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Biomedical subjects

R T Drew

Publications and source records attributed to R T Drew.

At least 37 records · Page 2Linked to original sources
PubMed1984

Carbon monoxide enhances development of hypertension in Dahl rats.

The influence of carbon monoxide (CO) on the development of systemic hypertension was studied in Dahl rats selectively bred for susceptibility (DS) and resistance (DR) to NaCl-induced hypertension. This study was designed to examine the interactions among rat line (DS or DR), NaCl content of diet, and exposure to CO. The rats were exposed to 500 ppm CO or conditioned air, 21 hr/day, for 62 to 63 consecutive days. Carbon monoxide exposures affected blood pressure only in DS rats fed a high NaCl diet, where it enhanced the development of NaCl-induced hypertension. Whole-body weights were not affected by CO, but organ weight changes in the form of cardiomegaly ranging from 22% (DR, low NaCl) to 36% (DS, high NaCl), and splenomegaly ranging from 29% (DR, low NaCl) to 98% (DS, high NaCl) were observed. The mean equilibrium carboxyhemoglobin concentration was 42% in the CO-exposed rats. The hematologic responses to the CO exposures were elevated total hemoglobin and hematocrit.

Animals↗
PubMed1984

Inhalation exposure methodology.

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).

Air Pollutants↗
PubMed1983

The effect of age and exposure duration on cancer induction by a known carcinogen in rats, mice, and hamsters.

Female Golden Syrian hamsters, F-344 rats, Swiss CD-1 mice, and B6C3F1 hybrid mice were exposed 6 hr/day, 5 days/week to carcinogenic levels of vinyl chloride (VC) for 6, 12, 18, or 24 months (rats and hamsters only). Other groups of rodents were held for 6 or 12 months and then exposed for 6 or 12 months. At the end of the study the incidence of VC-induced neoplasms was compared in each of the groups to assess the effects of duration of exposure and age at the start of exposure on carcinogenicity of VC. In rats, with early initial exposure, hemangiosarcomas, hepatocellular carcinomas, and mammary gland carcinomas occurred with increasing incidence with longer exposure duration. Rats held for 6 months before exposure developed VC-related neoplasms, while rats held 12 months before the start of exposure failed to show a significantly increased incidence of these neoplasms. In hamsters, hemangiosarcomas, mammary gland carcinomas, gastric adenocarcinomas, and skin carcinomas resulted from VC exposure. The highest incidence of malignant neoplasms occurred in hamsters exposed for the first 12 months, whereas exposure begun after 12 months of age did not cause neoplasms. In both strains of mice, VC exposure during the first 6 months of the experiment induced a high incidence of hemangiosarcomas and mammary gland carcinomas. Swiss mice also developed lung carcinomas after only 6 months of exposure. In all three rodent species an initial 12 month exposure to VC was adequate to detect its carcinogenic potential, but the shortened survival of VC exposed mice and hamsters precluded a meaningful comparison with longer periods of exposure. Exposures were most effective when started early in life.

Age Factors↗
PubMed1983

Effect of in vivo exposure to benzene on the characteristics of bone marrow adherent cells.

The effect of benzene on the adherent cell population, cultured from the bone marrow of exposed mice was investigated in the presence and absence of hydrocortisone. The adherent CFUs from exposed animals did not differ either in numbers or self-replicate ability to those derived from shown exposed animals. Adherent layers from mice exposed to 100 or 400 pp-benzene were devoid of fat cells regardless of the presence or absence of hydrocortisone. Hydrocortisone was shown to influence the proportion of acid phosphatase-positive cells derived from benzene-exposed animals. Those results suggest that benzene exposure may influence the bone marrow stromal cells.

Acid Phosphatase↗
PubMed1983

Human methionine sulfoxide-peptide reductase, an enzyme capable of reactivating oxidized alpha-1-proteinase inhibitor in vitro.

The present study demonstrates the presence of methionine sulfoxide [Met(O)] peptide reductase activity in human lung homogenates and in lysates of polymorphonuclear leukocytes (PMN) and alveolar type II cells. Enzyme activity was not detected in human bronchoalveolar lavage fluid or in pulmonary alveolar macrophage lysates. The Met(O)-peptide reductase derived from PMN is capable of reactivating alpha-1-proteinase inhibitor (alpha 1Pl) oxidized by treatment with chloramine-T or a myeloperoxidase oxidizing system. However, the PMN-derived enzyme does not reactivate alpha 1Pl inactivated by treatment in vitro with aqueous solutions of cigarette smoke plus peroxide. In addition, after the instillation of oxidized human alpha 1Pl into lungs of normal or ozone-tolerant rats, no reactivated alpha 1Pl could be found in the pulmonary lavage obtained from these animals. Finally, patients with chronic obstructive pulmonary disease appear to have normal levels of PMN Met(O)-peptide reductase.

Animals↗
PubMed1982

Effects of benzene inhalation on murine pluripotent stem cells.

Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8--12 wk old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for up to 9 1/2 wk. At various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood cell (RBC) content. In addition, femora and tibiae were evaluated for total marrow cellularity, stem cell content (as measured by the spleen colony technique), and the percent of stem cells in DNA synthesis (as determined by the tritiated thymidine cytocide technique). Exogenous spleen colonies grown from marrow of exposed animals were counted, identified, and scored by histological type. Exposure to benzene caused significant depressions of RBCs and WBCs throughout the exposure period, which continued for at least 14 d after exposure. Bone marrow cellularity and stem cell content were also depressed in exposed animals throughout the study. Tritiated thymidine cytocide of spleen colony-forming cells was generally increased in exposed animals, perhaps indicating a compensatory response to the reduction of circulating cells. Spleen colonies of all types were depressed after exposure to benzene. The significance of the reduction in cellularity, stem cell content, and changes in morphology of spleen colonies is discussed in relation to cellular toxicity and residual injury.

Animals↗
PubMed1980

Cytogenetic effects of inhaled benzene in murine bone marrow: induction of sister chromatid exchanges, chromosomal aberrations, and cellular proliferation inhibition in DBA/2 mice.

Exposure of adult male and female DBA/2 mice to 3100 ppm benzene for 4 hr significantly increased the frequency of sister chromatid exchanges in bone marrow cells of both sexes, inhibited marrow cellular proliferation (but only in male mice), and did not significantly increase the frequency of chromosomal aberrations in either sex. Phenobarbital pretreatment synergistically interacted with benzene exposure to further increase sister chromatid exchanges in female mice, induce greater inhibition of cellular proliferation in male mice, and induce a significant level of chromatid-type chromosomal aberrations in both sexes. During the second day after exposure to benzene there was increased inhibition of cellular proliferation in male mice and both new DNA damage and persistance of old DNA damage in female mice. The differences in both the type and magnitude of the response of bone marrow cellular populations, as determined by different cytogenetic end points in male and female DBA/2 mice exposed to benzene or to phenobarbital and benzene, suggest not only that a metabolite of benzene is responsible for the observed effects, but that different metabolites may be involved in different end points.

Animals↗
PubMed1980

The major parameters affecting temperature inside inhalation chambers.

Variations in inhalation chamber temperature can produce alterations in animal physiology, metabolism of foreign compounds as well as the chemical interaction of pollutant aerosols. This report presents the results of an investigation of the different mechanisms of heat transfer in a 380 L inhalation chamber and discusses the relative effectiveness of various methods that may be used to maintain a uniform chamber temperature during animal exposures. The thermal characteristics of the inhalation chamber were studied using an array of 40 thermocouples, with and without rats in the chamber and with and without 5 cm fiber glass insulation surrounding the chamber. Temperature profiles were measured with different animal loadings and intake air temperatures. An effective heat transfer coefficient of 6.6 +/- 1.8 W/m2 degrees C was determined for the stainless steel walls of the chamber. Heat balance studies with rats in this chamber have shown that with room air intake at a flow rate of 100 L/min, the stainless steel chamber walls were effective at removing approximately ninety percent of the animal heat as compared to the airstream.

Animals↗
PubMed1980

Experimental approaches for exposure to sized glass fibers.

A number of studies have shown that glass fibers induce both malignant mesothelioma and fibrosis in rats and that these reactions may be primarily a function of the physical properties of the fiber. However, these studies were carried out with fibers having broad size distributions and used methods of administration which bear little resemblance to the way man is exposed. To better characterize the health effects of glass fibers, techniques have been developed to expose rats to glass fibers of defined sizes by intratracheal instillation of aqueous suspensions and by "nose only" inhalation exposure, and to determine the deposition, translocation, and ultimate fate of these fibers in the rat. The fibers have known size distributions with geometric mean diameters of 1.5 micrometers (sigma g = 1.1) and lengths of either 5 micrometers (sigma g = 1.49) or 60 micrometers (sigma g = 3.76). The fibers have been activated with neutron irradiation. Of the several resulting radionuclides, 65Zn appeared to be the most suitable for long-term clearance studies by use of in vivo whole body radioassay techniques. A fluidized bed aerosol generator has been developed to expose rats by "nose only" inhalation to approximately 500 fibers/cm3. The generator and exposure system permits reuse of fibers which pass through the exposure chamber and produces no significant alteration of the fiber size distribution. Rats were exposed by intratracheal instillations to 20 mg of the longer fibers and to equal numbers (2 mg) and equal mass (20 mg) of the shorter fibers. Through approximately 19 weeks little difference was observed in the whole rat clearance rate of long versus short fibers in the initial exposure group. Histopathology, however, showed differences at this time with the short fibers apparently successfully phagocytized by alveolar macrophages and cleared to the lymph nodes, while the long fibers were not.

Aerosols↗
PubMed1979

Cigarette smoke inhalation decreases alpha 1-antitrypsin activity in rat lung.

Brief inhalation exposure of rats to three or six puffs of cigarette smoke significantly decreases elastase inhibitory capacity per milligram of alpha 1-antitrypsin in lung lavage fluid. This effect is not observed in ozone-tolerant rats and can be reversed by treating the lung lavage fluid from smoke-exposed rats with reducing agents. Samples of human serum obtained immediately after smoking also show decreased elastase inhibitory capacity per milligram of alpha 1-antitrypsin. Again, elastase inhibitory capacity can be restored by treatment with a reducing agent. Cigarette smoking may cause emphysema by inactivating alpha 1-antitrypsin through oxidation.

Animals↗
PubMed1978

Cytogenetic effects of inhaled ozone.

We have repeated as closely as possible the experiments of Zelac et al., who observed significantly elevated levels of chromosome aberrations in short-term cultures of peripheral lymphocytes from Chinese hamsters that had inhaled ozone. Unlike Zelac et al., we observed no increase in chromosome-type aberration levels, though a small increase in chromatid-aberration levels similar to that reported for exposed human subjects by Merz et al. was seen. No increase in the levels of any chromosomal aberration type was seen in parallel direct bone-marrow preparations. Sister-chromatid exchange (SCE) levels and cell-replication rates, which were determined in the Chinese hamster peripheral lymphocyte cultures and also in bone-marrow samples from similarly treated mice, failed to show any ozone-induced changes.

Animals↗
PubMed1978

The Laskin aerosol generator.

This paper describes construction details and operating characteristics of a nebulizer developed by Sidney Laskin and used over a period of 30 yr in various laboratories to generate respirable aerosols for whole-animal inhalation exposure studies. Under the proper operating conditions, the device is capable of producing nearly monodisperse aerosols in the respirable size range (1.5 micron volume median diameter with a geometric standard deviation of 1.1) for long periods of time

Aerosols↗
PubMed1977

Effects in rats and guinea pigs of short-term exposures to sulfuric acid mist, ozone, and their combination.

Ozone and the oxides of sulfur are common environmental pollutants. The acute pulmonary lesions caused by ozone and sulfuric acid mist in rats and guinea pigs have been characterized. Rats are not affected by sulfuric acid mist in concentrations up to 100 mg/m3 except for reduced body weight at the higher doses. A true alveolitis develops in guinea pigs exposed to more than 20 mg/m3 sulfuric acid mist. The ozone lesion is primarily confined to the terminal bronchioles and proximal alveoli. In combination studies with up to 2 ppm ozone and up to 10 mg/m3 sulfuric acid mist, the pulmonary lesion and lung/body weight data were essentially the same as in exposure to ozone alone, and the number of statistically significant synergistic effects in rats and guinea pigs was about what one would expect to observe by chance alone.

Aerosols↗