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1.
Eur J Med Chem ; 167: 525-545, 2019 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30784884

RESUMEN

Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained. Overall, mitochondriotropic antioxidants showed remarkable antioxidant and chelating properties, presenting low cytotoxic effects on human differentiated neuronal (SH-SY5Y) and hepatocarcinoma (HepG2) cells and exhibited neuroprotective properties on SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2) oxidative insults. Moreover, compounds 58, 59, 62, 63, 66 and 67 were able to permeate a layer of hCMEC/D3 cells in a time-dependent manner. Mitochondriotropic antioxidant 67 stands out by its remarkable iron chelating and neuroprotective properties toward both H2O2 and 6-OHDA-induced oxidative damage, drug-like properties and BBB permeability.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/fisiopatología , Antioxidantes/síntesis química , Enfermedades Mitocondriales/prevención & control , Enfermedad de Alzheimer/patología , Antioxidantes/farmacología , Barrera Hematoencefálica/metabolismo , Línea Celular , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidopamina/antagonistas & inhibidores
2.
Chem Commun (Camb) ; 51(14): 2832-5, 2015 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-25579652

RESUMEN

The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds.


Asunto(s)
Descubrimiento de Drogas , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Cromanos/química , Cromanos/farmacología , Humanos , Modelos Moleculares , Conformación Molecular
3.
J Periodontol ; 68(11): 1093-7, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9407402

RESUMEN

The purpose of this study was to compare curets with a small blade to slim ultrasonic inserts on their efficacy in removing artificial deposits from the root trunk and furcation entrance areas of mandibular molars using an in vitro model simulating a clinically closed root debridement approach. The study was conducted on 100 artificial mandibular first molars (50 right side and 50 left side) with anatomical roots. Root trunks, furcation entrances, and furcation areas of each molar were colored by a coat of black model paint. The teeth were fixed in a custom acrylic model and maintained in a firm position by modified acrylic occlusal splints. The root areas were covered with a heavy rubber dam imitating gingival tissue. The model was attached to a mannequin and mounted on a dental chair. Fifty molars (25 right, 25 left) were instrumented with the experimental curets and an equivalent number of molars with the ultrasonic inserts. The instrumentation was carried out by one experienced operator, spending 4 minutes on each molar. The instrumented areas were individually analyzed to determine the percentage of deposits remaining, using a computerized imaging routine system. One-way analysis of variance was conducted to test for differences between both types of instruments. Results revealed that the curets were significantly more efficient (P < 0.01) than the ultrasonic inserts in removing paint from both root trunks and furcation entrances. These findings should be corroborated in a clinical study to determine the potential value of the instruments tested during initial therapy or supportive care of involved mandibular furcations.


Asunto(s)
Raspado Dental/instrumentación , Defectos de Furcación/terapia , Diente Molar/patología , Aplanamiento de la Raíz/instrumentación , Raíz del Diente/patología , Resinas Acrílicas , Análisis de Varianza , Legrado/instrumentación , Desbridamiento , Depósitos Dentarios/patología , Depósitos Dentarios/terapia , Raspado Dental/métodos , Diseño de Equipo , Defectos de Furcación/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Mandíbula , Modelos Anatómicos , Modelos Dentales , Periodoncia , Aplanamiento de la Raíz/métodos , Diente Artificial , Terapia por Ultrasonido/instrumentación
4.
J Periodontol ; 68(11): 1098-101, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9407403

RESUMEN

The purpose of this study was to demonstrate the extent of deposits removed from within the furcation area of mandibular first molars following the use of curets with a modified blade and slim ultrasonic inserts in an in vitro model simulating a closed root debridement approach to furcation treatment. The furcation areas of 100 artificial mandibular first molars were uniformly coated with black model paint. The molars were fixed into a custom acrylic model, maintained in a firm position with modified occlusal splints, and the roots covered with a heavy rubber dam. The model was set in a mannequin and mounted on a dental chair recreating a clinical situation. Fifty molars (25 right, 25 left) were instrumented with the experimental curets and an equivalent number of molars with the ultrasonic inserts. An experienced dental hygienist completed all the instrumentation, spending 4 minutes on each molar. The molars were sectioned buccolingually from the crown apically to separate the roots, and areas in the internal surface of mesial and distal roots were analyzed to determine the percentage of deposits remaining using a computerized imaging routine system. A 2-factor analysis of variance was conducted to test for differences between both types of instruments. The curets produced furcation root surfaces with significantly less percentage of residual deposits than the ultrasonic inserts (P < 0.01). This study indicates the potential value of small bladed curets in debriding involved furcations during initial therapy and supportive periodontal therapy. The current findings should be corroborated in a clinical study.


Asunto(s)
Raspado Dental/instrumentación , Defectos de Furcación/terapia , Diente Molar/patología , Aplanamiento de la Raíz/instrumentación , Raíz del Diente/patología , Resinas Acrílicas , Análisis de Varianza , Legrado/instrumentación , Desbridamiento , Depósitos Dentarios/patología , Depósitos Dentarios/terapia , Higienistas Dentales , Defectos de Furcación/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Mandíbula , Modelos Anatómicos , Modelos Dentales , Enfermedades Periodontales/terapia , Diente Artificial , Terapia por Ultrasonido/instrumentación
5.
J Periodontol ; 67(6): 611-6, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8794973

RESUMEN

This report describes 9 cases presenting exostosis at mandibular and maxillary sites where autogenous gingival grafts have been used to increase the amount of attached gingiva. The exostoses were recognized during routine dental examinations and identified by palpation, horizontal sounding, occlusal radiographs, and in one case by histologic examination. Only in three cases was there a surgical removal of exostosis and recurrence was not observed during a follow-up evaluation. The remainder of the cases were not treated and the exostoses appeared to have limited growth. Apparently, a correlation between the presence of tori and the development of exostosis could not be established in these series of case reports, but a possible explanation with respect to the mechanism of bone formation is discussed along with the clinical implications of this interesting clinical finding.


Asunto(s)
Exostosis/etiología , Encía/trasplante , Gingivoplastia/efectos adversos , Enfermedades Maxilomandibulares/etiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Osteogénesis/fisiología , Complicaciones Posoperatorias , Trasplante Autólogo/efectos adversos
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