Sepsis: an arginine deficiency state?

Objective: Sepsis is a major health problem considering its significant morbidity and mortality rate. The amino acid L-arginine has recently received substantial attention in relation to human sepsis. However, knowledge of arginine metabolism during sepsis is limited.

Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow.

Background/aims: The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia.

Methods: Twenty-one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28-54) mmHg); and those that did not (ICP< or =20 mmHg, group 2: n=13, ICP: 15 (10-20) mmHg).

De novo glutamine synthesis induced by corticosteroids in vivo in rats is secondary to weight loss.

Introduction: Corticosteroid treatment affects muscle protein and glutamine metabolism. In the present study we aimed to clarify to what extent anorexia, weight loss and corticosteroids determine protein and glutamine metabolism in muscle.

Methods: The study was performed in Wistar rats (300-350 g, n = 40) given triamcinolone (0.

Plasma citrulline concentration: a surrogate end point for radiation-induced mucosal atrophy of the small bowel. A feasibility study in 23 patients.

Purpose: Plasma citrulline, a nitrogen end product of glutamine metabolism in small-bowel enterocytes, was suggested as a marker of radiation-induced small-bowel epithelial cell loss in mice after single-dose whole-body irradiation. Our objective was to evaluate the feasibility of citrulline as a marker for radiation-induced small-intestinal mucosal atrophy in patients during and after abdominal fractionated radiotherapy.

Methods And Materials: Twenty-three patients were studied weekly during treatment and at intervals of 2 weeks and 3 and 6 months after treatment by postabsorptive plasma citrulline concentration and clinical toxicity grading.

The liquid chromatography mass spectrometry approach to measure amino acid isotope ratios.

Purpose Of Review: Although the application of liquid chromatography mass spectrometry has seen a rapid development in the world of clinical science since the introduction of atmospheric pressure ionization, its potential is still hardly recognized in the field of stable isotope biomedical research, as indicated by the small number of publications on this topic. Nevertheless, considering the polar nature of many biological substrates of interest as well as the non-destructive nature of electrospray ionization, a liquid chromatography mass spectrometry approach simplifies mass spectrometric spectra, allows the application of multiple labelled tracers, and provides an easy on-line sample processing, thus minimizing labour while at the same time providing concentration data and good reproducibility in low quantities of sample.

Recent Findings: These features make it an excellent tool to perform both clinical and animal experiments that usually generate large numbers of samples, which when processed through the classic approach employing gas chromatography combustion isotope ratio mass spectrometry systems would require much more work and time and thus analytical costs.

Time course of nitric oxide production after endotoxin challenge in mice.

Nitric oxide (NO) regulates numerous processes during endotoxemia and inflammation. However, the sequential changes in whole body (Wb) nitric oxide (NO) production during endotoxemia in vivo remain to be clarified. Male Swiss mice were injected intraperitoneally with saline (control group) or lipopolysaccharide (LPS group).

Acute reduction of circulating arginine in mice does not compromise whole body NO production.

The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We have now studied the role of acutely reducing circulating arginine on whole body NO production in mice. Measurements were performed in 4 groups of mice, treated with saline (SAL) or arginase (ASE), and SAL or bacterial endotoxin (LPS).

Acute tryptophan depletion induced by a gelatin-based mixture impairs object memory but not affective behavior and spatial learning in the rat.

One manner to study the role of serotonin (5-HT) in behavioral functions is through nutritional manipulation of its precursor tryptophan (TRP). By means of the method of acute TRP depletion, plasma TRP levels can be reduced in a reversible way in both humans and rats. In the present study a TRP-free protein-carbohydrate mixture was used to investigate the behavioral effects of lowering TRP and 5-HT concentrations in adult male rats.

Assessment of whole body protein metabolism in critically ill children: can we use the [15N]glycine single oral dose method?

Background & Aims: Most stable-isotope methods to evaluate whole body protein metabolism in patients are invasive and difficult to use in children. In this study protein metabolism was evaluated with the non-invasive [15N]glycine single oral dose method in critically ill children and the value of the method is discussed.

Methods: [15N]glycine (100mg) was given orally to children (mean age 5.

Renal metabolism of amino acids: its role in interorgan amino acid exchange.

The kidneys play a role in the synthesis and interorgan exchange of several amino acids. The quantitative importance of renal amino acid metabolism in the body is not, however, clear. We review here the role of the kidney in the interorgan exchange of amino acids, with emphasis on quantitative aspects.

Citrulline: a physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage.

Purpose: Small bowel irradiation results in epithelial cell loss and consequently impairs function and metabolism. We investigated whether citrulline, a metabolic end product of small bowel enterocytes, can be used for quantifying radiation-induced epithelial cell loss.

Methods And Materials: NMRI mice were subjected to single-dose whole body irradiation (WBI).

Pulmonary glutamine production: effects of sepsis and pulmonary infiltrates.

Objective: To define the role of the lung in the production of glutamine in the critically ill and to determine the effects of the presence of pulmonary infiltrates and the presence and severity of sepsis.

Design And Setting: Prospective clinical study in a single center; interdisciplinary intensive care unit at a university hospital.

Patients: Eleven critically ill patients were compared to ten patients prior to cardiac bypass surgery.

Moderate hypothermia prevents cerebral hyperemia and increase in intracranial pressure in patients undergoing liver transplantation for acute liver failure.

Background: During orthotopic liver transplantation (OLT) for acute liver failure (ALF), some patients develop acute increases in intracranial pressure (ICP). The authors tested the hypothesis that increases in ICP during OLT for ALF can be prevented by moderate hypothermia.

Methods: Sixteen patients with ALF undergoing OLT were studied.

Attenuated metabolic response to surgery in tumor-bearing rats.

Background: During cancer, proteins are chronically wasted, including proteins of the gut. Surgical stress acutely increases protein breakdown of the gut. Surgery in cancer patients may thus have a double effect on the gut and lead to exhaustion and functional loss of the gut.

The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis.

Upper gastrointestinal (UGI) bleeding in cirrhosis is associated with enhanced ammoniagenesis, the site of which is thought to be the colon. The aims of this study were to evaluate interorgan metabolism of ammonia following an UGI bleed in patients with cirrhosis. Study 1: UGI bleed was simulated in 8 patients with cirrhosis and a transjugular intrahepatic portasystemic stent-shunt (TIPSS) by intragastric infusion of an amino acid solution that mimics the hemoglobin molecule.

NO production by cNOS and iNOS reflects blood pressure changes in LPS-challenged mice.

Increased nitric oxide (NO) production is the cause of hypotension and shock during sepsis. In the present experiments, we have measured the contribution of endothelial (e) and inducible (i) nitric oxide synthase (NOS) to systemic NO production in mice under baseline conditions and upon LPS treatment (100 microg/10 g ip LPS). NO synthesis was measured by the rate of conversion of l-[guanidino-15N2]arginine to l-[ureido-15N]citrulline, and the contribution of the specific NOS isoforms was evaluated by comparing NO production in eNOS-deficient [(-/-)] and iNOS(-/-) mice with that in wild-type (WT) mice.

Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis.

Hyperammonemia is a universal finding after gastrointestinal hemorrhage in cirrhosis. We administered an oral amino acid solution mimicking the hemoglobin molecule to examine neuropsychological changes, brain glutamine levels, and brain magnetization transfer ratio (MTR). Forty-eight metabolically stable patients with cirrhosis and no evidence of "overt" hepatic encephalopathy (HE) were randomized to receive 75 g of amino acid solution or placebo; measurements were performed before and 4 hours after administration.

Response of whole-body protein and urea turnover to exercise differs between patients with chronic obstructive pulmonary disease with and without emphysema.

Background: Exercise is known to improve physical capacity and muscle mass in patients with chronic obstructive pulmonary disease (COPD). However, recent evidence suggests that exercise may also negatively influence metabolism in COPD.

Objective: The objective was to investigate whether exercise influences whole-body protein metabolism differently in COPD patients and control subjects and to elucidate the effect of the specific underlying lung disease.

Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver.

This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery.

Measuring whole-body actin/myosin protein breakdown in mice using a primed constant stable isotope-infusion protocol.

To measure actin/myosin protein breakdown, the 24 h excretion of N (tau)-methylhistidine (3MH) is used. However, in mice, this method is invalid. Therefore we have developed a liquid chromatography-MS technique to measure the tracer/tracee ratio and concentration of 3MH in plasma, enabling an in vivo primed constant infusion protocol with a deuterated stable isotope of 3MH.

Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis.

Although glucose and protein metabolism have been investigated extensively in experimental models of hypodynamic sepsis, relatively little information is available regarding the compensated stage of sepsis. We investigated interorgan amino acid and glucose metabolism in a porcine model of compensated hyperdynamic sepsis. Fasting catheterized pigs received endotoxin ( Escherichia coli lipopolysaccharide; 3 microg.

Isotopic investigation of nitric oxide metabolism in disease.

Purpose Of Review: Nitric oxide is an important mediator of both physiological and pathophysiological processes. Nitric oxide is produced during direct conversion of arginine to citrulline. Nitric oxide is rapidly metabolized, mainly to nitrite/nitrate, and finally excreted as urinary nitrate.

Effect of prolonged hyperdynamic endotoxemia on jejunal motility in fasted and enterally fed pigs.

Objective: To determine the effects of hyperdynamic endotoxemia on the motility of the small intestine.

Summary Background Data: Motility disorders of the gastrointestinal tract are a common complication of sepsis. It has been suggested that gram-negative endotoxin plays a role in the pathogenesis of the accompanying diarrhea frequently observed.

In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia.

1. During prolonged endotoxaemia, an increase in arginine catabolism may result in limiting substrate availability for nitric oxide (NO) production. These effects were quantitated in a chronically instrumented porcine endotoxaemia model.