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Biomedical subjects

R B Franklin

Publications and source records attributed to R B Franklin.

108 records · Page 6Linked to original sources
PubMed1975

Intravenous infusion of prostaglandin E2 raises plasma calcium concentration in the rat.

Constant intravenous infusion (65 to 260 ng/min) of prostaglandin E2 (PGE2) produced an elevation of the plasma calcium concentration in unanesthetized rats in a period of 4 h. The increase in plasma calcium was related to the amount of PGE2 infused, and the hypercalcemia persisted for at least 10 h during continuous infusion. There was also a small increase in plasma inorganic phosphorus concentration. The increase in plasma calcium was not due to hemoconcentration; in fact, there was a small decrease in hematocrit during infusion of PGE2, and no change in total plasma protein concentration was detected. Infusion of PGF2, did not raise plasma calcium concentration. We conclude that under appropriate conditions, the exogenous administration of PGE2 can cause an elevation of plasma calcium in the intact rat.

Animals↗
PubMed1975

The fate of amphetamine and norephedrine in the Tamarin monkey compared with man.

When [14C] (+/-)-amphetamine sulphate (0.3 mg/kg) was injected into Tamarin monkeys, some 70-80% of the 14C was excreted in the urine in 24 hours. Some 75% of the 24-hour excretion was unchanged drug, 7% was free and conjugated benzoic acid and 7% was hydroxylated in the aromatic ring to give mainly 4-hydroxyamphetamine (Paredrine). With similar doses of [14C] norephedrine hydrochloride nearly 90% of the 14C was excreted in 24 hours, most of this being unchanged drug. Only 3-4% was metabolized at the side chain and there was no aromatic hydroxylation. The results were compared with those obtained earlier in man, rat, rabbit and guinea pig. Quantitatively the metabolites of amphetamine, norephedrine and preludin in the tamarin were more like those in man than in the other three species.

Amphetamine↗
PubMedDate not supplied

Pulmonary toxicity of 2-methylnaphthalene: lack of a relationship between toxicity, dihydrodiol formation and irreversible binding to cellular macromolecules in DBA/2J mice.

Intraperitoneal doses of 2-methylnaphthalene (2-MN) have been shown to cause pulmonary toxicity in DBA/2J mice. Pretreatment with the monooxygenase inducers sodium phenobarbital and 3-methylcholanthrene (3-MC) failed to protect the DBA/2J mice from the toxic effect of 2-methylnaphthalene. Pretreatment of DBA/2J mice with the monooxygenase inhibitors, SKF 525-A and piperonyl butoxide also failed to enhance or attentuate the pulmonary lesions. Pulmonary and hepatic microsomes from DBA/2J mice metabolized 2-methylnaphthalene to three dihydrodiols, 2-naphthyl alcohol and other unidentified metabolites. Kidney microsomes produced 2-naphthyl alcohol but no detectable dihydrodiols. In comparison to control animals, hepatic microsomes from animals pretreated with sodium phenobarbital produced more of the least polar dihydrodiol, while amounts of the other two dihydrodiols were unaffected. 3-Methylcholanthrene, piperonyl butoxide and diethylmaleate failed to affect dihydrodiol formation in both pulmonary and hepatic microsomes. After the administration of a lung toxic dose (400 mg/kg, i.p.) of 2-MN, irreversible binding was highest in the liver, followed by the kidney, the lung and lastly skeletal muscle. Of the pretreatments given to the mice, only phenobarbital demonstrated a significant effect, and this elevation was apparent only in the liver. A pulmonary toxic dose of 2-MN (400 mg/kg, i.p.) administered to DBA/2J mice significantly depleted reduced GSH in the liver and lung and to a lesser extent, in the kidney. There appeared no good correlation between the pulmonary toxicity of 2-MN-dihydrodiol and/or alcohol formation or the in vivo irreversible binding to macromolecules. These results are compared with those reported previously in C57BL/6J mice.

Animals↗
PubMedDate not supplied

Comparative effects of hexachloro- and hexabromobenzene on hepatic monooxygenase activity of male and female rats.

Male and female Sprague-Dawley rats were treated once with either crude or purified hexachlorobenzene (HCB) or crude or purified hexabromobenzene (HBB) at 150 mg/kg, intraperitoneally. Examination of hepatic microsomes 4 d later revealed an increase in cytochrome P-450 levels in both HCB- and HBB-pretreated animals. HBB produced a slight but statistically significant hypsochromic shift. Both HCB and HBB produced an increase in benzphetamine N-dealkylation: HCB produced a greater effect than HBB, and male rat microsomes produced more HCHO than female rat microsomes from the N-demethylation of benzphetamine. HCB and HBB both enhanced ethoxycoumarin and ethoxyresorufin O-dealkylation. Liver-to-body weight ratios were not significantly affected by pretreatment with either halogenated compound. There appeared to be no difference between the crude and purified halogenated compounds. Electrophoresis of microsomes from male rats pretreated with purified HBB indicated the presence of a band at 53,000 daltons, which was also seen in microsomes from rats pretreated with 3-methylcholanthrene. This band was absent in microsomes from rats pretreated with phenobarbital. Evidence from other laboratories has demonstrated the mixed type of P-450(s) induction after HCB administration, as does this report using enzymic and electrophoretic data.

Animals↗
PubMedDate not supplied

Observations on the absorption, distribution, metabolism, and excretion of the dopamine (D2) agonist, quinelorane, in rats, mice, dogs, and monkeys.

Following the oral administration of [14C]quinelorane, a potent and highly specific dopamine (D2) agonist, to rats, mice, and monkeys, the compound was well absorbed, with 50% or more of the radioactivity appearing in the urine within 24 hr. Dogs were pretreated with 22 consecutive daily doses of quinelorane by the oral route (in order to induce tachyphylaxis to the emetic effect) before receiving an iv dose of [14C]quinelorane; just over 80% of the radioactivity was excreted into the urine. A tissue-distribution study in rats receiving a single oral dose of 0.1 mg/kg [14C]quinelorane indicated a widespread distribution of radioactivity, with levels being notably low in the blood and plasma and high in the salivary gland, adrenals, pancreas, and spleen; levels were highest in the stomach and kidneys. The Tmax of radiocarbon in the 22 tissues varied between 0.5 and 6 hr, with some tissues showing a plateau of radioactivity between these time-points. After 8 hr, levels of radioactivity were clearly decreasing, and by 48 hr, background levels were attained. Following the oral and iv administration of quinelorane to rats, the systemic bioavailability was calculated to be 16% and the volume of distribution was found to approximate that of total extracellular water, i.e. approximately 300 ml/kg. Since absorption was satisfactory and the tissue distribution study indicated widespread radioactivity, the low bioavailability may be due to first-pass metabolism. Rats excreted marginally more of the N-despropyl metabolite than unchanged drug into the urine, and dogs excreted principally unchanged quinelorane into their urine, followed by the N-despropyl metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Metabolism of 2-methylnaphthalene to isomeric dihydrodiols by hepatic microsomes of rat and rainbow trout.

The metabolism of 2-methylnaphthalene in rats (in vivo and in vitro) and rainbow trout (in vitro) has been investigated. Three isomeric dihydrodiols were formed by microsomal preparations and these were isolated and identified by high-pressure liquid chromatography and gas chromatography/mass spectroscopy. The temperature, microsomal protein content, and incubation time were varied to obtain the optimum conditions for their formation. The conversion of 2-methylnaphthalene to both monohydroxylated compounds and dihydrodiols was reduced by incubation with carbon monoxide, the omission of NADPH, or use of heat-denatured microsomes, implying the involvement of cytochrome(s) P-450-linked mixed-function oxidase activity. The three dihydrodiols obtained in vitro in microsomes from both rat and fish were identical with those compounds isolated from rat urine. Pretreatment with phenobarbital and beta-naphthoflavone selectively altered the rate of formation of specific dihydrodiols by rat liver microsomes. Although phenobarbital had no significant effect on the rate of dihydrodiol formation in trout liver microsomes, beta-naphthoflavone was a strong inducer and its selectivity in increasing the rate of dihydrodiol formation was similar to that seen with rat liver microsomes.

Animals↗
PubMedDate not supplied

Further structural analysis of rat liver microsomal metabolites of 2-methylnaphthalene.

The oxidative metabolites of 2-methylnaphthalene (2-MN) were extracted from rat liver microsome suspensions. One monohydroxylated and three isomeric dihydrodiol metabolites of 2-MN were isolated and purified by HPLC. The metabolites were characterized by GC-MS together with 1H Fourier transform (1HFT) NMR. The identification of a 2-MN-monohydroxylated product as 2-hydroxymethylnaphthalene was confirmed by comparison of its HPLC retention time and NMR spectrum with that of a synthetic standard. The three isomeric dihydrodiol metabolites had different HPLC retention times, fragmentation patterns, ultraviolet, and 1H NMR spectra. GC-MS of the silylated dihydrodiols revealed the consistent presence of an ion peak at m/z 320, indicative of a disilylated dihydrodiol. Analysis of the 1H FT NMR spectra revealed the metabolites to be the 3,4-dihydrodiol, 5,6-dihydrodiol, and 7,8-dihydrodiol of 2-methylnaphthalene.

Animals↗