Effects of beta3-integrin blockade (c7E3) on the response to angioplasty and intra-arterial stenting in atherosclerotic nonhuman primates

Because the beta3-antagonist abciximab (c7E3 Fab) has significantly improved late outcomes after coronary angioplasty, the beta3 integrins have been implicated in the arterial response to injury. However, the mechanisms underlying this benefit are unknown. The observation that c7E3 binds beta3 integrins on vascular cells (alphavbeta3) with affinity equal to that for the platelet glycoprotein IIb/IIIa integrin has led to the hypothesis that c7E3 may act directly on the artery wall to prevent restenosis after angioplasty. To test this hypothesis, we studied the effects of c7E3 on structural changes within the artery wall after angioplasty or stent angioplasty in 23 male cynomolgus monkeys with established atherosclerosis. Animals were randomly assigned to receive either a bolus of c7E3 (0.4 mg/kg IV, n=11) followed by a 48-hour infusion (0. 2 microg. kg-1. min-1) or an equal volume of vehicle (n=12). Animals received weight-adjusted aspirin and heparin and then underwent unilateral iliac artery experimental angioplasty and subclavian artery stent angioplasty (Palmaz). Iliac artery lumen diameter (LD) was determined by angiography at baseline (LDPre), after angioplasty (LDPost), and 35 days later (LDDay35). Arteries were then fixed by perfusion and removed for analysis. Lumen, intima, media, and external elastic lamina (EEL) areas were measured in iliac artery cross sections. Values from each injured iliac artery were normalized to the contralateral uninjured iliac artery to control for interanimal variability in baseline artery size and atherosclerosis extent. Intimal area was also measured in subclavian stent cross sections. c7E3 blocked platelet aggregation and prolonged the bleeding time from 2.8+/-1.1 to 19.8+/-2.5 minutes, P<0.001. Experimental angioplasty increased LDPost an average of 28%, and the initial gain was similar in both groups (P=NS). Despite an anti-platelet effect, c7E3 did not inhibit iliac lumen narrowing (LDDay35-LDPost: c7E3, -0.69+/-0.17 versus vehicle, -0.99+/-.17 mm, P=0.35); intimal hyperplasia (neointima area: c7E3, 1.12+/-.28 versus vehicle, 1.22+/-.20 mm2, P=0.77); or decrease in artery wall size (EEL area [percent of uninjured control]: c7E3, 101+/-7% versus vehicle, 121+/-7%). Stent intimal hyperplasia was also unaltered by c7E3 treatment (neointimal area: c7E3, 1.09+/-0.16 versus vehicle, 1. 28+/-0.11 mm2, P=0.36). These results suggest that the benefits of c7E3 treatment in coronary angioplasty were not from inhibition of intimal hyperplasia or improved artery wall remodeling. Alternative mechanisms should be explored to explain improved late outcomes after angioplasty in patients treated with c7E3.     

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis)

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.     

Basic properties of metal/insulator/semiconductor structures containing borazone and diamond layers produced by the reactive pulse plasma method

In this paper the results of an investigation of diamond and borazone layers produced by the reactive pulse plasma method on silicon substrates are presented. The properties of the layers were studied by conventional analysis of a metal/ insulator/semiconductor capacitor. The fundamental parameters (dielectric constant ε_ri of insulator, flat-band voltage U_FB, equivalent surface state density N_eff, interface trap density D_it and dielectric mobile charge density Q_m) of the structure were determined. The values of these parameters as well as the other structural and electrophysical properties of diamond and borazone layers, including their similarity to silicon, suggest possible applications of these layers in the technology of semiconductor devices. Nevertheless the exploitation of these advantages requires an improvement of the quality of the dielectric.     

Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry

A novel high-throughput method for characterizing heavily modified peptides from cone snail venom is described. Unpurified cone snail duct venom, consisting primarily of multiply disulfide-bonded peptides, is reduced and alkylated using a global procedure in order to simultaneously reduce and derivatize dozens of disulfide-bonded peptides. Samples of Conus victoriae venom are analyzed by online liquid chromatography-electrospray ionization-ion trap-mass spectrometry (LC-ESI-MS) with collisionally induced dissociation (CID). Comparison of the mass profiles of peptides and CID spectra before and after the global reduction and alkylation enables cysteine-containing conopeptides to be ascertained. In this case, over 40 conotoxins are characterized based on only two LC-ESI-MS experiments in terms of mass, number of disulfide-linked cysteine residues (and hence, potential toxin superfamilies), relative hydrophobicity, and other posttranslational modifications. Using this technique, over half of the amino acids (by mass) of several peptides are defined prior to any detailed sequencing studies. Further comparison of the mass data with previously published genetic information allows sequence verification of three novel peptides, termed vc5b, vc6b and vc6c, based on both LC-ESI-MS CID and nanoelectrospray ionization-ion trap-mass spectrometry (nanoESI-MS) experiments. This global method is ideally suited to the use of larger genetic databases in order to efficiently sequence peptides in Conus venoms and is also applicable to analysis of other disulfide-rich classes of peptides such as defensins, chemokines, and snake, spider, or other venoms.     

Bioaccumulation of platinum group elements and characterization of their species in Lolium multiflorum by size-exclusion chromatography coupled with ICP-MS

The bioaccumulation of Pt, Pd and Rh by grass grown hydroponically with nutrient solutions containing these ions at elevated (38.7 mg l(-1) Pt, 21.7 mg l(-1) Pd and 7.1 mg l(-1) Rh) and medium (3.6 mg l(-1) Pt, 4.4 mg l(-1) Pd and 0.5 mg l(-1) Rh) concentrations was studied by using inductively coupled plasma sector field mass spectrometry (ICP-SFMS). The highest bioaccumulation factors were obtained for Pd and Rh in roots and for Pt in leaves. The obtained results showed that most of the studied metals were accumulated in roots, and only a small fraction was really metabolised and transported to leaves. The multi-element capability of ICP-SFMS has been exploited to study the metabolism of platinum group elements (PGEs) in cultivated plants. The species of studied metals were extracted from roots and leaves and separated into two mass fractions by ultra-filtration. The low molecular mass (<10 kDa) fractions of the root and the leaf extracts were investigated by size-exclusion chromatography (SEC) coupled on-line to ICP-SFMS. The presence of Ca, Cu, S and C in the same fractions as Pt, Pd and Rh may indicate the interaction of PGEs with phytochelatins and carbohydrates.     

A round-robin programme on interfacial test methods

A round-robin programme has been undertaken to assess the compatibility in the micromechanical techniques used to evaluate the interfacial shear strength of the fibre/matrix bond in composite materials. The tests selected for evaluation were the single-fibre pull-out test, the microdebond test, the fragmentation test and the micro-indentation test. Twelve laboratories were invited to participate in this programme. Each laboratory was supplied with Caurtaulds XA fibre in the untreated condition and with a standard surface treatment, and a quantity of epoxy resin, hardener and catalyst, all from the same batch. Some laboratories were supplied with composite bars made with the same materials. A common cure cycle was chosen for sample preparation. Each laboratory conducted the tests to its own procedures. The results showed that the scatter within each laboratory was acceptable but the scatter between laboratories for a particular test was high. The results are discussed and possible explanations are presented for these observations. The indications are that the fundamental procedures used in each laboratory are sound. The results also suggest that there is great potential for achieving standard procedures and reducing the inter-laboratory scatter. A further round-robin programme is proposed to generate test protocols.     

Modeling of SOI-MOS capacitors C-V behavior: partially- andfully-depleted cases

A model is presented for the C-V characteristics of partially-depleted (PD) and fully-depleted (FD) SOI-MOS capacitors. The proposed model is flexible, allowing introduction of all types of nonidealities typical to MOS type structures. New formulae for the low- and high-frequency capacitances of these structures are derived. Due to the various charges stored in these structures, unusual and more complex C-V curves are obtained. C-V curves where interface-state densities have been individually introduced (one at a time) at all three SiO₂-Si interfaces of the SOI-MOS-C are also demonstrated. The model has been validated by fitting the predicted HF C-V curves for SOI-MOS-C and its inherent structure, the SIS capacitor, to the experimental data. The extracted electrophysical parameters of the studied structures, for both PD and FD cases, are very close, if not the same as the values determined during their fabrication     

Effect of wastewater spray irrigation on rotavirus infection rates in an exposed population

The Lubbock Infection Surveillance Study was conducted between June 1980 and October 1983 to detect potential increases in enteric infection and disease incidence in a community surrounding a wastewater spray irrigation site. This report concerns the incidence of rotavirus infections in study participates during that period. Rotavirus infection was defined as a > 2-fold increase in rotavirus serum antibody between blood collections which occurred approximately every 6 months. Antibody was detected by an enzyme-linked immunosorbent assay (ELISA). Of the 368 participants who provided 2 blood specimens, 67 seroconversions to rotavirus were detected, an average annual rate of 6.8 infections/100 subjects. One subject was infected twice. Seroconversions were observed in 32.7% (32/98) of children 16 years of age and in 12.7% (33/260) of adults ( 17 years old) with a single infection. Thus, significantly more (P < 0.0001) rotavirus infections occurred in children. Baseline rotavirus serum antibody titers were found to be significantly lower (P = 0.047) in subjects who seroconverted. However, many children and adults with high titers were also infected. More seroconversions were observed between June and December (January) than between December (January) and June. Wastewater spray irrigation had no detectable effect on the incidence of rotavirus infection.     

Allocation of research funds in competitive environment. A computerized negotiation system

The paper is concerned with the problem of financing of complex research programs. One of tasks to be solved consists in assigning research teams, willing to participate in a given program, to research projects being its elements, under conditions of constrained budget. It is assumed that the strategy of every research team head is to maximize the average time-discounted income per person. In the previous paper of the authors a special negotiation procedure has been proposed to solve this problem. This paper presents some possible extensions and modifications of the procedure. At each stage of this procedure the heads of research teams involved have to make decisions on the assignment of their workers to particular projects. The proposed system of interactions among the research teams heads provides a possibility of reaching the consensus in the matter of this assignment. Simultaneously, it makes possible to solve the problem of research funds allocation. Such a system is considered as a multiperson game of Nash type with the non-zero sum of the players payments.