PubMed Health⌕ Search

Biomedical subjects

F C Law

Publications and source records attributed to F C Law.

At least 37 records · Page 2Linked to original sources
PubMed1991

Absorption, degradation and excretion of benzo(a)pyrene in the cricket (Acheta domesticus).

1. The absorption, degradation and excretion of 3H-benzo(a)pyrene (3H-BP) was examined in the cricket (Acheta domesticus). 2. After 3H-BP injection, extractable 3H-BP declined in the internal compartment over a 48 period. 3. When 3H-BP was deposited on the surface of the insect it penetrated through the cuticle, as evidenced by decrease in 3H-BP recovered in surface rinses and accumulation of 3H-BP internally. 4. Administration of 3H-BP by topical application or injection resulted in a progressive association of radioactivity with tissue debris and low-level metabolism to highly polar compounds. Both parent compound and highly polar metabolites were detected in excreta. 5. Treatment of insects with piperonyl butoxide decreased accumulation of polar products in excreta after injection of 3H-BP.

Absorption↗
PubMed1991

The clinical significance of Tournay's pupillary phenomenon.

The act of lateral gaze in some normal individuals causes the pupil of the adducting eye to be smaller than that of the abducting eye. This phenomenon was described by Tournay more than 70 years ago, but it has generally been considered to have no clinical significance. We discuss two situations, episodic anisocoria and aberrant regeneration of the third nerve, in which Tournay's phenomenon should be considered by the clinician. We also describe familial occurrence of this interesting pupillary variant.

Adolescent↗
PubMed1990

Acute toxicity and toxicokinetics of chlorinated diphenyl ethers in trout.

1. The LC50 and the uptake and elimination kinetics of 4-chlorodiphenyl ether (4-CDE), 2,4-dichlorodiphenyl ether (2,4-diCDE), 2,4,4'-trichlorodiphenyl ether (2,4,4'-triCDE) and 2,4,5,4'-tetrachlorodiphenyl ether (2,4,5,4'-tetraCDE) were examined in brook trout (Salvelinus fontinalis). The chlorinated diphenyl ethers (CDE) were administered in the water. 2. The 96 h LC50 of 4-CDE and 2,4-diCDE were 0.73 and 0.66 mg/l, respectively. The LC50 of 2,4,4'-triCDE and 2,4,5,4'-tetraCDE could not be determined since they were greater than the water solubilities of these chemicals. 3. Uptake of the CDE by trout was rapid; the uptake rate ranged between 2.4 and 48.9 micrograms/day. However, CDE uptake by trout did not reach a steady state at the conclusion of a 7 day exposure. In contrast, depuration of the CDE from trout was slow; the depuration half-lives of the CDE ranged between 3.9 and 63 days. 4. The toxicokinetics of the CDE in trout could be described by a one-compartment open model with zero-order absorption and first-order elimination. The CDE were taken up initially into the blood and liver of trout before they were redistributed to adipose tissue and muscle. 5. CDE are significantly bioaccumulated by fish from water; the model-predicted maximum body burdens of trout exposed to 100 micrograms/l CDE in water are 146, 316, 1381, and 930 micrograms/g for 4-CDE, 2,4-CDE, 2,4,4'-triCDE and 2,4,5,4'-tetraCDE, respectively.

Adipose Tissue↗
PubMed1986

Biotransformation of diphenyl ether by trout and guinea-pigs after intraperitoneal administration.

Diphenyl ether (DPE) was administered intraperitoneally to rainbow trout (Salmo gairdneri) and guinea-pigs (Duncan Hartley). DPE metabolites in the urine and bile of trout and the urine of guinea-pigs were isolated and analysed by g.l.c.-mass spectrometry. No unchanged DPE was found in the biological fluids of guinea-pigs and trout. Only conjugated metabolites of DPE were present in the bile and urine of the trout: 4-hydroxy- and possible 3-hydroxy-DPE conjugates were found in the bile whereas 4-hydroxy- and 4,4-dihydroxy-DPE conjugates were detected in the urine. Both free and conjugated metabolites of DPE were isolated from the urine of guinea-pigs. These metabolites were 2-hydroxy-, 4-hydroxy, 4,4'-dihydroxy-, 4-methoxy-monohydroxy- and methoxy-dihydroxy-derivatives of DPE.

Animals↗
PubMed1985

Effects of chlorinated diphenyl ethers on the mixed-function oxidases and ultrastructure of rat and trout liver.

The effects of chlorinated diphenyl ethers (CDEs) on hepatic mixed-function oxidase (MFO) activities and ultrastructure were examined in the rat and trout after ip administration of 100 mg/kg/day of 4-chlorodiphenyl ether (4-CDE), 2,4-dichlorodiphenyl ether (2,4-diCDE), 2,4,4'-trichlorodiphenyl ether (2,4,4'-triCDE), or 2,4,5,4'-tetrachlorodiphenyl ether (2,4,5,4'-tetraCDE) for 3 days. The 4-CDE, 2,4-diCDE, and 2,4,4'-triCDE pretreatments did not alter significantly the MFO activities of trout liver; however, 2,4,5,4'-tetraCDE pretreatment increased significantly the hepatic cytochrome b5 content and 7-ethoxycoumarin O-deethylase activity of trout liver. No histological changes were observed in the hepatocytes of trout treated with any of the CDEs. Pretreatment of rats with 4-CDE and 2,4-diCDE also did not alter significantly the MFO activities of the liver. In contrast, pretreatment of rats with 2,4,4'-triCDE and 2,4,5,4'-tetraCDE increased significantly hepatic MFO activities and also caused a proliferation of smooth endoplasmic reticulum in the liver. 2,4,4'-triCDE and 2,4,5,4'-tetraCDE appear to be a phenobarbital-type inducer and a mixed-type inducer of rat liver MFO activity, respectively.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Effects of cigarette smoke and 3-methylcholanthrene on the disposition of phencyclidine and its N-ethylamine analogue in the isolated perfused lung of rats.

The isolated perfused lung (IPL) of rats were used to examine the pulmonary disposition and metabolism of radiolabeled phencyclidine (PCP) and N-ethyl-1-phenylcyclohexylamine (PCE). The IPL removed PCP and PCE from the perfusate and converted them to free and conjugated metabolites. At the conclusion of a 1-h perfusion, the lung accumulated at least 20% of the administered radioactivity and metabolized more than 30% of the added drug. Pretreatment of rats with 3-MC or cigarette smoke enhanced significantly PCP and PCE metabolism by the IPL. The concentration of conjugated PCE metabolite in the perfusate of the IPL was increased significantly by both 3-MC and cigarette smoke pretreatments whereas the concentration of conjugated PCP metabolite was not affected by cigarette smoke exposure and increased only slightly after 3-MC pretreatment. Pretreatment of rats with 3-MC or cigarette smoke also altered the amount of radioactivity accumulated by the lung tissue at the conclusion of a 1-h perfusion. Inasmuch as PCP and PCE are often abused by humans via smoke inhalation, a significant amount of these drugs may be stored or metabolized by the lung.

Animals↗
PubMed1984

Effects of drug and chemical pretreatments on biliary excretion of phenylcyclohexene in the rat.

The biliary excretion of 14C-phenylcyclohexene and its metabolites were studied in rats pretreated with an inducer or inhibitor of mixed-function oxidases or with an agent known to deplete liver glutathione. Pretreatment of rats with 3-methylcholanthrene or phenobarbital enhanced the biliary excretion of 14C-phenylcyclohexene and/or its metabolites. Conversely, pretreatment of rats with SKF-525A or piperonyl butoxide decreased the biliary excretion of 14C-phenylcyclohexene and/or its metabolites. In contrast, pretreatment of rats with diethylmaleate did not alter significantly the rate of biliary excretion of radioactivity.

Animals↗
PubMed1983

Metabolic disposition and irreversible binding of 1-phenylcyclohexene in rats.

The metabolic disposition of 1-[14C]phenylcyclohexene ([14C]PC) was examined in rats after ip or iv drug administration. Radioactivity, which was accumulated by various organs, peaked within 30 min after ip administration of [14C]PC (0.21 mg/kg). A significant amount of this radioactivity was not extractable by repeated methanol extractions, indicating irreversible binding of [14C]PC metabolite(s) to tissue proteins. Following iv administration of [14C]PC (0.42 mg/kg), [14C]PC concentrations in blood declined biphasically with time; the blood elimination half-life of [14C]PC is 77 min. About 83% of the dose given was excreted in urine and feces within 54 hr of administration. About 35% of the dose was excreted in the bile in 1 hr. At least four [14C]PC metabolites were detected in the urine or bile. The bulk of the urinary radioactivity was composed of metabolites since less than 6% of [14C]PC given was excreted unchanged in the urine.

Animals↗
PubMed1983

Disposition and metabolism of diphenyl ether in rats.

After i.p. administration of [14C]diphenyl ether (5 mg/kg) to rats, radioactivity was detected rapidly in all organs and tissues. After intragastric administration of [14C]diphenyl ether (10 mg/kg) to rats, unchanged diphenyl ether in the blood was at max. concn. within 15 h and decreased linearly with time, with a biological half-life of about 1.5 h. More than 90% of the intragastrically administered dose was excreted in urine and faeces within three days; greater than 80% dose was in the urine. From g.l.c. and mass-spectral data, it was shown that rats metabolized diphenyl ether to its 2-hydroxy, 4-hydroxy, 4,4'-dihydroxy, 4-methoxy-monohydroxy and 4-methoxy-dihydroxy derivatives.

Animals↗
PubMed1983

Irreversible binding of 14C-diphenyl ether-derived radioactivity to liver microsomes in vitro and tissue proteins in vivo.

Following ip administration of 14C-diphenyl ether (5 mg/kg) to rats, a significant amount of radioactivity was found to bind irreversibly with tissue proteins of liver, lung and kidney, indicating the in vivo formation of reactive diphenyl ether metabolite(s). Irreversibly bound 14C-diphenyl ether-derived radioactivity to these organs peaked 2-4 h after the chemical was administered. Incubation of 14C-diphenyl ether in rat liver microsomes demonstrated that the hepatic mixed-function oxidase system mediated the formation of the chemically reactive metabolite(s) of 14C-diphenyl ether. The apparent Vmax and Km were, respectively, 23.3 pmol/mg microsomal protein/min and 1.33 x 10(-4)M.

Animals↗
PubMed1976

Hepatic and extrahepatic metabolism of 14C-styrene oxide.

With 8-(14)C-styrene oxide as substrate, specific glutathione S-transferase and epoxide hydrase activities were determined in subcellular fractions of liver, lungs, kidney, and intestinal mucosa from rabbit, rat, and guinea pig. Liver had the highest enzyme activities in each species. Rat and guinea pig had higher glutathione S-transferase activity in both liver and kidney than rabbit. Rat testis also had appreciable glutathione S-transferase activity. The perinatal development of epoxide hydrase and glutathione S-transferase was followed in liver and several extrahepatic tissues of fetal and neonatal guinea pigs and rabbits. The rates at which enzyme activities reached adult levels in the extrahepatic tissues differed from the liver in both species. Epoxide hydrase and glutathione S-transferases developed at different rates in each organ, demonstrating that the relative importance of these two detoxifying pathways for styrene oxide may shift before and after birth. The effects of pretreating male and female rats with phenobarbital (PB), 1,2,3,4-dibenzanthracene (DBA), pregnenolone-16alpha-carbonitrile (PCN), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic and extrahepatic epoxide hydrase and glutathione S-transferase activities toward styrene oxide were determined. PB increased both enzyme activities in liver of both sexes. PCN induced only glutathione S-transferase activity in female liver. Extrahepatic epoxide hydrase and glutathione S-transferase activities were unaffected except that TCDD doubled female renal epoxide hydrase activity and PB increased intestinal epoxide hydrase activity in both sexes. Styrene oxide biotransformation was studied in isolated, perfused rat liver and rabbit lung preparations. Conjugation with glutathione was a major metabolic pathway although significant amounts of diol were also formed in each instance. In rat liver, 27-40% of the administered styrene oxide was excreted via the bile mainly as S-(1-phenyl-2-hydroxyethyl)glutathione.

Aging↗
PubMed1976

Uptake, metabolism and efflux of methadone in "single pass" isolated perfused rabbit lungs.

The uptake, metabolism and persistence of racemic, d- and l-methadone were studied in the isolated perfused rabbit lung. The removal of the drug from the perfusate was resolved into two uptake processes (I1 and I2Y. The unidirectional flux of methadone from the perfusate into the lung was linear with respect to perfusate concentration, suggesting an uptake mechanism involving diffusion and/or binding. The uptake of d- and l-methadone was identical. In the absence of methadone in the perfusate, methadone that previously had accumulated in the lung effluxed at three rates (T1/2 = 0.37, 1.65 and 8.9 minutes) suggesting that accumulated methadone was stored in at least three pools (E1, E2, and E3) In addition, a pool with a half-life in excess of 5 hours (noneffuxable pool) was detected; this noneffluxable pool was shown not to be the result of irreversible covalent binding. Methadone was biotransformed to a small extent by the isolated perfused lung to mono- and di-N-demethylated metabolites. Although unchanged methadone and its N-demethylated metabolites were consistently found in the lung at the end of efflux, the mono-N-demethylated metabolite was not always detectable in the perfusate. Nevertheless, the decrease in the rate of efflux of the metabolites with respect to time was identical to that of unchanged methadone.

Animals↗