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M Oratz

Publications and source records attributed to M Oratz.

83 records · Page 5Linked to original sources
PubMedDate not supplied

Acute effects of ethanol on hepatic uptake and distribution of narcotics in the isolated perfused rabbit liver.

This study was performed as an initial step in systematically defining the hepatic interactions between ethanol and opioids using a controlled in vitro system. The acute effects of ethanol on the initial uptake and distribution of long- and short-acting narcotics were studied using isolated rabbit liver perfused with rabbit blood without or with ethanol. A pulse injection of 1.5 mg of 14C-labeled narcotic [methadone, 1-alpha-acetylmethadol (LAAM), morphine, or meperidine] was made into the portal vein cannula followed by perfusion for 2 min. Radioactivity was determined in liver homogenates and subcellular fractions; methadone and its metabolites were measured by thin-layer chromatography with zonal scanning in each fraction. Ethanol preperfusion and concomitant ethanol perfusion did not effect hepatic uptake of methadone, LAAM, morphine, or meperidine. Although subcellular localization of morphine and meperidine differed from that of methadone and LAAM, perfusion with ethanol did not alter the acute hepatic uptake and distribution of any of the narcotics. These findings suggest that acute exposure to ethanol does not alter the acute hepatic disposition of narcotics.

Animals↗
PubMedDate not supplied

The role of the urea cycle and polyamines in albumin synthesis.

Albumin synthesis is stimulated by those amino acids which increase urea synthesis and membrane bound polysome aggregation. Ornithine, an amino acid not incorporated into protein and produced from arginine in the urea cycle, is an albumin-stimulating amino acid and is the precursor of the polyamines, and we have shown that the polyamine spermine promotes bound polysome aggregation. To test the concept that ureogenesis with its generation of ornithine might play a key role in albumin synthesis regulation via the polyamine pathway, isolated livers from fasted donors were perfused with ornithine, alpha-difluoromethyl ornithine (DFMO), and spermine. In control experiments, albumin synthesis was 13.4 +/- 0.8 mg per 100 gm liver per hr and polysome aggregation was 47%. These were increased in the presence of ornithine (26.0 +/- 2.6 mg and 59%); if the livers were preperfused with DFMO before the addition of ornithine, then the expected increase in albumin synthesis and polysome reaggregation did not occur (16.3 +/- 1.4 mg and 47%). However, if spermine was present with DFMO during the preperfusion, then the addition of ornithine had the expected effect (albumin synthesis = 26.1 +/- 1.2 mg and polysome aggregation = 62%). This suggests that if the ornithine to putrescine pathway is blocked, ornithine does not stimulate albumin synthesis and offers support to the concepts that (a) ornithine stimulation of albumin production is via polyamine synthesis and (b) that the urea cycle plays a more important role in protein metabolism than simply the pathway for nitrogen disposal.

Albumins↗
PubMedDate not supplied

The effects of ethanol and hyperosmotic perfusates on albumin synthesis and release.

Sucrose and ethanol inhibit albumin synthesis; sucrose via an osmotic mechanism and ethanol during its metabolism. The present study was undertaken to compare the effects of both of these agents on albumin synthesis and secretion, and to see if ethanol inhibition could be related to an osmotic effect. Male, fed rabbits served as liver donors in all studies. There were a total of 35 studies: 13 control; 10 ethanol (39 to 52 mM); 4 cycloheximide (0.5 mM), and 8 sucrose (1%). Plasma volume was measured with 125I-albumin (human) and extracellular volume measured with either 99mTc diethylenetriamine pentaacetic acid or [14C]sucrose. During perfusion, rabbit albumin content in the perfusate was measured immunologically every 15 to 30 min for 225 min. Interstitial albumin efflux was measured by the rate of appearance in the perfusate of 125I-albumin given to 10 other rabbits 3 days prior to hepatic removal and perfusion. During the initial 75 min of perfusion, 74% of the in vivo equilibrated exchangeable 125I-albumin appeared in the perfusate, and during this period the rabbit albumin that entered the perfusate was taken to represent efflux from the interstitial volume plus synthesis. Rabbit albumin appearing in the perfusate during the later period of 150 min was taken to represent mainly synthesis and was used to calculate the amount of albumin that would be synthesized in 75 min. The difference between these two values would be hepatic interstitial albumin appearing in the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMedDate not supplied

Serum albumin.

The liver manufactures albumin at a massive rate and decreases production in times of environmental, nutritional, toxic and trauma stress. Osmotic pressure is a basic evolutionary regulatory factor, and hormonal control over albumin production has been demonstrated. Where and why new or old albumin is degraded are questions which have not been clarified, although the vascular endothelium may well be the degradative site. Albumin is important as a transport protein, as a measure of evolution and as a model to study secretion following synthesis without the intervening steps of glycosylation. Investigations as to how this protein enters the endoplasmic membrane may well answer some of the questions concerning signal peptide insertion (288). The role of the urea cycle intermediate ornithine and its participation in polyamine synthesis, which has a positive effect on albumin synthesis, is under study. Likewise, the inverse relation between acute-phase protein synthesis and albumin synthesis regulated by interleukin 1 and other cytokines will merit further study. These are a few of the concepts which will be tested in the future.

Aging↗
PubMedDate not supplied

Prolonged feeding of ethanol to the young growing guinea pig. II. A model to study the effects of severe ischemia on cardiac protein synthesis.

Although acute perfusion of guinea pig hearts with ethanol does not affect cardiac protein synthesis, the latter is inhibited after prolonged ingestion of ethanol when tested in an in vitro system with the working right ventricle. This study reports on the added stress of ischemia on such hearts. Hearts were removed from maturing guinea pigs after 13-16 weeks of ingesting 10% ethanol and were perfused in vitro under conditions of relative ischemia (one-sixth of normal coronary flow) with maintenance of right ventricular load and outflow resistance identical to normal pre-ischemic levels. With this degree of ischemia, there was a 4-6 fold increase in lactate production, an 80% drop in ATP, and a 90% decrease in creatine phosphate after 150 min of the ischemia. Incorporation of both labeled lysine and phenylalanine into cardiac protein was also diminished to 35% of control in the left ventricle and 55% of control in the right. This diminution of protein synthesis was the same in hearts from ethanol-drinking and matched control animals. Thus, prior prolonged ingestion of ethanol did not worsen the inhibition of protein synthesis by oxygen deprivation. There were, however, two significant differences in hemodynamic response to the ischemia by the right ventricles of hearts from ethanol-drinking guinea pigs compared to their matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗