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Biomedical subjects

L Berger

Publications and source records attributed to L Berger.

At least 109 records · Page 6Linked to original sources

Metabolism of carprofen, a nonsteroid anti-inflammatory agent, in rats, dogs, and humans.

The metabolic disposition of 14C-labeled carprofen [(+/-)-6-chloro-alpha-methylcarbazole-2-acetic acid] was investigated in rats, dogs, and humans. Carprofen is eliminated predominantly by biotransformation in these three species. In dogs and rats, the direct conjugation of carprofen to form an ester glucuronide and oxidation to the C-7 and the C-8 phenols followed by their conjugation represent the major metabolic pathways. Small amounts of the alpha-hydroxy derivative also are formed by these species and are excreted free in the urine. In dogs, biliary secretion predominates, and 70% of an intravenous dose of carprofen is excreted in the feces while 8--15% of the dose is excreted in the urine. In rats, fecal excretion due to biliary secretion varies from 60 to 75%, and urinary excretion accounts for 20--30% of an intravenous dose. In humans direct conjugation of carprofen represents the only significant pathway of metabolism. Between 65 and 70% of the orally administered carprofen was found to be excreted as the ester glucuronide in the urine, and most of the remaining dose was estimated to be secreted as this metabolite in the bile. Due to enterohepatic circulation, only a fraction of the biliary metabolite was recovered in the feces in humans. Less than 5% of the dose was excreted in human urine as free, intact carprofen. In dogs and humans, plasma levels of carprofen and of total radioactivity exhibit a multiphasic decline. In the three human subjects studied, the terminal component declined with a 13--26 hr half-life; the terminal half-life was approximately 40 hr in dogs.

Adult↗

Renal function in gout. V. Factors influencing the renal hemodynamics.

Renal hemodynamics as measured by inulin clearance (Cinulin) and para-aminohippurate clearance (CPAH) was evaluated in 149 patients with primary gout over intervals of two to 22 years. In over 30 per cent of the patients plasma urate was greater than 10 mg/dl and urinary uric acid greater than 800 mg/min. A linear trend in decreasing frequency of hyperuricemia and excessive uricosuria is significantly related to the patient's age at the onset of gout. Group I consisted of 84 patients with uncomplicated gout in both clearance studies. Cinulin and CPAH were somewhat lower in patients larger than or equal to 50 years of age with longer duration of gout. Further reduction in clearances was minimal at the second clearance study in intervals of approximately 10 years. Group II included 27 patients who had no associated disease at the time of the first clearance study but in whom associated disease had developed by the time of the second clearance study. A striking reduction in Cinulin and CPAH was noted, especially in those 50 years old or above. There were 38 patients in group III with associated diseases at the time of both clearance studies. They had lower Cinulin and CPAH at the time of the first study, particularly the older patients. Further reduction during the second study was less striking than that in group II. Analyses of variance suggest that various coexisting vascular diseases with associated nephropathy have the most significant impact on the status of renal function in gout, with aging the second most important and duration of gout, the third.

Adult↗

Performance of animals fed crop residues.

Ruminants can utilize crop residues as sources of energy, but productivity is low because of the high level of cell walls and lignin. Chemicals, especially sodium hydroxide, have been used to increase the digestibility of crop residues. Hemicellulose is solubilized and the extent and rate of cellulose and hemicellulose digestion are increased. Two systems have been developed for chemical treatment. The first involves pelleting finely ground residue in combination with sodium hydroxide treatment. A dense, easily transported feed-stuff is produced. The second method is an "on-the-farm" method that utilizes a minimum amount of equipment. In vitro and in vivo digestibilities have been increased from 10 to 20 percentage units by sodium hydroxide treatment. While lamb and cattle gains have generally been increased by feeding chemically treated residues, the level of performance often has not been as great as would be predicted from in vitro digestibilities. Sodium residues following chemical treatment have been shown to increase rate of passage from the rumen and reduce rumen fiber digestion. The use of alfalfa with sodium hydroxide-treated residues and the use of ammonium or calcium hydroxides for treatment have good potential.

Ammonia↗

Comparative study of DNA methylation in three unicellular eucaryotes.

We have analyzed the nature/content of methylated bases in the nuclear DNA of three unicellular eucaryotes. The pattern of methylation was different for each of the three organisms studied: Saccharomyces cerevisiae contained only 5-methylcytosine; Tetrahymena pyriformis contained only N6-methyladenine; and Chlamydomonas reinhardi contained both modified bases.

Adenine↗

The effect of the interaction of pyrazinamide and probenecid on urinary uric acid excretion in man.

Complex interactions occur between pyrazinamide (PZA) and probenecid in man involving both the metabolism and distribution of the drugs, and their effects on renal tubules. Pretreatment with PZA prolonged the half-life (T 1/2) of probenecid without changing its plasma-binding. As the rate of probenecid metabolism is decreased, its uricosuric action tends to be prolonged and the effect of PZA lessened. The PZA-suppressible urate level is increased to values well above control after the administration of probenecid; it is less after alkalinization of urine, although still larger than the value for PZA-suppressible urate after the administration of PZA alone. Urinary probenecid excretion is much greater when urine is alkalinized. These observed drug interactions, plus the known effect of probenecid to block secretion of PZA, have to be considered in evaluating the effect of the two drugs given together, compared to the effect of each drug given separately.

Adult↗

The effect of ascorbic acid on uric acid excretion with a commentary on the renal handling of ascorbic acid.

Under spontaneous conditions in man and dog, very little ascorbic acid is excreted in urine. Ascorbic acid clearance (C ascorbic acid) is promptly augmented when plasma ascorbic acid is increased by intravenous injection. No net tubular secretion of ascorbic acid is demonstrable in either man or dog when plasma ascorbic acid is elevated to levels as high as 12 mg/100 ml in man, and 28 mg/100 ml in the dog. Nevertheless, both in men and the Dalmatian dog, when the glomerular filtration rate (GFR) is decreased, excreted ascorbic acid in relation to the amount filtered is exaggerated so that C ascorbic acid:GFR approaches unity. It is possible that secreted ascorbic acid is masked under ordinary circumstances, with a more significant contribution of secreted ascorbic acid to total urinary ascorbic acid becoming apparent under conditions of low GFR. In man, when the plasma ascorbic acid level is raised to above 6 mg/100 ml, C urate:GFR rises from control value of 0.081 +/- 0.020, to 0.116 +/- 0.026. In both mongrel and Dalmatian dogs an effect of ascorbic acid on urate excretion is not conclusively shown. The uricosuric effect of ascorbic acid in man may be due to competition with uric acid for renal tubular reabsorptive transport. The difference in the metabolism of ascorbic acid in the dog as compared to man may help account for the inconsistent effect of ascorbic acid on uric acid excretion in the dog.

Aged↗

In vivo methylation by Escherichia coli K-12 mec+ deoxyribonucleic acid-cytosine methylase protects against in vitro cleavage by the RII restriction endonuclease (R. Eco RII).

We have analyzed the susceptibility of the deoxyribonucleic acid (DNA) of phage fd replicative form (RF) and of Escherichia coli to in vitro cleavage by purified RII restriction endonuclease (R. Eco RII). The results are summarized as follows: (i) fd, mec- RFI, isolated from infected E. coli K-12 mec- bacteria (a mutant strain lacking DNA-cytosine methylase activity), is cleaved into at least two fragments, whereas fd. mec+ RFI, isolated from the parental mec+ strain, is not cleaved. (ii) E. coli mec- DNA is extensively degraded, whereas mec+ DNA-cytosine methylase acts as an RII modification enzyme.

Coliphages↗

Renal function in gout. IV. An analysis of 524 gouty subjects including long-term follow-up studies.

Renal function studies were performed in 524 gouty subjects, including follow-up studies at intervals up to 12 years in 112 of them. In 49 subjects, the glomerular filtration rate was less than 70 ml/min and Curate:glomerular filtration rate ratio tended to rise as the glomerular filtration rate decreased, reflecting a relatively stable urate excretion over varying filtered urate loads. The increment in Tsurate:glomerular filtration rate was small with spontaneous Purate between 7 and 9 mg/100 ml. It was modest with Purate up to 10 mg/100 ml. The increment in Tsurate:glomerular filtration rate became much higher beyond Purate of 10 mg/100 ml. Urinary urate levels above 800 mug/min, designated as excess urate excretion, occurred more commonly in subjects with Purate above 9 mg/100 ml, and with better preserved renal function. Tophi were more frequently observed in subjects with low glomerular filtration rate and proteinuria; but incidence of urolithiasis seemed to be less affected by a decrease in the glomerular filtration rate. Hyperuricemia alone had no deleterious effect on renal function as evidenced by follow-up studies over periods up to 12 years. Deterioration of renal function was largely associated with aging, renal vascular disease, renal calculi with pyelonephritis or independently occurring nephropathy. In only very few instances was diminished renal function ascribable to gout alone.

Adult↗