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[PMID]: 12408361 [Au] Autor: Thomopoulos GN; Garrett JR; Proctor GB [Ad] Endereço: Department of Biology, Aristotle University, School of Sciences, Thessaloniki, Greece. thomopgn@bio.auth.gr [Ti] Título: Ultrastructural histochemical studies of secretory granule replenishment in rat submandibular granular tubules after cyclocytidine-induced secretion. [So] Source: J Submicrosc Cytol Pathol;34(3):279-89, 2002 Jul. [Is] ISSN: 1122-9497 [Cp] País de publicação: Italy [La] Idioma: eng [Ab] Resumo: Rat submandibular glands have been examined electron microscopically at various times after degranulating the granular tubules by injecting cyclocytidine (75 mg/kg i.p.), to study events in the reformation of secretory granules in these cells. The changes were progressive but not synchronous in the cells. The first evidence of recovery was the re-appearance of glycogen particles 6 h after injection. Residual secretory granules were small and located periluminally at that time. More granules were present at 15 h after injection but they were still small and placed periluminally. There was more glycogen in the cells and some was present in aggregates. At 1 day after injection there were more secretory granules and they tended to be larger than previously. The secretory granules increased in size and number progressively thereafter and the cells appeared like normal controls by day 7. During the recovery, fusion profiles were seen between granules from 2 days onwards. Throughout, few Golgi complexes were detected and this may be related with the low glycosylation of the secretory proteins in these cells. The results confirm that the reformation of the secretory granules in granular tubule cells is a slow process that involves fusions of smaller granules. [Mh] Termos MeSH primário: Ancitabina/farmacologia Antimetabólitos Antineoplásicos/farmacologia Vesículas Secretórias/efeitos dos fármacos Glândula Submandibular/efeitos dos fármacos [Mh] Termos MeSH secundário: Ancitabina/administração & dosagem Animais Antimetabólitos Antineoplásicos/administração & dosagem Glicogênio/metabolismo Glicogênio/ultraestrutura Complexo de Golgi/efeitos dos fármacos Complexo de Golgi/ultraestrutura Injeções Intraperitoneais Masculino Microscopia Eletrônica Ratos Ratos Wistar Vesículas Secretórias/metabolismo Vesículas Secretórias/ultraestrutura Glândula Submandibular/secreção Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antimetabolites, Antineoplastic); 9005-79-2 (Glycogen); DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 0303 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 021101 [St] Status: MEDLINE

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[PMID]: 10694903 [Au] Autor: Thomopoulos GN; Garrett JR; Proctor GB [Ad] Endereço: School of Sciences, Department of Biology, Aristotle University, Thessaloniki, Greece. [Ti] Título: Ultrastructural histochemical studies of secretory processes in rat submandibular granular tubules during intermittent sympathetic nerve stimulation. [So] Source: Eur J Morphol;38(2):69-79, 2000 Apr. [Is] ISSN: 0924-3860 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Secretory changes in the cells of granular tubules in rat submandibular glands have been studied sequentially during electrical stimulation of their sympathetic nerves. Results were assessed in a series of biopsied lobes from the same gland, taken at different times during the sympathetic stimulation. Changes were not synchronous between adjacent cells and it appeared that the time for the onset of secretory events differed between cells but, once set in action, a chain of similar events occurred. Nevertheless, some cells appeared to remain refractory throughout. Initially, some alignment of granules to the adjacent plasma membrane occurred and occasional evidence for classical exocytosis was seen. However, from early on microvesicles appeared in more luminally located granule membranes and were associated with granule fusions, that became common and led to the formation of large irregular aggregates. Most of the secretion of granule contents appeared to be through openings of aggregates into lumina. With granule fusions the intra-membrane microvesicles became internalised and tended to increase in size with time; they were commonly expelled with the contents of the aggregates. Fragments of cytoplasm also became incorporated in aggregate formation. Cytoplasm, often containing glycogen, also formed luminal blebs over some granular tubule cells and appeared to pass into the secretion by an apocrine process. At the end of stimulation multivesicular bodies were seen in association with redundant aggregates. [Mh] Termos MeSH primário: Grânulos Citoplasmáticos/secreção Glândula Submandibular/ultraestrutura Sistema Nervoso Simpático/fisiologia [Mh] Termos MeSH secundário: Ancitabina/farmacologia Animais Biópsia Citoplasma/ultraestrutura Estimulação Elétrica Exocitose/efeitos dos fármacos Masculino Fusão de Membrana Microscopia Eletrônica Ratos Ratos Wistar Glândula Submandibular/efeitos dos fármacos Glândula Submandibular/inervação Glândula Submandibular/secreção [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 0005 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 000301 [St] Status: MEDLINE

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[PMID]: 9457838 [Au] Autor: Nagler RM; Laufer D [Ad] Endereço: Department of Maxillofacial Surgery, Rambam Medical Center and Faculty of Medicine, Technion, Israel Institute of Technology, Haifa. [Ti] Título: Protection against irradiation-induced damage to salivary glands by adrenergic agonist administration. [So] Source: Int J Radiat Oncol Biol Phys;40(2):477-81, 1998 Jan 15. [Is] ISSN: 0360-3016 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: Irradiation [IR]-induced damage to major salivary glands is an entity first described at the beginning of our century, yet its underlying mechanism is still enigmatic. Exposure of the salivary glands to IR is often inevitable when delivering radiotherapy for malignancies of the head and neck region. Frequently, this results in rapidly developing, life-long severe xerostomia for which no adequate prevention or treatment is available. The purpose of this study was to examine the role of secretion granules in serous cells of the parotid (P) and submandibular (SM) glands as mediators in the IR-induced salivary damage. Functional parameters (flow rate and gland weight), and total body weight were examined at both early term (4 days) and extended term (2 months) post-IR in male Wistar rats exposed to 15 Gy of head and neck irradiation following stimulation for granule secretion (degranulation). METHODS AND MATERIALS: At 4 days, it was demonstrated that IR reduced P flow rate, P gland weight, total body weight, and submandibular/sublingual gland weight by 89, 33, 30, and 32% (p < 0.01), respectively, while SM flow rate was not altered significantly. At 2 months, these parameters were reduced by 59, 37, 31, and 37%, respectively, and the SM flow rate was reduced by 39% (p < 0.01). RESULTS: Pilocarpine, a muscarinsic agonist which, albeit its efficacy as a salivary watery secretion stimulator, causes only limited degranulation, did not protect significantly any of the reduced parameters at either term. In contrast, cyclocytidine, an adrenergic agonist that is a very potent salivary degranulating agent, protected the P against the weight loss at 4 days and 2 months, and against the flow rate reduction at 2 months. The P weight and flow rate were protected to the extent that their values were not significantly different than those of the nonirradiated controls. Cyclocytidine also partially protected against the body weight reduction at 2 months. Our results emphasize the importance of secretion granules as mediatory agents in IR-induced P damage, and more so at the extended term. The demonstrated protective role of adrenergic agonists against IR damage to the P may be of importance in the clinical setting. [Mh] Termos MeSH primário: Agonistas Adrenérgicos/farmacologia Glândula Parótida/efeitos dos fármacos Glândula Parótida/efeitos da radiação Lesões Experimentais por Radiação/prevenção & controle Proteção Radiológica/métodos Glândula Submandibular/efeitos dos fármacos Glândula Submandibular/efeitos da radiação [Mh] Termos MeSH secundário: Ancitabina/farmacologia Animais Degranulação Celular/efeitos dos fármacos Degranulação Celular/efeitos da radiação Grânulos Citoplasmáticos/efeitos dos fármacos Grânulos Citoplasmáticos/efeitos da radiação Masculino Glândula Parótida/fisiologia Pilocarpina/farmacologia Ratos Ratos Wistar Glândula Submandibular/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Adrenergic Agonists); 01MI4Q9DI3 (Pilocarpine); DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 9802 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 980211 [St] Status: MEDLINE

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[PMID]: 9305252 [Au] Autor: Nagler RM; Kitrossky N; Chevion M [Ad] Endereço: Hebrew University-Hadassah Medical Schools of Medicine and Dental Medicine, Jerusalem, Israel. [Ti] Título: Antioxidant activity of rat parotid saliva. [So] Source: Arch Otolaryngol Head Neck Surg;123(9):989-93, 1997 Sep. [Is] ISSN: 0886-4470 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: The healing-promotion property of saliva has been observed in the past, but its underlying mechanism has never been elucidated. We hypothesized a mechanism based on salivary proteins binding to redox active metal ions, rendering them nonactive in their capacity for free radical production. METHODS: Examination of this mechanism was conducted by comparing the redox activity of protein-rich saliva with protein-poor saliva. We also examined the redox activity mediated by these 2 kinds of saliva following the in vitro addition of iron, copper, and manganese. Saliva samples were analyzed for their redox activity by measuring the ascorbate-driven and saliva (diluted 1:2)-mediated conversion of salicylate to its 2,3- and 2.5-dihydroxybenzoates and catechol metabolites. RESULTS: The concentrations of salicylate metabolites formed by protein-rich saliva were significantly lower by 45% (P < .05), 66% (P < .01), and 54% (P < .05), respectively, when compared with those formed by protein-poor saliva. The capacity of saliva in suppressing redox activity was found to be inversely related to the concentrations of iron and copper added (but not manganese), but correlated well with the protein content. When the highest concentrations of iron (15 mumol/L) and copper (10 mumol/L) were added to protein-rich saliva, the concentrations of salicylate metabolites produced were only 0.3% to 1% of those of non-saliva-containing controls (P < .01). However, when these concentrations of iron and copper were added to protein-poor saliva, significantly higher values of redox activity were detected, and the concentrations of the salicylate derivatives produced were 2.1% to 8.1% of those of non-saliva-containing controls (P < .01). In contrast, when the lowest concentrations of iron (2 mumol/L) and copper (0.1 mumol/L) were added, 2.8 to 4 times lower concentrations of salicylate derivatives were produced (P < .01). CONCLUSION: These results substantiate our hypothesis that saliva has a profound capacity for reducing redox activity rendered by transition metal ions, correlating well with its protein content. [Mh] Termos MeSH primário: Antioxidantes/farmacologia Gentisatos Glândula Parótida/secreção Saliva/fisiologia Proteínas e Peptídeos Salivares/farmacologia [Mh] Termos MeSH secundário: Ancitabina/farmacologia Animais Antimetabólitos Antineoplásicos/farmacologia Ácido Ascórbico/metabolismo Catecóis/metabolismo Cobre/farmacologia Radicais Livres/metabolismo Hidroxibenzoatos/metabolismo Ferro/farmacologia Quelantes de Ferro/metabolismo Masculino Manganês/farmacologia Metais/metabolismo Oxirredução Parassimpatomiméticos/farmacologia Glândula Parótida/efeitos dos fármacos Pilocarpina/farmacologia Ligação Proteica Ratos Ratos Wistar Salicilatos/metabolismo Cicatrização [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antimetabolites, Antineoplastic); 0 (Antioxidants); 0 (Catechols); 0 (Free Radicals); 0 (Gentisates); 0 (Hydroxybenzoates); 0 (Iron Chelating Agents); 0 (Metals); 0 (Parasympathomimetics); 0 (Salicylates); 0 (Salivary Proteins and Peptides); 01MI4Q9DI3 (Pilocarpine); 42Z2K6ZL8P (Manganese); 70D5FBB392 (2,3-dihydroxybenzoic acid); 789U1901C5 (Copper); DO2D32W0VC (Ancitabine); E1UOL152H7 (Iron); LF3AJ089DQ (catechol); PQ6CK8PD0R (Ascorbic Acid); VP36V95O3T (2,5-dihydroxybenzoic acid) [Em] Mês de entrada: 9710 [Cu] Atualização por classe: 151119 [Lr] Data última revisão: 151119 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 970926 [St] Status: MEDLINE

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[PMID]: 9092927 [Au] Autor: Nagler R; Marmary Y; Fox PC; Baum BJ; Har-El R; Chevion M [Ad] Endereço: The Department of Cellular Biochemistry, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. [Ti] Título: Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper. [So] Source: Radiat Res;147(4):468-76, 1997 Apr. [Is] ISSN: 0033-7587 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue. [Mh] Termos MeSH primário: Cobre/metabolismo Grânulos Citoplasmáticos/efeitos da radiação Ferro/metabolismo Glândula Parótida/efeitos da radiação Saliva/secreção Glândula Submandibular/efeitos da radiação [Mh] Termos MeSH secundário: Ancitabina/farmacologia Animais Grânulos Citoplasmáticos/efeitos dos fármacos Grânulos Citoplasmáticos/ultraestrutura Masculino Oxirredução Glândula Parótida/patologia Glândula Parótida/fisiologia Pilocarpina/farmacologia Proteção Radiológica Ratos Ratos Wistar Saliva/efeitos da radiação Glândula Submandibular/patologia Glândula Submandibular/fisiologia Raios X [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 01MI4Q9DI3 (Pilocarpine); 789U1901C5 (Copper); DO2D32W0VC (Ancitabine); E1UOL152H7 (Iron) [Em] Mês de entrada: 9704 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM; S [Da] Data de entrada para processamento: 970401 [St] Status: MEDLINE

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[PMID]: 9056926 [Au] Autor: Shori DK; Proctor GB; Garrett JR; Zhang XS; Carpenter GH [Ad] Endereço: Secretory and Soft Tissue Research Unit, Kings College School of Medicine and Dentistry, Rayne Institute, London. [Ti] Título: Histochemical staining of ducts in submandibular glands by DMAB-nitrite detects stored tissue kallikreins. [So] Source: Biochem Soc Trans;25(1):28S, 1997 Feb. [Is] ISSN: 0300-5127 [Cp] País de publicação: England [La] Idioma: eng [Mh] Termos MeSH primário: Calicreínas/análise Ductos Salivares/citologia Glândula Submandibular/citologia [Mh] Termos MeSH secundário: Ancitabina/farmacologia Animais Benzaldeídos Gatos Corantes Grânulos Citoplasmáticos/efeitos dos fármacos Grânulos Citoplasmáticos/metabolismo Grânulos Citoplasmáticos/ultraestrutura Cães Furões Histocitoquímica Calicreínas/metabolismo Camundongos Ductos Salivares/efeitos dos fármacos Ductos Salivares/metabolismo Nitrito de Sódio Glândula Submandibular/efeitos dos fármacos Glândula Submandibular/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Benzaldehydes); 0 (Coloring Agents); DO2D32W0VC (Ancitabine); EC 3.4.21.- (Kallikreins); M0KG633D4F (Sodium Nitrite); V7E88PR1YB (p-dimethylaminobenzaldehyde) [Em] Mês de entrada: 9705 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 970201 [St] Status: MEDLINE

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[PMID]: 8989766 [Au] Autor: Thomopoulos GN; Garrett JR; Proctor GB; Hartley R; Zhang XS [Ad] Endereço: Aristotle University of Thessaloniki, School of Sciences, Department of Biology, Greece. [Ti] Título: Exocytosis from rat submandibular granular tubules during cyclocytidine stimulation shows unusual features, including changes in the granule membrane. [So] Source: Microsc Res Tech;35(5):365-76, 1996 Dec 01. [Is] ISSN: 1059-910X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Sequential secretory changes in granular tubule cells caused by the secretagogue cyclocytidine (75 mg/kg i.p.) were studied at the ultrastructural level, in perfusion (n = 5 animals) and immersion (n = 8 animals) fixed rat submandibular glands, using the periodic acid-thiocarbohydrazide-silver proteinate technique (PA-TCH-SP). The onset of secretion varied from 45 to 75 minutes after administering the cyclocytidine. During the initial stages of overt secretion, structural changes occurred irregularly in a progressive fashion with: (1) an increase in granule membrane staining with PA-TCH-SP and a parallel alignment of the secretory granules with the adjacent apical plasma membrane, which developed a honeycomb-like appearance; (2) docking of these secretory granules to the apical plasma membrane; (3) early secretion of some secretory granules in a semiclassical exocytotic fashion (but this was rarely witnessed). During stages (1) and (2), the cytochemical characteristics of the membrane of the secretory granules, as well as of the plasma membrane, suggest a priming process is occurring. After these initial preparatory phases, further structural changes occurred in the granule membranes with a gradually progressive formation of microvesicles and granule fusions; secretion continued in an explosive manner with proteinaceous material being transferred to lumina in at least three different ways: (1) by typical exocytosis (but it was infrequent); (2) from granules fused intracellularly into aggregates (compound exocytosis); and (3) some apocrine-type of secretion through bleb formation. The formation of these intracellular aggregations was associated with the microvesicles in the granule membranes and some aggregates became very large. Secretion of their contents into lumina occurred through elongated membrane channels. The material secreted included microvesicular forms that had become interiorised in the granular aggregates, and any cytoplasm that may also have been entrapped. [Mh] Termos MeSH primário: Ancitabina/farmacologia Grânulos Citoplasmáticos/ultraestrutura Exocitose Glândula Submandibular/ultraestrutura [Mh] Termos MeSH secundário: Animais Membrana Celular/efeitos dos fármacos Membrana Celular/ultraestrutura Grânulos Citoplasmáticos/efeitos dos fármacos Grânulos Citoplasmáticos/fisiologia Masculino Microscopia Eletrônica Ratos Ratos Wistar Glândula Submandibular/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 9703 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 961201 [St] Status: MEDLINE

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[PMID]: 8758385 [Au] Autor: Chen Z; Song J; Chen K [Ad] Endereço: Henan Institute of Ophthalmology, Zhengzhou. [Ti] Título: [Anti-herpes simplex virus action of combined therapy with cyclocytidine and ganciclovir]. [So] Source: Zhonghua Yan Ke Za Zhi;32(1):25-8, 1996 Jan. [Is] ISSN: 0412-4081 [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: OBJECTIVE: The study was designed to investigate the combined effect of cyclocytidine (CC) and ganciclovir (GCV) on herpes simplex virus-1 (HSV-1) in cell culture. METHODS: The 50% inhibition concentrations of HSV-1 plaque formation (IC50) of CC, GCV alone and in combination were determined by the inhibitory test of plaque formation. The combined anti-HSV-1 effect of CC and GCV was evaluated by a graphic method and fractional inhibitory concentration (FIC) indexes. RESULTS: IC50 of CC and GCV was 0.19 and 0.1 micrograms/ml, respectively. The combination of CC with GCV produced significantly synergistic activity against HSV-1 in cell culture. FIC indexes were all below 0.75. The combined therapy of CC and GCV can also decrease and delay the emergence of drug-resistant variants. CONCLUSION: These results suggest that this combined therapy of CC and GCV may be a potentially effective means in the management of patients with HSV-1 ocular infection. [Mh] Termos MeSH primário: Ancitabina/farmacologia Antivirais/farmacologia Ganciclovir/farmacologia Herpesvirus Humano 1/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Cercopithecus aethiops Sinergismo Farmacológico Herpesvirus Humano 1/crescimento & desenvolvimento Seres Humanos Células Vero Ensaio de Placa Viral [Pt] Tipo de publicação: ENGLISH ABSTRACT; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antiviral Agents); DO2D32W0VC (Ancitabine); P9G3CKZ4P5 (Ganciclovir) [Em] Mês de entrada: 9610 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 960101 [St] Status: MEDLINE

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[PMID]: 8552205 [Au] Autor: Stankovicová M; Rauko P; Bachratá M; Blesová M; Sveda P [Ad] Endereço: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia. [Ti] Título: In vitro antileukemic activity and chemical transformation of the 5'-chloro-5'-deoxy derivative of cyclocytidine. [So] Source: Neoplasma;42(5):255-8, 1995. [Is] ISSN: 0028-2685 [Cp] País de publicação: Slovakia [La] Idioma: eng [Ab] Resumo: Hydrochloride of 5'-chloro-5'-deoxy-cyclocytidine (Cl-cC) is an analogue of cyclocytine hydrochloride (cC), a prodrug of the compound with the strong antileukemic activity arabinosylcytosine (araC). This paper is devoted to the study of its cytotoxic activity in vitro and to the effect of acid and alkaline conditions and temperature on its stability. Cl-cC inhibits not only the growth of L1210 leukemia cells in vitro and the DNA synthesis (IC50 = 0.09 mumol/l) but, at the same time, it has a weak effect on RNA synthesis (IC50 > 250 mumol/l) and no effect on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5'-chloro-araC and 2',5'-anhydro-araC but is more stable in acid solutions. [Mh] Termos MeSH primário: Ancitabina/farmacologia Antimetabólitos Antineoplásicos/farmacologia Leucemia/tratamento farmacológico [Mh] Termos MeSH secundário: Ancitabina/análogos & derivados Ancitabina/química Animais DNA/biossíntese Estabilidade de Medicamentos Leucemia L1210/tratamento farmacológico Leucemia L1210/patologia Camundongos Biossíntese de Proteínas RNA/biossíntese Células Tumorais Cultivadas [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antimetabolites, Antineoplastic); 63231-63-0 (RNA); 9007-49-2 (DNA); DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 9602 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 950101 [St] Status: MEDLINE

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[PMID]: 7525096 [Au] Autor: Mirzayans R; Cubitt S; Enns L; Karimian K; Radatus B; Hirani-Hojatti S; Murthy K; Paterson MC [Ad] Endereço: Molecular Oncology Program, Cross Cancer Institute, Edmonton, Alberta, Canada. [Ti] Título: Comparative genotoxicity of 2,3'-O-cyclocytidine, beta-xylocytidine and 1-beta-D-arabinofuranosylcytosine in human tumor cell lines. [So] Source: Carcinogenesis;15(10):2319-24, 1994 Oct. [Is] ISSN: 0143-3334 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: We have investigated the genotoxicity of two 3'-derivatives of cytidine, 2,3'-O-cyclocytidine (3'-cycloC) and beta-xylocytidine (xyloC), in human leukemia and solid tumor cell lines. Both derivatives were found to be cytotoxic at micromolar concentrations. For example, in the alveolar tumor cell line A549 which was included in all experiments as a reference, drug concentrations required to induce 50% inhibition of cell growth (D50 values) equalled 55 microM for 3'-cycloC and 80 microM for xyloC. Compared with the response of this reference cell line, none of the solid tumor cell lines tested--representing five different malignancies--displayed significant hypersensitivity to these drugs, while the acute lymphoblastic leukemia cell lines proved to be hypersensitive (range of D50 values, 5-13 microM). To gain insight into the modes of cytotoxic action of xyloC and 3'-cycloC, we compared the effect on DNA metabolism of these compounds with that of 1-beta-D-arabinofuranosylcytosine (araC), a potent inhibitor of semi-conservative DNA replication and long-patch excision repair. As seen with araC, the xylo compound strongly inhibited both DNA replicative synthesis and the repair of DNA damage induced by UV light and 60Co gamma-radiation. In gamma-irradiated A549 cells, the extent of repair inhibition by 1 mM xyloC was approximately 40% of that inhibited by araC, and concomitant exposure of the irradiated cultures to xyloC plus araC gave rise to a synergistic response. Since araC was employed at a concentration (0.1 mM) which produced a maximal effect on DNA repair when applied alone, the observed synergistic response implies that the mode of action of xyloC on DNA repair is different from that of araC. In contrast to that observed with xyloC, 3'-cycloC proved to be a very weak inhibitor of DNA replication and repair, strongly suggesting that the genotoxic action of the latter analog may be through a mechanism other than inhibition of DNA synthesis. [Mh] Termos MeSH primário: Ancitabina/toxicidade Citarabina/toxicidade Citidina/análogos & derivados Leucemia/tratamento farmacológico Leucemia/genética Neoplasias/tratamento farmacológico Neoplasias/genética [Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade Divisão Celular/efeitos dos fármacos Sobrevivência Celular/efeitos dos fármacos Criança Citarabina/administração & dosagem Citidina/toxicidade Dano ao DNA Reparo do DNA/efeitos dos fármacos Replicação do DNA/efeitos dos fármacos DNA de Neoplasias/biossíntese DNA de Neoplasias/efeitos dos fármacos DNA de Neoplasias/efeitos da radiação Ensaios de Seleção de Medicamentos Antitumorais Sinergismo Farmacológico Seres Humanos Leucemia/patologia Neoplasias/patologia Células Tumorais Cultivadas/efeitos dos fármacos Células Tumorais Cultivadas/efeitos da radiação [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (DNA, Neoplasm); 04079A1RDZ (Cytarabine); 3530-56-1 (xylocytidine); 5CSZ8459RP (Cytidine); DO2D32W0VC (Ancitabine) [Em] Mês de entrada: 9411 [Cu] Atualização por classe: 131121 [Lr] Data última revisão: 131121 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 941001 [St] Status: MEDLINE

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