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Biomedical subjects

C H Dejong

Publications and source records attributed to C H Dejong.

At least 19 recordsLinked to original sources

Intestinal function and metabolism in the early adaptive phase after massive small bowel resection in the rat.

PURPOSE: The aim of this study was to investigate the early adaptive responses in metabolism and gut function after massive small bowel resection. METHODS: Male Wistar rats underwent an 80% small bowel resection (Ent group, n = 9) or a transection and reanastomozing (Sham group, n = 7). After 24 hours, substrate fluxes across the gut were determined together with intestinal protein synthesis, polyamine concentrations in gut tissue, and gut function by testing intestinal permeability using the urinary recovery of lactulose and rhamnose. To test for the effect of starvation, healthy starved rats were studied. RESULTS: In the Ent group, intestinal uptake of glucose, lactate, glutamine, phenylalanine, branched chain amino acids, and total amino acids were equal to or higher than that in Sham rats. Intestinal protein synthesis increased, accompanied by an increase in spermidine to spermine polyamine ratios in the ileum and in the jejunal muscular layer. The urinary lactulose to rhamnose ratio also increased, suggesting increased intestinal permeability. CONCLUSIONS: 24 hours after massive small bowel resection, adaptive responses in metabolism and gut function already can be observed, as indicated by increased intestinal uptake of substrates and increased protein synthesis. This, however, is accompanied by an increase in intestinal permeability, which may indicate impaired intestinal barrier function. J Pediatr Surg 36:1746-1751.

Adaptation, Physiological↗

Virtual hepatic resection using three-dimensional reconstruction of helical computed tomography angioportograms.

OBJECTIVE: To establish the accuracy of virtual hepatic resection using three-dimensional (3D) models constructed from computed tomography angioportography (CTAP) images in determining the liver volume (LV) resected during resectional liver surgery. SUMMARY BACKGROUND DATA: The ability to measure LV before surgery could be useful in determining the extent and nature of hepatic resection. Accurate assessment of LV and an estimate of liver function may also allow prediction of postoperative liver failure in patients undergoing resection, assist in volume-enhancing embolization procedures, help with the planning of staged hepatic resection for bilobar disease, and aid in selection of living-related liver donors. METHODS: A retrospective study was conducted involving 27 patients scheduled for liver resection. Using mapping technology, 3D models were constructed from helical CTAP images. From these 3D models, tumor volume, total LV, and functional LV were calculated and were compared with body weight. The 3D liver models were subjected to a virtual hepatectomy along established anatomical planes, and the resected LV was calculated. The resected volume predicted by radiologists (unaware of the actual weight) was compared with the specimen weight measured after actual surgical resection. RESULTS: A significant correlation was found between body weight and functional LV but not total LV. The computer prediction of resected LV after virtual hepatectomy of 3D models compared well with resected liver weight. CONCLUSION: Virtual hepatectomy of 3D CTAP reconstructed images provides an accurate prediction of liver mass removed during subsequent hepatic resection. The authors intend to combine this technology with an assessment of liver function to attempt to predict patients at risk for liver failure after hepatic resection.

Adult↗

Nutrition in patients with acute pancreatitis.

Acute pancreatitis is a disease with varying severity. Patients with the mild form do not require nutritional support because oral intake is resumed rapidly. Studies on nutritional support in acute pancreatitis have included patients with both mild and severe disease. In this heterogeneous group, total parenteral nutrition did not improve outcome compared with no nutrition at all. This is caused in part by an increase in septic complications during total parenteral nutrition. Likewise, no benefit from enteral nutrition was observed compared with no nutrition, probably because the group was heterogeneous or because nutritional goals were not achieved. Patients with severe acute pancreatitis become profoundly catabolic. This group undoubtedly requires nutritional support to treat undernutrition. The limited available data indicate that enteral nutrition, if well tolerated, is superior to parenteral nutrition for patients with severe acute pancreatitis. Based on current knowledge, a combination of early total parenteral nutrition and enteral nutrition is advisable as soon as enteral nutrition is tolerated. Monitoring of gut function is crucial in this situation.

Acute Disease↗

Renal amino acid metabolism during endotoxemia in the rat.

BACKGROUND: The kidney has an important function in the exchange of nitrogenous metabolites. Glutamine is the most important substrate for renal ammoniagenesis and thus plays a crucial role in acid-base homeostasis. Furthermore, the kidney is the main endogenous source for de novo arginine production from citrulline, which in turn is derived from intestinal glutamine metabolism. Sepsis is a condition in which glutamine availability is reduced, whereas the need for arginine biosynthesis may be increased. Limited bioavailability of glutamine may affect arginine synthesis, which may have consequences for nitric oxide (NO) synthesis. Therefore, we studied renal glutamine and arginine metabolism in a rat model of endotoxemia and related this to NO metabolism. MATERIALS AND METHODS: Rats were subject to double hit endotoxemia, and control rats received 0.9% NaCl. Renal blood flow was measured using para-aminohippuric acid. Concentrations of plasma amino acids and nitrate were measured in the aorta and renal vein to calculate net renal uptake or release of amino acids and address NO production. RESULTS: The arterial concentrations of glutamine and ammonia were not changed in endotoxemic rats. Although renal glutamine uptake was reduced, total renal ammonia production was not changed during endotoxemia. The arterial concentration of citrulline and renal citrulline uptake was not altered in endotoxin-treated rats, but renal arginine production was increased. However, no effect was observed on nitric oxide production. CONCLUSIONS: Although the kidney has very important functions in the excretion of waste products and in interorgan metabolism, this study suggests that the kidney has a limited role in glutamine, arginine, and NO metabolism during late endotoxemia in rats.

Amino Acids↗

Splenic abscess after appendicitis.

We report an appendicitis complicated by a splenic abscess in a patient with polycystic kidneys and multiple cystic lesions in the liver. Clinical decision making for operative intervention was made difficult by the extensive intra-abdominal abnormalities seen on computer tomography. Finally curation was achieved by splenectomy and appendectomy.

Abdominal Abscess↗

Effects of parenteral arginine supplementation on the intestinal adaptive response after massive small bowel resection in the rat.

BACKGROUND: Arginine (ARG) and its metabolic products (polyamines and nitric oxide) are known to affect gut function and protein synthesis in various tissues. The aim was to study the effect of parenteral ARG supplementation on intestinal adaptation and intestinal function in rats after massive small bowel resection (SBR). METHODS: Fasted rats (275 g) were studied 24 h after 80% SBR. At t = 6 h, t = 12 h, and t = 18 h after SBR, a 300 mM ARG solution (ARG, n = 9), 5 ml/100 g body weight, was given subcutaneously. Controls received iso-osmolaric amounts of NaCl (NaCl, n = 9) or alanine (ALA, n = 8). Twenty-four hours after operation substrate fluxes across the gut were determined together with intestinal protein synthesis, polyamine concentrations in gut tissue, and gut function by testing intestinal permeability using the urinary recovery of lactulose and rhamnose. RESULTS: Intestinal fluxes did not differ among groups, except for an increased production of ornithine and a decreased uptake of glutamine after ARG supplementation. Also, intracellular arginine and ornithine concentrations were higher in the jejunum, accompanied by lower concentrations of other amino acids. Intracellular putrescine and gamma-aminobutyric acid, a breakdown product of putrescine, were higher. However, spermidine and spermine were not. Protein synthesis was lower in the ARG group, while intestinal permeability decreased. CONCLUSIONS: Parenteral arginine supplementation in rats with massive SBR leads to a slowing of intestinal adaptation, indicated by reduced glutamine uptake and protein synthesis. The exact mechanism of this inhibitory effect remains to be elucidated. Intestinal permeability, however, benefits from arginine supplementation, possibly related to better enterocyte differentiation.

Adaptation, Physiological↗

Enhanced renal vein ammonia efflux after a protein meal in the pig.

BACKGROUND/AIMS: The intake of dietary protein has been associated with increased arterial ammonia levels. However, the origin of this rise in ammonia levels is unknown. This study was designed to examine whether this increase is caused by ammonia formed by the gut escaping hepatic clearance, or ammonia formed by the kidney and subsequently released into the circulation. METHODS: Splanchnic and renal fluxes of ammonia and amino acids were studied in 10 pigs that were fed in a randomized cross-over design with a protein meal (n = 8), a meal with an equimolar amount of free amino acids (n = 8) or an iso-osmolar NaCl solution (n = 6). RESULTS: After the protein meal, and less pronounced after the amino acid meal, arterial ammonia levels increased from approximately 25 to 75 micromol/l. Arterial pH changes and splanchnic ammonia release were negligible. The renal vein ammonia efflux increased after the protein meal (0.67+/-0.10 to 1.94+/-0.35 micromol/kg bw/min) and to a lesser degree after the amino acid meal (to 1.20+/-0.39 micromol/kg bw/ min). Renal uptake of alanine, and not glutamine, increased stoichiometrically, paralleling the enhanced renal vein ammonia efflux. CONCLUSIONS: Arterial ammonia increases after a meal in pigs, coinciding with a negligible splanchnic ammonia release, but increased renal vein ammonia efflux. Thus, post-prandial plasma ammonia levels appear to be mainly related to renal ammoniagenesis. Alanine appears to be the main precursor for this renal ammoniagenesis in the pig.

Ammonia↗

Upper gastrointestinal bleeding: an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule.

Upper gastrointestinal bleeding causes increased urea concentrations in patients with normal liver function and high ammonia concentrations in patients with impaired liver function. This ammoniagenesis may precipitate encephalopathy. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and has high amounts of leucine and valine. Upper gastrointestinal bleeding therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce a cascade of events culminating in net catabolism. This may influence the function of rapidly dividing cells and short half-life proteins. We hypothesize that, following a variceal bleed in a cirrhotic patient, the lack of isoleucine in blood protein is the cause of the exaggerated ammoniagenesis and catabolism. We propose that intravenous administration of isoleucine may serve as a simple therapeutic that transforms blood protein in a balanced protein, resulting in only a short-lived rise in ammonia and urea production, and preventing interference with protein synthesis.

Ammonia↗

[Uremia after hemorrhages in the upper digestive tract].

Haemorrhages in the upper GI tract may lead to severe uraemia and, in patients with liver failure, to hyperammonaemia. The cause of this is not yet sufficiently clear. Recently we observed a decrease in arterial isoleucine levels after intragastric blood administration in pigs. This contrasted with elevated levels of most other amino acids, ammonia and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relationship between the arterial isoleucine decrease and uraemia after gastrointestinal (GI) haemorrhage. Analysis of blood protein showed a complete absence of the essential amino acid isoleucine, making it a protein of low biological value. In additional porcine experiments, uraemia after intragastric blood administration could be prevented by simultaneous intravenous isoleucine administration. This led to the hypothesis that there was a causal relationship between the absence of isoleucine in blood protein and the uraemia and hyperammonaemia observed after GI bleeding. Similar results were seen in patients with intact and with impaired liver functions. These results support the hypothesis that the absence of isoleucine in blood protein causes decreased plasma and tissue isoleucine levels after GI haemorrhage. This might inhibit protein synthesis, and may contribute to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after GI haemorrhage could be beneficial.

Ammonia↗

Renal arginine metabolism in fasted rats with subacute short bowel syndrome.

1. Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.2. Renal amino acid metabolism was studied 24 h after 75% small bowel resection in rats fasted overnight (16 h) (n=12; total fast 40 h). Sham-operated (n=9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n=8/n=7). During anaesthesia, L-(2, 3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.3. Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23+/-3 versus 44+/-6 microM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36+/-7 and 38+/-6 nmol.min-1. 100 g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 nmol.min-1.100 g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.4. In conclusion, net renal arginine production is reduced 24 h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.

Amino Acids↗

[Pseudomyxoma peritonei].

Pseudomyxoma peritonei was diagnosed in 3 men aged 38, 66 and 54 years with weight loss and distension of the abdomen. Pseudomyxoma peritonei results from seeding of the peritoneal cavity with mucus-producing epithelium. The disease is traditionally characterized by accumulation of huge amounts of mucinous ascites, relatively long survival and absence of distant, extraperitoneal metastases. Mostly, the primary tumour is an appendicular adenoma or adenocarcinoma. Sometimes, the primary tumor is localized in the ovaries. Extensive surgical debulking with postoperative intraperitoneal chemotherapy appears to be the treatment of choice.

Adult↗

Decreased plasma and tissue isoleucine levels after simulated gastrointestinal bleeding by blood gavages in chronic portacaval shunted rats.

BACKGROUND: Previously, arterial concentrations of the essential branched chain amino acid isoleucine (Ile) were found to have decreased by more than 50% after gastrointestinal haemorrhage in patients and after intragastric blood administration in healthy humans and pigs. Hypothetically, this induced hypoisoleucinaemia could deplete tissue Ile pools. AIMS: To study the effect of repeated blood gavages on arterial and tissue Ile levels during normal and impaired liver function. SUBJECTS: Male Wistar rats. METHODS: 14 days after portacaval shunting or sham surgery, rats received 3 ml bovine erythrocytes or saline at 0, 1, 2, and 3 hours via a gastrostomy catheter in the duodenum. At 0, 2, 4, 6 and 8 hours arterial blood and at 8 hours intestine, liver, muscle, and cerebral cortex were sampled for determination of ammonia and amino acid concentrations. RESULTS: In both groups repeated blood administration resulted in a marked decrease in plasma Ile (40-60%). This was accompanied by decreased tissue Ile concentrations in liver (50%), muscle (40-60%), and cerebral cortex (40-50%), but unaltered intestinal Ile levels. In contrast, the arterial and tissue concentrations of ammonia, urea, and of most amino acids increased, most strikingly of the other two branched chain amino acids, valine and leucine. CONCLUSIONS: Simulated gastrointestinal bleeding by blood gavages in rats with and without impaired liver function leads to hypoisoleucinaemia and decreased tissue Ile pools.

Ammonia↗

Effects of simulated upper gastrointestinal hemorrhage on ammonia and related amino acids in blood and brain of chronic portacaval-shunted rats.

Gastrointestinal (GI) hemorrhage during compromised liver function is known to precipitate portal-systemic encephalopathy (PSE). Hypothetically, the induced hyperammonemia depletes cerebral glutamate pools. To investigate this hypothesis, rats were studied 14 days after portacaval shunt (PCS) or sham surgery (SHAM). Rats received 3 mL bovine erythrocytes or saline at t = 0, 1, 2, and 3h via a previously placed gastrostomy catheter. At t = 0, 2, 4, 6 and 8h arterial blood and at t = 8h cerebral cortex were sampled for determination of ammonia and amino acids. Control rats (NORM) were sampled without previous surgery. Repeated intragastric blood administration increased the already elevated arterial ammonia levels in PCS rats further. This resulted in higher cerebral cortex ammonia and glutamine levels after blood administration. Despite the accumulation of ammonia and glutamine, cerebral cortex glutamate concentrations remained unaltered. Yet, PCS rats became more encephalopathic after blood gavages, suggesting that there is not a clear-cut relation between cerebral cortex glutamate concentrations and degree of PSE. Interestingly, cerebral cortex concentrations of GABA, tyrosine and phenylalanine were markedly increased. Whether these observations are pathogenetically related to PSE remains to be established. The present model of simulated GI hemorrhage in PCS rats seems to be a suitable, clinically valid model for future research regarding hepatic encephalopathy.

Amino Acids↗

Prospective evaluation of faecal fatty acid excretion in short bowel syndrome in newborns.

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.

Fatty Acids↗

Supplementation of enteral nutrition with butyrate leads to increased portal efflux of amino acids in growing pigs with short bowel syndrome.

Previously, short-chain fatty acids (SCFAs) infused into the hindgut or administered intravenously have been shown to stimulate intestinal adaptation after massive small bowel resection. To study the effects of enterally supplemented n-butyrate on food digestion and absorption in growing pigs with short bowel syndrome, the authors examined the portal efflux of glucose and amino acids during a meal. In 12 growing pigs, 75% of the small intestine was resected. Five control (CONT) animals underwent transection and reanastomosis of the small bowel. A splenic vein, the aorta, the portal vein, and the stomach were catheterized. Postoperatively, seven enterectomized (ENT) pigs and the CONT pigs were fed by infusion of a liquid diet, without SCFAs, through the gastrostomy catheter. Five enterectomized animals received the same diet, supplemented with butyrate (ENTB) (0.26 g/kg body weight/d). After 3 weeks, the portal efflux of amino acids and glucose was measured after 2 hours of constant feeding. The portal efflux of glucose expressed per kilogram of body weight in the ENT group was 10% of that in the CONT group, and in the ENTB group it was 42%. No significant difference in portal glucose efflux between the ENT and the ENTB groups was found. The portal efflux of amino acids during a meal in the ENT group in relation to the CONT groups was 34%; in the ENTB group it was 63%. These data suggest that enteral supplementation with SCFAs leads to improvement of intestinal food digestion and absorption during short bowel syndrome, possibly related to improved intestinal adaptation.

Amino Acids↗

Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.

BACKGROUND: A decrease in arterial isoleucine values after intragastric blood administration in pigs has been observed. This contrasted with increased values of most other amino acids, ammonia, and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relation between the arterial isoleucine decrease and uraemia after gastrointestinal haemorrhage. METHODS: To extend these findings to humans, plasma amino acids were determined after gastrointestinal haemorrhage in patients with peptic ulcers (n = 9) or oesophageal varices induced by liver cirrhosis (n = 4) and compared with preoperative patients (n = 106). RESULTS: After gastrointestinal haemorrhage, isoleucine decreased in all patients by more than 60% and normalised within 48 hours. Most other amino acids increased and also normalised within 48 hours. Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver cirrhosis. CONCLUSIONS: These results confirm previous findings in animals and healthy volunteers that plasma isoleucine decreases after simulated upper gastrointestinal haemorrhage. This supports the hypothesis that the absence of isoleucine in blood protein causes decreased plasma isoleucine values after gastrointestinal haemorrhage, and may be a contributory factor to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after gastrointestinal haemorrhage could be beneficial and will be the subject of further research.

Adult↗

Ammonia and glutamine metabolism during liver insufficiency: the role of kidney and brain in interorgan nitrogen exchange.

BACKGROUND: During liver failure, urea synthesis capacity is impaired. In this situation the most important alternative pathway for ammonia detoxification is the formation of glutamine from ammonia and glutamate. Information is lacking about the quantitative and qualitative role of kidney and brain in ammonia detoxification during liver failure. METHODS: This review is based on own experiments considered against literature data. RESULTS AND CONCLUSIONS: Brain detoxifies ammonia during liver failure by ammonia uptake from the blood, glutamine synthesis and subsequent glutamine release into the blood. Although quantitatively unimportant, this may be qualitatively important, because it may influence metabolic and/or neurotransmitter glutamate concentrations. The kidney plays an important role in adaptation to hyperammonaemia by reversing the ratio of ammonia excreted in the urine versus ammonia released into the blood from 0.5 to 2. Thus, the kidney changes into an organ that netto removes ammonia from the body as opposed to the normal situation in which it adds ammonia to the body pools.

Ammonia↗