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1.
An Acad Bras Cienc ; 92(3): e20191442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33111821

RESUMO

We report the study on the formation of the Cu2[Fe(CN)6] nanocomposite, which was obtained from copper oxide nanoparticles (CuO NPs) and Prussian Blue precursors. UV-vis analysis indicated that Cu2+ ions are released from CuO NPs, while Fe3+ ions are adsorbed onto the structure of CuO due to a sharp increase in zeta potential (from -30 to 0 mV) after the formation of the Cu2[Fe(CN)6]. Moreover, energy dispersive spectroscopy confirmed that Fe3+ ions are trapped in the CuO NPs structure. The CuO/Cu2[Fe(CN)6] nanocomposite exhibited the monoclinic and face-centered cubic phases that correspond to the CuO and Cu2[Fe(CN)6] components. Cyclic voltammetry (CV) for the Nanocomposite modified electrode revealed two well-defined redox couples at -0.073 ((E1/2)1) and 0.665 mV ((E1/2)2), attributed to the conversion of Cu2+ to Cu+ and CuFe2+ CuFe3+ pairs, respectively, which is similar to those in the CuO and Cu2[Fe(CN)6]components. Furthermore, the catalytic activity of the nanocomposite towards hydrogen was investigated through CV, where the reduction of H2O2 led to increased currents for the electrochemical process associated with the first redox pair. In contrast, for isolated materials (CuO NPs and Cu2[Fe(CN)6]), there was no significant increase in the current associated with either redox pair.


Assuntos
Cobre , Nanocompostos , Nanopartículas , Eletrodos , Peróxido de Hidrogênio
2.
Phys Chem Chem Phys ; 13(26): 12155-62, 2011 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-21643578

RESUMO

This paper presents studies about the molecular interactions and redox processes involved in the formation of palladium nanoparticles associated to glucose oxidase (GOx-PdNPs) in a supramolecular arrangement. The synthesis occurs in two steps, the Pd reduction and the formation of the 80 nm sized supramolecular aggregates containing multiples units of GOx associated to 3.5 nm sized PdNPs. During synthesis, GOx molecules interact with Pd salt leading to metal ion and FAD reduction probably via the thiol group of the cysteine 521 residue. For the growing of PdNPs, formic acid was necessary as a co-adjuvant reducing agent. Besides the contribution for the redox processes, GOx is also necessary for the NP stability preventing the formation of precipitates resulted from uncontrolled growing of NPs Cyclic voltammetry of the GOx-PdNPs demonstrated electroactivity of the bionanocomposite immobilized on ITO (indium-tin oxide) electrode surface and also the NP is partially blocked due to strong interaction GOx and the surface of PdNPs. Vibrational spectroscopy (FTIR) showed that significant structural changes occurred in GOx after the association to PdNP. These mechanistics and structural studies can contribute for modulation of bionanocomposites properties.


Assuntos
Aspergillus niger/enzimologia , Enzimas Imobilizadas/química , Glucose Oxidase/química , Nanopartículas/química , Paládio/química , Eletroquímica , Nanopartículas/ultraestrutura , Oxirredução , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Phys Chem Chem Phys ; 11(25): 5086-91, 2009 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-19562139

RESUMO

The concept of constitutional dynamic chemistry (CDC) based on the control of non-covalent interactions in supramolecular structures is promising for having a large impact on nanoscience and nanotechnology if adequate nanoscale manipulation methods are used. In this study, we demonstrate that the layer-by-layer (LbL) technique may be used to produce electroactive electrodes with ITO coated by tetrasulfonated nickel phthalocyanine (NiTsPc) alternated with poly(allylamine hydrochloride) (PAH) incorporating gold nanoparticles (AuNP), in which synergy has been achieved in the interaction between the nanoparticles and NiTsPc. The catalytic activity toward hydrogen peroxide (H(2)O(2)) in multilayer films was investigated using cyclic voltammetry, where oxidation of H(2)O(2) led to increased currents in the PAH-AuNP/NiTsPc films for the electrochemical processes associated with the phthalocyanine ring and nickel at 0.52 and 0.81 V vs. SCE, respectively, while for PAH/NiTsPc films (without AuNP) only the first redox process was affected. In control experiments we found out that the catalytic activity was not solely due to the presence of AuNP, but rather to the nanoparticles inducing NiTsPc supramolecular structures that favored access to their redox sites, thus yielding strong charge transfer. The combined effects of NiTsPc and AuNP, which could only be observed in nanostructured LbL films, point to another avenue to pursue within the CDC paradigm.


Assuntos
Ouro/química , Indóis/química , Nanopartículas/química , Níquel/química , Peróxido de Hidrogênio/química , Isoindóis , Modelos Moleculares , Estrutura Molecular , Oxirredução , Propriedades de Superfície
4.
J Cell Biochem ; 100(3): 679-92, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16986113

RESUMO

Cells experience a variety of physiological and non-physiological stresses and consequently have appropriate mechanisms to deal with such deviations from homeostasis. Particularly subject to mechanical stress and shear forces are the cells that make up the bones. Osteoblastic cells can interpret this stress as a stimulus for proliferation; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have identified annexin II as being specifically upregulated in mechanically stressed osteoblasts and found that increased levels of this protein are necessary for 1[alpha],25-dihydroxyvitamin D(3) mediated augmentation of the proliferative response of osteoblasts after mechanical stress. Our data demonstrate a novel interaction between 1[alpha],25-dihydroxyvitamin D(3) and annexin II in the proliferative response of osteoblasts as well as a novel function for annexin II in the stress response. These findings may offer new therapeutic opportunities for conditions that require regenerative osteoblastic activity such as osteoporosis.


Assuntos
Anexina A2/fisiologia , Calcitriol/farmacologia , Proliferação de Células/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Adulto , Idoso , Animais , Western Blotting , Linhagem Celular , Eletroforese em Gel Bidimensional , Humanos , Camundongos , Pessoa de Meia-Idade , Osteoblastos/citologia
5.
Ultraschall Med ; 26(1): 9-16, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15700222

RESUMO

Between July 2000 and December 2003, a total number of 3,472 fetuses was evaluated by two-dimensional (2D) and three-dimensional (3D) ultrasonography. All examinations were carried out as part of a detailed level III ultrasound examination for fetal anomalies. The gestational age was between 11 and 35 weeks. A 3D endovaginal probe (5 - 7 MHz) was used for examinations between 11 and 13 weeks, and an abdominal 3D probe (5 MHz) after 13 weeks. Four different 3D image display modes were employed in visualizing fetal malformations: triplanar orthogonal display; surface display; transparent display; and the combined transparent and color display (= glass body-rendering). In 906 of the 3,472 high-risk pregnancies, fetuses with one to five fetal defects were found (mean 1.17). The total number of detected defects was 1,012, exclusive of 48 fetal heart defects. Fetal heart defects were excluded from this study since a reliable demonstration of these defects was not possible by 3D ultrasound. Comparing the 2D and 3D techniques, 3D sonography proved advantageous in 60.8 % of the defects, with the benefit derived from the exact tomographic survey using the multiplanar view in 69.9 % of these cases, from a more precise demonstration of the defect in the surface view in 25.2 %, from a distinct demonstration in the transparent view in 3.9 %, and from a precise demonstration in the combined transparent and color view in 1.0 %. In 42 of the 1,012 malformations (4.2 %), a defect was accurately identified or verified with 3D ultrasound only. 3D ultrasound proves not only a useful tool in appreciating the severity of a fetal defect, but also provides more convincing evidence of a normal fetus than conventional two-dimensional sonograms in cases with increased risk of a recurrent surface malformation.


Assuntos
Anormalidades Congênitas/diagnóstico por imagem , Anormalidades Congênitas/embriologia , Desenho de Equipamento , Face/diagnóstico por imagem , Face/embriologia , Feminino , Idade Gestacional , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/embriologia , Humanos , Imageamento Tridimensional , Neoplasias/diagnóstico por imagem , Neoplasias/embriologia , Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ultrassonografia Pré-Natal
6.
J Pathol ; 205(5): 623-32, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15726650

RESUMO

Eight members of the nm23-gene family have been described. The involvement of nm23-H1 and nm23-H2 in tumour progression and metastasis, as well as in gene regulation and apoptosis, has been shown in numerous studies. Whether nm23-H4, -H6, and -H7 play a role in tumours is, however, largely unknown. This study describes data on the expression of these three nm23 homologues in human colon and gastric cancer by real-time RT-PCR and immunohistochemistry. Increased expression of these genes, most strikingly nm23-H4 and -H7, was observed in the majority of tumours analysed. No correlation with tumour stage according to the TNM classification was found. In contrast, by immunohistochemical analysis, nm23-H4 and -H6 overexpression correlated with the intestinal tumour type in gastric cancer tissues, whereas no increased immunoreactivity for the three nm23 proteins was noted in the diffuse type tumour specimens. These findings indicate that nm23-H6, and particularly nm23-H4 and -H7, may be involved in the development of colon and gastric carcinoma, the latter possibly in a type-specific manner. A contribution to tumour progression or metastasis could not, however, be proven. Elucidation of the specific mechanisms by which the nm23 homologues nm23-H4, -H6, and -H7 are involved in tumour development requires further studies.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Núcleosídeo-Difosfato Quinase/metabolismo , Neoplasias Gástricas/metabolismo , Expressão Gênica , Genes Supressores de Tumor , Humanos , Técnicas Imunoenzimáticas , Nucleosídeo NM23 Difosfato Quinases , Nucleosídeo Difosfato Quinase D , Núcleosídeo-Difosfato Quinase/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
7.
Inorg Chem ; 42(21): 6898-906, 2003 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-14552641

RESUMO

The compounds [Ru(NH(3))(5)(dtdp)](TFMS)(3), [Os(NH(3))(5)(dtdp)](TFMS)(3), [(NH(3))(5)Os(dtdp)Os(NH(3))(5)](TFMS)(6), [(NH(3))(5)Os(dtdp)Ru(NH(3))(5)](TFMS)(3)(PF(6))(2), and [(NH(3))(5)Os(dtdp)Fe(CN)(5)] (dtdp = 4,4'-dithiodipyridine, TFMS = trifluoromethanesulfonate) have been synthesized and characterized by elemental analysis, cyclic voltammetry, electronic, vibrational, EPR, and (1)H NMR spectroscopies. Changes in the electronic and voltammetric spectra of the ion complex [Os(NH(3))(5)(dtdp)](3+) as a function of the solution pH enable us to calculate the pK(a) for the [Os(NH(3))(5)(dtdpH)](4+) and [Os(NH(3))(5)(dtdpH)](3+) acids as 3.5 and 5.5, respectively. The comparison of the above pK(a) data with that for the free ligand (pK(1) = 4.8) provides evidence for the -S-S- bridge efficiency as an electron conductor between the two pyridine rings. The symmetric complex, [(NH(3))(5)Os(dtdp)Os(NH(3))(5)](6+), is found to exist in two geometric forms, and the most abundant form (most probably trans) has a strong conductivity through the -S-S- bridge, as is shown by EPR, which finds it to have an S = 1 spin state with a spin-spin interaction parameter of 150-200 G both in the solid sate and in frozen solution. Further the NMR of the same complex shows a large displacement of unpaired spin into the pi orbitals of the dttp ligand relative to that found in [Os(NH(3))(5)(dtdp)](3+). The comproportionation constant, K(c) = 2.0 x 10(5), for the equilibrium equation [Os(II)Os(II)] + [Os(III)Os(III)] right harpoon over left harpoon 2[Os(II)Os(III)] and the near-infrared band energy for the mixed-valence species (MMCT), [(NH(3))(5)Os(dtdp)Os(NH(3))(5)](5+) (lambda(MMCT) = 1665 nm, epsilon = 3.5 x 10(3) M(-)(1) cm(-)(1), deltanu(1/2) = 3.7 x 10(3) cm(-)(1), alpha = 0.13, and H(AB) = 7.8 x 10(2) cm(-)(1)), are quite indicative of strong electron delocalization between the two osmium centers. The electrochemical and spectroscopic data for the unsymmetrical binuclear complexes [(NH(3))(5)Os(III)(dtdp)Ru(II)(NH(3))(5)](5+) (lambda(MMCT) = 965 nm, epsilon = 2.2 x 10(2) M(-)(1) cm(-)(1), deltanu(1/2) = 3.0 x 10(3) cm(-)(1), and H(AB) = 2.2 x 10(2) cm(-)(1)) and [(NH(3))(5)Os(III)(dtdp)Fe(II)(CN)(5)] (lambda(MMCT) = 790 nm, epsilon = 7.5 x 10 M(-)(1) cm(-)(1), deltanu(1/2) = 5.4 x 10(3) cm(-)(1), and H(AB) = 2.0 x 10(2) cm(-)(1)) also suggest a considerable electron delocalization through the S-S bridge. As indicated by a comparison of K(c) and energy of the MMCT process in the iron, ruthenium, and osmium complexes, the electron delocalization between the two metal centers increases in the following order: Fe < Ru < Os.

9.
Anticancer Res ; 21(4A): 2821-5, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11724361

RESUMO

A new member of the nm23 gene family, designated nm23-H4, was cloned recently. Nm23-H4 is a mitochondrial protein. To determine whether nm23-H4 could have a function in tumour progression like nm23-H1 or nm23-H2, we analysed nm23-H4 expression in 18 renal tumours and 42 colorectal carcinomas obtained from patients who underwent curative resection. As compared to the corresponding healthy tissue, 14 renal tumours and 41 colorectal carcinomas showed increased nm23-H4 mRNA expression. While the increase was only moderate in renal cell carcinoma, a strong overexpression of nm23-H4 was noted in most colorectal carcinomas, possibly indicating a role of this gene in tumour genesis. The nm23-H4 transcript levels did not correlate with tumour stage, grade of differentiation or lymph node involvement.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Renais/metabolismo , Proteínas Monoméricas de Ligação ao GTP/biossíntese , Núcleosídeo-Difosfato Quinase , RNA Neoplásico/biossíntese , Fatores de Transcrição/biossíntese , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Northern Blotting , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas Monoméricas de Ligação ao GTP/genética , Nucleosídeo NM23 Difosfato Quinases , Estadiamento de Neoplasias , Nucleosídeo Difosfato Quinase D , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/genética , Fatores de Transcrição/genética
10.
Eur J Cardiothorac Surg ; 20(6): 1128-34, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11717016

RESUMO

OBJECTIVE: The cytokine vascular endothelial growth factor (VEGF) is capable of triggering angiogenesis and at higher concentrations vasculogenesis. We report on a pilot study where VEGF-DNA as an additional therapy to coronary artery bypass grafting was injected into the myocardium in 24 patients (pts) with proximal coronary artery stenosis and diffuse peripheral disease. One region of the myocardium with proven ischemia remained unsupplied after surgery because the respective epicardial coronary artery was not graftable. METHODS AND RESULTS: Plasmid DNA encoding for the 165- and 167-amino acid isoform of the human VEGF genes was injected directly into the myocardium, not amenable to surgical revascularization at a dosage of 1000 microg each, using a standardized protocol. A (99m)Tc-sestamibi-SPECT at rest performed 7 days prior to the operation, had shown decreased marker activity in the region of interest. Controls were made 1 week and 80-100 days postoperatively. Transmural scarring was ruled out intraoperatively. Coronary and left ventricular angiographies were performed preoperatively and 3 months postsurgery, respectively. One or more of the following angiographic items were found in 16/24 patients postoperatively. (1) Improvement of regional left ventricular function at the VEGF treated myocardial sector (5/24 pts). (2) Newly visible vessels considered as collaterals (8/24 pts). (3) Earlier filling of parent vessels (6/24 pts). (4) An increase in diameter of preoperatively existing collateral vessels (7/24). An increased perfusion at rest in the region of gene application was detected in 3/24 patients by early postoperative (99m)Tc-sestamibi-SPECT investigation. In six additional cases, local perfusion increased markedly until the late examination. No perioperative myocardial infarctions and no signs of inflammation were observed. Newly developed abnormal vasculature was not detected in any patient. CONCLUSIONS: Direct intramyocardial administration of VEGF(165)-DNA and VEGF(167)-DNA may result occasionally in an enhancement of collateral vascularization in regions with diffuse peripheral coronary artery disease not surgically amenable. During midterm follow-up no adverse effects of VEGF-DNA application are observed so far. The very slight midterm improvements caused us to stop further VEGF-DNA application and, in our opinion, do not justify a prospective, and randomized study with a control group.


Assuntos
Doença das Coronárias/terapia , Fatores de Crescimento Endotelial/genética , Terapia Genética/métodos , Linfocinas/genética , Revascularização Miocárdica , Idoso , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , DNA/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cintilografia , Tecnécio Tc 99m Sestamibi , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
11.
Zentralbl Gynakol ; 123(8): 435-7, 2001 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-11562804

RESUMO

Personal digital assistants (PDAs) are increasingly used by many professional and private users. They replace and combine common calendars, directories, to-do-lists and much more. Supplemented by useful additional software they can assist the clinician in his daily routine work. This concerns typical medical information as well as administrative work but gets more importance with regard to the planned introduction of diagnosis related groups in Germany however. Exact coding of medical performance is essential for this future invoice system. How PDAs can be used convenient in this respect will be shown with examples from our department.


Assuntos
Grupos Diagnósticos Relacionados , Computação em Informática Médica , Microcomputadores , Software , Feminino , Alemanha , Ginecologia , Humanos , Recém-Nascido , Obstetrícia , Gravidez
13.
Ultrasound Obstet Gynecol ; 17(1): 42-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11244655

RESUMO

OBJECTIVES: It was the aim of the present study to calculate new Doppler reference ranges for blood flow velocities (Vmax, Vmean, Vmin) and resistance indices (PI, RI) for the fetal descending aorta by automatic waveform analysis. DESIGN: Cross-sectional prospective study. SUBJECTS: Nine hundred and twenty-six low-risk pregnancies at 18-41 weeks' gestation. METHODS: Aortic blood flow velocities were derived with pulsed-wave color Doppler. Measurements were carried out at the level of the diaphragm. Reference ranges for the individual measuring parameters were constructed based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. Further investigated were intra-observer reliability and the influence exerted by different measuring sites (aortic arch, diaphragm, below the renal vessels) on the aortic Doppler flow spectrum. RESULTS: Although a significant increase in aortic blood flow velocity was observed at 18-41 weeks' gestation (Vmax = 48.2 cm/s to 110.3 cm/s (P < 0.001), Vmean = 20 cm/s to 47.5 cm/s (P < 0.001) and Vmin = 7.6 cm/s to 18.6 cm/s (P < 0.001)), there were no significant changes in the pulsatility or resistance indices. The resistance indices PI and RI as well as absolute blood flow velocities (Vmax, Vmin) were significantly lower with increasing distance from the heart. Initial decreases were measured between the aortic arch and the diaphragm: PI, 2.34 to 1.87 (P < 0.0001); RI, 0.87 to 0.79 (P < 0.0001); Vmin: 8.5 cm/s to 15.0 cm/s (P < 0.0001). Furthermore, systolic blood flow velocities (Vmax) were decreased below the renal vessels from 97 cm/s to 64 cm/s (P < 0.0007). No significant changes were recorded in intensity-weighted mean flow velocities (Vmean). The intra-observer reliability was low, but of no clinical relevance. CONCLUSIONS: At constant measuring conditions, the reference ranges for blood flow velocities and resistance indices in the fetal aorta calculated by the authors serve as the basis for Doppler ultrasound antenatal examinations in a normal patient population and enable the early diagnosis of fetal risk.


Assuntos
Aorta Torácica/diagnóstico por imagem , Feto/irrigação sanguínea , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Aorta Torácica/embriologia , Velocidade do Fluxo Sanguíneo , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Variações Dependentes do Observador , Gravidez , Estudos Prospectivos , Valores de Referência
14.
Histochem J ; 33(8): 459-67, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11931386

RESUMO

Mutations in the mismatch DNA repair gene human MutS homologen 2 (hMSH2) are causative for microsatellite instability and carcinogenesis in various human tumours, including hereditary nonpolyposis colorectal cancer. Because microsatellite instability has been detected in malignant melanoma, we have investigated hMSH2 in melanocytic tumours. We found strong nuclear immunoreactivity for hMSH2 that was elevated in malignant melanoma and melanoma metastases as compared to acquired nevi. These findings suggest that increased genomic instability in malignant melanoma is associated with elevated protein levels of this DNA repair enzyme. hMSH2 is not exclusively regulated by proliferative activity in melanocytes, because there was no correlation between staining patterns of hMSH2 and the proliferation marker Ki-67. In contrast, immunoreactivity scores for hMSH2 and p53 were both upregulated in malignant melanocytic tumours. These findings support the concept that hMSH2 gene expression may be regulated in melanocytes by the p53 protein, as has been reported previously in other tissues. Using the reverse transcription-polymerase chain reaction, we detected strong hMSH2 mRNA expression in each of 8 melanoma cell lines analysed (highest amounts in SK-MEL-25 cells, lowest amounts in MML-I cells). In conclusion, our findings indicate that hMSH-2 may be of importance for genetic stability, tumorigenesis and progression of malignant melanoma.


Assuntos
Pareamento Incorreto de Bases , Reparo do DNA , Proteínas de Ligação a DNA , Melanoma/enzimologia , Nevo Pigmentado/enzimologia , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/enzimologia , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/metabolismo , Melanoma/genética , Melanoma/secundário , Proteína 2 Homóloga a MutS , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas/enzimologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
15.
Comp Med ; 50(4): 385-90, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11020156

RESUMO

BACKGROUND AND PURPOSE: Left ventricular dysfunction following myocardial infarction is the most important predictor of adverse prognosis. Novel treatment options in infarction require an appropriate experimental model with a standardized, hemodynamically relevant myocardial injury. We evaluated a cryoinjury model in rodents that allows quantitative analysis of systolic and diastolic dysfunction. METHODS: Anesthetized, orally intubated, and ventilated Lewis rats (n = 12) underwent sternotomy. Myocardial necrosis was induced by use of a standardized cryolesion to the obtuse margin of the left ventricle, freezing for 3 minutes to -160 degrees C. Left ventricular performance was analyzed at day 120 after cryoinjury. Sham-operated animals (n = 10) served as controls. RESULTS: Cryoinjured animals behaved normally and gained weight up to day 120. Average heart weight of cryoinjured animals significantly exceeded that of controls. Left ventricular systolic pressure and systolic, diastolic, and mean aortic pressures were lower 4 months after cryoinjury, whereas left ventricular end-diastolic pressure was significantly increased. Cryoinjured animals had reduced aortic blood flow, as well as impaired maximal left ventricular dP/dt during aortic occlusion and aortic occlusion-provoked peak systolic pressure. Analysis of maximal rates of isovolumic pressure decrease revealed significant reduction in peak negative dP/dt in cryoinjured animals. Finally, time constants of isovolumic pressure decline were significantly prolonged in cryoinjured animals. CONCLUSION: Standardized cryothermia induces a myocardial lesion that results in highly reproducible impairment of left ventricular performance 120 days after cryothermia. The model is ideally suited to test novel therapeutic strategies for myocardial dysfunction.


Assuntos
Cardiomiopatias/fisiopatologia , Diástole , Modelos Animais de Doenças , Congelamento , Miocárdio/patologia , Sístole , Animais , Aorta/fisiopatologia , Pressão Sanguínea , Cardiomiopatias/etiologia , Eletrocardiografia , Feminino , Necrose , Ratos , Ratos Endogâmicos Lew , Função Ventricular Esquerda
16.
J Biol Chem ; 275(48): 37469-73, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10984493

RESUMO

The tumor suppresser protein p53 is critical for guarding the genome from incorporation of damaged DNA (Lane, D. P. (1992) Nature 358, 15-16). A relevant stress that activates p53 function is UV light (Noda, A., Toma-Aiba, Y., and Fujiwara, Y. (2000) Oncogene 19, 21-31). Another well known component of the mammalian UV response is the transcription factor c-Jun (Angel, P., and Karin, M. (1991) Biochim. Biophys. Acta 1072, 129-157). We show here that upon UV irradiation p53 activates transcription of the human mismatch repair gene MSH2. Interestingly, this up-regulation critically depends on functional interaction with c-Jun. Hence, the synergistic interaction of a proto-oncogene with a tumor suppresser gene is required for the regulation of the mammalian stress response through activation of expression of MSH2.


Assuntos
Reparo do DNA/genética , Proteínas de Ligação a DNA , Regulação da Expressão Gênica/efeitos da radiação , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta , Sequência de Bases , Linhagem Celular , DNA , Humanos , Proteína 2 Homóloga a MutS , Regiões Promotoras Genéticas , Proto-Oncogene Mas , Células Tumorais Cultivadas
17.
Prenat Diagn ; 20(8): 623-34, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10951472

RESUMO

In recent years, investigations of the venous vascular system have become increasingly important in the assessment of fetal myocardial function. The aim of the present Doppler ultrasound study was to establish both new reference ranges for blood flow velocity during the different phases of the cardiac cycle (S, SD, D, a) and various calculated indices ((S-a)/S, (S-a)/V(mean), (S-a)D, S/D, a/S, S/a) for the ductus venosus. Pulsed-wave colour Doppler was used in this prospective cross-sectional study to examine 696 women with low-risk pregnancies during the period from 14 to 41 weeks' gestation. Reference curves were constructed for the individual measuring parameters based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. A significant increase in blood flow velocity from 48 cm/s to 65.8 cm/s was observed during ventricular systole (=S) from 14 to 41 week's gestation. Similarly, increases in blood flow velocity were recorded during the endsystolic phase (=SD) (35.5 cm/s to 50.7 cm/s during early ventricular diastole (=D) (41.7 cm/s to 58 cm/s, p=0.0001) and atrial contraction (=a) (11.2 cm/s to 35 cm/s, p=0.0001), as well as for intensity-weighted mean velocity (30 cm/s to 48.3 cm/s). The venous indices were associated with significant decreases in the individual parameters with increasing gestational age: (S-a)/S from 0.77 to 0.47, (S-a)/V(mean) from 1.21 to 0.67, (S-a)/D from 0.89 to 0.54, S/a from 4.5 to 1.99. A significant increase from 0.23 to 0.53 was observed only for the quotient a/S. There were no changes in the S/D quotient (from 1.15 to 1.13). Regarding intra-observer reliability, more favourable results were obtained for calculated indices than for measurements of absolute blood flow velocities. At constant measuring conditions, the reference ranges established by this study for blood flow velocities and calculated indices in the ductus venosus may serve as the basis for Doppler ultrasound follow-up in a normal patient population as well as for the diagnosis of fetal myocardial insufficiency of hypoxic and congestive origin.


Assuntos
Coração Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Veias/diagnóstico por imagem , Veias/embriologia , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo , Estudos Transversais , Diástole , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Sístole , Ultrassonografia Doppler , Veias/fisiologia
19.
Histochem J ; 32(2): 93-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10816073

RESUMO

We have analysed the expression and distribution of the DNA mismatch repair enzyme hMSH-2 in normal skin and basal cell carcinomas. hMSH-2 protein was investigated immunohistochemically (normal human skin: n = 10; basal cell carcinomas: n = 16) on frozen sections using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). In normal human skin, we found nuclear immunoreactivity for hMSH-2 in epidermal keratinocytes of the basal and first 1-3 suprabasal cell layers. All basal cell carcinomas analysed revealed strong nuclear imunoreactivity that was pronounced in peripheral tumour cells and cells of the palisade. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of the carcinomas as compared to adjacent unaffected epidermis or epidermis of normal human skin. Twelve of the sixteen carcinomas analysed revealed no visual correlation in comparing the labelling patterns for hMSH-2 with the labelling pattern for the proliferation marker Ki-67. Our findings indicate that (a) hMSH-2 is expressed in human epidermal keratinocytes, predominantly in lower cell layers of the viable epidermis; (b) expression of hMSH-2 protein is strongly upregulated in basal cell carcinomas as compared to unaffected epidermis; (c) the level of hMSH-2 proteins in the carcinomas is not exclusively regulated by the proliferative activity of these tumour cells; (d) inactivating mutations of the hMSH-2 gene may in the carcinomas not be involved in the carcinogenesis or microsatellite instability secondary to replication errors; (e) expression of hMSH-2 may be of importance for the genetic stability of basal cell carcinomas in vivo.


Assuntos
Adenosina Trifosfatases/metabolismo , Pareamento Incorreto de Bases , Carcinoma Basocelular/enzimologia , Reparo do DNA , Proteínas de Ligação a DNA , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/enzimologia , Pele/enzimologia , Carcinoma Basocelular/patologia , Humanos , Técnicas Imunoenzimáticas , Queratinócitos/enzimologia , Antígeno Ki-67/metabolismo , Proteína 2 Homóloga a MutS , Neoplasias Cutâneas/patologia , Regulação para Cima
20.
Ultrasound Obstet Gynecol ; 16(6): 564-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11169352

RESUMO

OBJECTIVES: To evaluate the improvement of image quality and diagnostic value of fetal face examinations using the electric scalpel. METHODS: A total of 232 cases were examined. The fetuses were separated into two groups: Group A, including normal fetuses (n = 152) and Group B, fetuses with facial pathology (n = 80). The fetuses were divided into eight subgroups according to gestational age (9-12 weeks, 13-16 weeks, 17-20 weeks, 21-24 weeks, 25-28 weeks, 29-32 weeks, 33-36 weeks and 37-40 weeks). RESULTS: The number of cutting steps for the improvement of image quality ranged from 1 to 9 (mean value 3) in the group of normal fetuses and from 1 to 10 (mean value 3) in the group of fetuses with facial pathology. In the group of normal fetuses, superior image quality improvement was achieved in 68.4% of cases, moderate improvement in 28.9% and poor improvement in 2.6%. In the group of fetuses with facial pathology, high image quality improvement was obtained in 72.5% of cases, moderate improvement in 25.0% and insufficient improvement in 2.5%. There were no differences among the eight subgroups in the number of steps required relating to gestational age. CONCLUSIONS: The use of the electronic scalpel was associated with diagnostic improvement in 71.1% of cases in the group of normal fetuses, and in 75.0% in the group of fetuses with facial pathology.


Assuntos
Face/anormalidades , Doenças Fetais/diagnóstico por imagem , Imageamento Tridimensional , Ultrassonografia Pré-Natal/métodos , Face/embriologia , Feminino , Humanos , Gravidez
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