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Biomedical subjects

D Adamiker

Publications and source records attributed to D Adamiker.

At least 19 recordsLinked to original sources

Creatine reduces collagen accumulation in the kidneys of diabetic db/db mice.

In the present study, we tested the hypothesis whether creatine, a metabolite of arginine metabolism, shares the pharmacological activities of arginine reducing collagen accumulation in the diabetic kidney. Ten db/db mice were given, for 3 months, a solution containing a daily dosage of creatine of 50 mg/kg body weight. Eleven db/db mice served as controls. At the end of the 3-month study period, the mean N-carboxymethyllysine concentration in the untreated group was significantly higher than in the treated group (0.163 +/- 0.18 versus 0.096 +/- 0.017 nmol/mumol hydroxyproline, p < 0.001). Collagen accumulation was also significantly higher in the untreated than in the treated group (2.21 +/- 0.24 versus 1.68 +/- 0.22 mumol hydroxyproline/100 mg kidney weight, p < 0.001). We conclude that creatine led to a significant reduction in collagen type IV accumulation resembling arginine or aminoguanidine action. We do suggest that the guanidino group common to both compounds is able to block reactive carbonyls.

Animals

Reduced tumour incidence in mice with inherited seborrhoeic dermatitis.

121 mice homozygous for the gene seb (inherited seborrhoeic dermatitis) and their 142 unaffected heterozygous littermates were kept for their natural lifespan. Heterozygotes showed 84.1% total tumour incidence in males and 95.9% in females. The most common neoplasms were lymphomas, osteomas, lung tumours and neoplasms of the female genital tract. Homozygotes showed a tumour incidence of 36.1% in males and 45.0% in females. The reduction in incidence included all types of neoplasms except epithelial tumours of the skin: skin tumours were detected in 11 homozygous but only in one heterozygous animal. Life expectancy was not affected significantly by genotype. Homozygous mice showed rough and greasy fur and became alopecic with age. Energy intake was increased but growth and depository fat was reduced compared with heterozygous mice. Higher heat loss may incompletely be compensated by higher metabolic rate and thus 'dietary restriction' results in decreased tumour rates. As females show small gonads and a higher increase in food consumption hormonal factors may also be involved.

Animals

Evidence for the existence of differential O-glycosylated alpha 5-subunits of the gamma-aminobutyric acidA receptor in the rat brain.

Polyclonal antibodies were raised to synthetic peptides having amino acid sequences corresponding with the N- or C-terminal part of the gamma-aminobutyric acidA (GABAA) receptor alpha 5-subunit. These anti-peptide alpha 5(2-10) or anti-peptide alpha 5(427-433) antibodies reacted specifically with GABAA receptors purified from the brains of 5-10-day-old rats in an enzyme-linked immunosorbent assay and were able to dose-dependently immunoprecipitate up to 6.3 or 13.1% of the GABAA receptors present in the incubation, respectively. In immunoblots, each of these antibodies reacted with the same two protein bands with apparent molecular mass of 53 or 57 kDa. After exhaustive treatment of purified GABAA receptors with N-Glycanase, each of these antibodies identified two proteins with apparent molecular masses of 46 and 48 kDa. Additional treatment of GABAA receptors with neuraminidase and O-Glycanase resulted in an apparently single protein with molecular mass of 47 kDa, which again was identified by both the anti-peptide alpha 5(2-10) and the anti-peptide alpha 5(427-433) antibody. These results indicate the existence of at least two different alpha 5-subunits of the GABAA receptor that differ in their carbohydrate content. In contrast to other alpha- or beta-subunits of GABAA receptors so far investigated, at least one of these two alpha 5-subunits contains O-linked carbohydrates.

Animals

N-deglycosylation and immunological identification indicates the existence of beta-subunit isoforms of the rat GABAA receptor.

beta 2- and beta 3-subunits of GABAA receptors purified from the brains of 5-10-day-old rats were investigated in the intact or completely N-deglycosylated state using the beta-subunit-specific monoclonal antibody bd-17 and polyclonal antibodies directed against synthetic amino acid sequences specific for the GABAA receptor beta 2- or beta 3-subunits. The present results seem to indicate the existence of two different isoforms of the beta 3-subunit and several different isoforms of the beta 2-subunit of the GABAA receptor which probably are produced by alternative splicing.

Amidohydrolases

[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

Identification of alpha 2- and alpha 3-subunits of the GABAA-benzodiazepine receptor complex purified from the brains of young rats.

Polyclonal antibodies were raised to synthetic amino acid sequences of the bovine GABAA receptor alpha 2- and alpha 3-subunits and purified by affinity chromatography on a column coupled with the respective peptide. Anti-peptide alpha 2(416-424) and anti-peptide alpha 3(459-467) antibodies immunoprecipitated GABAA receptors and recognized a protein of 53 kDa (P53) and 59 kDa (P59), respectively, in Western blots of GABAA receptors purified from the brains of 5-10 day old rats. P53 as well as P59 are specifically photolabeled by [3H]flunitrazepam and are recognized by the alpha-subunit specific monoclonal antibody bd 28.

Animals

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

Effects of burns on amino acid levels in rat plasma, liver and muscle.

In this study the influence of a severe catabolic situation (scalding and nitrogen deprivation) on amino acid (AA) metabolism was investigated in an experimental rat model. Scalding of 25 per cent of the total body surface area (TBSA) and hypocaloric alimentation (5.6 kcal per 100 g rat per day, no nitrogen) resulted in mean daily nitrogen losses of -0.27 +/- 0.3 g. Compared to anabolic growing rats this nitrogen catabolism significantly reduced the total free AA content of muscle (-47 per cent, P less than 0.001) and liver (-39 per cent, P less than 0.001). The total plasma AA concentrations were slightly increased in catabolic rats (+10 per cent). In catabolic rats muscle glycine concentrations dropped significantly (-79 per cent, P less than 0.001), while glutamine concentrations decreased by 22 per cent, which was not significant. Branched chain AA and phenylalanine were significantly elevated both in muscle and in plasma. Scalding and nitrogen depletion in rats leads to characteristic changes in plasma, muscle and liver AA concentrations, which are comparable to the results obtained in catabolic patients. However, the low muscle glycine concentrations in burned rats differ from the clinical observations where glutamine rather than glycine concentrations in muscle tissue are reduced. The rat model seems to be well suited for studying the influence of various therapeutic approaches such as different forms of parenteral nutrition or hormonal substitution on nitrogen catabolism.

Amino Acids

Insulin and the in vitro protein synthesis of liver and skeletal muscle ribosomes in experimental acute uraemia.

Tissue dependent alteration of liver and muscle protein synthesis was previously observed in acute uraemia, when intracellular amino acids were used as substrate. Since protein synthesis depends also on substrate availability, it was of interest to investigate the role of isolated liver and skeletal muscle ribosomes of nephrectomized rats and their susceptibility to in vivo insulin stimulation. Under marked uraemic conditions, no difference was demonstrated between controls and uraemic animals; after insulin administration and in the presence of endogenous messenger both liver and muscle ribosomes showed an enhancement of [3H]-phenylalanine incorporation of 20% and 54% respectively in controls, and of 32% and 45% respectively in uraemic rats. This study may rule out the influence of acute uraemia on protein synthesis capacity of isolated ribosomes and emphasize the importance of intracellular amino acid availability in altered protein synthesis.

Acute Disease