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Biomedical subjects

H W Leber

Publications and source records attributed to H W Leber.

At least 19 recordsLinked to original sources
PubMed1979

Influence of the plasticiser di-2-ethylhexyl-phthalate on drug metabolising enzymes in the liver of uraemic rats.

After bilateral or subtotal nephrectomy male rats were given intraperitoneal injections of the plasticiser di-2-ethylhexylphthalate (DEHP) at differing time intervals in doses that do not affect the liver of normal rats. 200mg DEHP/100g body weight had no influence on the parameters measured. After administering 7 x 200mg/100g body weight for 14 days, liver weight and in vitro activity of the mixed function oxidation system increased significantly. In addition, the hexobarbital sleeping time decreased, indicating a stimulation of the activity of drug metabolising enzymes in vivo. Similar results were obtained after the administration of 56 x 50mg DEHP/100g body weight for 19 weeks. It is concluded that uraemic rats are more susceptible to inducing effects, but that the DEHP toxicity is of little importance.

Animals↗
PubMed1978

Influence of essential amino acids and keto acids on protein metabolism and anemia of patients on intermittent hemodialysis.

Ten patients were treated with 10 g/day of essential amino acids orally; nine patients received 9.5 g/day of a mixture of essential amino acids (lysine, threonine, tryprophan, histidine, and tyrosine) and keto analogues of isoleucine, leucine, phenylalanine, valine, and methionine. A control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1 g of protein per kilogram of body weight and 31 kcal/kg of body weight daily. Before and 3 months after the beginning of the supplementation, the following parameters were measured: amino acids, albumin, transferrin, urea and creatinine concentrations in plasma, hemoglobin, and hematocrit in blood. None of these parameters was altered by either treatment. It is concluded that supplementation with essential amino acids or their keto analogues is ineffective in well-nourished dialysis patients.

Administration, Oral↗
PubMed1978

Influence of middle molecules on the anemia of uremic patients.

To evaluate their toxicity at the cellular level, middle molecules from uremic serum were incubated with erythrocytes from healthy subjects and the activity of the enzyme Delta-aminolevulinic acid dehydrase (D-ALA-D) and peroxidative hemolysis were investigated. Uremic middle molecules caused a significant decrease of the D-ALA-D activity of normal erythrocytes which was not due to differences in the concentrations of Pb, Cd or Zn. The decreased enzyme activity could be restored by adding reduced glutathione (GSH; 5 mmol/L) together with the middle molecules to the assay system. Uremic middle molecules caused a significant increase of peroxidative hemolysis in normal erythrocytes. Uremic middle molecules contribute to the anemia of uremic patients by impeding hemoglobin synthesis and by increasing peroxidative hemolysis, possibly by affecting SH-groups. H2O2-producing compounds should be avoided in uremic patients.

Anemia↗
PubMed1978

Hemodiafiltration: a new alternative to hemofiltration and conventional hemodialysis.

A new dialysis method, termed hemodiafiltration, is proposed. The procedure consists of the combination of hemofiltration and conventional hemodialysis using high flux membranes with a transmembrane pressure (TMP) of 300--500 mmHg and a dialysate flow of 900 ml/min. Due to the combination of convective mass transfer and diffusion, the clearance values of both small and larger molecules are significantly higher than during hemofiltration or hemodialysis alone with the same membranes. The removal of excess water is better tolerated than during hemodialysis. With this new method, six patients have been successfully treated for six months (three times per week, three hours per treatment) without side effects. Thus hemodiafiltration appears to be the method of choice to shorten dialysis time.

Creatinine↗
PubMed1978

Simultaneous hemofiltration/hemodialysis: an effective alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients.

Hemofiltration and hemodialysis were performed simultaneously with the Polyacrylnitrile membrane in a single pass dialyzate flow system. Due to the combination of convective mass transfer and diffusion, the clearances of both small and large molecules were significantly higher than during hemofiltration or hemodialysis alone. The removal of excess water was better tolerated than during hemodialysis. Six patients have been treated by this technique for 6 months 3 X 3 hr/week without side effects, and the new procedure appears to be the method of choice to shorten dialysis time.

Humans↗
PubMed1978

Enzyme induction in the uremic liver.

Forty-five days after subtotal nephrectomy or sham-operation of male rats, microsomal enzymes were investigated in vitro. The activities (per milligram) of microsomal protein of two esterases and of two glucuronyltransferases were normal in the uremic rats. The mixed-function oxidation system had lower activities per milligram of protein than that in sham-operated controls. Due to a decrease of the microsomal protein content of the uremic liver, the activities of these enzymes were decreased when calculated for the whole liver. In contrast, the glucoronidation of phenolphthalein remained normal when related to the whole liver, due to an increased activity per mg of protein. Treatment with the plasticizer di-(2-ethylhexyl)-phthalate caused a significant increase of the liver wet weight, the microsomal protein content, and the activity per mg of protein for the demethylation of aminopyrine in subtotally nephrectomized rats but was without influence on the liver of sham-operated controls. It is concluded that uremia itself does not induce liver microsomal enzymes. The microsomal enzymes, however, remain inducible by foreign compounds even under uremic conditions.

Animals↗
PubMed1977

Influence of essential amino acids and keto acids on protein metabolism and the anaemia of patients on chronic intermittent haemodialysis.

Ten patients were treated with 10 g essential amino acids per day orally; 9 patients received 9.5 g of a mixture of essential amino acids (Lys, Thr, Try, His, Tyr) and ketoanalogues of Ile, Leu, Phe, Val, Met per day and a control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1g protein/kg body weight and 31 kcal/kg body weight daily. Before and three months after the beginning of supplementation the following parameters were measured: serum concentrations of albumin, transferrin, urea, creatinine, blood haemoglobin content and haematocrit, activities of the enzymes delta-aminolevulinic acid dehydrase and porpho-bilinogen desaminase, and globin synthesis in peripheral red blood cells. After treatment with either essential amino acids or keto acids a significant stimulation of globin synthesis occurred. None of the other parameters was altered. It is concluded that in well-nourished patients supplements of essential amino acids or keto acids are ineffective.

Amino Acids, Essential↗
PubMed1976

[Carbromal intoxication: influence of hemodialysis and hemoperfusion].

It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients.

Charcoal↗
PubMed1976

Influence of silymarin on drug metabolizing enzymes in rat and man.

Male rats weighing 100-130 g were treated orally with a daily dose of 1 X 10 mg Legalon (active principle: silymarin)/100 g b.w. daily for 4 or 10 days. 4 and 10 days after the beginning of the pretreatment a significant increase of the activity of the mixed function oxidation system (Cytochrome P-450, aminopyrine demethylation, p-nitroanisole demethylation) was observed. No alteration of the body weight, the liver wet weight, the microsomal protein content, the cytochrome b5 content and the activities of glucose-6-phosphatase (G-6-Pase) and of a glucoronidase (4-methylumbelliferone) took place after the Legalon treatment. 4 h after the oral administration of 0.5 ml CCl4/kg b.w. the activity of the mixed function oxidation system and of the G-6-Pase was markedly decreased. This effect could not be prevented by the oral administration of 1 X 10 mg Legalon/100 g b.w. 6 h prior to CCl4 application. In human subjects the treatment with daily doses of 3 X 70 mg Legalon during 28 days had no influence on the metabolism of aminopyrine and phenylbutazone. From our results it is concluded that Legalon despite its effects in experimental animals has no influence on drug metabolism in man, when applied in therapeutic amounts.

Adult↗