Glomerular filtration rate estimated by 3-sample plasma clearance of iohexol in 118 healthy dogs.

BACKGROUND: Glomerular filtration rate (GFR) decreases in the aging human kidney, but limited data exist in dogs. HYPOTHESIS: There is an effect of age and body size on estimated GFR in healthy dogs. ANIMALS: One hundred and eighteen healthy dogs of various breeds, ages, and body weights presenting to 3 referral centers. METHODS: GFR was estimated in clinically healthy dogs between 1 and 14 years of age. GFR was estimated from the plasma clearance of iohexol, by a compartmental model and an empirical correction formula, normalized to body weight in kilograms or liters of extracellular fluid volume (ECFV). For data analysis, dogs were divided into body weight quartiles 1.8-12.4, 13.2-25.5, 25.7-31.6, and 32.0-70.3 kg. RESULTS: In the complete data set, there was no trend toward lower estimated GFR/kg or GFR/ECFV with increasing age. GFR decreased with age in dogs in the smallest weight quartile only. A significant negative linear relationship was detected between body weight and estimated GFR/kg and GFR/ECFV. Reference ranges in different weight quartiles were 1.54-4.25, 1.29-3.50, 0.95-3.36, and 1.12-3.39 mL/min/kg, respectively. Standardization to ECFV rather than kilogram body weight did not produce substantial changes in the relationships between GFR estimates and age or weight. CONCLUSIONS AND CLINICAL IMPORTANCE: Interpretation of GFR results for early diagnosis of renal failure should take into account the weight and the age of the patient for small dogs.

Polyamines in the gastro-intestinal tract of goat kids and in the regenerating ruminal epithelium of sheep.

The aim of the present study was to investigate whether temporal changes in polyamine concentration and synthesis could be found in the luminal content and wall tissue of the rumen and abomasum, two organs which have entirely different growth patterns during the first month of life. In the abomasal mucosa there was a marked gradual decrease in the ornithine decarboxylase (ODC) activity during the first month of life, while the ODC activity in the ruminal mucosa was low during the whole experimental period. However, injury of the rumen wall was followed by increased ODC activity. The ODC activity in duodenal mucosa was about 10 times higher than in the ileal mucosa and the ruminal epithelium. In ruminal liquid a clear peak in ODC activity was observed during the period 51-70 days after birth. The polyamine concentration did not parallel the ODC activity, in either the ruminal epithelium or the ruminal liquid. Of the polyamines, the spermine concentration was always highest, and with the exception of duodenal mucosa, the putrescine concentration was lowest. In liver a clear decrease in spermidine concentration from day 1 to about day 60 after birth was observed. Otherwise no marked temporal changes in tissue polyamine concentrations were observed. Two and a half hours after oral administration of 14C-labelled spermine, nearly all of the radioactivity was found in the lumen of the gastrointestinal tract. On the other hand, 1 h after intravenous injection of polyamines the walls of the gastrointestinal tract were strongly labelled. In conclusion, the polyamines needed for ruminal epithelial development seem to come from sources other than the ruminal epithelium itself or the ruminal lumen.

Effects of dietary polyamines and clofibrate on metabolism of polyamines in the rat.

The activities of catalase, polyamine oxidase, diamine oxidase, ornithine decarboxylase, and peroxisomal beta-oxidation were assayed in homogenates from liver and small intestinal mucosa of rats which had been fed either a diet very low in polyamines or a diet containing five times the levels of dietary polyamines (putrescine, spermine, and spermidine) found in a standard rat diet. In rats fed the high polyamine diet, hepatic activities of catalase and polyamine oxidase were significantly decreased. Levels of the other activities were unchanged, except that intestinal ornithine decarboxylase was decreased. In rats treated simultaneously with clofibrate, the high polyamine diet restored activities of catalase, ornithine decarboxylase, and polyamine oxidase back to levels found in rats fed the low polyamine diet. The expected increase in activity of peroxisomal beta-oxidation was observed, although this was somewhat diminished in rats fed the high polyamine diet. Intestinal diamine oxidase activity was stimulated by clofibrate, particularly in rats fed the high polyamine diet. For the duration of the experiment (20 days), levels of putrescine, spermine, and spermidine in blood remained remarkably constant irrespective of treatment, suggesting that polyamine homeostasis is essentially independent of dietary supply of polyamines. It is suggested that intestinal absorption/metabolism of polyamines is of significance in this respect. Treatment with clofibrate appeared to alter polyamine homeostasis.

Role for a YY1-binding element in replication-dependent mouse histone gene expression.

Expression of the highly conserved replication-dependent histone gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated alpha, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 alpha element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 alpha sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro histone alpha DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone alpha DNA-YY1 interaction alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo. Because all mutations or deletions of the histone alpha sequence both abolish interactions in vitro and cause an in vivo decrease in histone gene expression, the recognition of the histone alpha element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon.

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose-dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.

Plasma insulin, glucagon, glucagon-like peptide and glucose levels in response to feeding, starvation and life long restricted feed ration in salmonids.

Plasma insulin, glucagon, glucagon-like peptide (GLP) and glucose were measured in samples taken from rainbow trout,Oncorhynchus mykiss. (1.5 years of age) before feeding and at selected times up to 9 days after feeding. The feed contained 21.7% carbohydrate (65% digestibe) in the dry matter. The fish responded to feeding with an elevated plasma insulin level (p<0.005) 0.5 h post-feeding, which may account for the unchanged plasma glucose levels. Twentyfour hours after feeding, plasma insulin level had returned to prefeeding levels, while 4-9 days after feeding, a significant reduction compared to pre-feeding levels was observed (p<0.001). During this period plasma glucose levels remained unchanged. The corresponding plasma glucagon or GLP levels showed no significant elevation in response to starvation, the plasma GLP concentration was even significantly reduced on days 4-9 post-feeding (p<0.01-0.001).Atlantic salmon,Salmo salar, (3.5 years of age) fed a calculated satiation ration (RL=100) throughout their lifetime had, in addition to a higher body weight, significantly higher plasma insulin (p<0.005) glucagon (p<0.0001) and GLP levels (p<0.0001) than fish fed half the satiation ration. The plasma glucose levels were, however, not significant different between the groups.

No effect of prolonged fluoride exposure on cytochrome P-450 and associated monooxygenases or on the level of polyamines in the rat.

When exposing rats to drinking water containing 100 p.p.m. fluoride for 8 weeks, no effect could be detected in biochemical parameters of the liver, such as the concentrations of the polyamines putrescine, spermidine and spermine; the levels of microsomal protein and cytochrome P-450; or the activities of two associated monooxygenases, aryl hydrocarbon hydroxylase and ethylmorphine N-demethylase. Neither was there any increase in plasma glutamic-oxalacetic transaminase indicative of liver damage.

A new histamine metabolite, quantitatively important in chicken.

After i.v. injection of 14C-histamine to chicken, we identified one of the histamine metabolites as N-acetylmethylhistamine in the urine. This new metabolite accounted for about 20% of the urinary or 14% of the administered radioactivity.