摘要:

A reference range data base containing serum chemistry and hematology values on over 3000 animals is described. Data listed include the mean, standard deviation, and 10th and 90th percentiles for each of the following parameters. Serum chemistry: sodium, potassium, chloride, calcium, inorganic phosphorus, urea nitrogen, creatinine, total bilirubin, total protein, glucose, cholesterol, triglycerides, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma‐glutamyl‐transferase (monkey only), lactate dehydrogenase (dog only), and creatine kinase (dog only). Hematology: hematocrit, hemoglobin, red blood cells, reticulocytes, mean cell volume, mean cell hemoglobin, mean cell hemoglobin percent, platelets, white blood cells, neutrophils, eosinophils, basophils, lymphocytes, monocytes, and stabs. The species included are mouse, rat, hamster, rabbit, beagle dog, and cynomolgus monkey. The use of the reference ranges in routine computerized data collection is discussed.

ISSN:0098-4108    

DOI:10.1080/15287398609530859

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The effects of a water extract of cotton bracts (CBE) on guinea pig isolated trachealis smooth muscle was studied. The ability of CBE to evoke tension responses, to modify tissue reactivity to excitatory and inhibitory agents, and to modify electric field stimulation‐induced neurogenic responses was evaluated. CBE caused contraction in low concentrations, which were not mediated by histamine H1‐, muscarinic, or 5‐hydroxy‐tryptamine (5‐HT) receptors, and caused relaxation in high concentrations. In the presence of CBE, the maximum contractile response to 5‐HT and the sensitivity to KCI were reduced. The maximum relaxation responses and sensitivities to adenosine and ATP were increased by CBE. In contrast, contractile responses to histamine and methacholine and relaxation responses to isoproterenol were unaffected. Neurogenic cholinergic excitatory responses and neurogenic adrenergic responses did not appear to be affected by CBE. However, the relaxant effect of nonadrenergic inhibitory nerve stimulation was increased in the presence of CBE. These findings differ from previous ones observed in our laboratory for dog isolated trachealis smooth muscle preparations, which indicates that the effects of CBE in isolated airways is species‐dependent. Virtually all of the contractile activity of CBE was dialyzable (molecular weight <14,000) and retained in ashed samples. Inorganic constituents may contribute to the spasmogenic activity of CBE.

ISSN:0098-4108    

DOI:10.1080/15287398609530860

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

This study was designed to examine the in vivo reduction of theN‐oxidation products of nicotine metabolism in rats. Male Fischer‐344 rats were divided into one control and three experimental groups (n = 20). Each treatment group received either 0.02% trans‐nicotineN‘ ‐oxide, 0.02%cis‐nicotineN‘ ‐oxide, or 0.02% nicotineN,N‘‐dioxide in drinking water for 3 wk. After 7 d of metabolite administration, plasma nicotine levels in the trans‐nicotineN‘ ‐oxide group rose to twice that of the cis‐nicotineN‘ ‐oxide or nicotineN,N‘ ‐dioxide group. Plasma cotinine [1 ‐methyl‐5‐(3‐pyridinyl)‐2‐pyrrolidinone] concentrations reached maximum levels during wk 1 in thecis‐nicotineN‘ ‐oxide and nicotineN,N‘ ‐dioxide groups but continued to increase for another 7 d in the trans‐nicotineN‘‐oxide group. At d 15 and again at d 21, rats from each group (n = 10) were placed in metabolism chambers and given 50 ml tap water over a 24‐h period. Analysis of urine obtained from a metabolism‐chamber study conducted after 15 d of consumption revealed concentrations of nicotine in the trans‐nicotineN‘‐oxide group that were 3 times higher than cis‐nicotineN‘‐oxide‐treated animals. Urinary cotinine levels were similar in all three groups. Results from a second chamber study (d 21) showed similar urinary nicotine and cotinine values in all treatment groups. Plasma total triiodothyronine (TT3) concentrations were reduced in all treatment groups during the first week. Plasma total thyronine (TT4) concentrations were reduced (p < 0.05) in the trans‐nicotineN‘‐oxide and cis‐nicotineN‘‐oxide treatment groups during wk 3. An improved method for the preparation synthesis of cis‐nicotineN‘‐oxide is presented. An analytical method for separation of nicotine, cotinine, andcis‐ and trans‐nicotineN‘‐oxide, as well ascis‐ and trans‐nicotineN,N'‐dioxide, is also outlined.

ISSN:0098-4108    

DOI:10.1080/15287398609530861

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Five air samplers (Millipore, all‐glass impinger, centrifugal, Andersen, and absorbent cotton) were evaluated for their ability to collect airborne grain particles contaminated with aflatoxin B1.Corn dust containing 100 μg aflatoxin B1/g was aerosolized within a containment system. Each device sampled 100 I air, thus exchanging the air in the chamber two times. Aflatoxin B1was extracted from all sampling matrices and was detected and quantitated with thin‐layer chromatography and scanning fluoro‐densitometry. The highest efficiency was obtained with the Millipore sampler, while the efficiencies of the centrifugal and the cotton samplers were almost identical. Efficiency of an Andersen was less, with no toxin recovered from an all‐glass impinger. Measurement of particle size was accomplished with the Andersen sampler

ISSN:0098-4108    

DOI:10.1080/15287398609530862

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The purpose of this study was to compare the effects of various regimens of pyridostigmine administration on the contractile strength of skeletal muscle. Rats were exposed to pyridostigmine according to 3 dosing schedules: 2 mglkg ip daily, 5 mg/kg • d by sc infusion, and 25 mg/kg • d by sc infusion. After 1, 4, 10, and 20 d of exposure, measurements were made of muscle tension during tetanic stimulation, and of muscle mass, erythrocyte acetylcholinesterase activity, and body weight. Pyridostigmine produced a dose‐dependent decrement in the contracture generated during tetanic stimulation. Peak effect was observed after 4 d of exposure but remained depressed after 20 d. The magnitude of the decrement correlated with the frequency of the tetanic stimulation (from 20 to 100 Hz). Muscle tension at the end of the tetanic stimulus was affected to a greater extent than the initial tension. The 25‐mg/kg infusion of pyridostigmine significantly depressed erythrocyte acetylcholinesterase activity throughout the study and also decreased body weight on d 1–4. No change in muscle mass was observed in any treatment group. These results show that pyridostigmine exposure results in decrements in skeletal muscle contracture that are dose‐dependent, frequency‐dependent, and time‐dependent. The effect is probably not the result of muscle wasting and does not correlate well with erythrocyte acetylcholinesterase inhibition. The results are consistent with effects of pyridostigmine, both presynaptically and postsynaptically, at the neuromuscular junction that affect neurotransmitter release and receptor responsiveness.

ISSN:0098-4108    

DOI:10.1080/15287398609530863

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Doxorubicin is an anthracycline antibiotic with a very wide spectrum of anticancer activity. It has a great potential for clinical cardiotoxicity, however. One mechanism suggested for the cardiotoxicity is inhibition of ubiquinone‐dependent enzymes. It was our purpose to study this possible mechanism using ubiquinone antagonists as probes. The effect on doxorubicin toxicity of three in vitro ubiquinone antagonists was tested in mice. Two of the antagonists, 2‐hydroxy‐3‐n‐dodecylmercapto‐1,4‐naphthoquinone and 2,3‐dimethoxy‐5‐beta‐naphthylmercapto‐1,4‐benzoquinone, enhanced doxorubicin toxicity in vivo as measured by survival. The latter was significantly toxic to mice, by itself. This effect was completely blocked by ubiquinone pretreatment, but only reduced by tocopherol pretreatment. Neither ubiquinone nor tocopherol was able to decrease the toxic interaction between doxorubicin and either of the ubiquinone antagonists. Cardiac and hepatic glutathione reductase and glutathione peroxidase activities were measured in studies using the 2,3‐dimethoxy‐5‐beta‐naphthylmercapto‐1,4‐benzoquinone. This compound appeared to cause a slight reduction in the activity of hepatic glutathione reductase. It appears that these antagonists are not useful to probe the relationship between doxorubicin cardiotoxicity and ubiquinone enzyme inhibition.

ISSN:0098-4108    

DOI:10.1080/15287398609530864

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The disposition and metabolism of pesticides used in combination, especially carbaryl and malathion, is of considerable toxicological importance. Radioactivity was rapidly absorbed from the rat gastrointestinal tract (GIT) following the administration of 0.25 ml of 10 mg/kg [14C]carbaryl (0.80 μCi), 10/10 mg/kg [14C]carbaryl/malathion (0.80 μCi), 10 mg/kg [14C]malathion (1.03 μCi), or 10/10 mg/kg [14C]malathion/carbaryl (0.86 μCi). The administration of carbaryl or malathion, individually and in combination, followed a two‐phase elimination model. The presence of malathion decreased the rate constants of absorption and β‐phase elimination of [14C]carbaryl. In the mean time, the length of the distribution phase and the area under the curve of [14C]carbaryl were decreased by malathion administration. Although [14C]malathion's absorption half‐life was unchanged in the presence of carbaryl, increases were noted in the length of the distribution phase, β‐phase elimination half‐life, and area under the curve for malathion when administered simultaneously with carbaryl.

ISSN:0098-4108    

DOI:10.1080/15287398609530865

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The metabolism of benzo[a]pyrene (BaP) may be altered by xenobiotic compounds. The effects of p‐xylene and ethanol on the lung metabolism of BaP were studied. p‐Xylene was administered by ip injection at doses ranging from 0.1 to 1.0 g/kg (1:1 in soybean oil). Ethanol was administered po at 5 g/kg (40% w/v). Rats given p‐xylene, ethanol, or p‐xylene and ethanol were sacrificed 1 h after treatment. Additional time points of 75 min, 30 min, 4 h, and 24 h after p‐xylene (1 g/kg) were examined. 3‐Hy‐droxy‐BaP (3‐OH) formation was measured fluorometrically as aryl hydrocarbon hy‐droxylase activity (AHH) in lung microsomes. p‐Xylene (1 g/kg) inhibited the formation of 3‐OH BaP 40% at 15 min, 27% at 30 min, 43% at 1 h, and 39% at 4 h after treatment. Inhibition of AHH activity was still present 24 h after dosing (41%). AHH activity was inhibited 27% and 46% at 0.5 mg/kg and 1.0 mg/kg p‐xylene (1 h), respectively, while the lowest dose (0.7 mg/kg) did not change activity. Analysis of the major metabolites of BaP by high‐performance liquid chromatography (HPLC) demonstrated that the formation of 3‐OH and 4,5‐diol BaP were inhibited 32% and 50%, respectively, in lung microsomes prepared 24 h after a single injection of p‐xylene (1 glkg). None of the other metabolites analyzed were changed by p‐xylene. Ethanol had no effect on 3‐OH BaP formation during a 1‐h treatment. A combined dose of ethanol and p‐xylene moderately inhibited 3‐OH BaP formation. These findings indicate that BaP detoxication (i.e., 3‐OH formation) in rat lung is selectively inhibited by p‐xylene but not ethanol. Ethanol appears to modify the inhibitory effect of p‐xylene.

ISSN:0098-4108    

DOI:10.1080/15287398609530866

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The metabolism and disposition ofortho‐benzyl‐para‐chlorophenol (BCP) has been investigated in the male rat following an oral dose of 69 mg/kg or 206 mg/kg. BCP was rapidly eliminated at both dose levels with 45–49% of the dose appearing in the urine and 44–49% in the feces during the 5‐d period after dosing. After 5 d only 0.28–0.3% of the dose remained in the body, with almost half this value accounted for in the liver and kidney. The dynamics for the overall elimination of radioactivity from the body was biphasic at both dose levels. The initial rapid a phase had a well defined half‐life of 8–9 h, and the slower β phase had an estimated half‐life of approximately 52–140 h.

ISSN:0098-4108    

DOI:10.1080/15287398609530867

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Thecis‐ and trans‐decalin stereoisomers have found many uses as solvents and fuel components. The metabolism of the decalin isomers in male and female Fischer‐344 rats and the effects of the decalins on renal damage were evaluated. Only male rats had kidney damage. Metabolism of cis‐decalin yieldedcis,trans‐7‐decalol andcis, cis‐2‐decalol in the urine of both sexes, with the male also producing cis,cis‐1‐decalol. The urinary metabolites of trans‐decalin included trans, cis‐2‐decalol in both male and female rats andtrans,trans‐7‐decalol in males. Extracts of kidney homogenates from male rats, but not from females, dosed with cis‐ and trans‐decalin yieldedcis‐2‐deca‐lone andtrans‐2‐decalone, respectively. A single male rat treated with trans‐decalin produced no 2‐decalone in the kidney extract and also showed no renal damage.

ISSN:0098-4108    

DOI:10.1080/15287398609530868

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor