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Biomedical subjects

M K Smith

Publications and source records attributed to M K Smith.

At least 91 records · Page 5Linked to original sources
PubMed1984

Effects of trichloroethylene exposure on male reproductive function in rats.

The present study was designed to evaluate the influences of trichloroethylene (TCE) on the reproductive system of male rats. In addition, information was obtained on the distribution and metabolism of TCE. At 100 days of age, male rats were allowed to copulate with ovariectomized, hormonally primed females and copulatory behaviors scored. Fifteen minutes post-ejaculation, females were sacrificed and ejaculate and semen plug recovered from the uterus and vagina for evaluation. These data served as a pre-exposure baseline for each animal. TCE exposure was then initiated with animals intubated with either 0, 10, 100, or 1000 mg/kg of TCE (10 males/group) for 5 days/week for 6 weeks. Copulatory behaviors and semen evaluations were conducted at Weeks 1 and 5 as well as 4 weeks post-exposure. Three males/group were sacrificed at the end of the sixth week of exposure and levels of TCE and its metabolites measured in various organs and blood. The remaining animals were sacrificed at the end of Week 10. TCE-related effects were seen primarily in the 1000 mg/kg group as reduced body weight gain, elevated liver/body weight ratios, and impaired copulatory behavior. However, the copulatory performance of the "affected" males had returned to normal by the fifth week of exposure. Although TCE and its metabolites concentrated to a significant extent in the male reproductive organs, semen evaluations failed to reveal any indices of spermatotoxicity. The initial alterations in copulatory behavior may be attributed to the narcotic properties of TCE. Tolerance to this pharmacological effect may explain the absence of these effects by the fifth week of exposure.

Animals↗
PubMed1983

A selection of candidate compounds for in vitro teratogenesis test validation.

The Consensus Workshop on In Vitro Teratogenesis Testing recommended that test validation be facilitated by a listing of agents with defined teratogenicity; subsequently, a panel was convened to review and select such agents. This communication established a list of 47 compounds or conditions which demonstrate a wide range of teratogenicity in vivo. The agents were chosen primarily on the strength of the literature base denoting their in vivo effects. The tables note a number of general biological and toxicological characteristics for each agent, and the details of representative in vivo teratology studies are summarized and referenced. This list is intended to serve as a base for in vitro teratogenesis test validation and should prove useful in developing and identifying those systems which will contribute to a more effective testing program.

Abnormalities, Drug-Induced↗
PubMed1983

A comparison of the in vivo and in vitro response of mammalian embryos to a teratogenic insult.

This study serves to further define the capabilities of the whole embryo culture system using the known teratogen, hydroxyurea (HU). An initial in vivo study was performed whereby day 9 pregnant mothers were injected i.p. with 300 mg/kg HU. Dams were sacrificed 2 days later and embryos were analyzed for malformations and total embryonic protein. In addition, the peak plasma value from injected dams was found to be approximately 300 micrograms/ml with a plasma half-life of 30 min. These values were then reproduced in the culture system with results noted in cultured embryos with respect to the types of malformations found. Additional in vitro experiments were performed varying both exposure time and drug level concentrations. Results indicate that both of these parameters are important considerations when designing in vitro experiments.

Abnormalities, Drug-Induced↗
PubMed1982

Animal virus screens for potential teratogens. I. Poxvirus morphogenesis.

The growth of poxvirions in cell culture is considered a teratogen screening test, since this virus has a rapid, simple morphogenetic pathway that is dependent upon cell proliferation. Vaccinia WR-infected BSC 40 monolayers were exposed to 42 known teratogens and 9 nonteratogens at dosages from 1 microM to 100 mM. After 24 h of infection, the number of functional virions was determined by plaque assay. Thirty-three of the 42 teratogens inhibited the virus, 3 teratogens stimulated the virus, and 6 teratogens were false-negatives. Eight of the 9 nonteratogens had no effect on virus proliferation at dosages as high as 600 times the lowest reported teratogenic dosage. The number of new virions could be directly related to the concentration of the teratogen in vitro, thus allowing each compound to be characterized by an RD50. The RD50 dosage in milligrams per liter was 98% correlated with the lowest reported teratogenic dose in vivo in milligrams per kilogram. In sum, vaccinia-infected cells have an easily identifiable endpoint, plaque-forming units, which may be an accurate prognosticator of teratogenesis.

Poxviridae↗
PubMed1979

MINET in K.C.

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Fees and Charges↗
PubMed1975

Left ventricular function in patients with and without myocardial infarction and one, two or three vessel coronary artery disease.

Ninety-six patients with chest pain were studied to determine the relation between left ventricular function and severity of coronary artery disease in patients with and without a history of myocardial infarction. Coronary arteriography was performed obtaining cineangiograms (60 frames/sec) and large roll film angiograms (2 to 6 frames/sec) for precise definition of the coronary anatomy. The criteria for diagnosis of myocardial infarction were a typical history, a rise and fall in serum glutamic oxaloacetic transaminase levels and evolutionary S-T segment changes associated with Q waves of at least 0.03 second. Left ventricular function was assessed by measurement of left ventricular end-diastolic pressure and volume, and left ventricular ejection fraction, mass and compliance. Fifteen patients had normal findings; 81 were classified according to number of diseased vessels and presence or absence of myocardial infarction. There were no group differences in age or heart rate. Left ventricular end-diastolic pressure was abnormally increased in patients with three vessel disease and myocardial infarction. Left ventricular end-diastolic volume was increased and the ejection fraction was reduced in patients in each vessel disease group with myocardial infarction. Although ejection fraction was reduced in patients with three vessel disease without myocardial infarction, it was further reduced when infarction occurred. Left ventricular mass increased in patients with three vessel disease with or without myocardial infarction. Values for ventricular compliance were reduced in all patients with myocardial infarction and were lower in those with two and three vessel disease and infarction than in those with two and three vessel disease without infarction. These findings suggest that a previous history of myocardial infarction needs to be considered together with anatomic abnormalities of the coronary arteries in assessing cardiac performance in patients with ischemic heart disease, a previous myocardial infarction significantly alters left ventricular performance; the ejection fraction is a more sensitive measurement of left ventricular function than left ventricular end-diastolic pressure or volume.

Adult↗
PubMedDate not supplied

The automated analysis of rat sperm motility following subchronic epichlorohydrin administration: methodologic and statistical considerations.

The automated analysis of sperm motion endpoints is potentially useful in identifying male reproductive toxicants and ultimately in predicting fertility in humans. The present study was designed to evaluate the automated analysis of rat sperm motility characteristics following subchronic administration of epichlorohydrin. This type of validation is a prerequisite for inclusion of sperm motion measurements in the process of reproductive risk assessment. In the present studies videotapes were made of cauda epididymal spermatozoa from Long-Evans rats, both untreated and treated with epichlorohydrin. From analysis of videotapes of control epididymal spermatozoa, the relationship of various sperm motion endpoints and settings of the CellSoft computer-assisted sperm motion analysis system (Cryo Resources, Ltd., New York, NY) is described. Optimal settings of the system for analysis of rat spermatozoa are detailed. Employing data from both control and epichlorohydrin-treated animals, a statistical methodology is described that evaluates: (1) the distributions of CellSoft generated sperm motion endpoints, (2) the correlations between these endpoints, and (3) techniques for detection of dose-related effects.

Animals↗
PubMedDate not supplied

The uterine lumen of the pregnant guinea-pig contains a large macrophage population.

Cellular constituents of the uterine lumen were investigated. Fourteen pregnant sows of 40 + days' gestation were anaesthetized and naturally occurring peritoneal fluid was collected. A uterine horn was delivered and 0.25 ml Gey's solution injected into the uterine lumen to collect free cells. The fluid was aspirated into a syringe and the cells extracted, counted and prepared for phagocytosis experiments and microscopy. The cells were stained with alpha-naphthyl-acetate-esterase (ANAE) to determine the fraction that was non-specific esterase-positive, a feature of mononuclear phagocytes. Differential cells counts were also made. Both uterine and peritoneal compartments yielded large numbers of cells (greater than 10(6)/ml). Peritoneal fluid cells were 47 +/- 6 per cent (SD) macrophages and 49 +/- 6 per cent eosinophils (the remainder being 'other' cells); 47 +/- 6 per cent also stained positively for ANAE. Uterine cells were 78 +/- 12 per cent macrophages, the remainder being mostly lymphocytes (18 +/- 11 per cent); 85 +/- 13 per cent stained positively with ANAE. Electron microscopy of the uterine cells confirmed that most had morphology consistent with being mononuclear phagocytes. Uterine and peritoneal cells phagocytized carbon particles and yeast cells when incubated at 37 degrees C. The origin and role of this macrophage population is unknown but uterine lumenal macrophages may be present to remove antigen-antibody complexes thus facilitating uptake of maternally derived IgG by the fetal yolk sac.

Animals↗