Supraacetabular insufficiency fractures

Insufficiency fractures in the supraacetabular region were identified in five women, aged 55-83 years. Factors contributing to the diminished resistance of their bones included postmenopausal osteoporosis, steroid therapy, radiation therapy, and rheumatoid arthritis. The supraacetabular fractures were seen on routine radiographs as hazy bands of sclerosis located immediately above and parallel to the acetabular roof. All five patients had additional fractures in the spine or pelvis. Supraacetabular insufficiency fractures may be an unsuspected cause of hip pain, especially in older women.     

Impact on late toxicity of using transabdominal ultrasound for prostate cancer patients treated with intensity modulated radiotherapy

An analysis of the effects of using the B-mode ultrasound Acquisition and Targeting (BAT) system for positioning of prostate cancer patients receiving external beam radiotherapy (EBRT) on late gastrointestinal (GI) and genitourinary (GU) toxicity is provided. The records of 49 consecutive patients treated using the BAT were reviewed; additionally, a comparison (No-BAT) group treated in a similar manner was identified, consisting of 49 patients treated immediately prior to this BAT group. There were no other fundamental differences between the two groups. The daily BAT movements were charted and late toxicity was scored for all patients using established toxicity scales. The results demonstrated similar GU toxicity rates between the two groups, but slightly lower rates of GI toxicity in the BAT group vs. the No-BAT group. However, regression analyses revealed that no factors, including BAT use, were significantly correlated with late GI or GU toxicity. Further efforts, perhaps better undertaken in a multi-institutional setting, are needed to determine whether BAT use can significantly reduce late GI toxicity.     

Further insights into the potential of pulp and paper mill effluents to affect fish reproduction

As part of a continuing survey, effluents from five mills in Canada were tested in the laboratory for their potential to affect fish reproduction. The study included effluents from two thermomechanical pulp (TMP) mills, two kraft pulp mills, and one mill that used both chemical and mechanical pulping. The laboratory test used adult fathead minnows and involved a 21-day exposure to each effluent. All the effluents were tested at 2 and 20% concentration. The effluent from 1 of the kraft mills was also tested at 40% concentration. The endpoints of the test included, egg production, gonad size, sex steroids, secondary sexual characteristics, and vitellogenin concentration in males, considered to be an indicator of estrogenicity. The results of this study were similar to the results of our previous survey. None of the effluents produced noteworthy changes at 2% concentration. At 20% concentration, only the effluent from the multiprocess mill produced a significant reduction in eggs, which was considered to be the most important indicator of reproductive performance. Some effluents did produce an increase and/or a decrease in a variety of endpoints other than egg production, but the most consistent response was an induction of vitellogenin in males exposed to three of the five effluents tested. In summary, these results indicate that most mill effluents up to 20 or 40% concentration do not affect the overall reproductive capacity of minnows in the laboratory. However, the mill effluents do seem to contain substances that cause vitellogenin induction.     

Modulation of MPP<Superscript>+</Superscript> uptake by tea and some of its components in Caco-2 cells

The entry of most xeno/endobiotics into the organism is limited by their intestinal absorption. The interference of certain foods with the therapeutic efficacy of drugs or with chemical toxicity is becoming evident and growing attention is being given to these subjects. The aim of this work was to study the effect of green tea (GT) and black tea (BT), as well as some of their components, on the transport of organic cation molecules. For this purpose, ³H-MPP⁺ (radiolabeled 1-methyl-4-phenylpyridinium) was used as a model organic cation and Caco-2 cells were used as an intestinal epithelial model. Our results showed that both GT and BT significantly increased ³H-MPP⁺ absorption in these cells. Additionally, we studied the effect of epigallocatechin-3-gallate (EGCG), myricetin, caffeine, and theophylline. Whereas EGCG (2 mM) increased, myricetin (50 μM) and caffeine (1 mM) decreased, and theophylline (1 mM) had no effect on the uptake of ³H-MPP⁺ into Caco-2 cells. When GT was supplemented with caffeine or theophylline, we observed a partial loss of its effect. When BT was supplemented with EGCG, its ability to increase ³H-MPP⁺ uptake was much more pronounced than that observed with BT alone. In conclusion, this study showed that GT and BT might interfere with the absorption of the model organic cation MPP⁺ by the intestinal epithelium. Since important compounds are organic cations, the consequences of this interference may have an impact on human health. Although this constitutes only preliminary work and further studies are needed, tea should be included in the growing list of foodstuffs that have the potential to be involved in food–drug interactions.     

Effects of Dietary Administration of CL-20 on Japanese QuailCoturnix coturnix japonica

Hexanitrohexaazaisowurtzitane, or CL-20, is an emerging highly energetic compound currently under consideration for military applications. With the anticipated wide use of CL-20, there is the potential for soil and groundwater contamination resulting in adverse toxicologic effects on environmental receptors. Presently, there is a lack of data describing the toxic effects of CL-20 on avian species. The present study describes the effect of CL-20 on Japanese quail (Coturnix coturnix japonica) modified from standard toxicity test guidelines. First, a 14-day subacute assay was adopted using repeated gavage doses (0, 307, 964, 2439, 3475, or 5304 mg CL-20/kg body weight (BW)/d for 5 days followed by no CL-20 exposure (vehicle only) for 10 days. Second, a subchronic feeding assay (0, 11, 114, or 1085 mg CL-20/kg feed) was done for 42 days. During both studies, no overt toxicity was observed in the CL-20–treated birds. During the first 5 days of the subacute study, CL-20–exposed birds showed a dose-dependent decrease in BW gain, whereas increased liver weight, plasma sodium, and creatinine levels were observed in birds receiving the highest dose tested. For the subchronic study, embryo weights were significantly decreased in a dose-dependent manner. Embryos from CL-20–exposed birds were observed to have multiple cranial and facial deformities, beak curvatures, possible mid-brain enlargement, and classic one-sided development with micro-opthalamia (nonstatistical comparisons with control embryos). A trend toward decreased number of eggs laid per female bird was also observed. We conclude that CL-20 (or its degradation products) elicits few effects in adults but may affect avian development, although these preliminary findings should be confirmed.     

Clinical practice guidelines: medical follow-up of patients with asthma--adults and adolescents

The follow-up of patients with asthma should focus on asthma control (disease course over a number of weeks).     

Fluorometric monitoring of the effects of adrenergic agents on oxidative metabolism in intact cerebral cortex.

Amphetamine and other adrenergic agents were shown to alter the rate of oxidative metabolic activity measured by nicotinamide-adenine dinucleotide (NADH) fluorometry in intact cerebral cortex of cats and rats. Both amphetamine and isoproterenol administration produced a similar triphasic metabolic response pattern in brain: (1) an initial decrease in the NADH level, followed by (2) a more prolonged increase in the NADH redox level, and (3) a later large decrease in the level of reduced coenzyme. This pattern is interpreted to reflect increased “recovery” metabolism associated with enhanced cellular activity. Reserpine administration resulted in similar metabolic redox patterns except this drug produced a later increase in NADH level to a greater than baseline level. Chlorpromazine and propranolol increased the NADH level. Propranolol blocked the triphasic response patterns of both amphetamine and isoproterenol. When propranolol or chlorpromazine were given after either amphetamine or isoproterenol, the injection was followed by an increased level of NADH. It is thought that the effects of propranolol, chlorpromazine and reserpine are due to decreased tissue activity while the amphetamine and isoproterenol actions are mediated through central β-receptors. These experiments demonstrate the feasibility of optically monitoring oxidative metabolic activity in situ during drug administration and indicate the importance of combining this technique with biochemical assay procedures.     

Preliminary investigation of the feasibility of magnetic propulsion for future microdevices in blood vessels

The Magnetic Resonance Submarine (MR-Sub) project is a first attempt to validate a new propulsion method for future small magnetically controlled microdevices suited for minimally invasive applications in blood vessels. A Magnetic Resonance Imaging (MRI) system provides the driving force in three dimensions to a ferromagnetic core that could be embedded onto a specialised microdevice. The paper describes preliminary tests made to match the magnetic force induced by an MRI system on a ferromagnetic sphere with the drag force it encompasses in a cylindrical tube. These tests provide a proof of concept demonstrating that this new method of propulsion is very promising within the constraints of such types of operations. This conclusion is based on specific measurements showing that 1010/1020 carbon steel spheres (3.175 mm and 2.381 mm in diameter) can withstand a maximum flow of 0.370 +/- 0.0064 l/min (19.5 cm/s) and 0.311 +/- 0.01209 l/min (16.4 cm/s) respectively when placed inside a 6.35 mm diameter PMMA tube and subjected to a 18 mT/m magnetic field gradient.     

AMPA receptor phosphorylation is selectively regulated by constitutive phospholipase A(2) and 5-lipoxygenase activities

The present investigation provides the first indication that constitutive, calcium-independent phospholipase A2 activity (iPLA2) modulates phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of glutamate receptors. Preincubation of frozen-thawed brain sections with two iPLA2 inhibitors, bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACO), produced a dose-dependent enhancement in phosphorylation at both Ser831 and Ser845 sites on the GluR1 subunit of AMPA receptors. This effect was not associated with changes in phosphorylation at the Ser sites of either the GluR2/3 subunits of AMPA receptors or the NR1 subunits of N-methyl-D-aspartate (NMDA) receptors, nor was it reproduced by inhibition of the calcium-dependent form of PLA2 activity. These results suggest that the effects of these inhibitors are selective to GluR1 subunits and that they are dependent on iPLA2 activity. The ability of iPLA2 inhibitors to increase GluR1 phosphorylation was mimicked by the 5-lipoxygenase (5-LO) inhibitor MK-886, but not by blockers of 12-lipoxygenase (12-LO) or cyclooxygenase. Additional experiments indicated that calcium-mediated truncation of GluR1 subunits was reduced by iPLA2 inhibitors, an effect that was not correlated with overall changes in the distribution of AMPA receptors between intracellular and membrane compartments prepared from whole brain sections. However, quantitative autoradiographic analysis indicated enhanced 3H-AMPA binding to the CA1 stratum radiatum of the hippocampus in BEL-treated sections. Saturation kinetics experiments demonstrated that this binding augmentation was due to an increase in the maximal number of AMPA binding sites. Altogether, our results point to the conclusion that basal iPLA2 activity, through the generation of 5-LO metabolites, regulates AMPA receptor phosphorylation of GluR1 subunits, an effect that might selectively influence the number of membrane receptors in area CA1 of the hippocampus.