6 alpha,7 alpha-cyclopropane derivatives of androst-4-ene: a novel class of competitive aromatase inhibitors.

6 alpha,7 alpha-Cyclopropane steroids were found to be potent competitive inhibitors of human placental aromatase. 6 beta,7 beta-Dihydro-3'H-cyclopropa [6,7]-androst-4-en-17-one (4) has extremely high affinity for aromatase (Ki = 5 nM) but does not cause a time-dependent inactivation of the enzyme.

Drug interaction effects on antitumour drugs (X): exacerbation of cisplatin lethality by bacterial lipopolysaccharide in mice.

To determine whether bacterial endotoxin (lipopolysaccharide, LPS from Escherichia coli) could modulate the lethality of cisplatin (CDDP) in mice, animals were treated with LPS (1 mg/kg, intraperitoneally) 24 hr and 1 hr before administration of cisplatin. A 1.6-fold increase in 8-day cumulative mortality was observed in LPS-treated mice compared to the mortality of those injected with saline before CDDP administration.

Solid phase synthesis and opioid receptor binding properties of presumable dermorphin precursor derivatives.

Presumable dermorphin precursor peptide derivatives comprised of 35 amino acids and their fragments, which are based on the amino acid sequence determined by recombinant deoxyribonucleic acid (DNA) techniques, were synthesized by the solid phase method. A 35-residue peptide amide containing L-Ala2-dermorphin sequence at the N-terminus (1) as well as its D-Ala2 isomer (2) and the C-terminal 20-residue peptide amide were found to be unexpectedly stable against aminopeptidase M digestion and in rat brain membrane fractions mixture, suggesting that the C-terminal Glu-rich moiety of 1 and 2 serves to protect from enzymatic breakdown. In the opioid receptor binding assay, 2 showed 40 and 25-fold higher affinities than 1 for mu and delta-receptors, respectively.

Induction of hepatic cytochrome P-450 and drug metabolism by doxapram in the mouse.

The ability of doxapram (20 mg/kg, i.p. daily for 5 days) to induce hepatic cytochrome P-450 and xenobiotic metabolism was examined in male mice.

Influence of chlorpromazine on the toxicity of pirarubicin in mice.

The influence of chlorpromazine (CPZ) on the toxicity of pirarubicin (THP) was examined in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by THP. These results demonstrate that that in vivo combination of THP and CPZ at high doses will result in an increase of toxicity in mice.

Endotoxin- and inflammation-induced depression of the hepatic drug metabolism in rats.

Carrageenan-induced inflammation and exposure to endotoxin considerably decreased the content of cytochrome P-450 and activities of ethylmorphine N-demethylase and meperidine N-demethylase, but did not decrease the activities of aniline hydroxylase or NADPH-cytochrome c reductase, compared with the respective activities in rats treated with carrageenan alone. These results suggest that under these experimental conditions, the two host-related environmental factors interact and enhance a decrease in rat hepatic microsomal drug metabolizing enzymes depending on the substrate used.

Effects of d-, l- and dl-chlorpheniramine on dopamine and 3,4-dihydroxyphenylacetic acid levels in the regional parts of rat brain.

The purpose of this study was to further investigate the differences in the effects of optical isomers of chlorpheniramine (d-, l- and dl-forms) on the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the regional parts of rat brain. After the intravenous administration of each form of chlorpheniramine at a dose of 20 mg/kg, the DA and DOPAC levels were measured by HPLC system. Each form of chlorpheniramine is effective in reducing DOPAC, but not DA levels in the brain of rats.

[Diarrhea and biogenic amines: regional changes in brain histamine concentration and serotonin metabolism following castor oil-induced diarrhea in rats].

Regional changes in concentrations of histamine (HA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the rat brain were investigated after diarrhea induced by castor oil. Significant decreases in body weight were observed from the 3rd day after daily oral administration of castor oil (2.5 ml/kg).

Candida albicans serotype A strains grow in yeast extract-added Sabouraud liquid medium at pH 2.0, elaborating mannans without beta-1,2 linkage and phosphate group.

Cultivation of three Candida albicans strains, NIH A-207, J-1012, and NIH B-792, abbreviated as A-, J-, and B-strains, respectively, in yeast extract-enrich Sabouraud liquid medium at pH 2.0 provided the following findings, i.e.

Perturbation of metabolism and disposition of cyclophosphamide by interferon and poly I:C, an interferon inducer, in mice.

The effects of interferon and poly I:C on the metabolism and disposition of cyclophosphamide were investigated in mice. Elimination of cyclophosphamide from the blood was decreased in mice treated 24 hr previously with interferon (2.5 x 10(6) U/kg, intraperitoneally) or poly I:C (10 mg/kg, intraperitoneally).

Effect of chlorpromazine on the toxicity of doxorubicin in mice.

The effect of chlorpromazine (CPZ) on the toxicity of doxorubicin (DOX) were investigated in mice. CPZ significantly enhanced the acute toxicity and bone marrow toxicity induced by DOX. These results suggest the potentiation of DOX toxicity by CPZ is due to increase of sensitivity of mice to DOX.

Potentiation of pirarubicin cytotoxicity by dipyridamole in doxorubicin-resistant mouse P388 leukemia cells.

The activity of dipyridamole and its possible mechanisms which reverse the resistance of pirarubicin were studied in a P388 mouse leukemia cell lines. Dipyridamole alone was minimally cytotoxic in both of the doxorubicin-resistant cell line (P388/DOX) and the sensitive parent cell line (P388/S), but reversed pirarubicin-resistance in a dose-related manner in P388/DOX cells. A similar dose-response relationship was observed for dipyridamole by increasing net intracellular pirarubicin accumulation.

Hepatic drug metabolizing activity in rats with carrageenan-induced inflammation.

Effect of carrageenan-induced inflammation on hepatic drug metabolism was studied in male and female Wistar rats. One day after treatment of male and female Wistar rats with carrageenan (1%, 0.1 ml, s.

Preliminary evidence for bacterial endotoxin therapeutics of paraquat lethality in mice.

In mice treated with endotoxin (LPS) extracted from Escherichia coli (1 mg/kg, i.p.), 3 hr after paraquat (70 mg/kg, i.

Effect of cepharanthine on doxorubicin cytotoxicity in P388 murine leukemia cells in vitro and in vivo.

The effect of cepharanthine on the cytotoxicity of doxorubicin (DOX) in p388 leukemia cells was studied in vitro and in vivo. Nontoxic levels of cepharanthine enhanced the sensitivity to doxorubicin in p388 cells in vitro. The potentiation of antitumor activity of DOX by cepharanthine against mice bearing p388 cells was also observed.

Changes in transglutaminase activity in carbon tetrachloride-damaged rat liver.

A significant decrease in transglutaminase (TGase) activity was observed in the cytosol and nuclear fractions of carbon tetrachloride-damaged rat liver. The degree of decrease in TGase activity in the cytosol fraction was closely related to the serum transaminase level. Gel filtration studies revealed that TGase activity in 80 kDa fractions significantly decreased, but that in 160 kDa fractions slightly increased after carbon tetrachloride treatment.

Studies on 67Ga uptake by mouse granuloma tissues.

In connection with the uptake of 67Ga into the inflammatory tissues, such as granuloma tissues produced with turpentine oil, the influence of Fe3+ on the uptake of 67Ga into mouse granuloma and normal tissues and on the uptake of 125I-labeled transferrin and 59Fe were investigated. Fe3+ decreased the uptake of 67Ga into the liver and spleen, but had no influence on the uptake of 67Ga into the granuloma tissues. The uptake patterns of 125I-labeled transferrin and 59Fe in the granuloma tissues were not consistent with that of 67Ga at all.

Preventive effects of a Chinese herb medicine (sho-saiko-to) against lethality after recombinant human tumor necrosis factor administration in mice.

We observed the effects of a chinese herb medicine Sho-saiko-to on the lethal and antitumor activities of recombinant human tumor necrosis factor (rhTNF) administered in mice. Sho-saiko-to was noted to protect the rhTNF-induced lethality in galactosamine-hypersensitized mice, and also Sho-saiko-to pretreated mice was protected against the decrease of rectal temperature after rhTNF administration. On the other hand, there was a remarkable enhancement of antitumor activity of rhTNF by Sho-saiko-to pretreatment.

Biphasic effects of yohimbine on the ejaculatory response in the dog.

The effects of various doses (0.01-1.00 mg/kg) of yohimbine, an alpha-2 adrenoceptor antagonist, on the erectile and ejaculatory response elicited by manual penile stimulation were investigated in male dogs.

Drug interaction effects on antitumour drugs (VIII): prevention of ifosfamide-induced urotoxicity by disulfiram and its effect on antitumour activity and acute toxicity of alkylating agents in mice.

To reduce the side-effects and to enhance the antitumour activities of antitumour agents, we have been investigating their combined use with routine drugs. In the present study, we examined the effects of disulfiram (DSF) in combination with ifosfamide (IFX). DSF prevented IFX-induced bladder damage in a dose-dependent manner in tumour-free ddY mice when orally administered simultaneously with antitumour agent, but failed to diminish the acute lethal toxicity or leukocytotoxicity of IFX.

Detection of Bacillus cereus flagellar antigen by enzyme-linked immunosorbent assay (ELISA).

A serological typing scheme of Bacillus cereus has been developed by immunochemical analyses of flagellar antigen using an agglutination method. Enzyme-linked immunosorbent assay (ELISA) for the classification of flagellar serotype of Bacillus cereus had greater sensitivity. 10-500 times, than that of agglutination method.

Diminution of ejaculatory capacity induced by frequent ejaculation in dogs: prevention and reversal by yohimbine.

The effect of yohimbine, an alpha-2 adrenoceptor antagonist, on diminished ejaculatory capacity induced by frequent ejaculation was investigated in dogs. Ejaculation was elicited by manual penile stimulation (for 5 min) 5-8 times every 30 min. The amount of ejaculate produced by the stimulation was drastically reduced during a period of frequent ejaculation in a frequency-dependent manner.

Potentiation of cisplatin lethality by bacterial lipopolysaccharide pretreatment in mice.

The present study was designed to determine whether bacterial endotoxin (LPS) affects the lethality of cisplatin. Mice treated with LPS (1 mg/kg, i.p.

Modulation of zoxazolamine metabolism in carrageenan-induced inflammation in rats.

In male rats bearing carrageenan-induced paw edema twenty-four hours after treatment with carrageenan the duration of hexobarbital hypnosis was prolonged and the rate of hepatic hexobarbital metabolism was inhibited. By contrast, treatment with carrageenan potentiates zoxazolamine paralysis time and inhibits zoxazolamine metabolism in both male and female rats. Thus, sex-related differences in the rats bearing carrageenan-induced paw edema and inhibition of drug metabolism are apparently substrate dependent.

Potentiation of antitumor activity of pirarubicin by chlorpromazine in mice bearing doxorubicin-resistant P388 leukemia.

Chlorpromazine enhanced the cytotoxicity of pirarubicin against doxorubicin-resistant P388 leukemia cells in colony forming assays. Chlorpromazine also prolonged the survival of mice bearing doxorubicin-resistant P388 leukemia, when given in combination with pirarubicin.