Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.     

Helicobacter pylori: the mouth, stomach, and gut axis

The aim of this study was to identify the natural reservoir and route of transmission of Helicobacter pylori infection. Two hundred eight (208) dyspeptic patients (114 males, 94 females; peak age of cohort, 50-59.9) were recruited. Specimens were collected from saliva, supra- and subgingival dental plaque, tongue scrapings, and oropharyngeal swabs. At subsequent endoscopy, gastric antral biopsy was performed for the rapid urease test (RUT), microbiological culture, and, in some patients, histology. Gastric juice samples were aspirated, and in 50 patients duodenal aspirate was collected. Polymerase chain reaction (PCR) with primers targeted to the 16S rRNA sequence of H. pylori was also employed for each of the specimens. In those patients where H. pylori was detected from multiple sites (dental plaque, gastric juice, gastric biopsy, and duodenal aspirate), restriction endonuclease digestion with Hae III was performed to determine if they were epidemiologically linked. The results indicated that 15/208 patients (7%) tested positively for H. pylori by PCR in dental plaque; only 2 samples were positive by culture. In none of the other oral sites sampled was H. pylori detected by any test used in the study. Gastric juice and gastric biopsy specimens from 36/ 208 patients (17%) and 114/208 patients (55%), respectively, were positive by PCR. Duodenal aspirate from 6/50 patients (12%) also tested positively by PCR. All specimens tested by restriction endonuclease digestion with Hae III (15/15 patients) were positive in both antral biopsy and gastric juice specimens, as well as 5 specimens from the duodenal aspirate. Four of the dental plaque strains had restriction patterns similar to those of the stomach and duodenal sites, providing evidence that these sites were infected with the same strain of H. pylori. In conclusion, the results suggest that H. pylori selects the gastric mucosa as its preferred site. The detection in dental plaque could indicate that the oral cavity may act as a reservoir or sanctuary for the organism. Whether H. pylori is a resident or transient oral microorganism is still unclear, although it is more likely to be transient in nature.     

Comparison of quantification strategies for one-point standard addition calibration: The heteroscedastic case

Two quantification strategies for one-point standard addition calibration have been compared mathematically. One strategy involved the extrapolation of measurement points to their intercept with the x-axis to determine the analyte content in the unknown sample, and the other strategy is based upon direct calculation of the analyte content in the unknown sample using the instrumental responses obtained during measurement. The cases of both conventional standard addition calibration (C-SAC) and sequential standard addition calibration (S-SAC) have been considered. The heteroscedastic situation has been considered, where the relative precision of instrumental responses is constant.     

Stay on Your Feet Safety Walks Group

The Safety Walks Group is an initiative that evolved from the Stay on Your Feet Program. The strategies used in this program target both behavioural and environmental change and are based on the five areas for action under the Ottawa Charter (WHO, 1986) and Jakarta Declaration (WHO, 1997). The Safety Walks Group addresses the issue of public hazards via the use of a standard checklist covering pedestrian areas, business houses and accommodation. The project provided a forum for seniors to be proactive, working with the authorities to address the issue of public hazards and make the environment safer.     

In vivo radiofrequency thermal balloon angioplasty of porcine coronary arteries: histologic effects and safety

The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating.     

Human cytochrome P450 enzymes expressed in bacteria: reagents to probe molecular interactions in toxicology

1. Phase I metabolism of drugs is accomplished by the concerted actions of a limited number of cytochrome P450 enzymes with wide but often overlapping substrate specificites. Although metabolism generally accelerates the clearance of drugs, reactive products may also be generated that cause toxic effects. 2. Because individuals vary in the range and levels of different P450 forms, it is useful to be able to determine the specific isoforms involved in a particular metabolic reaction, in order to estimate the extent of variation within a population in the pharmacokinetics of specific drugs. Such studies may also allow predictions to be made regarding the relative susceptibility of different individuals to possible adverse effects associated with drug treatment. 3. Human cytochrome P450 enzymes are now routinely expressed as recombinant proteins in many different systems, including mammalian cell culture, yeast, baculovirus and Escherichia coli. The latter system is particularly useful when large amounts of protein are required for biophysical studies, but can also be adapted to routine examination of pathways of drug metabolism and toxicology. 4. The present review provides an analysis of strategies used for enhancing cytochrome P450 expression in bacteria and for examining the activity of the recombinant proteins. The potential applications of recombinant P450 are discussed, with particular emphasis on investigation of the roles of cytochrome P450 forms in the metabolism and the toxicity of drugs.     

The applications-assured infrastructure

Accurate knowledge of how applications are performing across a corporate enterprise infrastructure is a key factor in developing strategy for enterprise IT optimisation aligned to business drivers. BT’s applications-assured infrastructure proposition provides the ability for customers to understand where their application bottle-necks are, fix problems, optimise performance and provide long-term enterprise IT health monitoring. This is a big step towards the goal of supporting guaranteed end-to-end applications performance — the next level of quality-of-service-based product requirements.     

The Dentin Disc surface: a plausible model for dentin physiology and dentin sensitivity evaluation

Dentin sensitivity (DS) is a painful clinical condition which may affect 8-35% of the population. Various treatment modalities have claimed success in relieving DS, although at present there does not appear to be a universally accepted desensitizing agent. Current opinion based on Br?nnstr?m's Hydrodynamic Theory would suggest that following exposure of the dentin surface (through attrition, abrasion, or erosion), the presence of open dentinal tubules, patent to the pulp, may be a prerequisite for DS. The concept of tubule occlusion as a method of dentin desensitization, therefore, is a logical conclusion from the hydrodynamic theory. The fact that many of the agents used clinically to desensitize dentin are also effective in reducing dentin permeability tends to support the hydrodynamic theory. This paper reviews the in vitro evaluation of desensitizing agents, the techniques used to characterize their effects on the prepared dentin surface, and the ability of these agents to reduce permeability through tubule occlusion, and presents recent findings from ongoing research based on the Pashley Dentin Disc model. It can be concluded that the use of this model to determine surface characteristics, and reductions in dentin permeability through tubule narrowing or occlusion, provides a useful screening method for evaluating potential desensitizing agents. Interpreting changes observed in vitro is difficult, and extrapolation to the clinical situation must be tempered with caution.     

Upregulation of actin gene expression in cells expressing exogenous beta-amyloid precursor protein

We investigated the effects of beta-amyloid peptide precursor (APP) overexpression upon the levels of other mRNAs. Using quantitative slot-blot hybridization and immunoblot analysis we observed that enhanced levels of APP elevated the levels of beta-actin and beta-actin mRNA. Our results also suggest that the cytoplasmic domain of APP is crucial for the elevation in beta-actin gene expression.