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1.
Reumatismo ; 71(2): 81-84, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31309778

RESUMO

Synovial chondromatosis (SC) is a rare condition with a very variable clinical presentation, thus making the diagnosis not immediate. We report a case of massive primary SC of the knee, properly evaluated with X-rays, ultrasonography and magnetic resonance imaging and successfully treated with an arthroscopic approach.


Assuntos
Condromatose Sinovial/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Adulto , Humanos , Masculino , Radiografia
2.
Ann Oncol ; 26(6): 1069-1080, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25605746

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, accounting for 35%-40% of all cases. The combination of the anti-CD20 monoclonal antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to complete remission in most and can cure more than half of patients with DLBCL. The diversity in clinical presentation, as well as the pathologic and biologic heterogeneity, suggests that DLBCL comprises several disease entities that might ultimately benefit from different therapeutic approaches. In this review, we summarize the current literature focusing on the genetic lesions identified in DLBCL.


Assuntos
Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Predisposição Genética para Doença , Testes Genéticos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Terapia de Alvo Molecular , Farmacogenética , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Indução de Remissão , Fatores de Risco , Resultado do Tratamento
3.
Ann Oncol ; 23(3): 729-735, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21693768

RESUMO

BACKGROUND: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21). PATIENTS AND METHODS: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years. RESULTS: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21. CONCLUSIONS: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Perfilação da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real
4.
Radiology ; 221(3): 731-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11719669

RESUMO

PURPOSE: To determine whether gadobenate dimeglumine (Gd-BOPTA) is able to provide morphologic and functional information for characterization of focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Sixty-three consecutive patients with proved FNH were retrospectively examined. Magnetic resonance (MR) imaging with T2-weighted turbo spin-echo and T1-weighted gradient-echo sequences was performed. Images were acquired prior to and during the dynamic phase of contrast-material enhancement and 1-3 hours after administration of 0.1 mmol/kg Gd-BOPTA. Qualitative analysis of signal intensity and homogeneity on images in the various phases of the MR study and examination for the presence of central scar or atypical features were performed. On the basis of features observed in the precontrast and dynamic phases, lesions were defined as typical or atypical. Intensity and enhancement patterns of the lesions and scars were also evaluated in the delayed phase. RESULTS: One hundred FNHs were depicted on MR images. Seventy-nine of 100 lesions demonstrated typical morphologic and enhancement characteristics. On delayed phase images, 72% of 100 FNHs appeared hyperintense; 21%, isointense; and 7%, slightly hypointense. The delayed pattern of enhancement was homogeneous, heterogeneous, and peripheral in 58%, 22%, and 20% of 100 FNHs, respectively. Atypical morphologic features and lesion and/or scar enhancement were observed in 21 of 100 FNHs. On delayed phase images, 76% of 100 atypical FNHs appeared hyperintense, 14% isointense, and 10% slightly hypointense. Hyperintensity and isointensity allowed the correct characterization in 90% of atypical FNHs. CONCLUSION: Gd-BOPTA during both dynamic and delayed phases provides morphologic and functional information for the characterization of FNH.


Assuntos
Meios de Contraste , Hiperplasia Nodular Focal do Fígado/diagnóstico , Imageamento por Ressonância Magnética , Meglumina/análogos & derivados , Compostos Organometálicos , Adolescente , Adulto , Criança , Feminino , Hiperplasia Nodular Focal do Fígado/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos
5.
Biomaterials ; 22(7): 717-23, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11246966

RESUMO

Using ceramic materials it is possible to obtain a number of beneficial mechanical properties such as considerable hardness, good chemical resistance, high tensile strength, and a good fracture toughness. The use of ceramic-on-ceramic as bearing surfaces for hip joint prostheses has been reported to produce a lower wear rate than other combinations (i.e. metal-on-polyethylene and ceramic-on-polyethylene) in total hip artroplasty. These advantages may increase the life expectancy of hip implants and improve the life of patients. Two new types of mixed-oxide ceramics (alumina and yttria-stabilised zirconia) femoral heads and acetabular cups containing different ratios of alumina and zirconia were compared with pure commercial alumina in terms of wear behaviour in a hip joint simulator. Hip joint wear simulator studies were carried out with a full-peak load of 2030 N and a frequency of 1 Hz in bovine calf serum. After 10 million cycles the measured weight loss of all specimens was very low. However, the experimental results did not show any significant difference between the new experimental mixed-oxide ceramics prototype and the commercial ceramic material couplings.


Assuntos
Materiais Biocompatíveis , Cerâmica , Prótese de Quadril , Óxido de Alumínio/química , Animais , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Bovinos , Cerâmica/química , Humanos , Técnicas In Vitro , Teste de Materiais , Desenho de Prótese , Falha de Prótese , Zircônio/química
6.
Tumori ; 86(4): 341-2, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11016723

RESUMO

Biopsy of head and neck sentinel nodes (SNs) can be technically problematic due to the unpredictable and variable drainage patterns of this anatomic region. The aim of the present study was to evaluate the feasibility of SN biopsy for cutaneous melanoma of the head and neck. We performed SN biopsy in 17 patients affected by stage I cutaneous melanoma of the head and neck on the basis of lymphoscintigraphy, blue dye and gamma probe. A total of 24 procedures were performed. Drainage to more than one lymphatic basin was observed in five patients (two basins in three cases and three basins in two cases) and in all cases SN biopsy was performed in all basins. The biopsy distribution by site was: six cervical nodes, five parotid nodes, four supraclavicular and submandibular nodes, three auricular and axillary nodes. The SN identification rate was 87.5% (21/24); metastases were discovered in four cases, with a positivity rate of 23.6%. At the time of writing, 1 patient is alive with local disease, 3 patients are dead and 13 are alive and free of disease with a follow-up ranging from 1 to 40 months (median, 21 months) following SN biopsy. In our opinion preoperative lymphoscintigraphy and the intraoperative use of a gamma probe are useful for the identification of lymphatic drainage of cutaneous melanoma of the head and neck.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologia , Corantes , Estudos de Viabilidade , Raios gama , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Cintilografia , Corantes de Rosanilina , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Agregado de Albumina Marcado com Tecnécio Tc 99m
7.
Eur Radiol ; 10(4): 601-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10795542

RESUMO

This work analyses the diagnostic capability of radiographic images taken from patients with total hip arthroplasty and visualised on monitor. Images were obtained with digital acquisition of conventional X-ray films. The investigated pathology is the absence of direct contact between bone and prosthesis (radiolucency). Three senior orthopaedists defined the diagnostic "truth" on well-defined regions of interest on 22 conventional X-ray films of total hip arthroplasty, obtaining a total of 110 reference ratings. Films were digitised by use of an X-ray scanner. Four readers evaluated the X-ray images, applying conventional and monitor visualisation. To show any difference between ratings on film and ratings on monitor a sensitivity, specificity and accuracy study jointly with a receiver operating characteristics (ROC) study were performed for each reader and for all combined readings. The intra-observer reproducibility of the radiographic protocol was equal to 87% and the inter-observer one was in the range 85-92%. The sensitivity, specificity and accuracy study together with the ROC analysis did not show significant differences between the two evaluation modes. The evaluation of radiolucency from digitised X-ray films visualised on a monitor resulted statistically comparable with the conventional evaluation on X-ray films.


Assuntos
Diagnóstico por Computador , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril , Complicações Pós-Operatórias/diagnóstico por imagem , Humanos , Variações Dependentes do Observador , Curva ROC , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Biomaterials ; 20(20): 1925-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10514069

RESUMO

Three different types of mixed-oxides ceramic ball heads have been investigated for their wear behaviour against acetabular cups of the same materials in a hip joint simulator. Mixed-oxides ceramics have been indicated in literature as a promising compromise between strength and wear but no reports are available on the influence of a percentage of zirconia in a ceramic femoral head when sliding against itself. Mixed-oxides ceramic acetabular cups and femoral heads were tested on a simulator apparatus with a sinusoidal load in presence of bovine calf serum. The experimental results did not show any significant difference between the experimental and commercial ceramic material couplings. These results were found to be in accord with those developed in Part 1.


Assuntos
Cerâmica , Prótese de Quadril , Teste de Materiais/métodos , Zircônio , Acetábulo , Óxido de Alumínio , Animais , Sangue , Bovinos , Fêmur , Teste de Materiais/instrumentação , Resistência à Tração
9.
Biomaterials ; 20(10): 971-5, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10353651

RESUMO

Although mixed oxides ceramics have been indicated in the literature as a promising compromise between strength and wear, to the authors' knowledge no reports are available on the influence of the percentage of zirconia in ceramic femoral heads when sliding against polyethylene cups. Two types of mixed oxides ceramic ball heads (alumina plus, respectively, 60 and 80% of zirconia) were compared to pure zirconia and pure alumina heads in terms of wear behaviour against UHMWPE in a hip joint simulator. Polyethylene cups and ceramic femoral heads were fixed on a simulator apparatus with a sinusoidal movement and load in presence of bovine calf serum. The experimental results did not show significant difference between the two experimental ceramic materials or in comparison with pure materials. Considering that all specimens, regardless of the material, had the same level of surface roughness, this roughness factor seems to have a more relevant role than the mix of oxides used to manufacture the ceramic head. Wear tests are conducted on materials used in prosthetic hip implants in order to obtain quality control and to acquire further knowledge of the tribological processes that involve joint prostheses, therefore reducing the risk of implant failure of innovative prostheses.


Assuntos
Materiais Biocompatíveis , Cerâmica , Prótese de Quadril , Animais , Bovinos , Humanos , Teste de Materiais/instrumentação , Polietilenos , Falha de Prótese , Estresse Mecânico , Zircônio
10.
Chir Organi Mov ; 84(1): 37-48, 1999.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-11569014

RESUMO

The authors report the results of 56 prosthetic implants on previous femoral osteotomy. The cases submitted to surgery, some time after the operation, present with clinical-radiographic results (movement and risk of loosening) that are worse than those cases that had not undergone osteotomy. Among complications, a higher incidence of intraoperative fractures and nerve paralysis were observed. Fractures always occurred when instrumentation was removed during the same prosthetic implantation procedure.


Assuntos
Artroplastia de Quadril , Fêmur/cirurgia , Osteotomia , Adolescente , Adulto , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia
11.
Chir Organi Mov ; 84(2): 135-43, 1999.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-11569072

RESUMO

Prosthetic hip reimplantation is considered to be a procedure at risk for the development of periprosthetic heterotopic ossification, which may be responsible for functional limitations of the hip operated on. Preventive treatment may be carried out with radiation or drug therapy. The authors report the results of 54 cases submitted to prosthetic reimplantation and treated by cobalt therapy, as compared to the results of 76 reimplantations (control group) that did not undergo any kind of treatment: the occurrence of high grade ossification (exceeding Brooker grade III) was 2% in cases treated, as compared to 9% in those not treated. Males were more at risk for the development of ossification.


Assuntos
Artroplastia de Quadril/efeitos adversos , Radioisótopos de Cobalto/uso terapêutico , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação
13.
Chir Organi Mov ; 83(4): 323-35, 1998.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-10369012

RESUMO

The need to improve the features of resistance and duration of prosthetic implants, based on the constant increase in the number per year of total hip substitutions has encouraged the study of the causes of aseptic loosening of implants, in particular, any relationship between femoral morphology, features of the implanted prosthesis (size and coating), degree of contact between the latter and the host bone, and the occurrence of changes in bone trophism. The documentation relative to 143 patients, corresponding to 149 primary hip arthroplasties, was evaluated clinically (according to Merle d'Aubigné modified by Charnley) and radiographically, using a computerized radiographic evaluation system devised by our group. In particular, on x-rays (anteroposterior view) obtained in the area corresponding to the upper and lower margins of the smaller trochanter and of the femoral isthmus, measurements relative to femoral diameters, to the distance between them, and to the corresponding flare indexes were obtained; bone thickness, degree of bone-prosthesis correspondence and any changes in bone trophism caused by stress-shielding and stress-concentration were also measured. An analysis of the data was carried out using non-parametric statistical tests, that allowed us to reveal the surgeon's good standardization in preparation of the femur; the tendency for the cortex to thicken for prostheses of the short type, and the narrowing of the standard type prostheses, the influence of the degree of fit of the prosthesis on trophism of the femoral cortex.


Assuntos
Cabeça do Fêmur/anatomia & histologia , Colo do Fêmur/anatomia & histologia , Prótese de Quadril , Falha de Prótese , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/patologia , Humanos , Radiografia
14.
Chir Organi Mov ; 82(3): 211-9, 1997.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-9494238

RESUMO

The authors report the results of 54 primary hip arthroplasty implants performed in patients aged over 75 years. The cases examined demonstrated that this type of surgery is not contraindicated in elderly patients as the occurrence of complications and perioperative risks are not higher if compared with a "younger" population. Preoperative anesthesiological evaluation that is extremely accurate is required.


Assuntos
Artroplastia de Quadril , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Complicações Pós-Operatórias
15.
Chir Organi Mov ; 82(2): 165-76, 1997.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-9428177

RESUMO

The authors report the results obtained with antibiotic and antithromboembolic prophylaxis used in 700 consecutive primary total hip arthroplasties. As for antibiotic prophylaxis (5 cases of infection: 0.7%) the various types of antibiotic used always kept the infection rate under 1%, confirming the effectiveness of the preventive use of antibioticotherapy. The incidence of deep venous thrombosis and pulmonary embolia were 3.7% and 0.7%, respectively (26 cases of DVT and 5 of PET). The incidence of DVT rose to 34.4% in a selected group of cases in which phlebography had been carried out even in the absence of symptoms of DVT. This confirms that the routine use of this method would without a doubt be useful in preventing complications with a high risk for the life of the patient (pulmonary embolia). As for pharmacological prophylaxis, indobufene and calcium heparin were the drugs used most: their effectiveness was nearly similar, despite the fact that the use of calcium heparin in patients considered to be at a higher risk for thromboembolic complications should be made clear.


Assuntos
Artroplastia de Quadril/métodos , Embolia Pulmonar/prevenção & controle , Tromboembolia/prevenção & controle , Tromboflebite/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue Autóloga , Cefazolina/uso terapêutico , Cefotaxima/administração & dosagem , Cefalosporinas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Tromboflebite/tratamento farmacológico
16.
Mutat Res ; 373(2): 201-6, 1997 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-9042401

RESUMO

The effect of several free radicals scavengers on DNA damage and clastogenesis induced by streptonigrin (SN) in CHO cells was investigated. The addition of the antioxidant enzymes superoxide dismutase and/or catalase on CHO cell cultures did not prevent the induction of DNA and chromosome damage by SN. In fact, when superoxide dismutase was added to the culture medium an increase on the frequency of SN-induced chromosome aberrations was observed. Moreover, the addition of the hydroxyl radicals scavenger mannitol caused a significant increase in DNA and chromosome damage induced by SN. On the contrary, when all the antioxidants mentioned above were added-alone or in different combinations-encapsulated into liposomes, a significant decrease in the yield of SN-induced chromosome aberrations and DNA damage was observed. These findings indicate that free radicals are involved in the production of DNA and chromosome damage by SN and that this damage can be partially inhibited through the incorporation of antioxidants by the cells.


Assuntos
Antioxidantes/farmacologia , Aberrações Cromossômicas , Dano ao DNA/efeitos dos fármacos , Estreptonigrina/farmacologia , Animais , Antioxidantes/administração & dosagem , Células CHO , Catalase/farmacologia , Cricetinae , Lipossomos , Manitol/farmacologia , Superóxido Dismutase/farmacologia
17.
Radiol Med ; 92(3): 193-8, 1996 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-8975301

RESUMO

This work suggests a densitometric protocol for femoral studies in arthrosic patients candidate to total hip arthroplasty. The protocol was applied retrospectively to 60 cases to investigate its possible future use as a tool for the preoperative planning of prosthetic stem fixation techniques-i.e., cemented vs. uncemented. The well-known standard procedures for femoral densitometric studies by dual-energy X-ray absorptiometry (DXA), are usually applied to the femoral neck, Ward's triangle and the greater trochanter. Unfortunately, these analyses lose their significance if applied to arthrosic hips, and arthrosis is the main condition requiring total hip arthroplasty. Our protocol for femoral studies in arthrosic patients includes the preoperative analysis of 7 regions of interest in the proximal shaft, similar to Gruen's regions. In vivo precision tests show variation coefficients ranging 0.9-3.7%. The protocol was applied to a series of 60 arthrosic patients who were submitted to total hip arthroplasty by the same surgical staff. Twenty of them were implanted a cemented stem and the other 40 an uncemented ("press-fit") stem. Densitometric results were communicated only after surgery, to avoid any bias on the normal decision-making process usually used to choose the fixation technique for the prosthetic stem. The two groups of cemented vs. uncemented stems had different distribution of densitometric values. Therefore, the information obtained with femoral densitometric studies preoperatively can play a major role in the choice between cemented and uncemented stems. Moreover, if femoral densitometric studies are carried out preoperatively, their results can be closely related to periprosthetic tissue remodeling and implant follow-up.


Assuntos
Densidade Óssea , Cimentação , Fêmur , Prótese de Quadril , Adulto , Idoso , Idoso de 80 Anos ou mais , Densitometria , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Retrospectivos
18.
Chir Organi Mov ; 81(2): 89-106, 1996.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-8968113

RESUMO

The occurrence of heterotopic ossification after total hip arthroplasty may be prevented by radiation or medical therapy. The authors report the results obtained in 96 cases treated by cobalt therapy: the occurrence of high grade ossification (Brooker III and IV) is equal to 1% in cases treated, as compared to 9% in cases not treated. Male patients of advanced age and who are characterized by primary arthrosis are more at risk for ossification.


Assuntos
Radioisótopos de Cobalto/uso terapêutico , Prótese de Quadril , Ossificação Heterotópica/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Articulação do Quadril/diagnóstico por imagem , Prótese de Quadril/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Fatores de Risco , Fatores de Tempo
19.
Mutat Res ; 359(1): 31-7, 1996 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-8569800

RESUMO

We treated CHO cells with streptonigrin (SN) alone, in combination with BrdUrd or IdUrd substitution, and with or without the addition of caffeine. The cells assessed for chromosome damage by SN were in the G2 period and the magnitude of the damage was expressed as monosubstituted chromatid breaks, bisubstituted chromatid breaks and boundary regions breaks (boundary regions indicate the point of exchange of mono- and bisubstituted chromatids). We found that the combination of BrdUrd or IdUrd substitution with SN treatments produced a remarkable increase in the frequency of breaks over the frequencies observed with the halogenated compound only. The effect was more evident with IdUrd than with BrdUrd, and more dramatic in bisubstituted than in monosubstituted chromatids. The frequency of boundary breaks in cells treated with BrdUrd plus SN was similar to the frequency of breaks in monosubstituted chromatids treated similarly. Conversely, the damage in boundary regions was almost similar to that in bisubstituted chromatids in cells challenged with IdUrd plus SN. The addition of caffeine to BrdUrd-substituted chromosomes gave rise to a marked enhancement of breakages with a gradient of chromatid damage that was: bisubstituted > monosubstituted > boundary regions. A further increase of chromatin breaks maintaining the gradient indicated above was obtained when the cells were treated with BrdUrd plus SN plus caffeine. We propose that BrdUrd and IdUrd substitution alone or in combination with caffeine treatments and with SN in its capacity to bind DNA, give rise to different chromatin structures capable of modulating the DNA damage induced along the chromatin fibril by the active oxygen species liberated by SN-DNA complexes.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Aberrações Cromossômicas , Dano ao DNA , Estreptonigrina/toxicidade , Animais , Bromodesoxiuridina/química , Células CHO , Cricetinae , DNA/química , Idoxuridina/química
20.
Mutat Res ; 334(1): 23-31, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7528335

RESUMO

CHO cells were pulse-treated for 20 min with increasing doses of streptonigrin (SN). First division cells analyzed 18 h after the end of treatment showed a combination of chromosome and chromatid aberrations with a typical dose-response curve. The frequency of SCEs in second division cells (24 h harvesting time) also exhibited a positive correlation with the SN dose. A high incidence of chromatid aberrations was detected in second and third division metaphases. This indicates that SN has a persistent clastogenic action that lasts for at least three cell cycles after the end of treatment. The kinetics of DNA damage and repair was studied by the alkaline unwinding and single cell gel methods. It was found that a pulse treatment with SN elicited a triphasic response characterized by repair-damage-repair. It is proposed that SN forms stable complexes with the DNA. These complexes by a continuous cycling redox process would produce active oxygen species inducing direct damage to DNA.


Assuntos
Cromossomos/efeitos dos fármacos , Dano ao DNA , Mutagênicos/toxicidade , Estreptonigrina/toxicidade , Animais , Células CHO , Cricetinae , Cinética , Desnaturação de Ácido Nucleico , Troca de Cromátide Irmã
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