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C J Nelson

Publications and source records attributed to C J Nelson.

83 records · Page 5Linked to original sources

A dose-response study of chronic cocaine on maternal behavior in rats.

To determine if there was a dose-response relationship with regard to cocaine treatment and maternal behavior exhibited by lactating rats at doses that had not been previously investigated, we examined the effects of three doses of chronic cocaine administration throughout gestation on both onset and established maternal behavior. Dams were injected (SC) with 6.3, 13, or 25 mg/kg cocaine HCl or an equivalent volume of saline throughout gestation; maternal behavior was tested on postpartum days 1 and 3. At the doses employed, cocaine disrupted the onset of only one pup-directed component of maternal behavior significantly in a dose-response manner, although there were several statistically nonsignificant dose-dependent trends of behavioral disruptions. No pup-directed behaviors were disrupted during testing for established maternal behavior. These results indicate that gestational cocaine treatment at doses of 25 mg/kg and less have only minimal effects on the onset and no effect on the maintenance of maternal behavior using our paradigm. The relationship of the present findings to previous work is discussed.

Animals↗

Benzidine dihydrochloride: toxicological assessment in mice during chronic exposures.

Although benzidine is recognized as a bladder carcinogen in humans and a liver carcinogen in laboratory animals, its toxicological effects appear to be extended to several other endpoints. This economically important chemical is the base for over 200 dyes and is used extensively in manufacturing. In a chronic lifespan study lasting 33 months, both sexes of F1 hybrid (genetically homogeneous) and monohybrid cross (genetically heterogeneous) mice from BALB/c male and C57BL/6 female crosses were exposed to benzidine dihydrochloride in their drinking water at concentrations of 0, 20, 30, 40, 60, 80, and 120 ppm for the females, and 0, 30, 40, 60, 80, 120, and 160 ppm for males. Animals were removed from the study when they were dead or moribund. In addition to hepatocellular carcinomas, there were several other toxicological end-points identified that appeared to be related to the administration of benzidine. Dose-response trends were noted for pigmentation of the spleen, hepatic cytological alterations, hyperplasia of the bile ducts, megakaryocytosis of the bone marrow, vacuolization of the brain, adenoma of the Harderian gland, atrophy of the ovaries, and angioma of the uterus. Also, dose-related effects were noted with respect to time to lung tumor and time to mortality due to reticulum-cell sarcomas.

Animals↗

Topics of conflict between parents and young adolescents.

ISSUES AND PURPOSE: Parents often examine and question interactions with their young teen and may ask the advice of healthcare professionals. Topics, frequency, and intensity of conflicts between young adolescents and parents were therefore examined. DESIGN AND METHODS: A descriptive survey using the 44-item Issues Checklist (Robin, 1975) with 163 parent and young adolescent (ages 11-14) dyads. RESULTS: Parents and teens were congruent about their reports of the topics, frequency, and intensity of conflict. Discussion of the topics generally was not angry. Mothers reported the greatest quantity of issues. Potentially sensitive topics such as substance use, dating, and sex were rarely approached by either parent or young adolescent. Sociodemographic characteristics did not distinguish or were not associated with IC scores. PRACTICE IMPLICATIONS: Conflict is a common component of the parent-young adolescent relationship. Families with children entering adolescence can expect conflict about issues that recur but usually are not that "hot". Anticipating topics may put conflict in perspective. Nurses help families resolve conflicts associated with day-to-day conflicts as a first step toward opening up larger, potentially sensitive topics.

Adolescent↗

Collaborative Behavioral Teratology Study: preliminary research.

Prior to the beginning of the Collaborative Behavioral Teratology Study (CBTS), extensive preliminary experiments were conducted. Several experiments were conducted to permit the selection and verification of dosage levels of d-amphetamine sulfate and methylmercuric chloride to be used in the CBTS. These studies included evaluations of any teratogenic effects produced by selected concentrations of the chemicals, the potential pathology produced in the dams and offspring, and the postnatal behavioral consequences of the prenatal exposures. This preliminary research allowed the determination of the most appropriate experimental design for the CBTS, verified the practicality of the schedule of work, assured that all necessary procedural details were specified, and provided a database for the determination of the most appropriate statistical techniques for the analyses of the data. This paper presents the details and results of the preliminary research performed prior to beginning the CBTS.

Animals↗

Collaborative Behavioral Teratology Study: protocol design and testing procedures.

This paper presents background information on the methods used in the Collaborative Behavioral Teratology Study (CBTS), the rationale behind the experimental design, and the design and specific procedures used in the CBTS. Each of the following methods is discussed: negative geotaxis, olfactory discrimination, auditory startle habituation, one-hour activity in the figure-8 maze, visual discrimination learning, 23-hour activity in the figure-8 maze, and amphetamine-stimulated activity. The CBTS was designed to determine the intra- and interlaboratory reliability of these test methods and the detection sensitivity of each method, as well as to determine the importance of several major variables (early test experience, gender, litter). The important design features which permitted these evaluations are discussed. Each laboratory conducted two independent experiments: one using d-amphetamine sulfate as the test agent and one using methylmercuric chloride. Other than the use of different agents and dosing regimens in the two studies, all other characteristics of experimental design were identical. Each study was conducted in four replicates with 4 litters/each of 4 treatment groups/replicate. The replicate design was an important feature which permitted reliability of the tests to be addressed under conditions in which several other sources of variation in responding could be identified and accounted for in the model. Other methods by which optimal testing conditions were implemented in the participating laboratories included the "blind" testing of all subjects in specific orders which were counterbalanced for treatment group, time of day, and the apparatus in which the animals were placed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Collaborative Behavioral Teratology Study: statistical approach.

The design of the Collaborative Behavioral Teratology Study included six laboratories and two test compounds, d-amphetamine sulfate and methylmercuric chloride. For each lab-compound combination, there were four doses, four replicates (reps), four litters within each dose-rep combination, and eight pups per litter (four males and four females). Two males and two females per litter had early experience testing, the other pups in each litter were naive until day 21 of age. A repeated measures analysis of variance was used to analyze the data. The three major questions addressed were reliability, sensitivity, and effects of early testing experience. The question of litter or pup being the appropriate experimental unit also is discussed. An explanation of interactions and an example of sample size calculations are included.

Amphetamine↗

Collaborative Behavioral Teratology Study: results.

Behavioral measures used in the Collaborative Behavioral Teratology Study (CBTS) were negative geotaxis (PNDs 7-10), olfactory discrimination (PNDs 9-11), auditory startle habituation (PNDs 18-19 and 57-58), 1-hr activity (PNDs 21, 60, 100 and 120), 23-hr activity (PND 100), activity following a pharmacological challenge (PND 120), and an operant, discrete trial visual discrimination task. Maternal and offspring body weights and the appearance of certain physical landmarks of development were also monitored. The design of the CBTS allowed evaluation of the reproducibility and detection sensitivity of these behavioral test methods, as well as the impact of early testing experience on later behavioral assessment, offspring sex differences in response levels and variability, and the contribution of litter-to-litter and animal-to-animal variation to behavioral measures in a standardized test protocol. The results obtained in this test system are discussed in relation to each of these factors and to the degree of overt toxicity obtained using prenatal treatment with 0, 0.5 or 2.0 mg/kg d-amphetamine sulfate, SC, on gestation days 12-15 (Study 1) or methylmercuric chloride, 0, 2.0 or 6.0 mg/kg by gavage, on gestation days 6-9 (Study 2).

Age Factors↗

Sex and strain differences in the developmental activity profile of rats prenatally exposed to sodium salicylate.

Pregnant Sprague-Dawley (CD) and Long-Evans (LE) rats were treated by gavage on days 8-10 of gestation with either 0, 125 or 175 mg/kg/day sodium salicylate. Locomotor activity was monitored repeatedly for 30 min in the offspring on postnatal days 12, 16, 20, 24, 30, 60, 90 and 120 in the presence or absence of olfactory cues from home cage bedding. Prenatal exposure during organogenesis to the doses of sodium salicylate used here resulted in subtle alterations in developmental locomotor activity, the pattern of which was dependent on sex, strain and bedding condition during testing. Many more dose-related changes in activity were found in LE rats and, with one exception, these were decreased levels in treated rats. All significant dose-related differences in CD rats were increased activity levels in treated animals relative to controls. Male rats showed more dose-related changes in activity than did females, and activity testing conducted in the absence of home cage bedding cues resulted in a clearer distinction of treatment-related changes than did testing in the presence of home cage bedding. These results suggest a behavioral teratogenic effect of sodium salicylate. In addition, they point out the subtle nature of many behavioral effects in the absence of more overt toxicity and the impact factors such as strain, sex and procedural variables may have on the conclusions drawn from these studies.

Animals↗

Ultrasonic vocalizations as diagnostic tools in studies of developmental toxicity: an investigation of the effects of prenatal treatment with methylmercuric chloride.

Ultrasonic vocalizations were recorded during two tasks from four groups of neonatal CD rat pups. Groups 0, 2, 4 and 6 were the offspring from pregnant dams treated with 0, 2, 4 or 6 mg/kg methylmercuric chloride by gavage on gestation day 7. On the day of birth, Day 1, litters were randomly culled to 8 pups (4 males, 4 females). The pups were weighed on Days 1, 7, 14, 21 and 30, and no weight differences due to treatment were observed. At 5, 7, 9 and 11 days of age, ultrasonic vocalizations were recorded from the animals for 1 minute. Individual animals were placed in a small test chamber containing either soiled home cage bedding or clean bedding material. Half of the pups in each litter were tested in each "odor" condition, and the rate and duration of the vocalizations were measured for 1 minute. On days 8 and 9, pups were tested on a negative geotaxis incline during which time vocalizations were recorded. In both the "odor" and negative geotaxis tests, methylmercuric chloride affected vocalization rates in a nonlinear dose-response fashion. Regardless of treatment group, the pups vocalized at a higher rate and for a longer duration in the clean than in the soiled bedding test condition. These data showed the variability of the ultrasonic vocalization responses to be smallest for the animals tested at 11 days of age in the clean bedding condition. The results of this study suggest that the value of ultrasonic calls as dependent measures of toxicity may be strengthened by the use of multiple stimulus conditions in order to elicit a graded response pattern. This would facilitate the interpretation of potential nonlinear dose-response effects.

Age Factors↗

Statistical analysis of teratologic data: problems and advancements.

A large scale replicated dose-response teratology study of 2,4,5-T was done in mice. Variability and variance of fecundity parameters and fetotoxicity endpoints are discussed. Another study on rats indicated less variation among teratologic endpoints than in mice. Calculations for the number of animals in strains of mice and rats needed to detect a 5 percent and 10 percent reduction in mean fetal weight or increase in resorptions are given. We concluded that at least 3 replicates with appropriate numbers of pregnant animals are needed to estimate variance for comparison among laboratories or among species. The utility of these calculations for standardizing teratologic studies is discussed.

2,4,5-Trichlorophenoxyacetic Acid↗