7 research outputs found
Epiphyseal separation associated with chronic osteomyelitis of femoral shaft fracture in a young child
Septic physeal separation of proximal femur in a newborn
In newborns physeal separations and septic osteomyelitis or arthritis are unusual, representing a problem in diagnosis and treatment. Therapy needs to be carried out soon in order to prevent anatomical and functional consequences. Association between septic event and physeal separation is rare. We report a 28-day-old female, admitted for elevated temperature, who underwent three nonorthopaedic surgical procedures before, and orthopaedic evaluation 8Â days after admission. After an X-ray and an ultrasonography a septic arthritis with consequent hip dislocation was supposed. Only at the time of surgery a separation between the epiphysio-trochanteric nuclei complex and the femoral shaft was observed, with clear hip joint. The interest in this case consists in the difficulty of the differential diagnosis at the first evaluation, the orthopaedic misdiagnosis based on the lack of complete preoperative imaging, and finally the long-term excellent result after a prompt surgical treatment
Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents
Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations
The ability to identify the site of a protein that can bind with high affinity to small, drug-like compounds has been an important goal in drug design. Sirtuin 2 (SIRT2), histone deacetylase protein family, plays a central role in the regulation of various pathways. Hence, identification of drug for SIRT2 has attracted great interest in the drug discovery community. To elucidate the molecular basis of the small molecules interactions to inhibit the SIRT2 function we employed the molecular docking, molecular dynamics simulations, and the molecular mechanism Poisson-Boltzmann/surface area (MM-PBSA) calculations. Five well know inhibitors such as suramin, mol-6, sirtinol, 67, and nf675 were selected to establish the nature of the binding mode of the inhibitors in the SIRT2 active site. The molecular docking and dynamics simulations results revealed that the hydrogen bonds between Arg97 and Gln167 are crucial to inhibit the function of SIRT2. In addition, the MM-PBSA calculations revealed that binding of inhibitors to SIRT2 is mainly driven by van der Waals/non-polar interactions. Although the five inhibitors are very different in structure, shape, and electrostatic potential, they are able to fit in the same bindingpocket. These findings from this study provide insights to elucidate the binding pattern of SIRT2 inhibitors and help in the rational structure-based design of novel SIRT2 inhibitors with improved potency and better resistance profile