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Biomedical subjects

H Graf

Publications and source records attributed to H Graf.

At least 145 records · Page 8Linked to original sources
PubMed1985

A new monooxygenase product from 7-ethoxycoumarin and its relation to the O-dealkylation reaction.

The widely used fluorometric microsomal monooxygenase test for 7-ethoxycoumarin O-dealkylation was reinvestigated with regard to other possible hydroxylation products. By HPLC-analysis no beta-hydroxylation of the ethyl group and no 8-hydroxylation could be detected. Only a small percentage of 6-hydroxylation occurred, but as a new major metabolite 7-ethoxy-3-hydroxycoumarin was found in quantities depending on the microsomal preparation used. The ratio of O-dealkylation to 3-hydroxylation varied according to species, induction, buffer and pH, suggesting that different isozymes of cytochrome P450 were involved. The isozyme mainly responsible for 3-hydroxylation exhibited a great dependence on cytochrome b5 as the donor for the second electron. The fluorometric test does not include 3-hydroxylation due to the virtual absence of an emission spectrum above 450 nm.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1985

Iron removal by desferrioxamine in patients on chronic hemodialysis--kinetic study and long-term results.

Serum ferritin levels, cumulative number of administered blood transfusions, number of monthly transfused blood units and total months on hemodialysis (HD) treatment differed significantly in 7 patients on hemodialysis with clinical, biochemical and histological evidence of hemosiderosis, when compared to 37 controls (p less than 0.001 for all parameters). As a new treatment method desferrioxamine (DFO) therapy was introduced for iron detoxification in these hemosiderotic chronically hemodialyzed patients. Hence, to maximize the biological half-time, 30 mg/kg body weight DFO were given after the end of HD in the iron-loaded patients. Iron removal during the subsequent HD and the increase of iron excretion by the stool after DFO was measured by atomic absorption spectroscopy. Iron removal by the artificial kidney was calculated by investigating the function (QDi + QF)CDo over the duration of HD treatment, which equals the total amount of iron removal during HD. Using numerical integration of measured data this removal was found to be 21.8 +/- 6.9 mg whereas cumulative iron loss via the feces was found to be 36.5 +/- 14.6 mg. Therefore, total iron elimination was calculated to be on average 50-60 mg after administration of a single dose of DFO. Furthermore, long-term treatment of 5 patients resulted in a significant decrease of serum ferritin levels from 2,309 +/- 295 to 715 +/- 177 ng WHO/ml (p less than 0.001) after a period of 36 +/- 5 months. We conclude, that DFO in a dosage of 30 mg/kg body weight given at the end of HD is able to remove more than 500 mg iron/month if it is administered following each HD. Long-term results indicate negative iron balance without significant change of transfusion frequency if not more than 2 U of blood (500 mg iron) are administered within 1 month. This treatment schedule might be superior compared to the previously used methods of administration where DFO was given at the beginning or throughout HD.

Adolescent↗
PubMed1984

Paracelsin; characterization by NMR spectroscopy and circular dichroism, and hemolytic properties of a peptaibol antibiotic from the cellulolytically active mold Trichoderma reesei. Part B.

Paracelsin, a hemolytic and membrane active polypeptide antibiotic of the peptaibol class which is excreted by the mold Trichoderma reesei, was obtained by a simplified and rapid isolation procedure utilizing hydrophobic adsorber resins. Investigation by 13C nuclear magnetic resonance spectroscopy and circular dichroism revealed considerable helical portions in solution, and the very recently accomplished sequence determination of paracelsin allows the discussion of the results with regard to the closely related analogues, alamethicin and suzukacillin. A selective cleavage of the peptide was achieved by careful treatment with various acids, and a buffer of pH 8.25 and of high ionic strength made possible the quantitative determination of the C-terminal phenylalaninol released by means of ion-exchange chromatography. The significance of the production of paracelsin and related mycotoxins of the peptaibol class, exhibiting various kinds of biological activity, is discussed with respect to the extensive effort being made towards biotechnological applications of species, strains and cellulolytically highly active mutants of the fungus Trichoderma.

Alamethicin↗
PubMed1984

Characterization of the benzene monooxygenase system in rabbit bone marrow.

The microsomal fraction of bone marrow contains cytochrome P-450 (39 +/- 11 pmoles/mg microsomal protein) and monooxygenase activity could be demonstrated by the O-dealkylation of 7-ethoxycoumarin (114 +/- 65 pmoles/(min X mg microsomal protein] and the hydroxylation of benzene to phenol (51 +/- 8.6 pmol/45 min X mg microsomal protein). This monooxygenase system differs from that in liver in various aspects. The conversion of benzene to phenol calculated as molecular activity was about 4 times higher than in liver and no induction by phenobarbital could be observed. Aroclor 1254 induced the cytochrome P-450 content about twofold but lowered the O-dealkylation activity of 7-ethoxycoumarin in contrast to liver. Pretreatment with benzene did not change the O-dealkylation in bone marrow, but had a stimulating effect on benzene monooxygenation and covalent binding of 14C-benzene metabolites. From these results we conclude that the bone marrow monooxygenase system develops its own pattern of cytochrome P-450 isoenzymes. Especially after chronic exposure to benzene this system can convert this chemical to phenol and secondary metabolites. The similar behaviour of phenol formation and covalent binding strengthens the hypothesis of a common pathway for metabolism and toxicity but the active intermediate still remains unknown.

Animals↗
PubMed1984

[Continuous arteriovenous hemofiltration in the therapy of acute renal insufficiency].

30 patients with acute renal failure were treated in an intensive care unit by continuous arterio-venous haemofiltration (CAVH). This procedure has less side effects as compared with intermittent haemodialysis, peritoneal dialysis and haemofiltration (hypotension, bio-incompatibility and lack of biochemical steady state) and CAVH is clearly superior with regard to fluid removal. In removing the uraemic toxins CAVH is more effective than peritoneal dialysis and, in most instances, satisfactory as sole renal replacement therapy in acute renal failure.

Acute Kidney Injury↗
PubMed1984

[15N-labeled lysine in colostomized laying hens. 5. 15N incorporation into blood fractions and the gastrointestinal tract].

In the metabolism experiment three colostomized laying hens received, together with a commercial ration of 120 g, 0,2% 15N-labelled L-lysine with an atom-% 15N-excess (15N') of 48%; subsequently the same ration was fed over a period of 4 days with 0.2% unlabelled L-lysine. After the end of the experiment the hens were slaughtered. The atom-% 15N' was determined in total, in the lysine, histidine and arginine N in the corpuscles, the plasma, the NPN-fraction of the blood in the stomachs, the small intestine, the caecum and the rectum. 15N' in the corpuscles was 0.11 atom-%, in the blood plasma 0.17 atom-%, in the NPN-fraction of the blood 0.09 atom-%, in the tissue of the gastro-intestinal tract 0.11 atom-% and in its contents 0,12 atom-%. On average the blood contained per hen 77.9% lysine-15N', 16.4% arginine-15N' and 5.7% histidine-15N' of the basic amino acid-15N'. For the gastro-intestinal tract 78.7% lysine-15N', 19.0% arginine-15N' and 2.3% histidine-15N' of the 15N' of the basic amino acids were ascertained. In comparison to histidine the alpha-amino-N of lysine is incorporated to a considerably higher degree into arginine. For lysine and arginine the atom-% 15N' in the contents of the gastro-intestinal tract for days after the end of the supplementation of labelled lysine is between 8 and 10 times higher than in the feces of the last day of the experiment. This indicates a considerable secretion of the two amino acids in the gastro-intestinal tract and their re-absorption to a large extent.

Amino Acids↗
PubMed1984

Oxygen tension (pO2) in untreated human periodontal pockets.

The purpose of this study was to assess the oxygen tension in untreated human periodontal pockets and test the hypothesis that the subgingival environmental is anaerobic in nature. Twenty-six patients with advanced chronic inflammatory periodontal disease participated. A total of 111 untreated pockets, 5 to 10 mm in depth, were selected for the pO2 measurements. Pocket depths, Plaque-Index and Gingival-Index were recorded. The pO2 at the base of the 111 pockets ranged from 5 to 27 mm Hg, with an average of 13.3 mm Hg (1.8% O2). Mean pocket depth was 6.9 mm. Moderately deep pockets (5-6 mm) had a mean pO2 of 15.0 mm Hg, whereas deep pockets (7-10 mm) showed a significantly lower pO2 of 11.6 mm Hg. No correlation was found between the pO2 and the Plaque-Index. Higher Gingival-Index scores tended to be associated with higher pO2 values. The pO2 in untreated periodontal pockets was low. However, it does not represent a completely anaerobic environment. Deep pockets contained less oxygen than moderately deep sites.

Adult↗
PubMed1984

Effect of desferrioxamine on aluminum kinetics during hemodialysis.

The effects of desferrioxamine administration on aluminum kinetics during hemodialysis were studied. Desferrioxamine leads to an increase of plasma aluminum levels in patients on chronic hemodialysis which could be attributed to mobilization of tissue aluminum. The in vivo protein binding of aluminum was found to be 70% after administration of desferrioxamine vs. 80% without a premedication with desferrioxamine, thus greatly enhancing the concentration gradient between free diffusible plasma aluminum and dialysate aluminum. Desferrioxamine therefore leads to increased aluminum removal during hemodialysis and should be considered in the therapy of aluminum toxicity syndromes.

Adolescent↗