Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
1.
Hernia ; 25(4): 883-890, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34363190

RESUMO

PURPOSE: Diastasis recti abdominis (DRA) or rectus diastasis is an acquired condition in which the rectus muscles are separated by an abnormal distance along their length, but with no fascia defect. To data there is no consensus about risk factors for DRA. The aim of this article is to critically review the literature about prevalence and risk factor of DRA. METHOD: A total of 13 papers were identified. RESULTS: The real prevalence of DRA is unknown because the prevalence rate varies with measurement method, measurement site and judgment criteria, but it is certainly an extremely frequent condition. Numbers of parity, BMI, diabetes are the most plausible risk factors. We identified a new anatomical variation in cadaveric dissection and in abdominal CT image evaluation: along the semilunar line the internal oblique aponeurosis could join the rectus sheath with only a posterior layer, so without a double layer (anterior and posterior) as usually described. We conducted a retrospective review of abdominal CT images and the presence of the posterior insertion only could be considered as a risk factor for DRA. CONCLUSION: Further studies with large sample size, including nulliparous, primiparous, pluriparous and men too, are necessary for identify the real prevalence.


Assuntos
Herniorrafia , Reto do Abdome , Feminino , Humanos , Masculino , Gravidez , Prevalência , Reto do Abdome/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco
2.
Morphologie ; 103(343): 148-160, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31786098

RESUMO

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two Virtual Physiological Human (VPH) projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, computational fluid-dynamics (CFD) and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.


Assuntos
Doença de Alzheimer/fisiopatologia , Dissecção Aórtica/fisiopatologia , Sistema Glinfático/fisiopatologia , Modelos Biológicos , Fluxo Sanguíneo Regional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/terapia , Aorta/diagnóstico por imagem , Aorta/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Estudos de Coortes , Simulação por Computador , Conjuntos de Dados como Assunto , Feminino , Humanos , Hidrodinâmica , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Fluxo de Trabalho
3.
Radiat Prot Dosimetry ; 180(1-4): 172-176, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036508

RESUMO

Tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of common TEPCs is ~0.3 µm. On the other hand, the pattern of particle interactions at the nanometer level is measured by only three different nanodosimeters worldwide: practical instruments are not yet available. In order to partially fill the gap between microdosimetry and track-nanodosimetry, a low-pressure avalanche-confinement TEPC was recently designed and constructed for simulating tissue-equivalent sites down to the nanometric region. The present article aims at describing the response of this newly developed TEPC in the range 0.3 µm-25 nm against a fast neutron field from a 241Am-Be source and a quasi-monoenergetic neutron beam. The experimental results are in good agreement with Monte Carlo simulations carried out with the FLUKA code.


Assuntos
Microtecnologia/instrumentação , Nanotecnologia/instrumentação , Nêutrons , Monitoramento de Radiação/instrumentação , Proteção Radiológica/instrumentação , Amerício/análise , Desenho de Equipamento , Doses de Radiação
5.
J Phys Chem A ; 116(46): 11406-13, 2012 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-22946659

RESUMO

We employ a simple multiconfiguration time-dependent Hartree (MCTDH) ansatz tailored to an effective-mode transformation of environmental variables that brings the bath into a linear chain form. In this form, important (primary) degrees of freedom can be easily identified and treated at a high correlation level, whereas secondary modes are left uncorrelated. The resulting approach scales linearly with the bath dimensions and allows us to easily access recurrence times much longer than usually possible, at a very small computational cost. Test calculations for model atom-surface problems show that the system dynamics is correctly reproduced in the relevant time window, and quantitative agreement is attained for energy relaxation and sticking, particularly in non-Markovian environments. These results pave the way for tackling realistic system-bath quantum dynamical problems on the picosecond scale.

6.
J Prev Med Hyg ; 53(1): 30-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22803317

RESUMO

INTRODUCTION: Pressure ulcer management represents a growing problem for medical and social health care systems all over the world, particularly in European Union countries where the incidence of pressure ulcers in older persons (> 60 years of age) is predicted to rise. OBJECTIVES: The aim of this study was to provide evidence for the lower impact on economic resources of using advanced dressings for the treatment of pressure ulcers with respect to conventional simple dressings. METHODS: Two different models of analysis, derived from Activity Based Costing and Health Technology Assessment, were used to measure, over a 30-day period, the direct costs incurred by pressure ulcer treatment for community-residing patients receiving integrated home care. RESULTS: Although the mean cost per home care visit was higher in the advanced dressings patient group than in the simple dressings patient one (E 22.31 versus E 16.03), analysis of the data revealed that the cost of using advanced dressings was lower due to fewer home care visits (22 versus 11). CONCLUSION: The results underline the fact that decision-makers need to improve their understanding of the advantages of taking a long-term view with regards to the purchase and use of materials. This could produce considerable savings of resources in addition to improving treatment efficacy for the benefit of patients and the health care system.


Assuntos
Visita Domiciliar/economia , Úlcera por Pressão/economia , Úlcera por Pressão/terapia , Atenção Primária à Saúde/economia , Adulto , Idoso , Bandagens/economia , Custos e Análise de Custo , Desbridamento/economia , Gerenciamento Clínico , União Europeia , Feminino , Visita Domiciliar/estatística & dados numéricos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/economia , Úlcera por Pressão/epidemiologia , Estudos Prospectivos , Higiene da Pele/economia , Resultado do Tratamento
7.
J Chem Phys ; 135(16): 164701, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-22047257

RESUMO

We investigated binding of hydrogen atoms to small polycyclic aromatic hydrocarbons (PAHs)--i.e., graphene dots with hydrogen-terminated edges--using density functional theory and correlated wavefunction techniques. We considered a number of PAHs with three to seven hexagonal rings and computed binding energies for most of the symmetry unique sites, along with the minimum energy paths for significant cases. The chosen PAHs are small enough to not present radical character at their edges, yet show a clear preference for adsorption at the edge sites which can be attributed to electronic effects. We show how the results, as obtained at different levels of theory, can be rationalized in detail with the help of a few simple concepts derivable from a tight-binding model of the π electrons.

8.
Vet Rec ; 168(18): 484, 2011 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-21527477

RESUMO

The effect of treatment with eprinomectin on milk yield, milk composition and somatic cell counts (SCCs) was studied in 105 dairy cows located on seven farms in South Tyrol, Italy. On each farm, half of the animals were treated with eprinomectin and the other half were used as an untreated control group. Three test day records per animal were obtained before treatment (days -117, -75 and -33) and another three test day records were obtained after treatment (days 22, 62 and 131). Test day records comprised milk yield, milk composition, SCC and days in milk. On the day of treatment, blood samples and faecal samples were taken for parasitological analysis. Cows with positive faecal egg counts yielded less milk. A significant effect of eprinomectin on milk yield was observed after treatment and was most pronounced on the second and the third test days after treatment (+1.90 kg [P=0.002] and +2.63 kg [P<0.001], respectively). Furthermore, a significant decrease in SCC was observed on the second test day after treatment.


Assuntos
Anti-Helmínticos/administração & dosagem , Contagem de Células/veterinária , Ivermectina/análogos & derivados , Lactação/efeitos dos fármacos , Leite , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/prevenção & controle , Indústria de Laticínios/métodos , Fezes/parasitologia , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/prevenção & controle , Gastroenteropatias/veterinária , Itália , Ivermectina/administração & dosagem , Lactação/fisiologia , Leite/química , Leite/citologia , Leite/metabolismo , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/prevenção & controle , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas/veterinária
9.
Ig Sanita Pubbl ; 64(6): 773-86, 2008.
Artigo em Italiano | MEDLINE | ID: mdl-19219086

RESUMO

"I don't smoke, and you?" is a project aimed at secondary school students and is part of a wider project called "Free from Smoke", implemented by the Lombardia Region and involving elementary and secondary school students. The project is a controlled non randomized study whose aim is to direct students toward a healthy and smoke-free way of living, by also involving parents and teachers. A total of 11,610 12 year-olds of both sexes were evaluated, 6392 of whom were enrolled in the program and 5218 of whom served as controls and only completed the questionnaire. Three years after the start of the program, a greater increase in the prevalence of smokers was found amongst the group of controls than amongst the enrolled group (108,3% vs +93.8%, p>0.001). The percentage of students who believe that smoking even a small number of cigarettes is harmful, increased in the enrolled group (+0.6%) while it diminished in controls (-2.1%). In addition, a strong association was found between receiving a weekly allowance and smoking habits. In conclusion, positive results were obtained as regards the prevalence of smokers and the perceived risk of smoking; however parents' attitude towards smoking and the availability of a weekly allowance were found to have a strong influence in students' smoking habits.


Assuntos
Psicologia do Adolescente , Psicologia da Criança , Serviços de Saúde Escolar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Adolescente , Criança , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/organização & administração , Humanos , Itália/epidemiologia , Masculino , Relações Pais-Filho , Grupo Associado , Prevalência , Avaliação de Programas e Projetos de Saúde , Risco , Serviços de Saúde Escolar/organização & administração , Fumar/efeitos adversos , Fumar/economia , Fumar/epidemiologia , Fumar/psicologia , Abandono do Hábito de Fumar , Inquéritos e Questionários
13.
Acta Gastroenterol Latinoam ; 31(3): 115-21, 2001.
Artigo em Espanhol | MEDLINE | ID: mdl-11577562

RESUMO

INTRODUCTION: The action of non-steroidal anti-inflammatory drugs (NSAIDs) on the Helicobacter Pylori (Hp) infected mucosa is a matter of debate. Some authors consider them to cause additive iatrogeny whilst others attribute a purportedly protective action to them. The development of on experimental animal model could help clarify this phenomenon. OBJECTIVES: 1--To develop an animal model of Hp gastric infection. 2--To evaluate the aggressiveness of NSAIDs in this model. MATERIALS AND METHODS: Male 6 month old BALC/C mice weighing 38 g were studied. Pylori Hp infection was ruled out. On three occasions, in the same week, 18 mice were inoculated intra-gastrically with 0.6 ml of Hp culture broth (brain-heart infusion) containing 1 x 10 8-1 x 10 9 CFU/ml. Another group of mice were inoculated with sterile saline. After two months the mice were killed and their stomachs studied. They were divided into groups: a) 6 Hp negative control mice. b) 8 Hp negative mice with prior intra-peritoneal injection of 25 mg/Kg indomethacin (24 hs.) c) 8 mice inoculated with Hp with indomethacin. d) 8 mice inoculated with Hp, without indomethacin. The stomachs were opened along the greater curvature and photographed macroscopically in order to map the necrotic area. The antrums were biopsied to test for urease and separate antrum and body specimens were send for staining with Warthin-Starry H & B and histopathology. RESULTS: All the mice inoculated with Hp acquired the infection. The necrotic area was larger in Group B: 55.5 +/- 7.87 mm than in Group C: 15 +/- 1.82 mm P < 0.00019. HISTOLOGY: Group A: normal mucosa. Group B: extensive coagulation necrosis and focal erosions. Group C: ulcers with inflammatory infiltrate and smaller necrotic area, presence of Hp on the surface epithelium. Group D: no ulcers, Hp present. CONCLUSION: An animal model of Hp infection was successfully developed Hp infection could play a potentially protective role against indomethacin aggression in the mouse.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter , Helicobacter pylori , Indometacina/efeitos adversos , Animais , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
Acta gastroenterol. latinoam ; 31(3): 115-121, 2001. ilus, gra
Artigo em Espanhol | BINACIS | ID: bin-8909

RESUMO

INTRODUCTION: The action of non-steroidal anti-inflammatory drugs (NSAIDs) on the Helicobacter Pylori (Hp) infected mucosa is a matter of debate. Some authors consider them to cause additive iatrogeny whilst others attribute a purportedly protective action to them. The development of on experimental animal model could help clarify this phenomenon. OBJECTIVES: 1--To develop an animal model of Hp gastric infection. 2--To evaluate the aggressiveness of NSAIDs in this model. MATERIALS AND METHODS: Male 6 month old BALC/C mice weighing 38 g were studied. Pylori Hp infection was ruled out. On three occasions, in the same week, 18 mice were inoculated intra-gastrically with 0.6 ml of Hp culture broth (brain-heart infusion) containing 1 x 10 8-1 x 10 9 CFU/ml. Another group of mice were inoculated with sterile saline. After two months the mice were killed and their stomachs studied. They were divided into groups: a) 6 Hp negative control mice. b) 8 Hp negative mice with prior intra-peritoneal injection of 25 mg/Kg indomethacin (24 hs.) c) 8 mice inoculated with Hp with indomethacin. d) 8 mice inoculated with Hp, without indomethacin. The stomachs were opened along the greater curvature and photographed macroscopically in order to map the necrotic area. The antrums were biopsied to test for urease and separate antrum and body specimens were send for staining with Warthin-Starry H & B and histopathology. RESULTS: All the mice inoculated with Hp acquired the infection. The necrotic area was larger in Group B: 55.5 +/- 7.87 mm than in Group C: 15 +/- 1.82 mm P < 0.00019. HISTOLOGY: Group A: normal mucosa. Group B: extensive coagulation necrosis and focal erosions. Group C: ulcers with inflammatory infiltrate and smaller necrotic area, presence of Hp on the surface epithelium. Group D: no ulcers, Hp present. CONCLUSION: An animal model of Hp infection was successfully developed Hp infection could play a potentially protective role against indomethacin aggression in the mouse. (AU)


Assuntos
Animais , Masculino , /efeitos adversos , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter , Helicobacter pylori , Indometacina/efeitos adversos , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia , Camundongos , Camundongos Endogâmicos BALB C
15.
Acta gastroenterol. latinoam ; 31(3): 115-21, 2001.
Artigo em Espanhol | BINACIS | ID: bin-39444

RESUMO

INTRODUCTION: The action of non-steroidal anti-inflammatory drugs (NSAIDs) on the Helicobacter Pylori (Hp) infected mucosa is a matter of debate. Some authors consider them to cause additive iatrogeny whilst others attribute a purportedly protective action to them. The development of on experimental animal model could help clarify this phenomenon. OBJECTIVES: 1--To develop an animal model of Hp gastric infection. 2--To evaluate the aggressiveness of NSAIDs in this model. MATERIALS AND METHODS: Male 6 month old BALC/C mice weighing 38 g were studied. Pylori Hp infection was ruled out. On three occasions, in the same week, 18 mice were inoculated intra-gastrically with 0.6 ml of Hp culture broth (brain-heart infusion) containing 1 x 10 8-1 x 10 9 CFU/ml. Another group of mice were inoculated with sterile saline. After two months the mice were killed and their stomachs studied. They were divided into groups: a) 6 Hp negative control mice. b) 8 Hp negative mice with prior intra-peritoneal injection of 25 mg/Kg indomethacin (24 hs.) c) 8 mice inoculated with Hp with indomethacin. d) 8 mice inoculated with Hp, without indomethacin. The stomachs were opened along the greater curvature and photographed macroscopically in order to map the necrotic area. The antrums were biopsied to test for urease and separate antrum and body specimens were send for staining with Warthin-Starry H & B and histopathology. RESULTS: All the mice inoculated with Hp acquired the infection. The necrotic area was larger in Group B: 55.5 +/- 7.87 mm than in Group C: 15 +/- 1.82 mm P < 0.00019. HISTOLOGY: Group A: normal mucosa. Group B: extensive coagulation necrosis and focal erosions. Group C: ulcers with inflammatory infiltrate and smaller necrotic area, presence of Hp on the surface epithelium. Group D: no ulcers, Hp present. CONCLUSION: An animal model of Hp infection was successfully developed Hp infection could play a potentially protective role against indomethacin aggression in the mouse.

16.
Acta gastroenterol. latinoam ; 31(3): 115-121, 2001. ilus, graf
Artigo em Espanhol | LILACS | ID: lil-305320

RESUMO

INTRODUCTION: The action of non-steroidal anti-inflammatory drugs (NSAIDs) on the Helicobacter Pylori (Hp) infected mucosa is a matter of debate. Some authors consider them to cause additive iatrogeny whilst others attribute a purportedly protective action to them. The development of on experimental animal model could help clarify this phenomenon. OBJECTIVES: 1--To develop an animal model of Hp gastric infection. 2--To evaluate the aggressiveness of NSAIDs in this model. MATERIALS AND METHODS: Male 6 month old BALC/C mice weighing 38 g were studied. Pylori Hp infection was ruled out. On three occasions, in the same week, 18 mice were inoculated intra-gastrically with 0.6 ml of Hp culture broth (brain-heart infusion) containing 1 x 10 8-1 x 10 9 CFU/ml. Another group of mice were inoculated with sterile saline. After two months the mice were killed and their stomachs studied. They were divided into groups: a) 6 Hp negative control mice. b) 8 Hp negative mice with prior intra-peritoneal injection of 25 mg/Kg indomethacin (24 hs.) c) 8 mice inoculated with Hp with indomethacin. d) 8 mice inoculated with Hp, without indomethacin. The stomachs were opened along the greater curvature and photographed macroscopically in order to map the necrotic area. The antrums were biopsied to test for urease and separate antrum and body specimens were send for staining with Warthin-Starry H & B and histopathology. RESULTS: All the mice inoculated with Hp acquired the infection. The necrotic area was larger in Group B: 55.5 +/- 7.87 mm than in Group C: 15 +/- 1.82 mm P < 0.00019. HISTOLOGY: Group A: normal mucosa. Group B: extensive coagulation necrosis and focal erosions. Group C: ulcers with inflammatory infiltrate and smaller necrotic area, presence of Hp on the surface epithelium. Group D: no ulcers, Hp present. CONCLUSION: An animal model of Hp infection was successfully developed Hp infection could play a potentially protective role against indomethacin aggression in the mouse.


Assuntos
Animais , Masculino , Anti-Inflamatórios não Esteroides , Modelos Animais de Doenças , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Indometacina , Mucosa Gástrica , Camundongos , Camundongos Endogâmicos BALB C
17.
Sci Justice ; 40(4): 241-56, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11094821

RESUMO

The capabilities of confocal scanning laser microscopy for the visualisation of marks on bullets and cartridge cases were investigated. Confocal microscopy provides solutions to important limitations of conventional comparison microscopy with grazing light incidence, as generally used for the examination of these marks. It is expected that confocal microscopy, thanks to its broad applicability within the field of firearms investigation and its capability of non-destructively gathering quantitative three-dimensional information, will lead to a more complete and objective forensic examination of bullets and cartridge cases.


Assuntos
Armas de Fogo , Medicina Legal/métodos , Microscopia Confocal/métodos , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador , Microscopia
18.
Ann Oncol ; 10(7): 831-8, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10470431

RESUMO

BACKGROUND: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. PATIENTS AND METHODS: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. RESULTS: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. CONCLUSIONS: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfócitos/enzimologia , O(6)-Metilguanina-DNA Metiltransferase/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/enzimologia , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Glioma/sangue , Glioma/tratamento farmacológico , Glioma/enzimologia , Humanos , Masculino , Melanoma/sangue , Melanoma/tratamento farmacológico , Melanoma/enzimologia , Pessoa de Meia-Idade , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/efeitos adversos , Compostos Organofosforados/administração & dosagem , Compostos Organofosforados/efeitos adversos , Temozolomida
19.
Anticancer Drug Des ; 14(3): 179-86, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10500494

RESUMO

Ecteinascidin-743 (ET-743) is a tetrahydroisoquinoline alkaloid isolated from Ecteinascidia turbinata, a tunicate growing in mangrove roots in Caribbean. It has been shown to bind in the minor groove of DNA forming covalent adducts by reaction of the N2 of guanine with the carbinolamine moiety. We investigated ET-743 ability to inhibit the binding of different transcription factors to their consensus sequences by using gel shift assays. We have selected three types of factors: (i) oncogene products such as MYC, c-MYB and Maf; (ii) transcriptional activators regulated during the cell cycle as E2F and SRF; and (iii) general transcription factors such as TATA binding protein (TBP), Sp1 and NF-Y. We observed no inhibition of the binding of Sp1, Maf, MYB and MYC. Inhibition of DNA binding was observed for TBP, E2F, SRF at ET-743 concentrations ranging from 50 to 300 microM. The inhibition of binding of NF-Y occurs at even lower concentrations (i.e. 10-30 microM) when the recombinant subunits of NF-Y are preincubated with the drug, indicating that the inhibition of NF-Y binding does not require previous ET-743 DNA binding. Since NF-Y is a trimer containing two subunits with high resemblance to histones H2B and H2A, we have investigated the effect of ET-743 on nucleosome reconstitution. ET-743 caused a decrease of the nucleosomal band at 100 nM, with the complete disappearance of the band at 3-10 microM. These data suggest that the mode of action of this novel anticancer drug is related to its ability to modify the interaction between some DNA binding proteins and DNA.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Dioxóis/farmacologia , Isoquinolinas/farmacologia , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Proteínas Estimuladoras de Ligação a CCAAT , Sequência Consenso , Proteínas de Ligação a DNA/antagonistas & inibidores , Eletroforese , Leucemia L1210/metabolismo , Camundongos , Oligonucleotídeos/antagonistas & inibidores , Oligonucleotídeos/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Fator de Transcrição Sp1/antagonistas & inibidores , Fator de Transcrição Sp1/metabolismo , Proteína de Ligação a TATA-Box , Tetra-Hidroisoquinolinas , Trabectedina , Fatores de Transcrição/antagonistas & inibidores
20.
Br J Cancer ; 80(7): 971-80, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10362104

RESUMO

Thiocoraline, a new anticancer agent derived from the marine actinomycete Micromonospora marina, was found to induce profound perturbations of the cell cycle. On both LoVo and SW620 human colon cancer cell lines, thiocoraline caused an arrest in G1 phase of the cell cycle and a decrease in the rate of S phase progression towards G2/M phases, as assessed by using bromodeoxyuridine/DNA biparametric flow cytometric analysis. Thiocoraline does not inhibit DNA-topoisomerase II enzymes in vitro, nor does it induce DNA breakage in cells exposed to effective drug concentrations. The cell cycle effects observed after exposure to thiocoraline appear related to the inhibition of DNA replication. By using a primer extension assay it was found that thiocoraline inhibited DNA elongation by DNA polymerase alpha at concentrations that inhibited cell cycle progression and clonogenicity. These studies indicate that the new anticancer drug thiocoraline probably acts by inhibiting DNA polymerase alpha activity.


Assuntos
Antibacterianos/farmacologia , Antibióticos Antineoplásicos/farmacologia , Depsipeptídeos , Peptídeos , Bromodesoxiuridina/metabolismo , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , DNA/efeitos dos fármacos , DNA/metabolismo , DNA Polimerase Dirigida por DNA/efeitos dos fármacos , Citometria de Fluxo , Humanos , Concentração Inibidora 50 , Fatores de Tempo , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-Tronco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...