[Gamma-emitter labelled amino sugars: organ distribution and metabolism of 103Ru-ruthenocene derivatives in mice].
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Biomedical subjects
Publications and source records attributed to M Wenzel.
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1. The influence of the cyclic N6-monobutyryladenosine-3':5'-monophosphate (mb-cAMP) on the neurogenesis was investigated by means of electron microscopic and morphometric methods at the explantate cultures of the fetal hippocampus of the rats in vitro. 2. After three days of the in vitro cultivation the neuroblasts of the treated cultures show not significantly changes of the total number of ribosomes in comparison to the controls. 3. After 7 and 14 days of the in vitro cultivation the neurogenesis is significantly stimulated under the influence of the mb-cAMP. The drug produces a significant increase of the free ribosomes and polysomes in company with a higher degree of differentiation of the granular endoplasmatic reticulum. Under the influence of the mb-cAMP the total number of ribosomes significantly increases by 32% (after 7 days) respectively 20% (after 14 days). 4. The results might suggest, that mb-cAMP might stimulate the protein synthesis in connection with an increased nerve fibre growth in vitro.
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Rat livers were preserved by ischemic hypothermic storage in extra- or intracellular type solutions for 24 h. A substitution of 85% of the tissue water by deuterium oxide (D2O) resulted in increased glycolytic energy production, better maintenance of the energy potential of the cells but a higher AMP loss, and a reduction of edema formation. Preservation using "retrograde oxygen persufflation" (ROP) resulted in optimal maintenance of the metabolic state which could be further influenced positively by D2O in the total nucleotide content.
1. In 40 three months old Wistar rats (16 trained animals, 14 active controls, 10 passive controls) the influence of learning (brightness discrimination) on the number of electronmicroscopically detectable synapses per area neuropil was studied in the stratum radiatum (CA 1) of the hippocampus. 2. 70 minutes after completion of training, the mean number of synapses has significantly increased as compared to active controls (trained animals 14.26 +/- 2.95 synapses/25 micrometer2; active controls 10.23 +/- 2.80 synapses/25 micrometer2; p less than 0.001). 3. 24 hours after training this increase in trained animals still persisted (trained animals 14.15 +/- 2.60, active controls 11.39 +/- 2.87 synapses/25 micrometer2; p less tha 0.001). 4. 14 days after training, the number of synapses has decreased considerably, but was nevertheless significantly higher than in the active controls (trained animals 12.49 +/- 2.76, active controls 11.45 +/- 3.10; p less than 0.001). 5. The results are discussed with regard to their significance to the different stages of memory formation in the CNS.
Hydroxyacetyl [103Ru]ruthenocene and its o-glucuronide were prepared in vitro by incubation of acetyl [103Ru]ruthenocene with rat-liver homogenate, NADPH, and UDP-glucuronate. The factors affecting hydroxylation and glucuronidation in vitro were optimized for acetylruthenocene. Hydroxyacetyl [103Ru]ruthenocene glucuronide showed no affinity for the adrenal glands, but after i.v. administration of hy droxyacetyl [103Ru]ruthenocene there was a distinct accumulation of Ru-103 in adrenals, similar to that found after administration of acetyl [103Ru]ruthenocene.
In tumor-free and tumor-bearing mice the body clearance and organ distribution of 57Co-BLM was measured in different time intervals after iv, sc, and it administration of the drug. No significant differences could be demonstrated in body clearances following different doses and routes of application of labeled BLM in tumor-free and tumor-bearing mice. The organ distribution studies showed higher concentrations following iv compared to sc or it application of 57Co-BLM; however, the activity in the ipsilateral injection sites were significantly increased after sc and it injection. In tumor-bearing mice the activity in the draining lymph nodes of the injection site were as high as that seen in draining lymph nodes following iv injection. However, on the contralateral side, the lymph node concentration was significantly reduced after it injection. These results indicate on the basis of organ distribution of 57Co-BLM a rational basis for it treatment of malignant tumors.
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The cytostatic drugs Chlorambucil and Bleomycin were labeled with 131I and with 57Co, respectively: Ruthenocenealdehyde-(N-methyl-N-beta-chlorethyl)-hydrazone and Ruthenocene-3-phenyl-prop.1-en-3-one were labeled with the gamma emitter 103Ru. In tumor-bearing mice the elimination and organ distribution of these radioactive substances were tested after intravenous (i.v.) and intratumoral (i.t.) injection of the drugs. The organ load showed lower values after i.t. than after i.v. application, while the radioactivity concentrations in the tumor were considerably increased after i.t. injection. The integrals of the concentration-time curves showed 10--80 times higher concentrations in the tumor after i.t. compared to i.v. injection of the drugs.
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In tumour-free and tumour-bearing mice the body clearance and organ distribution of 57Co-BLM was measured at different time intervals after iv., sc., and it. administration of the drug. No significant difference could be demonstrated in body clearance following different doses and routes of application of labelled BLM in tumour-free and tumour-bearing mice. The organ distribution studies showed higher concentrations following iv. compared to sc. or it. of 57Co-BLM; however, the activity in the ipsilateral injection sites was significantly increased after sc. and it. injection. In tumour-bearing mice the activity in the lymph nodes draining injection site was as high as that seen in the draining lymph nodes following iv. injection. However, on the contralateral side, the lymph node concentration was significantly reduced after it. injection. These results indicate on the basis or organ distribution of 57Co-BLM a rational basis for it. treatment of malignant tumours.
The hydroxylation of 5alpha-dihydrotestosterone at C-2 in guinea pigs was measured with [1alpha,2alpha-T]5alpha-dihydrotestosterone as substrate by isolation of the liberated HTO ("Stoffwechsel-labile Markierung"). The hydroxylation measured in vivo by radiospirometry (condensation of body water with HTO from the expired air) was much higher in males than in females, due to the high hydroxylation capacity of the lung in males. In addition to lung, adrenal and liver showed a high, sexual organ low hydroxylation capacity for 5alpha-dihydrotestosterone.
Individual parenteral alimentation with infusions of combined carbohydrates and amino-acids produced no clinical side effects, however, the electrolyte, acid-base and phosphate balance had to be observed strictly.
Three groups of patients who underwent Billroth II operation received infusions that differed in calory and amino-acid contents. In all groups the controlled parameters of serum and urine changes were similar and rarely abnormal. The elimination of amino-acids in urine is dependent on the kind of parenteral supply. The relation of the amino-acids in the different groups is, however, agreeable.
The tissue H2O of rabbit heart and rat liver was partially exchanged in situ with D2O. In rat liver, the loss of ATP, resulting from normothermic ischemia, was decreased after perfusion with D2O. The maximal protective effect was found when the proportion of D2O in the water of the liver tissue was 0.20. In both organs the protective effect of D2O could be correlated with a marked decrease in severe ischemic damage of cellular organelles, in particular mitochondria. D2O also increased the protective action of Mg-ions in the heart.
1. After oral administration of acetylruthenocene to rats, metabolites were detected in bile and urine. 2. The major metabolite, which is present in both bile and urine, is a glucuronide with the structure: C5H5-Ru-C5H4-CO-CH2-O-C6H9O6 3. The metabolite was identified by mass spectrometry of the permethylated glucuronide and mass spectrometry and n.m.r. of the aglycone. 4. The nature of the metabolite is discussed, and a comparison is made with the metabolism of the benzene analogue, acetophenone.
1. The metabolic fate, rate of excretion and organ distribution of [103Ru]ruthenocene, administered to mice intravenously, intraperitoneally and orally, were investigated. 2. Most of the 103Ru was eliminated from the body in 24 h; the remainder was located mostly in liver, gastro-intestinal tract and fat and was slowly excreted. 3. The 103Ru was excreted in the bile and urine as ruthenocene-O-glucuronide, as shown by enzymic hydrolysis and mass spectrum of the permethylated metabolite.
The hydroxylation of testosterone and 5alpha-dihydrotestosterone at C-2 was measured quantitatively in vivo and in vitro in rats by using "metabolically labile" tritium labelled substrates. The enzyme activity was dependent on the sex and age of the animals. There was a good correlation between in vivo and in vitro experiments. Whereas testosterone was hydroxylated only in liver, 5alpha-dihydrotestosterone was hydroxylated in adrenals, kidney, lung and prostate as well. Hydroxylation was not sex-dependent in adrenals and lungs.