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S Nissen

Publications and source records attributed to S Nissen.

50 records · Page 3Linked to original sources

In vivo metabolism of leucine and alpha-ketoisocaproate in the pig: influence of dietary glucose or sucrose.

The influence of dietary glucose (G) and sucrose (S) on leucine metabolism was evaluated in 10 immature pigs. The diets were isoenergetic and isonitrogenous with 40% of energy being derived from G or S. Animals were fed their diets at least 1 wk prior to the study. Each animal was studied by using a continuous infusion of L-[4,5-3H]leucine and [U-14C] alpha-ketoisocaproate (KIC) to permit measurement of the metabolism of leucine. After a meal, the pigs fed the glucose meal had higher mean plasma glucose and insulin concentrations than pigs fed a sucrose-containing meal. Arterial KIC concentration decreased after feeding either meal, but the arterial leucine concentration remained unchanged. In pigs fed sucrose, plasma fructose increased after the meal and was cleared by the hind limb in the same proportion as plasma glucose (11%). The hind limb glucose clearance was 16% in the glucose-fed pigs. Animals fed the glucose meal had three times greater hind limb uptake of leucine than animals fed the sucrose meal. No dietary influence on hind limb metabolism of KIC could be detected from arterial-venous differences. The whole-body leucine-KIC kinetic data suggested that preprandial tissue proteolysis was greater in pigs fed glucose than in those fed sucrose. Postprandial protein synthesis increased (24%) over fasting values only in pigs fed glucose. This was accompanied by a decrease in the percentage of the leucine pool converted to KIC. These observations indicate that both pre- and postprandial aspects of protein metabolism can be influenced by the dietary carbohydrate source.

Animals↗

Changes in leucine kinetics during meal absorption: effects of dietary leucine availability.

Whole-body leucine and alpha-ketoisocaproate (KIC) metabolism were estimated in mature dogs fed a complete meal, a meal devoid of branched-chain amino acids, and a meal devoid of all amino acids. Using a constant infusion of [4,5-3H]leucine and alpha-[1-14C]ketoisocaproate (KIC), combined with dietary [5,5,5-2H3]leucine, the rate of whole-body proteolysis, protein synthesis, leucine oxidation, and interconversion of leucine and KIC were estimated along with the rate of leucine absorption. Ingestion of the complete meal resulted in a decrease in the rate of endogenous proteolysis, a small increase in the estimated rate of leucine entering protein, and a twofold increase in the rate of leucine oxidation. Ingestion of either the meal devoid of branched-chain amino acids or devoid of all amino acids resulted in a decrease in estimates of whole-body rates of proteolysis and protein synthesis, decreased leucine oxidation, and a decrease in the interconversion of leucine and KIC. The decrease in whole-body proteolysis was closely associated with the rise in plasma insulin concentrations following meal ingestion. Together these data suggest that the transition from tissue catabolism to anabolism is the result, at least in part, of decreased whole-body proteolysis. This meal-related decrease in proteolysis is independent of the dietary amino acid composition or content. In contrast, the rate of protein synthesis was sustained only when the meal complete in all amino acids was provided, indicating an overriding control of protein synthesis by amino acid availability.

Absorption↗

Relationship of contractile state to ejection performance in patients with chronic aortic valve disease.

To assess the relative contributions of afterload mismatch and impaired contractility to pump dysfunction in patients with chronic aortic valve disease, simultaneous left ventricular cineangiography and micromanometry were performed in 56 patients: 21 with severe aortic stenosis, 16 with severe aortic regurgitation, and 19 normal control subjects. Left ventricular mass was increased in patients with aortic stenosis and aortic regurgitation (172 +/- 52 and 224 +/- 63 g/m2, respectively, vs 89 +/- 16 for control subjects; p less than .05) as were end-diastolic volume (101 +/- 39 and 167 +/- 44 vs 77 +/- 16 ml/m2; p less than .05) and end-systolic volume (50 +/- 40 and 84 +/- 43 vs 24 +/- 7 ml/m2; p less than .05). Although ejection fraction was depressed in both abnormal groups (0.56 +/- 0.18 for patients with aortic stenosis and 0.53 +/- 0.13 for those with aortic regurgitation vs 0.69 +/- 0.05 for control subjects; p less than .05), the decrease in ejection fraction was disproportionate to the mild degree of afterload mismatch (end ejection stress 129 +/- 17 in patients with aortic stenosis and 154 +/- 58 in those with aortic regurgitation vs 117 +/- 46 kdyn/cm2 in control subjects; p = NS) with 10 of 21 patients with aortic stenosis and 12 of 16 patients with aortic regurgitation falling below the 95% prediction limit of the linear inverse relationship between ejection fraction and end-systolic stress for controls (EF = 0.78 - 0.00074 X ESS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanics of postextrasystolic potentiation in normal subjects and patients with valvular heart disease.

To determine the relative influence of preload, afterload, and inotropic state on postextrasystolic potentiation (PESP) of ventricular performance in man, we computed angiographic left ventricular volume and wall stress frame by frame for a control and potentiated beat in each of 31 patients. In 10 normal subjects, PESP increased ejection fraction by 14%, while left ventricular end-diastolic volume increased by 8% (p less than .001) and end-systolic stress fell by 21% (p less than .005). Enhanced diastolic filling (+6%, p less than .005) with a small decline in end-systolic stress (-8%, p = NS) likewise contributed to potentiation of ejection fraction (+14%, p less than .001) in seven patients with aortic stenosis. Diastolic filling was not significantly augmented during the compensatory pause in six patients with isolated mitral regurgitation, nor in eight patients with aortic regurgitation (+2%, p = NS for both). Although afterload tended to fall for potentiated beats in patients with aortic (-11%, p = NS) and mitral regurgitation (-23%, p = NS), analysis of ejection fraction-end-systolic stress relationships demonstrated an independent effect of inotropic state on potentiated ejection performance. Thus, utilization of preload reserve contributed to PESP in normal subjects and patients with aortic stenosis, but not in those with volume overload imposed by chronic valvular regurgitation. Enhanced inotropic state independent of small changes in afterload was demonstrated in all subgroups.

Adult↗

Assessment of the severity of valvular regurgitation by digital subtraction angiography compared to cineangiography.

The purpose of this study was to evaluate whether the degree of valvular regurgitation could be reliably estimated by digital subtraction angiography using a 0 to 4+ scale of measurement identical to that applied in conventional cineangiography. Thirty-seven sets of angiograms, each consisting of a digital subtraction angiogram (DSA) and a cineangiogram (CINE) were obtained from 33 patients. Twenty-three angiogram sets were obtained from the ventricles, while 14 were performed in the ascending aorta. Both DSA and CINE images were analyzed for regurgitation by two independent observers. A weighted kappa statistical analysis, carried out to determine the extent to which the two observers agreed on DSA and CINE assessments, demonstrated excellent agreement. The degree of atrioventricular valve regurgitation manifested by DSA was not significantly different from that determined on CINE for either Observer A or B (1.8 +/- 1.2 by CINE vs 2.1 +/- 1.5 by DSA, 2.1 +/- 1.4 vs 2.5 +/- 1.0, respectively). However, occasional exceptions occurred in which the degree of atrioventricular valve regurgitation was overestimated by DSA as compared to CINE. Conversely, in 12 cases with aortic regurgitation, DSA overestimated the grade of regurgitation compared to CINE, 2.3 +/- 1.1 by CINE vs 3.2 +/- 0.8 by DSA (p less than 0.01) for Observer A and 2.1 +/- 1.2 vs 3.0 +/- 1.0 (p less than 0.01) for Observer B. The phenomenon which best explains these data is the occurrence of digital enhancement of myocardial opacification produced by coronary perfusion radiocontrast during angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of supplemental dietary energy on leucine metabolism in sheep.

1. Mixed-breed wethers (40-50 kg), 9 months old, were maintained on high-energy (HED) and low-energy (LED) diets for 2 weeks. 2. After a 15 h fast, a primed-dose constant infusion of L-[U-14C]leucine and alpha-[4,5-3H]ketoisocaproate (KIC) was given. 3. After 2 h, plasma samples were taken and plasma-specific radioactivities of 14C- and 3H-labelled leucine and KIC were measured and analysed by using an open two-pool model. 4. Less than 20% of the total leucine-C entering the circulation was converted to the KIC pool, and 42% of the KIC was converted back to the leucine pool; transamination of the leucine to KIC and reamination of KIC to leucine was much less than in other species. 5. Additional dietary energy resulted in a decrease in tissue protein synthesis, leucine oxidation and interconversion of leucine and KIC. Total leucine-C entry was also lower in sheep given HED, which was most likely due to a suppression of endogenous proteolysis. 6. Plasma glucagon concentration was significantly higher (P less than 0.05) in sheep given LED compared with those given HED. The concentration of glucagon was closely correlated in all treatments with the leucine-C entry (proteolysis + absorbed leucine) and also with KIC-C exit (oxidation).

Animals↗

Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion.

The widely occurring tetradecapeptide somatostatin (SRIF-14) has been variously implicated as a neurotransmitter, a neurohormone, a cybernin (local regulatory factor) and a hormone. In the first isolation of SRIF-14 from hypothalamic extracts and subsequent extracts of other tissues, peptides of higher molecular weight but with similar activity have been noted. Recently two such peptides have been characterized as the 28-amino acid SRIF-28 (from porcine gastro-intestinal tract and porcine and ovine hypothalamus and the 25-amino acid SRIF-25 (from ovine hypothalamus), each of which consists of an N-terminal extension of SRIF-14. We now report that SRIF-28 and SRIF-25 are more potent than SRIF-14 in the inhibition of insulin release, but that SRIF-14 preferentially inhibits glucagon release. This suggests that SRIF-28 and SRIF-25 are not mere biosynthetic precursors of SRIF-14 and that their differential release may be physiologically important.

Animals↗

Effects of fasting on flux and interconversion of leucine and alpha-ketoisocaproate in vivo.

To determine directly the interconversion of circulating leucine and alpha-ketoisocaproate (KIC) in vivo, as well as the effects of fasting on leucine and KIC metabolism, 14- and 96-h fasted dogs were studied during simultaneous infusion of L-[4,5-3H]leucine and [U-14C]KIC. The specific radioactivities of 3H- and 14C-labeled leucine and KIC were determined and transfer rates calculated using a two-pool reversible model. In both groups, approximately 32% of the total leucine carbon entering was converted to KIC, whereas 60% of circulating KIC is converted to leucine. Plasma [3H]KIC specific radioactivity was only half of the circulating [3H]leucine specific activity, suggesting entry of KIC from an unlabeled pool. Fasting decreased the leucine-KIC interconversion, entry of unlabeled KIC, and irreversible loss of KIC. These data demonstrate that interconversion of circulating leucine and KIC is extensive and that fasting decreases the conversion of leucine to KIC in the labeled and unlabeled KIC pools, suggesting that transamination is a major regulator of leucine metabolism in fasting dogs.

Animals↗

Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program.

We investigated whether creatine (CR) and beta-hydroxy-beta-methylbutyrate (HMB) act by similar or different mechanisms to increase lean body mass (LBM) and strength in humans undergoing progressive resistance-exercise training. In this double-blind, 3-wk study, subjects (n = 40) were randomized to placebo (PL; n = 10), CR (20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d; n = 11), HMB (3.0 g of HMB/d; n = 9), or CR-and-HMB (CR/HMB; n = 10) treatment groups. Over 3 wk, all subjects gained LBM, which was assessed by bioelectrical impedance analysis. The CR, HMB and CR/HMB groups gained 0.92, 0.39, and 1.54 kg of LBM, respectively, over the placebo group, with a significant effect with CR supplementation (main effect P = 0.05) and a trend with HMB supplementation (main effect P = 0.08). These effects were additive because there was no interaction between CR and HMB (CR x HMB main effect P = 0.73). Across all exercises, HMB, CR, and CR/HMB supplementation caused accumulative strength increases of 37.5, 39.1, and 51.9 kg, respectively, above the placebo group. The exercise-induced rise in serum creatine phosphokinase was markedly suppressed with HMB supplementation (main effect P = 0.01). However, CR supplementation antagonized the HMB effects on serum creatine phosphokinase (CR x HMB interactive effect P = 0.04). Urine urea nitrogen and plasma urea were not affected by CR supplementation, but both decreased with HMB supplementation (HMB effect P < 0.05), suggesting a nitrogen-sparing effect. In summary, CR and HMB can increase LBM and strength, and the effects are additive. Although not definitive, these results suggest that CR and HMB act by different mechanisms.

Adult↗

Influence of HMB (beta-hydroxy-beta-methylbutyrate) on antibody secreting cells (ASC) after in vitro and in vivo immunization with the anti-Yersinia ruckeri vaccine of rainbow trout (Oncorhynchus mykiss).

In practice, protection of fish against disease by immunization is of limited effectiveness. Therefore, research is concentrated on how to improve the potency and efficacy of vaccines and how to optimally activate the cell-mediated immunity and the specific antibody response. In the present study, the influence of HMB (beta-Hydroxy-beta-methylbutyrate) on the antibody secreting cells (ASC) after both in vitro and in vivo immunization of rainbow trout (Oncorhynchus mykiss) with the anti-yersiniosis vaccine was studied. For in vitro immunization, the spleens from 160 fish were sampled and placed each in 35 mm sterile wells with medium containing HMB at concentrations of 0, 0.1, 1, 5, 10, 25, 50 or 100 microg/mL of medium. The spleens from 80 fish were injected with the vaccine and incubated at 14 degrees C for 10 days. For the in vivo study, fish were fed pellets containing HMB at doses of 0, 10, 25 and 50 mg/kg bw per day. After 2 weeks of HMB supplementation, the fish were immunized by intraperitoneal injection of the vaccine. At 7, 14, 18, 21, 28 and 35 days after immunization, pronephros were taken from 10 fish in each group for testing. When analyzed by the ELISPOT assay, HMB increased the number of splenic ASC after in vitro immunization at concentrations between 10 and 100 microg/mL (P < 0.05). Dietary HMB also increased the number of total and specific ASC when the fish were vaccinated in vivo. In conclusion, the results of the present study showed that HMB increases the levels of specific ASC after both in vitro and in vivo immunization of rainbow trout with the anti-Yersinia ruckeri vaccine.

Animals↗

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters.

BACKGROUND: Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. METHODS: Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day. RESULTS: Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p < .05) when compared with placebo-supplemented subjects. Blood creatinine levels were not changed. However, blood urea nitrogen increased (p = .01) with HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation. CONCLUSION: These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

3-Hydroxybutyric Acid↗