Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chronically uremic rat has been used as a model to study amino acid metabolism in uremia. Uremic rats fed low protein diets (6% casein) survived longer than uremic rats receiving either higher levels of dietary protein or a low protein diet supplemented with a mixture of nonessential amino acids. Alterations in plasma amino acid levels were observed in the uremic rats and were similar to those found in patients with renal failure. Plasma concentrations of citrulline, free tryptophan, glycine and the methylhistidines were increased and levels of serine, ornithine, lysine, total tryptophan, tyrosine, and the tyrosine-phenylalanine ratio were reduced. The metabolic basis of the altered tyrosine-phenylalanine ratio in plasma was studied. Tyrosine aminotransferase (TAT) and phenylalanine hydroxylase (PHL) activity were normal in the liver, but renal PHL activity of was decreased as compared to control rats. Tissue concentrations of citrulline were also found to be raised in liver and muscle of uremic rats. The activity of ornithine transcarbamoylase, was reduced in the liver and arginine synthetase activity was decreased in the kidneys of uremic rats. Thus elevated citrulline levels in uremic tissue appear to be caused by a decrease conversion of citrulline to arginine in the kidney. Preliminary studies of tryptophan metabolism in uremic rats have shown elevated brain levels of 5-hydroxyindoleacetic acid and increased hepatic tryptophan oxygenase activity. Increased plasma amine levels were associated with altered activities of monoamine oxidase and diamine oxidase in kidney and other tissues.
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PMID:Amino acid metabolism in the chronically uremic rat. 23 43

The effectiveness of intravenous administration (i.v.) of L-tryptophan, which is the precursor of cerebral serotonin, was verified in the treatment of postoperative pain. The study was carried out on 45 female patients, aged between 34 and 61 years, undergoing cholecystectomy who were randomly divided into three groups. Group 1 (age: 50.33 +/- 8.64 years) received 100 ml of 5% mannitol solution i.v.; group 2 (age: 49.80 +/- 11.11 years) 100 ml of a mannitol solution containing 7.5 mg/kg L-tryptophan; and group 3 (age: 53.46 +/- 9.60 years) 100 ml of a mannitol solution containing 15 mg/kg L-tryptophan. Vital capacity (preoperative VC) was measured before surgery. Anesthesia used was isoflurane. Narcotics or neuroleptics were not used. Pain was assessed before treatment (T-0 min), at the end of administration (T-30) and at T-60, 120, 180, 240, 300 and 360 min by the following variables: respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), Scott-Huskisson test (VAS), pain vital capacity (PVC), analgesic vital capacity (AVC), and respiratory restoration factor (RRF) calculated from Bromage's formula (RRF = (AVC - PVC/preoperative VC - PVC) X 100). As regards variables RR, HR, MAP and VAS, differences between the values from T-30 to T-360 and the value at T-0 were calculated. Means and S.E.M. were calculated on the obtained values and on RRF values for each group. The significance of the differences between groups was calculated using Student's t test and Bonferroni's test. Results show a significant decrease of pain in groups 2 and 3 treated with L-tryptophan, in comparison with group 1 (controls). No significant difference was observed between the treated groups, although more lasting pain relief was observed in group 3 in comparison with group 2. Intravenous L-tryptophan showed its effectiveness in the treatment of postoperative pain even when used alone. Its use may be considered for patients with renal failure, in order to strengthen pharmacological analgesia or to prevent postoperative pain by its intraoperative administration.
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PMID:Postoperative pain treated by intravenous L-tryptophan: a double-blind study versus placebo in cholecystectomized patients. 176 11

The effect of chronic renal failure (CRF) on the pattern of plasma free amino acid concentrations was studied in 22 healthy controls (group 1); 43 CRF patients of which serum creatinine levels were 2-4.9 mg/dl (group 2, n = 11), 5-10 mg/dl (group 3, n = 10), more than 10 mg/dl (group 4, n = 9), and chronically hemodialysed patients (group 5, n = 13). In all renal failure groups, plasma concentrations of eight free essential amino acids-isoleucine, leucine, lysine, methionine, threonine, tryptophan, tyrosine and valine and those of three non-essential amino acids-alanine, glutamate and serine were significantly lower than those in controls. Plasma concentrations of free arginine, cystine, glutamate and serine were significantly higher in CRF patients. Patterns of change of plasma aminogram were similar among CRF patients regardless of the stages of renal function or dialytic treatment. Stepwise changes of some plasma free amino acids were observed as renal function became worse. The molar ratios of plasma free valine/glycine, serine/glycine and tyrosine/phenylalanine were decreased accordingly. Our study confirms the presence of abnormal plasma aminogram, specifically that of essential amino acids, in CRF. Therapeutic intervention is warranted but still needs further investigations.
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PMID:Plasma amino acid patterns in normal Thais and in patients with chronic renal failure. 194 Jul 7

We describe a rat model of renal failure that separates catabolic and anabolic states from each other. Muscle protein synthesis was compared during the anabolic period between sham (S) operated and renal failure (RF) rats that were fed different levels of dietary protein. Male rats weighing between 60 and 80 g first had a partial left nephrectomy and then were given a tryptophan deficient diet from four to six days to induce weight loss. On the second day of the diet either a renal decapsulation (S rats) or a simple right nephrectomy (RF rats) was done to enhance the catabolic response in both and to induce renal failure in the RF rats. Following the period of feeding the deficient diet, both groups were fed a nutritionally complete 14, 17, 20 or 30% protein diet for three to five days. This induced a brisk anabolic response as measured by weight gain. Differences in body weight between the S and RF rats after three to five days on the repletion diet generally was less than 10%. The rats then were fasted overnight, fed a standard meal and muscle protein synthesis (Sm%) was measured two hours post-feeding. Sm% was estimated from the incorporation of 3H phenylalanine (PHE) into muscle 10 minutes following the i.v. injection of 3HPHE (25 muCi/100 g body wt) with carrier PHE to flood all the precursor amino acid pools. Weight loss in the catabolic phase was greater and the net weight gain for the two phases was less in the RF group. Overall, renal failure resulted in a significant reduction in Sm% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of reduced renal function and dietary protein on muscle protein synthesis. 206

Horses suffering from trauma, sepsis, and severe burns need 12% to 16% of protein (dry matter basis) in their diet. Since reduced appetite may be a problem, relatively energy dense (greater than 2 Mcal DE/kg) feeds should be offered. In hepatic failure, maintenance protein requirements (8% on a dry matter basis for adult horses) should be met with feeds that are high in short branched-chain amino acids and arginine but low in aromatic amino acids and tryptophan (for example, milo, corn, soybean, or linseed meal) in addition to grass hay. Vitamins A, C, and E should also be supplemented. In cases with renal failure, protein, calcium, and phosphorus should be restricted to maintenance or lower levels. Grass hay and corn are the best feeds for horses with reduced renal function. Do not offer free-choice salt to horses with dependent edema from uncompensated chronic heart failure. Following gastrointestinal resection, legume hay and grain mixtures are the feeds of choice. Horses with diarrhea should not be deprived or oral or enteral alimentation for prolonged periods of time. Liquid formulas may be used if bulk or gastrointestinal motility are a problem. Apple cider vinegar and a high grain diet may reduce the incidence of enteroliths in horses prone to this problem. Pelleted feeds will reduce fecal volume and produce softer feces for horses that have had rectovaginal lacerations or surgery. Horses with small intestinal dysfunction or resection should be offered low residue diets initially, but long-term maintenance requires diets that promote large intestinal digestion (alfalfa hay, vegetable oil, restricted grain). Geriatric horses (greater than 20 years old need diets similar to those recommended for horses 6 to 18 months old.
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PMID:Clinical nutrition of adult horses. 220 96

Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading.
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PMID:Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. 221 43

The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable.
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PMID:Renal epithelial amino acid concentrations in mercury-induced and postischemic acute renal failure. 221 14

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A "New Formula" has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap
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PMID:Amino acid metabolism in uremia. 267 58

Decreased binding of aromatic acidic drugs and endogenous metabolites to plasma proteins of patients with severe renal failure appears to be due to accumulation of unknown solutes. Both the warfarin and indole binding sites of albumin, the principal binding protein for these ligands, are affected. We used a large number of endogenous aromatic acids and synthetic congeners as displacers (a) better to characterize the chemical requirements for binding to each site and (b) to derive clues to the chemical structure of the undefined binding inhibitors in uremic plasma. 14C-tryptophan, 14C-warfarin and 14C-salicylate were used as bound ligands. Numerous indoles, quinolines and phenyl derivatives were moderate to strong displacers with several structural correlates. Increasing apolar side chain length enhanced displacing potency. A hydroxyl group at the 5 position of indoles and at the para position of phenyl derivatives severely reduced activity. The two ends of amphophilic molecules showed opposite requirements for displacement of tryptophan: the greater the polarity at the hydrophilic end, the greater the tryptophan displacing potency. Conversely, the greater the total hydrophobic mass of the remainder of the molecule, the more potent the inhibition of binding. The dipeptides l-tryptophyl-l-tryptophan and l-tryptophyl-l-phenylalanine were potent displacers. Computer-assisted analysis of warfarin binding in the presence of xanthurenic acid revealed inhibition by a mechanism other than simple competition, probably via a third albumin binding locus. We conclude that decreased binding in uremic plasma is most likely the summation effect of a number of retained aromatic acids, peptides, or both types of ligands.
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PMID:Aromatic amino acid metabolites as potential protein binding inhibitors in human uremic plasma. 401 86

Surgical reduction of renal mass in the rat leads to proteinuria, hypertension, and progressive renal failure beyond that of the original physical destruction of renal mass. Both hypertension and proteinuria have been implicated in the process of progression of renal failure. The seven/eighths nephrectomized rats fed a diet supplemented with 4% tryptophan (UT) had a urinary albumin excretion rate of 0.055 +/- 0.056 mg/100 g body weight/hr compared to 0.02 +/- 0.029 mg/100 g body weight/hr in control rats, whereas the nephrectomized rats fed a regular diet (UR) excreted 1.12 +/- 0.730 mg/100 g body weight/hr (P less than 0.001). Hypertension was also prevented in the UT group but not in the UR group. Once hypertension and proteinuria were established during maintenance on a regular diet, they were not reversed by subsequent dietary tryptophan supplementation. If dietary tryptophan supplementation is continued, however, the progressive histopathology that develops after seven-eighths nephrectomy is not prevented despite avoidance of proteinuria and hypertension.
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PMID:Dietary tryptophan supplementation prevents proteinuria in the seven-eighths nephrectomized rat. 684 66


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