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1.
Clin Oral Implants Res ; 28(9): e121-e134, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27492799

RESUMEN

OBJECTIVES: This split-mouth study evaluated miRNA expression of tissues around implants with different surface treatments. MATERIAL AND METHODS: Each patient of the sample (five men and five women) received two implants (one control and one test) into an edentulous quadrant to support fixed partial dentures. The control implants (Osseotite) had a dual acid-etched (DAE) surface in the apical portion and a machined coronal part, test implants (Full Osseotite, FOSS) were completely DAE. Machined healing abutments were placed on control implants and DAE abutments on test ones. All implants were assigned codes for blinding. Standardized periapical radiographs were taken at baseline, 2 and 6 months, and 1 year after surgery. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded at 3 and 6 weeks, and 2, 3, 6, and 12 months post-implant placement. After 3 months, a mini-invasive sample of soft tissue was collected from seven patients (four women and three men) for miRNA microarray analysis. RESULTS: Control implants showed greater bone resorption (BR) and lower PI: this was not statistically significant. No statistically significant differences in BOP and PD appeared. miRNA modulated by implant surfaces as well as by other clinical conditions has been identified. miRNA microarray analysis revealed that: (i) implant sites with low PI and absence of BOP had a miRNA expression profile similar to those with plaque and absence of BOP; sites with high PI and high BOP had a different profile. (ii) Implant sites with BOP presented similar profiles independently from implant surface. (iii) Implant sites with high PI and normal BR differed from others for miRNA expression profile. (iv) Implant sites with normal BR despite high BOP differed from others. This profile resembled that of FOSS implants. (v) Implant surface affected BR; groups having similar BR clusterized differently according to the implant type. CONCLUSIONS: DAE surfaces induced lower BR and more plaque accumulation: This did not affect the health of soft tissues. miRNA analysis indicated that soft tissue inflammation is more related to gene expression profile than to plaque or to implant surface. Specific miRNA profile can protect implant sites from bleeding and BR irrespective of plaque accumulation.


Asunto(s)
Implantes Dentales , Prótesis Dental de Soporte Implantado , Periodoncio/metabolismo , Titanio , Diseño de Prótesis Dental , Femenino , Humanos , Masculino , MicroARNs/biosíntesis , Análisis por Micromatrices , Valor Predictivo de las Pruebas , Propiedades de Superficie , Resultado del Tratamiento
2.
J Oral Rehabil ; 44(5): 392-397, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28196278

RESUMEN

Frameworks made of carbon fibre-reinforced composites (CFRC) seem to be a viable alternative to traditional metal frameworks in implant prosthodontics. CFRC provide stiffness, rigidity and optimal biocompatibility. The aim of the present prospective study was to compare carbon fibre frameworks versus metal frameworks used to rigidly splint implants in full-arch immediate loading rehabilitations. Forty-two patients (test group) were rehabilitated with full-arch immediate loading rehabilitations of the upper jaw (total: 170 implants) following the Columbus Bridge Protocol with four to six implants with distal tilted implants. All patients were treated with resin screw-retained full-arch prostheses endowed with carbon fibre frameworks. The mean follow-up was 22 months (range: 18-24). Differences in the absolute change of bone resorption over time between the two implant sides (mesial and distal) were assessed performing a Mann-Whitney U-test. The outcomes were statistically compared with those of patients rehabilitated following the same protocol but using metal frameworks (control group: 34 patients with 163 implants - data reported in Tealdo, Menini, Bevilacqua, Pera, Pesce, Signori, Pera, Int J Prosthodont, 27, 2014, 207). Ten implants failed in the control group (6·1%); none failed in the test group (P = 0·002). A statistically significant difference in the absolute change of bone resorption around the implants was found between the two groups (P = 0·004), with greater mean peri-implant bone resorption in the control group (1 mm) compared to the test group (0·8 mm). Carbon fibre frameworks may be considered as a viable alternative to the metal ones and showed less marginal bone loss around implants and a greater implant survival rate during the observation period.


Asunto(s)
Carbono , Aleaciones Dentales , Implantación Dental Endoósea/instrumentación , Implantes Dentales , Prótesis Dental de Soporte Implantado , Retención de Dentadura/instrumentación , Carga Inmediata del Implante Dental/métodos , Pérdida de Hueso Alveolar , Fibra de Carbono , Implantación Dental Endoósea/métodos , Prótesis Dental de Soporte Implantado/instrumentación , Diseño de Dentadura , Femenino , Estudios de Seguimiento , Humanos , Masculino , Maxilar/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
3.
J Oral Rehabil ; 42(9): 663-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25882620

RESUMEN

Full-arch immediate loading implant rehabilitations provide patients with compromised dentition an effective treatment to improve their aesthetic and function. Aim of this prospective cohort study was to investigate the correlation between masticatory ability and gastric emptying rates among these patients. Ten subjects (five men and five women) with compromised dentition were tested in two occasions: before treatment and 30 days after the immediate loading rehabilitation. Masticatory ability was evaluated using the sieves test, and the gastric half emptying time (T(1/2)) was assessed by means of the 13C-octanoic acid breath test. A statistically significant increment (P < 0.005) in masticatory ability was found only in reference to the particles smaller than or equal to 4.75 mm, whereas the gastric emptying rate showed a statistically significant reduction between pre- and post-treatment (P = 0.003). A moderate negative correlation (rho = 0.64, P = 0.048) between the percentage change in masticatory ability and the percentage change in gastric emptying rate was evidenced. Patients with compromised dentition rehabilitated with full-arch immediate implant prostheses present a significant improvement of the gastric process.


Asunto(s)
Caprilatos/metabolismo , Prótesis Dental de Soporte Implantado , Vaciamiento Gástrico , Carga Inmediata del Implante Dental , Mandíbula/cirugía , Masticación , Adulto , Anciano , Pruebas Respiratorias , Isótopos de Carbono/metabolismo , Implantes Dentales , Diseño de Dentadura , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Carga Inmediata del Implante Dental/métodos , Masculino , Masticación/fisiología , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento
4.
J Prev Med Hyg ; 54(3): 138-45, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24783891

RESUMEN

Biphosphonate (BPN) are widely used in clinics to treat metastatic cancer and osteoporosis thus representing a problem not only for patients but also for workers involved in their preparation and administration. A similar exposure occurred years ago in match-making workers undergoing bone alterations similar to those consequent to BPN exposure. Osteonecrosis of the jaw (ONJ) is a main adverse effect related to BPN administration, which is performed in millions of patients worldwide for osteoporosis and cancer therapy, thus representing an emerging problem in public health. In susceptible patients, BPN induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular ONJ often triggered by dental surgery. BPN induced ONJ occurs in subjects depending on lifestyle factors of both environmental and endogenous origins. Exogenous risk factors include cigarette smoke, alcohol consumption, bacterial infections, and cyclosporine therapy. Endogenous risk factors include systemic diseases such as diabetes or hypertension and adverse polymorphisms of genes involved in metabolism (CYPs, MTHFR), thrombosis (Factor V, Prothrombin), and detoxification (MDR). Available molecular findings provide evidence that ONJ is related to risk-factors associated with environmental mutagenesis and gene-environment interactions. This issues may be useful to identify susceptible subjects by molecular analyses in order to prevent ONJ occurrence.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Interacción Gen-Ambiente , Biomarcadores/sangre , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Colágeno Tipo I/sangre , Ciclosporina/efectos adversos , Daño del ADN , Difosfonatos/efectos adversos , Inhibidores Enzimáticos/efectos adversos , Humanos , Procedimientos Quirúrgicos Orales/efectos adversos , Péptidos/sangre , Polimorfismo de Nucleótido Simple , Radiación Ionizante , Factores de Riesgo , Fumar/efectos adversos
5.
Oral Dis ; 18(4): 402-9, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22221343

RESUMEN

OBJECTIVES: As the oral cavity is regarded as a relevant site for Staphylococcus aureus colonization and interhuman transmission, this study aimed to investigate whether different oral conditions influence the rates of S. aureus oral carriage and genetic characters of S. aureus isolates. SUBJECTS AND METHODS: Staphylococcus aureus was searched in samples collected from cheek, gingival margin, and anterior nares of 45 healthy subjects, 27 periodontitis affected subjects, and 29 subjects with fixed prosthetic restorations. Isolates were screened for 17 genetic determinants, and Partial Least Square Discriminant Analysis was performed to evaluate whether specific characters correlated with oral condition or site of isolation. RESULTS: The three subject groups showed comparable nasal carriage rates but, both the periodontitis and prosthetic restoration groups showed significantly higher oral carriage rates, as compared to healthy subjects (P = 0.01 and 0.02, respectively). Moreover, periodontitis affected subjects hosted strains possessing a distinct genotypic and phenotypic background, characterized by the presence of a larger number of exotoxins encoding genes. CONCLUSIONS: These data confirm that the oral cavity is an important site of S. aureus colonization and demonstrate that conditions modifying the oral environment, as the presence of periodontitis and of fixed prosthetic restorations, promote S. aureus carriage and may favor the spread of more pathogenic strains.


Asunto(s)
Boca/microbiología , Staphylococcus aureus/fisiología , Adulto , Pérdida de Hueso Alveolar/microbiología , Carga Bacteriana , Fenómenos Fisiológicos Bacterianos , Toxinas Bacterianas/genética , Mejilla/microbiología , Periodontitis Crónica/microbiología , Índice de Placa Dental , Prótesis Dental/microbiología , Exotoxinas/genética , Femenino , Variación Genética/genética , Genotipo , Encía/microbiología , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Persona de Mediana Edad , Mucosa Bucal/microbiología , Nariz/microbiología , Índice Periodontal , Bolsa Periodontal/microbiología , Fenotipo , Staphylococcus aureus/genética , Factores de Virulencia/genética , Adulto Joven
6.
Rev Clin Esp (Barc) ; 221(8): 448-455, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34167923

RESUMEN

BACKGROUND AND OBJECTIVE: Therapeutic patient education (TPE) is effective and essential in the context of the growing prevalence of chronic diseases in which tools are needed for planning structured programs. The objective of this project was to develop guidelines for designing and assessing a TPE program. METHODS: 1) We assembled a multidisciplinary group of 8 leaders in TPE, chronicity, quality and safety from the hospital and the university. 2) We conducted an exhaustive review of the scientific literature on the planning of TPE programs directed at chronically ill patients, their relatives and caregivers. 3) The final text underwent comments and suggestions by participants from the hospital and primary care centre during a course on information and TPE methodology. The recommendations were unanimously agreed upon by the writing group. RESULTS: We obtained a standardised work procedure targeted at professionals involved in planning TPE programs, based on international recommendations. The document is structured into sections: a) Definition of the health problem and analysis of the situation; b) Program structure (human resources and materials); objectives (health-related, behaviour-related and educational) and methodology; c) Path the patient and family/caregiver follows in the program; and d) Assessment and indicators. Assessment of the procedure, within the framework of the methodology courses, was favourable. CONCLUSIONS: The methodology provided by this document serves as an instrument for the standardised and systematic planning of educational programs and unifies the criteria in their drafting. However, the document needs to be adapted to the condition and population to which each program is addressed.


Asunto(s)
Cuidadores , Atención Primaria de Salud , Enfermedad Crónica , Humanos
7.
Mutat Res ; 667(1-2): 118-31, 2009 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-19056406

RESUMEN

Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.


Asunto(s)
Daño del ADN , Ambiente , Enfermedades Maxilomandibulares/etiología , Enfermedades Maxilomandibulares/genética , Osteonecrosis/etiología , Osteonecrosis/genética , Enfermedades Periodontales/etiología , Enfermedades Periodontales/genética , Enfermedad Crónica , ADN Mitocondrial , Predisposición Genética a la Enfermedad , Humanos , Inflamación/complicaciones , Enfermedades Maxilomandibulares/complicaciones , Osteonecrosis/complicaciones , Enfermedades Periodontales/inmunología , Polimorfismo Genético , Factores de Riesgo , Fumar/efectos adversos
8.
J Natl Cancer Inst ; 93(16): 1234-45, 2001 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-11504769

RESUMEN

BACKGROUND: The taxane paclitaxel (Taxol) is often of limited efficacy in chemotherapeutic regimens because some cancer cells express high levels of the efflux pump, P-glycoprotein (Pgp), which removes the drug from the cells. The orally active paclitaxel analog IDN-5109 has been reported to overcome Pgp-mediated drug resistance. We tested whether IDN-5109 acts by modulating Pgp activity. METHODS: Human MDA435/LCC6mdr1 and MDA435/LCC6 breast carcinoma cells, which express and do not express Pgp, respectively, were incubated with [3H]IDN-5109 and paclitaxel to determine intracellular drug accumulation. Flow cytometry was used to analyze intracellular retention of two Pgp substrates, rhodamine 123 (Rh-123) and doxorubicin, in both breast carcinoma cell lines and in human colon carcinoma cells (SW-620, DLD1, and HCT-15, whose Pgp levels vary) treated with different taxanes. The effects of IDN-5109 and paclitaxel on tumor growth in vivo were studied with the use of tumors established through xenografts of Pgp-expressing SW-620 and DLD1 cells in severe combined immunodeficiency mice. All statistical tests were two-sided. RESULTS: Pgp-expressing cells treated with IDN-5109 or with the taxane-based drug resistance reversal agent tRA96023, which blocks Pgp activity, retained 8.1- and 9.4-fold more Rh-123 (P =.0001), respectively, and 1.7- and 1.9-fold more doxorubicin (P =.001), respectively, than cells treated with paclitaxel. Non-Pgp-expressing cells treated similarly demonstrated no increased retention of either substrate. MDA435/LCC6mdr1 cells retained 5.3-fold more [3H]IDN-5109 than [3H]paclitaxel after 2 hours (P =.01). IDN-5109 showed statistically significantly higher tumor growth inhibition than paclitaxel against the SW-620 xenograft (P =.003). CONCLUSIONS: IDN-5109 modulates Pgp activity, resulting in superior tumor growth inhibition against Pgp-expressing tumors as compared with paclitaxel. IDN-5109 may broaden the spectrum of taxane use to include colon tumors.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/farmacología , Neoplasias del Colon/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/farmacología , Taxoides , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/efectos de los fármacos , Administración Oral , Animales , Antibióticos Antineoplásicos , Antineoplásicos Fitogénicos/farmacocinética , Neoplasias de la Mama/metabolismo , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Neoplasias del Colon/metabolismo , Doxorrubicina/farmacocinética , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Citometría de Flujo , Fluorescencia , Humanos , Masculino , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Distribución Tisular , Trasplante Heterólogo , Células Tumorales Cultivadas
9.
Cancer Res ; 46(3): 1148-54, 1986 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3080234

RESUMEN

The effects of the enzyme-activated irreversible inhibitors of ornithine decarboxylase, alpha-difluoromethylornithine, alpha-(fluoromethyl)dehydroornithine, alpha-(fluoromethyl)dehydroornithine methyl ester, and (2R,5R)-6-heptyne-2,5-diamine (RR-MAP), on cell growth and parameters related to polyamine biosynthesis were compared in L5178Y and L1210 cells under identical culture conditions. The two lines are murine lymphocytic leukemia cells which differ in their ability to metabolize 5'-methylthioadenosine, the by-product of polyamine biosynthesis: L5178Y cells contain a specific 5'-methylthioadenosine phosphorylase; L1210 cells do not. In L1210 cells, the 50% inhibitory concentrations (lC50S) of the various analogues were 3.0 mM for alpha-difluoromethylornithine, 0.2 mM for alpha-(fluoromethyl)dehydroornithine, 0.1 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.01 mM for RR-MAP. L5178Y cells were somewhat more sensitive to the inhibitors with lC50 values of 0.5 mM for alpha-difluoromethylornithine, 0.06 mM for alpha-(fluoromethyl)dehydroornithine, 0.03 mM for alpha-(fluoromethyl)dehydroornithine methyl ester, and 0.002 mM for RR-MAP. In all cases, growth inhibition was fully prevented by exogenous putrescine. The effects of the inhibitors on parameters related to polyamine metabolism were compared at drug concentrations approximating the average of lC50 values for the two cell lines. Under these treatment conditions, polyamine pools were similarly affected by the various inhibitors. Typically, putrescine and spermidine were depleted, but effects on spermine pools differed according to the cell line, increasing slightly in L1210 cells and decreasing by about 50% in L5178Y cells. Spermine pools in L1210 cells could be reduced by RR-MAP at concentrations higher than the lC50 (i.e., 0.1 mM). Clonogenicity in soft agar was decreased about 50% by putrescine and spermidine depletion and was not further affected by spermine depletion. The inhibitors elevated S-adenosylmethionine decarboxylase activity in both cell lines with a 2-fold greater increase in L5178Y cells than in L1210 cells. Finally, the inhibitors decreased S-adenosylmethionine pools in L1210 cells by about 50% but had little effect on these pools in L5178Y cells with the exception of RR-MAP, which decreased S-adenosylmethionine pools by about 40%. Whether the different polyamine responses of the two cell lines are related to their ability to metabolize 5'-methylthioadenosine is uncertain. It is apparent, however, that the presence or absence of methylthioadenosine phosphorylase does not substantially modulate the antiproliferative activity of ornithine decarboxylase inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Diaminas/farmacología , Leucemia Linfoide/tratamiento farmacológico , Inhibidores de la Ornitina Descarboxilasa , Ornitina/análogos & derivados , Alquinos , Animales , Transporte Biológico , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Eflornitina , Leucemia L1210/tratamiento farmacológico , Leucemia L1210/enzimología , Leucemia L5178/tratamiento farmacológico , Leucemia L5178/enzimología , Leucemia Linfoide/enzimología , Ratones , Ornitina/farmacología , Poliaminas/biosíntesis , Purina-Nucleósido Fosforilasa/metabolismo , S-Adenosilmetionina/metabolismo
10.
Int J Oral Maxillofac Surg ; 45(3): 346-53, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26586300

RESUMEN

The aim of this split-mouth, double-blind, randomized study was to determine whether pulsed electromagnetic field therapy (PEMF) can improve swelling and the management of pain after full-arch immediate loading implant surgery. Eleven patients were selected for the study. Each patient received four distal tilted implants in the upper or lower jaw and underwent full-arch immediate loading rehabilitation. After surgery, two PEMF devices were applied to each patient, one on each cheek. In a random manner, one of these PEMF devices was switched on (test side); the other served as a placebo (control side). Forty-eight hours after surgery clinicians estimated postoperative swelling through photographic documentation, comparing the condition before and after surgery, while pain was assessed using a verbal rating scale. The patient's degree of comfort in relation to the PEMF devices was analyzed by questionnaire using a numerical rating scale. No statistically significant difference was observed between the test and control sides for swelling or pain (P>0.05). Most of the patients did not present swelling or pain at 48h after surgery, regardless of whether the PEMF device was activated or not. Various outcomes were found in the comfort evaluation. Within the limitations of this study, PEMF does not reduce postoperative swelling or pain after implant surgery.


Asunto(s)
Edema/prevención & control , Carga Inmediata del Implante Dental , Arcada Edéntula/rehabilitación , Magnetoterapia , Dolor Postoperatorio/prevención & control , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Resultado del Tratamiento
11.
Minerva Stomatol ; 54(6): 363-71, 2005 Jun.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-16175165

RESUMEN

AIM: The aim of this study was to investigate the in vitro cytotoxicity of 5 ceramic materials for metal-free fixed prosthodontics: In-Ceram, Cergo, IPS Empress II, Cercon ZrO2, Finesse All Ceram compared each other and to commercially pure Titanium (CpTi). METHODS: The materials, prepared directly from manufacturers as 10 mm diameter and 3 mm thickness disks, have been tested following the ISO 10993-l guidelines, performing the in vitro cytotoxicity test with the use of mouse's cells, fibroblasts L-929, isolated by muscular tissue and cultured in an appropriate medium. The MTT test has been used to evaluate the cell viability through the succinate dehydrogenase enzyme activity. The originality of this investigation is that all the materials examined have been tested under the same conditions: the cytotoxicity test has been performed on these materials at the same time, in the same period, under the same conditions of temperature and humidity and by the same operator. RESULTS: Not all tested materials were free from cytotoxicity. Cercon, within the limits of this in vitro study, showed the lower cytotoxicity. CONCLUSIONS: This in vitro study suggested that ceramic materials for metal free prosthetic substructures are in competition with the CpTi which is very used in implant prosthodontics.


Asunto(s)
Cerámica/toxicidad , Prótesis Dental , Ensayo de Materiales , Animales , Células Cultivadas , Diseño de Prótesis Dental , Ratas , Pruebas de Toxicidad
12.
J Med Chem ; 40(3): 279-85, 1997 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-9022794

RESUMEN

Several new nonaromatic taxoids are synthesized by means of the beta-lactam synthon method. These include taxoids modified with 3-methylbut-2-enoate, 3-methylbutanoate, and cyclohexanecarboxylate groups in place of the benzoate at the C-2 position. In addition, taxoids with 2-methylprop-1-enyl, 2-methylpropyl, (E)-prop-1-enyl, and cyclohexyl groups at the C-3' position are also prepared in combination with the modifications at C-2. The alkyl and alkenyl ester groups at C-2 displayed pronounced effects on the in vitro cytotoxicity. Two of the fully aliphatic taxoids possess similar or stronger activity than paclitaxel and docetaxel. It is clear that the 2-benzoate does not play a unique role, and replacement with the appropriate alkyl and alkenyl groups provides taxoids with equivalent or superior activity.


Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Paclitaxel/análogos & derivados , Taxoides , Antineoplásicos Fitogénicos/química , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Ésteres , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/síntesis química , Paclitaxel/química , Paclitaxel/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas
13.
J Med Chem ; 39(20): 3889-96, 1996 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-8831755

RESUMEN

A series of new 3'-(2-methyl-1-propenyl) and 3'-(2-methylpropyl) taxoids with modifications at C-10 was synthesized by means of the beta-lactam synthon method using 10-modified 7-(triethylsilyl)-10-deacetylbaccatin III derivatives. The new taxoids thus synthesized show excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines. All but one of these new taxoids possess better activity than paclitaxel and docetaxel in the same assay, i.e., the IC50 values of almost all the taxoids are in the subnanomolar level. It is found that a variety of modifications at C-10 is tolerated for the activity against normal cancer cell lines, but the activity against a drug-resistant human breast cancer cell line expressing MDR phenotype (MCF7-R) is highly dependent on the structure of the C-10 modifier. A number of the new taxoids exhibit remarkable activity (IC50 = 2.1-9.1 nM) against MCF7-R. Among these, three new taxoids, SB-T-1213 (4a), SB-T-1214 (4b), and SB-T-1102 (5a), are found to be exceptionally potent, possessing 2 orders of magnitude better activity than paclitaxel and docetaxel. The observed exceptional activity of these taxoids may well be ascribed to an effective inhibition of P-glycoprotein binding by the modified C-10 moieties. The new taxoid SB-T-1213 (4a) shows an excellent activity (T/C = 0% at 12.4 and 7.7 mg/kg/dose, log10 cell kill = 2.3 and 2.0, respectively) against B16 melanoma in B6D2F1 mice via intravenous administration.


Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Paclitaxel/análogos & derivados , Taxoides , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel , Resistencia a Antineoplásicos , Femenino , Humanos , Melanoma Experimental/tratamiento farmacológico , Ratones , Ratones Desnudos , Estructura Molecular , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/síntesis química , Paclitaxel/uso terapéutico , Relación Estructura-Actividad , Células Tumorales Cultivadas
14.
J Med Chem ; 40(3): 267-78, 1997 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-9022793

RESUMEN

A series of new taxoids derived from 14 beta-hydroxy-10-deacetylbaccatin III was synthesized by means of the beta-lactam synthon method. Most of the new taxoids thus synthesized possess excellent cytotoxicity against human ovarian (A121), non-small-cell lung (A549), colon (HT-29), and breast (MCF-7) cancer cell lines, and several of these taxoids show subnanomolar IC50 values which are severalfold to 1 order of magnitude better than those of paclitaxel and docetaxel. Modifications at the 3'- and 3'-N-positions exert marked effects on the activity. For the substituents at C-3', the cytotoxicity decreases in the order 2-furyl approximately 2-methyl-1-propenyl > or = 2-methylpropyl > (E)-1-propenyl > or = n-propyl > phenyl > > 2,2-dimethylpropyl. For the 3'-N substituents, the activity decreases in the order t-BuOCO > Ph > n-hexanoyl. A significant increase in the cytotoxicity against the doxorubicin-resistant human breast cancer cell line MCF7-R that expresses the multidrug resistance (MDR) phenotype is observed by the proper modification of the substituent at C-10. The observed remarkable effects of the substituents at C-10 on the activity against MCF7-R can be ascribed to the effective inhibition of the binding of these new taxoids to P-glycoprotein that is responsible for MDR.


Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Paclitaxel/análogos & derivados , Taxoides , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/metabolismo , Docetaxel , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estructura Molecular , Paclitaxel/síntesis química , Paclitaxel/química , Paclitaxel/metabolismo , Paclitaxel/farmacología , Relación Estructura-Actividad , Células Tumorales Cultivadas
15.
Ann N Y Acad Sci ; 922: 293-7, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11193904

RESUMEN

Preclinical studies at Roswell Park Cancer Institute by Minderman, Cao, and Rustum (unpublished results) showed that a combination of SN-38 and 5-FU against HCT-8 human colon carcinoma cells in vitro was synergistic, with the best interaction occurring when the drugs were added sequentially, SN-38 first. Their in vivo studies using HCT-8 tumor xenografts implanted s.c. in nude athymic mice demonstrated superior efficacy for a sequential i.v. administration of CPT-11, 24 hr before 5-FU. On the basis of these studies, our group has begun to evaluate effects of RFS2000 (9-nitro-20(S)-camptothecin) (9-NC) in combination with a series of other antitumor agents. Using a panel of human tumor cell lines including A121 ovarian cancer, HCT-8 colon cancer, H-460 NSCLC, HT-1080 fibrosarcoma, and MCF7 mammary cancer, we found that a 2-hr exposure to 9-NC resulted in ID50 values of < 1.0 microM, whereas continuous exposure to drug resulted in ID50 values of < 1.0 nM. Tumor growth inhibitory activities of 5-FU, gemcitabine, and paclitaxel were determined for comparison. Combinations of these agents were evaluated with 9-NC using the human HCT-8 colon tumor cell line. Concurrent and sequential combinations of 9-NC with 5-FU had some regions of the concentration-effect surface with local synergy and some with local antagonism. However, sequential combination of 9NC or SN-38 followed by 5-FU, 24 hr later appeared to be highly synergistic at high dose-effect levels (i.e., ID90), suggesting that sequential drug administration may be more efficacious at high effect level and that the order of drug addition is very important. Overall, our results were similar to that found earlier by Rustum's group with CPT11 (or SN-38) and 5-FU, suggesting that sequential combination of 9-NC (or other camptothecin analogues) followed by 5-FU has potential for the treatment of cancer in man.


Asunto(s)
Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Camptotecina/farmacología , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Fluorouracilo/administración & dosificación , Humanos , Células Tumorales Cultivadas/efectos de los fármacos
16.
J Dent Res ; 81(3): 179-81, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11876271

RESUMEN

The role of mastication on digestion efficiency remains to be demonstrated. This study investigates whether masticatory function influences gastric emptying rate. Twelve normal volunteers were studied on two occasions after ingestion of the same test meal containing ham cubes, crackers, and egg (mixed with 13C-octanoic acid), chewed, in random order, either with 50 masticatory cycles or with 25 cycles, swallowing ham cubes whole. Lag phase (Tlag) and gastric half-emptying time (T1/2) were measured by means of the 13C-octanoic acid breath test. Trituration performance was assessed by the sieve test, and was expressed as the percentage of ham particles < or = 1 mm after 50 masticatory cycles. Tlag and T1/2 were significantly shorter when the meal was chewed with 50 cycles than with 25 cycles (Tlag 25.9+/-3.8 vs. 36.4+/-4.1 min, p=0.017; T1/2 49.1+/-5.7 vs. 62.5+/-6 min, p=0.009). Trituration performance was inversely related to both Tlag (r=0.621, p=0.031) and T1/2 (r=0.699, p=0.012). Comminution of food influences significantly gastric emptying rates.


Asunto(s)
Vaciamiento Gástrico/fisiología , Masticación/fisiología , Adulto , Animales , Pruebas Respiratorias , Caprilatos , Dióxido de Carbono/análisis , Isótopos de Carbono , Grano Comestible , Huevos , Femenino , Contenido Digestivo , Humanos , Modelos Lineales , Masculino , Espectrometría de Masas , Carne , Persona de Mediana Edad , Antro Pilórico/fisiología , Estadística como Asunto , Porcinos , Factores de Tiempo , Agua
17.
Int J Oral Maxillofac Implants ; 13(3): 369-76, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9638007

RESUMEN

Transmission of masticatory load in mandibular implant-retained overdentures was evaluated using a three-dimensional finite element model. The reaction forces on the distal edentulous mucosa and the stress on the perimplant bone were compared in overdentures retained either by two ball attachments or by two clips on a bar connecting two implants. In the finite element model, a 35 N load on the first mandibular molar induced a greater reaction force on the distal edentulous ridge mucosa of the nonworking side when the overdenture was anchored by ball attachments than with the clips/bar attachment. Stress on peri-implant bone was greater with the clips/bar attachment than with the ball attachment.


Asunto(s)
Retención de Prótesis Dentales/métodos , Prótesis Dental de Soporte Implantado , Análisis del Estrés Dental/métodos , Prótesis de Recubrimiento , Proceso Alveolar/fisiología , Simulación por Computador , Abrazadera Dental , Retención de Prótesis Dentales/instrumentación , Ajuste de Precisión de Prótesis , Humanos , Arcada Edéntula/fisiopatología , Mandíbula/fisiología , Modelos Biológicos , Mucosa Bucal/fisiología
18.
Int J Oral Maxillofac Implants ; 13(6): 851-6, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9857597

RESUMEN

This in-vivo study aimed to investigate the load on the working-side implant and on the edentulous distal mucosa of the nonworking side in a mandibular implant-retained overdenture (MIR-OVD) anchored to 2 implants by either a ball- or a clips-and-bar attachment. Three female patients were provided with duplicate dentures anchored in the 2 ways. Strain on the implant was investigated using a strain-gauged abutment, and load on the mucosa was measured using a suitably placed load cell. Ball attachments appeared to provide greater stability to the MIR-OVD, since load was more evenly distributed onto the distal mucosa of both sides. When the MIR-OVD was bar-anchored, axial load on the working-side abutment increased.


Asunto(s)
Implantación Dental Endoósea , Implantes Dentales , Diseño de Prótesis Dental , Prótesis Dental de Soporte Implantado , Prótesis de Recubrimiento , Mandíbula/cirugía , Anciano , Fuerza de la Mordida , Pilares Dentales , Oclusión Dental Céntrica , Retención de Dentadura , Femenino , Humanos , Arcada Edéntula/rehabilitación , Arcada Edéntula/cirugía , Persona de Mediana Edad , Mucosa Bucal/fisiología , Procesamiento de Señales Asistido por Computador , Estrés Mecánico , Propiedades de Superficie
19.
Bioorg Khim ; 21(12): 925-32, 1995 Dec.
Artículo en Ruso | MEDLINE | ID: mdl-8602889

RESUMEN

Doxorubicin and 14-hydroxycarminomycin 14-O-hemiadipates and 14-O-hemipimelates, synthesized from 14-bromo derivatives of daunorubicin and carminomycin and monosodium adipate and pimelate, were converted to the corresponding N-trifluoroacetylated compounds. 13-(4-Methylpiperazine-1-yl)imino derivatives of the anthracycline antibiotics were also obtained. The cytostatic activity of the compounds synthesized was studied using a panel of human and animal tumor cell lines sensitive or resistant to doxorubicin. N-Trifluoroacetylation of the antibiotics resulted in a decrease in the cytostatic activity. The activity of the water-soluble 13-(4-methylpiperazine-l-yl)imino derivatives is close to that of the corresponding parent antibiotics.


Asunto(s)
Antibióticos Antineoplásicos/síntesis química , Daunorrubicina/química , Doxorrubicina/farmacología , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Daunorrubicina/farmacología , Resistencia a Antineoplásicos , Ésteres , Humanos , Hidrazonas/química , Leucemia P388/patología , Células Tumorales Cultivadas
20.
Minerva Stomatol ; 38(3): 299-306, 1989 Mar.
Artículo en Italiano | MEDLINE | ID: mdl-2657366

RESUMEN

The authors, after having considered some structural aspects of the temporomandibular joint, examine the histologic features of the degenerative disease (arthrosis, remodelling, deviation in form).


Asunto(s)
Osteoartritis/patología , Trastornos de la Articulación Temporomandibular/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
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