Processing of chimeric antisense oligonucleotides by human vascular smooth muscle cells and human atherosclerotic plaque. Implications for antisense therapy of restenosis after angioplasty

BACKGROUND: Antisense oligonucleotides have been used in animals to inhibit the accumulation of vascular smooth muscle cells (VSMCs) after arterial injury. This has raised prospects for an oligonucleotide-mediated approach to prevent restenosis in patients undergoing angioplasty. However, little is known about the processing of oligonucleotides by human VSMCs or their bioavailability in human atherosclerotic tissue. METHODS AND RESULTS: Oligonucleotides were synthesized with a mixture of unmodified and sulfur-modified linkages (S-chimeric oligonucleotides). These were more stable than unmodified oligonucleotides and could be recovered from within human VSMCs after 36 hours. Oligonucleotide antisense to human proliferating cell nuclear antigen mRNA specifically reduced DNA synthesis (P < .01) and proliferating cell nuclear antigen protein content (P < .05) in human VSMCs. Confocal microscopy of both live and fixed cells showed modest oligonucleotide uptake that was primarily nuclear. Surprisingly, cationic liposomes did not enhance nuclear uptake but led to extensive, punctated cytoplasmic loading without an enhanced antisense effect. Oligonucleotides incubated with human coronary atherosclerosis fragments associated with cells within 1 hour, despite the presence of abundant extracellular matrix. CONCLUSIONS: S-chimeric oligonucleotides are stable and can specifically inhibit gene expression in human VSMCs. Nuclear transport is a feature of oligonucleotide processing by human VSMCs, indicating a potential influence at the nuclear level rather than with cytoplasmic mRNA. Cationic liposomes increased oligonucleotide uptake but not intracellular bioavailability, and S-chimeric oligonucleotides can be incorporated into cells within human atherosclerotic plaque, despite the presence of a dense extracellular matrix.     

Risk factors for wound infection following celiotomy in horses

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.     

An introduction to the traditional fermented foods and beverages of Turkey

Fermented foods and beverages, whether of plant or animal origin, play an important role in the diet of people in many parts of the world. Fermented foods not only provide important sources of nutrients but have also great potential in maintaining health and preventing diseases. Lactic acid bacteria and yeasts are the major group of microorganisms associated with traditional fermented foods. Many different types of traditional fermented foods and beverages are produced at household level in Anatolia. These include fermented milks (yoghurt, torba yoghurt, kurut, ayran, kefir, koumiss), cereal-based fermented food (tarhana), and non-alcoholic beverage (boza), fermented fruits, and vegetables (tur?u, ?algam, hardaliye), and fermented meat (sucuk). However, there are some differences in the preparation of traditional foods and beverages from region to region. The focus of this article is to describe the traditional fermented foods and beverages of Turkey.     

Interstitial condensation in n+ GaAs

Transmission electron microscopy of annealed tellurium-doped gallium arsenide has shown that a high constitutional interstitial defect population is present in n⁺ as-grown material. The point defects precipitate into the form of perfect interstitial dislocation loops when annealed above 380°C. The equivalent point defect concentration within the loops remains constant during isochronal and isothermal anneals and is dependent on the tellurium level. Copper diffusion is also found to influence the point defect concentration and copper may be the element responsible for the formation of the precipitates often associated with the large dislocation loops.     

Stability of CdTe/CdS thin-film solar cells

The recent literature regarding the stability of CdTe/CdS photovoltaic cells (as distinguished from modules) is reviewed. Particular emphasis is given to the role of Cu as a major factor that can limit the stability of these devices. Cu is often added to improve the ohmic contact to p-CdTe and the overall cell photovoltaic performance. This may be due to the formation of a Cu₂Te/CdTe back contact. Excess Cu also enhances the instability of devices when under stress. The Cu, as Cu⁺, from either Cu₂Te or other sources, diffuses via grain boundaries to the CdTe/CdS active junction. Recent experimental data indicate that Cu, Cl and other diffusing species reach (and accumulate at) the CdS layer, which may not be expected on the basis of bulk diffusion. These observations may be factors in cell behavior and degradation, for which new mechanisms are suggested and areas for future study are highlighted. Other possible Cu-related degradation mechanisms, as well as some non-Cu-related issues for cell stability are discussed.     

Stabilization of gas cavitation nuclei by surface-active compounds

Gas bubbles are the primary agent in producing the pathogenic effects of decompression sickness. Numerous experiments indicate that bubbles originate in water, and probably also in man, as pre-existing gas nuclei. This is surprising considering that gas phases larger than 1 micron should rise to the surface of a standing liquid, whereas smaller ones should dissolve rapidly due to surface tension. Several stabilizing mechanisms have been suggested, and each has been refuted on experimental grounds. In this article, we propose a new model that arises out of a systematic study of the earlier theories. We review these theories and conclude that gas cavitation nuclei must be held intact by surface-active skins that are initially permeable. The first quantitative analysis of bubble formation data from supersaturated gelatin is summarized and leads to the further conclusion that skins can become impermeable if the ambient pressure is increased rapidly by a sufficient amount. Our model owes much to Sirotyuk, who "demonstrated experimentally that stabilization of gas bubbles acting as cavitation nuclei in water is always attributable to the presence of surface-active substances in the water".     

Myocardial blood flow distribution in miniature pigs during exercise

Total and regional myocardial blood flow was measured in miniature pigs at rest and during two levels of treadmill exercise, including maximal exercise. Exercise increased the myocardial blood flow in a linear manner with heart rate (r = 0.87). At rest the endocardial/epicardial blood flow ratio was significantly greater than unity with flow favoring the endocardium. Exercise failed to appreciably alter the distribution of coronary blood flow. Thus the myocardium was capable of further dilatation and perfusion of blood without compromising endocardial flow even during the most severe level of exercise when maximal heart rates were attained.