EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON "OPEN-FIELD TEST" IN MICE

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.     

Pressure recovery distal to a stenosis: potential cause of gradient "overestimation" by Doppler echocardiography

Doppler ultrasound is currently being widely applied to measure intracardiac pressure gradients noninvasively. In comparative invasive studies, it is generally assumed that pressure is effectively uniform distal to the stenosis. As the poststenotic jet expands, however, its velocity decreases, and pressure is recovered to the extent permitted by turbulence, so that the measured gradient will be lower if the distal catheter is positioned downstream from the vena contracta. This can lead to apparent Doppler "overestimation" of the pressure gradient because of this phenomenon of pressure recovery. This study demonstrates that pressure recovery can be important in a variety of clinical settings studied by in vitro models. Although most prominent in streamlined tunnels modeled after the obstruction in patients with hypertrophic cardiomyopathy, these effects are important even for central stenoses at physiologic flow rates. Because precise catheter position is not always known or controlled, these findings suggest an important advantage for Doppler gradient estimation, because it provides the maximal gradient at the vena contracta, which determines the load on the proximal chamber.     

Disposition and Elimination of Three Polychlorinated Dibenzofurans in the Liver of the Rat

Disposition and Elimination of Three Polychlorinated Dibenzofuransin the Liver of the Rat. VAN DEN BERG, M., DE JONGH, J., ECKHART,P., AND VAN DER WIELEN, F. W. M. (1989). Fundam. Appl. Toxicol.12, 738–747. The disposition and elimination of 1,2,3,6,7,8-HxCDF(HxCDF), 1,2,3,7,8-PnCDF (1-PnCDF), and 2,3,4,7,8-PnCDF (4-PnCDF)were studied in liver of female Sprague-Dawley rats after administrationof a single oral dose of 3.5–6.3 µg/kg. The dispositionof these PCDF congeners was structure and vehicle dependent.Administration in peanut oil caused the highest liver retention,compared with administration through the standard diet. Half-livesin liver for 1-PnCDF, 4-PnCDF, and HxCDF were 3.3, 108, and73 days, respectively. 4-PnCDF showed very high liver retention:70% of the dose in the first days after administration. To studykinetic interaction in the liver, mixtures of 1-PnCDF and 4-PnCDF(Experiment I) and of 4-PnCDF and HxCDF (Experiment II) wereadministered. The presence of 4-PnCDF in Experiment I did notsignificantly influence the half-life of I-PnCDF. In ExperimentII the estimated half-life of 4-PnCDF was again 108 days, butfor HxCDF an increased half-life was found, 156 days. It isconcluded that PCDFs with a chlorine substituent(s) adjacentto the oxygen bridge (4- and 6-positions) are eliminated vcryslowly with 14 much greater than that of TCDD.     

Individual Differences in Plasma Catecholamine and Corticosterone Stress Responses of Wild-Type Rats: Relationship With Aggression

Plasma noradrenaline (NA), adrenaline (A), and corticosterone (CS) responses to social and nonsocial stressors were studied in male members of a strain of wild-type rats, widely differing in their level of aggression. The aggressiveness was preliminarily established by measuring the latency time to attack (ALT) a male intruder in a standard resident-intruder test. Animals were then provided with a jugular vein cannula for blood sampling during stress exposure. Implanted rats were randomly assigned to 3 experimental treatments: social stress (defeat experience, SD), nonsocial stress (presentation of a shock-prod, SP) and control (animals undisturbed in their home cages, CTR). A significant correlation was found between ALT and the amount of time spent in burying the probe in SP rats: the more aggressive the animal, the higher the rate of burying behavior. SD induced a much stronger effect on plasma NA, A, and CS concentrations than SP. A significant negative correlation was found between ALT scores and values of the area under the response time curve for NA and A, in both SD and SP situations: the more aggressive the animal, the higher the catecholaminergic reactivity to the stressors. On the contrary, no evidence of a correlation between aggressiveness and plasma corticosterone responses was found, neither in SD nor in SP rats. These findings in an unselected strain of wild-type rats confirmed that an aggressive/active coping strategy is associated with a high sympathetic-adrenomedullary activation and support the concept of individual differentiation in coping styles as a coherent set of behavioral and neuroendocrine characteristics.     

Morphometric evaluation of hepatocellular proliferative lesions in the rat liver

Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies.     

Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

In patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F¹ hybrid mice were either castrated or ovariectomized and treated with 17β-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17β-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17β-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17β-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis.     

Viral Persistence in Neurons Alters Synaptic Plasticity and Cognitive Functions without Destruction of Brain Cells

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.