N63-carboxamides of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin and deglucoteicoplanin

The synthesis and biological properties of a series of N63-carboxamides of 15-N-alkylated derivatives of teicoplanin A2 (CTA) and its aglycone (TD) are described. Among the compounds, those carrying hydrophilic groups or ionizable amino functions on the N15-alkyl chain are more soluble in water than parent N15-methylated or unmodified amides. Selected compounds were more active in vitro than CTA or TD, and a few of them were also slightly more efficacious in vivo than the parent antibiotics in streptococcal septicemia in the mouse. Their degree of activity varied with the structure and length of the N15-alkyl chains.     

Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes

Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear leukocytes, under recirculating conditions (50 ml), and challenge with A-23187 (0.5 microM) caused an increase in coronary perfusion pressure (from a prechallenge value of 46 +/- 1.1 to 176.2 +/- 29.7 mm Hg, 30 min after challenge, n = 6-4), which was linearly correlated (P < .006) with formation of cysteinyl leukotrienes (29.7 +/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with the leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in significant protection against the increase in coronary perfusion pressure (76.7 +/- 12.8 mm Hg, 30 min after challenge) and in almost complete inhibition of sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml, 30 min after challenge). In in vivo experiments, ligation of the left anterior descending coronary artery in the rabbit (n = 10) resulted in acute myocardial infarction marked by a mortality rate of 60% compared with sham-operated animals (n = 10). Intravenous treatment of the rabbits with BAY X1005 (10 mg/kg/h, for 2 h) (n = 10) markedly reduced the mortality rate (20%), protected the rabbits against the marked electrocardiogram derangement and abolished the significant increase in plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase activity induced by coronary artery ligation. BAY X1005 exerts a significant cardioprotection and suggests that specific leukotriene synthesis inhibitors may lead to innovative therapy in myocardial ischemia.     

Coding of far and near space during walking in neglect patients.

Previous studies have shown that far space can be remapped as near when reached by a stick that artificially prolongs the participants' personal space. In the present study, the authors asked whether a similar remapping occurs when far space is reached not by using a toot but by locomotion. Neglect patients showed more severe neglect in far than in near space in bisection tasks executed from different distances either by pointing to a target line with a projection light pen or by walking across the line. A kinematic study of the walking performance of one of those neglect patients showed that, contrary to the prediction of remapping during locomotion, the walking trajectories were rectilinear. The authors interpreted these results as evidence that in their patients-at least for short, linear trajectories-no remapping of space took place during locomotion. The location of far objects was coded at the beginning of the movement, and the error in the bisection computation was generated within the 1st representation that was activated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of Curvature-Sensing Proteins in the Uptake of Nanoparticles with Different Mechanical Properties

Nanoparticles of different properties, such as size, charge, and rigidity, are used for drug delivery. Upon interaction with the cell membrane, because of their curvature, nanoparticles can bend the lipid bilayer. Recent results show that cellular proteins capable of sensing membrane curvature are involved in nanoparticle uptake; however, no information is yet available on whether nanoparticle mechanical properties also affect their activity. Here liposomes and liposome-coated silica are used as a model system to compare uptake and cell behavior of two nanoparticles of similar size and charge, but different mechanical properties. High-sensitivity flow cytometry, cryo-TEM, and fluorescence correlation spectroscopy confirm lipid deposition on the silica. Atomic force microscopy is used to quantify the deformation of individual nanoparticles at increasing imaging forces, confirming that the two nanoparticles display distinct mechanical properties. Uptake studies in HeLa and A549 cells indicate that liposome uptake is higher than for the liposome-coated silica. RNA interference studies to silence their expression show that different curvature-sensing proteins are involved in the uptake of both nanoparticles in both cell types. These results confirm that curvature-sensing proteins have a role in nanoparticle uptake, which is not restricted to harder nanoparticles, but includes softer nanomaterials commonly used for nanomedicine applications.     

An approach to planning and control of advanced projects

A conventional approach to project planning is inadequate whenever it is applied either to projects that are outside the standard market conditions, or to those (such as the implementation of important transport systems via offshore pipelines) that are subject to environmental situations outside human control. Under these circumstances, an analytical approach based on appropriate design information and simulation techniques is the management tool that allows an early anticipation of implementation and investment schedules and results in more successful project management. The broad outline of such a scheme used during the implementation of offshore pipeline projects in the Mediterranean Basin and the North Sea is described.     

New catalysts for poly(ethylene terephthalate)-bisphenol a polycarbonate reactive blending

The effects of various catalysts on the reactive blending of poly(ethylene terephthalate) (PET) and bisphenol A polycarbonate (PC) was investigated. The various catalysts employed for PET syntheses, Ti(OBu)4, SmL₃, EuL₃, Ca + Sb, CeAc₃, Er(NO₃)₃·B₁₂C₄ and Tb (acac)₃·diPy (where L is o-formylphenolate; B₁₂C₄ is a crown ether, benzo-12-crown-4; acac is acetylacetonate; and diPy is 2,2′-dipyridyl) have shown a different catalytic activity toward exchange reactions. Solubility tests, in solvents able to separate unreacted PET and PC, and selective degradation of the PC segments, combined with ¹H NMR spectroscopy and size exclusion chromatography, made it possible to order the catalysts according to their catalytic activity: Ti(OBu)4 ? SmL₃ > EuL₃ > Ca + Sb > CeAc₃～Er(NO₃)·B₁₂C₄ > Tb (Acac)₃·diPy ≈ 0. © 1995 John Wiley & Sons, Inc.     

Pregnancy and Infants’ Outcome: Nutritional and Metabolic Implications

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.     

Poly(1,4‐cyclohexylenedimethylene‐1, 4‐cyclohexanedicarboxylate): analysis of parameters affecting polymerization and cis–trans isomerization

Weatherable semicrystalline polyesters based on 1,4‐cyclohexanedimethanol, 1,4‐cyclohexanedicarboxylic acid (CHDA) or dimethyl 1,4‐cyclohexane dicarboxylate (DMCD) can be prepared under normal melt‐phase conditions, using titanium tetrabutoxide as catalyst. The effect of monomer ratio, reaction temperature and catalyst loading on the final polymer properties was studied. Under the proper polymerization conditions, poly(1,4‐cyclohexylenedimethylene‐1,4‐cyclohexanedicarboxylate) polymers with high molecular weight can be obtained. During polymerization, isomerization can occur towards the thermodynamically stable cis‐trans ratio of 34–66 mol%. Carboxylic acid end groups can catalyze the isomerization and therefore the polymerization is more critical starting from CHDA rather than DMCD. Moreover, temperature control becomes a key factor to avoid or to limit isomerization. The study of the isomerization of the different monomers permitted a better understanding of the isomerization and therefore of the polymerization process. Copyright © 2011 Society of Chemical Industry     

New catalysts for poly(butylene terephthalate) synthesis. Part 3: effect of phosphate co-catalysts

An exhaustive study of the co-catalytic activity of phosphates on titanium and titanium/hafnium based catalytic systems in poly(butylene terephthalate) synthesis was conducted in order to investigate any improvement in the process and/or in the properties of the final polymer with respect to the industrially used titanium based catalyst. Small scale polymerisation and subsequent scale up in higher capacity reactors showed a strong co-catalytic effect of phosphates. A screening on model compounds showed NaH₂PO₄ to be the most active co-catalyst. The co-catalysts had a stronger effect on titanium with respect to hafnium. Decreases in polymerisation time and tetrahydrofuran formation were observed, which in turn can improve the productivity of the whole process. Moreover, the use of phosphate improved the thermal stability of the final polymers.