Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Modification of the ultrasound induced activity by the presence of an electrode in a sonoreactor working at two low frequencies (20 and 40 kHz). Part I: Active zone visualization by laser tomography

Sonoelectrochemical experiments differ from sonochemical ones by the introduction of electrodes in the sonicated reaction vessel. The aim of the study is to characterize the changes of the ultrasonic activity induced by the presence of an electrode located in front of the transducer. The scope of our investigations concerns two low frequencies vibration modes: 20 and 40 kHz. For this purpose, two laser visualization techniques have been used. The first part of the study, described in the present paper (part I), deals with the laser tomography technique which provides an accurate picture of the reactor actives zones, related to numerous cavitation events. For each frequency, two parameters were studied: the electrical power supplied to the transducer and the electrode transducer distance. At both frequencies, without electrode, we can observe distinct zones corresponding to cavitation production and stationary waves establishment. When increasing the input power, bubble clouds tend to form a unique cloud near the transducer. In presence of the electrode, bubble cavitation clouds are largely influenced by the obstacle. The second part of the paper (part II) will describe the Particle Image Velocimetry (P.I.V.) technique which allows to measure the velocity vector field in the fluid portion between the horn and the electrode.     

ESI‐MS/MS of expanded porphyrins: a look into their structure and aromaticity

Electrospray mass spectrometry/mass spectrometry was used to investigate the gas‐phase properties of protonated expanded porphyrins, in order to correlate those with their structure and conformation. We have selected five expanded meso‐pentafluorophenyl porphyrins, respectively, a pair of oxidized/reduced fused pentaphyrins (22 and 24 π electrons), a pair of oxidized/reduced regular hexaphyrins (26 and 28 π electrons) and a regular doubly N‐fused hexaphyrin (28 π electrons). The gas‐phase behavior of the protonated species of oxidized and reduced expanded porphyrins is different. The oxidized species (aromatic Hückel systems) fragment more extensively, mainly by the loss of two HF molecules. The reduced species (Möbius aromatic or Möbius‐like aromatic systems) fragment less than their oxidized counterparts because of their increased flexibility. The protonated regular doubly fused hexaphyrin (non‐aromatic Hückel system) shows the least fragmentation even at higher collision energies. In general, cyclization through losses of HF molecules decreases from the aromatic Hückel systems to Möbius aromatic or Möbius‐like aromatic systems to non‐aromatic Hückel systems and is related to an increase in conformational distortion. Copyright © 2016 John Wiley & Sons, Ltd.     

Active control of the turbulent drag by a localized periodical blowing dissymmetric in time

Experimental results on the reaction of the near wall turbulence and drag to a localized time periodical blowing are reported. The injection velocity is periodical and dissymmetric in time, with a rapid acceleration phase followed by a slow deceleration one. The flow is relaminarized during 70% of the oscillation period mainly during the deceleration phase. The latter maintains stable the vorticity layer induced by the blowing and prevents its roll-up contrarily to a sinusoidal time periodical blowing. Thus, a time mean drag reduction of 50% is obtained in the region recovering 200 wall units downstream of the blowing slot and this is 40% larger than the drag reduction obtained by a steady blowing with the same time mean severity parameter. The dissymmetric blowing annihilates considerably the wall turbulence activity and gives better results in terms of drag reduction compared with steady and sinusoidal blowing.

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Respective contribution of cavitation and convective flow to local stirring in sonoreactors

The knowledge of respective parts of convection and cavitation to the stirring induced by ultrasound at one exact position into a sonoreactor is useful for all processes implementing surfaces exposed to sonication. PIV measurement allows real fluid motion determination, whereas the electrochemical technique gives an equivalent flow velocity considered as the sum of all stirring contributions to the electrode. Thus, by a simple subtraction between real fluid velocity and equivalent flow velocity, it is possible to identify the contribution of each phenomenon. Applied to low frequency reactors, it had been observed that cavitation is the preponderant phenomenon, with a contribution of stirring close to the electrode always more than 90%. High frequency reactors, frequently known to produce less cavitation, have shown that at the focal zone, if it concerns HIFU, cavitation becomes preponderant and reaches similar values to those close to the ultrasonic horn in low frequency sonoreactors.     

Investigating the vortex melting phenomenon in BSCCO crystals using magneto-optical imaging technique

Using a novel differential magneto-optical imaging technique we investigate the phenomenon of vortex lattice melting in crystals of Bi₂Sr₂CaCu₂O₈ (BSCCO). The images of melting reveal complex patterns in the formation and evolution of the vortex solid-liquid interface with varying field (H)/temperature (T). We believe that the complex melting patterns are due to a random distribution of material disorder/inhomogeneities across the sample, which create fluctuations in the local melting temperature or field value. To study the fluctuations in the local melting temperature/field, we have constructed maps of the melting landscape T _m(H, r), viz., the melting temperature (T _m) at a given location (r) in the sample at a given field (H). A study of these melting landscapes reveals an unexpected feature: the melting landscape is not fixed, but changes rather dramatically with varying field and temperature along the melting line. It is concluded that the changes in both the scale and shape of the landscape result from the competing contributions of different types of quenched disorder which have opposite effects on the local melting transition.     

Energy dependence of multiplicity in proton-nucleus collisions and models of multiparticle production

This is a continuation of our earlier investigation (Gurtuet al 1974Phys. Lett. 50 B 391) on multiparticle production in proton-nucleus collisions based on an exposure of emulsion stack to 200 GeV/c beam at the NAL. It is found that the ratioR _em = 〈n _s〉/〈n _ch〉, where 〈n _ch〉 is the charged particle multiplicity in pp-collisions, increases slowly from about 1 at 10 GeV/c to 1·6 at 68 GeV/c and attains a constant value of 1·71 ± 0·04 in the region 200 to 8000 GeV/c. Furthermore,R _em = 1·71 implies an effectiveA-dependence ofR _A =A ^0.18,i.e., a very weak dependence. Predictions ofR _em on various models are discussed and compared with the emulsion data. Data seem to favour models of hadron-nucleon collisions in which production of particles takes place through adouble step mechanism,e.g., diffractive excitation, hydrodynamical and energy flux cascade as opposed to models which envisage instantaneous production.     

A predictive model obtained by identification for the ultrasonic “equivalent” flow velocity at surface vicinity

In the specific applications of surface cleaning and electrochemistry which consist of processes implanting surface irradiation by ultrasound, design of large-scale devices requires us to understand acoustic field distribution together with its quantification. This observation allows systematic measurement of ultrasonic stirring throughout electrochemical determination of “equivalent” flow velocity versus various operating parameters (powers, electrode-horn distances, reactor geometry, frequencies, etc.). A numerical model was proposed to fit our curves and to identify some parameters by taking into account the characteristics of the ultrasonic wave (absorption coefficient, rate of cavitation bubbles and acoustic power). Nevertheless, the flicked behavior of the ultrasonic processes in the vicinity of the electrode as well as bubble presence which induce non-linearities in wave propagation lead us to propose a new approach based on parameter identification by methods currently used in chemical engineering. These parameters were related to physical criteria, and the global model was evaluated throughout analysis of its sensibility criteria.     

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

Background

Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.

Results

We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.

Conclusion

Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery.