Intoxicating effects of lorazepam and barbital in rat lines selected for differential sensitivity to ethanol

The motor impairing effects and plasma concentrations of barbital and lorazepam were studied in the alcohol tolerant (AT) and alcohol non-tolerant (ANT) rat lines developed for low and high sensitivity to motor impairment from ethanol. The mixed (M) line, from which the AT and ANT rats were derived, was also included in the study. Like ethanol, barbital and lorazepam impaired the performance of the ANT rats more than that of the AT rats. The motor performance of the M rats was relatively more impaired after barbital than after lorazepam administration at the same dose used in the AT and ANT rats. At the two latter time points (2.5 and 3.5 h) the sensitive ANT rats had significantly higher serum barbital concentrations than the AT rats. The serum barbital concentrations of the AT and ANT rats did not differ, however, at the two first time points (0.5 and 1.5 h) of the tilting plane tests, although the ANT rats were significantly more intoxicated. The concentrations of lorazepam in plasma do not explain the differential motor impairment either, since the sensitive ANT rats had lower plasma concentrations than the insensitive AT rats. The results, thus, suggest that the selection involved in the development of the AT and ANT lines has not been specific for ethanol. The results also support the idea that ethanol, barbiturates and benzodiazepines have some modes of action in common.     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.     

The Dodo Bird: Less a Verdict Than an Opportunity

I contend that although the Luborsky et al. findings on the Dodo bird verdict are noteworthy, the methodology on which they are based is significantly delimited. Amplifying Luborsky et al.'s moderate recognition of that delimitation, I propose a qualitative complement to the extant research. I call this complement "amalgamated" qualitative research and propose that it will deepen, clarify, and contextualize Luborsky et al.'s enigmatic findings. Until this amalgam is implemented, therapy research will be relegated to impressions rather than fine-grained illuminations.     

Bladder filling by autologous urine production during cystometry: a urodynamic pitfall!

AIMS: The rate of autologous urine production should not have a major disturbing influence on cystometric urodynamic parameters such as first filling sensation, normal desire to void, strong desire to void, and cystometric bladder capacity. Instructions to patients and drinking behavior can have considerable impact, especially if filling cystometry is preceded by free uroflowmetry. We studied the influence of autologous urine production during filling cystometry on total bladder volume. METHODS: Urodynamic investigations performed between September of 2000 and February of 2001 were analyzed. Only those urodynamic investigations for which total bladder capacity could be calculated were taken into account (i.e., catheterization before and after cystometry and no urine loss during the investigations). RESULTS: After screening, 186 investigations were used for further analysis. Mean filled volume (external infusion plus autologous urine production) was 346 +/- 152 mL, but mean real bladder capacity (i.e., voided volume + residual urine) was 391 +/- 170 mL. In all patients, 14% extra urine was produced due to autologous urine production (mean filling rate, 6.1 mL/min). In 42% of the investigations, the real bladder capacity was more than 110% of the infused volume. In 18% of the patients, the contribution of natural bladder filling was more than 25% of the infused volume. CONCLUSIONS: Natural bladder filling plays a substantial role during filling cystometry and has a disturbing influence on calculated urodynamic parameters. Attention should be paid to patient instructions before the urodynamic investigation. The combination of free uroflowmetry followed by filling cystometry should be avoided. This avoidance is especially important if interventional studies are performed. Careful interpretation of studies depending on bladder capacity parameters is mandatory, and such parameters should be corrected for autologous bladder filling.     

EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS

1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.     

Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against leukemia and myeloma: IV modulation of membrane fluidity of leukemic cell lines and tonsillar cell stimulated with McAbs

Summary In this study the technique of labelling the cell membrane with DPH fluorescence polarization was used to observe the membrane fluidity of B lymphocytic cell lines and tonsillar cells from healthy persons; the modulation effect on membrane-fluidity induced by McAbs against isotypic and idiotypic determinants of IgM from patients with leukemia was studied as well. The expression of the corresponding isotypic and idiotypic determinants of IgM on the cell membrane was determined. The results show that the membrane fluidity of leukemic cell lines is remarkably higher than that of tonsillar cells from healthy persons, and McAbs against isotypic determinants of leukemic IgM can enhance the membrane fluidity of all kinds of cells mentioned above. However, the anti-idiotypic monoclonal antibody increased only the membrane fluidity of leukemic cell lines. These results indicated that there was a close relationship between the effect of McAbs on cell membrane fluidity and the expression of corresponding isotypic and idiotypic determinants of IgM on the cell membrane.     

Monitoring of skin response to sodium lauryl sulphate: clinical scores versus bioengineering methods

The present trial was designed to evaluate clinical scores (single observer) of sodium lauryl sulphate (SLS)-induced skin irritation in a group of subjects (n = 10) over a 10-day period along with various skin function parameters. In order to avoid significant variations due to secondary phenomena, the following parameters were recorded with non-invasive instruments in this order: skin capacitance (C1; arbitrary units; CM420 Corneometer), transepidermal water loss (TEWL; g/m2.h; Evaporimeter) and laser Doppler flowmetry (CBFV: cutaneous blood flow values; Periflux). All examinations were performed during winter on reclined relaxed subjects present for at least 10 min in a test room with controlled temperature and relative humidity (t degrees: 19.5-20.7 degrees C and RH: 47.3-60.3%). The analysis of differential data (delta = value at tx-value before test; 2-way ANOVA) was made on single parameters as a function of site (volar forearm versus neck) and time (from 24 h after 48-h occlusion with 5% SLS up to 10 days later). The profile of erythema scores over time differed between neck and forearm, but the delta CBFV readings with the laser Doppler instrument did not detect significant site-time interactions. Roughness (blind evaluation with palpating finger) and capacitance readings (delta C1) showed significant differences between sites, but the profile over time was similar in both locations. delta TEWL did not differ according to anatomical location. The reason for different erythema scores on neck and forearm might be related to inherent regional variation of optical properties of the skin or to a substantial contribution of SLS-induced roughness to the readings of erythema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Water imbibition in the rat prostate during castration-induced regression

The present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70 degrees C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%-84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr-EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr-EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration-induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.