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Biomedical subjects

H Höger

Publications and source records attributed to H Höger.

35 records · Page 2Linked to original sources

L-arginine reduces glomerular basement membrane collagen N epsilon-carboxymethyllysine in the diabetic db/db mouse.

The present study was carried out to examine the effect of L-arginine on advanced stage nonenzymatic glycosylation end products in glomerular basement membrane (GBM) as represented by carboxymethyllysine (CML). Twelve db/db mice were given a solution containing a daily dosage of L-arginine of 50 mg/kg body weight orally. Twelve db/db mice served as controls. At the end of the 4-months study period treated animals had significantly lower concentrations of CML (0.084 +/- 0.008, 0.071-0.098 nmol/mumol OH-proline; mean +/- SD, range, p less than 0.01) compared to untreated controls (0.11 +/- 0.018, 0.095-0.152 nmol/mumol OH-proline). In addition, there was a significant positive correlation between GBM thickness and concentrations of CML (r = 0.86, p less than 0.001). We conclude that reduction of CML concentrations in treated db/db mice possibly reflects a beneficial effect of L-arginine on advanced stage nonenzymatic glycosylation end-products in GBM. In addition, measuring CML concentrations might have future clinical implications as a noninvasive parameter for basement membrane thickening.

Administration, Oral↗

Genetic drift in an outbred stock of mice.

Survey in protein polymorphism in the nucleus colony of the Him: OF 1-mouse outbred stock showed that 8 of 53 loci were variable in the stock. Allele frequencies of these eight loci (Idh-1, Mup-1, Pgm-1; Ldr-1, Gpi-1s, Hbb, Mod-1, Ce-2) changed between generations investigated. The average percentage of heterozygote animals for these loci decreased with generation. These suggested that genetic drift occurred in the breeding stock. Examination in the breeding record sheets showed that genetic drift was caused by mistakes in mating probably due to repeated personnel changes and insufficient training of the animal technicians. Mice had not been paired according to the schemes prescribed, pairing among relatives and reduction of the number of litters used for mating occurred. The increase in homozygosity showed only little effect on breeding parameters: The interval between pairing and first and second litter increased significantly.

Animals↗

[The tumor spectrum of Him:OFA rats].

The longevity and incidence of spontaneous tumors was investigated in 92 male and 182 female rats of the Sprague-Dawley (SD) derived stock Him: OFA. The overall tumour incidence was 85.9% in males and 97.8% in females with 32 different types of tumors in males and 30 in females. The most frequent neoplasms were mammary tumours in females with 84.6% incidence, followed in this sex by adrenal (36.8%), pituitary (32.9%) and thyroid neoplasms (10.9%). The incidence of all neoplasms in female genital tract was 12.6%. In male rats tumours of the adrenals have the highest incidence (53.2%, most of them cortical) followed by pituitary tumours (31.5%) and neoplasm of the mesenteric lymph nodes (14.1%, which is uncommonly high compared with other Sprague-Dawley stocks). All other tumours are below 10% incidence. The mean lifespan of females is with 719 +/- 142 d shorter than that of males with 752 +/- 108 d because of the high incidence of mammary tumours between 16 to 18 months of age.

Adrenal Gland Neoplasms↗

The effect of substance L on glucose-mediated cross-links of collagen in the diabetic db/db mouse.

Genetically diabetic mice (db/db) were given 50 mg/kg body weight/day substance L, a nontoxic basic amino acid and compared to control diabetic mice without treatment. The oral administration of the compound was started at the age of 3 months and the animals were sacrificed at the age of 7 months. No adverse effects were observed in animals given the substance L. Total food consumption, drinking water intake and body weight were comparable between the groups. Nonenzymatic glycosylation of serum proteins and hemoglobin was not significantly different in the groups. Renal pathological lesions in the control diabetic mice showed glomerular mesangial expansion and on electron microscopy thickened glomerular basement membranes with a mean thickness of 3,204 +/- 186 A. Treated animals showed significantly less mesangial crescents and thinner glomerular basement membrane thickness of 2,520 +/- 252 A (p less than 0.01). The experimental animals showed in addition a lower mean kidney weight. Glomerular but not tubular proteinuria was reduced in the treated group. Basement membrane collagen type IV isolated from kidneys of experimental animals was more soluble in acidity and showed a lower degree of cross-linking as evaluated by SDS-polyacrylamide gel electrophoresis. We conclude that substance L is beneficial to diabetic renal changes. We suggest that this positive effect could be due to the inhibition of glucose-mediated abnormal cross-linking of collagenous structures by the interaction of substance L with reactive carbonyl residues of glycosylation adducts of collagen. Other possible mechanisms are discussed.

Administration, Oral↗

Inherited seborrheic dermatitis--a new mutant in mice.

A new mutation, affecting skin and hair, occurred in an expansion colony of Him:OF1 mice. Test crosses showed that a single autosomal recessive gene was responsible for this trait. Homozygotes have sparse greasy fur and lower viability and fertility than normal littermates. Histological observations showed hypertrophy of sebaceous glands, hyperkeratosis, parakeratosis, acanthosis and signs of inflammation. The disease was named 'inherited seborrheic dermatitis' and the gene name seb is proposed.

Animals↗

Induction of arthritic processes by synovial fluids of rheumatoid arthritis patients in long-term experiments with mice.

Diluted synovial fluids derived from three patients with rheumatoid arthritis (RA) and applied subcutaneously once as a single dose in Swiss mice caused arthritic processes after a long period of latency (10 months). The arthritis-inducing effect was enhanced by storing the original synovial fluids at 4 degrees C for three months. The effects were followed histologically for at least 18 months. In contrast to the theory that RA is based on immunological processes, these preliminary observations support the finding of other authors that a transmissible agent which is rather slow-acting exists in the synovial fluid of RA patients.

Animals↗

[Effect of superoxide dismutase on an arthritis model in the rabbit. A scanning electron microscopy study].

The effect of superoxide dismutase (SOD) was studied in an experimental arthrosis model (fixation arthrosis in rabbits). Out of a total of 40 animals, 20 of which were to be treated with SOD and 20 with placebos, 5 animals each were given padded stiffened bandages to immobilize their right knee joints for 1 week, 2 weeks, 3 weeks and 4 weeks respectively. After removing the bandage and a two-week recovery period the SOD or placebo treatment respectively was begun. During this period the animals were allowed to move freely. In 20 animals 0.5 mg SOD in 0.2 ml of a 0.5% xylocaine solution were applied intraarticularly in both popliteal spaces once a week for a total of 4 weeks. 20 control animals likewise received 0.2 ml of a 0.5% xylocaine solution (placebo) in both popliteal spaces in the same time intervals. After treatment the animals were killed and examined. A further 5 animals were not given a stiffened bandage, but for 4 weeks they received intraarticular injections once a week of 0.2 ml of a 0.9% saline to act as controls. The evaluation of the changes in the joints was by histological examination and examination by scanning electron microscope. In comparison to the placebo treatment the SOD treatment in this animal experiment did not lead to a significant change in the arthrotic process.

Animals↗

[Histologic studies of the effect of superoxide dismutase on an arthrosis model in rabbits].

The effect of the enzyme superoxide dismutase (SOD) on experimentally induced osteoarthritis was investigated. Immobilization of the right knee of rabbits over variable periods (1-4 weeks) was used as the model for the study. SOD was applied intraarticularly. Distinct histological changes were detected in the immobilized joints in contrast to the freely mobile joints. In the group of rabbits treated with SOD, erosions, necroses, and inflammatory symptoms were more frequent than in the placebo group. The changes found in animals after SOD application indicate the enzyme has an intensifying effect on osteoarthritis.

Animals↗