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1.
Spine J ; 24(8): 1510-1516, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38685273

RESUMEN

BACKGROUND CONTEXT: Odontoid fractures are among the most common cervical spine fractures in the elderly and are associated with increased morbidity and mortality. Clinical evidence suggests improved survival and quality of life after operative intervention compared to nonoperative treatment. PURPOSE: This study seeks to examine the stability of an osteoporotic Type II odontoid fracture following posterior atlantoaxial fixation with either the Magerl transarticular fixation technique or the Harms C1 lateral mass screws C2 pedicle screw rod fixation. STUDY DESIGN: Biomechanical cadaveric study. METHODS: Eighteen cadaveric specimens extending from the cephalus to C7 were used in this study. Reflective marker arrays were attached to C1 and C2 and a single marker on the dens to measure movement of each during loading with C2-C3 and occiput-C1 being allowed to move freely. A biomechanical testing protocol imparted moments in flexion-extension, axial rotation, and lateral bending while a motion capture system recorded the motions of C1, C2, and the dens. The spines were instrumented with either the Harms fixation (n=9) or Magerl fixation (n=9) techniques, and a simulated Type II odontoid fracture was created. Motions of each instrumented spine were recorded for all moments, and then again after the instrumentation was removed to model the injured, noninstrumented state. RESULTS: Both Harms and Magerl posterior C1-C2 fixation allowed for C1, C2, and the dens to move as a relative unit. Without fixation the dens motion was coupled with C1. No significant differences were found in X, Y, Z translation motion of the dens, C1 or C2 during neutral zone motions between the Magerl and Harms fixation techniques. There were no significant differences found in Euler angle motion between the two techniques in either flexion-extension, axial rotation, or lateral bending motion. CONCLUSIONS: Our findings suggest that both Harms and Magerl fixation can significantly reduce dens motion in Type II odontoid fractures in an osteoporotic cadaveric bone model. CLINICAL SIGNIFICANCE: Both Harms and Magerl posterior atlantoaxial fixation techniques allowed for C1, C2, and the dens to move as a relative unit following odontoid fracture, establishing more anatomic stability to the upper cervical spine.


Asunto(s)
Articulación Atlantoaxoidea , Cadáver , Apófisis Odontoides , Fracturas de la Columna Vertebral , Humanos , Apófisis Odontoides/cirugía , Apófisis Odontoides/lesiones , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/fisiopatología , Articulación Atlantoaxoidea/cirugía , Fenómenos Biomecánicos , Anciano , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/fisiopatología , Masculino , Fusión Vertebral/métodos , Fusión Vertebral/instrumentación , Femenino , Vértebras Cervicales/cirugía , Vértebras Cervicales/lesiones , Anciano de 80 o más Años , Tornillos Pediculares
2.
J Med Chem ; 66(6): 3917-3933, 2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36877173

RESUMEN

Tetracyclines (TCs) are an important class of antibiotics threatened by an emerging new resistance mechanism─enzymatic inactivation. These TC-inactivating enzymes, also known as tetracycline destructases (TDases), inactivate all known TC antibiotics, including drugs of last resort. Combination therapies consisting of a TDase inhibitor and a TC antibiotic represent an attractive strategy for overcoming this type of antibiotic resistance. Here, we report the structure-based design, synthesis, and evaluation of bifunctional TDase inhibitors derived from anhydrotetracycline (aTC). By appending a nicotinamide isostere to the C9 position of the aTC D-ring, we generated bisubstrate TDase inhibitors. The bisubstrate inhibitors have extended interactions with TDases by spanning both the TC and presumed NADPH binding pockets. This simultaneously blocks TC binding and the reduction of FAD by NADPH while "locking" TDases in an unproductive FAD "out" conformation.


Asunto(s)
Compuestos Heterocíclicos , Tetraciclina , Tetraciclina/farmacología , Tetraciclina/metabolismo , NADP/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Tetraciclinas/farmacología , Inhibidores de la Síntesis de la Proteína , Oxidación-Reducción
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