Reticulocyte counts before and after exercise: Trained vs. sedentary

Summary Reticulocyte count comparisons were made on ten trained and ten sedentary college males before and immediately after heavy exercise and following 15 min of recovery. No significant differences occurred within or between groups; in fact, all means were within the normal range. Previous findings were discussed. It was concluded that a physiologically significant increase in reticulocytes does not occur as a result of exercise or training and therefore can not be a mechanism for increased maximal oxygen uptake.     

Utilization of carbohydrates and free fatty acids by the gastrocnemius of the dog during long lasting rhythmical exercise

Summary Utilization of carbohydrates and free fatty acids (FFA) has been investigated in gastrocnemii of dogs during long lasting isotonic rhythmical exercise induced by supramaximal stimulation of the sciatic nerve. Uptake or output of gases and substrates was determined according to the Fick principle. The first measurements were done at about 2 min after the beginning of work when blood flow has reached a steady state, and the latest at about 100 min after the beginning of exercise.During the first 7 min when the work performed exceeded 5 kg/100g×min and O₂ consumption exceeded 11 ml/100g×min, uptake of arterial glucose and FFA was low, accounting for less than 40% of the total O₂ consumption. Since the RQ values at the same time were about 1.0, glycogen must have been oxidized as the major aerobic energy source.About 13 min after the beginning of exercise, the work the muscles could perform declined to about half of the initial value and remained so for the following 90 min. During this time the oxygen extraction ratio of FFA was about 50% and of arterial glucose was 40–50%, while the RQ value was about 0.8.During initial strong exercise an output of lactic acid (LA) of about 10 mg/100 g×min was measured. With the decrease of work as a consequence of fatigue, LA output became negligible, and in many experiments small amounts of LA were taken up by the working gastrocnemii.It is concluded that glycogen is the major aerobic energy source for strong muscular exercise which cannot be substituted for by the oxidation of arterial glucose or FFA.Supported by the Deutsche Forschungsgemeinschaft.     

The rate of lactic acid removal in relation to different baselines of recovery exercise

Summary During strenuous exercise lactic acid (LA) appears in the blood as a result of anaerobic metabolism. The rate at which this LA was removed from the blood after exercise was seen to increase to a maximum with a certain level of post exercise activity. This maximum rate of removal of LA appears to be at approximately 40% of the individual's maximum oxygen uptake when the exercise is performed on a bicycle ergometer.     

Cellular distribution of phosphofructokinase activity and implications to metabolic regulation in human breast cancer

Neoplastic cells generally present profound changes in glucose metabolism. The mechanisms underlying such process are numerous and all may involve altered cellular hormonal responses. Here we report the first evidence that cellular location of phosphofructokinase activity in human breast cancer tissues is different from the one observed in control tissues and that this phenomenon may be involved in the increased glycolytic flux observed in those cells. Through co-sedimentation techniques, we observed that 60% of phosphofructokinase activity in neoplastic tissues is located in an actin-enriched fraction, against 36% in control tissues. Additionally, metastatic tumor tissues presented a two fold increase in this particulate activity when compared to non-metastatic tumor samples. We propose that the alteration in cellular distribution of phosphofructokinase activity in human breast cancer tissues is a mechanism associated to the process of cell transformation and may be a consequence of the altered hormonal milieu observed in several types of cancer.     

Correlation of flunisolide plasma levels to eosinopenic response in humans

Plasma levels of flunisolide were measured in healthy male volunteers after the administration of single doses of the drug by the intravenous, oral, intranasal, and bronchial inhalation routes. The systemic availability of a 1-mg dose orally was only 21%. After a single dose of approximately 0.117 mg intranasally plasma levels ranged up to 1 ng/ml. When 1 mg was administered by bronchial inhalation, peak or near peak plasma levels were recorded at 2 min and remained near this level throughout the first hour before declining at a rate similar to that observed after flunisolide intravenously (plasma ). Gargling with an alcoholic mouthwash immediately after inhalation reduced plasma levels at 30 and 60 min but not earlier, suggesting rate-limiting dissolution of flunisolide in bronchial fluids or rate-limiting diffusion across the mucociliary blanket or pulmonary membrane. The systemic availabilities of the inhaled-mouthwash and inhaled-no mouthwash doses were 32% and 39%, respectively. Systemic potency of flunisolide, measured by eosinopenic response, was oral < inhaled < intravenous and correlated with the systemic availability of flunisolide after drug administration by these three routes. These pharmacokinetic properties of flunisolide are clinically advantageous in that relatively small doses are delivered topically to the target organs, i.e., the nasal mucosa and lungs, whereas a large portion of the dose is swallowed and subsequently extensively metabolized to relatively inactive metabolites.     

Adjustment of metabolism,catecholamines and β-adrenoceptors to 90 min of cycle ergometry

Adrenaline infusion of 0.1 g · kg^–1 · min^–1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied -adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity -adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (–)¹²⁵ Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg · kg^–1 · min^–1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg · kg^–1 · min^–1 and from 0.40 (SD 0.05) to 0.32(SD 0.04) mg · kg^–1 · min^–1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol · l^–1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol · l^–1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol · 1^–1, respectively. The number of high affinity -adrenergic binding sites per cell (-adrenoceptors) nearly doubled from 770 (SD 130) to 1490 (SD 150) during 90 min of cycling. The observed endogenous plasma catecholamine concentrations were not sufficient to change significantly the relative receptor occupancy. This would seem to indicate that the aerobic exercise induced effects depended more on the absolute number of occupied -adrenoceptors than on their relative receptor occupancy. When compared to the results of the adrenaline infusion experiment the increases of the hepatic glucose production and the increase of -adrenoceptors were very similar in both groups despite ten times higher adrenaline plasma concentrations in the infusion group. This would seem to indicate that -adrenoceptors mediated effects do not correlate with catecholamine plasma concentrations.     

Influence of disodium ethane-1-hydroxy-1,1-diphosphonate on vitamin D metabolism in rats

Summary The metabolism and the organ distribution of double labelled vitamin D₃ (1,2-³H-4-¹⁴C-cholecalciferol) has been studied in rats in which the bone mineralization and the intestinal calcium absorption have been inhibited by a large pose (10 mg P/kg s.c. for 7–14 days) of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The most striking difference found was a reduced accumulation of radioactive cholecalciferol and its metabolites in the kidney of EHDP-treated rats. It is unlikely that this effect was due to an unspecific alteration of the functional renal tissue since blood urea, glomerular filtration rate and renal plasm a flow remained unaltered by this dose of EHDP. The EHDP-treated rats were able to form the metabolite eluted with peak IV of the silicic acid chromatographic system, that is 25-hydroxycholecalciferol. In these vitamin D repleted rats fed a high calcium diet, the tritium deficient metabolite eluted with peak V (1,25-dihydroxycholecalciferol) was only found in the intestinal mucosa of both control and EHDP groups three days after the injection of radioactive cholecalciferol, and this in a very small amount. Therefore no definitive conclusion can be drawn as to a possible interference of EHDP treatment on the production of 1,25-dihydroxycholecalciferol. The change in the renal metabolism of vitamin D in rats treated with a rachitogenic dose of EHDP may be caused by the modifications of the calcium metabolism brought about by the diphosphonate. Its relation, if any, with the decreased calcium absorption remains to be established.     

Energetics of karate kumite

It is speculated that anaerobic metabolism is the predominant source of energy in karate kumite. However, no experimental proof is currently available. The metabolic cost and fractions of aerobic and anaerobic energy of karate kumite fighting were investigated. Ten male nationally or internationally ranked karateka [means (SD) age 26.9 (3.8) years, height 1.80 (0.08) m, mass 77.2 (12.8) kg] performed two to four fights scheduled and judged like a championship. Oxygen uptake was measured continuously with a portable spirometric device. Blood lactate was determined immediately before, and minute by minute after, each fight. Aerobic, anaerobic alactic and anaerobic lactic energy were calculated from oxygen uptake during the fight (VO₂), the fast component of the post-fight oxygen uptake (VO_2PCr) above resting values and changes in blood lactate concentration (Net-BLC), respectively. Altogether, 36 fights lasting 267 (61) s were analysed. The referees decisions caused an activity-to-break ratio of approximately 2:1. VO₂, VO_2PCr, and Net-BLC per fight were 165.3 (52.4) ml^.kg^–1, 32.2 (7.2) ml^.kg^–1and 4.2 (1.9) mmol^.l^–1; the overall energy cost above rest was 334.3 (86.3) kJ per fight. Fractions of aerobic, anaerobic alactic, and lactic energy sources were 77.8 (5.8)%, 16.0 (4.6)%, and 6.2 (2.4)%, respectively. The results indicate a high metabolic rate in karate kumite. However, the acyclic activity profile implies that aerobic metabolism is the predominant source of energy and there is anaerobic supplementation, mainly by high-energy phosphates.     

Single nucleotide polymorphisms of the very low density lipoprotein receptor (VLDLR) gene

The very low density lipoprotein receptor (VLDLR) has a potentially important role in lipoprotein metabolism and Alzheimer's disease. We developed amplification primers for most of the coding region and 3′-untranslated region of VLDLR and used sequencing of genomic DNA to examine these regions of VLDLR in subjects with familial combined hyperlipidemia and in normal controls. We identified ten novel single nucleotide polymorphisms (SNPs) for VLDLR. We also found one rare coding sequence variant, S>R153, in a subject with familial combined hyperlipidemia, which was absent from 2360 normal alleles. The identification of intron–exon boundaries, amplification primers, and SNPs provides tools to investigate VLDLR for genetic association and linkage studies. Received: April 30, 2001 / Accepted: May 1, 2001