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1.
Nanotechnology ; 30(4): 045702, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30460927

RESUMO

Rare earth (RE) ions doped in Si-based materials, compatible with Si technology, are promising compounds with regards to optical communication and energy conversion. In this article, we show the emission properties of Nd-doped Si-rich Si oxynitride (Nd-SRSON) films, and their dependence on the dangling bond density and the nature of the sensitizer. These films were prepared by reactive magnetron sputtering and post-annealing. The film composition, microstructure, and emission properties were investigated as a function of deposition parameters and annealing temperatures. Both Fourier transform infrared (FTIR) and ellipsometry spectroscopy measurements have confirmed that the sample composition (Si/N ratio) can be carefully tuned by varying the ratio of reactive nitrogen to argon in the sputtering plasma. Moreover, FTIR and x-ray photoelectron spectroscopy measurements demonstrate the existence of both nitrogen and oxygen dangling bonds (N· and O·) in as-deposited samples. These dangling bonds were passivated during annealing. Under non-resonant excitation at 488 nm, the films exhibit a significant photoluminescence (PL) signal from Nd3+ ions demonstrating the occurrence of an effective sensitization of Nd3+ ions in the host matrix. Both PL excitation and ellipsometry results (the energy band gap from new amorphous model) exclude the sensitization by an exciton with energy over the band gap, whereas the presence of Si agglomerates, at the atomic scale, have been identified as effective sensitizers towards Nd3+ ions. This work not only provides knowledge to optimize Si-based materials for favorable emission properties, but also, presents a universal methodology to investigate the nature of sensitizers for RE emitters. This allows one to find correlations between composition, microstructure, and emission properties.

2.
Phys Chem Chem Phys ; 17(16): 10737-48, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25811299

RESUMO

Based on first-principles plane-wave calculations, functionalization of the two-dimensional single-layered GaSe structure through vacancy and chemical element doping has been investigated. Our calculations show that the pristine GaSe monolayer, which is normally a non-magnetic, indirect-band-gap semiconductor, can induce net magnetic moments by introduction of Ga mono-vacancy, Ga di-vacancy, and GaSe3 and Ga2Se6 vacancy complexes. Magnetic moments can also be induced by selectively doping specific transition-metal atoms as well as A group atoms. The introduced donor or acceptor states are localized in the band gap, which expands the utilization of the single-layered GaSe in nanoelectronics and spintronics. In spite of the intrinsic p-type character of the two-dimensional GaSe material, substitution of Si for Ga and substitution of Cl for Se exhibit n-type character at relatively low dopant concentrations. These findings will provide useful supplements to the experimental studies on the newly synthesized two-dimensional layered metal monochalcogenides, which allows us to go beyond the current scope that is limited to applications within graphene, BN, and transition-metal dichalcogenide-based nanostructures.

3.
J Periodontal Res ; 50(5): 594-601, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25369875

RESUMO

BACKGROUND AND OBJECTIVE: The influence of diabetes mellitus (DM) on the hemodynamics of periodontal tissues has not been assessed previously. The primary objective of this study was to validate optical spectroscopy as a periodontal diagnostic tool for subjects with type 2 DM and chronic periodontitis. MATERIAL AND METHODS: Using a portable optical near-infrared spectrometer, optical spectra were obtained from healthy (n = 127), gingivitis (n = 115), and periodontitis (n = 109) sites of 65 subjects with type 2 DM and chronic periodontitis. Healthy (n = 65) sites of 15 nondiabetic subjects without periodontitis were used as controls. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering-loss function was used to determine the relative contribution of deoxygenated hemoglobin and oxygenated hemoglobin (HbO2 ) to the overall spectrum. The balance between tissue oxygen delivery and oxygen utilization in periodontal tissues was assessed. RESULTS: In diabetic subjects, tissue oxygen saturation and HbO2 concentration were significantly decreased in the periodontitis sites (p < 0.01) compared with the healthy and gingivitis sites. Furthermore, tissue oxygenation in healthy sites of control subjects was significantly higher than that in sites of diabetic subjects (p < 0.01). CONCLUSION: In summary, the results of this study suggest that optical spectroscopy can monitor the hemodynamic profile in diabetic subjects with chronic periodontitis. Furthermore, healthy sites of diabetic subjects presented lower tissue oxygenation than did those of nondiabetic subjects.


Assuntos
Periodonto , Gengivite/diagnóstico , Hemodinâmica , Humanos , Periodontite , Análise Espectral
4.
Int J Oral Maxillofac Surg ; 41(5): 673-80, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22197592

RESUMO

This study evaluated the effectiveness of silk fibroin materials for wound repair confined to the buccal mucosa in a rat model by assessing several key clinical parameters and the associated local and systemic immune response. Ninety male SD rats were subjected to microscopic oral surgery to establish a full thickness wound on the buccal mucosa. Rats were randomly divided into three groups based on the treatments received: group A, covered with polyporous silk fibroin scaffold; group B, repaired with crosslinking silk fibroin film; and group C, control. Visual observation of the wounds suggests that wound shrinkage 5 days after the operation was significantly lower in both silk fibroin repaired groups (A and B) than that in the controls. The distribution of inflammatory neutrophils in group A was significantly lower than those in the control group throughout the entire study. The percentage of fibroblasts and capillary endothelia (CD34(+)), and the subgroups of peripheral lymphocytes (CD3(+), CD4(+), CD8(+)) were similar amongst the groups. The results revealed that placement of silk fibroin in an oral buccal defect can reduce the degree of wound shrinkage and enhance the growth of mucosal epithelial cells without any local or systemic immunological incompatibility.


Assuntos
Fibroínas/uso terapêutico , Mucosa Bucal/cirurgia , Técnicas de Fechamento de Ferimentos , Animais , Antígenos CD34/análise , Complexo CD3/análise , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Capilares/patologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Células Epiteliais/patologia , Fibroblastos/patologia , Queratinas/análise , Masculino , Membranas Artificiais , Modelos Animais , Mucosa Bucal/patologia , Neutrófilos/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tampões de Gaze Cirúrgicos , Subpopulações de Linfócitos T/classificação , Fatores de Tempo , Alicerces Teciduais , Cicatrização/fisiologia
5.
J Periodontal Res ; 46(3): 382-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21392007

RESUMO

BACKGROUND AND OBJECTIVE: Optical spectroscopy has been proposed to measure regional tissue hemodynamics in periodontal tissue. The objective of this study was to further evaluate the diagnostic potential of optical spectroscopy in peri-implant inflammation in vivo by assessing multiple inflammatory parameters (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) simultaneously. MATERIAL AND METHODS: A cross-sectional study was performed in a total of 64 individuals who presented with dental implants in different stages of inflammation. In brief, visible-near-infrared spectra were obtained, processed and evaluated from healthy (n = 151), mucositis (n = 70) and peri-implantitis sites (n = 75) using a portable spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was employed to determine the relative contribution of each inflammatory component to the overall spectrum. RESULTS: Tissue oxygenation at peri-implantitis sites was significantly decreased (p < 0.05) when compared with that at healthy sites, which was largely due to an increase in deoxyhemoglobin and a decrease in oxyhemoglobin at the peri-implantitis sites compared with the mucositis and healthy sites. In addition, the tissue hydration index derived from the optical spectra in mucositis was significantly higher than that in other groups (p < 0.05). CONCLUSION: In summary, the results of this study revealed that hemodynamic alterations can be detected around diseased peri-implant sites by optical spectroscopy, and this method may be considered an alternative and feasible approach for the monitoring and diagnosis of peri-implant diseases.


Assuntos
Peri-Implantite/diagnóstico , Análise Espectral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Perda do Osso Alveolar/classificação , Estudos Transversais , Índice de Placa Dentária , Edema/diagnóstico , Estudos de Viabilidade , Feminino , Hemorragia Gengival/classificação , Hemoglobinas/análise , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fibras Ópticas , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Oxiemoglobinas/análise , Peri-Implantite/patologia , Bolsa Periodontal/classificação , Periodonto/anatomia & histologia , Radiografia Dentária Digital , Espectrofotometria Infravermelho , Análise Espectral/instrumentação , Estomatite/diagnóstico
6.
J Periodontal Res ; 45(3): 345-52, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20337898

RESUMO

BACKGROUND AND OBJECTIVE: Periodontitis is currently diagnosed almost entirely on gross clinical manifestations that have been in situ for more than 50 years without significant improvement. The general objective of this study was, therefore, to evaluate whether mid-infrared spectroscopy can be used to identify disease-specific molecular alterations to the overall biochemical profile of tissues and body fluids. MATERIAL AND METHODS: A total of 190 gingival crevicular fluid samples were obtained from periodontitis (n = 64), gingivitis (n = 61) and normal sites (n = 65). Corresponding infrared absorption spectra of gingival crevicular fluid samples were acquired and processed, and the relative contributions of key functional groups in the infrared spectra were analysed. The qualitative assessment of clinical relevance of these gingival crevicular fluid spectra was interpreted with the multivariate statistical analysis-linear discriminant analysis. RESULTS: Using infrared spectroscopy, we have been able to identify four molecular signatures (representing vibrations in amide I, amide II/tyrosine rings and symmetric and asymmetric PO2- stretching vibrations of phosphodiester groups in DNA) in the gingival crevicular fluid of subjects with periodontitis or gingivitis and healthy control subjects that clearly demarcate healthy and diseased periodontal tissues. Furthermore, the diagnostic accuracy for distinction between periodontally healthy and periodontitis sites revealed by multivariate classification of gingival crevicular fluid spectra was 98.4% for a training set of samples and 93.1% for a validation set. CONCLUSION: We have established that mid-infrared spectroscopy can be used to identify periodontitis-specific molecular signatures in gingival crevicular fluid and to confirm clinical diagnoses. Future longitudinal studies will assess whether mid-infrared spectroscopy represents a potential prognostic tool, recognized as key to advancement of periodontics.


Assuntos
Biomarcadores/análise , Periodontite Crônica/metabolismo , Líquido do Sulco Gengival/química , Espectrofotometria Infravermelho/métodos , Amidas/química , Carbono/química , Feminino , Hemorragia Gengival/metabolismo , Gengivite/metabolismo , Humanos , Hidrogênio/química , Bases de Conhecimento , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Nitrogênio/química , Oxigênio/química , Perda da Inserção Periodontal/metabolismo , Bolsa Periodontal/metabolismo , Fosfatos/química , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier
7.
J Int Med Res ; 37(3): 662-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19589248

RESUMO

Chinese herbs are widely used in the treatment of chronic viral hepatitis B. The effectiveness of 2 months' treatment with Astragali compound (AC), containing Radix Astragali and adjuvant components, was studied for the treatment of chronic viral hepatitis in 116 patients; 92 patients were given other drugs in regular clinical use for viral hepatitis (controls). The clinical efficacy of AC was significantly better in AC-treated patients than in controls. Negative seroconversions of hepatitis B virus (HBV) antigen e and HBV DNA were also significantly higher in AC-treated patients than in controls. Of eight duck viral hepatitis B models infected with duck hepatitis B virus (DHBV) and treated with AC, three showed negative seroconversion of DHBV DNA and serum DHBV DNA levels significantly decreased after AC administration compared with the controls; DHBV DNA was negative in biopsied liver tissue by in situ hybridization and immunohistochemistry in two ducks treated with AC. Pathological changes were milder in AC-treated ducks than in controls. These results indicate that AC may promote recovery from viral hepatitis and inhibit HBV replication.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite Viral Animal/tratamento farmacológico , Animais , DNA Viral/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite B Crônica/sangue , Hepatite Viral Animal/sangue , Humanos , Resultado do Tratamento
8.
J Periodontal Res ; 44(1): 117-24, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18973538

RESUMO

BACKGROUND AND OBJECTIVE: Visible, near-infrared (optical) spectroscopy can be used to measure regional tissue hemodynamics and edema and therefore may represent an ideal tool with which to study periodontal inflammation in a noninvasive manner. The study objective was to evaluate the ability of optical spectroscopy to determine simultaneously multiple inflammatory indices (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) in periodontal tissues in vivo. MATERIAL AND METHODS: Spectra were obtained, processed and evaluated from healthy, gingivitis and periodontitis sites (n = 133) using a portable optical, near-infrared spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was used to determine the relative contribution of each inflammatory component to the overall spectrum. RESULTS: Optical spectroscopy was harnessed to generate complex inflammatory profiles of periodontal tissues. Tissue oxygenation at periodontitis sites was significantly decreased (p < 0.05) compared to sites with gingivitis and healthy controls. This was largely the result of an increase in deoxyhemoglobin in the periodontitis sites compared with healthy (p < 0.01) and gingivitis (p = 0.05) sites. Tissue water content per se showed no significant difference between the sites, but a water index associated with tissue electrolyte levels and temperature differed significantly between periodontitis sites and both healthy and gingivitis sites (p < 0.03). CONCLUSION: This study established that optical spectroscopy can simultaneously determine multiple inflammatory indices directly in the periodontal tissues in vivo. Visible, near-infrared spectroscopy has the potential to be developed into a simple, reagent-free, user-friendly, chairside, site-specific, diagnostic and prognostic test for periodontitis.


Assuntos
Periodontite Crônica/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Temperatura Corporal/fisiologia , Água Corporal/química , Periodontite Crônica/sangue , Periodontite Crônica/patologia , Edema/sangue , Edema/diagnóstico , Edema/patologia , Feminino , Hemorragia Gengival/patologia , Gengivite/sangue , Gengivite/diagnóstico , Gengivite/patologia , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Oxiemoglobinas/análise , Perda da Inserção Periodontal/patologia , Índice Periodontal , Bolsa Periodontal/patologia , Periodonto/metabolismo , Periodonto/patologia , Equilíbrio Hidroeletrolítico/fisiologia
9.
Biochim Biophys Acta ; 1762(8): 775-80, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16928431

RESUMO

Matrix metalloproteinase (MMP)-8 has been associated with the progression of periodontitis, a common inflammatory disease of the supporting structures of the teeth, and with other degradative diseases. Tobacco smokers are at high risk of developing periodontitis that may progress more rapidly and respond poorly to treatment. Therefore, MMP-8 expression was determined by immunofluorescence staining in 60 random, computer-selected fields in the excised periodontal tissues of smokers and non-smokers, balanced for age, gender, and periodontal status. Immunofluorescence intensity, representing MMP-8 expression, in the periodontal tissues of smokers (30 fields from 6 subjects, mean 1154+/-124 units) was significantly higher than that in the periodontal tissues of non-smokers (30 fields from 6 subjects, mean 817+/-60 units; p < 0.05). Serum MMP-8 concentrations were measured by ELISA and compared in a larger group of smokers (n = 20) and age- and gender-balanced non-smokers (n = 20). Systemic MMP-8 concentrations in smokers and non-smokers were not significantly different (p > 0.05). A local tobacco-related increase in MMP-8 burden may contribute to periodontal disease progression in tobacco smokers. This finding may also have relevance to other tobacco-induced inflammatory diseases, such as vascular and pulmonary diseases.


Assuntos
Tecido Conjuntivo/enzimologia , Metaloproteinase 8 da Matriz/metabolismo , Doenças Periodontais/enzimologia , Periodonto/enzimologia , Fumar/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Periodonto/citologia
10.
J Mol Med (Berl) ; 81(12): 788-94, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14556052

RESUMO

Infrared (IR) spectroscopy can distinguish differences in the characteristics of diverse molecules by using infrared radiation to probe chemical bonds. Consequently, alterations to the molecular characteristics of tissues and body fluids that help define specific pathological processes and conditions can be identified by IR spectroscopy. This study analyzed the molecular spectrum of cotinine by IR spectroscopy and determined tobacco-induced alterations to the IR profile of serum to establish whether these alterations can differentiate smokers and nonsmokers. The IR spectra of serum samples obtained from 20 smokers and 25 nonsmokers were captured using a FTS-40 IR spectrometer. Linear discriminant analysis method was used to partition the samples into smoker and nonsmoker groups according to the discriminatory patterns in the data and into a validation set to test the accuracy of the trained algorithm in distinguishing smokers and nonsmokers. Cotinine molecules were shown to exhibit a characteristic IR absorption spectrum. Several differences in the sera spectra of the two groups were observed, including an overall shift in the secondary structure of serum proteins favoring increased beta-sheet content in smokers. The overall accuracy of the training and validation sets was 96.7%, and 82.8%, respectively. The identification of specific absorption peaks for tobacco-induced alterations to the IR molecular profile of serum permits the development of an IR spectroscopy technique that can be used to differentiate smokers from nonsmokers. This further extends the utility of IR spectroscopy as a rapidly emerging tool in the field of molecular biodiagnostics.


Assuntos
Cotinina/sangue , Fumar/sangue , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Detecção do Abuso de Substâncias/métodos , Tabagismo/diagnóstico , Adulto , Cromatografia Gasosa , Cotinina/química , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Nicotina/sangue , Nicotina/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/normas , Detecção do Abuso de Substâncias/normas
11.
Apoptosis ; 6(4): 269-78, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11445669

RESUMO

Quantitation of apoptotic cell death in vivo has become an important issue for patients with acute leukemia. We describe herein a new analytical method, based on infrared (IR) spectroscopy, to estimate the percentage of apoptotic leukemic cells in two different cell lines (CEM and K562), induced with etoposide (VP-16). As the percentage of apoptosis increases, the protein structure shifts from dominantly beta-sheet to unordered (random coil), the overall lipid content increases and the amount of detectable DNA decreases. These changes can be directly related to the percentage of apoptosis as determined by two standard reference methods: flow cytometry and DNA ladder formation. The correlation between the significant IR spectral changes and the percentage of apoptotic leukemia cells in the two cell lines was optimal up to 24 h following etoposide treatment (r = 0.99 for CEM cells and r = 0.96 for K562 cells). Furthermore, IR spectroscopy is able to detect apoptotic changes in these cells already after 4 h treatment with VP-16, compared to flow cytometry which needs 6 h to observe significant changes. Our study suggests that IR spectroscopy may have potential clinical utility for the early, fast and reagent free assessment of chemotherapeutic efficacy in patients with leukemia.


Assuntos
Apoptose , Leucemia/patologia , Espectrofotometria Infravermelho , Contagem de Células , Etoposídeo/farmacologia , Citometria de Fluxo , Células Tumorais Cultivadas
12.
Am J Obstet Gynecol ; 183(1): 181-7, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10920328

RESUMO

OBJECTIVE: Infrared spectroscopic analysis of amniotic fluid was recently shown to be a potential useful method for the determination of fetal lung maturity. Those studies used thin-layer chromatography as a reference method for the calibration of the infrared-based technique. However, thin-layer chromatography is compromised by large intra-assay and interlaboratory coefficients of variation. Therefore in this study we have used a reference method that is based on fluorescence depolarization, the TDx FLM II assay, to verify the sensitivity and precision of infrared spectroscopy for assessment of fetal lung maturity status. STUDY DESIGN: Samples of amniotic fluid were obtained by amniocentesis from 101 patients between the 24th and 40th weeks of pregnancy. Small volumes (35 microL) of amniotic fluid specimens were dried, and the infrared spectra were measured with a commercial infrared spectrometer. The fetal lung surfactant/albumin ratio was determined separately for each specimen with the TDx FLM II assay. The proposed infrared method was then calibrated and tested with a partial least-squares regression analysis to quantitatively correlate the infrared spectra with the surfactant/albumin ratios provided by the TDx FLM II assays. RESULTS: A total of 144 training spectra were used to build the partial least-squares calibration model. The correlation coefficient for the training set was excellent (r = 0.92), with an SE between infrared-predicted and reference surfactant/albumin ratios of 17 mg/g. The model was then validated on a set of 69 test spectra and yielded an SE of 14 mg/g (r = 0.86). The final partial least-squares model included the 900- to 1500-cm(-1) and 2800- to 3200-cm(-1) spectral ranges and 6 partial least-squares factors. CONCLUSION: Because the infrared-based fetal lung maturity measurements correlated well with assays from both of the current standard clinical techniques (thin-layer chromatography and fluorescence depolarization) and the procedure is less labor and training intensive, we concluded that infrared spectroscopy has the potential to emerge as the method of choice for prediction of fetal lung maturity from amniotic fluid analysis.


Assuntos
Albuminas/análise , Líquido Amniótico/química , Maturidade dos Órgãos Fetais , Pulmão/embriologia , Surfactantes Pulmonares/análise , Espectrofotometria Infravermelho , Cromatografia em Camada Fina , Feminino , Fluorometria , Idade Gestacional , Humanos , Gravidez , Análise de Regressão , Sensibilidade e Especificidade
13.
Int J Mol Med ; 5(4): 341-7, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10719048

RESUMO

WSU-CLL cells, a fludarabine resistant B-cell chronic lymphocytic leukemia cell line, has been shown to exhibit enhanced sensitivity to 2-chlorodeoxyadenosine (2-CdA) following 48-72 h exposure to bryostatin 1. For 2-CdA to manifest its chemotherapeutic activity, it must first enter the cell through one of several specific nucleoside transporter systems. We present data to show that bryostatin 1-induced enhanced influx of 2-CdA is in part the result of bryostatin 1-induced modulation of nucleoside transporters in WSU-CLL cells. The bi-directional equilibrative NBMPR sensitive transporters in WSU-CLL cells were significantly down-regulated 90 min post-exposure to 1-200 nM bryostatin 1. This down-regulation was evident up to 144 h. In contrast, WSU-CLL cells exhibited a transient increase in Na+-dependent concentrative 2-CdA influx from 48 to 96 h after bryostatin 1 exposure which was evident for a longer duration than that accounted for by the increase in deocycytidine kinase activity. These data may, in part, explain the enhanced efficacy of 2-CdA seen in WSU-CLL cells following 48-72 h exposure to bryostatin 1. It may raise questions as to the importance of the bi-directional transporters in determining the resistance or sensitivity of CLL cells to 2-CdA or other nucleoside analogues.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Transporte/metabolismo , Cladribina/metabolismo , Lactonas/farmacologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Proteínas de Membrana/metabolismo , Idoso , Transporte Biológico Ativo/efeitos dos fármacos , Briostatinas , Desoxicitidina Quinase/metabolismo , Dipiridamol/farmacologia , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Macrolídeos , Masculino , Proteínas de Transporte de Nucleosídeos , Fosforilação , Tioinosina/análogos & derivados , Tioinosina/farmacologia , Células Tumorais Cultivadas , Vidarabina/análogos & derivados , Vidarabina/farmacologia
14.
Br J Haematol ; 107(4): 861-9, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10606895

RESUMO

Cells of solid tumours tend to rely on glycolysis for energy. On the other hand, increased glycolysis in solid tumour cells expressing the multidrug resistance protein MDR-1 has been associated with increased malignancy in tumours. We have previously shown that cells of the MDR-1-positive CEM/VLB100 leukaemic cell line have increased mitochondrial electron transport chain (mtETC) activity compared with parental CEM cells. In the present study we used infrared (IR) spectroscopy to demonstrate that the mitochondrial DNA (mtDNA) content in the CEM/VLB100 cell line was significantly increased compared to that in the parental CEM cells. The increase in mtDNA was not accompanied by an increase in mitochondrial protein as both lipid and protein levels were decreased in CEM/VLB100 mitochondria. The ATP content was similar in these two cell lines. However, the ATP-dependent membrane efflux pump function in CEM/VLB100 cells was significantly reduced when mitochondrial ATP synthesis was inhibited by oligomycin, a specific inhibitor of mitochondrial F0F1-ATPase. Proliferation of CEM/VLB100 cells was significantly decreased compared to parental CEM cells, and was independent of p53 expression. Thus, we conclude that: (1) IR spectroscopy is a potential powerful technique for detecting mtDNA, protein and lipid contents simultaneously; (2) leukaemic cells mainly rely on mtDNA for energy; (3) increased expression of an ATP-dependent membrane efflux pump such as Pgp may up-regulate ATP generation and mtDNA content. These metabolic perturbations may exist merely to serve the efflux pump and do not result in an increase in leukaemic cell proliferation. In addition, the associated reduction in mitochondrial lipid and protein may contribute to sensitize the cells to cytochrome c release.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , DNA Mitocondrial/metabolismo , Leucemia/metabolismo , Divisão Celular/fisiologia , Resistência a Múltiplos Medicamentos , Humanos , Leucemia/patologia , Células Tumorais Cultivadas
15.
Leukemia ; 13(8): 1273-80, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10450757

RESUMO

Previous studies on intact cells have shown that bryostatin 1 (Bryo 1) induces significant alterations in the membranes of WSU-CLL cells (a drug-resistant B-CLL cell line), changes which may play an important role in the mechanism of reduced drug resistance of B-CLL cells to 2-chlorodeoxyadenosine (2-CdA). However, it is not clear whether the plasma membranes or the mitochondria, or both are involved; nor is it known which of these two targets is more important for regaining the cells former drug sensitivity. For the present study, we treated WSU-CLL cells with Bryo 1, isolated plasma membranes and mitochondria, and then subjected the purified fractions to infrared (IR) spectroscopic and chromatographic analyses. IR spectroscopy revealed a decreased glycosylation of both plasma membranes and mitochondria in Bryo 1-treated cells compared to untreated cells. The amount of lipid relative to protein was increased in both types of membranes, but considerably more enhanced in the plasma membrane fraction of the Bryo 1-treated cells than in mitochondria. Quantitative lipid analysis by thin layer chromatography also revealed that Bryo 1 treatment significantly increased the phospholipid content in plasma membranes, whereas the lipids in the mitochondria remained essentially unchanged. Changes in lipid composition were quite dramatic for plasma membranes where phosphatidylcholines were decreased by 50%, phosphatidylethanolamines doubled and sphingomyelins increased five-fold compared to the lipid composition in plasma membranes of untreated cells. In addition, the IR spectroscopic analysis provided evidence for an increased plasma membrane fluidity in Bryo 1-treated cells, whereas the fluidity of the mitochondria remained essentially unchanged; marker bands indicating mitochondrial DNA decreased upon Bryo 1 treatment. These results suggest that Bryo 1 increases the sensitivity of WSU-CLL cells to chemotherapeutic agents such as 2-CdA by action on two cell targets: (1) introduction of significant changes in plasma membrane permeability or fluidity through modifications in lipid content and composition as well as by reducing the surface glycosylation; (2) introduction of changes in lipid and DNA content of the mitochondria. Small alterations in the lipid composition of the mitochondria may provide the conditions for an altered proton gradient and transmembrane potential leading to apoptosis and decreased cell survival.


Assuntos
Antineoplásicos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/patologia , Lactonas/farmacologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Antineoplásicos/uso terapêutico , Briostatinas , Membrana Celular/química , Resistencia a Medicamentos Antineoplásicos , Humanos , Lactonas/uso terapêutico , Macrolídeos , Lipídeos de Membrana/química , Proteínas de Membrana/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Células Tumorais Cultivadas
16.
Am J Obstet Gynecol ; 180(3 Pt 1): 696-702, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10076150

RESUMO

OBJECTIVE: The purpose of this study was to assess the feasibility of using infrared spectroscopy to simultaneously predict preterm infection, fetal distress, and fetal lung maturity. STUDY DESIGN: A total of 189 infrared spectra were acquired from amniotic fluid obtained by amniocentesis. The concentrations of glucose and lactate and the lecithin/sphingomyelin ratios were determined separately by accepted clinical chemistry methods for each sample. Infrared spectra were recorded with a commercial spectrometer and 35 microL amniotic fluid was used for each spectrum. Calibration models (partial least squares) were derived from the correlation between 102 infrared spectra and clinical standard analyses; the model was then validated with the remaining 87 spectra. RESULTS: By means of the multivariate technique of partial least squares regression, calibration models for glucose and lactate were developed that had excellent correlation coefficients (r = 0.97 for glucose and r = 0. 91 for lactate); the SEs of calibration were 0.04 mmol/L for glucose and 0.09 mmol/L for lactate. The validation sets for the quantitation of glucose and lactate predicted by the calibration models also yielded good outcomes (r = 0.95 for glucose and r = 0.71 for lactate, with SEs of prediction of 0.06 mmol/L and 0.18 mmol/L, respectively). CONCLUSION: Infrared spectroscopy has the potential to become the clinical method of choice for simultaneously predicting preterm infection, fetal distress, and fetal lung maturity.


Assuntos
Líquido Amniótico/química , Doenças Fetais/diagnóstico , Glucose/análise , Ácido Láctico/análise , Fosfatidilcolinas/análise , Esfingomielinas/análise , Feminino , Sofrimento Fetal/diagnóstico , Maturidade dos Órgãos Fetais , Humanos , Pulmão/embriologia , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Espectrofotometria Infravermelho/métodos
17.
Cardiovasc Pathol ; 8(1): 41-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10722247

RESUMO

Fibrillar collagens are major proteins of the cardiac extracellular matrix and play a significant role in the structural organization of the healthy heart. The aim of this study was (i) to investigate and compare the patterns of cardiac collagen deposition in different layers taken from both cardiomyopathic and normal myocardium using infrared (IR) microspectroscopy and (ii) to evaluate IR microspectroscopy as an alternative means for in vitro detection of collagen deposition in heart. Frozen sections from UM-X7.1 strain hamsters expressing the cardiomyopathic phenotype associated with ventricular remodeling and age-matched control (F1-beta) strain hamsters were examined using IR microspectroscopy. The presence of collagen was identified by the appearance of a typical collagen band at 1204 cm(-1), and the results were compared with identical tissue sections stained with trichrome, a routine discriminator for interstitial matrix proteins in cardiac myocytes. Spatial information addressing collagen deposition was obtained and viewed using contour mapping and three-dimensional band intensity maps at 1204 cm(-1). Perivascular and interstitial collagen deposition was detected in control samples taken from both ventricles as indicated with relative low intensities of the band of 1204 cm(-1). When compared with these control levels, the concentration of collagen was increased in cardiomyopathic left-ventricular samples with some focal depositions, and these results were confirmed with the trichrome references. Our study suggests that collagen deposition from normal and diseased hearts may be successfully analyzed directly in the absence of any chemihistological or immunological staining, by infrared microscopy.


Assuntos
Cardiomiopatias/metabolismo , Colágeno/metabolismo , Microscopia/métodos , Miocárdio/metabolismo , Animais , Peso Corporal , Cardiomiopatias/genética , Cardiomiopatias/patologia , Colágeno/análise , Cricetinae , Modelos Animais de Doenças , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Feminino , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Miocárdio/patologia , Tamanho do Órgão , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Oncol Res ; 10(5): 277-86, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9802063

RESUMO

Fourier transform infrared (FTIR) microspectroscopy is emerging as a promising new tool for histopathological investigations of tissue histochemistry. This study was designed to assess whether changes in tissue biochemistry induced by well-differentiated and poorly differentiated oral/oropharyngeal squamous cell carcinoma (SCC) can be detected by infrared spectroscopy. The biopsies analyzed were each proven SCC positive and compared with tissue taken from the contralateral normal site. Individual infrared spectra, recorded from specific tissue areas, were correlated with histopathological structures normally found in the oral mucosa. Infrared mapping of these areas allows the generation of biochemical images of molecular structures such as lipids, sugars, and proteins. The visualization of DNA and tissue structures containing keratin (well expressed in all epithelia) reveals distinct differences between normal and SCC-positive biopsies. Bivariate histogram analysis of cell components (e.g., DNA and keratin) indicated that cancer cells produce a relatively homogeneous and clearly abnormal cell biochemistry, whereas differentiated epithelial cells present a very heterogeneous distribution of cellular components. Using these features, tissue containing abnormal or cancer cells can easily be distinguished from normal epithelial structures. The abnormal keratin distribution in poorly differentiated SCC and in keratin pearls (present only in well-differentiated SCC) offers insight into the process of malignant tissue transformation in squamous epithelium. Applying infrared microspectroscopy in combination with bivariate statistics to histopathological tissue thin sections provides a potential diagnostic tool for detection of cell changes in epithelial cancers.


Assuntos
Carcinoma de Células Escamosas/patologia , Queratinas/metabolismo , Neoplasias Bucais/patologia , Neoplasias Faríngeas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , DNA/análise , Feminino , Humanos , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/química , Mucosa Bucal/citologia , Neoplasias Bucais/metabolismo , Neoplasias Faríngeas/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Anal Biochem ; 259(2): 181-6, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9618195

RESUMO

We report on the use of glass substrates for the infrared spectroscopic analysis of dried serum, amniotic fluid, and synovial fluid films. New analytical applications of infrared spectroscopy are emerging rapidly, spurred largely by ever-improving instrumentation, combined with the widespread availability of powerful chemometric methods. We have recently begun to focus upon potential applications in both clinical chemistry and medical diagnostics. For example, serum analysis, the determination of fetal lung maturity, and the differential diagnosis of arthritis have all recently been demonstrated to be feasible on the basis of the infrared spectra of films dried from the appropriate samples (serum, amniotic fluid, or synovial fluid). However, the transition from the laboratory into clinical usage hinges on the availability of IR-transparent substrates that are both inexpensive and readily obtainable. We have demonstrated in this study that despite limited transparency in the IR region, clinical analyses and diagnostic spectral classifications may nevertheless be carried out using glass as a substrate for the IR measurements.


Assuntos
Líquido Amniótico/química , Análise Química do Sangue , Vidro , Espectrofotometria Infravermelho/métodos , Líquido Sinovial/química , Artrite/diagnóstico , Diagnóstico Diferencial , Humanos , Fosfatidilcolinas/análise , Esfingomielinas/análise , Triglicerídeos/sangue
20.
Cancer Lett ; 127(1-2): 185-93, 1998 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-9619876

RESUMO

Infrared (IR) spectroscopy was used to compare the drug resistance mechanism of cells from chronic lymphocytic leukemia (CLL) patients with that of WSU-CLL cells. Bryostatin 1 (Bryo 1), a macrocyclic lactone and protein kinase C activator, was used to render WSU-CLL cells more susceptible to 2-chlorodeoxyadenosine (2-CdA). The IR spectroscopic analysis revealed some changes in protein and DNA content in Bryo 1-treated WSU-CLL cells, however, the most significant alterations were observed in the membrane lipids, which resemble those found between 2-CdA-sensitive and 2-CdA-resistant cells from CLL patients. In addition, Bryo 1 treatment induced WSU-CLL cells to become CD11c, CD25 and tartrate-resistant acid phosphatase-positive, specific markers for hairy cell leukemia, a disease exquisitely sensitive to 2-CdA. Our results suggest that 2-CdA-sensitive CLL cells have cellular characteristics resembling the hairy cell stage. The similarity between the membrane lipids in 2-CdA-sensitive CLL cells and the Bryo 1-treated WSU-CLL cell line supports the suggestion that membrane lipid alteration might be an important step in the drug resistance mechanism of CLL cells.


Assuntos
Cladribina/farmacologia , Lactonas/farmacologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/farmacologia , Briostatinas , Resistência a Medicamentos , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Macrolídeos , Masculino , Pessoa de Meia-Idade , Espectrofotometria Infravermelho , Células Tumorais Cultivadas
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