Acid Metabolism In Patients Research Articles

Abnormal fatty acid metabolism in patients in hopantenate therapy during clinical episodes

Calcium 4-(2,4-dihydroxy-3,3-dimethylbutyramido)butyrate hemihydrate (hopantenate), a cerebral metabolic enhancer used in Japan since 1978, is a homologue of pantothenic acid. Using mass spectrometry, we found urinary excretion of 4-hydroxydodecanedioic acid, 4-hydroxytetradecanedioic acid and a series of 2-hydroxydicarboxylic acids (C 8–C 14), in addition to a series of odd- and even-numbered dicarboxylic acids (C 5–C 12) and 3-hydroxydicarboxylic acids (C 8–C 14) in patients receiving hopantenate during episodes of Reye's-like syndrome. Our findings suggest that an acute intoxication associated with hopantenate occurs owing to pantothenic acid deficiency or the inhibition of CoA-requiring reactions during stress, i.e. infection, prolonged fasting, or malnutrition.

The Role of the Renal Dopaminergic and the Prostaglandin Systems in Renal Uric Acid Metabolism in Patients with Essential Hypertension

The present study aimed to elucidate the role of renal dopaminergic and prostaglandin (PG) systems in renal uric acid metabolism in essential hypertension. Mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), serum uric acid (SUA), urinary excretions of uric acid (UUAV) and sodium (UNaV), fractional excretions of uric acid (FEUA) and sodium (FENa), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before and after intravenous injection of a dopamine receptor antagonist, metoclopramide (MCP: 8 mg/m2.BSA), or before and after a single oral administration of prostaglandin synthesis inhibitor, indomethacin (IM: 75 mg), in 34 mild-to-moderate essential hypertensives (EHT). MCP injection or acute oral administration of IM caused significant decreases of UNaV and FENa in each group, whereas MAP, HR and SUA did not change in either group. Significant decreases in Ccr, UUAV and FEUA and increases in PRA and PAC were demonstrated by MCP injection, while no significant changes in these parameters were revealed by IM administration. There was a significant positive correlation between delta UUAV and delta Ccr or delta FEUA in both groups. In addition, a close positive correlation between delta UUAV and delta UNaV as well as between delta FEUA and delta FENa was found in the MCP group, but not in the IM group. On the other hand, no significant correlation was observed between delta UUAV and delta PRA or delta PAC in either MCP or IM administration. The decreases of UUAV and FEUA were significantly greater in MCP than in IM administration, despite similar changes in Ccr, UNaV and FENa between the two procedures. These data suggest that the endogenous renal dopaminergic system may contribute to renal uric acid metabolism, which is rather closely related to sodium handling in essential hypertension than the prostaglandin system. Furthermore, the attenuated renal dopaminergic activity may contribute to the elevation of serum uric acid level in patients with essential hypertension.

Prostaglandin and Fatty Acid Metabolism in Patients with Extrahepatic Biliary Atresia

The relationship between essential fatty acid (EFA) deficiency and disturbance of prostaglandin (PG) biosynthesis was studied in children after radical operation for extrahepatic biliary atresia (EBA). In addition, to investigate the method for treatment of postoperative EFA deficiency and disturbance of PG biosynthesis, the serum fatty acid and plasma PG levels were determined before and after supplementation of an EFA-rich powder (38 g of linoleic acid per 100 g of powder) through Suruga II enterostomy. Before administration of the EFA-rich powder, linoleic acid, arachidonic acid, PGE1, and PGF2 alpha levels were significantly lower in both good bile excretion and poor bile excretion groups than in the control group. After administration, linoleic acid and PGE1 levels significantly increased in the good bile excretion group as compared with the preadministration values. These results suggest that the supplementation of EFA-rich powder is an effective treatment for linoleic acid deficiency and disturbance of PGE1 biosynthesis in postoperative EBA patients.

Prostaglandin and Fatty Acid Metabolism in Patients with Extrahepatic Biliary Atresia

SummaryThe relationship between essential fatty acid (EFA) deficiency and disturbance of prostaglandin (PG) biosynthesis was studied in children after radical operation for extrahepatic biliary atresia (EBA). In addition, to investigate the method for treatment of postoperative EFA deficiency and disturbance of PG biosynthesis, the serum fatty acid and plasma PG levels were determined before and after supplementation of an EFA‐rich powder (38 g of linoeic acid per 100 g of powder) through Suruga II enterostomy. Before administration of the EFA‐rich powder, linoleic acid, arachidonic acid, PGE1, and PGF2α levels were significantly lower in both good bile excretion and poor bile excretion groups than in the control group. After administration, linoleic acid and PGE1 levels significantly increased in the good bile excretion group as compared with the preadministration values. These results suggest that the supplementation of EFA‐rich powder is an effective treatment for linoleic acid deficiency and disturbance of PGE1 biosynthesis in postoperative EBA patients.

Isotope labelling of lipids using the Favorsky rearrangement

The synthesis of tetradeuterated 10-methylundecanoic acid, dideuterated tetracos-2-enoic acid, (1-14C)pristanic acid and (1-14C)tetracos-2-enoic acid using the Favorsky rearrangement are described. They will be used for studies of long-chain fatty acid metabolism in patients. The positions of isotope labelling were determined by mass spectrometry.

Uric acid metabolism in patients with chronic glomerulonephritis

Serum uric acid (SUA), creatinine clearance (Ccr), urinary excretion of uric acid (UUAV) and uric acid clearance (CUA) were determined in 357 patients with IgA nephritis (IgAN) and 81 patients with membranous nephropathy (MGN) in an attempt to clarify uric acid metabolism in patients with chronic glomerulonephritis, and UUAV/Ccr and CUA/Ccr levels were measured to investigate their correlations. As a result, hyperuricemia that could hardly be explained with a decline of Ccr alone was recognized in many cases, since the patients with hyperuricemia exceeding 7.0 mg/100 ml of SUA registered even as high as 25.5% in IgAN and 33.3% in MGN, whereas those with the Ccr levels higher than 80 ml/min registered 22.3% in IgAN and 38.0% in MGN. Although the SUA level increased and the UUAV and CUA levels decreased along with a decline of Ccr in IgAN, no similar trends were recognized in MGN. When the distribution of UUAV was studied in the patients with the Ccr levels higher than 80 ml/min, the patients whose UUAV levels higher than 800 mg/24 hrs that suggested excessive uric acid production were markedly as low as 3.9% in IgAN and 3.7% in MGN. Thus, the cause of hyperuricemia could not be attributed to an amount in the uric acid production. On the other hand, the patients whose CUA levels lower than 6.0 ml/min in the distribution of CUA that suggested a decrease of uric acid excretion registered 47.4% in IgAN and 63.0% in MGN, respectively, which equally appeared to be a type of lowered excretion in a majority of patients whose hyperuricemia was recognized in IgAN and MGN. The mechanism of the lowered excretion of uric acids from the kidney despite the normal level of Ccr has yet to be clarified.

Uric acid metabolism in patients with primary hypothyroidism

Uric acid metabolism in patients with primary hypothyroidism

121 SHOULD DIETARY RESTRICTIONS ALWAYS BE PRESCRIBED IN THE TREATMENT OF GOUT?

Primary gout is commonly associated with other metabolic disorders such as obesity, arterial hypertension, hyperlipidemia and diabetes mellitus that usually require a dietary regimen. However, long-term compliance to dietary restrictions may be rejected by subjects with a chronic disease and a peculiar tendency for purine-rich food. Among 175 patients with primary gout, 133 (76%) had associated metabolic disorders: 75 were obese (43%), 63 had arterial hypertension (36%), 67 showed hypercholesterolemia or hypertriglyceridemia (38%) and 10 had diabetes mellitus (6%). Besides gout, 42 patients (24%) had no other metabolic derangements requiring dietary intervention. In these patients a purine-restricted diet (< 75 mg/24 h of purines) for 5 days diminished the serum urate concentration from a base-line value of (mean±SEM) 8.9±0.2 to 7.2±0.2 mg/dl (P< 0.001) and uric acid excretion from 792±53 to 478±29 mg/24 h (P < 0.001). The administration of allopurinol (300 mg/24 h) for 5 days, while patients were on a self-selected diet, reduced serum urate to 5.4±0.1 mg/dl (P<0.001) and uric acid excretion to 374±22 mg/24h (P<0.001). These data indicate that allopurinol normalises uric acid metabolism in patients with primary gout who had no associated metabolic disorders, despite the intake of a self-selected diet.

Hypogonadism in liver cirrhosis: Implication in altered amino acid metabolism in muscle

To investigate the relationship between hypogonadism and altered amino acid metabolism in patients with liver cirrhosis, we measured the basal levels of plasma testosterone, estradiol, and free amino acids, plus urinary 3-methylhistidine excretion, in 16 control and 19 cirrhotic patients. The concentration of plasma testosterone correlated significantly with that of plasma branched-chain amino acids, and inversely with urinary 3-methylhistidine excretion. This suggests that hypogonadism causes a disturbance in amino acid metabolism at least partly related to an augmented muscle protein turnover.

Short-term effects of an intravenous infusion of a nutrient solution containing amino acids, glucose and insulin on leucine turnover and amino acid metabolism in patients with liver failure

Tolerance to an intravenous nutrient infusion containing amino acids, glucose and insulin was assessed in 12 adult patients with clinical and biochemical evidence of liver failure. In six individuals, fasting plasma amino acid patterns and turnover rates were measured by a constant intravenous infusion of [1-14C]leucine tracer. In the remaining patients the same measurements were made after a 10 h intravenous infusion of a 'standard' commercial mixture of amino acids (3.4 g/h), dextrose (20 g/h) and insulin (1.6 units/h). On the second day, conditions were crossed over and measurements were repeated. With the exception of glycine, the infusion of the amino acid-containing solution failed to significantly increase plasma amino acid content. Plasma leucine flux measurements indicated that the explanation involved a reduction in input of amino acids derived from the breakdown of body proteins rather than an increased uptake of amino acids into protein; i.e., the rate of liberation of leucine from protein decreased by an average of 2.4 mmol/h (P less than 0.05) whilst intake only added 1.6 mmol/h. No consistent changes in encephalopathy were observed. In conclusion, the infusion of the amino acid solution together with glucose and insulin resulted in improved nutritional intake and had no deleterious short-term effects on encephalopathy. However, judging from the plasma amino acid concentrations, the composition of the commercial mixture could be improved by reducing the glycine content.

Microbial flora and bile acid metabolism in patients with an ileal reservoir.

Bacterial flora of ileum effluent and bile acid metabolism were investigated in 11 patients 11-44 months after construction of a Kock's continent ileostomy. Bacteriologic investigation showed significantly more microorganisms per millilitre (p less than 0.01) and a more colon-like flora--that is, anaerobic microorganisms (p less than 0.001)--in ileum effluent of continent ileostomy patients than in ileum effluent of patients with a conventional ileostomy. The reabsorptive capacity of the reservoir mucosa was tested by direct introduction of a radioactively labelled conjugated bile acid, 23-75Se-25-homotaurocholic acid (SeHCAT), into the ileal pouch. After 4 h, 90% of the SeHCAT activity had been reabsorbed from the reservoir. Quantitative and differential analysis of bile acids in the ileum effluent showed unconjugated and predominantly primary (88%) bile acids, suggesting a minimal influence of bacterial flora on bile acid metabolism. Moreover, total bile acid loss appeared to be within normal limits.

Effectiveness of orthotopic liver transplantation on the restoration of cholesterol metabolism in patients with end-stage liver disease

The effects of end-stage liver disease and orthotopic liver transplantation on components that modulate cholesterol esterification in plasma were assessed. In comparison with healthy controls, patients with end-stage liver disease had significantly decreased concentrations of lecithin-cholesterol acyltransferase mass, apolipoprotein A-1, total phospholipids, and both total and esterified cholesterol. Elevated phosphatidylcholine and reduced lysophosphatidylcholine fractions indicated impairment of cholesterol esterification by lecithin-cholesterol acyltransferase. Constituent fatty acids of the patients' phospholipids and cholesterol esters manifested increased saturation and a concomitant reduction of polyunsaturated fatty acids, indicative of impaired hepatic elongation and desaturation of essential fatty acids. By the third month after hepatic replacement, the plasma concentrations of total cholesterol, phospholipids, lecithin-cholesterol acyltransferase, and apolipoprotein A-1 were comparable to those of the healthy subjects. Despite the improvement in cholesterol esterification and the rapid normalization of the enzyme and cofactor involved in this process, the percentage of phosphatidylcholine remained significantly higher and the percentages of lysophosphatidylcholine and esterified cholesterol remained significantly lower than in the healthy subjects at 6 mo. Phospholipid and cholesterol ester fatty acid patterns attained normalcy by the sixth month after transplant. We conclude that hepatic transplantation effectively restores cholesterol and essential fatty acid metabolism in patients with end-stage liver disease.

Increased arachidonic acid composition of phospholipids in colonic mucosa from patients with active ulcerative colitis.

The long chain fatty acid composition of phospholipids in colonic mucosa was determined by high performance liquid chromatography in nine patients with active ulcerative colitis and eight healthy controls. The arachidonic acid composition was 12.5 +/- 1.4 mol % (mean +/- 2 SEM) in the inflamed colonic mucosa from the patients with active ulcerative colitis and 6.8 +/- 1.2 mol % in the intact mucosa from healthy controls (p less than 0.001). In the inflamed colonic mucosa, oleic acid and palmitoleic acid were concomitantly decreased (p less than 0.001 and p less than 0.02, respectively), while docosahexaenoic acid was increased (p less than 0.05). Histopathological examination showed that there was a three fold increase in the cell density of inflammatory infiltrate in the lamina propria of the inflamed colonic mucosa (p less than 0.001). The cell density of inflammatory infiltrate correlated with the arachidonic acid composition of phospholipids in colonic mucosa (r = 0.89, p less than 0.005). These findings indicate that inflammation alters the long chain fatty acid composition of phospholipids in colonic mucosa. The observed increase in the arachidonic acid composition of phospholipids in inflamed colonic mucosa may contribute to the enhanced arachidonic acid metabolism in patients with active ulcerative colitis.

Uric acid metabolism in patients with chronic renal failure under maintenance hemodialysis

Uric acid metabolism in patients with chronic renal failure under maintenance hemodialysis

本態性高血圧患者における徐効性Ｎｉｆｅｄｉｐｉｎｅ錠長期投与時の尿酸代謝の変動

本態性高血圧患者における徐効性Ｎｉｆｅｄｉｐｉｎｅ錠長期投与時の尿酸代謝の変動

Effects of treadmill and pacing stress testing on peripheral arterial thromboxane, platelet function and catecholamine activities in patients with chronic coronary artery disease.

Two different methods of causing myocardial oxygen demand and supply imbalance; symptom limited treadmill exercise and right atrial pacing stimulation, were used to examine the alteration of hemodynamics and the effects upon sympathetic nerve activities, platelet functions and prostaglandin synthesis in patients with coronary artery disease (CAD). Age and sex distributions, the cardiothoracic ratio, left ventricular end-diastolic pressure, ejection fraction and coronary artery obstructions of the patients did not differ significantly between the two tests. Arterial blood samples were obtained to assay for plasma catecholamine, beta-thromboglobulin (beta TG), platelet factor 4 (PF4), TXB2 (thromboxane B2) and 6 keto-PGF1-alpha (6 ketoprostaglandin F1-alpha) without any difficulties before and immediately after testing. The arterial systolic pressure and pressure rate product (PRP) were changed more significantly by treadmill exercise than pacing, while the DPTI/TTI (diastolic pressure time index/tension time index) ratio and ST segment deviations showed similar changes with both tests. The plasma NE (norepinephrine) level, beta TG, PF4, and TXB2/6 keto-PGF1-alpha were significantly elevated by treadmill exercise, but not by pacing. 6 keto-PGF1-alpha was not markedly affected by either tests. There were no significant differences between the patients with and without anginal pain either in hemodynamics or metabolites. Significant relationships were observed between changes in plasma NE levels and the PRP (r = 0.76, n = 26, p less than 0.01) and also changes in the arterial systolic pressure (r = 0.64, n = 26, p less than 0.01), but there were no significant correlations between any other hemodynamic parameters with plasma NE, platelet function, prostaglandin activity, or between each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile acid metabolism in patients with Crohn's disease in terminal ileum.

Bile acid metabolism was studied by means of the fractional turnover rate or orally ingested 14C-labeled taurocholic acid and by gas chromatographic determination of fecal excretion of the bile acids cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA). Thirty patients with Crohn's disease (CD) of the small bowel, of whom 19 had been operated on with limited ileal resections, were studied and compared with 11 healthy volunteers. The unoperated group of CD patients did not show significant increase in bile acid excretion in the stools in contrast to the CD patients with ileal resection. The fecal excretion consisted mostly of primary bile acids, and a significant correlation between length of resection and bile acid excretion was found (rs = 0.81, p less than 0.01). The fractional turnover rate of CA + DCA was significantly increased in both unoperated (0.21 l/day) and operated (0.44 l/day) patients compared with normal controls (0.06 l/day). The bile acid pool of CA + DCA, however, was normal in patients with ileal resections, indicating a compensatory increase in bile acid synthesis. In unoperated patients the bile acid pool of CA + DCA was slightly decreased (3.1 mmol) compared with operated patients (6.2 mmol) and normal controls (4.8 mmol). The pool size was not significantly correlated to mean transit time of dietary residue, feces excretion, loss of weight, or amount of fat in feces. The mean transit time of dietary residue was decreased in both operated and unoperated CD patients.

Amino acid metabolism in patients with chronic renal failure

Amino acid metabolism in patients with chronic renal failure

Bile acid metabolism in patients with non-strangulated intestinal obstruction.

The intraluminal changes of bile acids were studied in 42 patients with intestinal obstruction, treated from 1978-1982. Twenty-two patients received surgical treatment and twenty were treated conservatively. Bile acid analysis of the intestinal contents was performed by thin-layer and gas-liquid chromatography. A marked reduction of bile acid concentration was observed before treatment. A decreased percentage of deoxycholic acid, a lowered G : T ratio, and presence of deconjugated bile acids were also present. After relief and/or removal of the obstruction, the concentration of bile acids, the percentage of deoxycholic acid, and the G : T ratio increased. Bile acid deconjugation decreased immediately after surgical treatment but was not affected by conservative treatment. We conclude that bile acid metabolism is altered quantitatively and qualitatively in patients with an intestinal obstruction.

Comparison of animal and vegetable protein sources in the dietary management of hepatic encephalopathy

Theoretical considerations based on amino acid metabolism in patients with hepatic encephalopathy as well as some limited patient studies had led to the proposal that dietary protein derived from a vegetable source may be better tolerated and more efficacious in such patients. However, studies in normal humans have revealed that vegetable protein is not as nitrogen sparing as animal protein. This prompted us to study under metabolic ward conditions the effects of vegetable and animal protein sources in patients with hepatic encephalopathy with respect to mental status, nitrogen balance, and plasma amino acids. No significant differences regarding any of the parameters studied was observed in relationship to the source of dietary protein, but compliance to the regimen was more difficult with the vegetable protein diet.