Integrated computational and experimental approach for lead optimization and design of compstatin variants with improved activity.

A novel structure-activity-based combinatorial computational optimization methodology for the design of peptides that are candidates to become therapeutics is presented. This methodology has been successfully applied in the design of a 7-fold more active analogue, among other active analogues, in the case of the complement inhibitor compstatin. The main steps of the approach involve the availability of NMR-derived structural templates, combinatorial selection of sequences based on optimization of parametrized pairwise residue interaction potentials, prediction of fold stabilities using deterministic global optimization, and experimental validation with immunological activity measurements. This work is direct evidence that an integrated experimental and theoretical approach can make the engineering of compounds with enhanced immunological properties possible.

Kinetic analysis of the interactions of complement receptor 2 (CR2, CD21) with its ligands C3d, iC3b, and the EBV glycoprotein gp350/220.

The molecular mechanisms involved in the interaction of complement receptor 2 (CR2) with its natural ligands iC3b and C3d are still not well understood. In addition, studies regarding the binding site(s) of the receptor on C3 as well as the affinities of the C3 fragments for CR2 have produced contradictory results. In the present study, we have used surface plasmon resonance technology to study the interaction of CR2 with its ligands C3d, iC3b, and the EBV surface glycoprotein gp350/220. We measured the kinetics of binding of the receptor to its ligands, examined the influence of ionic contacts on these interactions, and assessed whether immobilized and soluble iC3b bound with similar kinetics to CR2. Our results indicate that 1) gp350 binding to CR2 follows a simple 1:1 interaction, whereas that of the C3 fragments is more complex and involves more than one intramolecular component; 2) kinetic differences exist between the binding of C3d and iC3b to CR2, which may be due to an additional binding site found on the C3c region of iC3b; and 3) iC3b binds to CR2 with different kinetics, depending on whether the iC3b is in solution or immobilized on the surface. These findings suggest that binding of CR2 to iC3b and C3d is more complex than previously thought.

Comparison of the dentofacial patterns for native Greek and American-Caucasian adolescents.

The study of the craniofacial relations and variations in man has long been used to differentiate various racial groups in physical anthropology. Morphologic features of different races and ethnic groups are not randomly distributed but appear in geographic clusters. Richardson wonders whether there is only one race, comprising ethnic groups separated by cultural, climatic, and geographic boundaries, causing subtle changes in facial morphology. Since the introduction of roentgenographic cephalometry in orthodontics, several methods of analysis have been developed for clinical diagnosis and treatment planning. Also, these methods have been used to establish the cephalometric norms of different ethnic groups: American Negro, Australian aborigine, American Mexican, Norwegian, Indian, Japanese, Swedish, and Iranian. Sassouni, Ricketts, and others have concluded that norms differ between Caucasians and other ethnic and racial groups. Ethnic differences in facial traits do exist. Awareness of the normal dentofacial pattern of each ethnic group will undoubtedly ensure better success of treatment to establish optimal facial harmony. These conclusions prompted the present investigation, which compares Greek and American-Caucasian dentofacial patterns of adolescents, and provides information on the facial characteristics of Greek adolescents. To date, no similar study has been made.

A comparative cephalometric investigation of the Greek craniofacial pattern through 4,000 years.

A comparative cephalometric investigation was conducted between modern and ancient Greeks to determine craniofacial characteristics and to examine the significance of ethnic heritage. The modern sample was composed of 54 individuals chosen on the basis of ethnic background, normal occlusion and facial harmony. The ancient sample consisted of 40 skulls with normal occlusion dated back to the Minoan civilization (ca. 1,800-1,200 B.C.). A remarkable similarity in craniofacial morphology was revealed between the two groups, suggesting a close genetic affinity between modern and ancient Greeks. The ability of the craniofacial complex to make compensatory or balancing changes was noted. The craniofacial complex was seen to function as an integrated biological entity. Moreover, the cranial base showed a definite influence on skeletal profile configuration. These results provide a more comprehensive understanding of how craniofacial variables interact and contribute to the morphology of the dentofacial skeleton.

Techniques for improving orthodontic results in the treatment of missing maxillary lateral incisors. A case report with literature review.

We have presented a case report of the orthodontic treatment of a patient with congenitally missing lateral incisors and with skeletal and dental deep bite. Information was provided on methods to improve clinical orthodontic results. Different sections deal with (1) various diagnostic criteria for the best treatment approach, (2) variations in maxillary arch wire manipulation, (3) biomechanical considerations, (4) modifications of clinical crown by special procedures so that the canines resemble and function as lateral incisors, (5) functional considerations of the occlusion, and (6) details in finishing. Particular emphasis was placed on the use of a special design of closing loops for simultaneous space closure and intrusion of the anterior teeth. This article has discussed the principles of incisor and canine intrusion, and has demonstrated that the closing loops described are capable of intruding incisors with minimal side effects on the posterior teeth. It has also demonstrated how control of the mechanical variables dramatically increased the efficiency and effectiveness of intra- and extraoral forces in the treatment of malocclusion.

The use of intravenous regional anaesthesia for the reduction of Colles' fractures.

Intravenous regional anaesthesia in the reduction of Colles' fracture was compared in 70 patients with 55 others who were treated with general anaesthetics. It was found to be easier and to involve a shorter waiting time, not to require patients to be supervised so long during recovery, and after this method it was less frequently necessary for patients to be taken home by ambulance. Its disadvantages were that it took longer, and could not be used for psychiatric patients or children.