Induction of chromosomal aberrations and spindle disturbances in Chinese hamster epithelial liver cells in culture by pyrene and benzo[a]pyrene quinones

Regioisomers of pyrene and benzo[a]pyrene quinones were testedfor their ability to induce structural and numerical aberrationsand spindle disturbance in Chinese hamster epithelial liver(CHEL) cells in culture. All quinones tested were clastogenicPyrene-1,8-quinone (P-1,8-Q) and benzo[a]pyrene–3,6–quinone(BP-3,6-Q) induced strikingly high levels of triradials. Inaddition, dicentrics and ring chromosomes were very common inBP-3,6-Q-treated cultures. Isomers of these compounds, pyrene-1,6-quinone(P-1,6-Q) and benzo[a]pyrene-1,6-quinone (BP-1,6-Q), inducedunobtrusive patterns of chromosomal aberrations. We suspectthat the P-1,8-Q and BP-3,6-Q moieties bound to the DNA werestill reactive, and formed crosslinks and/or underwent redoxcycling leading to high local concentrations of reactive oxygenspecies. In addition, P-1,8-Q and BP-3,6-Q induced c-mitoses,hyperdiploidies and polyploidies, in particular endoreduplications.These effects were not seen with the other two test compounds,or they were only detected at the highest concentrations used,which were strongly cytotoxic (c-mitoses with P-1,6-Q, polyploidieswith BP-1,6-Q). ⁶To whom correspondence should be addressed at: European Centre for the Validation of Alternative Methods (ECVAM), Joint Research Centre (JRC), TP58O, 1–21020 Ispra, Italy     

Learned alcohol aversions in rats: gustatory and olfactory components

The gustatory and olfactory basis of learned alcohol aversions was examined by testing rats with either gustatory neocortex ablations, olfactory bulb ablations, or a combination of both ablations. In the first experiment operated rats were compared with control rats in the acquisition of a learned alcohol aversion. In the second experiment, the effect of ablations on preoperatively-learned alcohol aversions was examined. Rats lacking gustatory neocortex learned and retained alcohol aversions normally although these rats extinguished the aversions faster than normal rats. Olfactory bulb ablation alone failed to disrupt normal aversion learning but completely eliminated retention of a previously acquired aversion. Combination ablations produced severe deficits both in acquisition and retention of learned alcohol aversions. The results indicate that, besides having gustatory qualities, the odor quality of alcohol is important in determining the associative and memorial characteristics of alcohol.     

Fast method for 1D non-cartesian parallel imaging using GRAPPA.

MRI with non-Cartesian sampling schemes can offer inherent advantages. Radial acquisitions are known to be very robust, even in the case of vast undersampling. This is also true for 1D non-Cartesian MRI, in which the center of k-space is oversampled or at least sampled at the Nyquist rate. There are two main reasons for the more relaxed foldover artifact behavior: First, due to the oversampling of the center, high-energy foldover artifacts originating from the center of k-space are avoided. Second, due to the non-equidistant sampling of k-space, the corresponding field of view (FOV) is no longer well defined. As a result, foldover artifacts are blurred over a broad range and appear less severe. The more relaxed foldover artifact behavior and the densely sampled central k-space make trajectories of this type an ideal complement to autocalibrated parallel MRI (pMRI) techniques, such as generalized autocalibrating partially parallel acquisitions (GRAPPA). Although pMRI can benefit from non-Cartesian trajectories, this combination has not yet entered routine clinical use. One of the main reasons for this is the need for long reconstruction times due to the complex calculations necessary for non-Cartesian pMRI. In this work it is shown that one can significantly reduce the complexity of the calculations by exploiting a few specific properties of k-space-based pMRI.     

Metabolic activation to a mutagen of 3-hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, a secondary metabolite of benzo[a]pyrene

3-Hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (3-OH-BP-7,8-diol)wag isolated from arylsulfatase/ß-glucuronidase-treatedbile of rats to which 3-hydroxybenzo[a]pyrene (3-OH-BP) hasbeen administered. This triol was investigated for mutagenicityin Salmonella typhimurium (reversion to histidine prototrophyof strains TA 97, TA 98, TA 100 and TA 1537) and in V79 Chinesehamster cells (acquisition of resistance to 6-thioguanine).When no exogenous metabolizing system was added the triol wasinactive, while 3-OH-BP showed weak mutagenic effects with allfour bacterial strains. In the presence of NADPH-fortified postmitochondrialsupernatant fraction (S9 mix) of liver homogenate from Aroclor1254-treated rats, the mutagenicity of 3-OH-BP was potentiated,and the triol was activated to a mutagen(s). In the presenceof S9 mix, the triol was 5—18 times more mutagenic than3-OH-BP in strains TA 97, TA 100 and TA 1537, but both compoundsshowed similar mutagenic potencies with strain TA 98. Thesestrain differences strongly suggest that the mutagenicity of3-OH-BP in the S9 mix-mediated test was not exclusively dueto metabolites of 3-OH-BP-7, 8-diol. Trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene(BP-7,8-diol), like the triol, showed mutagenic effects onlyin the presence of S9 mix. Strain TA 1537 was reverted by thetriol but not by the diol. In the other bacterial strains thediol was more mutagenic than the triol, the difference in potencybeing largest in strain TA 100 (2.5-to 10-fold, depending onthe experimental conditions). In V79 cells, the diol was a potentmutagen, while the triol showed only very weak mutagenic effects.However the triol was more cytotoxic than the diol. High cytotoxicityof the triol was observed even in the absence of S9 mix. Theresults of the present study demonstrate that metabolites of3-OH-BP-7, 8-diol) are biologically-active derivatives of benzo[a]pyrene.Comparison of the mutagenic effectiveness in different bacterialstrains also reveals that metabolites of 3-OH-BP-7, 8-diol andof BP-7, 8-diol substantially differ in the kind of geneticalterations they evoke.     

Open fractures of the elbow joint

Both in open and in closed elbow fractures, anatomical joint reconstruction and rigid internal fixation, which permit early initiation of motion, are essential for good joint function. However, in open distal intraarticular humerus fractures this is more difficult to achieve, owing to the high rate of comminuted types C 2 and C 3 fractures. In addition, the extensive soft tissue lesions often mean that physiotherapy cannot be started until later than would otherwise be desirable. This retrospective study shows that the functional results in 60 patients operated on for correction of open distal intraarticular humerus fractures were worse (1/3 "excellent/good", 2/3 "moderate/poor") than those in patients treated for closed fractures. Complications included superficial infection in 7 patients, osteitis in 11, late instability in 10, fatigue failure of the implants in 5, and non-union in 10 patients.     

Food service in Austrian hospitals: results of a survey]

130 medical and 130 administrative heads were asked to fill in a structured questionnaire to obtain an assessment of meals provided in Austrian hospitals. 62 questionnaires in each group were returned fully completed. Meals: ?S 46,--are available per patient and day; whereby the costs of special diets are ?S 11,--higher on average per day. Diets on offer: 96.8% of the questioned hospitals offered a diabetes diet; 95.2% a weight-reducing diet, 93.5% a light balanced diet and diet for patients with hyperlipidaemia and 90.3% a reduced salt diet (the worst accepted by the patients). 90.3% of these hospitals would consider dietary recommendations as a preventive measure. In fact, preventive dietary measure are implemented in 75.5% of the hospitals questioned. It was apparent that the staff in charge are aware of the influence of correct-nutrition in hospitals. It is recommended that nutritional advice should be offered more often in all wards (this is at present available in only 8.0% of the hospitals). It should be mentioned that financial resources concerning hospital meals should be increased for the more widespread establishment of "healthy food", too.     

Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages

Whereas local microglial cells of the CNS rapidly respond to injury, little is known about the functional role of resident macrophages of the peripheral nervous system in nerve pathology. Using bone marrow chimeric rats, we recently identified individual resident endoneurial macrophages that rapidly became activated after nerve injury. However, the extent of local macrophage activation and its quantitative contribution to the total macrophage response is unknown. We now have created chimeric mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated wild-type mice, allowing easy differentiation and quantification of hematogenous and resident endoneurial macrophages. After sciatic nerve crush injury, both GFP(-) and GFP(+) resident macrophages, the latter having undergone physiological turnover from the blood before injury, rapidly underwent morphological alterations and increased in number. Proliferating GFP(-) and GFP(+) resident macrophages were abundant and peaked 3 days after injury. A major lesion-induced influx of hematogenous macrophages with a disproportionate increase of GFP(+) macrophages was not observed until Day 4. Throughout all time points examined, GFP(-) resident macrophages were strikingly frequent, reaching maximum numbers 9.5-fold above baseline. There was also a notable proportion of GFP(-) resident endoneurial macrophages phagocytosing myelin and expressing major histocompatibility complex class II. Our results demonstrate for the first time that the rapid response of resident endoneurial macrophages to nerve injury is quantitatively important and that local macrophages contribute significantly to the total endoneurial macrophage pool during Wallerian degeneration.