Synthetic peptide from the V3 loop consensus motif with a potent anti-HIV activity inhibits ristocetin-mediated vWF-GPIb interaction

The V3 loop consensus motif. Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB), inhibits an interaction of HIV with CD4-positive lymphocytes. Recently, both proline-rich peptides and peptides containing proline-glycine loops (beta-turns) form a complex with ristocetin dimers. These peptides interact with ristocetin-loaded platelet membrane glycoprotein (GP) Ib and act as inhibitors of von Willebrand factor (vWF)-GPIb interaction by preventing the subsequent formation of ristocetin dimer bridges. The Pro-Gly sequence is also present in the V3 loop consensus motif, Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB). In this report, we have evaluated the effect of the HIV-1 IIIB peptide on vWF binding to GPIb. This peptide only inhibited vWF binding to GPIb as well as platelet aggregation in the presence of ristocetin while it had no effect on botrocetin-mediated vWF interaction with platelets. The peptide inhibited a binding of anti-vWF monoclonal antibody (RG-46) to immobilized vWF. Furthermore, ristocetin inhibited the binding of HIV-1 IIIB peptide to immobilized CXC-chemokine receptor-4 (CXCR-4) peptide. These results indicate that ristocetin may prevent HIV infection and would be useful a tool to understand the mechanism of HIV tissue tropism and infection.     

A self-retaining method to maintain vertical position of the maxilla during Le Fort I osteotomies

A simple technique that relies on a fine wire to maintain vertical relationships of the maxilla during Le Fort I osteotomy is described. The advantages are (1) the hands of the assistant are free to help adapt plates, (2) it decreases the assistant's need to maintain a pose, and (3) the time of the operation decreases.     

Neoadjuvant intraarterial chemotherapy for ten cases of inflammatory breast cancer by Seldinger's methods

The conventional methods (CM) of intraarterial (IA) chemotherapy for inflammatory breast cancer were catheterizations from superior epigastric and brachial artery under general anesthesia. Since 1997, we selected the Seldinger's methods (SM) for ten cases of the disease to control local effects and simplify the technique. Complications of the SM were slight, and side effects were equal to those with CM. The postoperative pathological findings of the SM showed the direct effects of chemotherapy to tumor cells (degenerative and necrotic changes) as compared with the embolism-like effects of CM. But the overall histological effects of chemotherapy by SM were almost equal to those for CM. The strong points of the SM were as follows: 1) More selective IA chemotherapy is available, 2) one can find the passage of the aim vessels and no trouble related to catheter, 3) general anesthesia is not necessary, and the techniques are simple, 4) the wounds are not remarkable. The disadvantages are as follows: 1) Patients must rest the day of IA chemotherapy, 2) in 20% of the procedures, one can not search the vessels, and 3) in 4 cases complications of stiffness of Mj or Mn pectral muscles were found. In future, we expect more effective results by dose escalation or combination chemotherapy.     

DNA microarray analysis suggests that zinc pyrithione causes iron starvation to the yeast Saccharomyces cerevisiae

Zinc pyrithione has been used in anti-dandruff shampoos and in anti-fouling paint on ships. However, little is known of its mode of action. We characterized the effects of sub-lethal concentrations of zinc pyrithione (Zpt) on Saccharomyces cerevisiae using DNA microarrays. The majority of the strongly upregulated genes are related to iron transport, and many of the strongly downregulated genes are related to the biosynthesis of cytochrome (heme). These data suggest that Zpt induces severe iron starvation. To confirm the DNA microarray data, we supplemented cultures containing Zpt with iron, and the growth of the yeast was restored significantly. From these results, we propose that the principal toxicity of zinc pyrithione arises from iron starvation.     

Synthesis and Characterization of Glycidyl Azide‐r‐(3,3‐bis(azidomethyl)oxetane) Copolymers

Glycidyl azide‐r‐(3,3‐bis(azidomethyl)oxetane) copolymers were synthesized by cationic copolymerization of epichlorohydrin and 3,3‐bis(bromomethyl)oxetane, using butane‐1,4‐diol as an initiator and boron trifluoride etherate as a catalyst, followed by azidation of the halogenated copolymer. The main objective of this work is the preparation of an OH‐terminated amorphous polymer with energetic content higher than that of the well‐known glycidyl azide homopolymer. The effect of experimental conditions, i.e., the rate of monomer feeding, on the final molecular weight and functionality of the copolymer has also been investigated. The obtained copolymers were extensively characterized to determine their composition and thermal stability. The heat of reaction for the polymerization of the halogenated key precursors has also been measured. It was found that even though both the operating conditions and the catalytic system were chosen in order to favor a living character of the polymerization, the final product seems to be the result of a combined living and active chain end mechanism. In particular, the latter is responsible for the formation of oligomers and not hydroxyl‐terminated chains. Nevertheless, the average number of OH groups is high enough to allow a cross‐linking of the polymeric chains, by addition of polyisocyanates and subsequent formation of inter‐chain urethanic bonds.     

Structure-Based Design,Synthesis, and Biological Evaluation of Imidazo[4,5-b]Pyridin-2-one-Based p38 MAP Kinase Inhibitors: Part 2

We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.     

Effects of Nd:YAG laser irradiation on morphometry and lung function in elastase-induced emphysema in rats

BACKGROUND & OBJECTIVE: Although thoracoscopic laser ablation therapy has been hailed as an effective surgical treatment for diffuse emphysema, no one has as yet made an in-depth study of the efficacy of this treatment. This investigation was undertaken to research the effects of laser pneumoplasty on an animal model of emphysema. STUDY DESIGN/MATERIALS AND METHODS: Eight weeks after elastase treatment, the rats' left lungs were irradiated using contact Nd:YAG laser. Pulmonary function tests were performed 4 weeks after irradiation and the lungs were prepared for histologic examination. RESULTS: Dense fibrous scars beneath the pleura were observed at 4 weeks after irradiation. Although mean linear intercept values of irradiated lungs were not much lower than those in the non-irradiated elastase-treated group, laser irradiation caused a significant decrease in lung volume. While there was no significant difference in quasistatic compliance, elastic recoil pressure of the lung increased to control levels at total lung capacity volume. CONCLUSION: We conclude that laser therapy does not cause normalization of compliance, or improvement in the deeper part of the emphysematous lung, but rather a peripheral volume reduction and "encasement effect" on the lungs as a result of fibrotic scars.     

Nucleating agent for poly(L‐lactic acid)—An optimization of chemical structure of hydrazide compound for advanced nucleation ability

A series of compounds having hydrazide groups was prepared and evaluated as nucleating agent for poly(L ‐lactic acid) by differential scanning calorimetry. Hydrazide compounds derived from benzoic acid, 2‐hydroxybenzoic acid, 3‐tert‐butylbenzoic acid, and 2‐aminobenzoic acid, where two of hydrazide compounds connected by four methylene chain were evaluated in series. Benzoylhydrazide type was found to be more effective on the enhancement of crystallization of poly(L ‐lactic acid). Effects of connecting length of methylene chain numbers between two of benzoylhydrazide on the nucleation ability were also evaluated. Benzoylhydrazide‐type compound having 10 methylenes, that is, decamethylenedicarboxylic dibenzoylhydrazide demonstrated excellent nucleation ability, and the resulted crystallization temperature and enthalpy of PLA with the compound of 1 wt % loading were 131°C and 46 J g^?1. The achieved crystallization temperature and enthalpy were over 10°C and over 10 J g^?1 higher than PLA with conventional nucleating agents, such as talc and ethylenebis (12‐hydroxystearylamide). Thus, the improvement in processability, productivity, and heat resistance of PLA is suggested to be achieved by using decamethylenedicarboxylic dibenzoylhydrazide as a nucleating agent. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 198–203, 2007