Analysis of electronic structures of physostigmine analogs.
AIM: To elucidate the action mechanism and structural prerequisites of 21 physostigmine analogs as acetylcholinesterase inhibitors at the molecular level, and help the rational design of these dihydroindoline inhibitors. METHODS: Initial structures of these compounds were built and minimized by SYBYL 6.2 molecular modeling software. Conformations of those molecules with the highest predictive abilities in the Comparative Molecular Field Analysis model were chosen to the semiempirical quantum chemical calculations. RESULTS: (1) The highest occupied molecular orbital (HOMO) consisted mainly of the orbitals in phenyl group and N1 atom; the lowest unoccupied molecular orbital (LUMO) of the molecules was contributed from phenyl group and C11 atom. While the HOMO energies did not show any recognizable relationship with activity, the LUMO energies showed a decreased tendency with increasing activity. The active compounds showed lower LUMO energies. (2) The carbon atom (C11) had the most positive net atom charge. The most active compound had the most positive charge on this carbon, but had the lower charges on the carbonyl oxygen (O12) which was the most negative charge atom. (3) The bond order of carbon-oxygen bond (C11-O10) was invariant across the series of the compounds. (4) Compounds with too high or too low total dipole moment had lower activities, while the most active one had a lower molecular polarizability. CONCLUSION: A molecular model was suggested to explain the possible mode of action by which these compounds inhibit acetylcholinesterase. (+info)
A 3D computer-aided design system applied to diagnosis and treatment planning in orthodontics and orthognathic surgery.
The purpose of this article is to describe a newly developed 3D computer-aided design (CAD) system for the diagnostic set-up of casts in orthodontic diagnosis and treatment planning, and its preliminary clinical applications. The system comprises a measuring unit which obtains 3D information from the dental model using laser scanning, and a personal computer to generate the 3D graphics. When measuring the 3D shape of the model, to minimize blind sectors, the model is scanned from two different directions with the slit-ray laser beam by rotating the mounting angle of the model on the measuring device. For computed simulation of tooth movement, the representative planes, defined by the anatomical reference points, are formed for each individual tooth and are arranged along a guideline descriptive of the individual arch form. Subsequently, the 3D shape is imparted to each of the teeth arranged on the representative plane to form an arrangement of the 3D profile. When necessary, orthognathic surgery can be simulated by moving the mandibular dental arch three-dimensionally to establish the optimum occlusal relationship. Compared with hand-made set-up models, the computed diagnostic cast has advantages such as high-speed processing and quantitative evaluation on the amount of 3D movement of the individual tooth relative to the craniofacial plane. Trial clinical applications demonstrated that the use of this system facilitated the otherwise complicated and time-consuming mock surgery for treatment planning in orthognathic surgery. (+info)
Targeting the HIV-protease in AIDS therapy: a current clinical perspective.
This review deals with clinical applications of compounds that inhibit the action of the protease encoded within the genome of human immunodeficiency virus (HIV). The HIV-protease is essential for viral maturation and represents an important therapeutic target in the fight against AIDS. Following a brief overview of the enzyme structure and function, the article focuses on a number of peptide and non-peptide based HIV-protease inhibitors that are in current clinical use. These drugs are discussed both with respect to their efficacy in treatment of AIDS, and to problems related to insurgence of viral resistance and side effects seen to date in patient populations. (+info)
Effect of polishing on cyclic fatigue strength of CAD/CAM ceramics.
The biaxial flexural strength and cyclic fatigue biaxial flexural strength of CAD/CAM ceramics polished with #220, 400, 600 and 1000 diamond pads were measured in an effort to determine the effect of surface roughness on fatigue behavior of dental ceramics. The surface roughness was improved after polishing with a smaller diamond grain pad. The flexural strengths of the specimens polished with #220, 400, 600 and 1000 diamond pad were 75.2, 76.6, 82.2, and 83.3 MPa, respectively; the fatigue flexural strength of those with #220, 400, 600 and 1000 were 53.0, 58.1, 60.0, and 61.5 MPa, respectively. Both the flexural and fatigue flexural strengths increased with improvement of surface profile. These results suggest the importance of polishing of dental ceramics for not only the static strength but also the cyclic fatigue strength. (+info)
Influence of filler content and gap dimension on wear resistance of resin composite luting cements around a CAD/CAM ceramic inlay restoration.
We investigated the influence of filler content and gap dimension on the wear resistance of composite luting cement around CAD/CAM ceramic inlay restorations. Experimental hybrid dual-cured composite luting cements containing 60, 70, 72, 74 and 80 wt% of silanated barium-silica fillers were used for cementing CAD/CAM ceramic inlay into the cavity. The specimens involving inlay-cement-tooth interfaces were subjected to a three-body wear test. The relation between the interfacial gap dimension and wear loss was also investigated using 60, 70 and 80 wt% filled cements. The cements containing more than 70 wt% filler presented significantly higher wear resistance than 60 wt% filled cement. There was a positive linear relationship between gap dimension and wear loss, and the inclination of the regression line decreased with increasing filler content. These results indicated that the higher filler content of the cement increased the wear resistance and this desirable influence appeared more remarkably in the wider horizontal gap dimension. (+info)
The Procera abutment--the fifth generation abutment for dental implants.
The Branemark dental implant has undergone progressive development in terms of both the implant body itself and the components connecting the implant to the prosthesis. Many screw and abutment designs have been developed, with various degrees of success. About 15 years ago, CAD (computer-assisted design)-CAM (computer-assisted manufacture) technology was introduced to dentists. More recently CAD-CAM has been used in the manufacture of abutments for implants. This article reviews currently available techniques for creating the Procera custom abutment (Nobel Biocare, Goteborg, Sweden) and outlines appropriate applications for this type of implant. (+info)
PrimeArray: genome-scale primer design for DNA-microarray construction.
PrimeArray is a Windows program that computes oligonuceotide primer pairs for genome-scale gene amplification by the Polymerase Chain Reaction (PCR). The program supports the automated extraction of coding sequences (CDS) from various input-file formats and allows highly automated primer pair-optimization. (+info)
Application of secondary structure prediction in antisense drug design targeting protein kinase C-alpha mRNA and QSAR analysis.
AIM: To optimize the design of antisense drug targeting protein kinase C-alpha (PKC-alpha) mRNA and obtain better antisense drugs than ISIS3521 that is undergoing clinical trials. METHODS: RNAstructure (version 3.21, 1999) was utilized to predict the optimal and suboptimal secondary structures of human PKC alpha mRNA (GenBank, X52479), and 29 antisense phosphorothioate oligodeoxynucleotides (S-ODN) targeting the secondary structural elements, 3 partly matched S-ODN and 1 scrambled 3521 were designed. ISIS3521 was set as positive control. Mean (n = 3-5) 50% inhibitory effects on proliferation of A549 cells (IC50) of S-ODN were evaluated. Free energies (delta G degree 37) relating to the target secondary structural elements were calculated according to the nearest neighbor model. The quantitative structure-activity relationship (QSAR) analysis through multiple regression was obtained by SPSS. RESULTS: Three S-ODN; (5'-AGCCCA-GCCGCTTGGCTGGG-3', 5'-AGGAGTGCAGCTGC-GTCAAG-3', 5'-TCAGAGGG-ACTGATGACTTT-3') had lower IC50[(48 +/- 7), (50 +/- 4), (64 +/- 2.7) nmol.L-1, respectively] than that of ISIS3521 [(81 +/- 25) nmol.L-1]. The number of bases comprising the target secondary structural element bulge loop, internal loop, and knot, the free energy of S-ODN (delta G degree 37S), and reaction (delta G degree 37R) were important parameters in QSAR equation. In the multiple regression, R was 0.68, P = 0.0193. Not tally with the equation, two S-ODN (5'-TCAAATGGAGG-CTGCCCGGC-3', 5'-AAAACGTCAGCCATGGTCCC-3') with favorable target structures and delta G degree 37 did not behave good activities. CONCLUSION: Computer aided design was helpful to obtain S-ODN with better in vitro effect than current positive drug. The degree of instability of secondary structural elements and delta G degree 37 were important factors for drug activity. Other important factors needed for further investigation. (+info)