Characteristics of Posed Smiles for Class III Female Patients Before and After Osteotomy Using Principal Component Analysis.

The purpose of this study was to clarify characteristics of posed smiles for Class III female patients before and after orthognathic surgery. Just before retrusion surgery and the removal of fixation plates, 2 sets of posed smiles were recorded for 7 Class III female patients. As normal controls, 7 healthy female volunteers were also recorded. Using our video-based motion analyzing system, range images and 5 × 5 virtual grids projected onto the lips were recorded for all patients while making a posed smile. The gravity for each area in the lips was calculated from the intersections of the virtual grids. Principal component analysis was applied to the normalized virtual grids, that is, a homologous model of lip shape, for all frames of the posed smiles. While the sample size was too small to generalize from these results, we found that the upper vermilion shifted posteriorly and laterally in posed smiles for Class III female patients after retrusion surgery as compared with the preoperative posed smiles. In addition, the characteristic lip movements during postoperative posed smiles for Class III female patients did not resemble those of the normal controls.

Frenum-like oral synechiae of the lip and vestibule.

Two cases where aberrant tissue was attached to the lower lip mimicking the inferior labial frenum were reported. The frenum-like tissue extended from the gingival margin between the lower left deciduous central and lateral incisors in case 1 and between the lower right deciduous central and lateral incisors in case 2, to the dry lower lip. Histologically, the resected specimen was regarded as normal oral mucosa covered with stratified squamous epithelium, without a clear amniotic band. The frenum-like tissue of the lower lip found in both our patients was diagnosed as a category of oral synechiae, of unknown origin.

Aib-containing peptide analogs: cellular uptake and utilization in oligonucleotide delivery.

α-Aminoisobutyric acid (Aib)-containing peptide analogs derived from TV-XIIa, a cell-penetrating peptide (CPP), were synthesized to explore structure-activity relationships. The replacement of Aib at position 1, 5, or 9 in the TV-XIIa amino acid sequence with alanine (Ala) suppressed the cellular uptake,whereas the simultaneous substitution of the two proline (Pro) residues at positions 6 and 10 with Aib(P-IV) considerably increased the cellular uptake. In order to explore the potential use of the Aib-containing peptide analogs for the cellular delivery of oligonucleotides (ODNs), we synthesized a covalent conjugate (P-IV-AON) of a 15-mer antisense ODN, which is complementary to luciferase gene, with P-IV, and the antisense effect of the P-IV-AON conjugate on luciferase expression in A549 cells was examined. Luciferase expression was decreased in the presence of the conjugate upon treatment with the reaction buffer at the concentrations of 5 and 10 µM.

Effect of Ala replacement with Aib in amphipathic cell-penetrating peptide on oligonucleotide delivery into cells.

A number of cell-penetrating peptides (CPPs) have been characterized and their usefulness as delivery tools has been clarified. As one of the CPPs, model amphipathic peptide (MAP) was developed by integrating both hydrophobic and hydrophilic amino acids in its sequence. In our previous work, we designed MAP(Aib) by replacing five alanine (Ala) residues on the hydrophobic face of the helix in the MAP sequence with α-aminoisobutyric acid (Aib) residues, and the replacement resulted in higher helix propensity, stronger resistance to protease, and higher cell membrane permeability than MAP. As a next step, we examined the efficiency of oligonucleotide (ODN) delivery into cells by MAP(Aib) in comparison with that by MAP. The electrostatically formed MAP(Aib)/ODN complex was more easily taken up by cells than the MAP/ODN complex, and the ODN delivery by MAP(Aib) was via an endocytic pathway. We demonstrated that the incorporation of Aib residues into CPPs enhances the delivery of hydrophilic molecules, such as ODN, into cells.

In vitro and in vivo antibacterial activity of modithromycin against streptococci and Haemophilus influenzae.

OBJECTIVES: In vitro and in vivo antibacterial activities of modithromycin against Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae were examined. METHODS: MICs were determined by the broth microdilution method. Experimental infection of epithelial cell line A549 was performed to compare the intracellular activity and lasting effects of the antimicrobial agents. To evaluate in vivo efficacy, the rat pulmonary infection model was used. RESULTS: Modithromycin had MICs of ≤ 1 mg/L against all the clinical strains of both streptococci, including erythromycin-resistant strains. In particular, the MICs of modithromycin for erm(B)- or mef(A)-carrying S. pyogenes were 16-32 times or 2-4 times lower than those of telithromycin, respectively. The MIC(90) of modithromycin for H. influenzae was 8 mg/L, which was 4 times higher than that of telithromycin. Modithromycin, as well as azithromycin, showed a lasting inhibitory effect on bacterial growth of cell-associated H. influenzae compared with telithromycin and levofloxacin after removal of the agents from the apical medium. In the pulmonary infection model, modithromycin showed greater or comparable efficacy against erm(B)-carrying S. pneumoniae and H. influenzae, respectively, than telithromycin, regardless of having an MIC that was 2 or 4 times higher for these strains. CONCLUSIONS: Modithromycin has the most potent anti-S. pyogenes activity of the antimicrobial agents tested. Modithromycin also has the better in vivo efficacy against S. pneumoniae and H. influenzae, which might be due to its lasting intracellular activity.