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1.
J Mech Behav Biomed Mater ; 87: 111-118, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30056308

RESUMEN

OBJECTIVES: The purpose of this study was to investigate the simulated cuspal deflection and flexural properties of high viscosity bulk-fill and conventional resin composites. METHODS: Seven high viscosity bulk-fill resin composites and eight conventional resin composites were used. Aluminum blocks (10 mm x 8 mm x 15 mm) with a mesio-occlusal-distal (MOD) cavity [4 (W) mm x 8 (L) mm x 4 (D) mm] were prepared and randomly divided into groups for different measurement techniques [micrometer vs CSLM] and further subdivided according to type of resin composite (high viscosity bulk-fill vs conventional resin composite). The simulated cuspal deflection resulting from the polymerization of resin composite bonded to a precisely machined MOD cavity within an aluminum block was measured with either a novel highly accurate submicron digimatic micrometer (MDH-25 M, Mitsutoyo, Tokyo, Japan) or a confocal laser scanning microscope (CLSM, VK-9710, Keyence, Tokyo, Japan) cuspal measurement method. In addition, flexural properties of tested resin composites were measured to investigate the relationship between simulated cuspal deflection and flexural properties. Scanning electron microscopy observation of tested resin composites was also conducted. RESULTS: The simulated cuspal deflection of high viscosity bulk-fill resin composites was similar to that of conventional resin composites, regardless of measurement method. There were no statistically significant differences (p > 0.05) between the micrometer and CLSM cuspal measurement methods. There were statistically significant differences (p < 0.05) in flexural strength and elastic modulus depending on the material, regardless of the type of resin composite. Pearson correlation analysis did not show any statistically significant (p < 0.05) relationship between flexural properties and cuspal deflection. CONCLUSIONS: The results of this study indicate that high viscosity bulk-fill resin composites show similar cuspal deflection with bulk-filling techniques, to those shown by conventional resin composites with incremental filling techniques. Simulated cuspal deflection can be measured using either a micrometer or CLSM, but this experiment failed to show any relationship between the flexural properties and simulated cuspal deflection of resin composites. SIGNIFICANCE: High viscosity bulk-fill resin composites produce the same level of cuspal deflection as a conventional incrementally filled resin composite.


Asunto(s)
Resinas Compuestas , Resistencia Flexional , Ensayo de Materiales/instrumentación , Viscosidad
2.
Gen Dent ; 66(3): 32-36, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29714697

RESUMEN

This in vitro study evaluated the marginal microleakage of a bioactive restorative with other restorative materials in standard Class V preparations. Sixty previously extracted, noncarious human molars were randomly assigned to 3 experimental groups (n = 20): a bioactive composite resin, a universal hybrid composite resin, and a resin-modified glass ionomer restorative. Class V cavities were prepared on the facial or lingual surface of each tooth so that coronal margins were located in enamel and apical margins in cementum (dentin). After the cavity preparations were restored with the appropriate material, the specimens were artificially aged in water baths. The root apices were sealed with utility wax, the tooth surfaces were coated with nail varnish to within 1 mm of the restoration, and specimens were immersed in 1% methylene dye solution for 8 hours. The teeth were invested in clear polymer resin, sectioned longitudinally, and examined under a stereomicroscope to assess dye penetration. Nonparametric scores indicated that microleakage was significantly greater at the apical margins than the coronal margins for all groups (P > 0.0001). The specimens restored with the bioactive material exhibited greater microleakage at both the coronal and apical margins than did specimens restored with the composite resin or resin-modified glass ionomer material, although the differences were not statistically significant (P > 0.05). Based on the results of the present study, the type of restorative material did not appear to have a significant influence on microleakage. Rather, the marginal position (coronal versus apical) of the restoration was the determining factor in microleakage.


Asunto(s)
Adaptación Marginal Dental , Restauración Dental Permanente/métodos , Resinas Compuestas/uso terapéutico , Caries Dental/cirugía , Preparación de la Cavidad Dental/métodos , Filtración Dental/etiología , Cementos de Ionómero Vítreo/uso terapéutico , Humanos , Técnicas In Vitro
3.
J Oral Sci ; 60(1): 29-36, 2018 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-29375099

RESUMEN

This study evaluated the simulated localized wear of resin luting cements for universal adhesive systems using different curing modes. Five resin luting cements for universal adhesive systems were evaluated and subsequently subjected to wear challenge in a Leinfelder-Suzuki wear simulation device. Overall, 20 specimens from each resin luting cement were photo-cured for 40 s (dual-cure group), and 20 specimens of each material were not photo-cured (chemical-cure group). Simulated localized wear was generated using a stainless steel ball-bearing antagonist in water slurry of polymethylmethacrylate beads. In addition, scanning electron microscopy (SEM) observations of resin luting cements and wear facets were conducted. Significant differences in simulated wear and SEM observations of wear facets were evident among the materials in the dual- and chemical-cure groups. The simulated wear and SEM observations of wear facets of G-CEM LinkForce and Panavia V5 were not influenced by the curing mode. SEM observations of resin luting cements were material dependent. In most cases, dual curing appears to ensure greater wear resistance of resin luting cements than chemical curing alone. The wear resistance of some resin luting cements appears to be material dependent and is not influenced by the curing mode.


Asunto(s)
Adhesivos , Cementos Dentales , Curación por Luz de Adhesivos Dentales , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Propiedades de Superficie
4.
Eur J Oral Sci ; 126(2): 135-145, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29344991

RESUMEN

The relationship between enamel bond fatigue durability and surface free-energy characteristics with universal adhesives was investigated. The initial shear bond strengths and shear fatigue strengths of five universal adhesives to enamel were determined with and without phosphoric acid pre-etching. The surface free-energy characteristics of adhesive-treated enamel with and without pre-etching were also determined. The initial shear bond strength and shear fatigue strength of universal adhesive to pre-etched enamel were higher than those to ground enamel. The initial shear bond strength and shear fatigue strength of universal adhesive to pre-etched enamel were material dependent, unlike those to ground enamel. The surface free-energy of the solid (γS ) and the hydrogen-bonding force (γSh) of universal adhesive-treated enamel were different depending on the adhesive, regardless of the presence or absence of pre-etching. The bond fatigue durability of universal adhesives was higher to pre-etched enamel than to ground enamel. In addition, the bond fatigue durability to pre-etched enamel was material dependent, unlike that to ground enamel. The surface free-energy characteristics of universal adhesive-treated enamel were influenced by the adhesive type, regardless of the presence or absence of pre-etching. The surface free-energy characteristics of universal adhesive-treated enamel were related to the results of the bond fatigue durability.


Asunto(s)
Recubrimiento Dental Adhesivo , Análisis del Estrés Dental , Recubrimientos Dentinarios , Resistencia al Corte , Grabado Ácido Dental , Ensayo de Materiales , Ácidos Fosfóricos , Propiedades de Superficie
5.
Eur J Oral Sci ; 125(3): 215-222, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28452076

RESUMEN

This aim of this study was to compare universal adhesives and two-step self-etch adhesives in terms of dentin bond fatigue durability in self-etch mode. Three universal adhesives - Clearfil Universal, G-Premio Bond, and Scotchbond Universal Adhesive - and three-two-step self-etch adhesives - Clearfil SE Bond, Clearfil SE Bond 2, and OptiBond XTR - were used. The initial shear bond strength and shear fatigue strength of resin composite bonded to adhesive on dentin in self-etch mode were determined. Scanning electron microscopy observations of fracture surfaces after bond strength tests were also made. The initial shear bond strength of universal adhesives was material dependent, unlike that of two-step self-etch adhesives. The shear fatigue strength of Scotchbond Universal Adhesive was not significantly different from that of two-step self-etch adhesives, unlike the other universal adhesives. The shear fatigue strength of universal adhesives differed depending on the type of adhesive, unlike those of two-step self-etch adhesives. The results of this study encourage the continued use of two-step self-etch adhesive over some universal adhesives but suggest that changes to the composition of universal adhesives may lead to a dentin bond fatigue durability similar to that of two-step self-etch adhesives.


Asunto(s)
Recubrimiento Dental Adhesivo/métodos , Cementos Dentales/uso terapéutico , Recubrimiento Dental Adhesivo/efectos adversos , Análisis del Estrés Dental , Humanos , Cementos de Resina/uso terapéutico
6.
Eur J Oral Sci ; 124(5): 480-489, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27696555

RESUMEN

The purpose of this study was to determine the relationship between mechanical properties and bond durability of short fiber-reinforced resin composite with universal adhesive. As controls, micro-hybrid and nano-hybrid resin composites were tested. The universal adhesives used were Scotchbond Universal, Adhese Universal, and G-Premio Bond. The fracture toughness and flexural properties of resin composites, and shear bond strength and shear fatigue strength of universal adhesive with resin composite using both total-etch and self-etch modes were determined. In the results, short fiber-reinforced resin composite showed significantly higher fracture toughness than did micro-hybrid and nano-hybrid resin composites. The flexural strength and modulus of short fiber-reinforced and nano-hybrid resin composites were significantly lower than were those of micro-hybrid resin composites. Regardless of etching mode, the shear bond strength of universal adhesives with short fiber-reinforced resin composite did not show any significant differences from micro-hybrid and nano-hybrid resin composites. The shear fatigue strength of universal adhesives with short fiber-reinforced resin composite and micro-hybrid resin composites were significantly higher than that of nano-hybrid resin composites. The results of this study suggest that the mechanical properties of short fiber-reinforced resin composite improve their bond durability with universal adhesive.


Asunto(s)
Resinas Compuestas , Cementos Dentales , Cementos de Resina , Recubrimiento Dental Adhesivo , Materiales Dentales , Ensayo de Materiales , Resistencia al Corte , Estrés Mecánico
7.
Eur J Oral Sci ; 124(4): 377-86, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27315775

RESUMEN

The purpose of this study was to evaluate the influence of duration of phosphoric acid pre-etching on the bond durability of universal adhesives and the surface free-energy characteristics of enamel. Three universal adhesives and extracted human molars were used. Two no-pre-etching groups were prepared: ground enamel; and enamel after ultrasonic cleaning with distilled water for 30 s to remove the smear layer. Four pre-etching groups were prepared: enamel pre-etched with phosphoric acid for 3, 5, 10, and 15 s. Shear bond strength (SBS) values of universal adhesive after no thermal cycling and after 30,000 or 60,000 thermal cycles, and surface free-energy values of enamel surfaces, calculated from contact angle measurements, were determined. The specimens that had been pre-etched showed significantly higher SBS and surface free-energy values than the specimens that had not been pre-etched, regardless of the aging condition and adhesive type. The SBS and surface free-energy values did not increase for pre-etching times of longer than 3 s. There were no significant differences in SBS values and surface free-energy characteristics between the specimens with and without a smear layer. The results of this study suggest that phosphoric acid pre-etching of enamel improves the bond durability of universal adhesives and the surface free-energy characteristics of enamel, but these bonding properties do not increase for phosphoric acid pre-etching times of longer than 3 s.


Asunto(s)
Grabado Ácido Dental , Ácidos Fosfóricos/farmacología , Cementos de Resina , Recubrimiento Dental Adhesivo , Cementos Dentales , Esmalte Dental , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Resistencia al Corte , Propiedades de Superficie
8.
Gen Dent ; 62(2): 37-42, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24598493

RESUMEN

This in vitro study investigated whether permanent anterior incisors that are endodontically treated with cemented fiber-reinforced composite (FRC) posts without additional canal preparation can potentially increase the resistance to fracture and thus reduce the rate of clinical failure in root canals. Extracted human permanent maxillary central incisors (n = 120) were randomly assigned to 2 experimental groups (n = 60): thermocycled (Group 1) and non-thermocycled (Group 2). These 2 groups were then further divided into 3 subgroups (n = 20). Subgroup 1.1 specimens had root canals prepared and obturated with FRC posts placed. Subgroup 1.2 specimens were prepared and obturated, but did not receive posts. Subgroup 1.3 specimens did not receive root canal preparation, and served as a control. The same processes were repeated for Subgroups 2.1, 2.2, and 2.3, respectively. Significant differences were found between the thermocycled and the non-thermocycled subgroups. Subgroup comparison within the thermocycled group (Group 1) showed significantly higher fracture resistance values for the teeth with post cementation (P < .0001).


Asunto(s)
Resinas Compuestas/uso terapéutico , Incisivo/cirugía , Técnica de Perno Muñón , Tratamiento del Conducto Radicular/métodos , Fracturas de los Dientes/prevención & control , Cementación/métodos , Fracaso de la Restauración Dental , Humanos , Técnicas In Vitro , Preparación del Conducto Radicular/métodos
9.
Am J Dent ; 26(5): 265-70, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24479278

RESUMEN

PURPOSE: To evaluate the mechanical strength and color stability of provisional restoration materials. METHODS: For mechanical testing, four groups [Trim (PEMA), Alike (PMMA), Versatemp (bis-acrylic resin composite, BARC) and Perfectemp II (bis-acrylic fluoride enriched resin, BAFC)] of resin disks were prepared for fracture toughness and shear punch strength testing, respectively. Five samples were fabricated for each group; therefore, a total of 20 resin disks for each testing method was prepared. The load at fracture and shear punch values of each specimen were recorded after 24-hour storage in distilled water. The stress intensity factors (K(Ic)) were calculated by the formula reported by Atkinson et al. For shear strength, the following formula was used: Shear strength = Force (N)/section thickness (mm) x punch circumference (mm). Values of each group in both tests were analyzed using one-way-ANOVA and Tukey multiple comparison test. For color stability testing, provisional resin disk specimens of the above mentioned materials were fabricated. Five samples were prepared for each subgroup (with and without a surface coating agent - Permaseal) and three different solutions (distilled water, red wine and curry); a total of 120 disk specimens were fabricated. Color values of each group were measured using a spectrophotometer after 24 hours and 2 weeks of aging in the aforementioned solutions. The color differences (deltaE*ab) between before and after aging were calculated by CIE Lab color-difference formula. The interaction of deltaE*ab values were analyzed by two-way analysis of variance followed by Newman-Keuls Multiple comparison test. RESULTS: The highest fracture toughness value [(MPa (m)1/2)] was obtained by PMMA (0.89) followed by BARC (0.67), PEMA (0.54) and BAFC (0.42). Significant differences were observed among all test groups (P < 0.05). The highest shear punch strength (MPa) was obtained by BARC (160), followed by PMMA (141) and PEMA (132). The lowest value was obtained by BAFC (106). BARC showed a significantly higher mean value than the other groups (P < 0.05). PEMA and PMMA demonstrated better color stability than the two bis-acrylic resin composites. Wine and curry showed higher stainability than water, recording higher deltaE*ab values than the clinically perceptible difference level of deltaE*ab 3.3. The surface coating agent groups demonstrated more staining than the non-coated groups. All groups, except for BARC, demonstrated significant differences dependent upon surface coating and solutions (P < 0.05).


Asunto(s)
Resinas Compuestas/química , Materiales Dentales/química , Restauración Dental Provisional , Materiales Biocompatibles Revestidos/química , Color , Condimentos , Dureza , Humanos , Ensayo de Materiales , Metilmetacrilatos/química , Ácidos Polimetacrílicos/química , Polimetil Metacrilato/química , Resistencia al Corte , Espectrofotometría , Especias , Estrés Mecánico , Propiedades de Superficie , Factores de Tiempo , Agua/química , Vino
10.
Drug Metab Dispos ; 39(2): 345-50, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21068193

RESUMEN

An investigational anticancer agent that contains a thiophene moiety, 3-[(quinolin-4-ylmethyl)-amino]-N-[4-trifluoromethox)phenyl] thiophene-2-carboxamide (OSI-930), was tested to investigate its ability to modulate the activities of several cytochrome P450 enzymes. Results showed that OSI-930 inactivated purified, recombinant cytochrome P450 (P450) 3A4 in the reconstituted system in a mechanism-based manner. The inactivation was dependent on cytochrome b(5) and required NADPH. Catalase did not protect against the inactivation. No inactivation was observed in studies with human 2B6, 2D6, or 3A5 either in the presence or in the absence of b(5). The inactivation of 3A4 by OSI-930 was time- and concentration-dependent. The inactivation of the 7-benzyloxy-4-(trifluoromethyl)coumarin catalytic activity of 3A4 was characterized by a K(I) of 24 µM and a k(inact) of 0.04 min(-1). This K(I) is significantly greater than the clinical OSI-930 C(max) of 1.7 µM at the maximum tolerated dose, indicating that clinical drug interactions of OSI-930 via this pathway are not likely. Spectral analysis of the inactivated protein indicated that the decrease in the reduced CO spectrum at 450 nm was comparable to the amount of inactivation, thereby suggesting that the inactivation was primarily due to modification of the heme. High-pressure liquid chromatography (HPLC) analysis with detection at 400 nm showed a loss of heme comparable to the activity loss, but a modified heme was not detected. This result suggests either that the heme must have been modified enough so as not to be observed in a HPLC chromatograph or, possibly, that it was destroyed. The partition ratio for the inactivation of P450 3A4 was approximately 23, suggesting that this P450 3A4-mediated pathway occurs with approximately 4% frequency during the metabolism of OSI-930. Modeling studies on the binding of OSI-930 to the active site of the P450 3A4 indicated that OSI-930 would be oriented properly in the active site for oxidation of the thiophene sulfur to give the sulfoxide, which has previously been shown to be a significant metabolite of OSI-930. Because OSI-930 is an inactivator of P450 3A4 but does not exhibit any effect on P450 3A5 activity under the same conditions, it may be an appropriate probe for exploring unique aspects of these two very similar P450s.


Asunto(s)
Antineoplásicos/metabolismo , Inhibidores del Citocromo P-450 CYP3A , Quinolinas/metabolismo , Tiofenos/metabolismo , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Sitios de Unión , Biotransformación , Cromatografía Líquida de Alta Presión , Citocromo P-450 CYP3A/genética , Citocromos b5/farmacología , Citocromos b5/fisiología , Relación Dosis-Respuesta a Droga , Escherichia coli/genética , Humanos , Estructura Molecular , Oxidación-Reducción , Unión Proteica , Quinolinas/farmacocinética , Quinolinas/farmacología , Tiofenos/farmacocinética , Tiofenos/farmacología
11.
Gen Dent ; 59(6): 466-73; quiz 474-5, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22313918

RESUMEN

The application of cleaning and polishing agents to a patient's dentition is a routine part of many dental practices. This study measured the surface roughness and surface gloss of tooth enamel, composite resin, and dental porcelain restorative materials when exposed to a paste-free prophylaxis polishing cup as well as a conventional prophylaxis polishing paste. Samples of human tooth enamel, a composite resin restorative material, and dental porcelain were prepared by a series of polishing papers to produce a flat smooth surface. The baseline average surface roughness (Ra) was measured using a contact stylus profilometer, and the surface gloss was measured with a glossmeter. The test samples were subjected to a standardized polishing routine using a paste-free prophylaxis polishing cup and a fine- or coarse-particle prophylaxis paste. Post-treatment surface roughness and gloss measurements were compared using a paired t statistical test. The conventional prophylaxis pastes increased surface roughness and decreased the gloss of the composite resin and tooth enamel test groups. The paste-free cups did not significantly affect the surface roughness of the enamel or the restorative materials. Dental porcelain surface roughness essentially was not affected by the application of paste-free cups and the fine and coarse pastes.


Asunto(s)
Esmalte Dental/anatomía & histología , Materiales Dentales/química , Profilaxis Dental/instrumentación , Restauración Dental Permanente , Pastas de Dientes/uso terapéutico , Resinas Compuestas/química , Porcelana Dental/química , Humanos , Luz , Tamaño de la Partícula , Propiedades de Superficie
12.
Quintessence Int ; 40(9): 763-72, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19862403

RESUMEN

OBJECTIVE: To evaluate the effect of adhesive agents and fissure morphology on the microleakage and penetrability of pit and fissure sealants. METHOD AND MATERIALS: Sealants used in this study included Aegis (Bosworth), conseal f (Southern Dental Industries), and Admira Seal (Voco). Adhesive agents included Optibond Solo Plus (sds/Kerr) and Clearfil S3Bond (Kuraray). Ninety extracted permanent molars were randomly assigned to 9 groups combining sealant and adhesive agent materials. A sealant and control group (phosphoric acid etch only) was also included. Dye penetration (microleakage), penetrability, and fissure morphology assessment was performed for the treatment groups through microscopic evaluation. RESULTS: Significant (P = .003) differences in microleakage were exhibited, with the Aegis + control and Aegis + Optibond Solo Plus groups displaying less leakage, while significant (P = .03) differences were also noted between groups regarding penetrability. Fissure morphology was not a significant (P = .82) factor affecting microleakage; however, fissure type did significantly (P < .001) impact penetrability. No correlation was found between the extent of microleakage and penetrability. CONCLUSION: Application of sealants using phosphoric acid as a conditioning agent revealed superior results, while the use of adhesives was found to be unnecessary.


Asunto(s)
Esmalte Dental/patología , Filtración Dental/clasificación , Selladores de Fosas y Fisuras/química , Cementos de Resina/química , Grabado Ácido Dental , Compuestos de Bario/química , Cerámica/química , Colorantes , Cementos Dentales/química , Recubrimientos Dentinarios/química , Fluoruros/química , Humanos , Ensayo de Materiales , Metacrilatos/química , Cerámicas Modificadas Orgánicamente , Ácidos Fosfóricos/química , Silanos/química , Silicatos/química , Siloxanos/química , Propiedades de Superficie , Temperatura , Factores de Tiempo
14.
Drug Metabol Drug Interact ; 24(2-4): 95-121, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20408495

RESUMEN

Cytochrome P450 can catalyze a wide array of remarkable oxidations, including O-dealkylations, which are performed via oxidation of the alpha-carbon of the ether. When C-H bonds are replaced with C-F bonds, however, the bond strength is much greater, and it significantly deters oxidation at the carbon. Another recently elucidated reaction catalyzed by P450, ipso substitution, results in displacement of aromatic ring substituents such as an alkoxy group via hydroxyl substitution. Through LC/MS/MS, we show the CYP-mediated oxidative displacement of the trifluoromethoxy group from the phenyl constituent in OSI-930, a novel small molecule c-Kit/VEGF-r inhibitor in clinical studies to treat cancer. Based on C-F bond strength, reported phenacetin studies, and alpha-quaternary alkylphenol studies, we propose an ipso-substitution mechanism for this oxidative biotransformation. In vivo, this hydroxylated metabolite goes on to form the ether conjugate with glucuronide.


Asunto(s)
Quinolinas/farmacocinética , Tiofenos/farmacocinética , Animales , Biotransformación , Cromatografía Liquida/métodos , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Microsomas Hepáticos/metabolismo , Oxidación-Reducción , Quinolinas/química , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Espectrometría de Masas en Tándem/métodos , Tiofenos/química
15.
Chem Res Toxicol ; 21(8): 1570-7, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18672911

RESUMEN

Compounds that are enzymatically transformed to reactive intermediates are common in nature. Some drugs and many phytochemicals that contain a thiophene ring are oxidized by cytochrome P450 to biological reactive intermediates (BRI) that can covalently bind to thiol nucleophiles. The investigational anticancer agent 3-[(quinolin-4-ylmethyl)-amino]-thiophene-2-carboxylic acid (4-trifluoromethoxy-phenyl)-amide (OSI-930) contains a thiophene moiety that can be oxidized by P450s to an apparent sulfoxide, which can react via Michael-addition to the 5-position of the thiophene ring, as demonstrated by mass spectral characterization of several thioether conjugates of the presumed thiophene S-oxide. Furthermore, a stable deuterium isotope retention experiment in which solvent deuterium was incorporated into the thiophene verifies the sulfoxide pathway. Various thiol nucleophiles are shown by tandem mass spectra to bind with this BRI, which is activated by P450 3A4 and to a slight degree, P450 2D6. Yet various safe drugs, phytochemicals, and endogenous molecules, all noted for their activation to BRI, are not toxic at a normal dose. Thus, multiple features determine any consequence of a BRI, with these complexities determining why one BRI is benign while another is not. The retention of covalent protein adducts of radio-labeled intermediate rat tissue has a half-life of about 1-1.5 days; hence, modified protein is cleared and replaced relatively quickly.


Asunto(s)
Antineoplásicos/farmacocinética , Sistema Enzimático del Citocromo P-450/metabolismo , Quinolinas/farmacocinética , Tiofenos/farmacocinética , Antineoplásicos/química , Cromatografía Líquida de Alta Presión , Sistema Enzimático del Citocromo P-450/química , Daño del ADN , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Glutatión/metabolismo , Semivida , Humanos , Hígado/metabolismo , Microsomas Hepáticos/metabolismo , Oxidación-Reducción , Unión Proteica , Quinolinas/química , Proteínas Recombinantes , Espectrometría de Masa por Ionización de Electrospray , Sulfóxidos/química , Sulfóxidos/metabolismo , Espectrometría de Masas en Tándem , Tiofenos/química
16.
Curr Drug Metab ; 9(4): 344-51, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18473753

RESUMEN

The metabolism of drugs and other xenobiotics is exemplified by cytochrome P450-mediated oxidation to more hydrophilic compounds. Enzymatic oxidation of some functional groups, however, can result in transient reactive intermediates--a transformation that is common in nature. Some drugs and many phytochemicals that contain, for example, a thiophene ring are oxidized by cytochrome P450 to reactive intermediates, such as sulfoxides, that can covalently bond to thiol nucleophiles in macromolecules, such as proteins. Many other functional groups can be oxidized to reactive intermediates--for instance, olefins, alkynes, alkylamines, furans, and p-aminophenols. Because any consequence of a biological reactive intermediate (BRI) is dependent on many factors a number of BRIs are benign. Toxicity is determined by complex and specific arrays of parallel and/or serial pathways and cellular states, not by entities or individual reactions. Because the formation of reactive intermediates can correlate with unacceptable toxicity, it is important to understand if or how a compound may undergo this type of transformation. Not all substances that form reactive intermediates are toxic; many are not. Therefore, it is critical to understand the mechanism of metabolism in considering any toxicity relevance and in evaluating animal models. Indeed, the complex nature of these many interactions and entities underscores the fact that the presence of a BRI is not an accurate indicator of human toxicity. A BRI is neither good nor a priori bad. It is a potential detoxication product and an incidental fate of the xenobiotic.


Asunto(s)
Biotransformación/fisiología , Preparaciones Farmacéuticas/metabolismo , Plantas/química , Xenobióticos/metabolismo , Animales , Humanos , Fitoterapia , Proteínas/metabolismo
17.
Drug Metab Rev ; 40(1): 101-47, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18259986

RESUMEN

One of the major clinical concerns is possible drug interactions that can be the result of abrogation of the P450 pathway(s) of metabolism causing toxicity due to elevated exposures of other drugs metabolized by these pathways. When the P450 substrate is catalytically activated to a reactive intermediate, this transient molecule may react with available nucleophilic residues from the enzyme - thereby resulting in the inactivation of the P450. The effects of CYP inactivation on the pharmacokinetics of co-administered drugs or on the inactivator itself depend on complex factors involving the molecular entities, the kinetics of inactivation (K(I), k(inact)), the partition ratio, the zero-order synthesis rate of new enzyme, multiple pathways of metabolism (competing pathways), the dose or exposure, and specific patient characteristics. This review summarizes the catalytic efficiencies of many inactivator drugs along with any consequent clinical relevance. The chemical agents described have been ranked for the kinetic efficiency of inactivation and contrasted with the known clinically relevant drug interactions. This will allow judicious consideration of the many factors that influence the importance of CYP inactivation and their relative contribution to systemic clearance of co-administered drugs. This study allows an improved characterization and dissection of potential physiological interactions with various drugs and nutrients. Knowing more about selective inactivation of cytochrome P450 by common xenobiotics, drugs and phytochemicals allows better understanding of expected interactions with chemotherapeutics and other xenobiotics.


Asunto(s)
Inhibidores Enzimáticos del Citocromo P-450 , Inhibidores Enzimáticos/farmacocinética , Preparaciones Farmacéuticas , Preparaciones de Plantas/farmacocinética , Animales , Sitios de Unión , Biotransformación , Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hígado/enzimología , Preparaciones Farmacéuticas/química , Preparaciones de Plantas/efectos adversos , Preparaciones de Plantas/química , Preparaciones de Plantas/uso terapéutico , Relación Estructura-Actividad , Especificidad por Sustrato
18.
Pediatr Dent ; 29(4): 308-14, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17867396

RESUMEN

PURPOSE: The purpose of this study was to evaluate the effect of material characteristics, preparation techniques, and fissure morphology on the microleakage and penetrability of pit and fissure sealants. METHODS: Sealants used in the study included: (1) Aegis; (2) Conseal f; (3) Admira Seal; (4) Triage; and (5) Delton Opaque. A total of 100 extracted permanent molars were randomly assigned to 10 groups that combined the materials and preparation technique (pumice prophylaxis and air abrasion). Following sealant placement, the specimens were: (1) subjected to thermal-cycling and dye immersion; (2) invested in acrylic; (3) sectioned for microscopic examination; and (4) assessed for dye penetration (microleakage) and penetrability. RESULTS: Significant differences in microleakage were seen. Aegis using pumice-prophylaxis surface pretreatment showed significantly less leakage than the other groups. Significant differences were also exhibited between groups seen regarding sealant penetrability, with Delton and Triage (pumice prophylaxis) revealing the greatest values. Fissure morphology was not a significant factor regarding microleakage. Morphology did significantly impact sealant penetrability, however, with u-type fissures displaying the greatest values. No correlation was found between the extent of microleakage and sealant penetrability. CONCLUSION: Material characteristics and fissure morphology were significant factors regarding sealant success, while surface preparation did not play an important role in sealant microleakage or fissure penetrability.


Asunto(s)
Permeabilidad del Esmalte Dental , Filtración Dental , Selladores de Fosas y Fisuras , Fisuras Dentales/patología , Fisuras Dentales/terapia , Humanos , Diente Molar , Análisis de Regresión , Estadísticas no Paramétricas , Preparación del Diente
19.
Oper Dent ; 32(1): 67-72, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17288331

RESUMEN

This in vitro study evaluated the coronal and apical marginal microleakage of four self-etch, seventh generation adhesive systems. Sixty non-carious human molars were randomly assigned to four groups (n = 12). Class V cavities were prepared on the facial or lingual surface of each tooth with coronal margins in enamel and apical margins in cementum (dentin) at the cementoenamel junction. The preparations were restored using four self-etch adhesive systems (iBond, G-Bond, Xeno IV and Clearfil S3 Bond) and a control (no adhesive), followed by insertion of Gradia Direct microfilled hybrid resin composite. The teeth (specimens) were thermocycled 1,000 cycles, immersed in 1% methylene blue dye for 24 hours and invested in acrylic resin. The specimen blocks were then sectioned longitudinally, with dye penetration (microleakage) examined using a 20x binocular microscope. Coronal and apical margins were scored separately for microleakage using a 0-3 ordinal ranking system. Data were analyzed using non-parametric tests at a p < 0.05 level of significance. A comparison of adhesive and control groups at the coronal and apical margins revealed that significant (p < .0001) differences were exhibited. At the coronal margin, Xeno IV revealed significantly less leakage than the other adhesives, with Clearfil S3 Bond exhibiting significantly less leakage at the apical margin. Groups with no adhesive treatment (control) showed significantly greater leakage at both the coronal and apical margin locations. A Wilcoxon signed rank test showed no significant differences at the coronal compared to the apical margins of the four adhesive systems and control tested.


Asunto(s)
Resinas Acrílicas/química , Resinas Compuestas/química , Recubrimiento Dental Adhesivo/métodos , Filtración Dental , Permeabilidad de la Dentina/efectos de los fármacos , Recubrimientos Dentinarios/química , Poliuretanos/química , Adaptación Marginal Dental , Humanos , Estadísticas no Paramétricas
20.
Oper Dent ; 31(4): 481-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16924989

RESUMEN

This study evaluated, in vitro, the effectiveness of 5 surface sealants (Biscover, Optiguard, Seal-n-Shine, PermaSeal and DuraFinish); 1 pit and fissure sealant (Helioseal) and 1 dentin bonding agent (Adper Scotchbond MultiPurpose Adhesive) on the marginal sealing ability of Class V hybrid resin composite (Esthet.X) restorations. Ninety-six non-carious human molars were randomly assigned to 8 groups (n=12). Class V cavities were prepared on either the facial or lingual surfaces, with coronal margins in enamel and apical margins in cementum (dentin), and restored following manufacturers' instructions. Following finishing and polishing procedures, the covering agents were applied to each restoration and adjacent tooth surface, except for the control group restorations, which were not sealed. The teeth were thermocycled, immersed in a 1% methylene blue dye solution, sectioned and analyzed for dye penetration (leakage) using a 20x binocular microscope. Microleakage was evaluated at the coronal and apical margins using an 0-3 ordinal grading scale. Non-parametric data was analyzed at a p< or =0.05 level of significance. The Kruskal-Wallis test showed a significant difference was exhibited among groups at the coronal margins, with Helioseal pit/fissure sealant and DuraFinish surface sealant exhibiting significantly less leakage than the control and Adper Scotchbond MultiPurpose adhesive. At the apical margins, DuraFinish surface sealant showed significantly less leakage than the Biscover, Seal-n-Shine and PermaSeal surface sealants or Helioseal pit/fissure sealant, Adper Scotchbond MultiPurpose adhesive and the control group. According to the Wicoxon signed-rank test, significantly greater leakage was revealed at the apical margins compared to the enamel margins of the material groups.


Asunto(s)
Resinas Compuestas/química , Recubrimiento Dental Adhesivo , Materiales Dentales/química , Restauración Dental Permanente/clasificación , Acrilatos/química , Colorantes , Preparación de la Cavidad Dental/clasificación , Cemento Dental/ultraestructura , Esmalte Dental/ultraestructura , Filtración Dental/clasificación , Adaptación Marginal Dental , Pulido Dental , Dentina/ultraestructura , Recubrimientos Dentinarios/química , Humanos , Ensayo de Materiales , Azul de Metileno , Permeabilidad , Selladores de Fosas y Fisuras/química , Cementos de Resina/química , Propiedades de Superficie
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