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[PMID]:28495614
[Au] Autor:Jost P; Fikrova P; Svobodova H; Pejchal J; Stetina R
[Ad] Endereço:Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic; Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic. Electronic address:
[Ti] Título:Protective potential of different compounds and their combinations with MESNA against sulfur mustard-induced cytotoxicity and genotoxicity.
[So] Source:Toxicol Lett;275:92-100, 2017 Jun 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to evaluate the efficacy of potential candidate molecules or their combinations against strong alkylation agent sulfur mustard (SM) on the human lung alveolar epithelial cell line A-549. Candidate molecules were chosen on the basis of their previously observed protective effects in vitro. The tested compounds, including antioxidants, sulfhydryl or other sulfur-containing molecules, nitrogen-containing molecules, PARP inhibitors and a NO synthase inhibitor, were applicated 30min before SM treatment. The efficiency of candidate molecules to protect cells against DNA damage and cell death induced by SM was determined using single-cell gel electrophoresis (comet assay) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction by viable cells. The damage of DNA was assessed 1 and 24h after dose 50µM SM. Cell survival was assessed 24 and 72h after the exposure. To achieve maximal cytoprotection, combinations of selected compounds with sodium 2-mercaptoethane sulphonate (MESNA) were tested. We found significant protective effects by several drugs used individually and also in combination with MESNA. High protection was achieved by sodium thiosulphate, which was further potentiated when combined with MESNA. Most of the selected compounds or mixture provided only moderate genoptotection without having any effect towards cell viability.
[Mh] Termos MeSH primário: Dano ao DNA
Mesna/farmacologia
Gás de Mostarda/toxicidade
Mutagênicos/toxicidade
Substâncias Protetoras/farmacologia
[Mh] Termos MeSH secundário: Células A549
Técnicas de Cultura de Células
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Citoproteção
Sinergismo Farmacológico
Seres Humanos
Mesna/química
Substâncias Protetoras/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutagens); 0 (Protective Agents); NR7O1405Q9 (Mesna); T8KEC9FH9P (Mustard Gas)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE


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[PMID]:28202211
[Au] Autor:Stoeckle E; Michot A; Rigal L; Babre F; Sargos P; Henriques de Figueiredo B; Brouste V; Italiano A; Toulmonde M; Le Loarer F; Kind M
[Ad] Endereço:Department of Surgery, Institut Bergonié, 229 cours de l'Argonne, F-33076, Bordeaux, France. Electronic address: e.stoeckle@bordeaux.unicancer.fr.
[Ti] Título:The risk of postoperative complications and functional impairment after multimodality treatment for limb and trunk wall soft-tissue sarcoma: Long term results from a monocentric series.
[So] Source:Eur J Surg Oncol;43(6):1117-1125, 2017 Jun.
[Is] ISSN:1532-2157
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVES: Conservative surgery for soft-tissue sarcoma (STS) within multimodality treatment attempts to reconcile two contradictory requirements: assuring a good oncological outcome through a wide resection and preserving the function. The aim of our study is to verify whether our conservative approach to STS met these objectives. METHODS: A retrospective database analysis was performed in adults with primary limb or trunk wall STS operated in a single center from 1989 to 2012. Predictive factors for postoperative complications and functional impairment were tested in a multivariate analysis. RESULTS: 728 patients were operated (resection R0: 68%). Neoadjuvant chemotherapy (NAC) was given to 28%, postoperative radiotherapy to 70% of patients. Median follow-up was 103 months. At five years, overall survival was 80% and local recurrences 11%. Major postoperative complications occurred in 8% and functional impairment in 13% of the patients. Independent predictive factors for postoperative complications were American Society of Anesthesiologist classes 2 and 3 (OR: 2.3, CI: 1.2-4.5 and 4.0 CI: 1.7-9.3), tumor size >80 mm (OR: 2.5, CI: 1.3-4.9), tumor site (trunk wall/lower limb, OR: 4.1, CI: 1.3-13.6) and multifocal/multicompartmental spread (OR: 2, CI: 1.1-3.6). Independent predictive factors for function impairment were postoperative complications (OR: 5.3, CI: 2.8-10.1), NAC (OR: 3.6, CI: 2.2-5.8), and bone or neurovascular involvement (OR 3.3, CI 2.0-5.3), whereas Early Rehabilitation after Surgery (ERAS) improved outcome (OR: 0.5, CI: 0.3-0.9). CONCLUSION: Postoperative complications induced functional impairment. They may be reduced by acting on comorbidity factors and careful tumor evaluation prior to surgery. Furthermore, ERAS measures improved function.
[Mh] Termos MeSH primário: Atividades Cotidianas
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Quimioterapia do Câncer por Perfusão Regional/métodos
Extremidades/cirurgia
Complicações Pós-Operatórias/epidemiologia
Radioterapia Adjuvante/métodos
Sarcoma/terapia
Neoplasias de Tecidos Moles/terapia
Tronco/cirurgia
[Mh] Termos MeSH secundário: Parede Abdominal
Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Terapia Combinada
Dacarbazina/uso terapêutico
Doxorrubicina/uso terapêutico
Feminino
Seguimentos
Seres Humanos
Ifosfamida/uso terapêutico
Masculino
Mesna/uso terapêutico
Meia-Idade
Análise Multivariada
Terapia Neoadjuvante/métodos
Estudos Retrospectivos
Fatores de Risco
Sarcoma/patologia
Neoplasias de Tecidos Moles/patologia
Taxa de Sobrevida
Parede Torácica
Carga Tumoral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7GR28W0FJI (Dacarbazine); 80168379AG (Doxorubicin); NR7O1405Q9 (Mesna); UM20QQM95Y (Ifosfamide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE


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[PMID]:27995828
[Au] Autor:Ismi O; Karabulut YY; Bal KK; Vayisoglu Y; Unal M
[Ad] Endereço:Department of Otorhinolaryngology,Faculty of Medicine,University of Mersin,Turkey.
[Ti] Título:Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation.
[So] Source:J Laryngol Otol;131(3):215-220, 2017 Mar.
[Is] ISSN:1748-5460
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation. METHODS: A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation. RESULTS: The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups. CONCLUSION: Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.
[Mh] Termos MeSH primário: Colesteatoma da Orelha Média/prevenção & controle
Mesna/administração & dosagem
Substâncias Protetoras/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Colesteatoma da Orelha Média/induzido quimicamente
Colesteatoma da Orelha Média/patologia
Fibrose
Tecido de Granulação/patologia
Hiperplasia
Injeção Intratimpânica
Masculino
Propilenoglicol
Ratos
Ratos Wistar
Solventes
Osso Temporal/patologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protective Agents); 0 (Solvents); 6DC9Q167V3 (Propylene Glycol); NR7O1405Q9 (Mesna)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE
[do] DOI:10.1017/S002221511600983X


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[PMID]:27932776
[Au] Autor:Al Shawabkeh MA; Al Sulaiti M; Al Sa'ey H; Ganesan S
[Ad] Endereço:Department of Otolaryngology, Hamad Medical Corporation, Doha, Qatar.
[Ti] Título:Nasal Type Extranodal Natural Killer/T (NK/T) Cell Lymphoma Presenting as Periorbital Cellulitis: A Case Report.
[So] Source:Am J Case Rep;17:934-938, 2016 Dec 09.
[Is] ISSN:1941-5923
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Extranodal lymphoma of the paranasal sinuses is a rare clinical entity seen in only 5-8% of extranodal lymphomas of the head and neck. Nasal natural killer/T cell lymphoma (Nasal NKTCL), which is a subtype of peripheral T cell lymphoma, constitutes about 1.4% of all lymphomas. NKTCL is usually diagnosed at a late stage because it presents with nonspecific symptoms in the early stages. CASE REPORT We report the case of a 25-year-old male patient who presented with periorbital swelling treated as fungal sinusitis but proven to have NKTCL. We review the literature and discuss the clinical manifestations of the disease, its relation to EBV virus, the histological and radiological characteristics, the prognostic indicators, and treatment options. This case report shows physicians that NKTCL lymphoma can present as periorbital cellulitis, although few similar cases are found in the literature. CONCLUSIONS NKTCL is a destructive midline tumor that should be kept in mind as a differential diagnosis of paranasal sinus lesions to help in early diagnosis, which can improve the prognosis.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
Linfoma Extranodal de Células T-NK/complicações
Linfoma Extranodal de Células T-NK/tratamento farmacológico
Celulite Orbitária/tratamento farmacológico
Celulite Orbitária/etiologia
Neoplasias dos Seios Paranasais/complicações
Neoplasias dos Seios Paranasais/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Dexametasona/administração & dosagem
Diagnóstico Diferencial
Etoposídeo/administração & dosagem
Seres Humanos
Ifosfamida/administração & dosagem
Linfoma Extranodal de Células T-NK/diagnóstico
Masculino
Mesna/administração & dosagem
Metotrexato/administração & dosagem
Celulite Orbitária/diagnóstico
Neoplasias dos Seios Paranasais/diagnóstico
Prognóstico
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
143011-72-7 (Granulocyte Colony-Stimulating Factor); 6PLQ3CP4P3 (Etoposide); 7S5I7G3JQL (Dexamethasone); NR7O1405Q9 (Mesna); UM20QQM95Y (Ifosfamide); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170320
[Lr] Data última revisão:
170320
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE


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[PMID]:27749816
[Au] Autor:Laso-Pérez R; Wegener G; Knittel K; Widdel F; Harding KJ; Krukenberg V; Meier DV; Richter M; Tegetmeyer HE; Riedel D; Richnow HH; Adrian L; Reemtsma T; Lechtenfeld OJ; Musat F
[Ad] Endereço:Max-Planck Institute for Marine Microbiology, 28359 Bremen, Germany.
[Ti] Título:Thermophilic archaea activate butane via alkyl-coenzyme M formation.
[So] Source:Nature;539(7629):396-401, 2016 11 17.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The anaerobic formation and oxidation of methane involve unique enzymatic mechanisms and cofactors, all of which are believed to be specific for C -compounds. Here we show that an anaerobic thermophilic enrichment culture composed of dense consortia of archaea and bacteria apparently uses partly similar pathways to oxidize the C hydrocarbon butane. The archaea, proposed genus 'Candidatus Syntrophoarchaeum', show the characteristic autofluorescence of methanogens, and contain highly expressed genes encoding enzymes similar to methyl-coenzyme M reductase. We detect butyl-coenzyme M, indicating archaeal butane activation analogous to the first step in anaerobic methane oxidation. In addition, Ca. Syntrophoarchaeum expresses the genes encoding ß-oxidation enzymes, carbon monoxide dehydrogenase and reversible C methanogenesis enzymes. This allows for the complete oxidation of butane. Reducing equivalents are seemingly channelled to HotSeep-1, a thermophilic sulfate-reducing partner bacterium known from the anaerobic oxidation of methane. Genes encoding 16S rRNA and methyl-coenzyme M reductase similar to those identifying Ca. Syntrophoarchaeum were repeatedly retrieved from marine subsurface sediments, suggesting that the presented activation mechanism is naturally widespread in the anaerobic oxidation of short-chain hydrocarbons.
[Mh] Termos MeSH primário: Archaea/metabolismo
Butanos/metabolismo
Mesna/química
Mesna/metabolismo
[Mh] Termos MeSH secundário: Alquilação
Anaerobiose
Archaea/genética
Proteínas Arqueais/química
Proteínas Arqueais/genética
Proteínas Arqueais/metabolismo
Biocatálise
Evolução Molecular
Oxirredução
Sulfatos/metabolismo
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Archaeal Proteins); 0 (Butanes); 0 (Sulfates); 6LV4FOR43R (butane); NR7O1405Q9 (Mesna)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170314
[Lr] Data última revisão:
170314
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE
[do] DOI:10.1038/nature20152


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[PMID]:27380806
[Au] Autor:Saito Y; Kumamoto T; Makino Y; Tamai I; Ogawa C; Terakado H
[Ad] Endereço:Department of Pharmacy, National Cancer Center Hospital, Tokyo Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa yoshsait@ncc.go.jp.
[Ti] Título:A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors.
[So] Source:Jpn J Clin Oncol;46(9):856-61, 2016 Sep.
[Is] ISSN:1465-3621
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC. METHODS: In this retrospective study, patients (<30-year-old) with malignant solid tumors who had been treated with IFO-based chemotherapy, were categorized according to the presence or absence of HC, and were analyzed possible risk factors for IFO-induced HC. In our institution, continuous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) are used for prophylaxis of IFO-induced HC. Increased hydration and dosage of mesna are administered to patients who develop IFO-induced HC; they also receive 24-h continuous infusion of mesna in subsequent treatment cycles. RESULTS: Nine treatment regimens were used in the 70 study patients. The range of daily IFO dosage was 1.2-3.0 g/m(2). HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean ± SD) in patients with or without HC were 2.23 ± 0.58 g/m(2) and 1.85 ± 0.50 g/m(2), respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment. CONCLUSION: The incidence of IFO-induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m(2)/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC.
[Mh] Termos MeSH primário: Cistite/etiologia
Ifosfamida/uso terapêutico
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
Cistite/epidemiologia
Esquema de Medicação
Feminino
Hemorragia
Seres Humanos
Ifosfamida/efeitos adversos
Incidência
Lactente
Masculino
Mesna/uso terapêutico
Substâncias Protetoras/uso terapêutico
Estudos Retrospectivos
Fatores de Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protective Agents); NR7O1405Q9 (Mesna); UM20QQM95Y (Ifosfamide)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160707
[St] Status:MEDLINE
[do] DOI:10.1093/jjco/hyw093


  7 / 1129 MEDLINE  
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[PMID]:27266402
[Au] Autor:Furmaniak P; Kubalczyk P; Stachniuk J; Glowacki R
[Ad] Endereço:University of Lódz, Faculty of Chemistry, Department of Environmental Chemistry, Poland.
[Ti] Título:Novel MEKC method for determination of sodium 2-mercaptoethanesulfonate in human plasma with in-capillary derivatization and UV detection.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1027:88-95, 2016 Aug 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sensitive electrophoretic method for determination of total sodium 2-mercaptoethanesulfonate (mesna) in human plasma, based on the stacking with high salt concentration in MEKC and in-capillary derivatization with 2-chloro-1-methyllepidinium tetrafluoroborate followed by UV detection was developed. In the method 0.03molL(-1)pH 7 phosphate buffer with the addition of 0.01molL(-1) SDS, and 10% ACN was used as a BGE. The limit of quantification (LOQ) of the method was 0.5µmolL(-1). Linearity in detector response was observed over the range of 0.5-10µmolL(-1) with the correlation coefficient 0.9971. The intra- and inter-day accuracy (three concentration levels, 5 days, n=3) of the method ranged from 97.2 to 110.0% and from 94.0 to 101.2%, respectively. The novel MEKC method with UV detection proved to be suitable for determination of total mesna in human plasma.
[Mh] Termos MeSH primário: Cromatografia Capilar Eletrocinética Micelar/métodos
Mesna/análise
Mesna/sangue
Substâncias Protetoras/análise
[Mh] Termos MeSH secundário: Cromatografia Capilar Eletrocinética Micelar/economia
Seres Humanos
Limite de Detecção
Substâncias Protetoras/farmacocinética
Compostos de Quinolínio/química
Sais/química
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-chloro-1-methyllepidinium); 0 (Protective Agents); 0 (Quinolinium Compounds); 0 (Salts); NR7O1405Q9 (Mesna)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170213
[Lr] Data última revisão:
170213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160609
[St] Status:MEDLINE


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[PMID]:27234646
[Au] Autor:Abdi SA; Najmi AK; Raisuddin S
[Ad] Endereço:Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
[Ti] Título:Cyclophosphamide-induced Down-Regulation of Uroplakin II in the Mouse Urinary Bladder Epithelium is Prevented by S-Allyl Cysteine.
[So] Source:Basic Clin Pharmacol Toxicol;119(6):598-603, 2016 Dec.
[Is] ISSN:1742-7843
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The alkylating anticancer drug, cyclophosphamide (CP), induces a number of toxic effects including haemorrhagic cystitis (HC) in the urinary bladder. Uroplakins are unique urinary transmembrane proteins of urothelium, which may become potential targets of CP metabolites and reactive free radicals. Natural compounds, especially those rich in thiols, have shown protective effects against CP-induced HC. In this study, we studied the modulatory effect of the thiol-rich compound S-allyl cysteine (SAC) on the mRNA level of uroplakin II by real-time polymerase chain reaction and expression of uroplakin II protein by immunoblotting. SAC (150 mg/kg) showed significant (p < 0.001) protective effects against CP (200 mg/kg)-induced alteration in mRNA level and protein expression of uroplakin II. SAC also protected animals from CP-induced HC as assessed by gross morphological examination of urinary bladder. When compared with mercaptoethane sulphonic acid (mesna) (40 mg/kg), a known thiol-rich drug used in clinical application, SAC was found to be more efficacious in affording protection in urinary bladder tissues. Role of uroplakins in CP-induced urinary bladder toxicity has not been well investigated. This study demonstrated that uroplakins may be the potential target of toxic metabolites of CP and natural compounds such as SAC have the capacity to modulate their expression leading to reduced toxicity burden on the urinary bladder epithelium.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/efeitos adversos
Ciclofosfamida/efeitos adversos
Cisteína/análogos & derivados
Cistite/prevenção & controle
Bexiga Urinária/efeitos dos fármacos
Uroplaquina II/antagonistas & inibidores
Urotélio/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Antineoplásicos Alquilantes/química
Ciclofosfamida/antagonistas & inibidores
Cisteína/uso terapêutico
Cistite/induzido quimicamente
Cistite/metabolismo
Cistite/patologia
Regulação para Baixo/efeitos dos fármacos
Edema/induzido quimicamente
Edema/metabolismo
Edema/patologia
Edema/prevenção & controle
Regulação da Expressão Gênica/efeitos dos fármacos
Hemorragia/induzido quimicamente
Hemorragia/metabolismo
Hemorragia/patologia
Hemorragia/prevenção & controle
Mesna/uso terapêutico
Camundongos
Tamanho do Órgão/efeitos dos fármacos
Substâncias Protetoras/uso terapêutico
RNA Mensageiro/metabolismo
Distribuição Aleatória
Bexiga Urinária/imunologia
Bexiga Urinária/metabolismo
Bexiga Urinária/patologia
Uroplaquina II/genética
Uroplaquina II/metabolismo
Urotélio/imunologia
Urotélio/metabolismo
Urotélio/patologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antineoplastic Agents, Alkylating); 0 (Protective Agents); 0 (RNA, Messenger); 0 (Upk2 protein, mouse); 0 (Uroplakin II); 81R3X99M15 (S-allylcysteine); 8N3DW7272P (Cyclophosphamide); K848JZ4886 (Cysteine); NR7O1405Q9 (Mesna)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170208
[Lr] Data última revisão:
170208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160529
[St] Status:MEDLINE
[do] DOI:10.1111/bcpt.12627


  9 / 1129 MEDLINE  
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[PMID]:27172745
[Au] Autor:Abu-Khalaf MM; Raza MA; Hatzis C; Wang H; Lin K; Higgins S; Ratner E; Silasi DA; Azodi M; Rutherford TJ; Santin AD; Schwartz PE
[Ti] Título:Efficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma.
[So] Source:Eur J Gynaecol Oncol;37(2):199-203, 2016.
[Is] ISSN:0392-2936
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:PURPOSE OF INVESTIGATION: A retrospective study to evaluate six cycles of cisplatin 40 mg/m2 on day 1 and ifosfamide 1,200 mg/m2 daily on days 1 to 4 with Mesna every four weeks as first line treatment for 29 patients with a diagnosis of uterine carcinosarcoma. MATERIALS AND METHODS: A total of 23 of 29 patients received high dose rate intracavitary vaginal cuff brachytherapy (VCBT) with two fractions of seven Gy each. Median age was 65 years (range 40-82); 13 (44.8%) had Stage I disease, three (10.3%) had Stage II, eight (27.6%) had Stage III, and five (17.2%) patients had Stage IV disease. RESULTS: Most common toxicities were anemia grade 1 (35%)/grade 2 (45%), and neutropenia grade 3 (17%)/grade 4 (6.9%). Eleven dose modifications, four treatment discontinuations, and one patient withdrawal occurred. At a median follow up of 45 months (range 9 to 144), Progression free survival (PFS) was 20% and overall survival (OS) was 40% for Stage IV, PFS 75% and OS 62.5% for Stage III, compared to a PFS 75% and OS 72.2% for Stages I-II. Median OS for the entire group was 12.43 years (95% CI 3.69 to inf); for Stage I-III 12.4 years (6.1 to inf), and for Stage IV 15.6 months (95% CI 9.4 to inf). CONCLUSIONS: Cisplatin and ifosfamide chemotherapy with VCBT was well tolerated and has promising activity in uterine carcinosarcoma.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Braquiterapia/métodos
Carcinossarcoma/terapia
Neoplasias Uterinas/terapia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anemia/induzido quimicamente
Carcinossarcoma/patologia
Quimiorradioterapia
Cisplatino/administração & dosagem
Intervalo Livre de Doença
Feminino
Seres Humanos
Ifosfamida/administração & dosagem
Mesna/uso terapêutico
Meia-Idade
Estadiamento de Neoplasias
Neutropenia/induzido quimicamente
Substâncias Protetoras/uso terapêutico
Estudos Retrospectivos
Resultado do Tratamento
Neoplasias Uterinas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protective Agents); NR7O1405Q9 (Mesna); Q20Q21Q62J (Cisplatin); UM20QQM95Y (Ifosfamide)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160513
[Lr] Data última revisão:
160513
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160514
[St] Status:MEDLINE


  10 / 1129 MEDLINE  
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[PMID]:27161644
[Au] Autor:Wachino J; Yamaguchi Y; Mori S; Jin W; Kimura K; Kurosaki H; Arakawa Y
[Ad] Endereço:Department of Bacteriology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan wachino@med.nagoya-u.ac.jp.
[Ti] Título:Structural Insights into Recognition of Hydrolyzed Carbapenems and Inhibitors by Subclass B3 Metallo-ß-Lactamase SMB-1.
[So] Source:Antimicrob Agents Chemother;60(7):4274-82, 2016 Jul.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metallo-ß-lactamases (MBLs) confer resistance to carbapenems, and their increasing global prevalence is a growing clinical concern. To elucidate the mechanisms by which these enzymes recognize and hydrolyze carbapenems, we solved 1.4 to 1.6 Å crystal structures of SMB-1 (Serratia metallo-ß-lactamase 1), a subclass B3 MBL, bound to hydrolyzed carbapenems (doripenem, meropenem, and imipenem). In these structures, SMB-1 interacts mainly with the carbapenem core structure via elements in the active site, including a zinc ion (Zn-2), Q157[113] (where the position in the SMB-1 sequence is in brackets after the BBL number), S221[175], and T223[177]. There is less contact with the carbapenem R2 side chains, strongly indicating that SMB-1 primarily recognizes the carbapenem core structure. This is the first report describing how a subclass B3 MBL recognizes carbapenems. We also solved the crystal structure of SMB-1 in complex with the approved drugs captopril, an inhibitor of the angiotensin-converting enzyme, and 2-mercaptoethanesulfonate, a chemoprotectant. These drugs are inhibitors of SMB-1 with Ki values of 8.9 and 184 µM, respectively. Like carbapenems, these inhibitors interact with Q157[113] and T223[177] and their thiol groups coordinate the zinc ions in the active site. Taken together, the data indicate that Q157[113], S221[175], T223[177], and the two zinc ions in the active site are key targets in the design of SMB-1 inhibitors with enhanced affinity. The structural data provide a solid foundation for the development of effective inhibitors that would overcome the carbapenem resistance of MBL-producing multidrug-resistant microbes.
[Mh] Termos MeSH primário: Antibacterianos/química
Carbapenêmicos/química
beta-Lactamases/química
[Mh] Termos MeSH secundário: Inibidores da Enzima Conversora de Angiotensina/química
Captopril/química
Domínio Catalítico
Cristalografia por Raios X
Imipenem/química
Mesna/química
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Serratia marcescens/enzimologia
Tienamicinas/química
beta-Lactamases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Anti-Bacterial Agents); 0 (Carbapenems); 0 (Thienamycins); 71OTZ9ZE0A (Imipenem); 9G64RSX1XD (Captopril); BHV525JOBH (doripenem); EC 3.5.2.6 (beta-Lactamases); FV9J3JU8B1 (meropenem); NR7O1405Q9 (Mesna)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160511
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.03108-15



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