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Biomedical subjects

E T Wei

Publications and source records attributed to E T Wei.

At least 73 records · Page 4Linked to original sources
PubMed1981

Identification of 2-nitrofluorene in diesel exhaust particulates.

Diesel exhaust particulates contain mutagens which are direct-acting in the Ames test. A dichloromethane extract of these particulates was separated by liquid chromatography and analyzed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). 2-Nitrofluorene, a known carcinogen and direct mutagen, was positively identified by comaxima of ion fragments and retention time on the gas chromatograph.

Air Pollutants↗
PubMed1981

Antimutagenic properties of liver homogenates, proteins and glutathione on diesel exhaust particulates.

Diesel exhaust particulates contain mutagens which are active in the Ames Salmonella typhimurium assay. The mutagens do not require liver enzymes for activation and, in fact, the addition of liver homogenates (S-9) to the Ames system decreases the mutagenicity of diesel exhaust samples. We have examined here the properties and components of S-9 that account for its antimutagenic effect. The antimutagenic effect of S-9 is not changed by heating S-9 in a boiling water bath for 5 min or by omission of the NADPH-generating system in the cofactor mixture. These experiments showed that the antimutagenic effect on S-9 is not enzymatic. The antimutagenicity of S-9 disappeared after the protein component of S-9 was removed by filtration. Exogenous albumin added to the Ames system mimicked the antimutagenic effect. Analysis of the albumin content of liver cytosol showed that 90% of the antimutagenic effect could be accounted for by the amount of albumin present. Glutathione added to diesel exhausts reduced mutagenicity, but the qualities of glutathione present in S-9 are too small to account for the antimutagenic effect of S-9. We conclude that the antimutagenic effect of S-9 is non-enzymatic and is most likely the result of non-specific protein binding of mutagens to liver albumin. The antimutagenic effect of glutathione on diesel exhausts suggests that the mutagens present are electrophiles.

Albumins↗
PubMed1981

Pharmacological aspects of shaking behavior produced by TRH, AG-3-5, and morphine withdrawal.

In virtually all fur-coated and feathered animals, shaking movements of the body, similar to that made by a dog when wet, occur in response to irritation of the skin or in response to sensations of intense cold. Vigorous shaking movements occur in rats undergoing opiate withdrawal. I was led by this observation to investigations on the pharmacology of agents that stimulate or inhibit shaking. Thyrotropin-releasing hormone, injected centrally at submicrogram doses, produced in nondependent, barbiturate-anesthetized animals, shaking behavior identical in its general features to that of morphine withdrawal. AG-3-5 (1-[2-hydroxyphenyl]-4[3-nitrophenyl]-1,2,3,6-tetrahydropyrimidine-2-one), another chemical stimulant of shaking, produced specific sensations of cold in man by a peripheral site of action. In this context, it should be noted that sensations of cold, and the associated emotional discomfort, are conspicuous symptoms of opiate withdrawal in man. Shaking movements elicited by a variety of stimuli were inhibited by central administration of nanomolar doses of drugs that act as agonists on opiate, muscarinic, and alpha-adrenergic receptors. These observations may provide information on a) the identity of substances in brain that, when released, provoke opiate withdrawal signs and symptoms; b) the chemical nature of substances that stimulate peripheral cold receptors; and c) the pharmacologic classification of centrally acting agents that attenuate withdrawal and produce antinociception.

Animals↗
PubMed1981

Enkephalin analogs and physical dependence.

A novel method of drug delivery, the osmotic minipump, was used to measure the ability of morphine and eight enkephalin analogs to produce physical dependence. After 3 days of morphine or peptide infusions into the rat brain, the dependent state was established and revealed by naloxone challenge; escape behavior, shaking, tachycardia and an increased respiration rate provided objective evidence of withdrawal. The minipump method required only small amounts of test materials; 6 micrograms of morphine sulfate or 0.17 microgram of FK 33,824, the most potent enkephalin analog, infused for 3 days per rat, were sufficient to induce dependence in all animals tested at these dose levels. A positive rank correlation was obtained between the short-term activities of the eight enkephalin analogs in inhibiting a motor response to a noxious stimuli and the long-term activities of the enkephalin analogs in producing physical dependence.

Animals↗
PubMed1980

Hexahydro derivative of (D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence.

Filippi et al. (1979) have claimed that substitution of cyclohexylalanine for phenylalanine in leucine-enkephalin and its L-Ser3 derivative resulted in synthetic analogs which were non-addicting. We have examined the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin, a potent analgesic agent, to determine if dependence liability can be separated from short-term opiate actions after hydrogenation of the phenylalanine residue. In contrast to Filippi et al.'s observations, we found that the hexahydro derivative of [D-Met2, Pro-NH2(5)]-enkephalin gives rise to physical dependence and that its short-term potencies generally paralleled its long-term ability to produce physical dependence.

Animals↗
PubMed1980

beta-Endorphin: central sites of analgesia, catalepsy and body temperature changes in rats.

beta-Endorphin was microinjected into rat brain in order to localize central sites associated with some of its pharmacologic effects: namely, analgesia (inhibition of the tail-flick response), catalepsy and changes in body temperature. Microinjections (1 microliter) were made bilaterally under halothane anesthesia and the effects of beta-endorphin were repeatedly assessed at 15- or 30-min intervals for 2 hr. beta-Endorphin produced analgesia and catalepsy when it was injected at low doses (ED50, 1.3 to 2.7 micrograms) into the medial preoptic area, nucleus accumbens, anterior hypothalamus and the periaqueductal gray-4th ventricular spaces. Brain areas of intermediate sensitivities (ED50, 3.7 to 16 micrograms) were the medial thalamus, posterior hypothalamus and areas around the fasciculus retroflexus. The frontal cortex, striatum and lateral areas of the brain were relatively insensitive (ED50 greater than 17 micrograms) to the effects of beta-endorphin on analgesia and catalepsy. beta-Endorphin had complex effects on body temperature. For example, when beta-endorphin was injected into the nucleus accumbens or preoptic area, low doses (1.1--2.1 micrograms) produced hyperthermia; higher doses (8.5 micrograms) produced hypothermia. The brain regions in which low doses of beta-endorphin elicit pharmacologic effects correspond to the anatomic areas in which the endogenous beta-endorphin system is distributed. Similar correspondence to the endogenous enkephalin system was not obtained.

Analgesics↗
PubMed1979

Volatilization of mutagens from beef during cooking.

The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 degrees C and 252 degrees C. However, the amount of mutagenic activity remaining in the meat was only 1--7% of that which was volatilized into the air. The ingested dose of mutagens may therefore be significantly influenced by factors which restrict the dissipation of mutagens from the container, as well as by cooking temperature. Inhalation of airborne mutagens from cooking, as an alternative route of exposure, should be investigated when considered in light of some epidemiological data showing an excess of lung and bladder cancer among cooks and kitchen workers.

Animals↗
PubMed1979

Mutagenic activity of marihuana smoke condensates.

Smoke condensates prepared from marihuana cigaretts were mutagenic in strain TA98 of the Ames Salmonella/microsome test, a short-term bioassay which estimates the mutagenic and carcinogenic potential of some chemicals. The mutagens in marihuana smoke condensates required liver enzymes to be activated. The specific mutagenic activity of marihuana smoke condensates were similar to that of tobacco smoke condensates prepared from American cigarettes. Fractionation studies of the marihuana smoke condensates showed that basic components accounted for 76% of the recovered mutagenic activity.

Cannabis↗
PubMed1978

Direct-acting mutagens in automobile exhaust.

Particulate matter in city air contains chemicals which are mutagenic in the Ames Salmonella typhimurium assay. In residential urban areas, the principal mutagens in air do not require liver enzymes to be activated. The source of these liver independent (direct-acting) mutagens may be automobile exhaust because (1) the mutagenic activities were correlated to the lead content or air, (2) the mutagens were found exhaust samples from automobiles and from an experimental CFR single-cylinder gasoline engine, and (3) these mutagens were not found in fuel or unused motor oil, but were found in used motor oil. The strain specificity and the fact that liver enzymes were not required for activation indicated that the exhaust and airborne mutagens were not unsubstituted polycyclic aromatic hydrocarbons (PAH), aromatic amines, alkylnitrosamines or aliphatic epoxides, peroxides and hydroepoxides. A number of nitro-substituted aromatic compounds are direct-acting mutagens in the Ames test, and it is possible that nitration of PAH in exhaust may form the compounds observed here. We synthesized 6-nitrobenzo [a] pyrene and found it to be a potent, direct-acting mutagen with activity comparable to that of benzo-[a] pyrene.

Animals↗
PubMed1978

Radioimmunoassay for benzo[a]pyrene.

A benzo[a]pyrene (BP)-bovine serum albumin conjugate was synthesized and used to immunize 2.5- to 3.0-kg New Zealand White rabbits. The resulting antisera to BP bound trace amounts of [3H] (55 pg; 6,000 counts/min). A radioimmunoassay (RIA) to BP was developed by the antiserum first being titered with the [3H]BP and then a standard curve being constructed from the addition of unlabeled BP (0.4-15.8 pmoles; 0.1-4.0 ng/assay tube). The RIA could reliably detect 0.4 pmoles (0.1 ng) BP. The specificity with respect to structurally related polycyclic aromatic hydrocarbons was examined by means of competitive binding. Here concentrations of 4.0-400 pmoles of the compound were used, and the resulting competitive curves were compared for relative cross-reactivity at 50% B/B0 (counts per minute labeled BP bound to antiserum in the presence of corresponding concentrations of unlabeled BP/counts per minute labeled BP bound to antiserum in the absence of unlabeled BP). The antiserum B4-3 was specific to BP with the closest cross-reacting substance being 3-hydroxybenzo[a]pyrene (20% relative cross-reactivity). BP added to pooled human serum was measurable by the RIA at 1 ng/ml. A BP RIA may have potential use for the quantification of the absorbed dose of this carcinogen in man.

Animals↗