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Biomedical subjects

D B Menzel

Publications and source records attributed to D B Menzel.

At least 37 records · Page 2Linked to original sources
PubMed1986

Accumulation and efflux of nickel from cultured pneumocytes.

The accumulation and efflux of nickel from three kinds of cultured pneumocytes were studied. Nickel rapidly penetrated the cells examined. The concentration of nickel in the cells was related to the volume of cytoplasm and surface area of the cells. Some metabolic inhibitors (NaN3, NaCN, NaAsO2) reduced the accumulation of nickel by up to 74%. Extracellular calcium regulated the accumulation of nickel into the cells. CaCl2 at 10 mM inhibited partially the accumulation of nickel, while nickel accumulation was enhanced in calcium free medium. From the efflux experiment, nickel was shown to be distributed to three different compartments in the cells, i.e., cell membrane, cytoplasm and intracellular constituents. Three rate constants were determined as k1 = 1.67-5.33, k2 = 0.031-0.037 and k3 = 0.002-0.007 min-1. These results suggest that cell membrane is readily permeable to nickel and that saturable nickel-binding sites might exist in the pneumocytes examined.

Animals↗
PubMed1985

A model of the regional uptake of gaseous pollutants in the lung. I. The sensitivity of the uptake of ozone in the human lung to lower respiratory tract secretions and exercise.

An ozone (O3) dosimetry model is presented that takes into account convection and diffusion of O3 in the lumen and airspaces of the lower respiratory tract and transport and chemical reactions in the mucous and surfactant layers and in the underlying tissue and capillaries. The model was applied to human airway morphometric data. Values for the chemical and physical parameters that define the liquid tissue and blood compartments were based on reported experimental data. Simulation results illustrate the variability of results due to an uncertainty in the knowledge of transport parameters, liquid, tissue, and blood compartment thicknesses, and chemical reaction rates. Results were most sensitive to mucous compartment thickness and reaction rate constant and least sensitive to transport and blood parameters. Exercise was simulated, showing little effect on tracheobronchial uptake but a pronounced effect on pulmonary uptake.

Air Pollutants↗
PubMed1985

Glutathione S-sulfonate, a sulfur dioxide metabolite, as a competitive inhibitor of glutathione S-transferase, and its reduction by glutathione reductase.

Glutathione S-sulfonate (GSSO3H) is a reaction product of glutathione disulfide (GSSG) and sulfite, the hydrated form of sulfur dioxide. In the present study, GSSO3H was found to be a potent competitive inhibitor of the glutathione S-transferases (GST) in the rat liver (Ki = 14 microM) and lung (Ki = 9 microM), and in human lung tumor-derived A549 cells (Ki = 4 microM). GSSO3H was also reduced by a cytosolic enzyme in the rat liver (Km = 313 microM) and lung (Km = 200 microM), and human lung A549 cells (Km = 400 microM). These results suggest that SO2 may affect the detoxification of xenobiotic compounds by inhibiting, via formation of GSSO3H, the enzymatic conjugation of glutathione (GSH) and reactive electrophiles. Although GSSO3H can be enzymatically degraded, the high substrate Km value suggests that this compound may not be readily reduced at low concentrations.

Animals↗
PubMed1985

Picomole analysis of glutathione, glutathione disulfide, glutathione S-sulfonate, and cysteine S-sulfonate by high-performance liquid chromatography.

A method for simultaneous detection of picomole quantities of glutathione (GSH), glutathione disulfide (GSSG), glutathione S-sulfonate (GSSO3H), and cysteine S-sulfonate (CYSSO3H) by high-performance liquid chromatography has been developed. Compounds are separated by anion-exchange chromatography using a citric acid buffer system, and then derivatized postcolumn using o-phthalaldehyde with 2-mercaptoethanol, heated to 70 degrees C, and detected by fluorescence. The compounds elute with retention times of 12.5 min for GSH, 27.5 min for CYSSO3H, 29.8 min for GSSG, and 33.0 minutes for GSSO3H, with detection limits of 10, 200, 10, and 50 pmol, respectively. Recoveries are 103% for GSH, 102% for GSSG, 100% for CYSSO3H, and 96% for GSSO3H. Determination of target compounds in cells is described.

Animals↗
PubMed1985

Erythrocytes from ozone-exposed mice exhibit decreased deformability.

Injury from short-term exposure to ozone (O3) was detected by a simple test of red blood cell (RBC) filterability. This test measures changes in the ability of the RBC to deform--as occurs during passage through small capillaries. Male CD-1 mice were exposed to 1.0, 0.7, or 0.3 ppm O3 for 4 hr, and blood samples were obtained by heart puncture. RBCs were suspended in Tris-HCl buffer, pH 7.4, containing 10 mg/dl glucose. After incubation in air for up to 6 hr, the time required for 2 ml RBC suspension to pass through a 3-micron-pore-size polycarbonate filter was determined. A significant increase in the 6-hr filtration time for O3-exposed (1.0 ppm) mice over unexposed mice and a lack of protection by vitamin E were shown. The increases in RBC filtration times for O3-exposed mice appeared to be dose related. Ozone exposure (1.0 ppm) caused a significant increase in the hematocrit of both vitamin E-deficient and -supplemented mice. Vitamin E supplementation appeared to partially prevent this increase in hematocrit. Measurement of lipid peroxidation by the thiobarbituric acid (TBA) test revealed no detectable levels of TBA-reactive material in RBC from O3-exposed mice. These results suggest that measurement of RBC filterability may be feasible as a clinical test for short-term injury from exposure to oxidant gases.

Animals↗
PubMed1984

Interactions of heavy metals with the pulmonary metabolism of [3H]benzo[a]pyrene.

To test the hypothesis that the inhalation of heavy metal aerosols from polluted air or cigarette smoke could alter the metabolism of polycyclic aromatic hydrocarbons, isolated, ventilated, and perfused rat lungs were used to study the effects of NiCl2, CdCl2, and CoCl2 on the pulmonary metabolism of [3H]benzo[a]pyrene [( 3H]BAP). Five minutes prior to removing the lungs from a rat, 100 microliter of isotonic sucrose containing 1 mumole of NiCl2, CdCl2, or CoCl2 was instilled intratracheally. The lungs were placed in the perfusion system and washed free of blood. After 10 min, 5 nmole of [3H]BAP dissolved in 100 microliter of dimethylsulfoxide was introduced in the arterial circulation. After 45 min, the lungs were homogenized and the homogenates and perfusates were extracted with ethyl acetate:acetone (2:1, v/v) for analysis by HPLC. Binding of [3H]BAP metabolites to lung tissue was also determined. The metabolism of [3H]BAP was found to be inducible by pretreatment of rats with beta-naphthoflavone (80 mg/kg) and to be inhibited by the inclusion of metyrapone (1.0 mM) or indomethacin (0.1 mM) in the perfusate. Instillation of NiCl2 resulted in a slight inhibition of metabolism. In the presence of CdCl2, 20% more of the parent compound was metabolized compared to sucrose-treated controls, but the fraction of organic solvent extractable metabolites increased to 213% of controls. CoCl2 was without effect on [3H]BAP metabolism. In all cases, the extent of covalent binding to lung macromolecules was proportional to the extent of metabolism of the [3H]BAP. Since heavy metals and polycyclic aromatic hydrocarbons coexist in the same atmospheric aerosols, heavy metal exposure from polluted urban or occupational air or cigarette smoking may have profound effects upon the bioactivity of a common organic carcinogen.

Animals↗
PubMed1984

Ozone: an overview of its toxicity in man and animals.

Ozone is one of the most toxic and ubiquitous air pollutants. This review focuses on the toxic effects of ozone in animals and on the similarities and disimilarities between the toxic effects in animals and humans. The molecular basis for the toxicity of ozone is discussed, based on the vigorous oxidizing properties of ozone. Despite the existence of anatomical differences between human, subhuman primate, and dog lungs versus common experimental rodent lungs, the anatomical lesion of ozone inhalation occurs at the functionally equivalent site of the junction between the conducting airway and the respiratory region. Ciliated cells of the upper airways and the type 1 cell of the centriacinar region are most affected. Type 2 cell proliferation is a hallmark of ozone toxicity. A wide variety of biochemical and physiological changes have been noted in several animal species and in humans. Considerable evidence for a free-radical-mediated or lipid peroxide-mediated toxicity is evident, especially in the induction of the glutathione peroxidase system and the protective effects of vitamins C and E. Ozone appears to be a weak mutagen and to produce chromosomal abnormalities. Defects in defense against airborne infection are present in animals, which are more susceptible to airborne infection after ozone exposure. Epidemiological studies, however, fail to detect increased respiratory infections in humans due to ozone. Despite the variety of toxic effects, few qualitative differences between species are apparent; rather, quantitative differences do occur. Ozone may thus be an ideal compound for quantitative extrapolation of toxicity from animals to humans.

Animals↗
PubMed1983

Effects of culture conditions on glutathione content in A549 cells.

The effects of varying culture conditions on glutathione content in A549 (human type II lung tumor derived) cells were examined. Parameters studied were growth time, serum concentration, and the presence or absence of a mixture of insulin, transferrin, and selenous acid. Glutathione content increased with serum concentration. When cells were grown with serum, glutathione increased sharply 24 hours after passage and decreased thereafter. Insulin, transferrin, and selenous acid had little effect on cell growth or glutathione content. Replacement of media with fresh media containing 10% serum did not prevent the growth dependent decrease in glutathione. These results demonstrate that glutathione content in A549 cells is strongly affected by culture conditions.

Animals↗
PubMed1982

Disruption of phospholipid metabolism by paraquat in cultured pneumocytes.

Paraquat (PQ) has specific pneumotoxicity in humans. Its effects on phospholipid metabolism in type 2 pneumocytes, A-549, and in lung fibroblasts, WI-38, were examined. PQ inhibited the incorporation of palmitic acid into phosphatidyl-ethanolamine by 42%, but did not inhibit the incorporation into phosphatidylcholine. PQ also inhibited the incorporation of acetate into phosphatidylcholine and ethanolamine by 82-88% in A-549 cells and by 92% in WI-38 cells. PQ inhibited the incorporation of choline into phosphatidylcholine and ethanolamine by 55 and 73%, respectively. Phosphatidylcholine was detected in the medium of A-549 cells. PQ completely inhibited this phosphatidylcholine secretion. These results suggest that PQ has inhibitory effects on phospholipid synthesis and excretion in human type 2 pneumocytes.

Cells, Cultured↗
PubMed1982

Inadvertent change of volatile anesthetics in anesthesia machines.

Each month for 4 months, the contents of the enflurane and halothane vaporizers of 25 North American Dräger anesthesia machines were analyzed for enflurane and halothane by gas liquid chromatography. On five occasions a mixture of the two agents was found in a vaporizer. Such a mixture may lead to the unknowing delivery of markedly different anesthetic concentrations than expected and may endanger the patient. Analysis of the contents of 35 vaporizers of Ohio and Foregger machines did not show any case of accidental filling with the wrong agent. The vaporizers of the Ohio and Foregger machines are conspicuously different in appearance and location, while the similar appearance of the two vaporizers of the Dräger machine may have contributed to the mistakes in filling. We conclude that standard-keyed filling devices for volatile anesthetics are desirable.

Anesthesia, Inhalation↗