Biomedical subjects

D B Menzel

Publications and source records attributed to D B Menzel.

At least 73 records · Page 4Linked to original sources

PubMed1976

Heavy metal enhancement of airway sulfate absorption in the perfused rat lung.

The effect of heavy metal cations in enhancing the absorption of sulfate ions from the airways of the isolated, ventilated and perfused rat lung (IVPL) into the lung vasculature was studied. The cations investigated included Cd++, Co++, Hg+++, Ni++, Fe+++, Mn++ and Zn++. The cations increased the sulfate ion absorption from the rat IVPL 199-264% as compared to absorption in the presence of Na+ ions. An exception was Mn++, in which absorption did not differ significantly from the Na+ control. The uptake of sulfate ions from the vasculature of the IVPL could not be demonstrated.

Animals↗

PubMed1976

Monocyclic peroxides as inhibitors of arachidonic acid and prostaglandin endoperoxide analog initiated aggregation of human platelets.

Arachidonic acid initiates the irreveresible aggregation of human platelets on conversion to the bicyclic prostaglandin endoperoxides, PGG2 and PGH2. An enzyme in arterial walls catalyzes the conversion of PGG2 and PGH2 to PGX, which inhibits human platelet aggregation. Preincubation with monocyclic peroxides (3-(alpha-hydroxyethyl)-1,2-dioxane, 3-(alpha-hydroxypropyl)-1,2-dioxolane or 3-methyl-3-(hydroxymethyl)-1,2-dioxolane) completely inhibited arachidonic acid initiated aggregation. Similarly, two analogs of PGH2, (15S)-hydroxy-9 alpha, 11 alpha-(epoxymethano)prosta-5Z, 13E-dienoic and (15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acids, initiated irreversible aggregation of platelets. but were completely blocked by the monocyclic peroxides. Aggregation initiated by ADP or epinephrine was also completely inhibited by the cyclic peroxides. Aggregation of human platelets appears initiated through an endoperoxide receptor which can combine with either the natural bicyclic prostaglandin peroxides or the synthetic monocyclic peroxides. Natural inhibitors, such as PGX, may well be monocyclic endoperoxides similar to the compounds studied here.

Arachidonic Acids↗

PubMed1976

Ozone exposure modifies prostaglandin biosynthesis in perfused rat lungs.

Exposure of perfused rat lungs to 3.0 ppm of ozone produced a rapid onset of edema and an increased resistance to inflation. Both the Km and Vmax of the enzymic conversion of arachidonic acid to prostaglandins were decreased by ozone exposure suggesting an uncompetitive inhibition of prostaglandin synthetase by O3. Reduced glutathione failed to prevent the inhibition of prostaglandin synthesis by O3.

Air↗

PubMed1975

Kinetic measurements of the release of prostaglandins from perfused rat lungs.

Prostaglandins released from isolated ventilated and perfused rat lungs were measured by a simple modification of the Vane technique using the rat stomach fundus as a continuous bioassay tissue. Exogenously supplied arachidonic acid was converted mainly to PGF2alpha which was determined by bioassay. A novel method for mixing a stream of inhibitors with the perfusate was used to determine PGF2alpha in the presence of substrate amounts of arachidonic acid. Using this system the apparent Km for PGF2alpha production with arachidonic acid as the substrate was found to be 1.90 X 10(-4)M, while the Ki for aspirin was found to 2.47 X 10(-4)M. These kinetic parameters are close to those reported for cell free systems and subcellular fractions suggesting that both substrate and inhibitor have ready access to the site of prostaglandin synthesis. The method appears to be generally useful to determine the effect of drugs and environment factors on the release of prostaglandins by the lung.

Animals↗

PubMed1975

Prevention of Ozonide-Induced Heinz Bodies in human Erythrocytes by Vitamin E.

Methyl oleate ozonide, a proposed intermediary in ozone intoxication, produced Heinz body inclusions in human erythrocytes at concentrations of from 10-4 to 2 x 10-3 M. Daily oral supplementation with either 100 mg or 200 mg of D-alpha-tocopheryl acetate prevented Heinz body formation by methyl oleate ozonide. These observations suggest that the protective effects of vitamin E against ozone-produced toxicants occurs in man as well as in animals.

Environmental Exposure↗

PubMed1975

Heinz bodies formed in erythrocytes by fatty acid ozonides and ozone.

Ozonides of the methyl esters of oleic, linoleic, linolenic and arachidonic acids were found to produce Heinz body inclusions in human and mouse erythrocytes. No simple relationships between structure and activity were noted. Concomitant with Heinz body formation, methemoglobin and loss of cellular thiols were observed. Methyl ozonides readily oxidized glutathione and 1 mole of oxidized glutathione was formed per mole of methyl oleate ozonide. Methyl ozonides catalyzed the formation of disulfide-linked interchain polymers between hemoglobin and ovalbumin. Heinz bodies were not produced with ozone in the absence of unsaturated lipids. Heinz bodies were observed in the blood of mice exposed to ozone (0.85 ppm) for 48 hours. These observations suggest that fatty acid ozonides could serve as a toxic chemical species formed on ozone inhalation and could explain the divergent protective effects of lipid antioxidants and thiol generating systems in vivo.

Animals↗

PubMed1975

Ammonium and sulfate ion release of histamine from lung fragments.

In vitro studies with guinea pig lung fragments incubated with 10- to 200-mM concentrations of ammonium ion demonstrated the release of substanial quantities of histamine. Of the anions tested with ammonium ion, sulfate was the most potent, while nitrate and acetate ions were of intermediate potency and chloride was less potent. An osmotic effect is unlikely since equal concentrations of sodium chloride failed to release histamine. Isoproterenol, known to decrease anaphylactic histamine release, and acetycholine, known to increase histamine release, had no effect on the ammonium sulfate-mediated release of histamine. N-6 2'-O-Dibutyryladenosine 3',5' monophosphate (dibutyryl c-AMP) was also ineffective. These studies suggest that the inhalation irritation associated with certain sulfate and other salts, may be a function of their ability to release histamine in the presence of amonium ion.

Acetates↗

PubMed1975

Absorption of sulfate ions in the rat lung.

To investigate the absorption of 35S-sulfate ions from the rat lung in the presence of sodium, ammonium, and chloride ions, 0.1 ml of isotonic sucrose solution containing the salts was instilled via a tracheal cannula into anesthetized animals. After various times the lungs were removed and assayed for 35S-radioactivity. Sulfate ion absorption was found to be nonsaturable and proportional to the concentration of sulfate ion, with a t 1/2 =34.5 minutes. Ammonium ions enhanced the absorption of sulfate ions by 10.8 +/- 3.1% and chloride ions decreased the absorption of sulfate ions by 6.6 +/- 3.0%.

Absorption↗

PubMed1975

Spin labeled acetylcholine analogs: studies of cholinergic receptor.

Some spin-labeled acetylcholine analogs, in which the number of methylene groups between the quaternary nitrogen and the ether oxygen ranged between 1-5, were synthesized to study drug interacitons with acetylcholine receptors. None of the compounds tested, with the exception of the one that contained 2 methylene groups (SL-2) had any cholinergic activity. SL-2 was not capable of producing any nicotinic cholinomimetic activity. On the other hand it proved to have a very weak nicotinic cholinolytic activity on the receptors of the frog satorius muscle. This compound exhibited strong antagonism against muscarinic receptors of the isolated frog heart. The muscarinic cholinolytic action of the spin-label ACh analog is discussed in terms of the molecular perturbation theory of drug action.

Acetylcholine↗

PubMed1972