The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise.

The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.

Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency.

The purpose of this study was to investigate the hypothesis that cycling efficiency in vivo is related to mitochondrial efficiency measured in vitro and to investigate the effect of training status on these parameters. Nine endurance trained and nine untrained male subjects (V(O2peak) = 60.4 +/- 1.4 and 37.0 +/- 2.0 ml kg(-1) min(-1), respectively) completed an incremental submaximal efficiency test for determination of cycling efficiency (gross efficiency, work efficiency (WE) and delta efficiency). Muscle biopsies were taken from m. vastus lateralis and analysed for mitochondrial respiration, mitochondrial efficiency (MEff; i.e. P/O ratio), UCP3 protein content and fibre type composition (% MHC I). MEff was determined in isolated mitochondria during maximal (state 3) and submaximal (constant rate of ADP infusion) rates of respiration with pyruvate. The rates of mitochondrial respiration and oxidative phosphorylation per muscle mass were about 40% higher in trained subjects but were not different when expressed per unit citrate synthase (CS) activity (a marker of mitochondrial density). Training status had no influence on WE (trained 28.0 +/- 0.5, untrained 27.7 +/- 0.8%, N.S.). Muscle UCP3 was 52% higher in untrained subjects, when expressed per muscle mass (P < 0.05 versus trained). WE was inversely correlated to UCP3 (r = -0.57, P < 0.05) and positively correlated to percentage MHC I (r = 0.58, P < 0.05). MEff was lower (P < 0.05) at submaximal respiration rates (2.39 +/- 0.01 at 50% V(O2max)) than at state 3 (2.48 +/- 0.01) but was neither influenced by training status nor correlated to cycling efficiency. In conclusion cycling efficiency was not influenced by training status and not correlated to MEff, but was related to type I fibres and inversely related to UCP3. The inverse correlation between WE and UCP3 indicates that extrinsic factors may influence UCP3 activity and thus MEff in vivo.

Biological variation in variables associated with exercise training.

To be able to identify a training induced change in a certain variable, it is necessary to know the background variation. In this study the coefficient of variation (total, between-subjects, within-subjects), the relative sources of variance (between-subjects and within-subjects), and the critical difference (within-subjects) were estimated in four categories of variables (performance and physiological variables, metabolic and hormonal variables, immunological variables, and mood state variables) in 15 moderately trained male runners measured on three different occasions over a period of 7 weeks. In the performance and physiological variables, 78.9 % of the variance was due to variation between subjects and they had the lowest critical difference (11.9 %). In contrast, the metabolic and hormonal variables had the highest critical difference (59.9 %) and 53.4 % of the variance was due to variations within subjects. The immunological and psychological variables had about two thirds of the variance arising from variation between subjects. However, the critical difference for the immunological variables was high (47.4 %), while it was relatively low for the psychological variables (26.8 %). The low critical difference and variation within subjects of the psychological and in particular the performance and physiological variables indicate that they may be beneficial as primary markers of training induced changes.

Nasal bioavailability of peptide T in rabbits: absorption enhancement by sodium glycocholate and glycofurol.

The aim of the present study was to investigate the absolute nasal bioavailability of Peptide T from aqueous formulations containing sodium glycocholate, an absorption enhancer with known effect on epithelial tight junctions, and/or glycofurol in a crossover study in rabbits. Additionally, the reversibility of the absorption enhancing effect of sodium glycocholate was studied by applying enhancer and peptide T with different time intervals and calculating Area Under the Curve of the peptide in plasma. It was shown that the bioavailability of Peptide T was significantly enhanced when glycofurol or sodium glycocholate was added to a nasal formulation. The nasal bioavailability of Peptide T in water (control formulation), 5% glycofurol, 5% glycofurol+1% sodium glycocholate and 1% sodium glycocholate was 5.9, 22, 29 and 59%, respectively. As indicated by the differences in t(max), C(max) and time-concentration profiles different patterns of Peptide T absorption were seen from the vehicles containing glycofurol and sodium glycocholate. In the reversibility study, the enhancing effect of sodium glycocholate on nasal absorption of Peptide T was found to be reversible within 4 h. It was concluded, that nasal absorption of Peptide T in rabbits was effectively enhanced by co-administration of sodium glycocholate, which also provided very fast absorption rates as well as a relatively short lasting effect of the absorption enhancing effect. Co-administration of glycofurol leads to enhanced and prolonged absorption of the peptide. Combining the two enhancers did not lead to increased peptide T absorption compared to 5% glycofurol alone.

Intranasal bioavailability of buprenorphine in rabbit correlated to sheep and man.

The purpose of the present study of buprenorphine is to add information about the correlation between various animal models and nasal bioavailabilities in man. PEG 300 was added to one formulation to study whether the addition of the co-solvent results in the same absorption pattern as seen for sheep. The bioavailability of intranasal buprenorphine 0.6 mg in PEG 300 and 5% dextrose was assessed in a cross-over study in six rabbits. The mean bioavailabilities, Tmax and Cmax were 46% (S.D. +/-13) and 53% (S.D. +/-17), 8 and 12 min, 28 and 27 ng/ml for 30% PEG 300 and 5% dextrose, respectively. No significant differences were found between the nasal buprenorphine formulations. The bioavailabilities in rabbit and sheep, respectively, were approximately 2.5 and four times higher than for man. The absorption rate was faster for rabbit and sheep than for man. It appears that rabbit and sheep bioavailability differ from humans, especially with respect to rate. PEG 300 do not increase the bioavailability of buprenorphine.

High-performance liquid chromatographic analysis of Peptide T in rabbit plasma with on-line column enrichment.

The present paper describes the development of a simple and sensitive analytical method for quantification of Peptide T (PT) in rabbit plasma, using standard analytical equipment and on-line column enrichment, without prior extraction, clean-up or derivatization. The analytical procedure was found to be accurate, precise and linear. The accuracy was 100% (range 97-103%) and the mean precision was 8% (range 3-14%) for all (n=6) concentrations (0, 15, 50, 100 and 200 ng/ml). The total recovery was found to be approximately 80%, and it was found to be dependent upon the injection rate onto the extraction column. The correlation between added and found concentrations was 0.9982, and the limit of detection was estimated to be around 5 ng/ml. The method is therefore found to be suitable for bioavailability studies, involving Peptide T, in rabbits.

Dietary fibres reduce blood pressure, serum total cholesterol and platelet aggregation in rats.

The effects of dietary fat and dietary fibres on blood pressure, serum lipids and platelet aggregation in spontaneously hypertensive and Wistar-Kyoto rats have been investigated. The systolic and diastolic blood pressure values were increased with increasing amounts of dietary fat and normalized by dietary fibre supplementation. The greatest reduction in blood pressure was obtained by a combination of reduced dietary fat and supplementary dietary fibre. Addition of dietary fibre when the amount of dietary fat was high or reduction of dietary fat when the amount of dietary fibre was low gave a smaller effect. In both rat strains the decreases in systolic and diastolic blood pressure values after reducing dietary fat and/or increasing dietary fibre were about 10-15 mmHg. Serum total cholesterol and serum HDL-cholesterol concentrations were reduced by reduction of dietary fat or a combination of dietary fat reduction and dietary fibre addition. A combination of dietary fat reduction and dietary fibre addition was the most effective dietary change for reducing serum triacylglycerol concentration and platelet aggregation. The present study demonstrates that in this experimental model it is possible to reduce risk indicators of coronary heart disease significantly by changing dietary habits.

A simple and inexpensive device for administration of continuous positive airway pressure breathing.

A simple system for administration of continuous positive airway pressure breathing uses a corrugated hose in the modified Mapleson D system for anaesthesia. The only mechanical component of the system is a spring-loaded valve for positive end expiratory pressure.