of Descouvemont and Baye. We recommend a 'best' value, S17(0) = 21.4 +/- 0.5(expt) +/- 0.6(theor) eV b, based on the mean of all modern direct measurements below the 1+ resonance

43

A comment on the 7Be(p,?)8B cross section and the solar neutrino problem  

International Nuclear Information System (INIS)

Evidence is presented which indicates that the accepted value for the cross section of the 7Be(p,?)8B reaction at stellar energies is probably too large. It is suggested that the accepted value of the 7Li(d,p)8Li cross section, which has been used for normalization purposes, is too large; that the accepted value for the ratio of the 7Be(p,?)8B and 7Li(d,p)8Li cross sections is too large; and that the energy dependence used to extrapolate to stellar energies from the higher energies at which measurements have been made is inaccurate. The consequent reduction of the 7Be(p,?)8B cross section by about 30% would not be sufficient to resolve the solar neutrino problem but would significantly lessen the discrepancy between observation and calculation

44

Acute respiratory failure induced by bleomycin and hyperoxia  

International Nuclear Information System (INIS)

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

45

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

Science.gov (United States)

The low-energy bare-nucleus cross section for 9Be(p,?)6Li has been extracted by means of the Trojan horse method (THM) applied to the 2H(9Be, ?,6Li)n reaction at a beam energy of Be9 of 22.35 MeV. For the first time, we assume an intermediate process, 9Be+2H?9Be+p+n, and considered this process as one criterion of the quasifree condition. Accordingly, sequential decay processes were eliminated. The derived astrophysical S(E) factor for the two-body process 9Be(p,?)6Li is compared with that obtained from direct experiments. We have found good agreement between the two results, leading to an improved determination of the S(E) with S(0)=21.0±0.8 MeV b. Furthermore, the electron screening potential energy Ue=676±86 eV has also been extracted in a model-independent way by comparing the direct and THM data. The value is significantly higher than that predicted by current theoretical models, whereas it is lower than Ue?830 eV, which was extracted from direct measurements with inclusion of the Ec.m.=-23 keV subthreshold resonance.

Wen, Qun-Gang; Li, Cheng-Bo; Zhou, Shu-Hua; Meng, Qiu-Ying; Zhou, Jing; Li, Xiao-Mei; Hu, Shou-Yang; Fu, Yuan-Yong; Spitaleri, C.; Tumino, A.; Pizzone, R. G.; Rapisarda, G. G.

2008-09-01

46

Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins  

Science.gov (United States)

When the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture and fungi die. This fungicidal activity was discovered previously on nonproliferating Saccharomyces cerevisiae cells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated effects of bleomycin on growing fungal organisms. These included the medically important Aspergillus fumigatus and Cryptococcus neoformans, as well as the emerging human pathogen and fungal model, S. cerevisiae. Bleomycin had its highest potency against A. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics. Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed when A. fumigatus was grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination, hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle of S. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and alters isolated cell walls as well as intact cell walls on nongrowing cells. PMID:14506042

Moore, Carol W.; McKoy, Judith; Del Valle, Robert; Armstrong, Donald; Bernard, Edward M.; Katz, Norman; Gordon, Ronald E.

2003-01-01

47

The Rise and Attenuation of the Basic Education Programme (BEP) in Botswana: A Global-Local Dialectic Approach  

Science.gov (United States)

Using a global-local dialectic approach, this paper traces the rise of the basic education programme in the 1980s and 1990s in Botswana and its subsequent attenuation in the 2000s. Amongst the local forces that led to the rise of BEP were Botswana's political project of nation-building; the country's dire human resources situation in the decades…

Tabulawa, Richard

2011-01-01

48

Carbohydrate dependent targeting of cancer cells by bleomycin-microbubble conjugates.  

Science.gov (United States)

Biotinylated bleomycin A(5) was attached to streptavidin-derivatized microbubbles, and a solution containing the conjugate was passed over a monolayer of cultured MCF-7 cells. The bleomycin-derivatized microbubbles adhered to the MCF-7 cells, and the association could be monitored by the use of a microscope. Three other cancer cell lines gave similar results. The bleomycin-microbubble conjugate did not bind to a normal breast cell line (MCF-10A) or to the matched noncancer cell lines corresponding to the other cancer cell lines targeted by bleomycin. No binding to any tested cell line was observed when the microbubbles lacked conjugated bleomycin A(5) or when the microbubble contained a bleomycin A(5) analogue lacking the carbohydrate moiety. PMID:19187019

Chapuis, Jean-Charles; Schmaltz, Ryan M; Tsosie, Krystal S; Belohlavek, Marek; Hecht, Sidney M

2009-02-25

49

Angiotensin-Converting Enzyme N-Terminal Inactivation Alleviates Bleomycin-Induced Lung Injury  

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Bleomycin has potent anti-oncogenic properties for several neoplasms, but drug administration is limited by bleomycin-induced lung fibrosis. Inhibition of the renin-angiotensin system has been suggested to decrease bleomycin toxicity, but the efficacy of such strategies remains uncertain and somewhat contradictory. Our hypothesis is that, besides angiotensin II, other substrates of angiotensin-converting enzyme (ACE), such as the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), pl...

Li, Ping; Xiao, Hong D.; Xu, Jianguo; Ong, Frank S.; Kwon, Mike; Roman, Jesse; Gal, Anthony; Bernstein, Kenneth E.; Fuchs, Sebastien

2010-01-01

50

Static and dynamic mechanics of the murine lung after intratracheal bleomycin  

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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 ...

Papiris Spyridon; Roussos Charis; Karabela Sophia P; Psallidas Ioannis; Kotanidou Anastasia; Triantafillidou Christina; Moschos Charalampos; Manali Effrosyni D; Armaganidis Apostolos; Stathopoulos Georgios T; Maniatis Nikolaos A

2011-01-01

51

A fatal hyperpyrexial response to bleomycin following prior therapy: a case report and literature review.  

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Bleomycin is an effective drug used in the therapy of many malignant diseases. Such toxicities as fever, chills, and pulmonary fibrosis are well known to occur following administration of this drug. A rare fatal hyperpyrexial response has also been noted with this agent. We describe a case of fatal hyperthermia after an injection of bleomycin. Unlike earlier reported cases, our patient developed her reaction following prior uneventful therapy with bleomycin rather than as a response to initia...

Rosenfelt, F.; Palmer, J.; Weinstein, I.; Rosenbloom, B.

1982-01-01

52

Constraints on the 7Be(p,?)8B radiative capture rate from charge symmetry  

International Nuclear Information System (INIS)

Cross sections for the dipole radiative capture reactions 7Li(n,?)8Li and 7Be(p,?)8B are calculated in a two-body model, which is based on a Woods-Saxon parametrization of the nuclear interaction. The well depth is adjusted for each reaction channel so that the measured separation energies and s-wave scattering lengths are reproduced. The calculations are repeated for a wide range of the radius and the diffuseness of the interaction. The predicted S factor for the radiative proton capture on 7Be falls within a surprisingly narrow range of values when the model is calibrated to reproduce measurements of the mirror reaction 7Li(n,?)8Li. The simplified model used here is consistent with the shell model approach for proton capture on 7Be but it gives a significantly smaller cross section for neutron capture on 7Li

53

Precise measurement of the 7Be(p,?)8B S factor  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from Ec.m.=116 to 2460 keV (where c.m. means center-of-mass), which incorporate several improvements over our previously published experiment, also discussed here. Our new measurements lead to S17(0)=22.1±0.6(expt)±0.6(theor) eV b based on data from Ec.m.=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. The theoretical error estimate is based on the fit of 12 different theories to our low-energy data. We compare our results to other S17(0) values extracted from both direct [7Be(p,?)8B] and indirect (Coulomb-dissociation and heavy-ion reaction) measurements, and show that the results of these three types of experiments are not mutually compatible. We recommend a 'best' value, S17(0)=21.4±0.5(expt)±0.6(theor) eV b, based on the mean of all modern direct measurements below the 1+ resonance. We also present S factors at 20 keV which is near the center of the Gamow window: the result of our measurements is S17(20)=21.4±0.6(expt)±0.6(theor) eV b, and the recommended value is S17(20)=20.6±0.5(expt)±0.6(theor) eV b

54

Pharmacology and therapeutic efficacy of bleomycin administered by continuous infusion  

International Nuclear Information System (INIS)

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

55

111In-bleomycin imaging of breast tumours  

International Nuclear Information System (INIS)

Forty female patients with 15 malignant breast tumours and 25 benign growths, all verified histologically, were studied before surgery using mammography and 111In-Bleomycin scintigraphy. The patient was studied lying prone on a table with an opening so that one breast could hang in front of the gamma camera. The true positive and negative scintigraphy results are slightly poorer (70%) than the mammography results (80%) and there are more false negative scintigraphy interpretations mostly in small lesions. (orig.)

56

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

Science.gov (United States)

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

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

2013-07-01

57

Radiotherapy Does Not Influence the Severe Pulmonary Toxicity Observed With the Administration of Gemcitabine and Bleomycin in Patients With Advanced-Stage Hodgkin's Lymphoma Treated With the BAGCOPP Regimen: A Report by the German Hodgkin's Lymphoma Study Group  

International Nuclear Information System (INIS)

Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supportolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy

58

Eosinophilic pneumonia associated with bleomycin in a patient with mediastinal seminoma: a case report  

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Abstract Introduction Lung toxicities resulting from the chemotherapeutic agent bleomycin encompass a variety of pathological changes, including bronchiolitis obliterans organizing pneumonia, interstitial pneumonitis and progressive interstitial fibrosis. We report a rare case of eosinophilic pneumonia associated with bleomycin. Case presentation A 44-year-old Hispanic man with a primary mediastinal seminoma complicated by superior vena cava syndrome underwent t...

Chu David; Hapani Sanjaykumar; Wu Shenhong

2010-01-01

59

Effects of curcumin on bleomycin?induced oxidative stress in malignant testicular germ cell tumors.  

Science.gov (United States)

Bleomycin is commonly used in the treatment of testicular cancer. Bleomycin generates oxygen radicals, induces the oxidative cleavage of DNA strands and induces cancer cell apoptosis. Curcumin (diferuloylmethane) is a potent antioxidant and chief component of the spice turmeric. No study investigating the effects of curcumin on intrinsic and bleomycin-induced oxidative stress in testicular germ cell tumors has been reported in the literature. For this reason, the present study aimed to examine the effects of curcumin on oxidative stress produced in wild-type NTera-2 and p53-mutant NCCIT testicular cancer cells incubated with bleomycin and the results were compared with cells treated with H2O2 which directly produces oxidative stress. The protein carbonyl content, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), 8-isoprostane, lipid hydroperoxide (LPO) levels and total antioxidant capacity in the two testicular cancer cell lines were determined. Results showed that bleomycin and H2O2 significantly increased protein carbonyl, TBARS, 8-isoprostane and LPO levels in the NTera-2 and NCCIT cell lines. Bleomycin and H2O2 significantly decreased the antioxidant capacity and GSH levels in NTera-2 cells. Curcumin significantly decreased LPO, 8-isoprostane and protein carbonyl content, and TBARS levels increased in cells treated with bleomycin and H2O2. Curcumin enhanced GSH levels and the antioxidant capacity of NTera-2 cells. In conclusion, curcumin inhibits bleomycin and H2O2-induced oxidative stress in human testicular cancer cells. PMID:22825355

Cort, Aysegul; Ozdemir, Evrim; Timur, Mujgan; Ozben, Tomris

2012-10-01

60

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

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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.)

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

 
 
 
 
61

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

International Nuclear Information System (INIS)

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.)

62

Deformation and target spin-dependent effects in 9Be+p vector at 220 MeV  

International Nuclear Information System (INIS)

Cross-section and analyzing-power measurements were performed for the 9Be(p vector,p0)9Be and 9Be(p vector,p2)9Besup(*) reactions. The depolarization parameter D was also measured on the first reaction. The data were analyzed in terms of standard optical-model and macroscopic DWBA as well as coupled-channel calculations. The former approach does not reproduce well the elastic and inelastic analyzing-power data. Coupled-channel calculations provide a good description of both the cross-section and analyzing-power data. The D-data are interpreted in terms of contributions from both the quadrupole spin-flip mechanism and the nucleon-nucleus spin-spin interactions. (orig.)

63

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

International Nuclear Information System (INIS)

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

64

The astrophysical S-factor of the reaction 7Be(p,?)8B in the direct capture model  

International Nuclear Information System (INIS)

The astrophysical S-factor for the reaction 7Be(p, ?)8B up to an energy of 2 MeV (c.m.) and the capture cross section of 7Li(n, ?)8Li up to 1 MeV (c.m.) are calculated using the Direct Capture model (DC). Both calculations are in good agreement with experimental data. (orig.)

65

Radiologic-pathologic correlation of experimental bleomycin-induced pneumonitis  

International Nuclear Information System (INIS)

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

66

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

Directory of Open Access Journals (Sweden)

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

Ardavan Rahimian

2013-01-01

67

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

CERN Document Server

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+...

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

68

Research on 7Be(p,?)8Be reaction by Coulomb decomposition reaction  

International Nuclear Information System (INIS)

The measurement of solar neutrino flux has been carried out at four stations, and it has been known that it was considerably less than the expected neutrino flux by the standard solar model. This phenomenon is called solar neutrino problem. In the observation at Homestake and Kamiokande, it has been known that the threshold values of the measurable energy were high, and most of the neutrino flux were the high energy neutrinos formed by 8B?8Be+e++? reaction. The measurement of the reaction cross section for making 8B is considered as one of the keys for resolving the solar neutrino problem. The research on low energy 7Be(p,?)8B reaction carried out so far is reviewed. The author measured this cross section by using Coulomb decomposition method. The Coulomb decomposition reaction of 8B is discussed, and the calculated cross section is shown. The 8B beam supplied by the RIKEN projectile fragment separator (RIPS) was irradiated on a lead target in the atmosphere, and the decomposed 7Be and protons were measured with a telescope. The relative energy distributions of the protons and 7Be obtained by the experiment are shown. Also the Monte Carlo calculation was carried out. The resulted reaction cross section was compared with the other data. The effect of Coulomb acceleration was examined. (K.I.)

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A new measurement of 7Be(p,?)8B cross section and its astrophysical meaning  

International Nuclear Information System (INIS)

We measured the 7Be(p,?)8B cross section from Ep = 221 keV to 1376 keV. A uniformly distributed beam that illuminated the whole area of a small diameter target was used to eliminate systematic error from 7Be target non-uniformity. The energy loss profile of the target to the incident beam was measured using the 7Be(?,?)11C resonance at E? 1376 keV. The (?,?) measurement also demonstrated that the target had a high 7Be atomic purity. The measured yield of the detected 8B was normalized to the activity of the target and the solid angle of the counting detector. Corrections for 8B decay during bombardment and arm rotation were applied. For the first time, the correction due to lost 8B from backscattering was determined experimentally. A new experiment is presently underway, extending to lower proton energy. Due to a problem in the determination of the ?-detector solid angle in the first measurement, the solid angle in the new measurement will be determined by a different technique using a 148Gd ? source and a silicon detector whose distance to the source can be precisely adjusted

70

Decontamination of urine after administration of 57Co-bleomycin  

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Diagnostic application of 57Co-bleomycin (57Co-BLM) is considerably limited by the problem of patients urine contamination with the long-lived radionuclide (T1/2 = 270 days). A method for decontamination of urine using charcoal (Carbosorb pulvis) was tested in 10 patients examinated by the 57Co-BLM scan. About 95% of activity excreted into the urine was eliminated during the first 24 hours after injection. An average decontamination efficiency of 91.8% was obtained using the ratio of 10 g of charcoal/l of contaminated urine. (author)

71

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

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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 ?-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-?1-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. PMID:25595642

Chen, Li-Jun; Ye, Hong; Zhang, Qian; Li, Feng-Zhi; Song, Lin-Jie; Yang, Jie; Mu, Qing; Rao, Shan-Shan; Cai, Peng-Cheng; Xiang, Fei; Zhang, Jian-Chu; Su, Yunchao; Xin, Jian-Bao; Ma, Wan-Li

2015-03-01

72

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

International Nuclear Information System (INIS)

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

73

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

International Nuclear Information System (INIS)

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

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No effect of pirfenidone treatment in fulminant bleomycin-induced pneumonitis  

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Bleomycin-induced pneumonitis (BIP) is a serious and potentially fatal adverse effect of bleomycin. Currently, BIP is treated on an empirical basis with high dose steroid. Pirfenidone is a new antifibrotic drug, which has been proven beneficial in idiopathic pulmonary fibrosis and is able to inhibit or reverse BIP in animal models. Here, the first two cases of human BIP treated with pirfenidone in addition to steroid therapy are presented. Unfortunately, both patients died, which may be explained by the initiation of therapy at a late stage. Therefore, studies of early or prophylactic treatment with pirfenidone in relation to bleomycin-containing chemotherapy regimens are needed.

Bendstrup, Elisabeth; Hyldgaard, Charlotte; Agerbæk, Mads; Andersen, Charlotte U.; Hilberg, Ole

2014-01-01

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A method for labelling bleomycin and mannitol using a solid reductant  

International Nuclear Information System (INIS)

Bleomycin and mannitol seem to localize particularly in animal neoplastic tissue. Analyzing the structure of the two molecules, the presence of sites combining /sup 99m/Tc can be hypothesized, particularly for bleomycin. Many methods for labelling bleomycin with /sup 99m/Tc have been reported, but these radiopharmaceuticals have not often been used clinically. The aims of this study were: (1) to compare a method based on the utilization of a solid reductant (SnO) with a more often used method involving the utilization of Sn Cl/sub 2/ as a reductant; (2) to propose two reliable labelling methods which prove easy to perform in any laboratory

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Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin  

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

Fadi Atwan

2012-07-01

77

Metal Matrix Superconductor Composites for SMES-Driven, Ultra High Power BEP Applications: Part 1  

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A superconducting magnetic energy storage (SMES) `battery' of order 0.25-1 km diameter is designed to demonstrate theoretical feasibility for large scale beamed energy propulsion (BEP) applications, charging at ˜300e MW from solar or nuclear sources, and discharging the full energy load into a gyrotron network in 1-2 minutes. The superconducting coil, whose storage capacity is 2.5 TJ, is made of structural carbon fiber filaments with a superconducting MgCNi3 high current density film surface layer, imbedded in a high electrical and thermal conductivity stabilizer metal, such as copper and/or beryllium. The SMES energy density is compared to other energy storage means and appears superior at the proposed operations scale and prolonged, frequent cycling duty. It is demonstrated that a toroidal coil with solenoidal winding configuration is most effective in specific energy (J/kg). Concurrently the high modulus and yield strength of the coil composite perform well for tensile hoop stress along the winding conductors, as well as transversely, to resist a self generated effective external pressure tending to buckling conditions in the thin walls. As such the toroid cross-section is re-enforced with periodic discrete rings. To achieve this hyper rigidity, the coil composite requires exclusion of traditional soft insulators (like epoxy), making use of a CVD (with tough metal-bonded Al2O3) continuous process of wire insulation and integration into a coil structural lattice, which ultimately needs to withstand very large quench voltages. The coil is built on a modular inflatable mandrel which is removed after assembly. A Part 2 associated paper treats the electromagnetic problem.

Gross, Dan A.; Myrabo, Leik N.

2006-05-01

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Effects of Recombinant Activated Protein C Derived From Drotrecogin-Alpha on Bleomycin-Induced Pulmonary Fibrosis in Rats Compared with Methyl-Prednisolone  

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Full Text Available OBJECTIVE: In this study, we aimed to test the preventive effects of intraperitoneally administered drotrecogin alpha which is derived from activated protein C (APC, on bleomycin-induced pulmonary fibrosis in rats, and to compare the effects of APC with the effects of methyl-prednisolone, a traditional therapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were randomly allocated into four groups: 1. Saline alone (n=6; 2. Bleomycin+placebo (n=7; 3. Bleomycin+methyl-prednisolone (n=7; 4. Bleomycin+APC (n=10. The rats (except for the control group were given intratracheal bleomycin (2.5 mg/kg. The bleomycin+APC group was given APC (100 µg/kg/day and methyl-prednisolone treated rats were injected with 5mg/kg/day methyl-prednisolone intraperitoneally two days before the bleomycin injection; the drug was administered at the same dose for 16 days. All of the rats were killed 14 days after the intratracheal injection of bleomycin. Fibrotic changes in the lungs were demonstrated by analysing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content.RESULTS: Fibrosis was experimentally induced in the lungs of rats using bleomycin. Fibrosis scores in the bleomycin+methyl-prednisolone and the bleomycin+APC groups were significantly lower than in the bleomycin+placebo group (p<0.05. The scores of the bleomycin+APC group and the bleomycin+methyl-prednisolone group were similar. The lung tissue hydroxyproline contents in the bleomycin+placebo and bleomycin+methyl-prednisolone groups were significantly higher than the control group (p<0.05, but the hydroxyproline content in the bleomycin+APC group was significantly lower than in the other groups (p<0.05. CONCLUSION: Drotrecogin alpha that is derived from recombinant APC has a protective effect on the pulmonary fibrosis induced by bleomycin. The protective effect seen with methyl-prednisolone is similar.

Kadir Y?ld?z

2013-04-01

79

Eosinophilic pneumonia associated with bleomycin in a patient with mediastinal seminoma: a case report  

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Full Text Available Abstract Introduction Lung toxicities resulting from the chemotherapeutic agent bleomycin encompass a variety of pathological changes, including bronchiolitis obliterans organizing pneumonia, interstitial pneumonitis and progressive interstitial fibrosis. We report a rare case of eosinophilic pneumonia associated with bleomycin. Case presentation A 44-year-old Hispanic man with a primary mediastinal seminoma complicated by superior vena cava syndrome underwent treatment with four cycles of bleomycin, etoposide and cisplatin. He had a complete positive response to the chemotherapy. However, three months after treatment he presented with shortness of breath and severe hypoxemia associated with peripheral eosinophilia. Computed tomography showed bilateral diffuse interstitial infiltrates that were refractory to antibiotic treatment. A lung biopsy showed eosinophilic pneumonia. He was subsequently treated with high-dose prednisone, resulting in a complete resolution of his symptoms and lung infiltrates. Conclusion This case illustrates that eosinophilic pneumonia may be a late sequela of bleomycin toxicity, and may respond dramatically to steroid treatment.

Chu David

2010-04-01

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The effect of ionizing radiation and bleomycin on transfecting ability of Bacillus subtilis phage DNA  

International Nuclear Information System (INIS)

Infectious DNA of Bacillus subtilis phage 029 and SPP1 has been subjected to ionizing radiation and/or bleomycin treatment. The extent of degradation of the treated DNA was determined on sucrose gradients and biological activity was analyzed using the transfection principle. It was found that loss of biological activity following irradiation or bleomycin treatment of the DNA cannot be accounted for by the production of single- or double-strand breaks. Furthermore, it was observed that pre-irradiation exhibits a synergistic effect on loss of biological activity and production of strand breaks following bleomycin treatment. The authors propose here a simple system capable of detecting biological damage in DNA following irradiation doses as low as 0.5 Gy prior to bleomycin treatment. (Auth.)

 
 
 
 
81

In-111 BLEDTA: a conjugate of bleomycin with a bifunctional chelating agent for tumor localization  

International Nuclear Information System (INIS)

BLEDTA, a bleomycin A2 analog containing an EDTA group was labeled in the EDTA group to a specific activity of 70 mCi/mg and used for animal and human studies. KHJJ mouse tumor uptake was higher than the orange Co-57 bleomycin isomer and the tumor/organ ratios were >1 for all organs except the kidney. In 29 biopsy proven cancer patients the scan done 24 hours post I.V. with 1-2 mCi of In-111 BLEDTA was positive in all clinically known sites in 18, and in some clinically known sites in 11. The In-111 BLEDTA clinical results are similar to reported Co-57 bleomycin clinical studies, and the method is proposed as an alternate way to produce a stable biologically active bleomycin labeled with In-111

82

HRCT findings of bleomycin-related lung toxicity: a report of 2 cases  

International Nuclear Information System (INIS)

Many drugs can result in a variety of pathologic reactions in the lung, especially the cytotoxic drugs. Among cytotoxic drugs bleomycin is a prototype. Bleomycin-related pulmonary toxicity is usually known as dose-dependent and can be enhanced with concurrent oxygen therapy, irradiation, or other chemotherapeutic agents. The incidence of bleomycin-induced pulmonary toxicity has been reported as varying from 2 to 46%, and 1% of fatal lung disease. We describe the radiographic and HRCT findings of bleomycin-related pulmonary toxicity developed in two patients: one in ovarian teratocarcinoma, the other malignant lymphoma patient. Chest radiographs and HRCT of these patients showed ground-glass opacities, consolidation, linear and reticular opacities, and interlobular septal thickening. These abnormalities were bilateral, and symmetrical and were found predominantly in the area of mid- and lower-lung zone

83

The 9Be(p,?)6Li and 9Be(p,d)8Be cross sections at low energies  

International Nuclear Information System (INIS)

Data for the 9Be(p,?)6Li and 9Be(p,d)8Be reactions with proton energies up to 700 keV are fitted using R-matrix formulae. The data include values of the astrophysical S factors and of the angular-distribution and analysing-power coefficients. A reasonable fit is obtained with two 1- and two 2+ levels of 10B, and one each of 2-, 1+ and 3+ levels. All represent levels outside the energy range fitted except for a 1- level at 6.87 MeV and a 2+ level at 6.95 MeV

84

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

International Nuclear Information System (INIS)

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

85

Asymptotic normalization coefficients for 14N?13C+p and 10B?9Be+p  

International Nuclear Information System (INIS)

The proton exchange reactions 13C(14N,13C)14N and 9Be(10B,9Be)10B were studied at energies where they are peripheral. Angular distributions for elastic scattering and proton transfer were measured, and the results were used to extract ANC's by comparison with modified DWBA calculations. These ANC's will be used together with proton transfer reactions with radioactive beams to determine astrophysical S-factors for radiative capture reactions, in particular S17(0) for 7Be(p,?)

86

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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AbstractBackground and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.Methods: Silymarin (50 mg/kg, i.p.) was administered two days before the bleomycin instillation (3 U/kg) and throughout the test interval in mice. After two weeks, lung tissues of mic...

Safaeian, L.; Jafarian Dehkordi, A.; Afshar-moghaddam, N.; Sarahroodi, S.

2009-01-01

87

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

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

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

2013-01-01

88

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

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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 ...

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

1999-01-01

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

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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 trea...

Saify B; Mozdarani H; Tiraihi T

2004-01-01

90

Bleomycin induced pulmonary to cytotoxicity in patients with germ cell tumours  

International Nuclear Information System (INIS)

Background: Bleomycin is a cytotoxic drug used in treatment of Germ Cell Tumours (GCTs) and is associated with pulmonary toxicity. Bleomycin pulmonary toxicity (BPT) manifests predominantly as pulmonary fibrosis, organising pneumonia (OP) or Nonspecific Interstitial Pneumonitis (NSIP). Our objectives were to determine the incidence of BPT, describe the common HRCT patterns of pulmonary toxicity and to find out the correlation of variables (cumulative dose of bleomycin, age and glomerular filtration rate) with pulmonary toxicity. Methods: The study included the data of 96 patients from March 2006 to September 2008. All patients had histologically proven GCT and received bleomycin containing regimes. Variables age, GFR at the time of initial presentation along with cumulative dose of bleomycin at completion of chemotherapy or at the time of BPT were recorded. The High resolution CT chest (HRCT) of these patients was independently reviewed by two radiologists. Bleomycin toxicity was reported on the radiologic features of pulmonary fibrosis, OP or NSIP. Results : Fourteen patients (14.6%) developed BPT. Common patterns of BPT were, pulmonary fibrosis (5.2%), OP (5.2%) and NSIP (4.2%). Using the Univariate regression analysis there was significant relationship between BPT and age, cumulative bleomycin dose an d initial GFR at the beginning of treatment. Conclusions: Because BPT can be progressive and fatal, early recognition is important. The diagnosis of pulmonary toxicitortant. The diagnosis of pulmonary toxicity should be considered in any patient with new or progressive respiratory complaints. BPT can be difficult to diagnose; therefore, knowledge and understanding of radiologic manifestations of toxicity caused by Bleomycin are necessary for institution of appropriate treatment. There is increasing incidence of BPT with increasing age, cumulative dose and decreasing GFR. (author)

91

Iron complexes and their reactivity in the bleomycin assay for radical-promoting loosely-bound iron.  

Science.gov (United States)

The sensitivity of the bleomycin assay for loosely-bound iron depends on the concentration of bleomycin and ascorbic acid and the pH of the reaction. The non-haem-iron proteins transferrin, conalbumin and ferritin release iron at an acid pH value, whereas the haem-iron proteins release iron more readily at an alkaline pH. In addition, haem proteins are liable to release iron when peroxides are present. Organic peroxides and hydrogen peroxide can be produced during the bleomycin reaction leading to iron release from haem proteins. However, this can be prevented from reacting with bleomycin by adding zinc ions to the reaction following addition of the sample. Iron already bound to bleomycin is not displaced by zinc whereas zinc bound to bleomycin is not displaced by iron allowing 'free' and 'released' iron to be discriminated. PMID:2463216

Gutteridge, J M; Hou, Y Y

1986-01-01

92

A validated HPLC method for the simultaneous determination of bleomycin A2 and B2 in human plasma  

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Full Text Available Bleomycin is an anti-neoplastic drug that has recently been used for the treatment of vascular anomalies. The plasma concentration of bleomycin following intralesional injection into vascular lesions is unknown. An expedient method was developed for the determination of plasma bleomycin levels using ion-paired reversed phase high performance liquid chromatography (HPLC. Prior to sample analysis using the HPLC, a one-step protein precipitation sample preparation procedure was used to remove proteins from the plasma. The calibration curve was linear over the range 0.1 - 0.8µg/mL bleomycin A2 and 0.2 – 1.0µg/mL bleomycin B2. Recovery was approximately 100%. This method provides a simple and rapid way of determining the levels of bleomycin A2 and B2 in patient plasma.

Peace Mabeta

2012-10-01

93

Development of 62Zn bleomycin as a possible PET tracer  

International Nuclear Information System (INIS)

Bleomycin (BLM), labeled with radioisotopes, is widely used in therapy and diagnosis. In this study, BLM was labeled with 62Zn for oncologic PET studies. The complex was obtained at pH = 2 in saline at 90oC in 25 min. Radio-TLC showed an overall radiochemical yield of 95-97% (radiochemical purity > 97%). Stability of complex was checked in vitro in mice and human plasma/urine. Preliminary in vivo studies were performed to determine complex stability and distribution of 62Zn BLM in normal and fibrosarcoma-bearing mice. 62Zn BLM accumulated significantly in induced fibrosarcoma tumors in mice according to biodistribution/imaging studies. 62Zn BLM can be used in PET oncology studies due to its suitable physicochemical properties as a diagnostic complex in vitro and in vivo. Further studies should be performed for evaluation of the complex behavior in larger mammals. (author)

94

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available AbstractBackground and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.Methods: Silymarin (50 mg/kg, i.p. was administered two days before the bleomycin instillation (3 U/kg and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant. Results: Pretreatment with Silymarin significantly (P<0.05 prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001. Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung.Keywords: Silymarin; Bleomycin; Pulmonary Fibrosis; Hydroxyproline.

L. Safaeian

2009-08-01

95

Production and biological studies of 111In-bleomycin for diagnosis/ therapy purposes  

International Nuclear Information System (INIS)

Fe mycin (Bleomycin) is an anti- neoplastic agent which is used in the treatment of squamous cell carcinoma, Hodgkin's lymphoma, and testicles carcinoma. Due to the progress in application and production of SPECT radioisotopes in nuclear medicine, bleomycin was labeled with In-111 which was well accepted in clinics, In mid 70' s un stability of 111 In-Bleomycin made scientists to ignore this agent as an imaging tool, but in 1984 a new stable complex was prepared and used in clinics. In order to obtain the best labeling reaction conditions, the complex formation was optimized for P H, temperature, time,and amount of bleomycin using I TLC and R TLC methods. The labeled compound was injected to normal rats (weighing 150-200 g). Autopsy on the rats at various time intervals after injection and the data was obtained and compared with In111 chloride in normal rats. The radio- labeling method, utilizes no chromatographic purification of desired compound, due to exact optimization of reaction conditions.Total labeling and formulation of 111In-Bleomycin took about 30 Min, with a yield of 99.8%. 111In-Bleomycin was examined by various chromatographic system and shown to have a consistent final specific activity in excess of 1.39 Ci/m mole (limit of detection). The radio-labeled complex was stable m aqueous solutions at leas for 24 hours species followed by filtration through a 0.22 u filteru filter

96

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

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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.

Dhar S

2009-01-01

97

Precision Measurements of the 7Be(p, ?)8B with Radioactive Beams and the 8B Solar Neutrino Flux  

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The 7Be(p, ?)8B reaction is one of the major source of uncertainties in estimating the 8B solar neutrino flux and is critical for understanding the Solar Neutrino Problem and neutrinos. The main source of uncertainty is the existence of conflicting data with different absolute normalization. Attempts to measure this reaction rate with 7Be beams are under way by the UConn-LLN collaboration, and we discuss a newly emerging method to extract this cross section from the Coulomb dissociation of the radioactive beam of 8B. We discuss some of the issues relevant for this study including the question of the E2 contribution to the Coulomb dissociation process which was measured to be small. The Coulomb dissociation appears to provide a viable alternative method for measuring the 7Be(p, ?)8B reaction rate, with a weighted average of the RIKEN1, RIKEN2 and GSI1 published results of S17(0) = 19.4 ± 1.3 eV-b.

Gai, Moshe

2001-04-01

98

In-vitro and in-vivo characterization of ruthenium-bleomycin compared to cobalt- and copper-bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM) has undergone extensive investigation both as a cancer chemotherapeutic agent, and as a carrier for radionuclides for tumor imaging. The available methods or the radionuclides used, however, have had limited effectiveness. Although labeling of BLM with 103Ru has been reported earlier, we carried out a study to develop a more reproducible method of labeling particularly for use with Brookhaven Linac Isotope Producer produced 97Ru. Ruthenium-97 has favorable physical properties that make it ideal for imaging applications: decay by electron capture; ? 216 keV, 85%; t/sub 1/2/ 2.9 d. A novel method based on the reduction of Ru3+ to Ru2+ using stannous chloride was investigated for labeling BLM with 97Ru and/or 103Ru. In-vitro and in vivo comparisons of the product(s) with 57Co and 67Cu-labeled BLM were also carried out. 4 refs., 3 tabs

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A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation  

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Full Text Available Objective: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM.Method: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor ?1?TGF-?1?and platelet-derived growth factor (PDGF in serum were measured on the 14th, 28th and 45th day of the experiment.Results: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P0.05. Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01, the level of serum TGF-?1 began to increase since 28 days after the experiment (P<0.05, P<0.01, and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05. And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups.Conclusion: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.

Wei ZHANG

2008-01-01

100

Distribution study of 57Co-, 51Cr-, 111In- and sup(99m)Tc- bleomycin in solid Ehrlich-carcinoma bearing mice  

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From the comparative studies of 57Co-, 51Cr-, 111In- and sup(99m)Tc-Bleomycin using 282 solid Ehrlich-carcinoma-bearing mice, 57Co was found to be the most suitable bleomycin preparation for tumor scintigraphy. The results obtained by 111In-Bleomycin of linear tumor cell absorption indicates a possible use of 111In-Bleomycin as an agent for objective histological differentiation also in cells previously treated with therapeutic agents. (orig.)

 
 
 
 
101

Study of the reactions 9Be(p, ?)6Li, 9Be(p,d)8Be from 300 keV to 900 keV  

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The experimental results concerning the two reactions 9Be(p,?)6Li and 9Be(p,d)8Be from 300 to 900 keV are presented. The angular distribution, excitation and total cross-section curves are expressed in absolute values after a normalization carried out using results given by Weber, Davis and Marion. (authors)

102

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Background and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.

Methods: Silymarin (50 mg/kg, i.p. was administered two days before the bleomycin instillation (3 U/kg and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant.

Results: Pretreatment with Silymarin significantly (P<0.05 prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001.    

Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung

L Safaeian

2012-05-01

103

Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice.  

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Collagens XII and XIV are members of a subfamily of fibril-associated collagens with interrupted triple-helices (FACITs) that facilitate the interactions of adjacent collagen fibrils. Using immunohistochemistry and in situ hybridization, we analyzed the spatial and temporal expression pattern of collagens XII and XIV during bleomycin-induced pulmonary fibrosis. C57Bl mice were treated with bleomycin (1 U, i.p., every other day for 8 days) or saline (control), and lung tissue samples were analyzed 2-12 weeks later. Collagen I protein expression was increased in the lung 2 weeks post bleomycin treatment and persisted for at least 12 weeks. In contrast, collagen XII and XIV expression was low until 4 weeks after bleomycin treatment. Whereas collagen XII expression was greatest between 4 weeks and 8 weeks, expression of collagen XIV persisted from 4 to 12 weeks, which suggests that these two proteins may play distinct roles in the fibrotic process. The mRNA for lysyl oxidase (LOX), an enzyme for cross-linking of collagens, had a delayed increase in the lung after bleomycin administration. It reached a maximum after 8 weeks, and persisted throughout the 12 weeks of the study. These data support the hypothesis that fibrosis is a multistep process that involves both collagen accumulation and changes in the molecules that modulate the biomechanical properties of fibrils. PMID:14613307

Tzortzaki, Eleni G; Tischfield, Jay A; Sahota, Amrik; Siafakas, Nikolaos M; Gordon, Marion K; Gerecke, Donald R

2003-12-01

104

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

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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)

105

Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation.  

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Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 ?g/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

Sonoda, Akinaga; Nitta, Norihisa; Tsuchiya, Keiko; Otani, Hideji; Watanabe, Shobu; Mukaisho, Kenichi; Tomozawa, Yuki; Nagatani, Yukihiro; Ohta, Shinichi; Takahashi, Masashi; Murata, Kiyoshi

2014-11-01

106

Bleomycin hydrolase and a genetic locus within the MHC affect risk for pulmonary fibrosis in mice.  

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Susceptibility to pulmonary fibrosis following environmental insults or cytotoxic cancer therapies has a genetic component. In mouse strains differing in susceptibility to bleomycin-induced lung fibrosis, we show highly significant linkage to only two loci. The first locus on chromosome 17 in the major histocompatibility complex (MHC), LOD = 17.4, named Blmpf1, is highly significant in both males and females, and accounts for approximately 20% of the phenotypic variance. We confirmed the presence of Blmpf1 in MHC congenic mice and narrowed the region to 2.7 cM in a reduced MHC congenic strain. The second locus on chromosome 11, LOD = 5.6, named Blmpf2, is significant in males only. A model including an interaction between Blmpf1 and Blmpf2 best fit the data in males. We confirmed Blmpf2 in a chromosome substitution strain, C57BL/6J-11(C3H), and found that its presence reduces the severity of fibrosis. Functional studies of bleomycin hydrolase activity indicate that this enzyme modulates bleomycin-induced pulmonary fibrosis, suggesting that it may be a candidate gene for Blmpf2. The data suggest sex-specific models of susceptibility to bleomycin-induced lung fibrosis, with an interaction between Blmpf2 and Blmpf1 for the more susceptible males and Blmpf1 as the major locus in females. A putative mechanism for the interaction between the two loci in males is that bleomycin hydrolase functions as an MHC class I epitope-processing protease. PMID:12140188

Haston, Christina K; Wang, Min; Dejournett, Robert E; Zhou, Xinhui; Ni, Dan; Gu, Xiangjun; King, Terri M; Weil, Michael M; Newman, Robert A; Amos, Christopher I; Travis, Elizabeth L

2002-08-01

107

Effects of N-acetyl-L-cysteine on bleomycin induced oxidative stress in malignant testicular germ cell tumors.  

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Testicular cancer is a very common cancer in males aged 15-44 years. Bleomycin is used in chemotherapy regimens in the treatment of patients having testicular germ-cell tumor. Bleomycin generates oxygen radicals, induces oxidative cleavage of DNA strand and induces apoptosis in cancer cells. There is no study in the literature investigating effects of N-Acetyl-L-Cysteine (NAC) on bleomycin-induced oxidative stress in testicular germ cell tumors. For this reason, we studied effects of NAC on oxidative stress produced in wild-type NTera-2 and p53-mutant NCCIT testis cancer cells incubated with bleomycin and compared the results with H(2)O(2) which directly produces oxidative stress. We determined protein carbonyl content, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), 8-isoprostane, lipid hydroperoxide levels and total antioxidant capacity in both testicular cancer cells. Bleomycin and H(2)O(2) significantly increased 8-isoprostane, TBARS, protein carbonyl and lipid hydroperoxide levels in NTera-2 and NCCIT cells. Bleomycin and H(2)O(2) significantly decreased antioxidant capacity and GSH levels in both cell lines. Co-incubation with NAC significantly decreased lipid hydroperoxide, 8-isoprostane, protein carbonyl content and TBARS levels increased by bleomycin and H(2)O(2). NAC enhanced GSH levels and antioxidant capacity in the NTera-2 and NCCIT cells. It can be concluded that NAC diminishes oxidative stress in human testicular cancer cells induced by bleomycin and H(2)O(2). PMID:22940535

Cort, Aysegul; Ozdemir, Evrim; Timur, Mujgan; Ozben, Tomris

2012-12-01

108

Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species  

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Bleomycin, an effective cancer chemotherapeutic agent, is associated with serious pulmonary toxicity. As an in vitro model of bleomycin pulmonary toxicity, this study examined the ability of bleomycin to injure chromium 51-labeled bovine pulmonary artery endothelial (BPAE) cells in an 18-hour cytotoxicity assay. The data indicate that bleomycin-mediated injury to cultured BPAE cells can be quantified by 51Cr release, expressed as cytotoxic index (CI). Bleomycin-mediated injury to 51Cr-labeled BPAE cells (CI 19.4 +/- 1.6) could be significantly reduced by the iron chelator deferoxamine, 10(-3) mol/L (CI 7.5 +/- 1.1, P less than 0.001), but not by ethylenediaminetetraacetic acid, 10(-5) mol/L (CI 19.8 +/- 2.2). Similarly, bleomycin-mediated injury to BPAE cells (monitored by lactate dehydrogenase release) with a CI 27.1 +/- 4.8 could be reduced by 10(-3) mol/L deferoxamine to CI 10.5 +/- 2.6 (P less than 0.01). In contrast, hyperoxia (95% O2) accelerated bleomycin (1 to 100 mU/ml) toxicity to BPAE cells (P less than 0.01, all comparisons). This study suggests that bleomycin-induced injury of pulmonary endothelial cells may be dependent in part on two critical factors in the cellular environment: the availability of iron to the cell and the ambient O2 concentration

109

Coulomb dissociation of 8B and the 7Be(p,?)8B reaction at low energies  

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The cross section for Coulomb dissociation of 8B---the 208Pb(8B,7Be p)208Pb reaction---was measured using a 8B radioactive beam of 46.5 MeV/nucleon energy, and the cross section for the 7Be(p,?)8B capture reaction was deduced at low energies; Ec.m.=0.6-1.7 MeV. The extracted astrophysical S17 factors were found to be consistent with the values measured by Vaughn et al. and Filippone et al. This result encourages further experimental studies extended to lower relative energies for a new determination of the S17 value relevant to the 8B solar neutrino flux

110

Biological basis of combination therapy with radiation and bleomycin  

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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.)

111

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

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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

112

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

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

113

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

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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.

Crimi Nunzio

2006-11-01

114

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

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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.

Saify B

2004-01-01

115

Latent Transforming Growth Factor-?1 Protects against Bleomycin-Induced Lung Injury in Mice.  

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Transforming growth factor (TGF)-?1 is a potent mediator known to induce lung fibrosis. However, the role of latent TGF-?1 in lung inflammation and fibrosis is unclear. To investigate the role of circulating latent TGF-?1 in bleomycin-induced lung injury, lung disease was induced in keratin-5 promoter-driven TGF-?1(wt) transgenic (Tg) mice by bleomycin. The role of latent TGF-?1 in pulmonary inflammation and fibrosis was examined at Days 7 and 28 after administration of bleomycin. Compared with littermate wild-type (WT) mice, TGF-?1(wt) Tg mice had over twofold-higher levels of latent TGF-?1 in both plasma and lung tissue, and were protected from bleomycin-induced pulmonary inflammation, such as up-regulation of IL-1?, TNF-?, and macrophage chemotactic protein-1, and infiltration of CD3(+) T cells and F4/80(+) macrophages. In addition, the severity of lung fibrosis with massive collagen matrix accumulation was markedly reduced in TGF-?1(wt) Tg mice. These protective effects were associated with higher levels of Smad7 and inactivation of both NF-?B and TGF-?/Smad3 signaling pathways, in addition to an increase in forkhead box P3 (Foxp3)-dependent regulatory T cells, but inhibition of T helper 17-mediated lung injury. In summary, mice overexpressing latent TGF-?1 are protected from bleomycin-induced lung injury. Triggering the Smad7 negative feedback mechanism to inhibit both NF-?B and TGF-?/Smad signaling pathways, and enhancing the regulatory T cell response to counter-regulate T helper 17-mediated lung injury, are potential mechanisms by which latent TGF-?1 protects against bleomycin-induced lung injury. PMID:24885478

Tang, Yong-Jiang; Xiao, Jun; Huang, Xiao Ru; Zhang, Yang; Yang, Chen; Meng, Xiao-Ming; Feng, Yu-Lin; Wang, Xiao-Jing; Hui, David S C; Yu, Cheuk-Man; Lan, Hui Yao

2014-12-01

116

Long term follow-up in patients with a naso-pharynx carcinoma after induction chemotherapy by cisplatin, 5-fluoro-uracil and bleomycin (pbf) followed by a bi-fractionated radiotherapy and a consolidation chemotherapy; Survie a long terme chez des patients atteints d'un carcinome du nasopharynx apres chimiotherapie d'induction par cisplatine, 5-fluoro-uracile et bleomycine (pbf) suivie d'une radiotherapie bifractionnee et une chimiotherapie de consolidation  

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

Djekkoun, R.; Boudaoud, K.; Ferdi, N.; Filali, T. [CAC CHU, Constantine (Algeria)

2009-10-15

117

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

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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.

Sales Magaly M.

1999-01-01

118

[Scintigraphy with 111In-bleomycin in the diagnosis of recurrences of rectal cancer].  

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Altogether 76 patients were examined using scintigraphy with 111In-bleomycin. Clinicoroentgenological diagnosis of recurring rectal cancer was confirmed in 62 of them. Fourteen patients were without signs of recurrence. A focus of RP hyperfixation in the small pelvis was revealed on scintigrams in 52 (84%) of 62 patients. In 4 cases the results of examination were considered doubtful, and in 6 cases the results were false positive. Of 14 recurrence-free patients 4 had recurring tumors at early stages prior to clinical manifestations. The authors pointed to the prospects of the employment of 111In-bleomycin for diagnosis of rectal cancer recurrences. PMID:2415800

Lenskaia, O P; Ozhiganov, E L; Bogdasarov, Iu B

1985-11-01

119

Treatment of advanced seminoma with Dactinomycin, Cyclophosphamide, vinblastine, Bleomycin and Cisplatinum (The Vab-6 protocol)  

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Eighteen patients with advanced seminoma (Stages IIC-III) were treated with chemotherapy. Surgery and/or radiotheraphy were used in some cases that presented residual masses or recurrences. The therapeutic methods are discussed. (M.A.C.)

120

Normal distribution of 111In-bleomycin on scintigram  

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Bleomycin labelled with 111In was used as a tumor-localizing agent in 36 patients (40 scintigrams), who were suspected of or clinically diagnosed as having malignant tumor. All patients were inpatients or outpatients of the department of Radiology, University of Tokyo. The sites where there was clinically suspected malignant disease and where there was an abnormal accumulation on scintigrams were excluded in estimating the normal distribution of 111In-BLM. All scintigrams were taken 48 hrs after injection of 111In-BLM 2 - 3 mCi. The score of normal distribution was as follows: liver 100, mediastinum 54.0, thyroid area 50.0, nasopharynx 48.5, salivary area 42.5, lumbar spine 40.5 and kidney 30.5. The large intestine, hip joints, eye area and lung fields were revealed in a few cases. Comparing this study with the previous study on normal distribution of 67Ca-citrate, the score of large intestine was shown to be 28.5 - 37 points on 67Ga-citrate scintigrams, but it was only 1.5 - 0 points on 111In-BLM scintigrams. The kidneys were not appreciated on 67Ga-citrate scintigrams, but its score was 31.5 on 111In-BLM scintigrams. On the chest, the heart was not revealed on 67Ga-citrate scintigrams, but its score was 37.5 on 111In-BLM scintigrams. We conclude that 111In-BLM would be more effective than 67Ga-citrate in detecting malignant tumors whichitrate in detecting malignant tumors which locate in lower abdomen. (auth.)

 
 
 
 
121

Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury  

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Full Text Available Abstract Background In the present study, by comparing the responses in wild-type mice (WT and mice lacking (KO the inducible (or type 2 nitric oxide synthase (iNOS, we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i lost of body weight, (ii mortality rate, (iii infiltration of the lung with polymorphonuclear neutrophils (MPO activity, (iv edema formation, (v histological evidence of lung injury, (vi lung collagen deposition and (vii lung Transforming Growth Factor beta1 (TGF-?1 expression. Methods Mice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice. Results The intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p. also significantly attenuated all of the above indicators of lung damage and inflammation. Conclusion Taken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice.

Crimi Nunzio

2005-06-01

122

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

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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

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

123

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

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

Araújo Maria Cristina P.

1999-01-01

124

Coulomb displacement energy and the low-energy astrophysical S17 factor for the 7Be(p,?)8B reaction  

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The relationship between the Coulomb displacement energy for the A=8, J=2+, T=1 state and the low-energy astrophysical S17 factor for the 7Be(p,?)8B reaction is discussed. The displacement energy is interpreted in a particle-hole model. The dependence of the particle displacement energy on the potential well geometry is investigated and is used to relate the particle displacement energy to the rms radius and the asymptotic normalization of the valence proton wave function in 8B. The asymptotic normalization is used to calculate the astrophysical S17 factor for the 7Be(p,?) reaction. The relationship to the 7Li(n,?) reaction, the 8B quadrupole moment, radial density, and break-up momentum distribution are also discussed. (orig.)

125

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Background and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.

Methods

Safaeian, L.

2012-01-01

126

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

International Nuclear Information System (INIS)

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

127

Preparation of phase I of clinical testing of kit for bleomycin labelling with 57Co  

International Nuclear Information System (INIS)

Experience is described gained in preclinical trials with a kit for bleomycin labelling with 57Co, of original manufacture. The 57Co-labelled bleomycin shows a positive tumor imaging potential. As against other labelled bleomycins described in the literature, it best meets the requirements of imaging tumors in the highest possible number of tissues and of good differentiation of tumors from the adjacent tissues. The three-component kit uses a phosphate buffer which makes it more suitable for i.v. administration and significantly increases bleomycin stability. The kit was found to show advantages over previously described radiopharmaceuticals of this type in that that it can quickly be reconstituted immediately prior to the application and that it is significantly cheaper to use, namely 140-fold cheaper than most other similar radiopharmaceuticals. Its disadvantage, i.e., the long half-life is balanced with a short biological half-life; within 24 hours following application 80 to 90% of the applied activity was found to be excreted from the organism. The short biological half-life is also beneficial for the patient in that the radiation load of the patient is 10 times lower than in the application of 67Ga. (L.O.)

128

Effect of pravastatin on bleomycin-induced acute lung injury and pulmonary fibrosis.  

Science.gov (United States)

1. Pravastatin is best known for its antilipidemic action. Recent studies have shown that statins have immunomodulatory and anti-inflammatory effects. The present study aimed to determine whether or not pravastatin can attenuate acute lung injury and fibrosis in a mouse model. 2. Bleomycin was given to C57BL6 mice through intratracheal instillation. Pravastatin was given through intraperitoneal injection. To study the effect of pravastatin on the early inflammatory phase and the late fibrotic phase, mice were killed on days 3, 7, 14 and 21. 3. Pravastatin attenuated the histopathological change of bleomycin-induced lung injury and fibrosis. The accumulation of neutrophils and increased production of tumor necrosis factor-? in bronchoalveolar lavage fluid were inhibited in the early inflammatory phase. Pravastatin effectively inhibited the increase of lung hydroxyproline content induced by bleomycin. Furthermore, pravastatin reduced the increased expression of transforming growth factor (TGF)-?1, connective tissue growth factor (CTGF), RhoA and cyclin D1. The increased levels of TGF-?1 and CTGF mRNA expression were also significantly inhibited by pravastatin. 4. Pravastatin effectively attenuated bleomycin-induced lung injury and pulmonary fibrosis in mice. Our results provide evidence for the therapeutic potential of pravastatin in the treatment of acute lung injury and pulmonary fibrosis. PMID:20659133

Kim, Jin Woo; Rhee, Chin Kook; Kim, Tae Jung; Kim, Yong Hyun; Lee, Sang Haak; Yoon, Hyung Kyu; Kim, Seok Chan; Lee, Sook Young; Kwon, Soon Suk; Kim, Kwan Hyung; Kim, Young Kyoon

2010-11-01

129

Characteristics of mutagenesis by bleomycin and adriamycin in Salmonella typhimurium: action of catalase.  

Science.gov (United States)

The influence of catalase activity in adriamycin and bleomycin mutagenesis was investigated in Salmonella typhimurium TA98 and TA102, respectively. The activity of catalase in bacterial cells was inhibited by sodium azide. Mutagenicity of both drugs was not changed in bacterial cells with depressed catalase activity. PMID:9415210

Ejchart, A; Ch?opkiewicz, B

1996-01-01

130

57Co-bleomycin scintigraphy for the postoperative detection and staging of lung tumors  

International Nuclear Information System (INIS)

In a patient with Pancoast tumor, obscured on radiograms by pleural thickening following earlier tuberculosis, the primary cancer was detected by 57Co-Bleomycin scintigraphy. It helped also in delineating the area which had to be subjected to external radiotherapy. (orig./MG)

131

Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice  

International Nuclear Information System (INIS)

The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity

132

A new determination of the astrophysical S-factor for the 7Be(p,?)8B reaction from direct cross section measurements  

International Nuclear Information System (INIS)

We measured the 7Be(p,?)8B cross section from E-barcm=186 to 1200 keV, with a statistical-plus-systematic precision per point of better than ±5%. All important systematic errors were measured including 8B backscattering losses. We obtain S17(0)=22.3±0.7(expt)±0.5(theor) eV-b from our data at E-barcm?300 keV and the theory of Descouvemont and Baye

133

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

International Nuclear Information System (INIS)

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

134

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

International Nuclear Information System (INIS)

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.

135

Increased breakage of chromosome 1 in lymphocytes of patients with testicular cancer after bleomycin treatment in vitro.  

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Chromosome damage in vitro after bleomycin treatment during the late S and G2 phases of the cell cycle was studied in the peripheral lymphocytes of 19 untreated patients with primary testicular tumours and 22 age-matched healthy men with no excess of cancer incidence in the families. The occurrence of spontaneous chromosome aberrations was not shown to be different in the studied groups. However, in the lymphocytes treated with bleomycin, cancer patients exhibited higher numbers of break even...

Vorechovsky, I.; Zaloudik, J.

1989-01-01

136

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

International Nuclear Information System (INIS)

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

137

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

International Nuclear Information System (INIS)

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

138

Structure-activity relationships involved in the site-specific fragmentation of linear duplex DNAs by talisomycin and bleomycin analogs.  

Science.gov (United States)

The fragmentation of Hind III- and Pst I-digested PM2 DNA and of Hind III-digested pBR322 DNA by bleomycin A2 and B2 and talisomycins A, B, S2b, and S10b was investigated. As observed by electrophoresis on agarose gels, the ethidium bromide staining band patterns produced following incubation of the various restriction endonuclease-digested DNAs with the compounds were different for the bleomycin analogs and for the talisomycin analogs. Quantitation of the degree of fragmentation of various segments of linear PM2 DNA by either bleomycin A2 or talisomycin A indicated that certain segments of the PM2 genome serve as better substrates than other segments for double-strand fragmentation by either of the two antitumor antibiotics. These results show that in this system bleomycin and talisomycin analog treatment of linear PM2 or pBR322 DNA resulted in breakage of DNA, producing different-length DNA fragments, and demonstrate the importance of the two amino acids and the 4-amino-4,6-dideoxy-L-talose sugar, which are located near the bithiazole in talisomycin but absent in the bleomycin structure in conferring a different site-specificity for DNA fragmentation to talisomycin than to bleomycin. PMID:6178526

Mirabelli, C K; Huang, C H; Prestayko, A W; Crooke, S T

1982-01-01

139

The synthesis of radioiodinated cobalt-bleomycin and its in vivo distributions in tumor-bearing animals  

International Nuclear Information System (INIS)

This study is the addition of radioactive iodine on cobalt-bleomycin without changing its tumor-localizing properties. Cobalt-bleomycin demethy-A2 was synthesized by adding CoCl2 to bleomycin demethyl-A2 aqueous solution. On the other side, 3-125I-iodobenzylalcohol was prepared by replacing iodine of 3-iodobenzylalcohol with iodine-125I. And 3-125I-iodobenzyliodide was produced by adding P2I4 to 3-125I-iodobenzylalcohol in CH2Cl2. 3-125I-iodobenzyl-cobalt-bleomycin was synthesized by coupling 3-125I-iodobenzyliodide to cobalt-bleomycin demethyl-A2. 3-125I-iodobenzyl-cobalt-bleomycin was injected intravenously to tumor-bearing mice. In vivo distributions of this compound were measured from 60 minutes to 24 hours after injection. Accumulation of this compound in tumor tissue was much more than other normal organs except kidney and liver. This new labeled compound showed considerably strong affinity to malignant tumor. (author)

140

FDG-PET in bleomycin-induced pneumonitis following ABVD chemotherapy for Hodgkin's disease--a useful tool for monitoring pulmonary toxicity and disease activity.  

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Bleomycin-related pneumonitis (BIP) has recently emerged as one of the main causes of death in Hodgkin's disease treated with standard chemotherapy ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). We used 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning in a patient with Hodgkin's disease who developed bleomycin lung toxicity following the 4(th) cycle of chemotherapy. The PET scan done two month after the acute presentation with BIP showed uptake of FDG in the l...

Buchler, T.; Bomanji, J.; Lee, S. M.

2007-01-01

 
 
 
 
141

Effects of Recombinant Activated Protein C Derived From Drotrecogin-Alpha on Bleomycin-Induced Pulmonary Fibrosis in Rats Compared with Methyl-Prednisolone  

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OBJECTIVE: In this study, we aimed to test the preventive effects of intraperitoneally administered drotrecogin alpha which is derived from activated protein C (APC), on bleomycin-induced pulmonary fibrosis in rats, and to compare the effects of APC with the effects of methyl-prednisolone, a traditional therapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were randomly allocated into four groups: 1. Saline alone (n=6); 2. Bleomycin+placebo (n=7); 3. Bleomycin+methyl-prednisolone (n=7...

Kadir Y?ld?z; Mustafa Iraz; Emine ?amdanc?; Elif Özerol; ?rfan Kuku; Zeynep Ayfer Aytemur

2013-01-01

142

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

International Nuclear Information System (INIS)

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

143

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

Directory of Open Access Journals (Sweden)

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.

NIKOS KATSAROS

2003-05-01

144

Successful treatment of disseminated interdigitating dendritic cell sarcoma with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy  

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Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the b...

Lee, Suk-young; Lee, Se Ryeon; Chang, Won Jin; Kim, Hye Sook; Kim, Byung Soo; Kim, In Sun

2012-01-01

145

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

Science.gov (United States)

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

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

2012-12-01

146

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

International Nuclear Information System (INIS)

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

147

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

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Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The load...

Yue Xu; Yi Lin; Lin Zhuang; Jiong Lin; Jiahong Lv; Qin Huang; Jiadong Sun

2013-01-01

148

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

Scientific Electronic Library Online (English)

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

Sandra, Cabrera Benítez.

2006-03-01

149

Epithelial-fibroblast interactions in bleomycin-induced lung injury and repair.  

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Intercellular communication between epithelial cells and fibroblasts of the alveolar wall contributes to regulatory control of each cell type. We examined whether lung injury and subsequent fibrosis are associated with disturbance of this mutual control system. Rats received bleomycin intratracheally, and after 10 days, when acute epithelial injury occurs, and at 6 weeks, when repair with fibrosis is found, pure populations of type 2 epithelial cells and lung fibroblasts were prepared to stud...

Young, L.; Adamson, I. Y.

1993-01-01

150

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

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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

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

2011-01-01

151

Role of E-selectin in bleomycin induced lung fibrosis in mice  

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BACKGROUND—Bleomycin (BLM), a well known anti-cancer drug, often causes acute lung injury and fibrosis by mechanisms that are not well understood. It is suspected that some proteases and active oxygen species generated from inflammatory cells cause the lung injury and subsequent lung fibrosis. It was therefore hypothesised that inhibition of adhesion of inflammatory cells to the endothelium might prevent these developments.?METHODS—BLM (100 mg/kg) was injected into ...

Azuma, A.; Takahashi, S.; Nose, M.; Araki, K.; Araki, M.; Takahashi, T.; Hirose, M.; Kawashima, H.; Miyasaka, M.; Kudoh, S.

2000-01-01

152

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice  

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Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1...

Kazuyuki Tobe; Hirofumi Ogawa; Takashi Kondo; Masakiyo Sasahara; Kensuke Suzuki; Tomomi Ichikawa; Ryuji Hayashi; Shingo Imanishi

2012-01-01

153

Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis  

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Fibrotic interstitial pneumonias are more prevalent in males of advancing age, although little is known about the underlying mechanisms. To evaluate the contributions of age and sex to the development of pulmonary fibrosis, we intratracheally instilled young (8–12 wk) and aged (52–54 wk) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration, and stereological...

Redente, Elizabeth F.; Jacobsen, Kristen M.; Solomon, Joshua J.; Lara, Abigail R.; Faubel, Sarah; Keith, Rebecca C.; Henson, Peter M.; Downey, Gregory P.; Riches, David W. H.

2011-01-01

154

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

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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 BL...

Suddek, Ghada M.; Salem, Hatem A.; Badary, Osama A.; Gameil, Nariman M.; El-kashef, Hassan A.

2014-01-01

155

Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs.  

Science.gov (United States)

Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-?-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bleomycin-induced lung injury with systemic TSG-6 administration may produce therapeutic effects such as preventing the deterioration of lung function and increasing survival by modulation of the inflammatory cascade. Lung injury in C57Bl/6J mice was induced by intratracheal administration of bleomycin. Mice then received intravenous injections of TSG-6 or sham controls. Pulse oximetry was used to monitor changes in lung function. Cell infiltration was evaluated by flow cytometry, cytokine expression was measured by ELISA assays, and lungs were assessed for histological attributes. The results demonstrated that intravenous infusion of TSG-6 during the early inflammatory phase decreased cellular infiltration into alveolar spaces. Most importantly, it improved both the subsequent decrease in arterial oxygen saturation levels and the survival of the mice. These findings demonstrated that the beneficial effects of TSG-6 in a model of bleomycin-induced lung injury are largely explained by the protein modulating the early inflammatory phase. Similar phase-directed strategy with TSG-6 or other therapeutic factors that MSCs produce may be useful for other lung diseases and diseases of other organs. PMID:24242012

Foskett, Andrea M; Bazhanov, Nikolay; Ti, Xinyu; Tiblow, April; Bartosh, Thomas J; Prockop, Darwin J

2014-01-01

156

Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-?-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bl...

Foskett, Andrea M.; Bazhanov, Nikolay; Ti, Xinyu; Tiblow, April; Bartosh, Thomas J.; Prockop, Darwin J.

2013-01-01

157

Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis.  

Science.gov (United States)

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures. PMID:11401889

Borzone, G; Moreno, R; Urrea, R; Meneses, M; Oyarzún, M; Lisboa, C

2001-06-01

158

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

International Nuclear Information System (INIS)

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

159

Protease activated receptor-1 deficiency diminishes bleomycin-induced skin fibrosis.  

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Accumulating evidence shows that protease-activated receptor-1 (PAR-1) plays an important role in the development of fibrosis, including lung fibrosis. However, whether PAR-1 also plays a role in the development of skin fibrosis remains elusive. The aim of this study was to determine the role of PAR-1 in the development of skin fibrosis. To explore possible mechanisms by which PAR-1 could play a role, human dermal fibroblasts and keratinocytes were stimulated with specific PAR-1 agonists or antagonists. To investigate the role of PAR-1 in skin fibrosis, we subjected wild-type and PAR-1-deficient mice to a model of bleomycin-induced skin fibrosis. PAR-1 activation leads to increased proliferation and extra cellular matrix (ECM) production, but not migration of human dermal fibroblasts (HDF) in vitro. Moreover, transforming growth factor (TGF)-? production was increased in keratinocytes upon PAR-1 activation, but not in HDF. The loss of PAR-1 in vivo significantly attenuated bleomycin-induced skin fibrosis. The bleomycin-induced increase in dermal thickness and ECM production was reduced significantly in PAR-1-deficient mice compared with wild-type mice. Moreover, TGF-? expression and the number of proliferating fibroblasts were reduced in PAR-1-deficient mice although the difference did not reach statistical significance. This study demonstrates that PAR-1 contributes to the development of skin fibrosis and we suggest that PAR-1 potentiates the fibrotic response mainly by inducing fibroblast proliferation and ECM production. PMID:24842054

Duitman, JanWillem; Ruela-de-Sousa, Roberta R; Shi, Kun; de Boer, Onno J; Borensztajn, Keren S; Florquin, Sandrine; Peppelenbosch, Maikel P; Spek, C Arnold

2014-01-01

160

Targeting Her-2+ breast cancer cells with bleomycin immunoliposomes linked to LLO.  

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Bleomycin is a membrane impermeable chemotherapeutic agent that is relatively innocuous extracellularly but highly cytotoxic when delivered directly to the cytoplasm. We report on the development of a liposome delivery system that targets Her-2 overexpressing breast cancer cells and breaches the endosomal barrier, delivering bleomycin to the cytoplasm. The liposomes are conjugated to the antibody trastuzumab, which results in specific binding and internalization of liposomes into Her-2 overexpressing cells. In addition, the liposomes are disulfide bonded to a pore-forming protein listeriolysin O (LLO) which forms pores in the endosome and allows the liposomal cargo to pass into the cytoplasm. We demonstrate specific delivery to Her-2 positive MCF-7/Her18 cells relative to Her-2 negative MCF-7 cells using a fluorescent probe calcein within the immunoliposomes. When calcein is replaced by bleomycin, the liposomes effectively reduce viability of five different Her-2 overexpressing cell lines (BT-474, SKBR-3, MCF-7/Her18, HCC-1954 and MDA-453) while harming to a much lesser extent Her-2 negative breast cell lines (MCF-7, MCF-12a and MCF-10a). The liposomes also affect trastuzumab-resistant cells, reducing MDA-453 cell number by 97% compared to untreated cells. Importantly, the concentration of drug needed to reduce tumor cell growth and viability using this liposome therapy is approximately 57,000-fold less than the concentration needed if drug is delivered extracellularly, raising the possibility of increased therapeutic specificity with decreased side effects. PMID:22621404

Kullberg, Max; Mann, Kristine; Anchordoquy, Thomas J

2012-07-01

 
 
 
 
161

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

Science.gov (United States)

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1? levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1? and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1?, BAFF and IL-17A. PMID:25441030

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

2015-01-01

162

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

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

Zuojun Xu

2012-07-01

163

Studies of 57Co-bleomycin in patients with carcinoma colli uteri  

International Nuclear Information System (INIS)

The kinetics of 57Co-Bleomycin was studied in twelve patients with histologically proven carcinoma colli uteri and in ten patients with benign gynaecological conditions. Measurements were carried out on the whole body, on parts of the body and on urine and blood using a whole body counter. Excretion of the tumour-seeking radiopharmaceutical is predominantly through the kidneys and can be described by a double compartment model. After 48 hours, 2 - 4% of the applied activity is still present in the body. Radiation exposure to the body, the kidneys and bladder was calculated from the measurements and MIRD tables as 0.02 rad/mci (total body), 0.4 rad/mCi (kidneys) and 0.2 raf/mCi (bladder). In view of the rapid elimination of 57Co-Bleomycin, these figures are lower than data data quoted in the literature. There was no evidence of significantly higher uptake of 57Co-Bleomycin in the carcinomatous epithelium of the collum uteri compared with benign diseases, using the total body counter in the scan node. As possible explanations for this, the authors suggest inadequate geometric resolution of the system and a low tumour/non-tumour distribution ratio. (orig.)

164

Study of the D(p,?+)T and 9Be(p,?+)10Be from 400 to 800MeV  

International Nuclear Information System (INIS)

Pion production on CD2 and 9Be targets has been observed using the high resolution, energy loss, spectrometer SPES I. Differential cross sections for the D(p,?+) reaction have been determined at 410, 605 and 809MeV and for the 9Be(p,?+) reaction at 410 and 605MeV. The 3.37MeV (2+) state in 10Be is populated preferentially, but a significant part of the transition strength seems to populate the ground state and the higher lying multiplets at about 6.1MeV, 7.4MeV and 9.4MeV

165

A windowless hydrogen gas target for the measurement of {sup 7}Be(p, {gamma}){sup 8}B with the recoil separator ERNA  

Energy Technology Data Exchange (ETDEWEB)

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

Schuermann, D.; Di Leva, A.; Imbriani, G.; Romano, M. [Sezione di Napoli, INFN, Napoli (Italy); Universita Federico II, Dipartimento di Scienze Fisiche, I-80126 (Italy); Gialanella, L.; De Cesare, M.; De Cesare, N.; D' Onofrio, A; Terrasi, F. [Sezione di Napoli, INFN, Napoli (Italy); Seconda Universita di Napoli, Dipartimento di Matematica e Fisica, Caserta (Italy); Romoli, M. [Sezione di Napoli, INFN, Napoli (Italy)

2013-06-15

166

Photochemical Internalization of Bleomycin Before External-Beam Radiotherapy Improves Locoregional Control in a Human Sarcoma Model  

International Nuclear Information System (INIS)

Purpose: The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol. Methods and Materials: A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS2a and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm2). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation. Results: Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time. Conclusion: Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding longin local tumor control while avoiding long-term sequelae from radiotherapy.

167

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

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

Bahram Yousefian

2012-07-01

168

A spatially explicit hydro-ecological modeling framework (BEPS-TerrainLab V2.0): Model description and test in a boreal ecosystem in Eastern North America  

Science.gov (United States)

SummaryA spatially explicit, process-based hydro-ecological model, BEPS-TerrainLab V2.0, was developed to improve the representation of ecophysiological, hydro-ecological and biogeochemical processes of boreal ecosystems in a tightly coupled manner. Several processes unique to boreal ecosystems were implemented including the sub-surface lateral water fluxes, stratification of vegetation into distinct layers for explicit ecophysiological representation, inclusion of novel spatial upscaling strategies and biogeochemical processes. To account for preferential water fluxes common in humid boreal ecosystems, a novel scheme was introduced based on laboratory analyses. Leaf-scale ecophysiological processes were upscaled to canopy-scale by explicitly considering leaf physiological conditions as affected by light and water stress. The modified model was tested with 2 years of continuous measurements taken at the Eastern Old Black Spruce Site of the Fluxnet-Canada Research Network located in a humid boreal watershed in eastern Canada. Comparison of the simulated and measured ET, water-table depth (WTD), volumetric soil water content (VSWC) and gross primary productivity (GPP) revealed that BEPS-TerrainLab V2.0 simulates hydro-ecological processes with reasonable accuracy. The model was able to explain 83% of the ET, 92% of the GPP variability and 72% of the WTD dynamics. The model suggests that in humid ecosystems such as eastern North American boreal watersheds, topographically driven sub-surface baseflow is the main mechanism of soil water partitioning which significantly affects the local-scale hydrological conditions.

Govind, Ajit; Chen, Jing Ming; Margolis, Hank; Ju, Weimin; Sonnentag, Oliver; Giasson, Marc-André

2009-04-01

169

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

International Nuclear Information System (INIS)

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

170

The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis.  

Science.gov (United States)

ABSTRACT 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. In this review, we compare the pathogenesis and histological features of human IPF and bleomycin-induced pulmonary fibrosis (BPF) induced in rodents by intratracheal delivery. We discuss the current understanding of IPF and BPF disease development, from the contribution of alveolar epithelial cells and inflammation to the role of fibroblasts and cytokines, and draw conclusions about what we have learned from the intratracheal bleomycin model of lung fibrosis. PMID:25514507

Williamson, James D; Sadofsky, Laura R; Hart, Simon P

2015-03-01

171

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

International Nuclear Information System (INIS)

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

172

IRAK-M Promotes Alternative Macrophage Activation and Fibroproliferation in Bleomycin-Induced Lung Injury.  

Science.gov (United States)

Idiopathic pulmonary fibrosis is a devastating lung disease characterized by inflammation and the development of excessive extracellular matrix deposition. Currently, there are only limited therapeutic intervenes to offer patients diagnosed with pulmonary fibrosis. Although previous studies focused on structural cells in promoting fibrosis, our study assessed the contribution of macrophages. Recently, TLR signaling has been identified as a regulator of pulmonary fibrosis. IL-1R-associated kinase-M (IRAK-M), a MyD88-dependent inhibitor of TLR signaling, suppresses deleterious inflammation, but may paradoxically promote fibrogenesis. Mice deficient in IRAK-M (IRAK-M(-/-)) were protected against bleomycin-induced fibrosis and displayed diminished collagen deposition in association with reduced production of IL-13 compared with wild-type (WT) control mice. Bone marrow chimera experiments indicated that IRAK-M expression by bone marrow-derived cells, rather than structural cells, promoted fibrosis. After bleomycin, WT macrophages displayed an alternatively activated phenotype, whereas IRAK-M(-/-) macrophages displayed higher expression of classically activated macrophage markers. Using an in vitro coculture system, macrophages isolated from in vivo bleomycin-challenged WT, but not IRAK-M(-/-), mice promoted increased collagen and ?-smooth muscle actin expression from lung fibroblasts in an IL-13-dependent fashion. Finally, IRAK-M expression is upregulated in peripheral blood cells from idiopathic pulmonary fibrosis patients and correlated with markers of alternative macrophage activation. These data indicate expression of IRAK-M skews lung macrophages toward an alternatively activated profibrotic phenotype, which promotes collagen production, leading to the progression of experimental pulmonary fibrosis. PMID:25595781

Ballinger, Megan N; Newstead, Michael W; Zeng, Xianying; Bhan, Urvashi; Mo, Xiaokui M; Kunkel, Steven L; Moore, Bethany B; Flavell, Richard; Christman, John W; Standiford, Theodore J

2015-02-15

173

Human Umbilical Cord Mesenchymal Stem Cells Reduce Fibrosis of Bleomycin-Induced Lung Injury  

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Acute respiratory distress syndrome is characterized by loss of lung tissue as a result of inflammation and fibrosis. Augmenting tissue repair by the use of mesenchymal stem cells may be an important advance in treating this condition. We evaluated the role of term human umbilical cord cells derived from Wharton’s jelly with a phenotype consistent with mesenchymal stem cells (uMSCs) in the treatment of a bleomycin-induced mouse model of lung injury. uMSCs were administered systemically, and...

Moodley, Yuben; Atienza, Daniel; Manuelpillai, Ursula; Samuel, Chrishan S.; Tchongue, Jorge; Ilancheran, Sivakami; Boyd, Richard; Trounson, Alan

2009-01-01

174

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

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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.Inúmeros trabalhos têm demonstrado que linfócitos de pacientes com síndrome de Down apresentam uma maior freqüência de aberrações cromossômicas quando expostos a radiação ionizante ou agentes químicos nas fases G0 ou G1 do ciclo celular, mas não em G2, quando comparados com controles normais. Para determinar a sensibilidade de linfócitos de pacientes com síndrome de Down, na fase G2, usou-se o radiomimético bleomicina em culturas de linfócitos de 24 pacientes. Todos os pacientes mostraram trissomia livre do cromossomo 21 (47,XX + 21 ou 47,XY + 21. Indivíduos que apresentaram freqüência média de quebras cromatídicas por célula superior a 0,8 foram considerados sensíveis à droga. Nenhum controle apresentou suscetibilidade à bleomicina e entre os 24 pacientes com síndrome de Down somente um foi sensível à droga. Não se observou qualquer diferença significativa entre os dois grupos em relação às freqüências de quebras cromatídicas em linfócitos em G2, o que está de acordo com outros trabalhos. A distribuição das quebras induzidas pela bleomicina, em cada grupo cromossômico, foi igual para pacientes e controles. Nenhuma diferença significativa foi observada na resposta à bleomicina entre homens e mulheres, nos dois grupos. Provavelmente, o principal fator envolvido na sensibilidade cromossômica de linfócitos de pacientes com síndrome de Down seja a fase do ciclo celular na qual a célula é tratada.

Marlise Ladvocat Bartholomei-Santos

1997-03-01

175

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

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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...

Marlise Ladvocat Bartholomei-Santos; Edmundo José de Lucca

1997-01-01

176

Modulation of the clastogenic activity of ionizing radiation and bleomycin by the aminothiol WR-1065  

International Nuclear Information System (INIS)

WR-1065 (2-[(aminopropyl)amino]ethanethiol) reduces the induction by ionizing radiation of genetic damage, including DNA single- and double-strand breaks, chromosomal aberrations, micronuclei, and hprt mutations in mammalian cells. The effectiveness of WR-1065 as a radioprotector is apparently enhanced by its tendency, a a cationic thiol, to concentrate near DNA. The authors have studied the modulation by WR-1065 of the induction of chromosome aberrations and micronuclei in G0 human lymphocytes by ionizing radiation and by the radiomimetic chemical bleomycin

177

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

LENUS (Irish Health Repository)

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.

Quintyne, Keith Ian

2011-09-01

178

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

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

Citro Gennaro

2008-11-01

179

Response of radiation-sensitive mutants of Saccharomyces cerevisiae to lethal effects of bleomycin  

International Nuclear Information System (INIS)

Haploid and diploid strains of yeast containing genes conferring radiation-sensitivity were studied under growing and nongrowing experimental conditions for their relative sensitivities to growth-inhibitory effects of bleomycin (BM). The rad1, rad2, rad3, rad4, rad5 (and allelic rev2), rad7, rad10, rad11, rad12, rad14, rad15, rad16 and rev3 strains exhibited responses similar to normal (Rad+) yeast strains. It is concluded from these findings that the excision repair function deficient in several of these mutant strains is not important for repair of bleomycin-induced damages in yeast. The sensitive strains contained rad6, rad9, rad18, rad22, rad50, rad51, rad52, rad53, rad54, rad55, rad56, rad57 and rs1. Strains bearing rad8 or rad19 could not be classified unambiguously. With one exception, all rad mutants found very sensitive to BM were sensitive to X-rays, suggesting that some aspect of the repair of BM- and X-ray induced damages in yeast may be similar. Sensitivities to BM and radiation co-segregated in pedigrees following meiosis, and several BM-resistant revertants isolated from two rad6 mutant strains sensitive to BM, X-rays and UV were cross-resistant to all three agents. These results confirm that the rad mutants were responsible for the cross-sensitivities in the original strains. (Auth.)

180

Povidone-Iodine and Bleomycin in the Management of Malignant Pleural Effusion  

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Full Text Available "nMalignant 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.

Ali Asghar Alavi

2011-09-01

 
 
 
 
181

Protective effect of dexpanthenol on bleomycin-induced pulmonary fibrosis in rats.  

Science.gov (United States)

Despite extensive studies, there is no effective treatment currently available other than pirfenidone for idiopathic pulmonary fibrosis. A protective effect of pantothenic acid and its derivatives on cell damage produced by oxygen radicals has been reported, but it has not been tested in bleomycin (BLM)--induced pulmonary fibrosis in rats. Therefore, we aimed to investigate the preventive effect of dexpanthenol (Dxp) on pulmonary fibrosis. Thirty-two rats were assigned to four groups as follows: (1) control group, (2) dexpanthenol (Dxp) group; 500 mg/kg Dxp continued intraperitoneally for 14 days, (3) bleomycin (BLM) group; a single intratracheal injection of BLM (2.5 mg/kg body weight in 0.25-ml phosphate buffered saline), and (4) BLM + Dxp-treated group; 500 mg/kg Dxp was administered 1 h before the intratracheal BLM injection and continued for 14 days i.p. The histopathological grades of lung inflammation and collagen deposition, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and myeloperoxidase (MPO) were measured. BLM provoked inflammation and collagen deposition (p 0.05). We showed that Dxp significantly prevents BLM-induced lung fibrosis in rats. Further studies are required to evaluate the role of Dxp in the treatment of lung fibrosis. PMID:23995256

Ermis, Hilal; Parlakpinar, Hakan; Gulbas, Gazi; Vardi, Nigar; Polat, Alaadin; Cetin, Asli; Kilic, Talat; Aytemur, Zeynep Ayfer

2013-12-01

182

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice  

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Full Text Available Diagnosis and management of interstitial lung diseases (ILDs, caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.

Kazuyuki Tobe

2012-02-01

183

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

International Nuclear Information System (INIS)

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

184

Effect of 0.25 ppm Ozone exposure on pulmonary damage induced by bleomycin  

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Full Text Available To study the effect of ozone in a chronically damaged lung, we used a bleomycin (BLM induced pulmonary fibrosis model. Both endotracheal instillation of BLM and O3 exposure both produce lung inflammation and fibrosis. Oxidative stress would be a common mechanism of damage for both BLM and O3. Our aim was to assess lung injury induced by 5 and 60 days of intermittent exposure to 0.25 ppm O3 in rats with bleomycin-induced pulmonary fibrosis. Thirty-day-old Sprague Dawley rats were endotracheally instilled with BLM (1 U/100 g body weight and, 30 days later, exposed to 0.25 ppm O3 (0.25 ppm 4 h per day, 5 days a week. Histopatology controls were instilled with saline and breathing room air. Histopathological evaluation of lungs was done 5 and 60 days after O3 exposure. BLM-induced lung damage did not change after 60 days of intermittent O3 exposure. Five days of O3 exposure increased the mean score of BLM-induced pulmonary inflammation and fibrosis (p=0.06. Frequency of bronchopneumonia increased from 1/7 to 6/6 (p <0.001, suggesting that a short-term exposure to O3 in a previously damaged lung might be a risk factor for developing further lung injury

MANUEL OYARZÚN

2005-01-01

185

Human Umbilical Cord Mesenchymal Stem Cells Reduce Fibrosis of Bleomycin-Induced Lung Injury  

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Acute respiratory distress syndrome is characterized by loss of lung tissue as a result of inflammation and fibrosis. Augmenting tissue repair by the use of mesenchymal stem cells may be an important advance in treating this condition. We evaluated the role of term human umbilical cord cells derived from Wharton’s jelly with a phenotype consistent with mesenchymal stem cells (uMSCs) in the treatment of a bleomycin-induced mouse model of lung injury. uMSCs were administered systemically, and lungs were harvested at 7, 14, and 28 days post-bleomycin. Injected uMSCs were located in the lung 2 weeks later only in areas of inflammation and fibrosis but not in healthy lung tissue. The administration of uMSCs reduced inflammation and inhibited the expression of transforming growth factor-?, interferon-?, and the proinflammatory cytokines macrophage migratory inhibitory factor and tumor necrosis factor-?. Collagen concentration in the lung was significantly reduced by uMSC treatment, which may have been a consequence of the simultaneous reduction in Smad2 phosphorylation (transforming growth factor-? activity). uMSCs also increased matrix metalloproteinase-2 levels and reduced their endogenous inhibitors, tissue inhibitors of matrix metalloproteinases, favoring a pro-degradative milieu following collagen deposition. Notably, injected human lung fibroblasts did not influence either collagen or matrix metalloproteinase levels in the lung. The results of this study suggest that uMSCs have antifibrotic properties and may augment lung repair if used to treat acute respiratory distress syndrome. PMID:19497992

Moodley, Yuben; Atienza, Daniel; Manuelpillai, Ursula; Samuel, Chrishan S.; Tchongue, Jorge; Ilancheran, Sivakami; Boyd, Richard; Trounson, Alan

2009-01-01

186

Three- and five-nucleon transfers in 9Be(p,?)6Li reaction at 25 and 30 MeV  

International Nuclear Information System (INIS)

Angular distributions of the 9Be(p,?)6Li reaction leading to the ground and first two excited states of 6Li were measured at incident energies of 25.0 and 30.0 MeV. Both the one-step three- and five-nucleon transfers were considered in the theoretical analysis using current shell-model wave functions. We reproduce fairly well with distorted-wave Born approximation theory the experimental energy dependence of the integrated cross sections for the ground and first excited states of 6Li. A marked disagreement is observed for the second excited state, whose experimental integrated cross section shows a steeper energy dependence than the calculated one

187

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

Scientific Electronic Library Online (English)

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

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

1999-09-01

188

A Comparison of Effects of ABVD and ChlVPP Chemotherapeutic Protocols for Hodgkin's Disease on Rats’ Epididiymal and Testicular Tissues  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine) group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone) group and two control groups one for each treatment group. One half of the lethal dose for 50% of...

Zare, S.; Mohammad Gholizad, L.; Eyshi Oskooii, A.; Nejati, V.

2010-01-01

189

Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin.  

Science.gov (United States)

The pathogenesis of pulmonary fibrosis involves lung epithelial injury and aberrant proliferation of fibroblasts, and results in progressive pulmonary scarring and declining lung function. In vitro, fibroblast growth factor (FGF) 2 promotes myofibroblast differentiation and proliferation in cooperation with the profibrotic growth factor, transforming growth factor-?1, but the in vivo requirement for FGF2 in the development of pulmonary fibrosis is not known. The bleomycin model of lung injury and pulmonary fibrosis was applied to Fgf2 knockout (Fgf2(-/-)) and littermate control mice. Weight loss, mortality, pulmonary fibrosis, and histology were analyzed after a single intranasal dose of bleomycin. Inflammation was evaluated in bronchoalveolar lavage (BAL) fluid, and epithelial barrier integrity was assessed by measuring BAL protein and Evans Blue dye permeability. Fgf2 is expressed in mouse and human lung epithelial and inflammatory cells, and, in response to bleomycin, Fgf2(-/-) mice have significantly increased mortality and weight loss. Analysis of BAL fluid and histology show that pulmonary fibrosis is unaltered, but Fgf2(-/-) mice fail to efficiently resolve inflammation, have increased BAL cellularity, and, importantly, deficient recovery of epithelial integrity. Fgf2(-/-) mice similarly have deficient recovery of club cell secretory protein(+) bronchial epithelium in response to naphthalene. We conclude that FGF2 is not required for bleomycin-induced pulmonary fibrosis, but rather is essential for epithelial repair and maintaining epithelial integrity after bleomycin-induced lung injury in mice. These data identify that FGF2 acts as a protective growth factor after lung epithelial injury, and call into question the role of FGF2 as a profibrotic growth factor in vivo. PMID:24988442

Guzy, Robert D; Stoilov, Ivan; Elton, Timothy J; Mecham, Robert P; Ornitz, David M

2015-01-01

190

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to 60Co ?-rays, 241Am ?-particles or bleomycin  

International Nuclear Information System (INIS)

The rejoining of DNA double strand breaks (dsb) induced by 60Co ?-rays, 241Am ?-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following ?-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by ?-rays or bleomycin. (author)

191

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to 60Co gamma-rays, 241Am alpha-particles or bleomycin.  

Science.gov (United States)

The rejoining of DNA double strand breaks (dsb) induced by 60Co gamma-rays, 241Am alpha-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following alpha-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by gamma-rays or bleomycin. PMID:2435666

Coquerelle, T M; Weibezahn, K F; Lücke-Huhle, C

1987-02-01

192

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

DEFF Research Database (Denmark)

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 unchanged within each treatment course but increased significantly (P less than 0.05) from the initial value to the last treatment course. Two months after cessation of treatment S-ACE returned to pretreatment values. Although the changes were modest they might mirror treatment-associated endothelial damage.

SØrensen, Peter G; RØmer, F K

1984-01-01

193

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Inúmeros trabalhos têm demonstrado que linfócitos de pacientes com síndrome de Down apresentam uma maior freqüência de aberrações cromossômicas quando expostos a radiação ionizante ou agentes químicos nas fases G0 ou G1 do ciclo celular, mas não em G2, quando comparados com controles normais. Para d [...] eterminar a sensibilidade de linfócitos de pacientes com síndrome de Down, na fase G2, usou-se o radiomimético bleomicina em culturas de linfócitos de 24 pacientes. Todos os pacientes mostraram trissomia livre do cromossomo 21 (47,XX + 21 ou 47,XY + 21). Indivíduos que apresentaram freqüência média de quebras cromatídicas por célula superior a 0,8 foram considerados sensíveis à droga. Nenhum controle apresentou suscetibilidade à bleomicina e entre os 24 pacientes com síndrome de Down somente um foi sensível à droga. Não se observou qualquer diferença significativa entre os dois grupos em relação às freqüências de quebras cromatídicas em linfócitos em G2, o que está de acordo com outros trabalhos. A distribuição das quebras induzidas pela bleomicina, em cada grupo cromossômico, foi igual para pacientes e controles. Nenhuma diferença significativa foi observada na resposta à bleomicina entre homens e mulheres, nos dois grupos. Provavelmente, o principal fator envolvido na sensibilidade cromossômica de linfócitos de pacientes com síndrome de Down seja a fase do ciclo celular na qual a célula é tratada. Abstract in english 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.

Marlise Ladvocat, Bartholomei-Santos; Edmundo José de, Lucca.

1997-03-01

194

Response of mouse sarcoma- 180 to bleomycin in combination with radiation and hyperthermia  

International Nuclear Information System (INIS)

The response of a transplantable mouse tumor, S-180, grown intradermally in inbred Balb/c mice, to bleomycin (BLM), irradiation (RT) and hyperthermia (HT) was studied by observing tumor growth changes up to 120 days after treatment. BLM, at 20 mg/kg body weight, and 10 Gy gamma radiation individually produced identical tumor cure, while hyperthermia at 42 C, 60' or 43 C, 30' resulted in a higher tumor response. Treatment with 43 C, 30' after BLM was more effective than hyperthermia after radiation in effecting tumor cure as well as in inducing regrowth delay. In the drug+HT combination the low drug dose was almost equal in effect as the higher drug dose when followed by 43 C, 30'. Combining the three modalities resulted in 100% tumor cure without any local recurrence during the observation period. The micronucleus study 24 h after treatment indicated enhanced cytogenetic damage by the combination treatments. (orig.)

195

Bleomycin as adjuvant in radiation therapy of advanced squamous cell carcinoma in head and neck  

International Nuclear Information System (INIS)

Since 1969, Bleomycin (BLM) has been used in three different ways at the Radium Centre in Copenhagen. First BLM given as the sole treatment led to complete regressions in 12% of 138 patients. Secondly BLM was used as simultaneous adjuvant in radiation therapy for 86 previously untreated patients, but 66% developed mucositis which disrupted the treatment. In a third period BLM was therefore combined sequentially with radiation, administered for 2 weeks prior to radiation therapy to 142 patients. The tumour shrinkage achieved with preirradiation BLM was very pronounced in 38 % of cases. 101 patients with T3 tumours have been observed for a minimum of 3 years. The prognostic value of the degree of shrinkage achieved with preirradiation BLM treatment is discussed. (author)

196

Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blmpf2 initially by histologically phenotyping the bleomycin-induced lung disease of sublines of congenic mice to reduce the linkage region to 13 genes. Of these genes, Trim16 was identified to have strain-dependent expression in the lung, which we determined was due to sequence variation in the promoter. Over-expression of Trim16 by plasmid injection increased pulmonary fibrosis, and bronchoalveolar lavage levels of both interleukin 12/23-p40 and neutrophils, in bleomycin treated B6.C3H-Blmpf2 subcongenic mice compared to subcongenic mice treated with bleomycin only, which follows the C57BL/6J versus C3H/HeJ strain difference in these traits. In summary we demonstrate that genetic variation in Trim16 leads to its strain-dependent expression, which alters susceptibility to bleomycin-induced pulmonary fibrosis in mice. PMID:23341783

Stefanov, Anguel N; Fox, Jessica; Depault, François; Haston, Christina K

2013-01-01

197

DNA degradation by bleomycin: evidence for 2'R-proton abstraction and for C-O bond cleavage accompanying base propenal formation  

International Nuclear Information System (INIS)

Reaction of poly(dA-[2'S-3H]dU) with activated bleomycin yields [3H] uracil propenal that completely retains the tritium label. In contrast, the authors have previously shown that reaction of poly(dA-[2'R-3H]dU) with activated bleomycin affords unlabeled uracil propenal. They have also prepared both cis- and trans-thymine propenals by chemical synthesis and have observed that the trans isomer is the exclusive product of the bleomycin reaction. Moreover, the cis isomer was found to be stable to the conditions of bleomycin-induced DNA degradation. Taken together, these results establish that the formation of trans-uracil propenal occurs via an anti-elimination mechanism with the stereospecific abstraction of the 2R proton. The question of phosphodiester bond cleavage during base propenal formation has also been addressed by the analysis of the fate of oxygen-18 in poly(dA-[3'-18O]dT) upon reaction with activated bleomycin. The 5'-monophosphate oligonucleotide ends produced from thymine propenal formation have been converted to inorganic phosphate by the action of alkaline phosphatase, and the phosphate has been analyzed for 18O content by 31P NMR spectroscopy. The oxygen-18 is retained in the inorganic phosphate, establishing that the formation of thymine propenal by activated bleomycin proceeds with C-O bond cleavage at the 3-position

198

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

International Nuclear Information System (INIS)

Objective: To investigate the possibility of using bleomycin-lipiodol emulsion (BLE) as an agent for functional pulmonary lobectomy. Methods: The bilateral lungs of sixteen healthy mongrel dogs were randomly divided into the Control group and the FPLT group. In FPLT group the target pulmonary, lobes were filled with BLE and then the target bronchi were occluded. In Control group the pulmonary lobes were done with nothing. The dogs were took X-ray films pre-procedure and post-procedure and then on 1st, 7th, 14th, 21st, and 28th day, respectively, some of them were sacrificed after procedure for histopathologieal examination. Results: Histopathologically in the early time the target pulmonary lobes were mainly inflammatory effusion. After seven days the alveoli collapsed, pulmonary interstitium widened and fibrous connective tissue proliferated. After twenty-eight days the target pulmonary lobes were atelectasis and entirely fibrosis. The fibrosis grade based on Ashcroft's semiquantitative grading system. The grade of pulmonary fibrosis was 0.66±0.06, 2.76±0.24, 4.70±0.22, 6.74±0.25 and 7.69±0.23 in FPLT group and 0.62±0.05, 0.63±0.10, 0.63±0.07, 0.62±011 and 0.63±0.10 in control group separately at 1st, 7th, 14th, 2lst and 28th day after procedure. There was significant difference in the corresponding period between the FPLT group and the control group (P<0.01) and between first day (0.66±0.06) and fourteenth day(40.66±0.06) and fourteenth day(4.70 ± 0.22) (P<0.01) and fourteenth day and twenty-eighth day (7.69±0.23) (P<0.01). Conclusion: Intra-bronchus embolization of bleomycin-lipiodol emulsion can result in atelectasis and fibrosis of the target pulmonary, lobes can achieve FPLT. (authors)

199

Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis  

Science.gov (United States)

Background and aims We have demonstrated recently that transplantation of placental membrane-derived cells reduces bleomycin-induced lung fibrosis in mice, despite a limited presence of transplanted cells in host lungs. Because placenta-derived cells are known to release factors with potential immunomodulatory and trophic activities, we hypothesized that transplanted cells may promote lung tissue repair via paracrine-acting molecules. To test this hypothesis, we examined whether administration of conditioned medium (CM) generated from human amniotic mesenchymal tissue cells (AMTC) was able to reduce lung fibrosis in this same animal model. Methods Bleomycin-challenged mice were either treated with AMTC-CM or control medium, or were left untreated (Bleo group). After 9 and 14 days, the distribution and severity of lung fibrosis were assessed histologically with a scoring system. Collagen deposition was also evaluated by quantitative image analysis. Results At day 14, lung fibrosis scores in AMTC-CM-treated mice were significantly lower (P<0.05) compared with mice of the Bleo group, in terms of fibrosis distribution [1.0 (interquartile range, IQR 0.9) versus 3.0 (IQR 1.8)], fibroblast proliferation [0.8 (IQR 0.4) versus 1.6 (IQR 1.0)], collagen deposition [1.4 (IQR 0.5) versus 2.0 (IQR 1.2)] and alveolar obliteration [2.3 (IQR 0.8) versus 3.2 (IQR 0.5)]. No differences were observed between mice of the Bleo group and mice treated with control medium. Quantitative analysis of collagen deposition confirmed these findings. Importantly, AMTC-CM treatment significantly reduced the fibrosis progression between the two observation time-points. Conclusions This pilot study supports the notion that AMTC exert anti-fibrotic effects through release of yet unknown soluble factors. PMID:21954836

Cargnoni, Anna; Ressel, Lorenzo; Rossi, Daniele; Poli, Alessandro; Arienti, Davide; Lombardi, Guerino; Parolini, Ornella

2012-01-01

200

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

Directory of Open Access Journals (Sweden)

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.

Inagaki Hirofumi

2006-01-01

 
 
 
 
201

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

Science.gov (United States)

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.

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

2013-12-01

202

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

Science.gov (United States)

The bleomycin (BLM) family of glycopeptide-derived antitumor antibiotics consists of BLMs, tallysomycins (TLMs), phleomycins (PLMs), and zorbamycin (ZBM). The self-resistant elements BlmB and TlmB, discovered from the BLM- and TLM-producing organisms Streptomyces verticillus ATCC15003 and Streptoalloteichus hindustanus E465-94 ATCC31158, respectively, are N-acetyltransferases that provide resistance to the producers by disrupting the metal-binding domain of the antibiotics required for activity. Although each member of the BLM family of antibiotics possesses a conserved metal-binding domain, the structural differences between each member, namely, the bithiazole moiety and C-terminal amine of BLMs, have been suggested to instill substrate specificity within BlmB. Here we report that BlmB and TlmB readily accept and acetylate BLMs, TLMs, PLMs, and ZBM in vitro but only in the metal-free forms. Kinetic analysis of BlmB and TlmB reveals there is no strong preference or rate enhancement for specific substrates, indicating that the structural differences between each member of the BLM family play a negligible role in substrate recognition, binding, or catalysis. Intriguingly, the zbm gene cluster from Streptomyces flavoviridis ATCC21892 does not contain an N-acetyltransferase, yet ZBM is readily acetylated by BlmB and TlmB. We subsequently established that S. flavoviridis lacks the homologue of BlmB and TlmB, and ZbmA, the ZBM-binding protein, alone is sufficient to provide ZBM resistance. We further confirmed that BlmB can indeed confer resistance to ZBM in vivo in S. flavoviridis, introduction of which into wild-type S. flavoviridis further increases the level of resistance. PMID:25299801

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

2014-11-11

203

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

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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

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

2010-07-01

204

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro  

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In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs) tested on human neuroblastoma IMR-32 (0.5×104 cells/100 µl of IMR) cells (EPA> DHA> ALA?=?GLA?=?AA> DGLA?=?LA: ?60, 40, 30, 10–20% respectively) at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2?, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4), 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA) and 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S),17(S)DiHDoHE), metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA) at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions. PMID:25536345

Polavarapu, Sailaja; Mani, Arul M.; Gundala, Naveen K. V.; Hari, Anasuya D.; Bathina, Siresha; Das, Undurti N.

2014-01-01

205

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

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

206

Extensive laminin and basement membrane accumulation occurs at the onset of bleomycin-induced rodent pulmonary fibrosis.  

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The distribution of laminin was studied during pulmonary fibrosis induced in rodents by bleomycin sulfate. Large accumulations of laminin associated with basement membranes were seen in thickened lung interstitial spaces by immunofluorescence microscopy, starting at 7 days (32-75% increases) and persisting through 28 days (66-79% increase). By electron microscopy, these laminin concentrations were skeinlike masses of reduplicated basement membranes localized at the surface of alveolar capilla...

Singer, I. I.; Kawka, D. W.; Mcnally, S. M.; Eiermann, G. J.; Metzger, J. M.; Peterson, L. B.

1986-01-01

207

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

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Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 and 500

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

1999-01-01

208

A hybrid NRPS-PKS gene cluster related to the bleomycin family of antitumor antibiotics in Alteromonas macleodii strains.  

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Although numerous marine bacteria are known to produce antibiotics via hybrid NRPS-PKS gene clusters, none have been previously described in an Alteromonas species. In this study, we describe in detail a novel hybrid NRPS-PKS cluster identified in the plasmid of the Alteromonasmacleodii strain AltDE1 and analyze its relatedness to other similar gene clusters in a sequence-based characterization. This is a mobile cluster, flanked by transposase-like genes, that has even been found inserted into the chromosome of some Alteromonasmacleodii strains. The cluster contains separate genes for NRPS and PKS activity. The sole PKS gene appears to carry a novel acyltransferase domain, quite divergent from those currently characterized. The predicted specificities of the adenylation domains of the NRPS genes suggest that the final compound has a backbone very similar to bleomycin related compounds. However, the lack of genes involved in sugar biosynthesis indicates that the final product is not a glycopeptide. Even in the absence of these genes, the presence of the cluster appears to confer complete or partial resistance to phleomycin, which may be attributed to a bleomycin-resistance-like protein identified within the cluster. This also suggests that the compound still shares significant structural similarity to bleomycin. Moreover, transcriptomic evidence indicates that the NRPS-PKS cluster is expressed. Such sequence-based approaches will be crucial to fully explore and analyze the diversity and potential of secondary metabolite production, especially from increasingly important sources like marine microbes. PMID:24069455

Mizuno, Carolina Megumi; Kimes, Nikole E; López-Pérez, Mario; Ausó, Eva; Rodriguez-Valera, Francisco; Ghai, Rohit

2013-01-01

209

Place occupied by gallium 67 citrate and 57Co-bleomycine scintigraphy in the evaluation and supervision of cancers  

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This work attempts to situate 57Co-bleomycine and gallium67 citrate scintigraphy in pre-treatment evaluation and supervision of solid tumours or malignant lymphomas. The results given by these two radiopharmaceuticals are compared for a series of 136 patients and a bibliograhical survey covering more than 3.000 cases is compiled. The purpose of the study is to establish the diagnostic capacity of each of these two tumoral tracers, according to the nature and location of the lesions, and, on this basis, to try to estimate the position it occupies as well as its indications and limits. The following are dealt with successively: - the biological properties, development of labelling techniques and tumoral fixation mechanisms of 57Co-bleomycine and 67Ga citrate reviewed historically. - The physical and technological foundations of the scintigraphic methods used. - The results obtained with 57Co bleomycine and 67Ga citrate in patients carrying solid tumours and malignant lymphomas. In the discussion these two radiotracers are compared as a function of the histological nature and location of the lesions. Finally these two isotopic methods are situated with respect to other complementary examinations and from this their indications and limits are inferred

210

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

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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

211

Bleomycin induced sensitivity to TRAIL/Apo-2L-mediated apoptosis in human seminomatous testicular cancer cells is correlated with upregulation of death receptors.  

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The most common solid tumor is testicular cancer among young men. Bleomycin is an antitumor antibiotic used for the therapy of testicular cancer. TRAIL is a proapoptotic cytokine that qualified as an apoptosis inducer in cancer cells. Killing cancer cells selectively via apoptosis induction is an encouraging therapeutic strategy in clinical settings. Combination of TRAIL with chemotherapeutics has been reported to enhance TRAIL-mediated apoptosis of different kinds of cancer cell lines. The molecular ground for sensitization of tumour cells to TRAIL by chemotherapeutics might involve upregulation of TRAIL-R1 (TR/1, DR4) and/or TRAIL-R2 (TR/2, DR5) receptors or activation of proapoptotic proteins including caspases. The curative potential of TRAIL to eradicate cancer cells selectively in testicular cancer has not been studied before. In this study, we investigated apoptotic effects of bleomycin, TRAIL, and their combined application in NTera-2 and NCCIT testicular cancer cell lines. We measured caspase 3 levels as an apoptosis indicator, and TRAIL receptor expressions using flow cytometry. Both NTera-2 and NCCIT cells were fairly resistant to TRAIL's apoptotic effect. Incubation of bleomycin alone caused a significant increase in caspase 3 activity in NCCIT. Combined incubation with bleomycin and TRAIL lead to elevated caspase 3 activity in Ntera-2. Exposure to 72 h of bleomycin increased TR/1, TR/2, and TR/3 cell-surface expressions in NTera-2. Elevation in TR/1 cell-surface expression was evident only at 24 h of bleomycin application in NCCIT. It can be concluded that TRAIL death receptor expressions in particular are increased in testicular cancer cells via bleomycin treatment, and TRAIL-induced apoptosis is initiated. PMID:25173558

Timur, Mujgan; Cort, Aysegul; Ozdemir, Evrim; Sarikcioglu, Sureyya Bilmen; Sanlioglu, Salih; Sanlioglu, Ahter Dilsad; Ozben, Tomris

2014-01-01

212

Voip Protocols  

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Full Text Available This article focuses on existing technologies in telecommunications but also on a comparative analysis of VoIP protocols. There will also be listed ways to extend networks and processes that contribute to the steady operation of the network as a set SLA with the support of a large number of simultaneous connections

Floriana GEREA

2012-06-01

213

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

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

Tagami Atsuro

2008-05-01

214

Evaluating the Ameliorative Potential of Quercetin against the Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats  

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The current study deals with the effect of a dietary flavanoid quercetin on fibrotic lung tissue in rats. Bleomycin was administered by single intratracheal instillation to Wistar rats to induce lung fibrosis. The pathologies associated with this included significantly reduced antioxidant capacity, ultimately leading to protracted inflammation of the lung tissue. The hallmark of this induced fibrosis condition was an excessive collagen deposition in peribronchial and perialveolar regions of the lung. Oral quercetin treatment over a period of twenty days resulted in significant reversal of the pathologies. The antioxidant defense in lung tissue was revived. Moreover, activity of the collagenase MMP-7, which was high in fibrotic tissue, was seen restored after quercetin administration. Trichome staining of lung tissue sections showed high collagen deposition in fibrotic rats, which may be a direct result of increased mobilization of collagen by MMP-7. This was appreciably reduced in quercetin treated animals. These results point towards an important protective role of quercetin against idiopathic lung fibrosis, which remains a widely prevalent yet incurable condition in the present times. PMID:24396596

Kushwah, Lokendra; Gohel, Darpesh; Patel, Manish; Marvania, Tulsi; Balakrishnan, Suresh

2013-01-01

215

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

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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.

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

216

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

International Nuclear Information System (INIS)

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

217

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

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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)

218

Antifibrotic effects of focal adhesion kinase inhibitor in bleomycin-induced pulmonary fibrosis in mice.  

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Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in various biological functions, including cell survival, proliferation, migration, and adhesion. FAK is an essential factor for transforming growth factor ? to induce myofibroblast differentiation. In the present study, we investigated whether the targeted inhibition of FAK by using a specific inhibitor, TAE226, has the potential to regulate pulmonary fibrosis. TAE226 showed inhibitory activity of autophosphorylation of FAK at tyrosine 397 in lung fibroblasts. The addition of TAE226 inhibited the proliferation of lung fibroblasts in response to various growth factors, including platelet-derived growth factor and insulin-like growth factor I, in vitro. TAE226 strongly suppressed the production of type I collagen by lung fibroblasts. Furthermore, treatment of fibroblasts with TAE226 reduced the expression of ?-smooth muscle actin induced by transforming growth factor ?, indicating the inhibition of differentiation of fibroblasts to myofibroblasts. Administration of TAE226 ameliorated the pulmonary fibrosis induced by bleomycin in mice even when used late in the treatment. The number of proliferating mesenchymal cells was reduced in the lungs of TAE226-treated mice. These data suggest that FAK signal plays a significant role in the progression of pulmonary fibrosis and that it can become a promising target for therapeutic approaches to pulmonary fibrosis. PMID:23642017

Kinoshita, Katsuhiro; Aono, Yoshinori; Azuma, Momoyo; Kishi, Jun; Takezaki, Akio; Kishi, Masami; Makino, Hideki; Okazaki, Hiroyasu; Uehara, Hisanori; Izumi, Keisuke; Sone, Saburo; Nishioka, Yasuhiko

2013-10-01

219

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

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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.

Ghada M. Suddek

2014-01-01

220

The distribution of a new /sup 111/In-Bleomycin complex in tumor cells by autoradiography  

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A new radioactive form of Bleomycin (/sup 111/In-BLMC) was effective for tumor imaging and therapy in mouse glioma and human small cell lung cancer (SCLC) cells. The distribution of drug in tumor cells was investigated by autoradiography. Human small cell lung cancer (N417 and H526, NCI) were exposed to /sup 111/ InCl/sub 3/ and (25-150 ?Ci/ml) or /sup 111/In-BLMC (25-150 ?Ci) carried by 15-25 ?g BLM/ml) in 370C for 1 hr, 3 hr or 24 hr, washed with fresh medium, and spread. The slides were smeared with NTB/sub 2/ or NTB/sub 3/ emulsion by using wet-mounting or dry-mounting technique and developed 3-14 days. The /sup 111/In-BLMC localized on the cell nucleus (47.8%) and nuclear membrane (29.2%); /sup 111/InCl/sub 3/ located mainly in the cytoplasm (45.8%). This indicates that the mechanism of killing of tumor cells may be related to the drug uptake and distribution of /sup 111/In-BLMC. A nuclear and nuclear membrane localization would favor damage to chromosomes and DNA

 
 
 
 
221

Intratumoral injection of 5-fluorouracil and bleomycin for inoperable cancer in the cardioesophageal region  

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The methods and results of combined therapy (drugs+radiation+intratumoral injection of 5-fluorouracil and chemoimmunotherapy+intratumoral injection of blemycin) were compared with the standard procedure (chemotherapy+radiation) for treating inoperable cancer in the cardioesophageal region. The study group included 47 patients aged 32-79. Tumors were inoperable due to considerable expansion in 32 and remote metastases in 15 patients. The single dose of 5-flyorouracil injected into tumor via a fibroendoscope at the start of chemoradiation treatment ranged 750-1000 mg (course dose of the drug - 2.75-4.25 g, total focal dose of radiation - 24-36 Gy). The single intratumoral dose of bleomycin injected prior to total polychemotherapy (vinblastin, ftorafur, cyclophosphamide) was 10-15 mg. In the control group receiving standard combined therapy, the total focal dose was 60-62 Gy and course dose of 5-fluorouracil - 5-7 g. Objective improvement was observed in 63.6% matched by a mean survival time of 14.6 months after combined therapy given in conjunction with supporting chemoimmunotherapy. This showed an improvement on the results of standard combination therapy which were 58.3% and 9.3 months, respectively

222

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

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

Liu Dai-Shun

2009-06-01

223

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats  

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Full Text Available SciELO Chile | Language: English Abstract in english Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effec [...] t of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-?, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p

Baykal, Tulek; Esen, Kiyan; Aysel, Kiyici; Hatice, Toy; Hulagu, Bariskaner; Mecit, Suerdem.

224

Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma.  

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Sclerosing cholangitis (SC) is a rarely reported morbidity secondary to transcatheter arterial chemoembolization (TACE) with bleomycin-iodinated oil (BIO) for liver cavernous hemangioma (LCH). This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO. Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts. Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy. Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy. Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area. Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy. Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC. PMID:25516686

Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Wang, Si-Yuan; Wang, Guang-Yi

2014-12-14

225

Cytotoxic activity, tumor accumulation, and tissue distribution of ruthenium-103-labeled bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM) was labeled with gamma-emitting 103Ru. Yields of 103Ru-labeled BLM as high as 50.6% were attained. 103Ru-labeled BLM was stable in vitro and the 103ru label was not displaced by large excesses of Cu (II) and Co (II) or Fe (III). Chromatography of the urine following 103Ru-labeled BLM injection indicated no in vivo decomposition. Pharmacokinetic studies in healthy inbred SD and tumor-bearing inbred BUF rats demonstrated tumor accumulations, tissue distributions, and clearance nearly identical with those reported for 3H-labeled BLM. Cytotoxicity studies on a WI-L2 human B-cell line showed that BLM labeled with nonradioactive Ru retained 100% of the activity demonstrated by native BLM. Thus BLM may be labeled with isotopes of Ru to form stable complexes by a simple, rapid reaction without loss of its chemotherapeutic properties or variations in its in vivo distribution. BLM labeled with the proper Ru isotope should prove useful as a gamma-emitting tracer for BLM or a beta-emitting compound capable of providing combination chemotherapy and radiotherapy of tumors

226

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

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Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish 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

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

2011-10-01

227

Kioto protocol  

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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)

228

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

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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.)

229

The combined effect of bleomycin and irradiation on mouse lip mucosa. 1. Influence of timing, sequence and mode of drug administration with single dose irradiation  

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The effect of the combination of single dose irradiation and bleomycin on the mucosa of the mouse lip was investigated. Bleomycin was administered either by IP injection or by subcutaneous continuous infusion. With the combined treatment an increased effect was observed compared to irradiation alone. The effect was drug-dose dependent in the range of doses used and was similar for both ways of drug administration. There was only a limited influence of timing and sequence of the two agents within a period of 4 days. Since the dose-response curves were shifted in a parallel way, a constant cell killing effect by bleomycin is suggested for all irradiation doses used. This could be due to independent cell kill by the drug, although some mechanism of interaction, such as interference with accumulation of sublethal radiation damage or a true dose modification can not be excluded. (Auth.)

230

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

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

231

Positional Cloning Reveals Strain-Dependent Expression of Trim16 to Alter Susceptibility to Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blm...

Stefanov, Anguel N.; Fox, Jessica; Haston, Christina K.

2013-01-01

232

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

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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)

233

Comparative distribution of 57Co-Bleomycin, 67Ga-citrate and 167Tm-citrate in murine tumor and in transplanted human tumor in nude mice  

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Tumoral tropism of 167Tm-citrate was compared to that of 67Ga-citrate and of 57Co-Bleomycin on a model of murine tumor and on a model of human tumor heterotransplanted in a mude mouse. In both experimental models, if the fixation in tumors and especially the tumor activity/other tissues activity ratio is taken into account, it appears that the 167Tm-citrate is better than the 67Ga-citrate and even better than 57Co Bleomycine. Among the radiopharmaceuticals with a tumoral tropism, the 167Tm-citrate has a privileged position due to its physical, chemical and biological characteristics

234

Semi-artificial hydroxylating enzymes created by flavins binding to cytochrome P450 2B4 and by bleomycin binding to NADPH-cytochrome P450 reductase.  

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To create a semi-artificial monomolecular oxygenase system, FAD or FMN were covalently bound to cytochrome P450 2B4 as electron donor centers and bleomycin to NADPH-cytochrome P450 reductase as a generator of active oxygen species. The most catalytically active was the conjugate of cytochrome P450 with FMN, able to initiate the reactions of dimethylaniline and aminopyrine demethylation along with the reaction of aniline p-hydroxylation. The conjugate of cytochrome P450 with FAD oxidized these substrates at a much slower rate. The bleomycin-reductase complex was capable of demethylating dimethylaniline and aminopyrine but failed to oxidize aniline. PMID:7513993

Uvarov VYu; Shumyantseva, V V; Bykhovskaya, E A; Kolyada, L N; Archakov, A I

1994-04-29

235

Prevention of bleomycin-induced lung inflammation and fibrosis in mice by naproxen and JNJ7777120 treatment.  

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Pulmonary fibrosis, a progressive and lethal lung disease characterized by inflammation and accumulation of extracellular matrix components, is a major therapeutic challenge for which new therapeutic strategies are warranted. Cyclooxygenase (COX) inhibitors have been previously utilized to reduce inflammation. Histamine H4 receptor (H4R), largely expressed in hematopoietic cells, has been identified as a novel target for inflammatory and immune disorders. The aim of this study was to evaluate the effect of JNJ7777120 (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine), a selective H4R antagonist, and naproxen, a well known nonsteroidal anti-inflammatory drug, and their combination in a murine model of bleomycin-induced fibrosis. Bleomycin (0.05 IU) was instilled intratracheally to C57BL/6 mice, which were then treated by micro-osmotic pump with vehicle, JNJ7777120 (40 mg/kg b.wt.), naproxen (21 mg/kg b.wt.), or a combination of both. Airway resistance to inflation, an index of lung stiffness, was assessed, and lung specimens were processed for inflammation, oxidative stress, and fibrosis markers. Both drugs alone were able to reduce the airway resistance to inflation induced by bleomycin and the inflammatory response by decreasing COX-2 and myeloperoxidase expression and activity and thiobarbituric acid-reactive substance and 8-hydroxy-2'-deoxyguanosine production. Lung fibrosis was inhibited, as demonstrated by the reduction of tissue levels of transforming growth factor-?, collagen deposition, relative goblet cell number, and smooth muscle layer thickness. Our results demonstrate that both JNJ7777120 and naproxen exert an anti-inflammatory and antifibrotic effect that is increased by their combination, which could be an effective therapeutic strategy in the treatment of pulmonary fibrosis. PMID:25185215

Rosa, Arianna Carolina; Pini, Alessandro; Lucarini, Laura; Lanzi, Cecilia; Veglia, Eleonora; Thurmond, Robin L; Stark, Holger; Masini, Emanuela

2014-11-01

236

Fli1 haploinsufficiency induces fibrosis, vascular activation and immune abnormalities resembling systemic sclerosis in bleomycin-treated mice.  

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Objectives: Friend leukemia virus integration 1 (Fli1) is a potential predisposing factor of systemic sclerosis (SSc), which is constitutively downregulated in the lesional skin of this disease by an epigenetic mechanism. To investigate the impact of Fli1 deficiency on the induction of an SSc phenotype in various cell types, we generated bleomycin-treated skin fibrosis in Fli1(+/-) mice and investigated the molecular mechanisms explaining its phenotypical alterations. Methods: mRNA levels and protein expression of target molecules were examined by quantitative reverse transcription PCR and immunostaining. Transforming growth factor (TGF)-? bioassay was used to evaluate the activation of latent TGF-?. The occupancy of the target gene promoters with Fli1 was assessed with chromatin immunoprecipitation. Results: Bleomycin induced greater dermal fibrosis in Fli1(+/-) mice than in wild type mice. Fli1 haploinsufficiency activated dermal fibroblasts via up-regulation of ?V?3 and ?V?5 integrins and activation of latent TGF-?. Dermal fibrosis in Fli1(+/-) mice was also attributable to endothelial-to-mesenchymal transition, which is directly induced by Fli1 deficiency and amplified by bleomycin. Th2/Th17 skewed inflammation and increased infiltration of mast cells and macrophages were seen partly due to the altered expression of cell adhesion molecules in endothelial cells as well as induction of the skin chemokines. Fli1(+/-) macrophages preferentially differentiated into an M2 phenotype by interleukin-4 or -13. Conclusions: These results provide strong evidence for the fundamental role of Fli1 deficiency in inducing SSc-like phenotypic alterations in dermal fibroblasts, endothelial cells, and macrophages in a manner consistent with human disease. © 2014 American College of Rheumatology. PMID:25385187

Taniguchi, Takashi; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Takahashi, Takehiro; Ichimura, Yohei; Toyama, Tetsuo; Trojanowska, Maria; Sato, Shinichi

2014-11-10

237

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

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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 bps 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

238

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

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

Xie, Ting; Liang, Jiurong; Guo, Rishu; Liu, Ningshan; Noble, Paul W.; Jiang, Dianhua

2011-01-01

239

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

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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 A...

Fung, Hua; Demple, Bruce

2011-01-01

240

The role of scintigraphy with 57Co-bleomycin in the detection and staging of planocellular carcinomas  

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Opinions of usefullness of 57Co-bleomycin in the diagnostics of planocellular carcinomas have been differing. This method was reported in early 70-ties but was never generally accepted because of some physical characteristics of 57Co (half-life of 57Co 270 days). The authors report two cases in which radiography and imaging with this agent helped to provide correct diagnosis: an unclear case of Pancoast tumor and a case of metastatic involvement of thoracic wall after laryngeal carcinoma. (author) 7 refs.; 4 figs

 
 
 
 
241

Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis  

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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.

Flower Roderick J

2011-10-01

242

Efficient nuclear DNA cleavage in human cancer cells by synthetic bleomycin mimics.  

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Iron complexes of N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity of these and related metal complexes were carried out in cell-free systems using plasmid DNA as substrate. The present study evaluated nuclear DNA cleavage activity and cell cytotoxicity of BLM and its synthetic mimics based on the ligand N4Py. The N4Py-based reagents induced nuclear DNA cleavage in living cells as efficiently as BLM and Fe(II)-BLM. Treatment of 2 cancer cell lines and 1 noncancerous cell line indicated improved cytotoxicity of N4Py when compared to BLM. Moreover, some level of selectivity was observed for N4Py on cancerous versus noncancerous cells. It was demonstrated that N4Py-based reagents and BLM induce cell death via different mechanistic pathways. BLM was shown to induce cell cycle arrest, ultimately resulting in mitotic catastrophe. In contrast, N4Py-based reagents were shown to induce apoptosis effectively. To the best of our knowledge, the present study is the first demonstration of efficient nuclear DNA cleavage activity of a synthetic BLM mimic within cells. The results presented here show that it is possible to design synthetic bioinorganic model complexes that are at least as active as the parent natural product and thereby are potentially interesting alternatives for BLM to induce antitumor activity. PMID:24527883

Li, Qian; van der Wijst, Monique G P; Kazemier, Hinke G; Rots, Marianne G; Roelfes, Gerard

2014-04-18

243

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

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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 tisions and through this effect shortened the latent time to epithelial denudation. (author)

244

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

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Background Bleomycin (B) is an antineoplastic drug that has pulmonary fibrosis as a side effect. There are few experimental studies about the effects of physical therapy treatment in this case. Objective The objective was to study rat lungs treated with B and precocious intervention by transcutaneous electrical diaphragmatic stimulation (TEDS). Method Wistar rats were divided into 4 groups (n=5): a control group (C); a stimulated group (TEDS); a group treated with a single dose of B (intratracheally, 2.5 mg/kg) (B); and a group treated with B and electric stimulation (B + TEDS). After the B instillation, the electrical stimulation was applied for 7 days, for a duration of 20 minutes. Lung fragments were histologically processed with hematoxylin and eosin (HE) and 8-isoprostane-PGF2? (8-iso-PGF2?). The density of the alveolar area was determined by planimetry, the inflammatory profile was defined by the number of cells, and the level of oxidative stress in the pulmonary tissue was evaluated by 8-iso-PGF2?. For statistical analysis of the data, the Shapiro-Wilk test was used, followed by a one-way ANOVA with the post-hoc Bonferroni test (p?0.05). Results The B group exhibited a significant reduction in the area density, and the acute treatment with B + TEDS prevented this reduction. There were increased numbers of fibroblasts, leukocytes, and macrophages in the B group, as well as increased lipid peroxidation, which was observed only in this group. Conclusion B promoted a reduction in the alveolar density area, thereby inducing the inflammatory process and increasing the production of free radicals. These effects were minimized by the application of TEDS at the initial treatment stage. PMID:24346295

Santos, Laisa A.; Silva, Carlos A.; Polacow, Maria L. O.

2013-01-01

245

Preventive effect of chrysin on bleomycin-induced lung fibrosis in rats.  

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The aim of the current study is determination of protective effect of chrysin (CRS), a natural flavonoid, on cell injury produced by lung fibrosis induced with bleomycin (BLC) in rats. Twenty-eight female rats were assigned to four groups as follows: control group, CRS group; 50 mg/kg CRS was continued orally for 14 days, BLC group; a single intratracheal injection of BLC (2.5 mg/kg body weight in 0.25 ml phosphate buffered saline), BLC?+?CRS group; 50 mg/kg CRS was administered 1 day before the intratracheal BLC injection and continued for 14 days orally. All animals were sacrificed at day 14th after BLC administration. The semiquantitative assessment of histopathological consisting of lung inflammation and collagen deposition, tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reducted glutathione (GSH) were measured. BLC provoked histological changes consisting of alveolar congestion, increase connective tissue, infiltration, and the thickness of alveolar wall were detected significantly when compared to the control group (p???0.0001). CRS supplementation significantly restored these histological damages (p???0.0001). The level of tissue TBARS was increased with BLC (p?

Kilic, Talat; Ciftci, Osman; Cetin, Asli; Kahraman, Hasan

2014-12-01

246

Nucleosome rearrangement in human cells following short patch repair of DNA damaged by bleomycin  

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We have examined the structure of newly repaired regions of chromatin in intact and permeabilized human cells following exposure to bleomycin (BLM). The average repair patch size (in permeabilized cells) was six to nine bases, following doses of 1-25 micrograms/mL BLM, and greater than 80% of the total repair synthesis was resistant to aphidicolin. In both intact and permeabilized cells, nascent repair patches were initially very sensitive to staphylococcal nuclease, analogous to repair induced by long patch agents, and are nearly absent from isolated nucleosome core DNA. Unlike long patch repair, however, the loss of nuclease sensitivity during subsequent chase periods was very slow in intact cells, or in permeabilized cells treated with a low dose of BLM (1 microgram/mL), and was abolished by treatment with hydroxyurea (HU) or aphidicolin (APC). The rate of repair patch ligation did not correlate with this slow rate of chromatin rearrangement since greater than 95% of the patches were ligated within 6 h after incorporation (even in the presence of HU or APC). In permeabilized cells, repair patches induced by either 5 or 25 micrograms/mL BLM, where significant levels of strand breaks occur in compact regions of chromatin, lost the enhanced nuclease sensitivity at a rate similar to that observed following long patch repair. This rapid rate of rearrangement was not affected by APC. These results indicate that short patch repair in linker regions of nucleosomes, and/or open regions of chromatin, involves much less nucleosome rearrangement than long patch repair or short patch repair in condensed chromatin domains.

Sidik, K.; Smerdon, M.J. (Washington State Univ., Pullman (USA))

1990-08-14

247

Analysis of DNA synthesis in micronuclei induced in human lymphocytes by X-ray irradiation, bleomycin and mitomycin C  

International Nuclear Information System (INIS)

We investigated the pattern of DNA synthesis in the micronucleus and main nucleus of human lymphocytes by applying immunostaining with a monoclonal antibody against bromodeoxyuridine (BrdU) after pulse labeling with BrdU. Lymphocytes were obtained from two healthy men and suspended in RPMI1640 medium plus 10% FCS with PHA. Micronuclei were induced by X-ray irradiation (6 Gy), bleomycin (10 ?g/ml) and mitomycin C (2 ?g/ml). After 71 h incubation, the cells were incubated in the presence of BrdU for an additional 1 h. The cells were spread by cytospin and stained with Giemsa solution. Micronucleated cells were recorded, and slides were restained by the immunocytochemical method. Four patterns of BrdU labeling were recorded; main nucleus/ micronucleus (+/+), (+/-), (-/+) and (-/-). These results suggested that the timing of DNA synthesis in micronucleus is different from that in the main nucleus in some cells. The labeling pattern after X-ray irradiation was similar to the pattern after bleomycin, and these groups had more (-/+) patterns induced than the groups treated with mitomycin C and the non-induced control. These findings show that the patterns of BrdU labeling in the main nucleus and micronucleus are changed by micronucleus inducers. (author)

248

SD rats response to the cyclophosphamide and bleomycin administration by means of the chromosomal aberration assay in bone marrow.  

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Full Text Available In this study we decided to evaluate and compare the SD rats response of both sexes in theadministration of two mutagenic substances by chromosomal aberrations assay in bonemarrow cells. Which were formed 5 experimental groups per sex, the first administered withNaCl 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 inductions of numeric and structural chromosome aberrations with the use of cyclophosphamide and bleomycin were administered 48 and 24 hours before sacrifice in SD rats of both sexes. This constitutes the best experimental design to induce a considerable number of chromosomal aberrations. Nevertheless high sensibility of this rat line in both sexes was evidenced to the action of both mutagens independently of the outline of used treatment.

Luis Alfredo Rosario Fernández

2010-03-01

249

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

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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.).

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

250

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

International Nuclear Information System (INIS)

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.)

251

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

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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.

Daniel Francisco Arencibia Arrebola

2010-04-01

252

Combined effects of bleomycin and X-rays on DNA synthesis in asynchronous Ehrlich ascites cells in suspension  

International Nuclear Information System (INIS)

Separate and combined effects of bleomycin and X-rays on rates of uptake of [14C]thymidine into Ehrlich ascites cells were assessed for extracellular drug concentrations of 12 ?m (20 ?g/ml) and radiation doses of 2.5 krad. Rates of DNA synthesis were followed by monitoring the activity of the acid-insoluble portion of the asynchronous culture. The 14C activity of the acid-soluble pool was assessed in determining the rate of passage of 14C-TdR across the cell membrane. The results reveal that whilst the effects of each agent on TdR uptake rates are markedly different, they both inhibit DNA synthesis. Combined studies with both agents, 2.5 krad X-rays plus 20 ?g/ml bleomycin before, simultaneously or after exposure to X-rays, produced additive or less than additive effects on rates of incorporation of TdR into DNA. However, when the drug dose is split 2 x 10 ?g/ml before and after exposure to 2.5 krad X-rays, a synergistic effect on inhibition of DNA synthesis is observed. (author)

253

Hypersensitivity of tumor cell lines with microsatellite instability to DNA double strand break producing chemotherapeutic agent bleomycin.  

Science.gov (United States)

Genetic or epigenetic inactivation of DNA mismatch repair genes results in a strong mutator phenotype, known as the microsatellite mutator phenotype or microsatellite instability (MSI). This mutator phenotype causes mutations in genes responsible for the regulation of cell growth and survival/death and thus promotes the development and progression of tumors. In addition to such tumorigenic lesions, mutations in genes of other types of DNA repair, for example, DNA double-strand break (DNA DSB) repair, are found in tumor cells with MSI. We report here that the majority of MSI-positive tumor cell lines of different tissue origins (endometrial, ovarian, prostate, and colorectal carcinomas) are hypersensitive to bleomycin, a DNA DSB producing chemotherapeutic drug. We suggest that this hypersensitivity may be a result of inactivation of the DNA DSB repair activity by concomitant mutations of different DNA DSB repair genes. To provide experimental support to this hypothesis, we show that the subclones of the MSI-positive colorectal cancer cell line HCT-8 that bear heterozygous frameshift mutations in the DNA DSB repair gene DNA-PK(CS) are more sensitive to a combined treatment with bleomycin and the DNA protein kinase inhibitor LY294002 than the original HCT-8 cells, which are wild type for this gene. These results may be useful in designing therapies for MSI-positive cancer. PMID:15256444

Li, Hai-Ri; Shagisultanova, Elena I; Yamashita, Kentaro; Piao, Zhe; Perucho, Manuel; Malkhosyan, Sergei R

2004-07-15

254

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

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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.

Bo Zhu

2013-12-01

255

Intratumoral 57Co-bleomycin administration in carcinomas of the oral cavity. Experiments in the xenogeneic nude mouse and clinical pilot study  

International Nuclear Information System (INIS)

Experiments concerning the kinetics and biodistribution of 57Co-bleomycin in three different lines of the squamous cell carcinoma of the oral cavity in a nude-mouse model yielded a more than tenfold higher concentration after single intratumoral application of an aqueous solution of 57Co-labelled bleomycin in spite of a remarkable drain of radioactivity in the tumor up to 48 hours post application, compared to intravenous injection. The distribution of the radiopharmaceutical within the tumor was determining by autoradiography. The xenografts were removed and cut (5 ?m) 1, 5, 24, and 28 hours after bleomycin administration, respectively. The preparations were covered with an autoradiographic film and exposed for about three weeks. Thereafter an inhomogenous distribution of the radioactive nuclide was produced within the tumor, and a particularly high activity concentration could be demonstrated in the necrotic tumor areas. The results obtained from the animal experiments have been corroborated by a pilot study consisting of bleomycin application in 9 patients with a carcinoma of the oral mucosa. (author)

256

Comparison of 67Ga-citrate, 111In-bleomycin and 99sup(m)Tc-citrate in the evaluation of pulmonary lesions  

International Nuclear Information System (INIS)

A total of 128 patients were examined using three tumor localizing agents, 99sup(m)Tc-citrate, 111In-bleomycin and 67Ga-citrate. All these patients had clinical symptoms of pulmonary disease and chest X-rays. Twenty-two patients were excluded from the original number. Of the 106 remaining patients, 14 were benign cases and 92 malignant. A scan with a ?-camera was performed 3 to 4 h following an intravenous injection of 15 mCi of 99sup(m)Tc-citrate. Upon completion of this examination, the patient was given 2.5 mCi of 67Ga-citrate and 72 h later, scans were obtained using a 5 in. rectilinear scanner. Fifteen days later 2.5 mCi of 111In-bleomycin was given and a similar examination to that of gallium was performed. In evaluating benign lesions, 99sup(m)Tc-citrate gave no false positive results, while 111In-bleomycin gave 5% and 67Ga-citrate 20%. In the case of malignant lesions, 67Ga-citrate gave 79% true positive diagnoses, 111In-bleomycin 65% and 99sup(m)Tc-citrate (of 57 evaluated patients) 46%. (orig.)

257

A young male with shortness of breath  

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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.

Khan Fahmi

2008-01-01

258

Effect of bleomycin on DNA, RNA, protein, chromatin and on cell transformation by oncogenic RNA viruses.  

Science.gov (United States)

Bleomycin (BLM) exclusively affects thymidine-containing compounds such as DNA and polydeoxyribonucleotides by releasing free thymine and leaving aldehyde functions. Molecular morphology and base sequence of the DNA strongly influence BLM activity. High BLM concentrations, besides modifying DNA into oligothyminic or athyminic nucleic acids, cause strand scissions. Enzymatic DNA and RNA synthesis is strongly influenced by BLM. The inhibition in DNA-dependent DNA polymerase and DNA-dependent RNA polymerase assays is of the non-competitive type. Protein biosynthesis in in vitro systems is not affected by BLM even at high concentrations. BLM turns out to be a strong inhibitor of DNase I and of DNase II; the inhibition is of the competitive type. The enzymatic activities of nucleases using RNA as substrate (RNase A, RNase B, Rnase T1, venom phosphodiesterase I and spleen phosphodiesterase II) are not influenced by this antibiotic. The antibiotic reduces cell proliferation (L5178y mouse lymphoma cells) in vitro in low concentrations by cytostasis and at higher concentrations by cytotoxicity. In BLM-treated L5178y cells, DNA synthesis is strongly reduced, while RNA and protein synthesis are not affected. In vivo, using growing quail oviducts, cell proliferation and cytodifferentiation are markedly inhibited after BLM treatment. This is attributed to the observed inhibition of DNA synthesis. RNA and protein synthesis as well as gene expression are not influenced by BLM under the conditions used. The selective inhibition of DNA synthesis in vivo may be caused by the following mechanisms: (1) competition of BLM with RNA; (2) blocking of the accessibility of DNA in chromatin to BLM, and (3) dependence from the repair processes. BLM inhibits growth of sarcomas, induced by oncogenic RNA viruses in vivo; well-developed tumours show regression after BLM treatment. Transformation of chick embryo fibroblasts by oncogenic RNA viruses in vitro and growth of these viruses is blocked by BLM; the most sensitive period for BLM inhibition is the time during the first period (integration of viral genome into cellular genome?) after infection. PMID:63969

Müller, W E; Zahn, R K

1976-01-01

259

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

International Nuclear Information System (INIS)

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

260

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to /sup 60/Co. gamma. -rays, /sup 241/Am. cap alpha. -particles or bleomycin  

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The rejoining of DNA double strand breaks (dsb) induced by /sup 60/Co ..gamma..-rays, /sup 241/Am ..cap alpha..-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following ..cap alpha..-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by ..gamma..-rays or bleomycin.

Coquerelle, T.M.; Luecke-Huhle, C.; Weibezahn, K.F.

1987-02-01

 
 
 
 
261

Transport Protocol Throughput Fairness  

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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 contro...

Saleem Bhatti; Martin Bateman

2009-01-01

262

Preparation, distribution, stability and tumor imaging properties of [62Zn] Bleomycin complex in normal and tumor-bearing mice  

International Nuclear Information System (INIS)

Backgrounds: Bleomycin (BLM) has been labeled with radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [62Zn] zinc chloride for oncologic PET studies. Materials and methods: The complex was obtained at the P H=2 normal saline at 90degC in 60 min. Radio-TLC showed on overall radiochemical yield of 95-97% (radiochemical purity>97%). Stability of complex was checked in vitro in mice and human plasma/urine. Results: Preliminary in vitro studies performed to determined complex stability and distribution of [62Zn] BLM in normal and fibrosarcoma tumors in mice according to bio-distribution/imaging studies. Conclusion: [62Zn] BLM can be used in PET oncology studies due to its suitable physico-chemical propertied as a diagnostic complex behavior in higher animals

263

Bleomycin but not its derivatives inhibits the in vivo shedding of a rat tumor-associated antigen.  

Science.gov (United States)

Rat fibrosarcoma (KMT-17) cells and their in vitro clone, 10% FCS A3 cells, shed a tumor-associated antigen (TAA), CE7, from the cell surface under growth-promoting conditions. We treated cells with the antitumor agent bleomycin (BLM) and its analogs peplomycin and liblomycin in vitro and in vivo in an attempt to increase expression of this antigen and induce an antitumor response. Although all three agents enhance antigen expression in vitro, proportionate to their direct antiproliferative effects, only BLM enhances antigen expression in vivo. The in vivo regulation of CE7 expression appears not to be related to the direct cytotoxic effects of the antitumor agents but rather to the immuno-augmenting effects of BLM. PMID:1283828

Micallef, M; Shibata, T; Hosokawa, M; Kobayashi, H

1992-12-01

264

The Effects of Bleomycin on the Structural Abnormalities of Human Chromosomes who were Exposed to Radition (X-Ray Chronically  

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Full Text Available Bleomycin in doses 0.3, 3 and 30 ?g/ml was used with periods 6, 24 and48 hours on 5 samples who were exposed to radiation chronically, in invitroconditions and under control so totally 2639 metaphases wereevaluated.Structural chromosome aberrations were influenced by the increases indosage. While the ratio total structural aberrations to the number ofmetaphases examined was 9.7% in control groups (individual werechronically-exposed to radiation. It was 44.8% in 0.3 ?g/ml group, 180.8%in 3 ?g/ml and rose up to 205.1% in 30 ?g/ml experiment group. In additiondue to the increases in dosage, there was an increase in structuralaberration quantities and qualities.

Turgay Budak

2004-01-01

265

Ethanol and acetaldehyde potentiate the clastogenicity of ultraviolet light, methol methanesulfonate, mitomycin C and bleomycin in Chinese hamster ovary cells  

International Nuclear Information System (INIS)

Ethanol itself did not induce any apparent chromosome aberrations in Chinese hamster ovary cells. However, posttreatment with ethanol potentiated the chromosome aberrations induced by ultraviolet light (UV), methyl methanesulfonate (MMS), mitomycin C (MMC) or bleomycin (BLM). Chromatid exchanges were predominantly increased in cultures treated with UV, MMS or MMC and then with ethanol, whereas chromosome breaks and chromatid exchange were the major types of aberrations increased in the cultures treated with BLM and ethanol. Posttreatment with acetaldehyde, the major metabolite of ethanol, also potentiated the chromosome aberrations induced by UV, MMS, MMC or BLM. The main types of aberrations potentiated by posttreatment with acetaldehyde were similar to those by posttreatment with ethanol. (author). 32 refs.; 3 figs.; 2 tabs

266

Protocol Implementation Generator  

DEFF Research Database (Denmark)

Users expect communication systems to guarantee, amongst others, privacy and integrity of their data. These can be ensured by using well-established protocols; the best protocol, however, is useless if not all parties involved in a communication have a correct implementation of the protocol and all necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implement new protocols throughout a network. PiG enables the sharing, verification, and translation of communication protocols. With it, partners can suggest a new protocol by sending its specification. After formally verifying the specification, each partner generates an implementation, which can then be used for establishing communication. We also present a practical realisation of the Protocol Implementation Generator framework based on the LySatool and a translator from the LySa language into C or Java.

Carvalho Quaresma, Jose Nuno; Probst, Christian W.

2010-01-01

267

Prevention of bleomycin-induced pulmonary fibrosis by a novel antifibrotic peptide with relaxin-like activity.  

Science.gov (United States)

Pulmonary fibrosis is a progressive and lethal lung disease characterized by accumulation of extracellular matrix and loss of pulmonary function. No cure exists for this pathologic condition, and current treatments often fail to slow its progression or relieve its symptoms. Relaxin was previously shown to induce a matrix-degrading phenotype in human lung fibroblasts in vitro and to inhibit pulmonary fibrosis in vivo. A novel peptide that targets the relaxin RXFP1/LGR7 receptor was recently identified using our computational platform designed to predict novel G protein-coupled receptor peptide agonists. In this study, we examined the antifibrotic properties of this novel peptide, designated CGEN25009, in human cell-based assays and in a murine model of bleomycin-induced pulmonary fibrosis. Similar to relaxin, CGEN25009 was found to have an inhibitory effect on transforming growth factor-?1-induced collagen deposition in human dermal fibroblasts and to enhance MMP-2 expression. The peptide's biological activity was also similar to relaxin in generating cellular stimulation of cAMP, cGMP, and NO in the THP-1 human cell line. In vivo, 2-week administration of CGEN25009 in a preventive or therapeutic mode (i.e., concurrently with or 7 days after bleomycin treatment, respectively) caused a significant reduction in lung inflammation and injury and ameliorated adverse airway remodeling and peribronchial fibrosis. The results of this study indicate that CGEN25009 displays antifibrotic and anti-inflammatory properties and may offer a new therapeutic option for the treatment of pulmonary fibrosis. PMID:20826567

Pini, Alessandro; Shemesh, Ronen; Samuel, Chrishan S; Bathgate, Ross A D; Zauberman, Arie; Hermesh, Chen; Wool, Assaf; Bani, Daniele; Rotman, Galit

2010-12-01

268

A new rat type I-like alveolar epithelial cell line R3/1: bleomycin effects on caveolin expression.  

Science.gov (United States)

The study of function and regulation of the phenotype of alveolar type I (AT I) epithelial cells is limited by the rareness of suitable cell lines or primary cultures of this cell type. We describe in the present study the type I-like rat epithelial cell line R3/1. This cell line displays in vitro a phenotype with several characteristic features of AT I cells. R3/1 cells were analysed for mRNA and protein content of markers related to the AT I cell type (T1alpha, ICAM-1, connexin-43, caveolins-1 and -2) and AT II phenotypes [surfactant proteins (SPs) A, B, C and D]. The mRNAs for SPs were found to be at a low level. Moderate protein levels for SP-A and SP-B were found, and SP-C and SP-D proteins were not detectable. R3/1 cells are positive for CD44s, E-cadherin, cytokeratin, vimentin and RAGE, and bind the lectins BPA and SBA. For demonstration of the suitability of R3/1 cells for in vitro studies on epithelial injury, the cells were treated with bleomycin. As shown by real-time RT-PCR and immunoblotting, bleomycin-treatment of R3/1 cells resulted in a decrease in mRNA and protein for both caveolin-1 and caveolin-2 in comparison with controls. The AT I-like cell line R3/1 may serve as a promising tool for the study of lung cell biology. PMID:15221420

Koslowski, Roland; Barth, Kathrin; Augstein, Antje; Tschernig, Thomas; Bargsten, Gerhard; Aufderheide, Michaela; Kasper, Michael

2004-06-01

269

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

International Nuclear Information System (INIS)

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

270

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

International Nuclear Information System (INIS)

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

271

Influence of radiotherapy upon tumor accumulation and organ distribution of 57Co-bleomycin in mice with chemically induced squamous cell carcinoma  

International Nuclear Information System (INIS)

Squamous cell carcinoma was induced in male 6 to 8-week old NMRI-mice by application of 9,10-dimethyl-1,2-benzanthracene on the skin. 15 weeks later macroscopically visible skin tumors are developed. Then organ distribution and tumor accumulation of 57Co-Bleomycin (spec. activity 1 mCi/3.3 mg) were studied 1 to 48 hours after injection. In squamous cell carcinoma a high uptake of this tumor-seeking agent can be demonstrated (n = 46). After radiotherapy (100 kV; 1.7 mm Al-filter; 18.8 Gy)(n=26), however, a significantly reduced uptake of 57Co-Bleomycin in tumor tissue is observed. Possible consequences from these animal studies for tumor scintigraphy with this radiopharmaceutical in man are discussed. (orig.)

272

Preparation and biological evaluation of [61Cu]bleomycin complex as a possible PET radiopharmaceutical in normal and fibrosarcoma-bearing animals  

International Nuclear Information System (INIS)

[61Cu]bleomycin ([61Cu]BLM) was prepared using [61Cu]CuCl2 produced via natZn(p,x)61Cu. [61Cu]BLM was prepared under optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 92.5-370 MBq 61CuCl2) with radiochemical purity over 98% shown by HPLC and RTLC. [61Cu]BLM was administered into normal and tumor bearing rodents up to 210 min followed by biodistribution and co-incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal sacrification or an imaging method. [61Cu]BLM can be a potential PET radiotracer for tumor imaging. (authors)

273

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

International Nuclear Information System (INIS)

Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, ?-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

274

Detection of epithelial to mesenchymal transition in airways of a bleomycin induced pulmonary fibrosis model derived from an ?-smooth muscle actin-Cre transgenic mouse  

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Abstract Background Epithelial to mesenchymal transition (EMT) in alveolar epithelial cells (AECs) has been widely observed in patients suffering interstitial pulmonary fibrosis. In vitro studies have also demonstrated that AECs could convert into myofibroblasts following exposure to TGF-?1. In this study, we examined whether EMT occurs in bleomycin (BLM) induced pulmonary fibrosis, and the involvement of bronchial epithelial cells (BECs) in the EMT. Using an ?-smooth muscl...

Yang Xiao; Cheng Xuan; Zhang Min; Cai Lin; Yang Leilei; Wu Zhuang; Xu Jun

2007-01-01

275

Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes.  

Science.gov (United States)

Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and all bud scars in serial sections exhibited many interruptions and breaks after 3 or 4 h of treatment. The discovery of extensive damage to cell walls was consistent with the preferential (approximately 70%) association of radiolabeled bleomycin with cell walls and perimeters of bud scar regions after short exposures (30 min). After longer exposures, the distribution of silver grains changed from a predominant association with cell walls (30 min) to an increased association with the cell cytoplasm (1 to 4 h). This correlated with increased ultrastructural damage, since damage to cell walls was generally more frequent and more severe with increasing length of treatment (30 min to 4 h) or dose (25 to 100 micrograms/ml). Although DNA lesions are believed to be the lethal properties of bleomycins, the lesions produced in cell walls are also lethal properties of the antibiotics. The distributions of lesions on cell walls suggested a generalized interaction of the antibiotic with a cell wall component. These results led us to hypothesize a mechanism of effective antifungal action for the bleomycin family of antibiotics. PMID:1283297

Moore, C W; Del Valle, R; McKoy, J; Pramanik, A; Gordon, R E

1992-11-01

276

Spin-Labelled 1-Ethyl-1-Nitrosourea Prevents Doxorubicin and Bleomycin-Induced Oxidative Stress in Lungs, Hearts and Kidneys of Tumour-Bearing Mice  

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This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) an...

Gadjeva, Veselina G.; Nikolova, Galina D.; Grigorov, Boncho G.; Zheleva, Antoaneta M.; Tolekova, Anna N.; Vasileva, Maya I.

2014-01-01

277

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

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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.

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

2013-09-01

278

Abnormalities of pathways of fibrin turnover in lung lavage of rats with oleic acid and bleomycin-induced lung injury support alveolar fibrin deposition.  

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Alveolar fibrin deposition commonly accompanies acute lung injury, but the nature of the local abnormalities of coagulation and fibrinolysis that support pathologic fibrin deposition are not well understood. The trended abnormalities of procoagulant and fibrinolytic activities occurring in lung lavage fluids of Fischer 344 rats after lung injury induced by intravenous oleic acid (OA) or intratracheal bleomycin were studied. After injury by either agent, bronchoalveolar lavage (BAL) contained ...

Idell, S.; James, K. K.; Gillies, C.; Fair, D. S.; Thrall, R. S.

1989-01-01

279

Quantitative measurement of single- and double-strand breakage of DNA in Escherichia coli by the antitumor antibiotics bleomycin and talisomycin.  

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We developed an assay in which single-strand breakage (ssb) and double-strand breakage (dsb) of intracellular DNA by chemical agents can be accurately quantitated and differentiated. Escherichia coli cells containing plasmid pBR322 DNA were incubated with the antitumor antibiotics bleomycin A2 (BLM A2) or talisomycin A (TLM A). The plasmid DNA was isolated and then analyzed by electrophoresis on 1% agarose gels to separate the following conformational forms of plasmid DNA: (i) native, covalen...

Mirabelli, C. K.; Huang, C. H.; Fenwick, R. G.; Crooke, S. T.

1985-01-01

280

Spin-Labelled 1-Ethyl-1-Nitrosourea Prevents Doxorubicin and Bleomycin-Induced Oxidative Stress in Lungs, Hearts and Kidneys of Tumour-Bearing Mice  

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Full Text Available This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl]-1-nitrosourea (SLENU, recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA levels and activities of the antioxidant enzymes, superoxide dismutase (SOD and catalase (CAT, were studied in lung, heart and kidney homogenates isolated from C57 black tumor-bearing mice after i.p. treatment with solutions of DOX (60 mg/kg and BLM (60 mg/kg. The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg. After treatment with doxorubicin, heart and kidney homogenates of mice had significantly higher productions of lipid peroxidation compared to lung homogenates. It was accompanied by increased activity of the antioxidant defence enzyme superoxide dismutase and decreased activity of catalase. Bleomycin-induced oxidative stress was confirmed by significantly higher production of lipid peroxidation in lungs compared to heart homogenates, elevation of the anti-oxidant activity of superoxide dismutase and decreased activity of catalase enzymes. After pre-treatment of the mice with SLENU, the levels of all studied oxidative stress biomarkers were significantly improved in comparison with those of the mice treated alone with either bleomycin, or doxorubicin. The present results and those from a previously demonstrated superoxide scavenging activities (SSA of the nitrosourea SLENU have enabled us to explain the protective effect of the spin-labelled nitrosourea on doxorubicin and bleomycin-induced oxidative stress by scavenging of  O2- and increased NO release.

Veselina G. Gadjeva

2014-08-01

 
 
 
 
281

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

Scientific Electronic Library Online (English)

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

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

2012-12-01

282

Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes.  

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Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and al...

Moore, C. W.; Del Valle, R.; Mckoy, J.; Pramanik, A.; Gordon, R. E.

1992-01-01

283

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.  

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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 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

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

284

Negative control glucose dependent mediated by the PreS2 region on the translation efficiency of the reporter Sh-bleomycin gene in Saccharomyces cerevisiae.  

Science.gov (United States)

Saccharomyces cerevisiae is able to sense and respond to environmental changes such as the availability of carbon sources. In a previous work, we showed that the expression of the PreS2-S gene of HBV in yeast was negatively regulated at the translational level dependent of glucose. In this study, we show that the S mRNA is detected in the polysomes indicating its active translation, while the PreS2-S mRNA was mainly found in monosomes. Moreover, we used the gene reporter assay based on Zeocin resistance, to better characterize the PreS2 region responsible for this control. Two chimeric genes composed of the N- and C-terminal part of the PreS2 fused to the Sh-bleomycin gene conferring the resistance to Zeocin were expressed in yeast. We found that the strain expressing the N-terminal part of the PreS2 was sensitive to Zeocin on rich medium with 2% glucose. In contrast, the strain harbouring the C-terminal part of the PreS2 fused to the Sh-bleomycin grew on Zeocin, indicating that the Sh-bleomycin mRNA is efficiently translated, subsequently conferring resistance to Zeocin. Our data suggest the establishment of a translational control via the N-terminal part of the PreS2 mediated by the presence of 2% glucose in the media. PMID:24151821

Hadiji-Abbes, Nadia; Borchani-Chabchoub, Istabrak; Gargouri, Ali; Mokdad-Gargouri, Raja

2014-03-01

285

Adaptation of TURN protocol to SIP protocol  

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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.

Guezouri, Mustapha; Keche, Mokhtar

2010-01-01

286

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

International Nuclear Information System (INIS)

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 ?g 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.)

287

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

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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 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

288

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

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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)

289

A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice  

International Nuclear Information System (INIS)

A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy

290

Bleomycin-induced changes of lung epithelial permeability in rats and the effects of glucocorticosteroid on it  

International Nuclear Information System (INIS)

Purpose: To observe changes of lung epithelial permeability (LEP) and effects of glucocorti-costeroid (GC) on it in bleomycin (BM)-induced pulmonary fibrosis rats. Methods: Fifty-eight adult male Wistar rats were divided into control group and experimental group (subdivided into 7 day, 14 day non-treated groups and 7 day, 14 day GC-treated groups). The rat pulmonary fibrosis was induced by a single intratracheal installations of BM. LEP was measured by inhalation of 99mTc-DTPA aerosol. Results: Seven days after injection of GC, alkaline phosphatase (AKP) in broncho-alveolar lavage fluid (BALF) and LEP of GC-treated group were lower than those of non-treated group, but in comparison with those of control group, they are still higher; LEP has a positive correlation with AKP in BALF. Conclusions: This study suggests: 1) at early stage, GC can reduce LEP of BM-induced pulmonary fibrosis; 2) the severer the damage of lung epithelium is, the higher LEP increases; and LEP can be used as a sensitive and noninvasive index for detecting lung epithelial damage

291

Neoadjuvant chemotherapy with bleomycin, ifosfamide and nedaplatin (NAC-BIN) followed by radiotherapy in locoregionally advanced uterine cervical cancer  

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Twelve patients with locoregionally advanced uterine cervical cancer (IIIB: 10, IVA: 2) were treated with neoadjuvant chemotherapy consisting of bleomycin, ifosfamide, and nedaplatin (NAC-BIN) and full dose radical radiotherapy. NAC-BIN achieved one complete response and seven partial responses, for a response rate of 67%. Hematologic toxicity was the most common side effect. Five experienced grade 3{<=}leukopenia, and three had grade 3{<=}anemia. With the mean follow-up of 25 months (range: 9-52 months), nine of 12 patients developed recurrence. Eight had pelvic recurrence alone, and one had both pelvic recurrence and distant metastases. The 2-year pelvic control rate, disease-free survival rate (DFS), and absolute survival rate (AS) were 25%, 25%, and 42%, respectively. The 2-year DFS and AS for patients who responded well to NAC-BIN (CR+PR) was 38% and 63%, whereas for those with a poor response (NC) were 0%. From these results, we consider that preoperative NAC-BIN should not be indicated for patients with unresectable stage (stage III{<=}) uterine cervical cancer, because poor responders must subsequently be treated with definitive radiotherapy and may suffer poor prognosis. (author)

Toita, Takafumi; Ogawa, Kazuhiko; Kakinohana, Yasumasa; Adachi, Genki; Nishikuramori, Yukiko; Murayama, Sadayuki [Ryukyus Univ., Nishihara, Okinawa (Japan). School of Medicine

2000-06-01

292

Retrospective analysis of concurrent chemoradiation with the combination of bleomycin, ifosfamide and cisplatin (BIP) for uterine cervical cancer  

International Nuclear Information System (INIS)

Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP) is recognized as one of the most effective chemotherapies for uterine cervical cancer. However, there have been no reports that evaluate concurrent use of radiation with BIP. The objective of this study was to evaluate the toxicity and response of the combination of BIP concurrent with radiation in patients with squamous cell carcinoma of the uterine cervix. Eligibility criteria included patients who underwent radical hysterectomy (Type III hysterectomy) as a primary treatment and revealed lymph node metastases or deep myometrial invasion (stage IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The patients received three courses of BIP chemoradiation, and the response and toxicity were evaluated. From January 2000 to December 2003, 30 patients met study eligibility criteria. All but three patients completed 3 courses of planned chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows: anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response. Complete response was achieved in 16 (72.7%) of patients, with a response rate of 90.9%. In conclusion, BIP chemoradiation seems to be superior to previously reported chemoradiation regimens, and has a potential as an optimal combin, and has a potential as an optimal combination chemotherapy concurrent with radiation. (author)

293

Neoadjuvant chemotherapy with bleomycin, ifosfamide and nedaplatin (NAC-BIN) followed by radiotherapy in locoregionally advanced uterine cervical cancer  

International Nuclear Information System (INIS)

Twelve patients with locoregionally advanced uterine cervical cancer (IIIB: 10, IVA: 2) were treated with neoadjuvant chemotherapy consisting of bleomycin, ifosfamide, and nedaplatin (NAC-BIN) and full dose radical radiotherapy. NAC-BIN achieved one complete response and seven partial responses, for a response rate of 67%. Hematologic toxicity was the most common side effect. Five experienced grade 3?leukopenia, and three had grade 3?anemia. With the mean follow-up of 25 months (range: 9-52 months), nine of 12 patients developed recurrence. Eight had pelvic recurrence alone, and one had both pelvic recurrence and distant metastases. The 2-year pelvic control rate, disease-free survival rate (DFS), and absolute survival rate (AS) were 25%, 25%, and 42%, respectively. The 2-year DFS and AS for patients who responded well to NAC-BIN (CR+PR) was 38% and 63%, whereas for those with a poor response (NC) were 0%. From these results, we consider that preoperative NAC-BIN should not be indicated for patients with unresectable stage (stage III?) uterine cervical cancer, because poor responders must subsequently be treated with definitive radiotherapy and may suffer poor prognosis. (author)

294

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

Science.gov (United States)

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

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

2004-10-01

295

Vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) in disseminated testicular cancer: preliminary report of a Southwest Oncology Group Study.  

Science.gov (United States)

Combination induction chemotherapy consisting of vinblastine, bleomycin, and cis-dichlorodiammineplatinum(II) was administered to 126 patients with advanced germ cell tumors of the testis. Following this 4-month induction therapy, maintenance treatment consisting of chlorambucil and actinomycin D alternating monthly with vinblastine was given for an additional 20-month period. Sixty-four patients (51%) achieved a complete remission, while 33 patients (26%) achieved a partial response. Responses were observed in all histologic categories. Seven patients (11%), who were in complete remission, have relapsed at a median time of 5 months. Median duration of remission is greater than 12 months for complete responders and 4 months for partial responders. Significant leukopenia was noted in 57% of evaluable courses and significant thrombocytopenia was noted in 18%. Less than 20% of patients were noted to have nephrotoxicity. Other toxic effects observed were gastrointestinal (42%), dermatologic (15%), pyrexia (14%), neuromuscular (9%), and pulmonary (less than 5%). Several pretreatment parameters are currently being evaluated to determine the impact on complete remission rate and survival. PMID:91435

Samson, M K; Stephens, R L; Rivkin, S; Opipari, M; Maloney, T; Groppe, C W; Fisher, R

1979-01-01

296

Bleomycin-induced ?H2AX foci map preferentially to replicating domains in CHO9 interphase nuclei.  

Science.gov (United States)

Exposure to DNA damaging agents triggers phosphorylation of histone variant H2AX (generating ?H2AX) in large chromatin regions flanking DNA lesions, allowing their immunodetection as nuclear foci. Even though a predominance of ?H2AX foci in euchromatin has been postulated, foci positioning when DNA insult occurs in replicating eu- or heterochromatin regions has not been extensively explored. Labeling of interphase nuclei with 5-ethynyl-2'-deoxyuridine (EdU) pulses has revealed that DNA replication is temporarily and spatially regulated: euchromatin replicates in early S (ES) and heterochromatin along mid and late S (MS/LS) phases. In order to map DNA damage with respect to replicating domains, the distribution of ?H2AX foci induced by the radiomimetic agent bleomycin was analyzed in CHO9 interphase nuclei by delineating euchromatic (H3K4me3+) and replicating (EdU+) regions. Quantification of overlapping pixels and 3D inter-object overlap in binary masks revealed colocalization between ?H2AX foci and EdU?+??domains both in ES and MS/LS nuclei, indicating that primary damage distribution is modulated by DNA synthesis. Further, we verified that EdU incorporation by itself did not influence BLEO-induced ?H2AX nuclear patterns. Our results also revealed a repeated localization of ?H2AX foci in replicating/nonreplicating interfaces which could reflect short-range chromatin migration following DNA insult. PMID:25035135

Liddle, Pablo; Lafon-Hughes, Laura; Di Tomaso, María Vittoria; Reyes-Ábalos, Ana Laura; Jara, Jorge; Cerda, Mauricio; Härtel, Steffen; Folle, Gustavo A

2014-12-01

297

Evaluation of Bleomycin-induced chromosome aberrations under simulated microgravity conditions in human lymphocytes using "FISH" techniques  

Science.gov (United States)

In the present investigation we report the effects of simulated microgravity conditions (clinostat) on the induction of chromosomal aberrations in human lymphocytes in vitro by ®Bleomycin. Chromosomal aberrations have been analysed by means of fluorescent in situ hybridisation (FISH) and chromosome-specific composite DNA probes (chromosome painting). The results obtained show that, under simulated microgravity conditions, the levels of both symmetrical and asymmetrical (dicentrics, rings), the number of cells bearing "complex" aberrations and hence the total numbers of aberrations were significantly elevated at any of the dose-levels assayed, compared to the parallel treatments performed as 1g control ("ground"). Furthermore, the ratio symmetrical:asymmetrical translocations was markedly elevated under simulated microgravity conditions, compared to the findings usually observed under "normal" 1g conditions. On these bases, we are much inclined to believe that simulated microgravity, rather than limiting the resealing of DNA double strand breaks (DSB's) induced by genotoxic agents is influencing in terms of enhancement the misrejoining of DSB's which is actually responsible for the fixation of the original lesions to DNA into chromosomal aberrations. In addition, the possible different misrepair processes leading to the formation of symmetrical and asymmetrical translocations might be differentially influenced by microgravity being the symmetrical translocations significantly more represented.

Mosesso, P.; Schuber, M.; Seibt, D.; Schatz, A.; Fosci, A.; Fonti, E.; Palitti, F.

298

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

International Nuclear Information System (INIS)

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

299

Towards GROUP protocol formalization  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Over recent years, we experienced a huge diffusion of internet connected computing devices. As a consequence, this leaded to research for efficient and scalable approaches for managing the burden caused by the highly increased volume of data to be exchanged and processed. Efficient communication protocols are fundamental building blocks for realizing such approaches [1], [2]. Thus, several peer-to-peer protocols have been proposed. Gossip protocols [3]-[7] are a family of peer-to-peer protoco...

Mordacchini, Matteo; Dazzi, Patrizio; Baraglia, Ranieri; Ricci, Laura

2013-01-01

300

Coded Splitting Tree Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 p...

Sørensen, Jesper H.; Stefanovic?, Cedomir; Popovski, Petar

2013-01-01

 
 
 
 
301

Security of RFID protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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...

Deursen, Ton

2011-01-01

302

Protocol Assuring Universal Language  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Conventionally, interfaces of objects export a set of messages with their types, and suggest nothing about the order in which these services may be accessed. This leaves room for a large number of runtime errors or misbehaviours in type correct designs. To mend this, we introduce the notion of protocol, expressing offered and expected orderings of messages, along with a notion of protocol correctness. We do this by defining the Protocol Assuring Universal Language Paul, which describes protoc...

Rein, Rick; Fokkinga, Maarten M.

1998-01-01

303

Cooperative Hybrid ARQ Protocols: Unified Frameworks for Protocol Analysis  

CERN Document Server

Cooperative hybrid-ARQ (HARQ) protocols, which can exploit the spatial and temporal diversities, have been widely studied. The efficiency of cooperative HARQ protocols is higher than that of cooperative protocols, because retransmissions are only performed when necessary. We classify cooperative HARQ protocols as three decode-and-forward based HARQ (DF-HARQ) protocols and two amplified-and-forward based (AF-HARQ) protocols. To compare these protocols and obtain the optimum parameters, two unified frameworks are developed for protocol analysis. Using the frameworks, we can evaluate and compare the maximum throughput and outage probabilities according to the SNR, the relay location, and the delay constraint for the protocols.

Byun, Ilmu

2008-01-01

304

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

International Nuclear Information System (INIS)

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

305

Abnormalities of pathways of fibrin turnover in lung lavage of rats with oleic acid and bleomycin-induced lung injury support alveolar fibrin deposition.  

Science.gov (United States)

Alveolar fibrin deposition commonly accompanies acute lung injury, but the nature of the local abnormalities of coagulation and fibrinolysis that support pathologic fibrin deposition are not well understood. The trended abnormalities of procoagulant and fibrinolytic activities occurring in lung lavage fluids of Fischer 344 rats after lung injury induced by intravenous oleic acid (OA) or intratracheal bleomycin were studied. After injury by either agent, bronchoalveolar lavage (BAL) contained increased procoagulant activity and decreased fibrinolytic activity. Lavage procoagulant activity was mainly due to an activator of Factor X attributable to the extrinsic coagulation pathway, and fibrinolytic activity was almost completely plasminogen dependent. Major mechanisms of inhibition of fibrinolytic activity involved both the inhibition of the plasminogen activator (PA) and plasmin. These abnormalities were temporally associated with prominent alveolar fibrin deposition in both models. In OA-treated animals, lavage fibrinolytic activity was absent or profoundly decreased, and antiplasmin and procoagulant activities were increased within 4 hours after the induction of acute lung injury. By 24 hours after OA, lavage PA inhibitor (PAI) activity was elevated with sustained antiplasmin activity. By 3 days after OA, these abnormalities had resolved in association with almost complete resolution of alveolar fibrin deposits. Within 3 days after bleomycin-induced lung injury, lavage procoagulant activity was increased and fibrinolytic activity was depressed due to increased antiplasmin and PAI activities. These conditions persisted for 2 weeks, during which time alveolar fibrin deposition was associated with the development of pulmonary fibrosis. These data indicate that a disruption of the normal balance between procoagulant and fibrinolytic activities occurs in alveolar lining fluids of rats with alveolitis induced by either OA or bleomycin, and that concurrent abnormalities of pathways of fibrin turnover that occur in alveolar lining fluids promote the alveolar fibrin deposition associated with these lung injuries. PMID:2476934

Idell, S; James, K K; Gillies, C; Fair, D S; Thrall, R S

1989-08-01

306

Therapeutic effect of human umbilical cord mesenchymal stem cells modified by angiotensin-converting enzyme 2 gene on bleomycin-induced lung fibrosis injury.  

Science.gov (United States)

The aim of the present study was to evaluate the therapeutic effects of human umbilical cord mesenchymal stem cells (uMSCs) in the presence of angiotensin?converting enzyme 2 gene (ACE2; ACE2?uMSCs) on bleomycin (BLM)?induced lung injury and pulmonary fibrosis in mice. A total of 100 male C57BL/6 mice were divided at random into five groups (n=20) as follows: Control group, BLM group, ACE2 group, uMSC group and ACE2?uMSC group. At 7, 14 and 28 days post?treatment, the following parameters were evaluated in lung tissue: Oxidation indexes [malondialedehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and oxidized glutathione (GSSG)]; fibrosis factors [tumor necrosis factor (TNF)??, interferon (IFN)?? and transforming growth factor (TGF)??]; inflammatory cytokines [Interleukin (IL)?1, IL?2, IL?6 and IL?10]; ACE2 gene expression; hydroxyproline and collagen type 1 messenger RNA (mRNA) concentration; as well as matrix metalloproteinase (MMPs; 2 and 9) and tissue inhibitor of metalloproteinase (TIMP)1?4 expression. ACE2?uMSC injection following bleomycin pretreatment significantly alleviated lung injury in mice. In addition, treatment with ACE2?uMSCs demonstrated a stronger therapeutic effect than ACE2? or uMSC treatment alone, indicated by decreased expression of MDA, GSSG, TNF??, IFN??, TGF??, IL?1, IL?2, IL?6, collagen type 1 mRNA, MMPs and TIMPs as well as hydroxyproline concentration, and upregulation of SOD, GSH and ACE2 and IL?10. In conclusion, the results of the present study demonstrated that ACE2 and uMSCs had a synergistic therapeutic effect on bleomycin?induced acute lung injury. PMID:25435005

Min, Fang; Gao, Fengying; Li, Qian; Liu, Zhenwei

2015-04-01

307

Biosafety Protocol - the Cartagena Protocol on Biosafety  

... 'The market is falling for genetically engineered food. People are avoiding this food like they would mushrooms from Chernobyl, Benny Haerlin ...to top BIOSAFETY PROTOCOL: HISTORIC STEP IN FIGHT AGAINST ENVIRONMENTAL DAMAGE FROM GENETICALLY MODIFIED ORGANISMS Greenpeace 29 January 2000 Montreal Greenpeace today congratulated ...delegations for adopting an international Biosafety Protocol to control the trade of genetically engineered organisms (GMOs). 'This is a historic step ... 'The market is falling for genetically engineered food. People are avoiding this food like they would mushrooms from Chernobyl, Haerlin explained,...

308

Absence of O6-alkylguanine-DNA alkyltransferase induction in chick embryo liver and brain following X-irradiation or treatment with bleomycin  

International Nuclear Information System (INIS)

The presence of O6-alkylguanine-DNA alkyltransferase (AT) in liver and brain of chick embryos, chicks and hens was demonstrated. An induction of AT activity has only been found in the liver of chicks and hens 48 h after X-irradiation. The administration of methylmethanesulphonate to the chick embryo resulted 3-24 hr later in strong inhibition of AT activity accompanied by DNA alkylation. Under the same conditions, X-irradiation, dimethylnitrosamine and bleomycin exhibited no effect. The results are compared with those obtained in mouse, rat and human foetal tissues. (author)

309

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  

Energy Technology Data Exchange (ETDEWEB)

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 (/sup 57/Co-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.

Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.

1986-10-01

310

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

International Nuclear Information System (INIS)

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

311

Functional characterization of tlmH in Streptoalloteichus hindustanus E465-94 ATCC 31158 unveiling new insight into tallysomycin biosynthesis and affording a novel bleomycin analog  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Tallysomycins (TLMs) belong to the bleomycin (BLM) family of anticancer antibiotics and differ from the BLMs principally by the presence of a 4-amino-4,6-dideoxy-L-talose attached to C-41 of the TLM backbone as part of a glycosylcarbinolamide. To facilitate an understanding of the differences in anticancer activities observed between TLMs and BLMs, we thought to generate des-talose TLM analogs by engineering TLM biosynthesis in Streptoalloteichus hindustanus E465-94 ATCC 31158. Here we report...

Tao, Meifeng; Wang, Liyan; Wendt-pienkowski, Evelyn; Zhang, Ningning; Yang, Dong; Galm, Ute; Coughlin, Jane M.; Xu, Zhinan; Shen, Ben

2010-01-01

312

[Salvage chemotherapy with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) for refractory malignant lymphoma].  

Science.gov (United States)

Twenty patients with refractory malignant lymphoma were treated with a combination of VP-16, ifosfamide, procarbazine, prednisolone, bleomycin and methotrexate (VIPP-BM) as salvage chemotherapy. These patients were either resistant to front-line therapy or refractory in their relapses. Two patients (10%) achieved a complete remission and eleven patients (55%) attained a partial remission. An overall response rate was 65%. Major toxicities were myelosuppression, nausea and vomiting, and mucositis. However they were well tolerated. This regimen has been effective in the treatment for the patients with refractory lymphoma. PMID:2475652

Ohnishi, K; Hotta, T; Murate, T; Inoue, C; Ichikawa, A; Ninomiya, N; Goto, S; Tsushita, K; Utsumi, M; Nagura, E

1989-03-01

313

Transport Protocol Throughput Fairness  

Directory of Open Access Journals (Sweden)

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.

Saleem Bhatti

2009-11-01

314

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

International Nuclear Information System (INIS)

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

315

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

Science.gov (United States)

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 4weeks. 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 (100mg/kg body weight/day) injected daily for 3weeks. 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. PMID:24726524

Zhou, Cheng-Fan; Zhou, Deng-Chuan; Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng; Wu, Chang-Hao; Zhu, Qi-Xing

2014-06-15

316

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

International Nuclear Information System (INIS)

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

317

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

318

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

International Nuclear Information System (INIS)

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

319

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-08-30

320

The Wireless Application Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The Wireless Application Protocol WAP is a protocol stack for wireless communication networks. WAP uses WTLS, a wireless variant of the SSL/TLS protocol, to secure the communication between the mobile phone and other parts of the WAP architecture. This paper describes the security architecture of WAP and some important properties of the WTLS protocol. There are however some security problems with WAP and the WTLS protocol. Privacy, data protection and integrity are not always provided. Users and developers of WAP-applications should be aware of this. In this paper, we address the security weaknesses of WAP and WTLS and propose some countermeasures and good practices when using WAP. We conclude with advising when to use WAP and when not.

Dave Singelee

2005-11-01

 
 
 
 
321

Coded Splitting Tree Protocols  

DEFF Research Database (Denmark)

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.

SØrensen, Jesper Hemming; Stefanovic, Cedomir

2013-01-01

322

Transforming Password Protocols to Compose  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Formal, symbolic techniques are extremely useful for modelling and analysing security protocols. They improved our understanding of security protocols, allowed to discover flaws, and also provide support for protocol design. However, such analyses usually consider that the protocol is executed in isolation or assume a bounded number of protocol sessions. Hence, no security guarantee is provided when the protocol is executed in a more complex environment. In this paper, we study whether...

Chevalier, Ce?line; Delaune, Ste?phanie; Kremer, Steve

2011-01-01

323

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.  

Science.gov (United States)

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study. PMID:1720279

Spiers, A S; Weens, J H; Rowe, J M; Smith, T J; Horton, J; Gordon, L I; Glick, J H

1991-12-01

324

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

International Nuclear Information System (INIS)

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

325

Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine  

Energy Technology Data Exchange (ETDEWEB)

Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function.

Cantor, J.O.; Osman, M.; Keller, S.; Cerreta, J.M.; Mandl, I.; Turino, G.M.

1984-03-01

326

Playing With Population Protocols  

Directory of Open Access Journals (Sweden)

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.

Xavier Koegler

2009-06-01

327

Playing With Population Protocols  

CERN Document Server

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.

Bournez, Olivier; Cohen, Johanne; Koegler, Xavier; 10.4204/EPTCS.1.1

2009-01-01

328

ATM and Internet protocol  

CERN Document Server

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

Bentall, M; Turton, B

2012-01-01

329

Diffusion-enhanced lanthanide energy-transfer study of DNA-bound cobalt(III) bleomycins: comparisons of accessibility and electrostatic potential with DNA complexes of ethidium and acridine orange.  

Science.gov (United States)

Energy transfer in the "rapid-diffusion" limit reflects the equilibrium properties of a donor-acceptor system. Rates of energy transfer from freely diffusing terbium chelates to DNA-binding chromophores change dramatically when DNA is added; energy transfer from an electrically neutral chelate is reduced because the energy acceptor becomes partially buried in DNA, while energy transfer from a positive chelate is increased because of electrostatic attraction. The rate constants for energy transfer to DNA-bound chromophores from a positively charged terbium chelate, relative to those from a neutral chelate, were used to estimate the following values for the electrostatic potential near the surface of each DNA-bound acceptor at 298 K in the presence of 1.0 mM added salt (in units of -e/kT): acridine orange, 4.54 +/- 0.11; ethidium, 4.66 +/- 0.07; green Co(III) bleomycin A2, 4.06 +/- 0.11; orange Co(III) bleomycin A2, 3.11 +/- 0.10. Smaller numbers indicate less negative potentials; these can be due to a combination of (1) positive charge on the chromophore, (2) location of the chromophore [particularly Co(III) bleomycin] away from the DNA phosphates, and/or (3) separation of DNA phosphate negative charges by an intercalator. The magnitudes of the individual rate constants indicate that all the DNA-bound chromophores can be directly encountered by the terbium probes. Energy-transfer rate constants from a neutral terbium chelate to DNA-bound and free acceptors can provide a measure of the accessibility of the terbium probe to each bound chromophore. The ratios of these rate constants were as follows: acridine orange, 0.17 +/- 0.01; ethidium, 0.27 +/- 0.02; green form of Co(III) bleomycin A2, 0.48 +/- 0.06; orange form of Co(III) bleomycin A2, 0.71 +/- 0.06. These results are consistent with the probable differences in binding mechanisms for the intercalating chromophores (ethidium and acridine orange) as compared to the Co(III) bleomycins (in which the relevant chromophores are nonintercalating metal centers). In addition, all the results imply that the green Co(III) bleomycin chromophore binds closer to DNA than the orange; this provides a first step toward understanding the structural basis for the different biological properties of these metallobleomycins. Control experiments and theoretical considerations necessary to establish the validity of the results are also presented. PMID:2410019

Wensel, T G; Chang, C H; Meares, C F

1985-06-01

330

Automated Composition of Security Protocols  

CERN Document Server

Determining if two protocols can be securely composed requires analyzing not only their additive properties but also their destructive properties. In this paper we propose a new composition method for constructing protocols based on existing ones found in the literature that can be fully automatized. The additive properties of the composed protocols are ensured by the composition of protocol preconditions and effects, denoting, respectively, the conditions that must hold for protocols to be executed and the conditions that hold after executing the protocols. The non-destructive property of the final composed protocol is verified by analyzing the independence of the involved protocols, a method proposed by the authors in their previous work. The fully automatized property is ensured by constructing a rich protocol model that contains explicit description of protocol preconditions, effects, generated terms and exchanged messages. The proposed method is validated by composing 17 protocol pairs and by verifying t...

Genge, Bela; Haller, Piroska

2009-01-01

331

Implementation of SAMPLE Protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Wireless networks are pervasive in our society. With an increased interest shown by the general public in wireless technologies, protocols and hardware are being actively developed by academic and industrial groups alike. Moblie ad hoc networks (MANET) are an important subset of wireless networks and have particular routing needs which are not supported by 802.11, the most widely deployed wireless protocol. They must operate in the presence of interference, contention and cope ...

Nash, Kevin

2005-01-01

332

On the AAGL Protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Recently the AAGL (Anshel-Anshel-Goldfeld-Lemieux) has been proposed which can be used for RFID tags. We give algorithms for the problem (we call the MSCSPv) on which the security of the AAGL protocol is based upon. Hence we give various attacks for general parameters on the recent AAGL protocol proposed. One of our attacks is a deterministic algorithm which has space complexity and time complexity both atleast exponentialin the worst case. In a better case using a probabili...

Chowdhury, M. M.

2007-01-01

333

Village Level Protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Here in this paper we have proposed for a protocol to be implemented at the village level. As at the village level as there are few agencies to be contacted at village level so this uses a local label addressing of 4 bits to support 16 agencies with 3 bits Time to live header which checks weather a packet is reached or not. Thus being small packet size this protocol is faster and able to support fast network service at village level.

Ankur Dumka

2014-01-01

334

Stream Control Transmission Protocol Steganography  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Fraczek, Wojciech; Mazurczyk, Wojciech; Szczypiorski, Krzysztof

2010-01-01

335

Unconditionally Secure Protocols  

DEFF Research Database (Denmark)

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

Meldgaard, Sigurd Torkel

2013-01-01

336

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

Directory of Open Access Journals (Sweden)

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.

Carol Wood Moore

2003-01-01

337

Security Protocol Design: A Case Study Using Key Distribution Protocols  

Directory of Open Access Journals (Sweden)

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.

Reiner Dojen

2009-10-01

338

Symmetric cryptographic protocols  

CERN Document Server

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

Ramkumar, Mahalingam

2014-01-01

339

Village Level Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available Here in this paper we have proposed for a protocol to be implemented at the village level. As at the village level as there are few agencies to be contacted at village level so this uses a local label addressing of 4 bits to support 16 agencies with 3 bits Time to live header which checks weather a packet is reached or not. Thus being small packet size this protocol is faster and able to support fast network service at village level.

Ankur Dumka

2014-02-01

340

Intra-arterial mitomycin C and intravenous bleomycin as induction chemotherapy in advanced head and neck cancer - a phase II study  

International Nuclear Information System (INIS)

Fifty-six patients with previously untreated, unresectable squamous cell carcinomas of the head and neck region were treated with repeated intra-arterial chemotherapy with mitomycin C using a selective or superselective angiographic technique, and bleomycin given i.v., followed by radical radiotherapy. In addition, restricted tumour-reductive surgery was done in 18 of these patients. The response rate (CR + PR) after completion of the integrated treatment was 89%, with 63% of the patients showing CR. The toxicity of this regimen was, however, far from negligible. The median survival for this series of patients with advanced head and neck cancers is 19 months, and 17 are still alive after 16+ - 66+ months. (Auth.)

 
 
 
 
341

Plasminogen activator inhibitor-1 deficiency augments visceral mesothelial organization, intrapleural coagulation, and lung restriction in mice with carbon black/bleomycin-induced pleural injury.  

Science.gov (United States)

Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1 have been implicated in the pathogenesis of pleural injury. However, their role in the control of pleural organization has been unclear. We found that a C57Bl/6j mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural organization resulting in pleural rind formation (14 d). In transgenic mice overexpressing human PAI-1, intrapleural fibrin deposition was increased, but visceral pleural thickness, lung volumes, and compliance were comparable to wild type. CBB injury in PAI-1(-/-) mice significantly increased visceral pleural thickness (P intrapleural fibrin deposition, PAI-1 deficiency promotes profibrogenic alterations of the mesothelium that exacerbate pleural organization and lung restriction. PMID:24024554

Tucker, Torry A; Jeffers, Ann; Alvarez, Alexia; Owens, Shuzi; Koenig, Kathleen; Quaid, Brandon; Komissarov, Andrey A; Florova, Galina; Kothari, Hema; Pendurthi, Usha; Mohan Rao, L Vijaya; Idell, Steven

2014-02-01

342

Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin  

International Nuclear Information System (INIS)

Purpose: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. Patients and Methods: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). Results: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. Conclusi difference between the 2 groups. Conclusion: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation

343

Growth Differentiation Factor 15 (GDF-15) Plasma Levels Increase during Bleomycin- and Cisplatin-Based Treatment of Testicular Cancer Patients and Relate to Endothelial Damage  

Science.gov (United States)

Introduction Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. Methods Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)). Results Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with ‘p53’ and ‘Diabetes Mellitus’ gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points. Conclusion An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage. PMID:25590623

Altena, Renske; Fehrmann, Rudolf S. N.; Boer, Hink; de Vries, Elisabeth G. E.; Meijer, Coby; Gietema, Jourik A.

2015-01-01

344

Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat  

Science.gov (United States)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-?) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 ?mol/kg/day, respectively). (5: Sham group: CAPE (10 ?mol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-? level, increase the animals? body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis. PMID:24082893

Larki, A.; Hemmati, A. A.; Arzi, A.; Borujerdnia, M. Ghafurian; Esmaeilzadeh, S.; Zad Karami, M. R.

2013-01-01

345

Knock Out of S1P3 Receptor Signaling Attenuates Inflammation and Fibrosis in Bleomycin-Induced Lung Injury Mice Model  

Science.gov (United States)

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein–coupled receptors (S1P1–5). Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO)) mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT) mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF) collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF) levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1) or transforming growth factor ?1 (TGF-?1) levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis. PMID:25198418

Murakami, Ken; Kohno, Masataka; Kadoya, Masatoshi; Nagahara, Hidetake; Fujii, Wataru; Seno, Takahiro; Yamamoto, Aihiro; Oda, Ryo; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Morita, Satoshi; Nakada, Hiroshi; Hla, Timothy; Kawahito, Yutaka

2014-01-01

346

Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat.  

Science.gov (United States)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-?) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 ?mol/kg/day, respectively). (5: Sham group: CAPE (10 ?mol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-? level, increase the animals' body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis. PMID:24082893

Larki, A; Hemmati, A A; Arzi, A; Borujerdnia, M Ghafurian; Esmaeilzadeh, S; Zad Karami, M R

2013-10-01

347

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

Directory of Open Access Journals (Sweden)

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 ? collagen (Col ? 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 ? 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.

Xian-mei Zhou

2012-02-01

348

DNA repair protocols  

DEFF Research Database (Denmark)

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 successful Methods in Molecular Biology? series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, DNA Repair Protocols, Third Edition provides expert guidance for DNA repair, recombination, and replication.

Bjergbæk, Lotte

2012-01-01

349

Coagulase Test Protocol  

Science.gov (United States)

This protocol describes the history and procedures of the coagulase test.  The coagulase test isused to differentiate species of Staphylococcus, especially the coagulase-positive Staphylococcus aureus from coagulase-negative staphylococcal species.  Both common versions of the test, the slide method and the test tube method, are described, and the mechanisms of the reactions are discussed.

American Society For Microbiology

2010-11-11

350

An automatic protocol composition checker  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Kojovic, Ivana

2012-01-01

351

Authenticated Tripartite Key Agreement Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available An authenticated tripartite key agreement mechanism based on Joux`s protocol is presented in this paper. The proposed protocol allows the three parties involved in the protocol to agree upon a common session key over an insecure network. The security of the proposed protocol is based on CDH problem and the strong hash function. Its security is improved under the random oracle model.

Chunbo Ma

2008-01-01

352

Synchronizing internet protocol security (SIPSec)  

CERN Document Server

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

Shoniregun, Charles A

2007-01-01

353

Automated Composition of Security Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Determining if two protocols can be securely composed requires analyzing not only their additive properties but also their destructive properties. In this paper we propose a new composition method for constructing protocols based on existing ones found in the literature that can be fully automatized. The additive properties of the composed protocols are ensured by the composition of protocol preconditions and effects, denoting, respectively, the conditions that must hold for...

Genge, Bela; Ignat, Iosif; Haller, Piroska

2009-01-01

354

Mitosis Methods & Protocols  

Directory of Open Access Journals (Sweden)

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..... 

CarloAlberto Redi

2010-06-01

355

Phototherapy Modalities and Protocols  

Directory of Open Access Journals (Sweden)

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.

Ayten Ferahba?

2010-12-01

356

Generalized Teleportation Protocol  

CERN Document Server

A generalized teleportation protocol (GTP) for N qubits is presented, where the teleportation channels are non-maximally entangled and all the free parameters of the protocol are considered: Alice's measurement basis, her sets of acceptable results, and Bob's unitary operations. The full range of Fidelity (F) of the teleported state and the Probability of Success (P_{suc}) to obtain a given fidelity are achieved by changing these free parameters. A channel capacity bound is found, where one can determine how to divide it between F and P_{suc}. A one qubit formulation is presented and then expanded to N qubits. A proposed experimental setup that implements the GTP is given using linear optics.

Gordon, G; Gordon, Goren; Rigolin, Gustavo

2005-01-01

357

Seismic protocol urges sensitivity  

International Nuclear Information System (INIS)

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

358

[Radiation-induced modification of human somatic cell chromosome sensitivity to the testing mutagenic exposure of bleomycin in vitro in lung cancer patients in delayed terms following Chernobyl accident].  

Science.gov (United States)

By using modified "G2-bleomycin sensitivity assay" above background level of cytogenetic effect considered as a marker of hidden chromosome instability (HCI) has been investigated in 3 groups--liquidators of Chernobyl accident (occupational group 1), patients with lung cancer who denied conscious contact--with ionizing radiation (group of comparison), liquidators with lung cancer (occupational group 2). Significant interindividual variations of cytogenetic effects induced with bleomycin and the lack of positive correlation between background and above background frequencies of chromosome aberrations have been shown in all observed groups. It had been established that occupational group 2 was the most burdened group by expression of the above background cytogenetic effect and, accordingly, number of persons with HCI. The data obtained permit to suggest the existence of the association between radiation-induced increase of individual sensitivity to testing mutagenic exposure and the realization of cancer in persons exposed to ionizing radiation. The results show acceptability of "G2-bleomycin sensitivity assay" under the cytogenetic examination of irradiated contingents for determining HCI as one of informative markers of predisposition to oncopathology. PMID:23285748

Pilinskaia, M A; Dybski?, S S; Dybskaia, E B; Shva?ko, L I

2012-01-01

359

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

Scientific Electronic Library Online (English)

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

Adriana Ignacio de, Padua; Célio Lopes, Silva; Simone Gusmão, Ramos; Lúcia Helena, Faccioli; José Antônio Baddini, Martinez.

2008-11-01

360

Very low dose and dose-rate X-ray induced adaptive response in human lymphocytes at various cell cycle stages against bleomycin induced chromatid aberrations  

International Nuclear Information System (INIS)

Complete text of publication follows. Objective: To study the adaptive response induced by very low doses of X-rays at very low dose rate in human lymphocytes at different cell cycle stages followed by a challenge dose of bleomycin sulphate at G2 phase. Materials and Methods: Human peripheral blood lymphocytes before (G0) and after PHA stimulation (G1 and G2) were exposed to 1 and 5 cGy X-rays generated by a fluoroscopy unit with a dose rate of 5.56 mGy/min and challenged with 5 ?g/ml bleomycin sulphate (BLM) 48 hours after culture initiation. Mitotic cells were arrested at metaphase by addition of colcemid in cultures 1.5 h before harvesting. Harvesting and slide preparation was performed using standard method. 100 well spread metaphases were analyzed for the presence of chromatid type aberrations for each sample. Results: Results obtained indicate that there is a linear relationship between the dose of BLM and chromatid aberrations below 5 ?g/ml (R=0.93, p<0.0001). The results also show that pretreatment of lymphocytes with low dose X-rays at G0, G1 and G2 phases of the cell cycle significantly reduced the sensitivity of lymphocytes to the clastogenic effects of BLM in G2. Much lower frequencies of chromatid aberrations were observed in X-ray irradiated lymphocytes following BLM treatment (p<0.05). The magnitudes of adaptation induced at different phases of the cell cycle were not significantly different. Furthermore, there was no a significant difference in the mwas no a significant difference in the magnitude of adaptive response induced by either 1 or 5 cGy X-rays. Conclusion: These observations might indicate that resistance of pre-exposure of lymphocytes to very low doses of X-rays protects them from clastogenic effects of BLM. This effect might be due to initial DNA damage induced in these cells leading to provocation of an active DNA repair mechanism independent of cell cycle stage.

 
 
 
 
361

Neuro MR: protocols.  

Science.gov (United States)

Clinical MRI depends on a symbiosis between MR physics and clinical requirements. The imaging solutions are based on a balance between the "palette" of available image contrasts derived from nuclear spin physics and tissue biophysics, and clinical determinants such as the anticipated pathology and efficient use of imaging time. Imaging is therefore optimized to maximize diagnostic sensitivity and specificity through the development of protocols organized along the lines of major disease categories. In the other part of this two-part review, the primary determinants of image contrast, including T1, T2, and T2*, were highlighted. The development of pulse sequences designed to optimize each of these image contrasts was discussed and the impact of technological innovation (parallel imaging and high-field systems) on the manner in which these sequences could be modified to improve clinical efficacy was further emphasized. The scope of that discussion was broadened to include the application of: 1) water diffusion imaging used primarily for detection of pathologies that restrict the free movement of water in the tissues and for defining fiber tracts in the brain; 2) the intravenous administration of exogenous contrast agents (gadolinium-diethylene triamine pentaacetic acid [GdDTPA]) for assessment of blood-brain-barrier (BBB) defects and brain blood flow; and 3) MR spectroscopy (MRS) for assessment of brain metabolites. The goal of this part is to discuss how these acquisitions are combined into specific protocols that can effectively detect and characterize, or in keeping with our artistic analogy, "paint" each of the major diseases affecting the central nervous system (CNS). This work concludes with a discussion of image artifacts and pitfalls in image interpretation, which, in spite our best efforts to minimize or eliminate them, continue to occur. Much of the ensuing discussion is based on our own institutional experience. Protocols, therefore, do not necessarily match those from other institutions due to variability in clinical emphasis, MR instruments, and available software. An attempt was made to focus on basic clinical sequences that are available on most modern MR systems, with protocols employing generally accepted clinical imaging philosophies. PMID:17896388

Mikulis, David J; Roberts, Timothy P L

2007-10-01

362

Sincalide - the final protocol  

International Nuclear Information System (INIS)

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

363

Hektoen Enteric Agar Protocol  

Science.gov (United States)

Hektoen enteric agar is a selective and differential media for the recovery of enteric gram-negative rods from mixed microbiota.  The growth of gram-positive organisms and nonpathogenic enteric coliforms is inhibited through the use of bile salts and dyes, allowing intestinal pathogens, such as Salmonella and Shigella, to be more easily recovered.  The media can also differentiate between organisms that produce H2S and those that do not due to the presence of an iron-containing compound.  The use and interpretation of growth on this media is discussed in this protocol.

American Society For Microbiology;

2010-11-11

364

FRENCH PROTOCOL CARDS  

CERN Multimedia

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.

Human Resources Division

2000-01-01

365

FRENCH PROTOCOL CARDS  

CERN Multimedia

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

Division du Personnel

1999-01-01

366

Stream Control Transmission Protocol Steganography  

CERN Document Server

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.

Fraczek, Wojciech; Szczypiorski, Krzysztof

2010-01-01

367

Security and SCADA protocols  

International Nuclear Information System (INIS)

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

368

Security and SCADA protocols  

Energy Technology Data Exchange (ETDEWEB)

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)

Igure, V. M.; Williams, R. D. [Dept. of Electrical and Computer Engineering, Univ. of Virginia, Box 400743, 351 McCormick Rd., Charlottesville, VA 22904-4743 (United States)

2006-07-01

369

Efficient Transport Protocol for Networked  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The performance of haptic application is highly sensitive to communication delays and losses of data. It implies several constraints in developing networked haptic applications. This paper describes a new internet protocol called Efficient Transport Protocol (ETP), which aims at developing distributed interactive applications. TCP and UDP are transport protocols commonly used in any kind of networked communication, but they are not focused on real time application. This new ...

Wirz, Rau?l; Ferre, Manuel; Mari?n Prades, Rau?l; Barrio, Jorge; Claver, Jose? M.; Ortego, Javier

2008-01-01

370

An Internet Protocol Testing Framework  

Digital Repository Infrastructure Vision for European Research (DRIVER)

As the Internet expands and proliferates it gives rise to new technologies that require supporting Internet protocols. Some recent examples include HTTP, POP, IMAP and IIOP. Internet applications are generally based on a client server model. This results in protocols being developed to support communication between the client and server. Additionally many existing protocols are updated regularly to support new and enhanced features. There is a user requirement for software prod...

Cashman, John

1998-01-01

371

Impersonation with the Echo Protocol  

CERN Document Server

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

Chung, Y; Chung, Yoo; Lee, Dongman

2005-01-01

372

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

International Nuclear Information System (INIS)

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

373

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

Energy Technology Data Exchange (ETDEWEB)

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.

Weichselbaum, R.R. (Harvard Medical School, Boston); Posner, M.R.; Ervin, T.J.; Fabian, R.L.; Miller, D.

1982-05-01

374

Comparison of DNA damage and single- and double-strand breakage activities on PM-2 DNA by talisomycin and bleomycin analogs.  

Science.gov (United States)

Single- and double-strand breakage of isolated PM-2 DNA by structural analogs of the glycopeptide antitumor antibiotics bleomycin (BLM) and talisomycin (TLM) was investigated. Breakage of PM-2 DNA was determined by two systems: an ethidium bromide fluorescence assay; and agarose gel electrophoresis. The fluorescence assay, which measures total breakage of DNA including single- and double-strand breakage and alkaline labile damage, showed that the BLM's, A2 and B2 induced more total DNA breakage than did the TLM's A, B, S2b, and S10b. As measured by the comparison of the concentration of analog required to cause 50% breakage of superhelical DNA, BLM's A2 and B2 were 10 times more active than TLM's S2b and S10b and 25 times more active than TLM's A and B. Gel electrophoresis, which measures the extent of both single- and double-strand breakage of DNA, showed that at equivalent levels of breakage of superhelical DNA each of the TLM's caused more double-strand breakage of DNA than did the BLM's. Thus, the structural alterations near the bithiazole in the TLM's, which distinguish them structurally from the BLM's, result in a reduction of the total PM-2 DNA breakage activity and enhanced production of double-strand breaks relative to single-strand breaks by TLM when compared to BLM. PMID:6162546

Mirabelli, C K; Huang, C H; Crooke, S T

1980-11-01

375

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

International Nuclear Information System (INIS)

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

376

Evaluation of the Effects of Caffeic Acid Phenethyl Ester on Prostaglandin E2 and Two Key Cytokines Involved in Bleomycin-induced Pulmonary Fibrosis  

Science.gov (United States)

Objective(s): Pulmonary fibrosis (PF) is the most common outcome of a collection of diverse lung disorders known as interstitial lung diseases. It is proposed that alterations in the levels of fibrogenic mediators and the profibrotic/antifibrotic imbalance play a substantial role in the progression of PF in animal models and possibly in humans. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has numerous biological effects. In the present study, the main objective was to investigate the effects of CAPE on some key mediators including TGF-?1, TNF-? and prostaglandin E2 (PGE2) involved in profibrotic/antifibrotic balance and pathogenesis of idiopathic pulmonary fibrosis (IPF). Materials and Methods: In this study, forty male Sprague–Dawley rats were divided into 5 groups (n=8). (1) “Bleomycin (BLM)-treated (Model) group”: BLM (5 mg/kg, single intratracheal dose), (2) “Saline-treated group”: the rats were given only saline, (3) “Treatment-1 group”: BLM + CAPE (5 ?mol/kg/day, 28 days, IP), (4) “Treatment-2 group”: BLM + CAPE (10 ?mol/kg/day, 28 days, IP) and (5) “Vehicle + CAPE group”: CAPE (10 ?mol/kg/day, 28 days, IP). Results: BLM could significantly increase the levels of TNF-? and TGF-?1 and decrease the PGE2 concentration compared to the saline control group. CAPE could considerably improve these values almost close to normal levels. Conclusion: Briefly, CAPE can be suggested as a novel, attractive and effective agent for prevention and treatment of pulmonary fibrosis. PMID:23997916

Larki-Harchegani, Amir; Hemmati, Ali Asghar; Arzi, Ardeshir; Ghafurian-Boroojerdnia, Mehri; Shabib, Somayeh; Zadkarami, Mohammad Reza; Esmaeilzadeh, Saleh

2013-01-01

377

Influence of chlorpromazine, bleomycin and WR-2721 singly or in combination on the formation of radiation-induced micronuclei in mice bone marrow  

International Nuclear Information System (INIS)

Female BALB/c mice were divided into 8 groups according to the treatment they received viz. 1. DDW (double distilled water), 2. chlorpromazine (CPZ) 10 mg/kg body-weight, 3. CPZ 15 mg/kg body-weight, 4. bleomycin (BLM), 5. WR-2721, 6. CPZ (10 mg)+WR-2721, 7. CPZ (15 mg)+WR-2721, 8. BLM+WR-2721. After 30 min of drug/s administration the animals were exposed to either 0 or 4 Gy of 60Co g-radiation. The animals were killed at 24 h post-irradiation by cervical dislocation and the micronuclei were prepared according to the method described by Jagetia. The administration of CPZ (10 or 15 mg) alone increased the frequency of micronuclei significantly when compared to the DDW treatment. The exposure of mice with 4 Gy resulted in a significant increase in the frequency of micronuclei compared to the concurrent control groups. The frequency of micronuclei increased significantly in CPZ (15 mg) and BLM+irradiated groups. However, treatment with WR-2721 before irradiation reduced the frequency of micronuclei by approximately 50% of the DDW+irradiated group. A further reduction in the frequency of micronuclei was observed when WR-2721 was combined with CPZ (10 and 15 mg) before irradiation. A combination of BLM with WR-2721 also resulted in a nonsignificant reduction in the frequency of micronuclei. (orig.)

378

Energy – Efficient MAC Protocol (EE-MAC Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available Because of the difficulty in recharging or replacing the batteries of each node in a Wireless Sensor Network, the energy efficiency of the system is a major issue in the area of network design. Other critical parameters such as delay, adaptability to traffic conditions, scalability, system fairness, and throughput and bandwidth utilization are mostly dealt as secondary objectives. Some sensor network applications adopt IEEE 802.11-like MAC protocol, which is however, not a good solution for sensor network applications because it suffers from energy inefficiency problem. The adaptive Sensor-MAC (S-MAC proposes enhanced schemes such as periodic sleep and overhearing avoidance to provide a better choice for different sensor network applications. In this research paper we propose an energy efficient MAC (EE-MAC protocol, which is based on adaptive S-MAC with added transmission power control techniques. The main contribution of our work is to introduce a controlled power transmission of RTS, CTS, DATA and ACK frames according to the adaptive S-MAC protocol. We simulate our proposed protocol i.e., EE-MAC protocol using ns-2.33 simulator for two parameters energy consumption and throughput, for determining the behavior of the proposed protocol. The simulation results show that our proposed EE-MAC protocol performs better than adaptive S-MAC protocol in terms of energy consumption and throughput.

Garima Bhardwaj

2013-01-01

379

Licklider Transmission Protocol Implementation  

Science.gov (United States)

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.

Burleigh, Scott C.; Krupiarz, Chris

2011-01-01

380

Protocols for Scholarly Communication  

CERN Document Server

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...

Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

2007-01-01

 
 
 
 
381

A Streaming Protocol for Memcached  

Directory of Open Access Journals (Sweden)

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.

W. Li

2012-01-01

382

Publishing protocols for partnered research.  

Science.gov (United States)

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 important. Using as illustration a suite of studies aimed at improving coordination and communication in the primary care setting, we sought to identify challenges in publishing PPR relative to traditional designs, present alternative solutions to PPR publication, and propose an initial checklist of content to be included in protocols of partnered research. Challenges to publishing PPR include reporting details of research components intended to be co-created with operational partners, changes to sampling and entry strategy, and alignment of scientific and operational goals. Proposed solutions include emulating reporting standards of qualitative research, participatory action research, and adaptive trial designs, as well as embracing technological tools that facilitate publishing adaptive protocols, with version histories that are able to be updated as major protocol changes occur. Finally, we present a proposed checklist of reporting elements for partnered research protocols. PMID:25355092

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

2014-12-01

383

Message Broadcasting Protocols in VANET  

Directory of Open Access Journals (Sweden)

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.

Ghassan Samara

2012-01-01

384

A Framework for the Development of Protocols  

DEFF Research Database (Denmark)

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

Crazzolara, Federico; Milicia, Giuseppe

2003-01-01

385

Session Initiation Protocol Attacks and Challenges  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 authenticatio...

Keshavarz, Hassan; Sattari, Mohammad Reza Jabbarpour; Noor, Rafidah Md

2012-01-01

386

Internet Protocol Television (IPTV  

Directory of Open Access Journals (Sweden)

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

Lokesh Mittal

2012-09-01

387

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The phenazines are redox-active secondary metabolites that a large number of bacterial strains produce and excrete into the environment. They possess antibiotic activity owing to the fact that they can reduce molecular oxygen to toxic reactive oxygen species. In order to take advantage of this activity, phenazine producers need to protect themselves against phenazine toxicity. Whereas it is believed that phenazine-producing pseudomonads possess highly active superoxide dismutases and catalases, it has recently been found that the plant-colonizing bacterium Enterobacter agglomerans expresses a small gene ehpR to render itself resistant towards D-alanyl-griseoluteic acid, the phenazine antibiotic produced by this strain. Results To understand the resistance mechanism installed by EhpR we have determined its crystal structure in the apo form at 2.15 Å resolution and in complex with griseoluteic acid at 1.01 Å, respectively. While EhpR shares a common fold with glyoxalase-I/bleomycin resistance proteins, the ligand binding site does not contain residues that some related proteins employ to chemically alter their substrates. Binding of the antibiotic is mediated by ?-stacking interactions of the aromatic moiety with the side chains of aromatic amino acids and by a few polar interactions. The dissociation constant KD between EhpR and griseoluteic acid was quantified as 244 ± 45 ?M by microscale thermophoresis measurements. Conclusions The data accumulated here suggest that EhpR confers resistance by binding D-alanyl-griseoluteic acid and acting as a chaperone involved in exporting the antibiotic rather than by altering it chemically. It is tempting to speculate that EhpR acts in concert with EhpJ, a transport protein of the major facilitator superfamily that is also encoded in the phenazine biosynthesis operon of E. agglomerans. The low affinity of EhpR for griseoluteic acid may be required for its physiological function.

Itzen Aymelt

2011-08-01

388

A Comparison of Effects of ABVD and ChlVPP Chemotherapeutic Protocols for Hodgkin's Disease on Rats’ Epididiymal and Testicular Tissues  

Directory of Open Access Journals (Sweden)

Full Text Available The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone group and two control groups one for each treatment group. One half of the lethal dose for 50% of population (LD50 was used for treatment of animals in each protocol. Testes and epididymis tissues were examined for structural changes and serum testosterone level was measured by Lission (chemiluminescence method. Body weight, testis and epididymis weights, in treated rats were significantly less than their control groups specifically in ABVD group was less than ChlVPP group. Decreasing of mean diameter of seminiferous tubules, height of spermatogenic cells and diameter of epididymis in caput, corpus and cauda in ABVD group were significantly more than ChlVPP and control group. The serum testosterone level in ABVD group was significantly less than ChlVPP and control group. According to this study results, the ChlVPP had fewer impairment effects than ABVD on testis and epididymis tissue in tolerance doses on male rats' reproductive system. More clinical trial studies are suggested on Hodgkin's patients. With equal treatment effectiveness, it will be better to use the most reliable and safe treatment especially in young patients.

S. Zare

2010-01-01

389

Cryptographic protocols with everyday objects  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Most security protocols appearing in the literature make use of cryptographic primitives that assume that the participants have access to some sort of computational device. However, there are times when there is need for a security mechanism to evaluate some result without leaking sensitive information, but computational devices are unavailable. We discuss here various protocols for solving cryptographic problems using everyday objects: coins, dice, cards, and envelopes. © 2013 British Compu...

Heather, J.; Schneider, S.; Teague, V.

2013-01-01

390

Genetic Programming and Protocol Configuration  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Dynamic protocol stacks have been identified as a method of improving the performance of process communication by constructing the protocol that meets it requirements with a minimum overhead. However, the design of these stacks is a complex process for human designers who must identify the correct elements and ordering. Genetic programming is a machine learning technique method for generating computer programs automatically. It has been applied to many areas including electronic circuit desig...

Grace, P.

2000-01-01

391

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

B6.Cg-Tg(S100b-v-erbB)4496Waw Cdkn2atm1Rdp/Nci PCR Protocol Strain: B6.Cg-Tg(S100b-v-erbB)4496Waw Cdkn2atm1Rdp/Nci Strain Code: 01XD3 Protocol Number: 1 Introductory Comment: Primers:  E001 :   5'-cTc AcA GcA ATc TcA AAG cTc ccc -3'  E002 :   5'-AGc

392

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

129X1/SvJ-Tg(TH-MYCN)41Waw/Nci PCR Protocol Strain: 129X1/SvJ-Tg(TH-MYCN)41Waw/Nci Strain Code: 01XD2 Protocol Number: 1 Introductory Comment: Primers:  N008 :   5'-TGG AAA GcT TcT TAT TGG TAG AAA cAA -3'  N009 :   5'-AGG GAT ccT TTc cGc ccc GTT cGT

393

Recent Advances in Population Protocols  

Science.gov (United States)

The population protocol model (PP) proposed by Angluin et al. [2] describes sensor networks consisting of passively mobile finite-state agents. The agents sense their environment and communicate in pairs to carry out some computation on the sensed values. The mediated population protocol model (MPP) [13] extended the PP model by communication links equipped with a constant size buffer. The MPP model was proved in [13] to be stronger than the PP model. However, its most important contribution is that it provides us with the ability to devise optimizing protocols, approximation protocols and protocols that decide properties of the communication graph on which they run. The latter case, suggests a simplified model, the GDM model, that was formally defined and studied in [11]. GDM is a special case of MPP that captures MPP’s ability to decide properties of the communication graph. Here we survey recent advances in the area initiated by the proposal of the PP model and at the same time we provide new protocols, novel ideas and results.

Chatzigiannakis, Ioannis; Michail, Othon; Spirakis, Paul G.

394

Secure E-payment Protocol  

Directory of Open Access Journals (Sweden)

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.

Sattar J Aboud

2009-11-01

395

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

International Nuclear Information System (INIS)

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

396

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  

Energy Technology Data Exchange (ETDEWEB)

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/m/sup 2/ (maximum of 2 mgs) by I.V. injection, followed by bleomycin drip for 48 hours (15 units/day), and then methotrexate (200 mgs/m/sup 2/ 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.

Marcial, V.A.; Velez-Garcia, E.; Figueroa-Valles, N.R.; Cintron, J.; Vallecillo, L.A.

1980-06-01

397

Monoclonal antibodies technology. Protocols  

International Nuclear Information System (INIS)

Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 ?g/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. Re

398

The Classically-Enhanced Father Protocol  

CERN Document Server

The classically-enhanced father protocol is an optimal protocol for a sender to transmit both classical and quantum information to a receiver by exploiting preshared entanglement and a large number of independent uses of a noisy quantum channel. We detail the proof of a quantum Shannon theorem that gives the three-dimensional capacity region containing all achievable rates that the classically-enhanced father protocol obtains. Points in the capacity region are rate triples consisting of the classical communication rate, the quantum communication rate, and the entanglement consumption rate of a particular coding scheme. The classically-enhanced father protocol is more general than any other protocol in the family tree of quantum Shannon theoretic protocols. Several previously known quantum protocols are now child protocols of the classically-enhanced father protocol. Interestingly, the classically-enhanced father protocol gives insight for constructing optimal classically-enhanced entanglement-assisted quantum...

Hsieh, Min-Hsiu

2008-01-01

399

The Network Protocol Analysis Technique in Snort  

Science.gov (United States)

Network protocol analysis is a network sniffer to capture data for further analysis and understanding of the technical means necessary packets. Network sniffing is intercepted by packet assembly binary format of the original message content. In order to obtain the information contained. Required based on TCP / IP protocol stack protocol specification. Again to restore the data packets at protocol format and content in each protocol layer. Actual data transferred, as well as the application tier.

Wu, Qing-Xiu

400

Optimistic Non-repudiation Protocol Analysis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Non-repudiation protocols with session labels have a number of vulnerabilities. Recently Cederquist, Corin and Dashti have proposed an optimistic non-repudiation protocol that avoids altogether the use of session labels. We have specified and analysed this protocol using an extended version of the AVISPA Tool and one important fault has been discovered. We describe the protocol, the analysis method, show two attack traces that exploit the fault and propose a correction to the protocol.

Santos Santiago, Judson; Vigneron, Laurent

2007-01-01

 
 
 
 
401

Surveillance vs. adjuvant therapy of clinical stage I testicular tumors - a review and the SWENOTECA experience.  

Science.gov (United States)

Although clinical stage I (CS I) testicular cancer is highly curable, the optimal management is controversial. The aims of the SWENOTECA studies for CS I non-seminoma (NS) and seminoma (S) have been to reduce treatment intensity while maintaining high survival rates, reduce the number of patients needing salvage treatment and implement patient autonomy with regard to adjuvant treatment. During 1998-2010 NS CSI patients with lymphovascular invasion (LVI) of the primary tumor (high risk) were recommended bleomycin, etoposide, cisplatin (BEP) × 1, whereas patients without LVI (low risk) had the choice of surveillance or BEP × 1. During 2000-2006 S CS I patients had the option to choose surveillance or adjuvant radiotherapy (AR). In 2004, carboplatin × 1 (AUC7) was added as a third treatment option. In 2007 a new risk-adapted treatment protocol for S CS I was initiated. Patients with two risk factors (tumor size > 4 cm, tumor growth in the rete testis) were recommended carboplatin × 1 and patients with 0-1 risk factor were recommended surveillance. All patients were provided with oral and written information of possible management options and could choose the other alternative. The relapse rate for NS CS I with BEP × 1 was 3.2% for high risk, and 1.6% for low-risk patients. Five-year cause-specific survival was 100%. For S CS I-patients treated before 2007, 14.3% on surveillance relapsed, 3.9% after carboplatin, and 0.8% after AR. Five-year cause-specific survival was 99.9%. For S CS I-patients treated from 2007, a relapse rate <3% was confirmed for patients without risk factors. SWENOTECA considers BEP × 1 standard adjuvant treatment in NS CS I high-risk patients. Low-risk patients should have the opportunity to receive BEP × 1 following thorough information regarding pros and cons. For S CS I patients without risk factors, adjuvant treatment is not necessary. For patients with risk factors, patient autonomy should be respected. PMID:25270123

Cohn-Cedermark, G; Stahl, O; Tandstad, T

2014-10-01

402

GDB: Group Distance Bounding Protocols  

CERN Document Server

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.

Defrawy, Karim El; Tsudik, Gene

2010-01-01

403

Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: Downregulation of TGF-{beta} and procollagen I and III gene expression  

Energy Technology Data Exchange (ETDEWEB)

The present study was undertaken to elucidate the mechanism for the antifibrotic effect of interferon gamma (IFN-{gamma}) in the bleomycin (BL)-mouse model of lung fibrosis. The expression of transforming growth factor (TGF-{beta}) and procollagen I and III and their mRNAs was investigated in the BL-mouse model of lung fibrosis with and without IFN-{gamma} treatment by Northern and slot blot analyses. Temporal changes in the content of procollagen and TGF-{beta} mRNAs in the lungs of mice receiving saline or BL by intratracheal route, with and without IFN-{gamma} treatment by intramuscular route, were quantitated. The level of TGF-{beta} mRNA increased rapidly and peaked at day 5, whereas the levels of mRNAs for procollagens {alpha}{sub 1}(I) and {alpha}{sub 1}(III) peaked at 10 days after BL instillation. The peak levels of these mRNAs in BL-treated animals were five- to seven-fold higher than those of the control. BL treatment also increased the hydroxyproline content significantly from 3 to 14 days as compared to the corresponding saline control groups. A maximal increase to 447 {mu}g/lung from 223 {mu}g/lung in saline control was obtained at 10 days after instillation. Daily treatment with IFN-{gamma} markedly reduced the BL-induced increases in the mRNA levels of TGF-{beta}, and procollagen {alpha}{sub 1}(I) and {alpha}{sub 1}(III) without any effect on the lung level of {beta}-actin mRNA. IFN-{gamma} treatment also caused significant reduction in the BL-induced increase in the lung hydroxyproline content from 417 to 283 {mu}g/lung at 7 days and from 447 to 264 {mu}g/lung at 10 days. It may be concluded from the findings of the present study that the cellular mechanisms for the antifibrotic effect of IFN-{gamma} in the BL-mouse model of lung fibrosis are to initially downregulate the BL-induced overexpression of TFG-{beta} mRNA, and subsequently procollagen mRNAs, leading to a decreased collagen content. 42 refs., 7 figs.

Gurujeyalakshmi, G.; Giri, S.N. [Univ. of California, Davis, CA (United States)

1995-12-31

404

Multicast communication protocols, programming, & applications  

CERN Document Server

The Internet is quickly becoming the backbone for the worldwide information society of the future. Point-to-point communication dominates the network today, however, group communication--using multicast technology--will rapidly gain importance as digital, audio, and video transmission, push technology for the Web, and distribution of software updates to millions of end users become ubiquitous. Multicast Communication: Protocols and Applications explains how and why multicast technology is the key to this transition. This book provides network engineers, designers, and administrators with the underlying concepts as well as a complete and detailed description of the protocols and algorithms that comprise multicast.* Presents information on the entire range of multicast protocols, including, PIM-SM, MFTP, and PGM and explains their mechanisms, trade-offs, and solid approaches to their implementation* Provides an in-depth examination of Quality of Service concepts, including: RSVP, ST2, IntServ, and DiffServ* ...

Wittmann, Ralph

2000-01-01

405

Cryptographic Protocols under Quantum Attacks  

CERN Document Server

The realm of this thesis is cryptographic protocol theory in the quantum world. We study the security of quantum and classical protocols against adversaries that are assumed to exploit quantum effects to their advantage. Security in the quantum world means that quantum computation does not jeopardize the assumption, underlying the protocol construction. But moreover, we encounter additional setbacks in the security proofs, which are mostly due to the fact that some well-known classical proof techniques are forbidden by certain properties of a quantum environment. Interestingly, we can exploit some of the very same properties to the benefit of quantum cryptography. Thus, this work lies right at the heart of the conflict between highly potential effects but likewise rather demanding conditions in the quantum world.

Lunemann, Carolin

2011-01-01

406

Modified LAR Multicast Authentication Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available Today there is a widening in digital technologies and increasing in new multimedia services like: pay-per-view TV, interactive simulations, teleconferencing. So there is an increasing demand for multicast communication. There is a number of security issues in multicast communication directly related to the specific nature of multicast. In this paper, we propose a new scheme for authenticating streamed data delivered in real-time over an insecure network we concentrate on the multicast authentication problem. Important requirements of multicast communication protocols are: to perform authentication in real-time, to resist packet loss to have low communication and computation overheads. In the present paper, a scheme for authenticating multicast data applications is proposed. The proposed protocol can be viewed as an improvement of LAR protocol (proposed by R.Latif et al in Jan 2011 [1]. The modified LAR doesn't assume the group members are honest as in LAR with lower communication overhead.

Reham Abdellatif Abouhogail

2012-10-01

407

Cryptographic Protocols: : Theory and Implementation  

DEFF Research Database (Denmark)

The art of keeping messages secret is ancient. It must have been invented only shortly after the invention of the messages themselves. Merchants and generals have always had a need to exchange critical messages while keeping them secret from the prying eyes of competitors or the enemy. Classical 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 and extensible framework. We call this framework VIFF, short for Virtual Ideal Functionality Framework. VIFF implements a UC functionality for general multiparty computation on asynchronous networks. We give a formal definition of the functionality in Chapter 3. There we also describe how we implemented the functionality with a variant of the classic BGW protocol. The protocol is secure against a semi-honest adversary. In Chapter 4 we describe a new protocol for VIFF that is secure against malicious adversaries. The protocol guarantees termination if the adversary allows a preprocessing phase to terminate, in which no information is released. The communication complexity of this protocol is the same as that of a passively secure solution up to a constant factor. It is secure against an adaptive and active adversary corrupting less than n=3 players. Following the presentation of VIFF, we turn to a more theoretical subject. Chapter 5 investigates the notion of a covert adversary — an adversary type that intuitively lies in between semi-honest and malicious adversaries. The main idea is that we accept that a cheating adversary may succeed with a given probability, which need not be negligible. The reasoning is that in many real-world cases, a large probability of being caught is sufficient to prevent the adversary from trying to cheat. We show how to compile a passively secure protocol for honest majority into a protocol that is secure against covert attacks, again for honest majority. The transformed protocol catches cheating with probability 1/4 . Though we present no implementation of this compiler, we believe it will be very efficient and practical to implement using, say, VIFF. The cost of the modified protocol is essentially twice that of the original plus an overhead that only depends on the number of inputs. We round off this dissertation with Chapter 6. There we return to the practical side of things and consider how users of online collaboration tools and network storage services place considerable trust in their providers. We presents a novel approach for protecting data integrity in revision control systems hosted by an untrusted provider. It guarantees atomic read and write operations on the shared data when the service is correct and preserves fork-linearizability when the service is faulty. A prototype has been implemented on top of the Subversion revision control system; benchmarks show that the approach is practical.

Geisler, Martin Joakim Bittel

2010-01-01

408

Developing protocols for obstetric emergencies.  

Science.gov (United States)

There is potential for important steps to be missed in emergency situations, even in the presence of many health care team members. Developing a clear plan of response for common emergencies can ensure that no tasks are redundant or omitted, and can create a more controlled environment that promotes positive health outcomes. A multidisciplinary team was assembled in a large community hospital to create protocols that would help ensure optimum care and continuity of practice in cases of postpartum hemorrhage, shoulder dystocia, emergency cesarean surgical birth, eclamptic seizure and maternal code. Assignment of team roles and responsibilities led to the evolution of standardized protocols for each emergency situation. PMID:25316538

Roth, Cheryl K; Parfitt, Sheryl E; Hering, Sandra L; Dent, Sarah A

2014-01-01

409

SECURITY PROTOCOL COMPOSITION FOR WEB SERVICES  

Directory of Open Access Journals (Sweden)

Full Text Available 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 automated security protocol composition methods in the field of Web services. Based on this middleware, we present a new video surveillance system, where services are automatically composed and security protocols are automatically implemented.

Genge Bela

2009-11-01

410

Session Initiation Protocol Attacks and Challenges  

CERN Document Server

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.