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1.
Materials (Basel) ; 14(19)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34640052

RESUMEN

The objective of this work was to measure and correlate the degree of conversion (DC), mechanical properties and monomer elution from self-, dual- and light-cured core composites. Five samples of each of the following materials were prepared for each test: Clearfil (Core, Photo Core, Automix), Bisco (Core-Flo, Light-Core and Bis-Core). DC was determined using FTIR, compressive and flexural strength and modulus of elasticity using a universal testing machine and microhardness using Vickers hardness. Elution was measured using HPLC. One-way ANOVA with Tukey's post-test and Pearson's correlation were used to statistically analyze the data. DC of Clearfil-Dual (70.1%) and Clerafil-Photo (66.8%) were higher than Clearfil-Self (55.4%) and all Bisco materials (51.4-55.3%). Flexural strength of Clearfilwas higher than that of Bisco composites. The Microhardness of Clearfil-Dual (119.8VHN) and Clearfil-Photo (118.0VHN) were higher compared to other materials. The greatest elution was detected from self-cured materials. DC positively correlated to microhardness and compressive/flexural strength and negatively to BisGMA elution. Clearfil-Photo and Automix showed higher conversion, lower monomer elution and, generally, better mechanical properties. Self-cured composites should not be recommended for routine clinical use as their performance was inferior to dual- and light-cured composites. Microhardness may be used as an indicator of elution.

2.
Med Sci Monit ; 25: 3397-3405, 2019 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-31066356

RESUMEN

BACKGROUND While several tests can be used in the laboratory evaluation of composite resin-based cement materials, the push-out test remains the most prevalent. Due to difficulties in sample preparation, as well as a highly complex procedure, we attempted to develop an alternative method for testing the bond strength of dental resin cement materials. MATERIAL AND METHODS Ninety-six experimental samples of 2 dual-cure resin cements and 1 fiber post system were prepared for the 2 testing procedures: the push-out test and the modified Microbond test. The degree of monomer conversion was measured by Fourier-transform infrared spectroscopy. RESULTS The push-out test results indicated that the bond strength of dual-cure resin cement differs depending on the tooth root region to which it is applied (p<0.05), In addition, our findings show that Variolink II exhibits a much lower bond strength relative to RelyX ARC. These findings were confirmed by the modified Microbond test results. The monomer conversion rate results indicate average conversion rates of 85.81% and 61.35% for RelyX ARC and Variolnik II, respectively. CONCLUSIONS Our study confirms the practical utility of the modified Microbond test in the assessment of bond strength of dental cement resin-based materials. The proposed test method is particularly useful given that, relative to the push-out test, it requires a much smaller number of preparation and execution steps, thus reducing the potential for introducing errors, while increasing the reliability of the obtained findings.


Asunto(s)
Recubrimiento Dental Adhesivo/métodos , Cementos Dentales/química , Cementos de Resina/química , Adhesivos , Bisfenol A Glicidil Metacrilato , Resinas Compuestas/química , Materiales Dentales/química , Porcelana Dental , Cavidad Pulpar , Análisis del Estrés Dental , Dentina , Humanos , Ensayo de Materiales , Polietilenglicoles , Ácidos Polimetacrílicos , Reproducibilidad de los Resultados , Resinas Sintéticas/química , Raíz del Diente
3.
Srp Arh Celok Lek ; 142(1-2): 10-6, 2014.
Artículo en Serbio | MEDLINE | ID: mdl-24684025

RESUMEN

INTRODUCTION: Periodontitis is a destructive inflammatory disease of the tooth-supporting tissues, primarily caused by Gram-negative microorganisms. Thus, the primary objective of cause-related initial periodontal therapy is disruption and removal of the subgingival biofilm. OBJECTIVE: The aim of this study was to evaluate the clinical and microbiological effects of the initial therapy in patients diagnosed with chronic periodontitis. METHODS: Forty patients with chronic periodontitis were included in the study. As a part of the clinical assessment undertaken prior to the initial therapy, as well as one month and three months post-therapy, plaque index, gingival index, papilla bleeding index, probing pocket depth and clinical attachment level were recorded. Microbiological testing was performed prior to the initial therapy and three months after therapy. Polymerase chain reaction assays were used to determine the presence of Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans. RESULTS: All clinical parameters were significantly reduced after therapy. The prevalence of Aggregatibacter actinomycetemcomitans was reduced by 22.5%, which was a statistically significant decrease compared to the baseline. The prevalence of Porphyromonas gingivalis, Tannerella forsythensis and Prevotella intermedia tended to decrease after therapy; however, the difference did not reach statistical significance. CONCLUSION: The results of the present study demonstrated the beneficial effects of the initial periodontal therapy on both the clinical and microbiological parameters.


Asunto(s)
Infecciones por Bacteroidaceae/terapia , Periodontitis Crónica/terapia , ADN Bacteriano/análisis , Infecciones por Pasteurellaceae/terapia , Desbridamiento Periodontal , Aggregatibacter actinomycetemcomitans/genética , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Periodontitis Crónica/microbiología , Índice de Placa Dental , Humanos , Índice Periodontal , Reacción en Cadena de la Polimerasa , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/aislamiento & purificación , Prevotella intermedia/genética , Prevotella intermedia/aislamiento & purificación , Resultado del Tratamiento
4.
J Prosthet Dent ; 111(4): 327-34, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24360017

RESUMEN

STATEMENT OF PROBLEM: Poly(methyl-methacrylate) (PMMA) represents the most popular current denture material. However, its major drawbacks are insufficient ductility and strength. PURPOSE: The purpose of this study was to improve the mechanical properties of PMMA in denture base application by adding small quantities of nanosilica. MATERIAL AND METHOD: Silica nanoparticles were added to the liquid component of the tested materials. The standard heat polymerizing procedure was followed to obtain 6 PMMA--silicon dioxide (/SiO2) concentrations (0.023%, 0.046%, 0.091%, 0.23%, 0.46%, and 0.91% by volume). Microhardness and fracture toughness of each set of specimens was compared with the unmodified specimens. Furthermore, differential scanning calorimetry and scanning electron microscopy analyses were conducted, and the results obtained were correlated with the results of mechanical properties. RESULTS: It was found that the maximum microhardness and fracture toughness values of the materials tested were obtained for the lowest nanosilica content. A nanosilica content of 0.023% resulted in an almost unchanged glass transition temperature (Tg), whereas the maximum amount of nanosilica induced a considerable increase in Tg. A higher Tg indicated the possible existence of a thicker interfacial layer caused by the chain immobility due to the presence of the particles. However, scanning electron microscopy results demonstrated extensive agglomeration at 0.91% nanosilica, which may have prevented the formation of a homogenous reinforced field. At a nanosilica content of 0.023%, no agglomeration was observed, which probably influenced a more homogenous distribution of nanoparticles as well as uniform reinforcing fields. CONCLUSIONS: Low nanoparticle content yields superior mechanical properties along with the lower cost of nanocomposite synthesis.


Asunto(s)
Materiales Dentales/química , Bases para Dentadura , Nanocompuestos/química , Polimetil Metacrilato/química , Dióxido de Silicio/química , Rastreo Diferencial de Calorimetría , Reactivos de Enlaces Cruzados/química , Vidrio/química , Dureza , Calor , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Metacrilatos/química , Metilmetacrilato/química , Microscopía Electrónica de Rastreo , Nanopartículas/química , Estrés Mecánico , Propiedades de Superficie , Temperatura de Transición
5.
Vojnosanit Pregl ; 70(5): 477-83, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23789287

RESUMEN

BACKGROUND/AIM: The main drawback of flowable dental composite resin is low strength compared to conventional composite resin, due to a low amount of filler, neccessary for achieving low viscosity and ease of handling. The aim of this study was to improve mechanical properties of flowable dental composite resin by adding small amount of nanoparticles, which would not compromise handling properties. METHODS: A commercially available flowable dental composite resin material was mixed with 7 nm aftertreated hydrophobic fumed silica and cured by an UV lamp. Four sets of samples were made: control sample (unmodified), the sample containing 0.05%, 0.2% and 1% nanosilica. Flexural modulus, flexural strength and microhardness were tested. One-way ANOVA followed by Tukey's test with the significance value of p < 0.05 was performed to statistically analyze the obtained results. Furthermore, differential scanning calorimetry (DSC) and SEM analysis were performed. To asses handling properties, slumping resistance was determined. RESULTS: It was found that 0.05% is the most effective nanosilica content. All the tested mechanical properties were improved by a significant margin. On the other hand, when 0.2% and 1% nanosilica content was tested, different results were obtained, some of the mechanical properties even dropped, while some were insignificantly improved. The difference between slumping resistance of unmodified and modified samples was found to be statistically insignificant. CONCLUSIONS: Low nanosilica addition proved more effective in improving mechanical properties compared to higher additions. Furthermore, handling properties are unaffected by nanosilica addition.


Asunto(s)
Resinas Acrílicas , Resinas Compuestas , Nanopartículas , Poliuretanos , Dióxido de Silicio , Fenómenos Biomecánicos , Técnicas In Vitro , Viscosidad
6.
Bosn J Basic Med Sci ; 13(1): 34-43, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23448609

RESUMEN

The aim of this study was to determine surface roughness and topography of polished dental resin-based nanocomposites. Four representative dental resin-based nanocomposites were tested in the study: two nanohybrids (Filtek Z550 and Tetric EvoCeram) and two nanofilled (Filtek Ultimate Body and Filtek Ultimate Translucent); and two reference materials: one microfilled (Gradia Direct) and one microhybrid (Filtek Z250). Polymerized cylindrical specimens (4 mm x 2 mm) were polished with multi-step polishing system- Super Snap. Immediately after the polishing, topography of each specimen was examined by Veeco di CP-II Atomic Force Microscope. Specimen's surface has been scanned in 6 points in contact mode with CONT20A-CP tips. 1 Hz scan rate and 256 × 256 resolution were used to obtain topography on a 90 µm × 90 µm scanning area. Measured topography data were processed by Image Processing and Data Analysis v2.1.15 software. Following parameters were compared among specimens: average roughness and maximum peak-to-valley distance. All of the tested materials had similar average surface roughness after finishing and polishing procedure. The lowest values occurred in the material Filtek Ultimate Body, and the highest in the Filtek Z550. When interpreting maximum peak-to-valley distance the larger differences in values (up to 100%) occurred in Filtek Z550, Filtek Z250 and Filtek Ultimate Body, which is a result of the deep polishing channels and tracks. Type, size, distribution of fillers and filler loading in tested materials, didn't influence average roughness values, but had an impact on maximum peak-to-valley distance values.


Asunto(s)
Nanocompuestos/ultraestructura , Resinas Sintéticas/química , Microscopía de Fuerza Atómica , Propiedades de Superficie
7.
Srp Arh Celok Lek ; 138(1-2): 19-25, 2010.
Artículo en Serbio | MEDLINE | ID: mdl-20422908

RESUMEN

INTRODUCTION: The mathematical model of the abutment tooth is the starting point of the finite element analysis of stress and deformation of dental structures. The simplest and easiest way is to form a model according to the literature data of dimensions and morphological characteristics of teeth. Our method is based on forming 3D models using standard geometrical forms (objects) in programmes for solid modeling. OBJECTIVE: Forming the mathematical model of abutment of the second upper premolar for finite element analysis of stress and deformation of dental structures. METHODS: The abutment tooth has a form of a complex geometric object. It is suitable for modeling in programs for solid modeling SolidWorks. After analysing the literature data about the morphological characteristics of teeth, we started the modeling dividing the tooth (complex geometric body) into simple geometric bodies (cylinder, cone, pyramid,...). Connecting simple geometric bodies together or substricting bodies from the basic body, we formed complex geometric body, tooth. The model is then transferred into Abaqus, a computational programme for finite element analysis. Transferring the data was done by standard file format for transferring 3D models ACIS SAT. RESULTS: Using the programme for solid modeling SolidWorks, we developed three models of abutment of the second maxillary premolar: the model of the intact abutment, the model of the endodontically treated tooth with two remaining cavity walls and the model of the endodontically treated tooth with two remaining walls and inserted post. CONCLUSION: Mathematical models of the abutment made according to the literature data are very similar with the real abutment and the simplifications are minimal. These models enable calculations of stress and deformation of the dental structures. The finite element analysis provides useful information in understanding biomechanical problems and gives guidance for clinical research.


Asunto(s)
Diente Premolar , Análisis de Elementos Finitos , Modelos Teóricos , Simulación por Computador , Pilares Dentales , Análisis del Estrés Dental , Humanos
8.
J Oral Pathol Med ; 38(2): 167-73, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18713235

RESUMEN

BACKGROUND: Oral reactivation of latent Herpes simplex virus (HSV) infection may easily occur in cancer patients. Virus reactivation can cause oral mucosa damage, worsen already existing lesions caused by stomatotoxic effect of cancer therapy and, whether symptomatic or asymptomatic, ample spreading and promote viral transmission. METHODS: Polymerase chain reaction (PCR), cell-culture and direct immunofluorescence have been used to determine the frequency of oral HSV reactivation in 60 patients undergoing chemotherapy for different malignancies. RESULTS: By means of PCR, the presence of viral DNA was detected in 71.7% of patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients before and 40.0% after chemotherapy were viral-culture positive, while 3.3% of patients before and 11.7% after chemotherapy were positive as shown by direct immunofluorescence. No significant difference in HSV-1 reactivation was found before and after chemotherapy. In addition, no significant difference was found when comparing HSV-1 reactivation in patients with and without mucositis. HSV-2 was not detected in any of the patients. CONCLUSIONS: Reactivation of latent HSV is exceptionally frequent in cancer patients. The results of this study suggest that virus reactivation occurs independently of cancer chemotherapy. The potential role of HSV reactivation in oral mucosa damage remains unclear.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Herpesvirus Humano 1/aislamiento & purificación , Mucosa Bucal/virología , Neoplasias/tratamiento farmacológico , Estomatitis Herpética/virología , Activación Viral , Adulto , Anciano , Animales , Chlorocebus aethiops , ADN Viral/análisis , Técnica del Anticuerpo Fluorescente Directa , Humanos , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Mucositis/inducido químicamente , Mucositis/virología , Reacción en Cadena de la Polimerasa , Células Vero/virología , Adulto Joven
9.
Coll Antropol ; 32(2): 535-41, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18756907

RESUMEN

The aim of this investigation was to establish precise indicators of the vertical dimension of occlusion (VDO) which could be used as objective parameters in prosthodontic treatment providing exact control of the reconstructed vertical dimension of occlusion, early detection of errors and correction of the vertical dimension of occlusion during complete denture manufacturing. A total of 60 lateral cephalometric radiographs of subjects with natural dentition and class I skeletal jaw relationship, of Serbian nationality from the region of Vojvodina, were included in the investigation. Thirty subjects were males, and thirty females, their age range was 20 to 29 years. Cephalometric analysis was performed by using "Dr. Ceph" computer software (FYI Technologies, GA, USA). By evaluation of the craniofacial complex in subjects with natural dentition, horizontal dentofacial developmental growth was established in the examined sample and it was based on the relationship between the posterior and anterior total facial height (S-Go:N-Me, female X=68.96%, male X=72.8%) and statistically significant differences were found between the sexes in almost all linear dimensions and in the relation between the posterior and the anterior total facial height. Highly significant differences (p<0.001) between the sexes were found in regard to anterior total facial height (N-Me, male X=120.75 mm, female X=112.72 mm) and the anterior lower facial height (ANS-Me, male X=67.87 mm, female X=61.50 mm) (p<0.05). The proportions of the upper and lower anterior facial heights (N-ANS:ANS-Me, male X=79.36%, female X=80.63%) were within normal values in both sexes. Facial harmony existed both in men and women. Cephalometric study of the subjects with complete natural dentition included in this study provided important and specific parameters for optimal reconstruction of vertical dimension of occlusion in the treatment of edentulous patients.


Asunto(s)
Cefalometría , Dimensión Vertical , Adulto , Croacia , Cara/anatomía & histología , Femenino , Humanos , Masculino , Valores de Referencia
10.
Med Pregl ; 60(11-12): 663-8, 2007.
Artículo en Serbio | MEDLINE | ID: mdl-18666615

RESUMEN

INTRODUCTION: This paper reviews recent trends in basic dental disciplines and advantages of new clinical procedures over conventional. PROSTHETIC RECONSTRUCTION OF DEPULPED TEETH: Post and core restoration is one of the most common treatment modalities applied when the remaining coronal tooth structure is not sufficient to provide the necessary retention form for restoration. Nowadays, the restoration of endodontically treated teeth is based on the use of materials with a modulus of elasticity similar to that of dentin. A NEW CONCEPT OF LIGHT INDUCED POLYMERIZATION OF ESTHETIC MATERIALS IN DENTISTRY: Polymerization contraction stress of resin based composite during light-activation process may be reduced by various illumination schemes. Successful curing depends on the calculated energy density values (spatial irradiance x irradiation period - J/cm2) rather than on light irradiance levels (mW/cm2). THE ASSOCIATION BETWEEN PERIODONTAL DISEASE AND GENERAL HEALTH: It is well documented that various systemic diseases have a profound effect on periodontal tissues. Recently, it has been speculated that periodontal disease may influence systemic health and represent the risk factor for cardiovascular diseases or adverse pregnancy outcomes. COMPUTER SYSTEMS FOR AUTOMATIC LANDMARK DETECTION: Computer systems, which will automatically identify relevant skeletal and soft tissue roentgencephalometric landmarks, will represent a great improvement in the field of orthodontic diagnosis. By using the Active Appearance Model, it is possible to identify most of roentgencephalometric bony landmarks with an average error well below 2 mm. CURRENT TRENDS IN CARIES TREATMENT: Chemomechanical caries removal was introduced as an alternative to conventional mechanical procedures. Its advantages are: selective removal of carious tissue, absence of pain, reduced need for local anesthesia and less potentially negative effects on the dental pulp. CONCLUSION: The introduction of the surgical operating microscope, microsurgical instruments, ultrasonic retrotips for root-end cavity preparation and new root-end filling materials opened a new era in periapical surgery, even on multi-rooted teeth, often called endodontic microsurgery.


Asunto(s)
Odontología/tendencias , Humanos
11.
Med Pregl ; 58(1-2): 23-6, 2005.
Artículo en Serbio | MEDLINE | ID: mdl-18257200

RESUMEN

INTRODUCTION: Tobacco use is an important risk factor for advanced histopathological findings on edentulous alveolar ridge mucosa. The aim of this study was to examine the effects of smoking on histopathological findings on edentulous alveolar ridge mucosa. MATERIAL AND METHODS: The experimental group consisted of 48 patients (29 smokers and 19 nonsmokers). The mean age of smokers was 42.6 and of nonsmokers 48.7 years. The anamnesis included the following data: age, sex, diseases and toxic habits--cigarette smoking. Biopsy samples were taken from the edentulous alveolar ridge mucosa without gross signs of symptoms. RESULTS: The mean number of cigarettes smoked per day was 11.5 +/- 7. The results of chi2 test proved that there were no statistically significant differences (p > 0.05) in histopathological findings on the alveolar ridge mucosa. The mean duration of smoking was 12.7 +/- 5 years. Hyperkeratosis was established in 76.92% of smokers who smoked longer than 15 years. The mean age at which smokers began smoking was 27.3 +/- 8 years and there were no statistically significant differences in histopathological findings on the alveolar ridge mucosa correlated with the beginning of smoking. CONCLUSION: On the basis of our research we conclude that smokers who have been smoking for 15 years are at risk for developing histopathological changes of the alveolar ridge mucosa, but there were no statistically significant differences in histopathological findings on the alveolar ridge mucosa correlated with the number of cigarettes per day and the beginning of smoking.


Asunto(s)
Proceso Alveolar , Arcada Parcialmente Edéntula/patología , Mucosa Bucal/patología , Fumar/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Med Pregl ; 57(11-12): 556-60, 2004.
Artículo en Serbio | MEDLINE | ID: mdl-16107002

RESUMEN

INTRODUCTION: Dimensional stability of polymer-based dental materials is compromised by polymerization reaction of the monomer. The conversion into a polymer is accompanied by a closer packing of molecules, which leads to volume reduction called curing contraction or polymerization shrinkage. Curing contraction may break the adhesion between the adhesive system and hard tooth tissues forming microgaps which may result in marginal deterioration, recurrent caries and pulp injury. POLYMERIZATION SHRINKAGE OF RESIN-BASED RESTORATIVE DENTAL MATERIALS: Polymerization of the organic phase (nonomer molecules) of resin-based dental materials causes shrinkage. The space occupied by filler particles is not associated with polymerization shrinkage. However, high filler loading within certain limits, can contribute to a lesser curing contraction. POLYMERIZATION SHRINKAGE STRESS AND STRESS REDUCTION POSSIBILITIES: Polymerization shrinkage stress of polymer-based dental resins can be controlled in various ways. The adhesive bond in tooth-restoration interface guides the contraction forces to cavity walls. If leakage occurs, complications like secondary caries and pulpal irritation may jeopardize the longevity of a restoration. Stress relieve can be obtained by modifications of the monomer and photoinitiator, or by specially designed tooth preparation and application of bases and liners of low modulus of elasticity. The polymerization contraction can be compensated by water absorption due to oral cavity surrounding. The newest approach to stress relief is based on modulation of polymerization initiation. CONCLUSION: This work deals with polymerization contraction and how to achieve leak-proof restoration. Restorative techniques that may reduce the negative effect of polymerization shrinkage stress need further research in order to confirm up-to-date findings.


Asunto(s)
Resinas Compuestas/química , Luz , Fotoquímica , Polímeros
13.
Med Pregl ; 56(9-10): 409-12, 2003.
Artículo en Serbio | MEDLINE | ID: mdl-14740528

RESUMEN

INTRODUCTION: Based on literature data it is obvious that there is a connection between smoking and periodontal diseases. Alveolar bone loss increases with smoking. Tobacco smoking affects the proportion of subgingival bacterial flora by influencing oxidoreduction potential of dental plaque and thus making conditions for development of anaerobic bacteria. According to some researchers, smoking affects the mineral component of bone tissue. Orthopantomograms show higher level of alveolar bone loss in smokers than in nonsmokers with the same level of oral hygiene. The aim of this study was to establish if smoking affects alveolar bone loss in complete denture wearers. MATERIAL AND METHODS: Our clinical investigation included 60 patients of both sexes (30 smokers and 30 nonsmokers) all complete dentures wearers. All patients met study criteria: jaw relation and smokers who smoke over 20 cigarettes per day. All subjects were interviewed, and after that orthopantomograms were made. They were used to calculate the degree of alveolar bone loss. RESULTS: The examined subjects were approximately of the same age. Mean age of smokers was 59.9 and nonsmokers 61.8. It was established that differences regarding resorption in men were not significant. The degree of resorption in women smokers and women non-smokers was different, but differences were not significant. DISCUSSION: It has been proven that the number of cigarettes smoked per day is very important. It is considered that the risk of oral epithelial dysplasia increases when smoking more than 20 cigarettes per day. Considering our results regarding resorption of edentulous alveolar ridge in smokers and nonsmokers, we concluded that there were no significant differences. There are opinions in literature that smoking is not an etiological factor in resorption, but there are some opinions that smoking is connected with the degree of resorption in periodontium. The analyses of resorptive changes in edentuolous smokers were done only around implants and it was estimated that smoking has more influence than other clinical risk factors. CONCLUSION: On the bases of our research we may conclude that smoking does not directly affect the degree of resorption of edentulous alveolar ridge with complete denture wearers.


Asunto(s)
Pérdida de Hueso Alveolar/etiología , Dentadura Completa , Fumar/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad
14.
J Virol ; 76(23): 12325-34, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12414973

RESUMEN

Hepatitis C virus (HCV), a major etiologic agent of hepatocellular carcinoma, presently infects approximately 400 million people worldwide, making the development of protective measures against HCV infection a key objective. Here we have generated a recombinant vesicular stomatitis virus (VSV), which expresses the HCV structural proteins, by inserting the contiguous Core, E1, and E2 coding region of HCV into the VSV genome. Recombinant VSV expressing HCV Core, E1, and E2 (VSV-HCV-C/E1/E2) grew to high titers in vitro and efficiently expressed the incorporated HCV gene product, which became fully processed into the individual HCV structural proteins. Biochemical and biophysical analysis indicated that the HCV Core, E1, and E2 proteins assembled to form HCV-like particles (HCV-LPs) possessing properties similar to the ultrastructural properties of HCV virions. Mice immunized with VSV-HCV-C/E1/E2 generated cell-mediated immune responses to all of the HCV structural proteins, and humoral responses, particularly to E2, were also readily evident. Our data collectively indicate that engineered VSVs expressing HCV Core, E1, and E2 and/or HCV-LPs represent useful tools in vaccine and immunotherapeutic strategies designed to address HCV infection.


Asunto(s)
Vectores Genéticos , Hepacivirus/genética , Hepacivirus/ultraestructura , Virus de la Estomatitis Vesicular Indiana/genética , Animales , Anticuerpos Antivirales/biosíntesis , Línea Celular , Cricetinae , Ingeniería Genética , Hepacivirus/inmunología , Hepacivirus/fisiología , Inmunización , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Recombinación Genética , Vacunas Sintéticas/genética , Vacunas Sintéticas/farmacología , Proteínas del Núcleo Viral/genética , Proteínas del Envoltorio Viral/genética , Vacunas contra Hepatitis Viral/genética , Vacunas contra Hepatitis Viral/farmacología , Ensamble de Virus
15.
J Virol ; 76(2): 895-904, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11752178

RESUMEN

We report here the generation of recombinant vesicular stomatitis virus (VSV) able to produce the suicide gene product thymidine kinase (TK) or cytokine interleukin 4 (IL-4). In vitro cells infected with the engineered viruses expressed remarkably high levels of biologically active TK or IL-4 and showed no defects in replication compared to the wild-type virus. Recombinant viruses retained their ability to induce potent apoptosis in a variety of cancer cells, while normal cells were evidently more resistant to infection and were completely protected by interferon. Significantly, following direct intratumoral inoculation, VSV expressing either TK or IL-4 exhibited considerably more oncolytic activity against syngeneic breast or melanoma tumors in murine models than did the wild-type virus or control recombinant viruses expressing green fluorescent protein (GFP). Complete regression of a number of tumors was achieved, and increased granulocyte-infiltrating activity with concomitant, antitumor cytotoxic T-cell responses was observed. Aside from discovering greater oncolytic activity following direct intratumoral inoculation, however, we also established that VSV expressing IL-4 or TK, but not GFP, was able to exert enhanced antitumor activity against metastatic disease. Following intravenous administration of the recombinant viruses, immunocompetent BALB/c mice inoculated with mammary adenocarcinoma exhibited prolonged survival against lethal lung metastasis. Our data demonstrate the validity of developing novel types of engineered VSV for recombinant protein production and as a gene therapy vector for the treatment of malignant and other disease.


Asunto(s)
Ingeniería Genética , Terapia Genética/métodos , Neoplasias/genética , Neoplasias/terapia , Virus de la Estomatitis Vesicular Indiana/genética , Animales , Secuencia de Bases , Células Cultivadas , Cricetinae , ADN Recombinante/genética , Ensayo de Inmunoadsorción Enzimática , Vectores Genéticos/genética , Vectores Genéticos/fisiología , Interferones/farmacología , Interleucina-4/análisis , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-4/uso terapéutico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Mamarias Animales/inmunología , Neoplasias Mamarias Animales/patología , Melanoma/inmunología , Melanoma/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Trasplante de Neoplasias , Neoplasias/patología , Análisis de Supervivencia , Timidina Quinasa/genética , Timidina Quinasa/metabolismo , Timidina Quinasa/uso terapéutico , Células Tumorales Cultivadas , Virus de la Estomatitis Vesicular Indiana/fisiología
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