Arzneimittel Forsch
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Arzneimittel Forsch · Nov 1995
Immunomodulating ability of galactoside-specific lectin standardized and depleted mistletoe extract.
Commercially available mistletoe extract standardized for the galactoside-specific lectin (ML-1; Eurixor) and a chromatographically ML-1-depleted preparation (same charge no. and composition of remaining components) were tested for their immunomodulating potency. In BALB/c-mice, regular subcutaneous administration of the optimal immunomodulating dosage (1 ng ML-1/kg body weight) could be shown to induce no influence on spleen weight, a non-significant increase of thymus weight, a significant increase of thymocyte, peritoneal macrophage, peripheral blood leukocyte, lymphocyte and monocyte and monocyte counts, and a significant decrease of peripheral blood granulocyte counts. Administration of analogue volumes (concentrations) of ML-1-depleted extract, however, did not induce any immunopotentiation. Accordingly, it may be assumed, that the galactoside-specific lectin (ML-1) represents the main immunomodulating component in commercially available mistletoe extracts.
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Arzneimittel Forsch · Jan 1995
Clinical TrialPrediction of phenotype for dextromethorphan O-demethylation by using polymerase chain reaction in healthy volunteers.
The polymorphism of dextromethorphan (CAS 125-71-3) metabolism is dependent on hepatic cytochrom P4502D6 (CYP2D6) activity. The relationship between the CYP2D6 genotype and the dextromethorphan phenotype was studied in 83 healthy unrelated subjects. Genotype was determined by allele-specific polymerase chain reaction (PCR). ⋯ The CYP2D6-B mutation was most frequently found, being present in 83% of PM and 8% of EM alleles. Heterozygous EMs (22% of the total population studied) were significantly underrepresented compared to the expected genotype frequency of 31% (p < 0.05). The extensive metabolizers who were heterozygous for the wild-type allele had a significantly higher metabolic ratio, compared to the homozygous EMs (log10DEM/DOR [95% = -1.99 [(-2.30)-(-1.69)] vs. -2.55 [(-2.67)-(-2.43)]; p < 0.001), indicating a gene-dose effect for CYP2D6.
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Galactoside-specific mistletoe lectin-1 (ML-1) was isolated by affinity chromatography from proprietary mistletoe extract and checked in BALB/c-mice for its immunoactive potency. To investigate the optimal immunomodulating dosage, ML-1 (0.5, 1.0, 2.5, 5.0 ng/kg body weight, b.w.) was subcutaneously administered for three subsequent days followed by another injection 48 h later. These studies proved that injections of 1 ng ML-1/kg b.w. induced optimal immunomodulation, since thymocyte proliferation, maturation and emigration were significantly enhanced in this murine model as compared to non-treated control mice. ⋯ Determination of immune responses after low dose ML-1 treatment (0.5 ng/kg b.w.) presented relevant (partly statistically significant) increases, too. However, high dose ML-1 treatment (2.5, 5.0 ng/kg b.w.) did not enhance (but suppress) relevant immune functions. For future clinical/therapeutical treatment strategies, ML-1 dosages ranging from 0.5-1.0 ng/kg b.w. may be supposed to be optimal.
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Arzneimittel Forsch · Oct 1994
Comparative StudyDiscriminative stimulus properties of diazepam and the novel anxiolytic agent 1-amino-5-bromouracil in rats.
A stimulus cue of 1-amino-5-bromouracil (ABU, CAS 127984-93-4) was compared with that of diazepam (DZP) using a drug discrimination paradigm in rats. Groups of rats were trained to discriminate DZP (1 mg/kg i.p.) or ABU (20 mg/kg i.p.) from vehicle. Generalization of the cue of the trained drug to pentobarbital was shown in DZP- and ABU-trained rats at a dose of 5 mg/kg. ⋯ Also partial generalization of that of DZP to imipramine and clonidine was found but not to 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) in DZP-trained rats. Full generalization of the stimulus cue of ABU to imipramine and partial generalization of that of ABU to clonidine and 8-OH-DPAT was observed in ABU-trained rats. The results suggest that the discriminative stimulus properties of ABU differ from those of DZP.
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Arzneimittel Forsch · Apr 1994
Randomized Controlled Trial Comparative Study Clinical TrialKetorolac versus diclofenac sodium in cancer pain.
In a randomized single-blind study carried out simultaneously in five Departments for Pain Therapy and Palliative Care, the analgesic efficacy and side effects of oral ketorolac (ketorolac tromethamine, Tora-Dol, CAS 74103-07-4) and diclofenac sodium were compared in a population of 100 advanced cancer patients suffering from somatic and/or visceral pain. The treatment was carried out in agreement with the first step of the WHO pharmacological strategy in cancer pain. ⋯ A greater number of keterolac patients could pass to the second WHO step later than diclofenac patients. As to the tolerability, both drugs turned out to be similar, except for "sleepiness", which was four times more frequent (p < 0.05) in the diclofenac group.