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Biomedical subjects

J Elsner

Publications and source records attributed to J Elsner.

85 records · Page 5Linked to original sources
PubMedDate not supplied

Detection limits of different approaches in behavioral teratology, and correlation of effects with neurochemical parameters.

Five laboratories collaborated in the evaluation of detection limits of different testing concepts in behavioral teratology. In one laboratory, rat dams were treated by gavage with five doses of methylmercury (0.0, 0.25, 0.05, 0.5, and 5.0 mg/kg/day). The treatment period was restricted to days 6 to 9 of gestation. The usual reproduction parameters were assessed in the dams. The offspring (88-99 per group) were subjected to a routine developmental and behavioral testing battery. After completion of these tests, random samples of the animals were further investigated in four other laboratories using the following techniques: auditory startle habituation, visual discrimination and figure-8 activity monitor; wheel-shaped activity monitor and spatial alternation operant conditioning; two-compartment locomotor activity, passive avoidance and male ultrasonic vocalization during sexual behavior; assays of the weight of different brain areas, their glial fibrillary acidic (GFA) protein and S-100 protein concentration. The following dose-dependent effects were noted in ascending dose sensitivity order: delayed vaginal opening; increased and more variable passiveness in spatial alternation; impaired swimming behavior, increased GFA protein concentration in the cerebellar vermis; increased auditory startle amplitude, decreased intertrial interval pokes in the visual discrimination test, increased percentage of visits in passive area of figure-8 activity monitor, increased path iteration frequencies and decreased local activity in the wheel-shaped activity monitor, decreased locomotor activity in the two-compartment monitor, increased cerebellar vermis weight, and decreased S-100 protein in the hippocampus. Therefore, this study showed comparable sensitivities for the behavioral testing battery, for some automated multiparametric test systems and for the neurochemical assays.

Animals↗
PubMedDate not supplied

Nocturnal hyperactivity induced by prenatal methylazoxymethanol administration as measured in a computerized residential maze.

Treatment of female Sprague-Dawley rats with 15 or 25 mg/kg (IP) of methylazoxymethanol acetate (MAM) at gestational day 15 (15 DG) resulted in a dose-dependent reduction of total brain weight of the adult offspring. When tested for spontaneous activity in a residential maze over a 23 hour period, those animals treated with the highest dose of MAM showed an increase in both locomotion and local activity during night hours without changes in the structure of behavior. Animals treated with 15 mg/kg of MAM showed no difference in activity compared to controls despite a significant reduction in brain weight.

Animals↗
PubMedDate not supplied

Microanalysis of ultrasound vocalizations of young rats: assessment of the behavioral teratogenicity of methylmercury.

An on-line real-time computer system for the analysis of ultrasound vocalizations of rats is presented. The calls of young rats are recorded by an ultrasound microphone, transformed by an amplitude envelope and a frequency to voltage converter, digitized and stored by a microcomputer. The data management and analysis of the recorded vocalizations are entirely automated, allowing a high throughput of experiments in a routine laboratory. The frequency values are analyzed with respect to number, duration, base-interval, and mean frequency of the calls. Also, the frequency distributions of the call to call intervals, the call durations and the ultrasound frequencies, as well as the power spectra of the frequency modulations, are calculated. This system was used for the assessment of the behavioral teratogenicity of methylmercury chloride. Wistar rat dams were treated with 0, 1.5 or 5 mg/l in their drinking water from two weeks prior to pairing until the end of the experiment. The ultrasound vocalizations of two female and two male offspring per litter were recorded on days 5, 7, 9, 11, 13, and 15 for one minute in a clean glass beaker cooled to 20 degrees C. Methylmercury treatment resulted in a developmental delay and an overall reduction in the number of calls, a shortening of the base-interval and the call durations, a flattening and shift of the frequency distributions, and an alteration in the development with age of the frequency distributions. The frequency modulations of the calls also differed, their power being lower (smaller frequency variation) on several occasions.

Animals↗
PubMedDate not supplied

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats.

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.

Animals↗
PubMedDate not supplied

The CC chemokine receptor antagonist met-RANTES inhibits eosinophil effector functions.

Eosinophils play an important role in allergic diseases such as allergic asthma, rhinoconjunctivitis and atopic dermatitis. Recruitement of eosinophils to the side of inflammation, the release of reactive oxygen species, leading to tissue damage, and the propagation of the inflammatory response are mediated by chemokines. Thus, the applicability of agents able to inhibit or antagonize chemokine-induced eosinophil activation seems to be of interest in the treatment of allergic diseases. Therefore, the effect of the CC chemokine antagonist, Met-RANTES, on its effect on human eosinophil effector functions in response to RANTES, MCP-3 and eotaxin was investigated. Met-RANTES had no intrinsic activity on [Ca2+]i transients in eosinophils and was able to dose-dependently inhibit [Ca2+]i transients in eosinophils following stimulation with RANTES, MCP-3 and eotaxin. Besides its effect on [Ca2+]i transients, Met-RANTES dose-dependently inhibited actin polymerization in eosinophils and the release of reactive oxygen species following stimulation with RANTES, MCP-3 and eotaxin. The results of this study lead to the conclusion that Met-RANTES is an effective and powerful compound to antagonize effector functions of human eosinophils following stimulation with RANTES, MCP-3 and eotaxin and is therefore a promising therapeutic approach to prevent the invasion and destructive power of eosinophils in allergic diseases.

Calcium↗
PubMedDate not supplied

Aminooxypentane-RANTES induces CCR3 activation and internalization of CCR3 from the surface of human eosinophils.

Eosinophils are predominant effector cells in allergic diseases attracted by several CC chemokines into the inflammatory tissue. According to their important role in attracting leukocytes, several kinds of chemokine receptor antagonists have been developed. Therefore, the aim of this study was to investigate the effect of aminooxypentane (AOP)-RANTES on the activation of the CC chemokine receptor 3, CCR3, exemplary on human eosinophils, because they represent the dominant CCR3+ cell type. AOP-RANTES dose-dependently induced an increase of intracellular calcium concentration ([Ca(2+)](i)) and a release of reactive oxygen species, which could be inhibited by pertussis toxin, in human eosinophils from normal nonatopic donors. AOP-RANTES was as effective as RANTES but less effective than eotaxin and eotaxin-2 in the activation of the respiratory burst. Flow-cytometric analyses revealed that eosinophils constitutively expressed the CC chemokine receptors CCR1 and CCR3, whereas CCR5 was not expressed. AOP-RANTES, RANTES, eotaxin and eotaxin-2, but not Met-RANTES, induced a downregulation of CCR3 at 37 degrees C. Reexpression of CCR3 on eosinophils was observed within 120 min. Whereas no differences of CCR3 downregulation and recycling after stimulation with AOP-RANTES, RANTES, eotaxin and eotaxin-2 were found there exists a distinct profile of activity with respect to the activation of the respiratory burst in human eosinophils.

Cells, Cultured↗
PubMedDate not supplied

Modulation of eosinophil effector functions: the potential role of monoclonal antibodies and chemokine receptor antagonists.

Increased numbers of eosinophils in the peripheral blood and inflammatory tissue are characteristic features of allergic diseases such as allergic asthma, rhinoconjunctivitis, and atopic dermatitis. Tissue damage and propagation of inflammation is thought to be mediated by the interaction among Th2-like T cells, antigen-presenting cells, and eosinophils. In this process eosinophils are activated by several inflammatory mediators, leading to the influx of eosinophils at sites of inflammation and to tissue damage by the release of reactive oxygen species and toxic granule proteins. Therefore, agents that would be able to inhibit or antagonize mediator-induced eosinophil activation seem to be possibilities as new therapeutic strategies. In this review we will focus on the modulation of human eosinophil effector functions by monoclonal antibodies and chemokine receptor antagonists. We will discuss whether modulation of eosinophil effector functions might be successful as a possible future strategy of diseases that are accompanied by activated eosinophils. Even when these compounds show antagonistic effects on human eosinophils, in vitro future studies will be necessary to investigate whether chemokine receptor antagonists and monoclonal antibodies are suitable in vivo in an animal model prior to studies in humans.

Antibodies, Monoclonal↗
PubMedDate not supplied

The chemokine network in eosinophil activation.

Eosinophils are predominant effector cells in allergic and autoimmune diseases attracted by several chemokines into the inflammatory tissue. In the past many new biologically active chemokines have been cloned exploring the gnomic DNA sequence data base in the vicinity of already-known chemokine sequences. This article will help to better understand the chemokine network in eosinophil activation according to the new nomenclature of chemokines. Moreover, possible new therapies, such as chemokine receptor antagonists, for the treatment of allergies are discussed.

Chemokines↗
PubMedDate not supplied

Activation of human eosinophil effector functions by CC chemokines.

Different kinds of mediators, particularly chemokines, are responsible for the attraction and activation of eosinophils to the site of inflammation. In the last decade, this new family of chemotactic cytokines have become interesting because of their restricted target cell specificity. This article focuses on the activation of eosinophil effector functions in response to different CC chemokines.

Chemokines↗
PubMedDate not supplied

Testing strategies in behavioral teratology: III. Microanalysis of behavior.

After having been tested in a standard behavioral teratology test battery, as reported in Part I of this study, a random sample of male offspring of rat dams exposed to methylmercury starting two weeks prior to pairing until weaning were further tested in a wheel-shaped activity monitor and in an operant conditioning paradigm (spatial alternation discrete trial acquisition). In the activity monitor a non-significant increase in locomotor activity, a significant interaction between locomotion and radial activity monitor compartments and a significant increase in stereotyped locomotion was observed. While the preliminary training phases of operant conditioning showed only weak effects due to methylmercury, strong and highly significant increases of the number of unresponded trials and of the response latency, as well as of the session to session variation of these measures were detected during the spatial alternation schedule. A microanalysis of this observation revealed that the number of unresponded trials and its instability were affected in essence due to an increased number of response pauses, and to a lesser degree to an increased length of these pauses. In addition, short attention spans (number of trials responded between two pauses) were about four times more frequent in treated animals. The distributions of both response latency and duration were shifted significantly to longer values. These observations are interpreted as an indication of a reduced attention and behavioral stability, induced by the schedule challenge. This interpretation is compared with the signs of minimal brain dysfunction in school-children.

Animals↗
PubMedDate not supplied

Testing strategies in behavioral teratology: IV. Review and general conclusions.

Three laboratories collaborated to evaluate and compare different test concepts to be used for routine testing in behavioral teratology. Rat dams were treated orally with methylmercury starting two weeks prior to pairing until weaning of their offspring. In the first laboratory, the usual reproduction parameters were assessed in the dams, and all offspring (96-103 per group) were subjected to a routine developmental and behavioral test battery. After termination of the tests a random selection of these animals was further tested by multiparametric automated techniques in the other two laboratories. In one of these laboratories 12-13 males and females per group (one of each per litter) were tested in a visual discrimination reversal schedule, using nose-poking as operand. In the other laboratory the free behavioral of eight randomly selected males per dose group was studied in a wheel-shaped activity monitor with respect to locomotion magnitude and structure. In the same laboratory eight other males per group were trained in a discrete trial spatial alternation schedule, using lever press as operand. Both the developmental and behavioral testing battery as well as the automated techniques showed some significant effects in the offspring even at the low dose, where no reproduction effects had been noted. However, whereas the testing battery results were of unspecific nature, results of the automated techniques gave precise and specific information. In order to obtain optimal information, it is proposed to combine both approaches for routine testing. This combination could be achieved by using a balanced testing battery in young pups followed by an appropriate operant conditioning schedule in selected young adults.

Animals↗
PubMedDate not supplied

Correlation of telemetered heart rate and locomotor behavior in cyclazocine treated rats.

Two experiments were performed to verify the validity of a biotelemetry system for 24 hour recording of heart rate (HR) of rats in behavioral toxicology. As test substance the hallucinogenic drug cyclazocine was used at various dose levels (0.1, 0.75, 1.5 and 3.0 mg/kg SC). In a first experiment, female rats were tested in their home cage. It was found that HR was altered by cyclazocine during the four hours following drug injection. This alteration was biphasic: immediately after injection, when control HR was high, cyclazocine lowered HR. In contrast, one hour after the injection, when control HR was low, cyclazocine increased HR. The duration of this increase of HR was dose-dependent, while the magnitude was not. In a second experiment male rats were tested in a residential maze: simultaneously to the rat's HR, locomotor activity was recorded. The results of the first experiment were confirmed and extended to males as well as to a different environmental situation. The additional behavioral data showed a different aspect of cyclazocine action: 0.75 mg/kg initially decreased and later increased activity while 3.0 mg/kg first did not alter activity and later increased it, leading to a dissociation between HR and activity. The findings demonstrate that recording of HR adds a new dimension to the data obtained in conventional behavioral tests. The results are discussed with regard to behavioral and neurochemical effects of the drug.

Animals↗