Method of measuring deposition of unlabeled monodisperse microspheres in rat lungs

A system to simultaneously measure the total deposition of four different sizes of monodisperse microspheres in normal and damaged lungs of rats was developed and tested. The system reproducibly measured the deposition of microspheres in control rats, and the procedure was shown to be sufficiently sensitive to measure ozone-induced changes in deposition rates. Rats exposed to 1.2 ppm ozone 6 h/d for 2 consecutive days showed greater deposition of the 1.09-micron-, 2.02-micron-, and 2.99-micron- but not of the 0.48-micron-diameter microspheres when compared to controls. After 8 consecutive days of exposure to the same concentration of ozone, there were no differences in deposition rates between control and ozone-exposed rats. Respiratory physiology and lung histopathology data provided evidence that subtle changes in the airway architecture and/or aerodynamics were likely to be responsible for the differential deposition rates as a function of the duration of ozone exposure.     

Age, personality, and the Holtzman Inkblot Technique

Recent longitudinal studies using personality questionnaires and ratings have shown remarkable stability across the adult years. In an investigation of age changes and differences in personality as measured by the Holtzman Inkblot Technique (HIT), ninety-three men and women aged twenty-five to ninety were administered Form A of the HIT; forty-four of these were retested one to three years later. Stability coefficients ranged from .07 for Form Appropriateness to .73 for Form Definiteness, with most variables showing significant but moderate stability. Repeated measures analyses of variance showed increases in six variables and decreases in two others, but only one of these changes was paralleled by cross-sectional age differences. Correlations with self-report measures of the broad personality domains of neuroticism, extraversion, and openness to experience failed to show hypothesized relations, and the associations seen were attributable to chance. It was concluded that the HIT measures perceptual-cognitive variables that are moderately stable in adulthood.     

Carotid surgery. Is regional anesthesia always appropriate?

We retrospectively studied a series of 385 carotid endarterectomies performed either under general anesthesia (242) or under local anesthesia (145) to compare the peri-operative mortality and morbidity rate and to identify factors which may influence the choice of anesthesia. The rate of transient ischaemic attacks (TIA), stroke, death, combined mortality, severe neurological and cardiac morbidity were not statistically different. Under general anesthesia, more shunts were inserted (17% versus 7%, p less than 0.05) and more myocardial infarctions occurred (5% versus 0%, p less than 0.05). However, more strokes due to technical imperfection were seen under regional anesthesia. We concluded that regional anesthesia is more appropriate in patients with coronary artery disease and in patients at risk of intolerance to cross clamping. General anesthesia is more appropriate in poorly cooperative patients or in those with unfavorable operative conditions.     

Interaction of short chain aliphatic alcohols with muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex from neonatal and adult rats.

Muscarinic receptor-stimulated phosphoinositide metabolism has been recently suggested as a possible target for the neurotoxic effects of ethanol during brain development. Since two other alcohols, tertiary butanol and n-propanol, have been shown to cause microencephaly in the rat when administered during the brain growth spurt, in the present study we investigated the in vitro effects of five short chain aliphatic alcohols on muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortical slices from 7 day-old rats. In neonatal animals all alcohols tested inhibited carbachol (1 mM)-stimulated [3H]inositol phosphates accumulation in a dose- and time-dependent manner. The order of potency was t-butanol greater than n-propanol greater than or equal to iso-propanol greater than ethanol greater than methanol. After 90 min of incubation, ethanol, n-propanol and t-butanol caused a significant inhibition of muscarinic receptor-stimulated inositol metabolism at doses as low as 15 - 50 mM, comparable to the blood concentrations reached after in vivo administration of doses able to induce developmental neurotoxicity. The inhibitory effect of ethanol was additive to that of iso-propanol or t-butanol. Differently from these effects in 7 day-old rats, in cortical slices from adult animals methanol and ethanol had no effect on carbachol-stimulated phosphoinositide metabolism, while the two propanol isomers and t-butanol were less effective than in neonatal animals. These results suggest that muscarinic receptor-coupled phosphoinositide metabolism might be a common neurochemical target for the developmental neurotoxicity of short chain aliphatic alcohols.     

Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death

The mechanism of delayed neurotoxicity, triggered by glutamate, was studied in 7-8-day-old primary cultures of rat cerebellar granule cells. Treatment of cultures for 15 min with 50 microM glutamate in Mg2+ -free medium, followed by removal of the excitoxin, resulted in neuronal death, which started to appear 2-3 hr after the termination of glutamate treatment. The number of dead neurons increased gradually in the next few hours and 80-85% of neurons were found dead 24 hr later. Antagonists of N-methyl-D-aspartate-sensitive glutamate receptors (phencyclidine) or 1.2 mM MgCl2, but not the antagonist of N-methyl-D-asparatate-insensitive glutamate receptors (6-cyano-7-nitroquinoxaline-2,3-dione), abolished the neurotoxic effect of kainate. Development of glutamate-induced neuronal death depends strongly on Ca2+. Removal of extracellular Ca2+ (with 1mM ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) immediately after the termination of glutamate exposure and before the appearance of the early signs of neuronal death (post-glutamate period) dramatically reduced neuronal degeneration. Neurotoxic concentrations of glutamate induced sustained increase of 45Ca2+ uptake in the post-glutamate period. The delayed increase of 45Ca2+ uptake, as well as the delayed neurotoxicity, were not affected by post-glutamate treatment with phencyclidine, dibenzocyclohepteneimine; DL-2-amino-5-phosphonovalerate, or MgCl2 or with voltage-dependent Ca2+ channel blockers (nitrendipine, verapamil, diltiazem). Neurotoxic concentrations of glutamate also induced a delayed sustained increase of [3H]phorbol-12,13-dibutyrate binding, reflecting an increased translocation of protein kinase C (PKC) from cytosol to the cell membrane during the post-glutamate period. Pretreatment of neurons with the ganglioside GT1b (trisialosylgangliotetraglycosylceramide), followed by removal of free GT1b from the incubation medium, prevented PKC translocation, the sustained increase of 45Ca2+ uptake in the post-glutamate period, and the delayed neuronal death. We suggest that the sustained activation and translocation of PKC primed by glutamate receptor stimulation may be the triggering event causing the protracted increase of neuronal Ca2+ influx. This influx is insensitive to voltage-dependent Ca2+ channel blockers and glutamate receptor antagonists. It appears that this delayed increase of Ca2+ influx may be important in causing neuronal death.     

Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-beta-cyclodextrins.

This work describes the synthesis of new amphiphilic perfluorohexyl- and perfluorooctyl-propanethio-beta-cyclodextrins and the comparison of the ability of these molecules and alkyl analogue, nonanethio-beta-cyclodextrin to form nanospheres. Nanospheres were prepared using nanoprecipitation method (perfluoroalkylthio-beta-cyclodextrin in THF [0.11 x 10(-3)M], stirring rate 700rpm, addition of aqueous phase at 64 degrees C into organic phase at 50 degrees C). They were characterised by Photon Correlation Spectroscopy (PCS) and by electron microscopy (SEM and cryo-TEM). The nanospheres prepared from these new beta-cyclodextrin derivatives have an average size of 260nm, and appear to be spherical in cryo-TEM images. Whereas alkyl analogue forms polydisperse aggregates with sizes in the range 60-350nm.     

Importance of the ratio between ionized and total Mg in serum or plasma: new data on the regulation of Mg status and practical importance of total Mg concentration in the investigation of Mg imbalance.

There is an inverse relationship between Mg balance and the ratio ionized Mg/total Mg in serum or plasma: in Mg excess, the ratio is decreased and in Mg deficiency the ratio is increased. It works as if a subtle homeostasic compensatory reaction modified the proportion of the most biologically active fraction of blood Mg in order to reduce the effects of Mg imbalance. Easy, available and unexpensive, the evaluation of total Mg in plasma or serum appears as a better marker than ionized Mg in Mg imbalance: it should be priviledged as the initial investigation in clinical practice.