Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17β-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.
- Keywords
- Anti-inflammatory activity, QSAR, Rational drug design,
- MeSH
- Anti-Inflammatory Agents adverse effects chemistry pharmacology MeSH
- Computer-Aided Design * MeSH
- Edema chemically induced drug therapy MeSH
- Glucocorticoids adverse effects chemistry pharmacology MeSH
- Croton Oil MeSH
- Rats MeSH
- Quantitative Structure-Activity Relationship MeSH
- Molecular Conformation MeSH
- Ear Diseases chemically induced drug therapy MeSH
- Rats, Wistar MeSH
- Drug Design MeSH
- Molecular Docking Simulation MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Inflammatory Agents MeSH
- Glucocorticoids MeSH
- Croton Oil MeSH
PURPOSE OF THE STUDY: Reinforcement rings are widely used for treatment of large acetabular defects but significant migration due to a lack of implant integration into the bone is a common problem. Although insufficient congruence between implant and acetabular bone has been identified main factor in early implant loosening, there are no reconstruction ring design parameters based upon anatomical data of the pelvis available. MATERIAL: In this study such parameters were calculated on the basis of standardized computer tomograms of the hip region of 10 male and 10 female patients (40 data sets). METHODS: The center of rotation, the acetabular entrance plane and the geometry of a simulated cranial and caudal flange of a reconstruction ring were determined. The flanges geometry was defined by the angles between the flanges and the entrance plane, the angle between the flange projections onto the entrance plane, the torsion and the width of each flange depending on the distance to the center of rotation, and the flanges torsion and width at their origin at the acetabular circumference. RESULTS: An optimal alignment between reconstruction ring and the periacetabular bone could be achieved with a medial angulation of 19.9 degrees +/- 19.4 degrees of the cranial and 14.7 degrees +/- 7.1 degrees of the caudal flange against the entrance plane. The angle between the flanges projections onto the entrance plane was calculated to be 162.2 degrees +/- 6.4 degrees . At its origin from the acetabular circumference the cranial flange is twisted 28.5 degrees , the caudal flange -0.8 degrees against the entrance plane. The maximal flanges widths were calculated to 21-54 mm for the cranial and 22-25 mm for the caudal flange depending on the distance from the acetabular circumference. DISCUSSION & CONCLUSION: The given design parameters may result in optimized implants respecting the pelvic anatomy and possibly providing improved fixation.
- MeSH
- Acetabulum * diagnostic imaging MeSH
- Computer-Aided Design * MeSH
- Hip Prosthesis * MeSH
- Middle Aged MeSH
- Humans MeSH
- Arthroplasty, Replacement, Hip * MeSH
- Pelvic Bones diagnostic imaging MeSH
- Tomography, X-Ray Computed * MeSH
- Prosthesis Design * MeSH
- Reoperation MeSH
- Prosthesis Failure MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The semiempirical quantum mechanical (SQM) methods used in drug design are commonly parametrized and tested on data sets of systems that may not be representative models for drug-biomolecule interactions in terms of both size and chemical composition. This is addressed here with a new benchmark data set, PLF547, derived from protein-ligand complexes, consisting of complexes of ligands with protein fragments (such as amino-acid side chains), with interaction energies based on MP2-F12 and DLPNO-CCSD(T) calculations. From these, composite benchmark interaction energies are also built for complexes of the ligand with the complete active site of the protein (PLA15 data set). These data sets are used to test multiple SQM methods with corrections for noncovalent interactions; the role of the solvation model in the calculations is tested as well.
- MeSH
- Quantum Theory * MeSH
- Pharmaceutical Preparations * MeSH
- Ligands MeSH
- Drug Design MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Pharmaceutical Preparations * MeSH
- Ligands MeSH
A microfluidic cell capture device was designed, fabricated, evaluated by numerical simulations and validated experimentally. The cell capture device was designed with a minimal footprint compartment comprising internal micropillars with the goal to obtain a compact, integrated bioanalytical system. The design of the device was accomplished by computational fluid dynamics (CFD) simulations. Various microdevice designs were rapidly prototyped in poly-dimethylsiloxane using conventional soft lithograpy technique applying micropatterned SU-8 epoxy based negative photoresist as moulding replica. The numerically modeled flow characteristics of the cell capture device were experimentally validated by tracing and microscopic recording the flow trajectories using yeast cells. Finally, we give some perspectives on how CFD modeling can be used in the early stage of microfluidics-based cell capture device development.
- MeSH
- Computer-Aided Design * MeSH
- Genetic Engineering * MeSH
- Crystallography, X-Ray * MeSH
- Drug Design * MeSH
- Publication type
- Journal Article MeSH
- Overall MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
PURPOSE: Breast ultrasonography (US) presents an alternative to mammography in young asymptomatic individuals and a complementary examination in screening of women with dense breasts. Handheld US is the standard-of-care, yet when used in whole-breast examination, no effort has been devoted to monitoring breast coverage and missed regions, which is the purpose of this study. METHODS: We introduce a computer-aided system assisting radiologists and US technologists in covering the whole breast with minimum alteration to the standard workflow. The proposed system comprises a standard US device, proprietary electromagnetic 3D tracking technology and software that combines US visual and tracking data to estimate a probe trajectory, total time spent in different breast segments, and a map of missed regions. A case study, which involved four radiologists (two junior and two senior) performing whole-breast ultrasound in 75 asymptomatic patients, was conducted to test the importance and relevance of the system. RESULTS: The mean process time per breast was [Formula: see text], with no statistically significant difference between the left and the right sides, and slightly longer examination time of junior radiologists. The process time density shows that central parts of the breast have better coverage compared to the periphery. Within the central part, missed regions of minimum detectable size of [Formula: see text] occur in [Formula: see text] of examinations, and non-negligible [Formula: see text] regions occur in [Formula: see text] of cases. CONCLUSION: The results of the case study indicate that missed regions are present in handheld whole-breast US, which renders the proposed system for tracking the probe position during examination a valuable tool for monitoring coverage.
- Keywords
- Breast, Cancer, Coverage, Screening, Tracking, Ultrasound,
- MeSH
- Equipment Design MeSH
- Diagnosis, Computer-Assisted * MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Mammography methods MeSH
- Breast Neoplasms diagnostic imaging MeSH
- Computers, Handheld MeSH
- Computer Systems MeSH
- Image Processing, Computer-Assisted MeSH
- Breast diagnostic imaging MeSH
- Reproducibility of Results MeSH
- Software MeSH
- Ultrasonography, Mammary methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
This study focuses on the drop foot case related to hyperthyroidism of the ankle joint resulting in the relaxation of the toes during walking. This condition requires treatment using an ankle-foot orthosis. Traditional orthosis techniques lack precision and depend on the skill of the fabricator. This research aims to make a bias in ankle-foot orthosis design and analysis methods, where a complete methodology of numerical design and testing has been proposed using advanced engineering software. A numerical model of the patient's foot was generated and used to design an ankle-foot orthosis model using SolidWorks. The designed model was mechanically analyzed by the finite element method using ANSYS Workbench 16.1 under different static and dynamic loading conditions. The ankle-foot orthosis model was numerically designed and analyzed before the manufacturing process. This is believed to reduce time and material loss and foster the use of numerical models in biomedical applications. This study suggests focusing on the design and analysis of orthoses according to the patient's measurements. This is expected to increase the comfort and raise the level of treatment. Numerical design methods also enable precise manufacturing using computerized devices such as three-dimensional printers.
- Keywords
- Drop foot, ankle–foot orthosis, energy dissipation, finite element analysis, rotational hardness,
- MeSH
- Finite Element Analysis MeSH
- Biomechanical Phenomena MeSH
- Walking physiology MeSH
- Computer-Aided Design MeSH
- Equipment Design methods MeSH
- Ankle Joint physiology MeSH
- Humans MeSH
- Gait Disorders, Neurologic * etiology physiopathology therapy MeSH
- Foot Orthoses * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The application of the pharmacophore concept to design new drugs is discussed. The focus is on the application of computer-assisted drug design methods (CADD) in the discovery of new leads.
- Keywords
- airway management, cleft lip, cleft palate, complications, difficult airway, protective obturator,
- MeSH
- Printing, Three-Dimensional MeSH
- Computer-Aided Design MeSH
- Child MeSH
- Humans MeSH
- Pilot Projects MeSH
- Cleft Palate * MeSH
- Cleft Lip * MeSH
- Airway Management MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Letter MeSH
A microfabricated pneumatic electrospray nebulizer has been developed and evaluated using computer simulations and experimental measurements of the MS signals. The microdevice under development is designed for electrospray MS interfacing without the need to fabricate an electrospray needle and can be used as a disposable or an integral part of a reusable system. The design of the chip layout was supported by computational fluid dynamics simulations. The tested microdevices were fabricated in glass using conventional photolithography, followed by wet chemical etching and thermal bonding. The performance of the microfabricated nebulizer was evaluated by means of TOF-MS with a peptide mixture. It was demonstrated that the nebulizer, operating at supersonic speed of the nebulizing gas, produced very stable nanospray (900 nL/min) as documented by less than 0.1% (SE) fluctuation in total mass spectrometric signal intensity.
- Keywords
- CFD, Electrospray, Microfabrication, Modeling, Nebulizer,
- MeSH
- Computer-Aided Design * MeSH
- Spectrometry, Mass, Electrospray Ionization methods MeSH
- Microfluidic Analytical Techniques instrumentation MeSH
- Nebulizers and Vaporizers * MeSH
- Computer Simulation * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
