Plasma Ammonia Concentrations Research Articles

THE EFFECTS OF LIQUID CARBOHYDRATE ON MARKERS OF ANABOLISM FOLLOWING HIGH INTENSITY RESISTANCE EXERCISE.

PURPOSE: To compare the effects of liquid carbohydrate supplementation (CHO) versus a placebo (PLC) on plasma cortisol (CORT), insulin (INS), ammonia (AMM), glucose (GLU) and urinary nitrogen (NH3+) concentrations following high intensity resistance training. METHODS: Healthy, young men (n = 9; age = 24.2; weight = 86.9 kg; height = 70.7 kg) performed two high intensity resistance training sessions that included 8 lifts, utilizing major muscle groups, for 3 sets at 100% of 10RM, with 1 min rest between sets. Sessions were performed at the same time of day and were separated by 14 days. Subjects consumed either CHO or PLC (vol = 1.0 g·kg−1) liquid pre and post exercise in a double blind design. Blood samples were collected at pre, post, 1.5 h, and 4 h post exercise and were analyzed for [CORT], [INS], [AMM], and [GLUC]. Urine was collected 24 h pre and 24 h post exercise and analyzed for urinary [NH3+]. RESULTS: There were no significant differences between treatments for any of the pre measures. There were no significant differences between treatments for [CORT], [AMM], or [GLUC]. There was a significant difference between treatments for [INS] at post (CHO 10.79 ± 2.60 vs PLC 4.51 ± 3.1 IU·ml−1) and 1.5 h (CHO 21.64 ± 8.50 vs PLC 4.70 ± 1.10 IU·ml−1). The following significant within group differences were found for PLC treatment: [CORT] pre to-post (14.91 ± 6.00 vs. 24.93 ± 6.83 μg·dl−1); [INS] pre to post (6.61 ± 3.70 vs 4.51 ± 3.10 IU·ml−1) and pre to 1.5 h (6.61 ± 3.70 vs 4.68 ± 1.10 IU·ml−1); and [AMM] pre to post (1.29 ± 0.70 vs 4.12 ± 2.60 μg·ml−1), and from pre to 1.5 h (1.29 ± 0.70 vs 1.61 ± 0.70μg·ml−1). The following significant within group differences were found for the CHO treatment: [CORT] post and 1.5 h (28.26 ± 4.50 vs 22.37 ± 9.60μg·dl−1), and post and 4 h (28.26 ± 4.50 vs 9.1 ± 4.00μg·dl−1); and [INS] pre to 1.5 h (8.26 ± 4.70 vs 21.64 ± 8.50 IU·ml−1). CONCLUSION: A CHO compared to a PLC consumed before and after a high intensity resistance training session increased plasma [insulin]. Liquid CHO appears to lead to a more favorable anabolic post-workout environment, however our indirect measure of protein degradation ([NH3+]) did not demonstrate this. Funded by Gatorade Sports Science Institute.

Arginine supplementation prevents necrotizing enterocolitis in the premature infant

Objectives: To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight ≤1250 g and gestational age ≤32 weeks. Study design: In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. Results: NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. Conclusions: Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC. (J Pediatr 2002;140:425-31)

Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes.

To analyze the effects of an extracorporeal bioartificial liver containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced acute hepatic failure. Prospective animal study. University and INSERM laboratory. Fifteen Large White/Pietrin female pigs weighing 20-30 kg. Acute hepatic failure was induced by end-to-side portocaval shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a thermostabilized column, containing a fluidized bed of alginate beads that embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline phosphatase, and lactate concentrations; and clotting factors were studied. The groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute hepatic failure treated with bioartificial liver containing empty beads (group 2, n = 4), or porcine hepatocytes (group 3, n = 5). In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After connection to the bioartificial liver, the survival of acute hepatic failure pigs was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3, intracranial pressure and bilirubin concentrations were reduced significantly compared with both group 1 and group 2. Neither signs of encephalopathy nor cerebral edema was observed in any animal of group 3. In all animals, plasma ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations increased and clotting factors decreased with no significant differences between the three groups. Autopsy revealed a total necrosis of the liver, which was histologically confirmed. The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.

Effect of pasture crude protein and fermentable energy supplementation on blood metabolite and progesterone concentrations and on embryo survival in heifers

AbstractSeasonal milk production systems rely on heavy inputs of nitrogenous fertilizer, which typically generate pastures with a high crude protein (CP) and low fermentable energy concentration. High intake of CP, particularly in association with low rumen fermentable energy, increases systemic ammonia and urea and has been associated with reduced fertility in cattle. The objective of this study was to examine the relationship between pasture protein intake and fermentable energy supplementation on a range of blood metabolites and on embryo survival and development in cattle.Oestrous synchronized, nulliparous beef heifers (no. = 175) were randomly assigned to one of four pasture-based dietary treatments in a 2✕2 factorial study carried out over 2 years. Animals were randomly allocated to either high (85 kg nitrogen (N) per ha; HN) or low (0·0 kg N per ha; LN) N fertilized pastures and within pasture treatment were randomly allocated to receive either zero or three (+3P) kg dry matter (DM) of molassed sugar-beet pulp (MSBP) per head per day as follows: (1) HN (no. = 44), (2) HN + 3P, (no. = 43), (3) LN (no. = 44), (4) LN + 3P (no. = 44). Blood samples were collected to measure systemic concentrations of ammonia, urea, insulin, glucose and progesterone. Heifers were artificially inseminated (AI) and pregnancy diagnosis was carried out by ultrasonography 30 days after AI. Subgroups of pregnant animals across treatments were slaughtered 40 days after AI to estimate conceptus development.The HN pasture had a higher CP (P&lt; 0·001) and lower water-soluble carbohydrate (P&lt; 0·01) concentration. Plasma concentrations of ammonia (P&lt; 0·05) and urea (P&lt; 0·001) were higher in the animals on the HN pastures and were reduced (P&lt; 0·05) by MSBP supplementation, but only in animals on the HN pastures. Embryo survival rate across treatments was high overall (71%) and not related to pasture CP concentration, fermentable energy supplementation or systemic concentrations of ammonia, urea, glucose or insulin. There was no relationship between dietary treatment or systemic metabolites and any of the estimates of conceptus development. Systemic insulin was not affected by pasture N treatment or MSBP supplementation (P&gt; 0·05). Systemic concentrations of glucose were not affected by pasture N treatment (P&gt; 0·05) but were increased by MSBP supplementation (P&lt; 0·05). Systemic progesterone was not affected by pasture CP or MSBP supplementation (P&gt; 0·05) but at day 7 after AI was positively related (P&lt; 0·05) to embryo survival. Intake of high CP herbage elevated systemic ammonia and urea but there was no association with embryo survival rate or embryo development in heifers.

Dietary lysine requirement of freshwater catfish (Mystus nemurus Cuv. &amp; Val.)

Production of freshwater catfish (Mystus numerus Cuv. & Val.) has soared to meet consumer demand, but little is known about the nutritional requirements of the species. This study was conducted to determine the dietary lysine requirement of juvenile Mystus numerus fed semipurified diets containing graded levels of lysine. The control diet contained fish meal, gelatin and crystalline amino acids simulating the amino acid profile of Mystus nemurus muscle protein except for lysine. Seven experimental diets were formulated to contain lysine as 0.7% (2.00%), 1.1% (3.14%), 1.5% (4.29%), 1.9% (5.43%), 2.3% (6.57%), 2.7% (7.71%) and 3.1% (8.86%) of the diet (% of protein). Triplicate groups of fish were fed to satiation for 90 days. Specific growth rate, feed efficiency ratio, protein efficiency ratio, productive protein value and daily net protein retention of fish fed diets containing lysine at 2.00% of protein were significantly lower than fish fed diets containing lysine at higher levels. Plasma ammonia concentrations were similar in all groups of fish. A digestibility trial between fish fed the experimental diet with 7.71% of lysine and a diet with fish meal as the sole source of protein showed that protein digestibility of the experimental diet was significantly higher than that of the fish meal based diet. Non-linear regression analysis of specific growth rate against dietary lysine levels indicated a lysine requirement of 3.47% of protein for this species.

EFFECTS OF DIETARY PROTEIN UPON CONCENTRATIONS OF UREA IN PERIPHERAL PLASMA AND UTERINE FLUID IN DAIRY CATTLE

There have been concerns that elevated urea nitrogen concentrations in uterine fluid had significant effects on bovine spermatozoal motility and survival. However, it is still uncertain whether dietary protein has any effects upon concentration of urea nitrogen and ammonia in the peripheral plasma and uterine fluid in dairy cattle. The objectives of the study were to investigate the effects of dietary protein intake on concentrations of (i) urea nitrogen in the uterine fluid, (ii) ammonia in the blood and (iii) urea nitrogen in the peripheral plasma. Six lactating, non-pregnant and normally cycling Friesian cows were used in two randomly divided equal groups, receiving either a low or high dietary protein intake. Uterine fluids and blood samples were collected from each cow and uterine urea nitrogen; blood ammonia and plasma urea nitrogen concentrations were measured. The study showed that the cows fed the high protein (HP) diet had significantly higher uterine urea nitrogen, blood ammonia and plasma urea nitrogen concentrations than cows fed the low protein (LP) diet. The results revealed that the concentration of urea nitrogen in the uterine fluid were higher in cows fed HP diet compared with those fed a LP diet. These results suggested that high concentrations of urea in the plasma could diffuse into the uterine lumen and might create a sub-optimal environment in the uterus, which might act as an antagonist to fertility. The high level of blood ammonia and plasma urea nitrogen concentration in the HP fed cows, which could occur due to high protein intake, may affect the viability of sperm, ova and embryos and the growth and survival of the foetus by producing biochemical, endocrionological and tissue derangement. Therefore, it is likely that excessive concentration of urea nitrogen in peripheral plasma and uterine fluid and plasma ammonia of high protein fed lactating cows may be detrimental to the viability of sperm, ova, embryos or foetus.

Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation

OBJECTIVEAdult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease...

The effect of crude protein and fermentable carbohydrate intake on blood metabolite concentrations and fertility in beef heifers

AbstractHigh intakes of crude protein (CP), in particular rumen degradable protein (RDP), have been associated with reduced fertility in cattle. This reduction in fertility has been attributed to putative toxic effects of elevated systemic concentrations of ammonia and, or urea, the by-products of protein metabolism, on gametes and embryos. The objective of the studies reported here was to examine the effect of CP and fermentable carbohydrate intake on various blood metabolites and on fertility, in beef heifers. In the first experiment, 40 heifers were randomly assigned to either low (no urea) or high (240 g urea) RDP, grass silage based diets, supplemented with 1.5 or 3.0 kg dry matter (DM) of either rolled barley (BAR) or molassed sugar beet pulp (MSBP) or no carbohydrate (control). The high RDP diet increased plasma ammonia and urea concentrations. MSBP at 3 kg DM/day was more effective than BAR in reducing ammonia (P&lt;0.05) and urea (P&lt;0.001). In animals fed no urea, MSBP at 3 kg DM/day was also more effective than BAR in reducing systemic ammonia (P&lt;0.001) and urea (P &lt; 0.05). In the second experiment, 83 beef cross-bred heifers were randomly assigned over two replicates to one of 4 treatment groups in a 2 x 2 factorial design. Animals consuming high (85 kg N/ha; HN) or low (0 kg N/ha; LN) nitrogen fertilised pastures were supplemented with either 0 or 3 kg dry matter (DM) MSBP daily as follows: 1) HN only (n=21); 2) HN + 3kg MSBP, (n=22); 3) LN only (n=21); 4) LN + 3kg MSBP (n=19). The HN pastures had higher (P&lt;0.001) CP and lower (P&lt;0.001) water soluble carbohydrate concentrations than LN pastures. Systemic ammonia (P&lt;0.05) and urea (P&lt;0.001) were higher in heifers on the HN pasture. Embryo survival rate was high overall (80%) and was not affected by systemic ammonia or urea concentrations or by supplementation with MSBP. Systemic progesterone, insulin and glucose were not affected by treatment. High CP intake coupled with low fermentable carbohydrate, lead to elevated systemic ammonia and urea concentrations in heifers. However, no adverse effect on fertility was observed.

The effect of condensed tannins in Lotus corniculatus upon reproductive efficiency and wool production in ewes during autumn

A grazing experiment, conducted for 81 days (from 13 February to 4 May) in the late summer/autumn of 1999 at Massey University, Palmerston North, New Zealand, compared the reproductive efficiency and wool growth of ewes grazing Lotus corniculatus (birdsfoot trefoil) or perennial ryegrass ( Lolium perenne)/white clover ( Trifolium repens) pasture (referred to as pasture). Half the ewes grazing L. corniculatus were given twice daily oral polyethylene glycol (PEG: molecular weight 3500) supplementation to inactivate the condensed tannins (CTs) in lotus. A rotational grazing system with 225 mixed age ewes (53.2±3.78 kg per ewe) was used, with 75 ewes per treatment. The effect of forage species and PEG supplementation upon voluntary feed intake (VFI), concentration of plasma metabolites, reproductive efficiency, wool production and wool length was measured during three synchronised oestrous cycles. The ewes were restricted to maintenance feeding for the first 12 days of each oestrous cycle and then increased to ad libitum for the 5 days prior to and including ovulation. Lotus contained 18 g total CT/kg dry matter in the feed offered. There were only trace amounts of total CT in pasture. In vitro organic matter digestibility (OMD) of the diet selected was higher for lotus (0.82 versus 0.74) than for pasture, whilst the two forages contained a similar nitrogen concentration. Mean ovulation rates (ORs) at cycle 3 for CT-acting and PEG sheep grazing lotus and for sheep grazing pasture were, respectively, 1.79, 1.58 and 1.48, with corresponding lambing percentages being 1.69, 1.39 and 1.22. Fecundity (number of corpora lutea (CL) per ewe ovulating) at cycle 3 ovulation and lambs born per ewe lambing were greater for ewes grazing lotus than pasture ( P<0.01), and for CT-acting than for PEG sheep grazing lotus ( P<0.05). Increases in fecundity were due to a lower proportion of single ovulations and a greater proportion of multiple ovulations. CT increased reproductive efficiency by increasing fecundity and by reducing embryonic loss. Rumen ammonia and blood plasma urea concentrations were lower for ewes grazing lotus than pasture ( P<0.01), and were generally lower for CT-acting than for PEG sheep grazing lotus. The nutritional treatments had little effect on plasma ammonia concentration. Organic matter intake (OMI) ( P<0.05), clean wool production ( P<0.01) and staple length ( P<0.001) were significantly higher for ewes grazing lotus than for pasture. Liveweight gain (LWG) was low, and lower for sheep grazing lotus than pasture. There was no difference in OMI and LWG due to CT in lotus, but wool length ( P<0.01) and clean wool production ( P=0.07) were higher for CT-acting than for PEG supplemented ewes (CT not acting). It was concluded that grazing lotus during mating increased the efficiency of reproduction and clean wool production, with a component due to the action of CT. Possible mechanisms for CT increasing reproductive efficiency are discussed.

Emergency treatment of neonatal hyperammonaemic coma with mild systemic hypothermia

An infant aged 3 days presented with hyperammonaemic coma and seizures, which were found to be a result of a urea-cycle defect. Haemofiltration, alternative pathway metabolites, and glucose and insulin failed to lower the plasma ammonia concentration below 2000 micromol/L. The infant was then cooled to a rectal temperature of 34 degrees C for 48 h and put on haemofiltration for 12 h. Plasma ammonia fell to around 100 micromol/L and remained at this concentration after haemofiltration. He roused from his coma, breathed spontaneously, and resumed bottle feeding. Hypothermia may be therapeutic in such instances of metabolic coma because it lowers the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.

Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds.

The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O2 content increased significantly with exercise in both treatments, while the mixed venous blood O2 content decreased as O2 extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.

Hyperammonaemia in critically ill septic infants

Three infants with subphrenic abscess, pyonephrosis, and obstructive ureterocoele respectively had grossly increased concentrations of plasma ammonia. This was considered to be a result of infections with urea splitting organisms....

The Effect of Storage on Ammonia Concentration in Canine Packed Red Blood Cells.

AbstractObjective: To determine the effect of storage on ammonia concentration in canine packed red blood cell (pRBC) units.Design: In vitro and in vivo study.Setting: University Veterinary Teaching Hospital.Interventions: Ammonia concentration was measured in 7 units of canine pRBC prepared in citrate‐phosphate‐dextrose (CPD) and Adsola on Days 1 and 35 of storage. Ammonia was measured in 4 additional units of canine pRBC on Days 0, 7, 14, 21, 28, and 35. Plasma ammonia was also determined in 5 anemic dogs receiving pRBC.Measurements and Main Results: Ammonia concentration increased from 73 ± 15 mmol/L (mean ± SD) on Day 1 to 800 ± 275 mmpl/L on Day (p&lt;0.001). When measured every 7 days in 4 units of canine pRBC, ammonia concentration increased from 23 ± 8 mmol/L on Day 0 to 179 ± 13 mmol/L (Day 7), 276 ± 56 mmol/L (Day 14). 383 ± 47 mmol/L (Day21), 466 ± 30 mmol/L (Day 28), and 562 ± 27 mmol/L (Day 35) (p&lt;0.05 for all comparisons). In a preliminary study, plasma ammonia concentration measured in blood samples from 5 anemic dogs without primary liver disease immediately before and after transfusion with 5–10 ml/kg of stored pRBC remained in the normal reference range.Conclusions: The ammonia concentration in stored canine pRBC increased markedly with time. In this preliminary study, ammonia concentrations in dogs without primary liver disease did not increase above the reference range after transfusion with pRBC.

Effects of diel un-ionized ammonia fluctuation on juvenile hybrid striped bass, channel catfish, and blue tilapia

The effects of variable and fluctuating sublethal ammonia concentrations on plasma ammonia concentration, growth, feed conversion ratio and survival of juvenile hybrid striped bass Morone chrysops ♀× M. saxatilis ♂, channel catfish Ictalurus punctatus and blue tilapia Oreochromis aureus were evaluated in each of three sequential growth periods. Fish were cultured in a flow-through system in which pH was controlled to represent the diel pH variation known to occur in eutrophic aquaculture ponds. During the first growth period (29 days), pH was maintained at 8.0. During the second growth period (22–43 days), pH was controlled to fluctuate daily from 7.75 to 9.00, and during the third growth period (47–53 days), pH was controlled to fluctuate daily from 7.50 to 9.50. Four nominal total ammonia-nitrogen (TAN) concentrations (0, 1, 2.5 and 5 mg l −1) were established as treatment groups. Plasma TAN concentrations of each species responded rapidly to changes in environmental NH 3–N concentration. Channel catfish most effectively excluded ammonia from blood. Plasma TAN concentrations of blue tilapia were greater than those of hybrid striped bass and channel catfish. Of the three species evaluated, hybrid striped bass was the most sensitive to unionized ammonia and died following brief daily exposure to 0.91 mg l −1 NH 3–N (2.5 mg l −1 TAN at pH 9.00). Hybrid striped bass growth was affected by daily brief exposure to 0.65 mg l −1 NH 3–N, but was not affected by brief daily exposure to 0.37 mg l −1 NH 3–N ( P>0.05). Brief daily exposure to 0.91 mg l −1 NH 3–N did not affect channel catfish or blue tilapia growth and feed conversion ratio. The results of this study, in combination with published reports of ammonia concentrations that are normally prevalent in eutrophic aquaculture ponds, suggest that sublethal ammonia exposure in such ponds has a minimal effect on fish growth.

Factor structure and ammonia-related modulation of the human retinal oscillatory potentials

Objective: To investigate in man the factor structure of retinal oscillatory potentials (OPs) to full-field luminance stimulation (0.9–9.5 cd.s.m −2) and the correlation with the spontaneous fluctuations of plasma ammonia. Methods: Six male healthy volunteers were studied. Five OP recordings and ammonia determinations (GLDH method) were obtained for each subject at 2 h interval during an 8 h experimental session. A standard factor analysis was applied on the OP latency (time from stimulus to peak) and amplitudes values. Results: Two consecutive factors on latencies and two factors on amplitudes were identified, consistent with reported differences between the earlier and later OP waves. The model explained a large portion of the OP variance. Both factors on latencies and factor 1 on amplitudes were directly correlated to the stimulus intensity and the ammonia plasma concentration in the 15.8–39.5 μmol/l range. Factors 1 and 2 on latencies decreased and factor 1 on amplitude increased at increasing stimulus intensities. The latency factors decreased and the amplitude factor increased with increasing ammonia concentration. Factor 2 on amplitudes did not correlate with the stimulus intensity or ammonia concentration. Conclusions: The factor structure further supports the evidence of functional differences between early and late OP waves. The observed correlation conceivably reflects a role of ammonia in the modulation of retinal electrophysiology in physiological conditions and potentially accounts for spontaneous variability in otherwise controlled electrophysiological studies.

Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1-h cycle test

We investigated the effect of oral creatine supplementation (20 g d(-1) for 7 days) on metabolism during a 1-h cycling performance trial. Twenty endurance-trained cyclists participated in this double-blind placebo controlled study. Five days after familiarization with the exercise test, the subjects underwent a baseline muscle biopsy. Thereafter, a cannula was inserted into a forearm vein before performing the baseline maximal 1-h cycle (test 1 (T1)). Blood samples were drawn at regular intervals during exercise and recovery. After creatine (Cr) loading, the muscle biopsy, 1-h cycling test (test 2 (T2)) and blood sampling were repeated. Resting muscle total creatine (TCr), measured by high performance liquid chromatography, was increased (P < 0.001) in the creatine group from 123.0 +/- 3.8 - 159.8 +/- 7.9 mmol kg(-1) dry wt, but was unchanged in the placebo group (126.7 +/- 4.7 - 127.5 +/- 3.6 mmol kg(-1) dry wt). The extent of Cr loading was unrelated to baseline Cr levels (r=0.33, not significant). Supplementation did not significantly improve exercise performance (Cr group: 39.1 +/- 0.9 vs. 39.8 +/- 0.8 km and placebo group: 39.3 +/- 0.8 vs. 39.2 +/- 1.1 km) or change plasma lactate concentrations. Plasma concentrations of ammonia (NH(3)) (P < 0.05) and hypoxanthine (Hx) (P < 0.01) were lower in the Cr group from T1 to T2. Our results indicate that Cr supplementation alters the metabolic response during sustained high-intensity submaximal exercise. Plasma data suggest that nett intramuscular adenine nucleotide degradation may be decreased in the presence of enhanced intramuscular TCr concentration even during submaximal exercise.

Continuous Renal Replacement Therapy in the Initial Management of Neonatal Hyperammonemia Due to Urea Cycle Defects

After completing this article, readers should be able to: 1. Describe the metabolic acidosis that may be seen in urea cycle defects. 2. Delineate the most important factor in determining neurologic outcome in urea cycle defects. 3. Explain the factors that affect the blood ammonia concentration in continuous renal replacement therapy (CRRT). 4. Delineate the most difficult issue in pursuing CRRT in neonates. 5. Describe the morbidities associated with CRRT. MP was born at 39 weeks' estimated gestational age by vaginal delivery to a 35-year-old gravida 3 para 2 woman who had an uncomplicated pregnancy. The 3- and 6-year-old female siblings of the patient were healthy. Apgar scores were 8 at 1 minute and 9 at 5 minutes. The newborn was discharged to home after a 2-day stay in the well baby nursery during which time she appeared to be alert and was breastfeeding appropriately. She presented to the emergency department less than 1 day later after her parents noted increasing lethargy and very poor feeding at home. She was admitted to the neonatal intensive care unit (NICU). Results of a complete blood count with differential count and C-reactive protein evaluation were unremarkable, but the patient progressed to worsening lethargy, respiratory failure, and abdominal distension requiring intubation within hours of admission. The anterior fontanelle was soft on admission physical examination. Further testing revealed a base deficit of 6.1 on arterial blood gas, serum ammonia level of 810 mcmol/L (1,134 mcg/dL), serum lactate level of 5.6 mmol/L (5.6 mEq/L), and serum pyruvate level of 0.06 mmol/L. Results of liver function tests were abnormal, and the infant had a prothrombin time of 35.9 seconds, a partial thromboplastin time of 54.3 seconds, and a fibrinogen concentration of 1.75 g/L (175 mg/dL). Genetic and nephrology consultations were requested immediately. Additional metabolic studies were obtained, including measurement of plasma amino …

Effect of training status and relative exercise intensity on physiological responses in men.

This study examined the effect of training status and relative exercise intensity on physiological responses to endurance exercise in humans. Seven endurance trained (TR: peak oxygen uptake [VO2peak] = 65.8 +/- 2.4 mL x kg(-1) min(-1)) and six untrained (UT: VO2peak = 46.2 +/- 1.9 mL x kg(-1) x min(-1)) men cycled for 60 min, either at a work rate corresponding to approximately 70% VO2peak or approximately 95% lactate threshold (LT). The work rate and relative exercise intensity (i.e., % VO2peak) for UT 95% LT were lower (P < 0.01) than for all of the other trials. Although the work rate for UT 70% VO2peak was lower (P < 0.001) than for TR 70% VO2peak and TR 95% LT, average heart rate (HR) for the trial was higher (P < 0.01) throughout exercise in UT 70% VO2peak compared with all of the other trials. Plasma lactate and ammonia concentrations were greater (P < 0.01) during exercise in UT 70% VO2peak compared with all of the other trials. There was a tendency (P = 0.077) for plasma hypoxanthine to be greater at 60 min in UT 70% VO2peak compared with the other trials. At no time were any of the plasma metabolite concentrations different between the UT 95% LT, TR 95% LT and TR 70% VO2peak trials. These data demonstrate that HR and plasma markers of metabolic stress were greater in UT compared with TR when exercise was performed at 70% VO2peak but were similar during exercise at 95% LT.

Impaired cognitive performance in ornithine transcarbamylase-deficient mice on arginine-free diet

Sparse-fur ( spf) mice are a model for the congenital deficiency of ornithine transcarbamylase (OTC), the most common inborn error of urea synthesis in man. In this study, performance of clinically stable spf and control mice (8–10-weeks-old) on two learning tests was assessed under normal Arg(+) or arginine-free Arg(−) diet conditions. Used as an indicator of the metabolic status of the animals, plasma ammonia concentrations were significantly higher in spf than in controls on normal diet, and increased even more during the Arg(−) diet episode. Behaviourally, we found no difference in passive avoidance learning between control and spf mice on Arg(+) diet, whereas in spf mice receiving Arg(−) diet during training, retention performance was significantly reduced. In the hidden-platform water maze, spf mice on Arg(+) diet only showed decreased swimming velocity compared to controls. In mice on Arg(−) diet during the first week of acquisition training, performance on acquisition and retention (probe) trials showed that spf mice experienced more difficulties in actually locating the platform. Visible-platform control experiments only showed a reduction in swimming velocity in spf mice on either diet. We conclude that cognitive performance is impaired in spf mice as a consequence of Arg(−) diet-induced neurochemical alterations.

Comparative study on the correlation of plasma γ-aminobutyric acid and pipecolic acid with liver function in patients with liver cirrhosis

γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, elevated in plasma of patients with liver cirrhosis. Pipecolic acid (PA), a metabolite of lysine, and known to be a GABA receptor agonist, is also seen high levels in the plasma. To clarify the relationship of GABA, PA and liver function, plasma GABA and PA in three groups of chronic liver diseases (compensated cirrhosis, decompensated cirrhosis and decompensated cirrhosis with hepatic encephalopathy, HE) were analyzed and their liver functions were compared. This analysis demonstrated that both plasma GABA and PA were higher in these patients than in normal subjects. Plasma PA, but not plasma GABA, was closely correlated with plasma ammonia concentration in each group. No correlation was noted between plasma GABA and PA in each group. Plasma pipecolic acid was significantly higher in patients with esophageal varices than in patients with no varices. These findings suggest that increased PA may reflect the degree of portal hypertension. Although both GABA and PA are increased in chronic liver disease, they may have a different origin and disappearance rate including metabolic mechanism.