PubMed Health⌕ Search

Biomedical subjects

E W Van Stee

Publications and source records attributed to E W Van Stee.

At least 19 recordsLinked to original sources
PubMed1995

Endogenous formation of N-nitrosomorpholine in mice from 15NO2 by inhalation and morpholine by gavage.

Male CD-1 mice were exposed to an nominal concentration of 20 p.p.m. of 15N-nitrogen dioxide (15NO2) for 6 h/day for 4 days and for 2 h on the day 5, and to 1 g morpholine/kg body wt by gavage daily for five consecutive days. N-Nitrosomorpholine (NMOR) was found in whole mice, stomachs, skins with hair, and remains. The sum of individual tissue concentrations measured separately was 3421 ng/tissue, where the average skin weighed 4.3 g, the average stomach weighed 1.0 g and the average remains weighed 22.2 g. The average whole mouse weighed 27.7 g and contained a total of 3903 ng of NMOR. The concentration of NMOR was highest in the skin, next highest in the stomach, and lowest in the remains. However, the total quantity of NMOR per tissue, while highest in the skin (83%), was next highest in the remains (14.8%) and lowest in the stomach (2.2%). GC-MS analysis served to distinguish between the NMOR of 15NO2 origin and that of other origin. All of the NMOR in the whole mouse homogenates was identified as 15NMOR. In the stomach 73% was identified as 14NMOR, representing 1.6% of the total NMOR in the mouse, and 27% as 15NMOR, representing 0.6% of the total NMOR in the mouse. N-Nitrosamine formation in vivo is discussed as a possibly ongoing mammalian process.

Administration, Inhalation↗
PubMed1989

Hepatic cholesterol metabolism following exposure to carbon disulfide in phenobarbital-treated rats.

Male F344 rats were exposed either to 1.87 mg/L (600 ppm) carbon disulfide (CS2) for 6 hr/day by inhalation for 1, 2, or 3 consecutive days, or to 0.1% phenobarbital (PB) in the drinking water starting 5 days before exposure to CS2, or to both. Combined treatments (CS2 + PB) resulted in a decrease in hepatic cholesterol synthesis, increases in hepatic cholesterol concentration and relative liver weight, and histopathologic damage. Maximal inhibition of cholesterol synthesis was observed following 1 day of combined treatments, while the increases in hepatic cholesterol concentration were similar following 1, 2, or 3 days of combined treatments. Exposure to CS2 only produced a pattern of inhibition of cholesterol synthesis that was similar to, though less extensive than, that seen following combined treatments. All reported alterations caused by combined treatments of CS2 + PB were reversible; recovery was, in all cases, essentially complete by day 11 after a single exposure to 1.87 mg/L CS2. With the exception of cholesterol concentration where time to recovery was decreased by continuation of PB, the time required for recovery from the effects of combined treatments of CS2 + PB was not affected by whether or not PB was continued after CS2 exposure. The reported observations support the theory that metabolism of CS2 is involved in the expression of CS2-mediated alterations of hepatic cholesterol metabolism.

Animals↗
PubMed1988

Hepatic cholesterol metabolism as a function of carbon disulfide concentration and treatment with phenobarbital.

Male F344 rats were exposed to carbon disulfide (CS2) at 0, 30, 75, 150, 300, or 600 ppm for 6 hr by inhalation in the presence or absence of 0.1% phenobarbital (PB) in the drinking water starting 5 days before exposure to CS2. Exposure to 600 ppm CS2 only resulted in a decrease in hepatic cholesterol synthesis and an increase in the liver-to-body-weight ratio (relative liver weight); however, it caused no histopathological damage and had little or no consistent effect on the concentration of hepatic cholesterol or on hepatic water content. Treatment with PB alone resulted in increases in the concentration of hepatic cholesterol and relative liver weight. Exposure to 300 ppm CS2 + PB or to 600 ppm CS2 + PB resulted in a decrease in hepatic cholesterol synthesis and increases in the concentration of hepatic cholesterol, relative liver weight, hepatic water content, and histopathological damage. A concentration-response relationship was demonstrated between exposure to CS2 only and decreased hepatic cholesterol synthesis. A concentration-response relationship also was demonstrated between exposure to CS2 in rats that had been treated with PB and decreased hepatic cholesterol synthesis, increased hepatic cholesterol concentration, increased relative liver weight, increased hepatic water content, and histopathological damage. Treatment with PB lowered the concentration of CS2 required to alter hepatic cholesterol metabolism. The reported observations are consistent with the theory that oxidative metabolism is involved in the expression of CS2-mediated alterations of hepatic cholesterol metabolism.

Animals↗
PubMed1986

Failure of carbon disulfide and levothyroxine to modify the cardiovascular response of rabbits to a high-cholesterol diet.

Exposure of rabbits for 12 weeks to 300 ppm carbon disulfide (CS2) for 6 h/day, 5 days/week, or to 25 mg/day of thiourea or 2% cholesterol in the diet, or to any combination thereof caused a significant reduction in the concentration of serum thyroxine (T4). The reduction of the concentration of serum T4 in rabbits by the treatments was completely offset by the inclusion of 0.1 mg/day of sodium levothyroxine in the diet. Ingestion of feed containing 2% cholesterol significantly increased the degree of atherosclerosis present in the aortic arch and significantly increased the oil red O positive lipid present in the heart and the aorta, with the aortic arch being the most severely affected. The response of the aorta and the heart to the 2% cholesterol diet was not significantly modified by concurrent exposure to CS2 by inhalation or by treatment with thiourea, a metabolite of CS2. We found no evidence that the development of cardiovascular lesions induced by a 2% cholesterol diet in rabbits was mediated by a mechanism involving a component of hypothyroidism.

Animals↗
PubMed1986

Oncogenic response of strain A/J mice to inhaled chemicals.

Strain A/J mice were exposed by inhalation for 6 h/d, 5 d/wk, for 6 mo to carbon disulfide, 1,2-dibromoethane, ethylene oxide, naphthalene, nitrogen dioxide, or vinyl chloride. Significant increases in pulmonary adenoma formation were observed following exposure to 300 ppm carbon disulfide; 20 and 50 ppm 1,2-dibromoethane; 70 and 200 ppm ethylene oxide; 10 ppm nitrogen dioxide; and 50, 200, and 500 ppm vinyl chloride compared to control animals. Repeated studies with 1,2-dibromoethane, ethylene oxide, and vinyl chloride gave similarly significant results. Exposure of mice to 30 ppm naphthalene did not elicit a significant adenoma response. Histopathological examination of lungs from animals in these studies revealed multiple alveolar adenomas. Results from earlier studies with these chemicals, using strain A mice and Swiss mice, and bioassay information with rats and mice were compared with these data. These results provide further information for the validation of this in vivo model as a tool for predicting oncogenic potential following chemical exposure.

Adenoma↗
PubMed1984

Overview of a system for the computer-assisted operation of a small animal inhalation facility.

Automatic monitoring of the concentration of test gases and other environmental variables in small animal inhalation exposure chambers, coupled with computing capability and feedback control of the concentration of test gas, allows almost fully automatic operation of the chambers with a minimal amount of human intervention. Time-varying exposure profiles may be generated repeatedly with great accuracy, thus allowing a more realistic simulation of real-life exposures than is approached by operating chambers manually at ostensibly constant concentrations of test gases. Carefully conducted, pre-experimental calibration procedures are performed, and daily calibration checks allow statistical control of daily chamber operation and longer term quality control. At the conclusion of each experiment the investigator is supplied with records that document chamber conditions that have been monitored throughout the entire experiment, with estimates of the accuracy that was achieved in creating the specified exposure profile. A purpose of this report is to help to bridge the gap between the practicing inhalation toxicologist and the engineer in order to encourage their cooperation and mutual understanding of the technical problems involved in developing computer-assistance packages for inhalation facilities.

Animals↗
PubMed1984

Calibration of a system for the computer-assisted operation of a small animal inhalation facility.

The initialization of chambers in the computer-assisted inhalation facility at the National Institute of Environmental Health Sciences (1) includes a series of operations that we call "characterization." Characterization consists of two parts, the first of which is one of the topics of this report. In the first part of the characterization the mathematical relationship between the concentration of the chemical of interest and the output of the analyzer is approximated. This amounts to establishing a standard against which subsequent, daily calibrations can be compared. The second part of the characterization represents a wholly automatic operation in which certain dynamic characteristics of the system are quantified. A daily calibration is performed at the beginning of each day of chamber operation after the system has been characterized. The daily calibration data are checked against the characterization standard. The conversion equation for the daily operation of the chamber is derived from the daily calibration data combined with the characterization data. An equation that converts the output of the analyzer to units of concentration of the chemical of interest is at the heart of the computer-assisted monitoring and control system for our inhalation facility. The equation is derived from a calibration procedure that is conducted prior to starting each day's chamber operation. Quality control requires that, in addition to having a daily calibration of the system, a standard of reference be available against which each day's calibration data can be checked. This practice provides protection against the introduction of spurious calibration data on a daily basis, as well as providing a means for the detection of longer term drift.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

In vivo formation of N-nitrosomorpholine in CD-1 mice exposed by inhalation to nitrogen dioxide and by gavage to morpholine.

Male CD-1 mice were exposed to approximately 20 ppm nitrogen dioxide (NO2) for 5-6 hours, to 1 g morpholine/kg body weight by gavage, or to both. Treatments were repeated daily for 5 consecutive days. N-nitrosomorpholine (NMOR) was found in whole carcasses (16-146 ng NMOR/mouse) in all animals that had been exposed to both NO2 and to morpholine, but NMOR was not found in tissues from animals that had been exposed to either chemical alone. Approximately one-third of the NMOR was found in the gastrointestinal tract, mainly in the stomach. The coadministration of 2 g sodium ascorbate/kg body weight or 1 g alpha-tocopheryl acetate/kg body weight had no effect on the amount of NMOR that was found in any tissue. Another possible product of the interaction of NO2 and morpholine, N-nitromorpholine, was not detected in any tissue. We concluded that the repeated, concurrent exposures of mice to NO2 by inhalation and to morpholine by gavage resulted in the in vivo formation of significant quantities of NMOR. The biological significance of the observation remains unknown.

Animals↗
PubMed1981

Distribution and disposition of morpholine in the rabbit.

The results of a variety of in vivo and in vitro experiments suggested that the kidneys were the primary route of elimination of morpholine in the rabbit. Morpholine was not bound to serum proteins and was excreted 90% unchanged. The concentration of [14C]morpholine in the renal cortex was 6.6 times the concentration in the blood, and in the renal medulla was 15.3 times the concentration in the blood 30 min after the intravenous injection of single boluses of labelled compound. The chemical appeared to be distributed mainly to the extracellular space, and its rate of elimination was enhanced by acidification of the urine.

Animals↗
PubMed1978

Autonomic innervation of the heart.

This brief review describes recent advances in the areas of myocardial receptors that discharge into nonmyelinated, afferent, vagal C-fibers and the regional distribution of sympathetic postganglionic neurons to the myocardium. Complex, nonencapsulated nerve endings discharging into myelinated afferents have been known to exist for many years. More recently, however, indirect evidence for the existence of cardiac receptors that are either silent or exhibit low resting rates of activity, and discharge into slowly conducting C-type fibers, has been demonstrated. The receptors themselves have not yet been identified histologically. Cardiac receptors include subpopulations that are preferentially activated by chemical stimuli, including a variety of exogenous chemicals as well as prostaglandins. Another subpopulation is preferentially activated by mechanical stresses in the physiological range. Further investigation may reveal their participation in overall cardiovascular regulation, and mediation of responses to exogenous chemical stimuli. Four principal cardiac sympathetic nerves have been identified in the right thoracic region and three on the left. Most carry sympathetic and parasympathetic fibers. Stimulation of individual nerves, before and after parasympathetic blockade, results in regionally, well-defined myocardial responses.

Animals↗