Search PubMed⌕ Search

Biomedical subjects

F L Weber

Publications and source records attributed to F L Weber.

At least 37 records · Page 2Linked to original sources

Effects of branched-chain amino acids on nitrogen metabolism in patients with cirrhosis.

This study was conducted to determine whether an amino acid solution enriched with branched-chain amino acids altered protein catabolic rates and plasma ammonia in patients with cirrhosis. Nine stable subjects were given two peripheral intravenous infusions: a standard amino acid solution (solution A) and a branched-chain-enriched solution containing 97% more leucine (solution B). Each solution was given for separate 9-day (group 1, n = 6) or 3-day (group 2, n = 3) periods. Amino acid solutions delivered 0.7 gm protein.kg-1.day-1. Diets provided an additional 0.3 gm protein plus maintenance calories. Protein turnover was assessed by a primed continuous infusion of [1-14C] leucine in six patients (three patients in group 1 and three patients in group 2). Nitrogen balance and urinary 3-methyl histidine excretion were determined in group 1 patients. Compared with solution A, solution B increased leucine flux and leucine oxidation but had no significant effect on protein synthesis or catabolism based on the plasma specific activity of either leucine or alpha-ketoisocaproic acid. The additional leucine infused with solution B was quantitatively oxidized. Nitrogen balance did not differ with the two solutions and there was also no difference in the urinary excretion of 3-methyl histidine, suggesting that muscle protein catabolism was unchanged. Plasma ammonia concentration decreased significantly during the infusion of solution B and was associated with a slight fall in plasma glucagon concentration. The results indicated that a branched-chain-enriched amino acid solution did not alter protein synthesis or catabolism although it did lower the plasma ammonia when compared with a standard amino acid formula in stable cirrhotic patients.

Amino Acids↗

Stimulation of jejunal mucosal protein synthesis by luminal glucose. Effects with luminal and vascular leucine in fed and fasted rats.

This study was conducted to determine whether short-term (1.75 h) luminal glucose perfusion increases the mucosal protein synthesis rate in rat small intestine. A luminal perfusate containing 56 mM glucose was compared with a control perfusate containing mannitol in two jejunal segments constructed in the same animal. Mucosal protein synthesis rates were determined when the tracer amino acid was administered intravenously and intraluminally. The results indicated that luminal glucose perfusion rapidly stimulated mucosal protein synthesis in the fed state by 20% and 37% with the labeled amino acid derived from the vascular and luminal compartment, respectively. A 16-h fast abolished the stimulatory effect of glucose when the labeled amino acid was given intravascularly but not intraluminally. These effects of glucose could be ascribed to a direct alteration of mucosal metabolism rather than to indirect systemic effects.

Animals↗

Ammonia production from intraluminal amino acids in canine jejunum.

Dietary protein increases the blood ammonia concentration when hepatic metabolic function is impaired, but the site of ammonia production and its specific precursors have not been clearly defined. The purpose of this study is to determine if individual luminal amino acids are metabolized to ammonia by the jejunum during the process of absorption. In anesthetized, fasted dogs, a cannula was inserted into the mesenteric vein draining a segment of the jejunum weighing approximately 18 g, and the ends of the segment were ligated to isolate its blood flow. Ammonia and amino acids were determined in luminal fluid as well as arterial and mesenteric venous blood. One of six amino acids (10 mM) was luminally perfused for a 15-min equilibration period and two 15-min collection periods, and the results were compared with control periods that preceded and followed the amino acid perfusion. Alanine, leucine, and glutamine significantly (P less than 0.01) increased ammonia release into mesenteric venous blood by 37, 42, and 106%, respectively, whereas threonine, serine, and glycine had no effect. Net jejunal uptake of glutamine from arterial blood, which accounts for ammonia release by the jejunum in the basal state, was not altered by perfusions other than with glutamine. Luminal glycine perfusion also caused an increased release of serine into mesenteric venous blood and alanine perfusion increased the release of glutamate. Glutamine perfusion caused increased release of glutamate, alanine, proline, and citrulline. These results indicate that some, but not all, luminal amino acids are partially metabolized to ammonia during the process of absorption in the small intestine.

Amino Acids↗

Nitrogen in fecal bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin.

To determine how lactulose and lactulose plus neomycin might alter nitrogen metabolism in the colon we investigated the effect of these agents on the distribution of nitrogen in the bacterial, soluble, and fiber fractions of stool. The alterations in fecal nitrogen excretion were additionally correlated with changes in total body urea synthesis and degradation rates. Six patients with stable cirrhosis received a control diet alone followed by the administration of lactulose (56 +/- 6 gm/day), and eight similar patients received lactulose alone (63 +/- 5 gm/day) followed by the addition of neomycin (4 gm/day). Their feces were partitioned into individual fractions by physical separation. Lactulose administration increased nitrogen excreted in the bacterial fraction by 165% (from 0.52 +/- 0.14 gm/day to 1.38 +/- 0.21 gm/day) and by 135% in the soluble fraction (from 0.58 +/- 0.08 gm/day to 1.36 +/- 0.23 gm/day). When lactulose was supplemented with neomycin, the nitrogen content of the bacterial fraction decreased by 28%. Lactulose caused a 23% reduction in the urea production rate that was mainly accounted for by increase in fecal nitrogen excretion. The addition of neomycin caused a further reduction in urea production that was explained by an inhibition of urea degradation. These results demonstrate that a major effect of lactulose was to augment the incorporation of nitrogen into fecal bacteria although nitrogen in the soluble fraction also increased. The additional nitrogen excreted in the fecal bacterial and soluble fractions caused a reduction in urea synthesis.

Aged↗

Selenium absorption by canine jejunum.

Deficiency of the trace element selenium causes disease in domestic animals and may also be implicated in the pathogenesis of some human illness. In this study, the triple-lumen perfusion method was used to measure the rate of absorption of trace quantities of selenium (50 micrograms/liter in a physiological electrolyte solution) from the jejunum when given as D,L-selenomethione, D,L-selenocystine, or sodium selenite to healthy dogs in vivo. Selenium absorption from the test segment (expressed as percent administered dose per centimeter +/- SEM) was 1.97 +/- 0.04 from D,L-selenomethionine, 1.15 +/- 0.06 from D,L-selenocystine, and 0.51 +/- 0.07 from sodium selenite (P less than 0.01, N = 5). In separate studies in four anesthetized dogs, the jejunum was perfused with L-[75Se] selenomethionine while concentrations of 75Se were measured in the portal venous blood; these studies established that [75Se]selenomethionine disappearing from the gut lumen corresponded quantitatively to 75Se appearing in the portal venous effluent (74 +/- 6%) and incorporated into intestinal tissue (24 +/- 5%). These results are consistent with the hypothesis that the absorption of amino acid-bound selenium is accelerated by the specific amino acid active transport mechanisms in the gut mucosa. Sodium selenite is absorbed more slowly, possibly by simple diffusion through the intestinal mucosa, than the amino acid-bound selenium compounds.

Animals↗

Effects of vegetable diets on nitrogen metabolism in cirrhotic subjects.

This study compared the effect of a vegetable diet with an animal protein diet on various aspects of nitrogen metabolism to identify what components of the vegetable diet might be causing beneficial therapeutic effects in hepatic encephalopathy. Vegetable diets contained 4.5-fold greater amounts of fiber (56 +/- 3 g/day) and reduced amounts of methionine, tyrosine, and tryptophan. In 6 stable cirrhotic subjects without encephalopathy, vegetable diets caused a significant reduction in the urea production rate from 106 +/- 5 to 89 +/- 5 mg X kg-1 X 24 h-1 of urea nitrogen. This was mainly accounted for by a fall in urinary urea output. Vegetable diets also caused a fall in total urinary nitrogen, which was accounted for by the fall in urea nitrogen, and a comparable increase in fecal nitrogen from 12 +/- 2 to 28 +/- 5 mg X kg-1 X 24 h-1. The fecal bacterial fraction contained 63% of the increase in stool nitrogen. Most plasma amino acids, including methionine, tyrosine, phenylalanine, as well as total and free tryptophan, were unchanged. The effect of vegetable diets on nitrogen metabolism can be mainly accounted for by the increased intake of dietary fiber and increased incorporation and elimination of nitrogen in fecal bacteria.

Aged↗

Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.

Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth.

Animals↗

Relationship of plasma amino acids to nitrogen balance and portal-systemic encephalopathy in alcoholic liver disease.

Plasma amino acids were compared in three groups of patients with alcoholic liver disease including stable cirrhosis, acute alcoholic hepatitis without portal-systemic encephalopathy, and cirrhosis with encephalopathy. In addition, plasma amino acids were correlated with nitrogen balance in patients with acute alcoholic hepatitis and with clinical improvement in patients with encephalopathy. Significant differences in plasma amino acids within these groups were present. Plasma amino acids did not change with improvement in portal-systemic encephalopathy, and abnormalities of plasma amino acids did not prevent maintenance or attainment of positive nitrogen balance in patients with acute alcoholic hepatitis.

Acute Disease↗

Stimulation of ammonia production from glutamine by intraluminal glucose in small intestine of dogs.

Previous studies have shown that the quantity of ammonia derived from the small intestinal metabolism of arterial glutamine was equal to ammonia released by the colon. Little is known, however, about processes that may alter small intestinal glutamine metabolism. The purpose of this study was to evaluate the effect of intraluminal, nonnitrogenous compounds on ammonia release into mesenteric venous blood and glutamine uptake from arterial blood by in situ intestinal segments in anesthetized, fasted dogs. In paired luminal perfusion studies, either 50 mM glucose, 3-O-methylglucose, or 3-hydroxybutyric acid was compared with a control perfusate containing 50 mM mannitol. In the jejunum, glucose perfusion significantly increased ammonia release into mesenteric venous blood by 21 +/- 5 nmol.min-1.g intestine-1 or 32 +/- 7% and glutamine uptake from arterial blood by 21 +/- 3 nmol.min-1.g intestine-1. Perfusion of ileum with glucose also significantly increased ammonia release by 8 +/- 1 nmol.min-1.g intestine-1 or 12 +/- 2% and glutamine uptake by 11 +/- 4 nmol.min-1.g intestine-1, although the increments were less than in the jejunum. Perfusion of the jejunum with 3-hydroxybutyric acid or nonmetabolizable 3-O-methylglucose caused no increase in ammonia release, even though glucose, 3-hydroxybutyric acid, and 3-O-methylglucose were absorbed at similar rates and there were similar increments in water absorption. The results indicated that glucose absorbed from the lumen of both the jejunum and ileum stimulated glutamine uptake from arterial blood and ammonia release into mesenteric venous blood. These effects were quantitatively greater in the jejunum. Stimulation of intestinal glutamine metabolism was probably related to cellular metabolism of glucose and could not be attributed to a stimulation of solute or water absorption.

Absorption↗

Effects of lactulose and neomycin on urea metabolism in cirrhotic subjects.

In our previous studies of cirrhotic subjects lactulose caused a 25% decrease in the urea production rate associated with a decrease in urinary urea excretion and an increase in stool nitrogen. The decrease in the rate of urea production was an indirect measure of reduction in gut ammonia production. The present study was designed to determined if the poorly adsorbed antibiotic neomycin had an additive effect in reducing ammonia production when administered in combination with lactulose. Six stable cirrhotic subjects received isonitrogenous diets during separate lactulose and lactulose + neomycin treatment periods. The addition of neomycin to a lactulose regimen caused a 17% reduction in the urea production rate that was quantitatively accounted for by a 70% reduction in the urea degradation rate. The intestinal urea clearance rate demonstrated a parallel reduction, indicating an inhibition of bacterial ureolysis. There was no evidence that neomycin altered the effects of lactulose since urinary urea excretion did not rise, fecal nitrogen remained high, and stools remained acidic. These results demonstrate that neomycin inhibited bacterial ureolysis when administered with lactulose while lactulose itself was metabolized and its individual effect on nitrogen metabolism persisted. Lactulose and neomycin, when administered together, had an additive effect in reducing gut ammonia production in cirrhotic subjects.

Aged↗

Reversible hepatotoxicity associated with hepatic vitamin A accumulation in a protein-deficient patient.

A 62-yr-old white male presented with edema, protein malnutrition, and abnormal liver function. He had ingested from 40,000-50,000 IU of vitamin A per day for 7 yr. Examination of liver tissue by light and electron microscopy revealed findings characteristic of an excessive accumulation of vitamin A. Liver tissue contained massive amounts of vitamin A (19,000 IU/g); however, both the serum concentration of vitamin A and retinol-binding protein were below normal, and serum RBP was not saturated. On a normal diet the patient was able to mobilize hepatic vitamin A, as indicated 71 days later by a repeat biopsy of the liver, which then contained 9000 IU of vitamin A/g. During this time his nutrition improved, serum vitamin A rose, and serum RBP became transiently saturated. The amount of vitamin A ingested by this patient was less than that usually producing recognizable hepatotoxicity, and he had no extra hepatic manifestations of vitamin toxicity, consistent with a low serum vitamin A concentration and a low vitamin A to retinol-binding protein ratio. At presentation he was apparently unable to normally mobilize vitamin A from his liver, which may have been due to an accompanying protein deficiency.

Biopsy↗

Effects of insulin and glucagon on the uptake of amino acids from arterial blood by canine ileum.

Insulin and glucagon have variable effects in altering arteriovenous differences for amino acids and glucose in liver and muscle. It has not been determined whether these hormones may similarly affect intestine. Acute effects of intraarterial insulin and glucagon were evaluated in in situ, luminally cleansed ileal segments in anesthetized, fasted dogs. Insulin significantly increased th ileal uptake of valine, isoleucine, leucine, tyrosine, threonine, and serine from arterial blood: uptake of these amino acids was approximately doubled 45 min after the end of the insulin infusion. Insulin had no effect on glucose uptake or release. Glucagon decreased ileal glutamate release into mesenteric venous blood 45 min after the end of infusion but the uptake or release of other amino acids and ammonia was not changed. Glucagon did increase mesenteric blood flow acutely and caused a net release of glucose into mesenteric venous blood. The results indicate that insulin and glucagon directly after metabolism of the ileum in vivo.

Amino Acids↗

Intravascular papillary endothelial hyperplasia of the orbit.

Intravascular papillary endothelial hyperplasia is a rare vascular benign tumour bearing some similarities to malignant angiosarcoma. The case reported here in a 20-year-old girl is of particular interest because the orbital tumour, despite its entirely benign nature, invaded the temporal fossa through the lateral bone of the orbit.

Adult↗

Acute lymphoblastic leukemia in an adult patient.

A case of acute lymphoblastic leukemia in an adult patient has been presented. Acute lymphoblastic leukemia is a neoplastic process in which the leukocyte precursors have been transformed and no longer respond to the forces that normally regulate their proliferation and maturation. The symptomatology, diagnostic procedures, and treatment modality have been discussed. Unfortunately, although complete remission was obtained for two years, the patient developed recurrent acute lymphoblastic leukemia and subsequently died from a massive, uncontrollable infection.

Adult↗

Comparative effects of lactulose and magnesium sulfate on urea metabolism and nitrogen excretion in cirrhotic subjects.

In previous studies with cirrhotic subjects administration of oral lactulose caused a reduction in the urea production rate associated with an increase in fecal nitrogen excretion. The change in urea production rate in response to lactulose therapy was an indirect measure of a reduction in total gut ammonia production. In this study, the effect of magnesium sulfate administration was compared with lactulose therapy in 5 cirrhotic subjects to determine whether the effects of lactulose on nitrogen metabolism might be attributed to a nonspecific, cathartic effect. Both magnesium sulfate (5-15 g/day) and lactulose (40-80 g/day) caused significant and comparable increases in stool weight, solids, and total nitrogen. Only lactulose caused a reduction in fecal pH. Magnesium sulfate had no significant effect on the urea production rate or urinary nitrogen excretion, whereas lactulose caused a 25% reduction in the urea production rate and an 18% reduction in urinary nitrogen excretion. The latter was accounted for by a fall in urinary urea. Nitrogen balance was more negative during magnesium sulfate than during control or lactulose periods since magnesium sulfate increased fecal nitrogen without altering urinary nitrogen excretion. These data demonstrated that the effects of lactulose on nitrogen excretion and urea metabolism were not duplicated by equivalent cathartic doses of magnesium sulfate.

Disaccharides↗