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Daily physical activity and blood lactate indices of aerobic fitness in children.

This study examined the relationship between daily physical activity and aerobic fitness in 11-16-year-olds. Habitual physical activity was assessed in 28 boys (mean(s.d.) age 13.6(1.3) years) and 45 girls (mean(s.d) age 13.7(1.3) years) from minute-by-minute heart rate monitoring during 3 school days. Aerobic fitness was assessed by determining the percentage peak VO2 at blood lactate reference values of 2.5 and 4.0 mmol l-1 during incremental treadmill running. The 4.0 mmol l-1 level occurred at a mean(s.d.) value of 89(7)% peak VO2 in both boys and girls and mean(s.d.) values at the 2.5 mmol l-1 level were 82(9)% peak VO2 in girls. Mean(s.d.) percentage time with heart rates at or above 140 beats min-1 was 6(3)% in boys and 5(3)% in girls. Corresponding values for percentage time at or above 160 beats min-1 were 3(2) for boys and 2(1) for girls. The number of 10- and 20-min periods of activity with the heart rate sustained above the 140 and 160 beats min-1 thresholds were also totalled over the 3 days. No significant relationships were identified between percentage peak VO2 at the 2.5 or 4.0 mmol l-1 blood lactate reference levels and either percentage time or number of 10- or 20-min periods above 140 or 160 beats min-1 (P > 0.05). These results support the hypothesis that daily physical activity levels in 11-16-year-old children do not stress aerobic metabolism sufficiently to influence aerobic fitness.

Adolescent↗

The 1H NMR visibility of intracellular lactate in Streptococcus faecalis.

1H NMR studies of glycolysis in washed cell suspensions of Streptococcus faecalis indicated that intracellular lactate is not 1H NMR visible. Evidence for this was gained from time course studies of glycolysis at increasing concentrations of glucose. A close correlation existed between the relative increase in the lactate integral and the enzymatically determined extracellular lactate concentration [Lo]. When ionophores which cause the collapse of the positive intracellular/extracellular lactate gradient were added to cell suspensions following fermentation of 5, 10 and 50 mM glucose, the increase in the lactate integral was proportional to the respective increase in [Lo]. A more direct method for determining the origin of the lactate signal involved centrifugation of a cell suspension after fermentation of 50 mM glucose and measurement of lactate in the extracellular and intracellular fluid. 1H spectra of the cell suspension, supernatant and sonicated pellet revealed that the lactate observed in the cell suspension was equivalent to the lactate in the supernatant alone. The intracellular lactate contained in the pellet represented 42% of the total lactate, indicating that only 58% of lactate is detected by in vivo 1H MRS of S. faecalis. This result is in contrast with the high percentage (70-90%) of in vitro lactate which is detected by in vivo 1H MRS of mammalian brain tissue (Williams S. R. et al. Magn. Res. Med. 7, 425-431, 1988). This may be due to a higher proportion of extracellular lactate in mammalian tissue or differences in the intracellular environments of bacterial and mammalian cells.

Enterococcus faecalis↗

Use of endogenous triglycerides to support gluconeogenesis in the perfused isolated rat liver.

The carbon balances in isolated perfused rat liver during gluconeogenesis from L-alanine and sodium L-lactate indicate that assuming the substrate unaccounted for were fully oxidized the energy yielded was not sufficient to support the observed rates of glucose synthesis. This observation indicates that endogenous substrates must also be oxidized. The possibility that endogenous fatty acid oxidation was the source of the energy needed to support glucose synthesis was investigated by measuring the rate of 14CO2 formation from tracer quantities of added [U-14C] palmitate. Short pulses of L-alanine or sodium L-lactate infusion produced an increased rate of 14CO2 production paralleled by increases in oxygen uptake indicating that more endogenous fuel is being mobilized. That the rate of 14CO2 output is an expression of fatty acid mobilization was supported by experiments demonstrating that the addition of octanoate to dilute the fatty acid pool produced an immediate fall in the rate of 14CO2 output. On the other hand, the administration of glucose produced no changes in oxygen uptake or 14CO2 output. However, lactate even in the presence of glucose induced a rise in 14CO2 production which occurred in parallel with the enhancement in oxygen uptake. It is concluded that mobilization of hepatic endogenous fatty acid is a metabolic event intimately associated with enhancement of gluconeogenesis. Consequently the control of the different steps of this process may indirectly control gluconeogenesis.

Animals↗

Adenine nucleotide degradation in the thoroughbred horse with increasing exercise duration.

Adenine nucleotide (AN) degradation has been shown to occur during intense exercise in the horse and in man, at or close to the point of fatigue. The aim of the study was to compare the concentrations of muscle inosine 5'-monophosphate (IMP) and plasma ammonia (NH3) during intense exercise with the concentrations of muscle and blood lactate. Seven trained thoroughbred horses were used in the study. Each exercised on a treadmill for periods of between 30 s and 150 s, at 11 and/or 12 m.s-1. Blood and muscle samples were taken and analysed for lactate and NH3 and adenosine 5'-triphosphate (ATP), phosphorylcreatine (PCr), IMP, creatine, lactate and glycerol-3-phosphate respectively. Horses showed varying degrees of AN degradation as indicated by plasma [NH3] and muscle [ATP] and [IMP]. Comparisons of [IMP] with muscle [lactate], and plasma [NH3] with that of blood [lactate] indicated a threshold to the start of AN degradation. This threshold corresponded to a lactate content of around 80 mmol.kg-1 dry muscle and 15 mmol.l-1 in blood. We discuss the mechanisms which have been proposed to account for AN degradation and suggest that IMP formation occurs as a result of a sudden rise in the concentration of adenosine 5'-diphosphate (ADP) and consequently the concentration of adenosine 5'-monophosphate. The data suggest a critical pH below which there may be a substantial reduction in the kinetics of ADP rephosphorylation provided by PCr resulting in an increase in [ADP], which is the stimulus to AN degradation during intense exercise.

Adenine Nucleotides↗

Cholesterol ester hydrolase activity in mammary tissue of the lactating rat.

Cholesterol ester hydrolase activity has been studied in mammary glands of rats. Subcellular fractionation of the glands obtained in mid-lactation indicated that around 80% of the recovered activity was associated with particulate fractions. Two distinct cholesterol ester hydrolase activities were identified, one with an optimum pH of 7.5-9.0 and the second (approximately 5% of the total activity) with a more acidic pH optimum. Although the neutral cholesterol ester hydrolase had some properties in common with the lipoprotein lipase in mammary tissue, it was shown to be a separate entity by several criteria. Its activity could be increased following treatment with Mg-ATP and cAMP-dependent protein kinase, suggesting identity with the hormone sensitive lipase of adipose tissue. The cholesterol ester hydrolase activity in mammary glands just after parturition was greater than in glands obtained either from late-pregnant or midlactating animals. The subcellular distribution of the neutral cholesterol ester hydrolase suggested that it may have a different function to the neutral cholesterol ester hydrolase of adrenals and other tissues. Nevertheless the fact that the activity of the enzyme can be modulated by cAMP-dependent protein kinase suggests the possibility that hormonal control of this enzyme may be involved in the regulation of cholesterol metabolism in the mammary gland.

Adenosine Triphosphate↗

Characteristics of uptake of short chain fatty acids by luminal membrane vesicles from rabbit kidney.

The mechanisms of renal transport of short chain fatty acids by luminal membrane vesicles prepared from pars convoluta or pars recta of rabbit proximal tubule were studied by a Millipore filtration technique and by a spectrophotometric method using a potential-sensitive carbocyanine dye. Both luminal membrane vesicle preparations take up propionate and butyrate by strictly Na+-dependent transport systems, although with different characteristics. The uptake of short chain fatty acids by membrane vesicles from the pars convoluta was insensitive to changes in membrane potential, which is indicative of electroneutral transport of these compounds. Furthermore, kinetic studies showed that the Na+-dependent, but electrically silent transport of propionate is saturable (Km = 10.9 +/- 1.1 mM and Vmax = 3.6 +/- 0.2 nmol/mg protein per 20 s) and is unaffected by the presence of L- and D-lactate, indicating that these monocarboxylic acids did not share the same common transport system. In the luminal membrane vesicles from the pars recta, the uptake of propionate and butyrate was mediated by an Na+-dependent electrogenic transport process, since addition of the organic compounds to these vesicle/dye suspensions depolarized the membrane vesicles and the renal uptake of propionate and butyrate was enhanced by K+ diffusion potential induced by valinomycin. Competition experiments revealed that in contrast to the transport of propionate by vesicles from the pars convoluta, the Na+-dependent electrogenic transport of short chain fatty acids in vesicles from the pars recta occurred via the same transport system that is responsible for the reabsorption of L- and D-lactate in this region of rabbit kidney proximal tubule.

Animals↗

Chronic exercise training alters kinetic properties of rat skeletal muscle and myocardial lactate dehydrogenase.

10 weeks of treadmill running dramatically altered the kinetic properties of lactate dehydrogenase (EC 1.1.1.27) in skeletal muscle and myocardium in the rat. These changes, including Vmax, Km and optimal concentrations for pyruvate and lactate, indicate that exercise training induces the formation of H-isozyme in skeletal muscle and M-isozyme in the heart and represent metabolic adaptations of these tissues to chronic aerobic exercise.

Animals↗

Multigeneration study of FD & C Blue No. 2 in rats.

In a three-generation reproduction study, groups of ten male and 20 female Charles River CD rats were fed FD & C Blue No. 2 at dietary levels providing intakes of 0.0, 2.5, 25, 75 and 250 mg/kg body weight/day. Slightly bluish-coloured fur was noted in rats at the 250-mg/kg/day dose level and bluish-green-coloured faeces were produced by rats in the 75- and 250-mg/kg/day groups. The gestation, viability and lactation indices of all litters were comparable for the control and treated groups. The fertility indices for female rats in the 2.5- and 25-mg/kg/day groups were significantly lower than those for control females in the case of the F2 litters. However, there was no reduction in the female fertility indices for the F2 litters at the two higher dosage levels, nor for the F1 and F3 litters at any dosage level. Although fertility indices were reduced for some groups of male rats in the F2b and F2c litters, these changes were not considered to be compound-related. Examination of the ovaries and uteri of all dams killed on day 19 of gestation of the F2c and F3c litters revealed no gross anatomical abnormalities. No unusual changes were observed in the stillborn pups or in pups dying during the study. There were no compound-related gross or microscopic pathological lesions in any of the F1 or F3a rats that were killed and necropsied, and no compound-related organ-weight variations were recorded in the F1 parental rats.

Animals↗

Fructose prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced ATP depletion and toxicity in isolated hepatocytes.

The loss of viability of isolated rat hepatocytes exposed to either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) was prevented by addition of fructose to the incubation medium. This protection was dependent on fructose concentration, being complete at 10 mM. Addition of fructose dramatically delayed MPTP- and MPP+-induced depletion of ATP and was accompanied by a significant accumulation of lactate, indicating the occurrence of enhanced glycolytic production of ATP. Glucose was much less effective against MPTP and MPP+ toxicity, probably because it is a relatively poor substrate for glycolysis in liver cells. We conclude that depletion of ATP is a critical event in MPTP cytotoxicity in our in vitro model system, and that the use of alternative sources of ATP production may represent an important protective device against the effects of this toxic agent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Hormonal activation of mammary gland peroxidase.

Ultrastructural cytochemistry was used to detect an endogenous peroxidase in the rat mammary gland. The enzyme was identified only during the latter half of pregnancy and during lactation, indicating its possible dependence upon hormones. To test this hypothesis, specific hormones associated with the development and differentiation of the mammary gland were used both in vivo and in vitro in an effort to induce, or unmask, the activity of the enzyme. Estrogen injected into nonpregnant rats induced some peroxidase activity in the mammary glands of a few animals. Two hormone combinations tested in organ cultures of mouse mammary gland were able to activate the enzyme: (1) dexamethasone + insulin and (2) dexamethasone + insulin + prolactin.

Animals↗

Cerebrospinal fluid lactate and pH in patients with acute severe head injury.

Cerebral ventricular fluid (CSF) lactate and pH were measured repeatedly in 21 comatose patients with severe head injury during the first three weeks after trauma. In addition, regional cerebral 133Xe blood flow (rCBF) was measured two to four times in each patient at various time intervals, depending on the indications for carotid angiography, and the pressure in the cerebral ventricular system (IVP) was measured continuously. The series was divided into three groups: (1) patients with local cortical cerebral lesions, (2) patients with brain-stem symptoms, and (3) patients with both local cortical lesions and brain-stem symptoms. The results showed that a high CSF lactate level in patients with severe acute brain injury suggested severe and extensive brain lesions and predicted a poor outcome of the injury. In the individual patients, increasing CSF lactate foreboded clinical deterioration, whereas decreasing CSF lactate indicated recovery. The CSF pH was decreased in most patients, but very low pH levels (below 7.20) were seen only in three patients who all had a poor outcome. Correlation was not observed between CSF lactate and rCBF or between CSF pH and rCBF. It is concluded that repeated determination of CSF lactate and pH during the post-traumatic period may be a valuable tool in the assessment of the course and outcome of the brain injury.

Adolescent↗

Effect of subclinical mastitis on milk plasminogen and plasmin compared with that on sodium, antitrypsin and N-acetyl-beta-D-glucosaminidase.

The effect of subclinical mastitis on levels of plasminogen and plasmin in milk from cows in a high-yielding herd was investigated. Comparisons were made with levels of milk Na, antitrypsin and N-acetyl-beta-D-glucosaminidase (NAGase). In samples from mastitic quarters plasminogen activity, as measured after activation to plasmin, increased by only 21% and plasmin by 82%, while NAGase increased by 307%. Plasminogen was the only component that was normally distributed, all other components showed more or less skewed distributions. Plasmin and plasminogen were significantly related to the other components. However, plasminogen plateaued when the other components continued to increase. There was thus no further increase in plasminogen with the severity of inflammation as with the other components. Plasmin showed a similar although less pronounced tendency. Results of treatment of mastitic whey samples with acid suggested that the non-linear increase in plasmin activity was due to interaction with acid-labile proteinase inhibitors. Mastitis led to dissociation of plasminogen and plasmin from the casein micelles. The degree of activation of plasminogen was higher with casein-associated than with soluble plasminogen in both healthy and mastitic milks. Plasmin was very closely related to milk Na, which is a sensitive indicator of epithelial integrity. It is suggested that plasmin contributes to Na leakage into milk by degrading membrane proteins of the epithelial lining. Plasminogen and antitrypsin, which are both plasma proteins, were not identically affected by stage of lactation, indicating nonidentical modes of transport from plasma to milk.

Acetylglucosaminidase↗

Quantification of glucose cycling and the extent of equilibration of glucose 6-phosphate with fructose 6-phosphate in islets from ob/ob mice.

Pancreatic islets from fed and fasted obese hyperglycaemic (ob/ob) mice were incubated with [1-14C]glucose at 5.5 mM and 16.7 mM, [1-14C]mannose at 16.7 mM, and 3H2O. Yields of 14CO2 and 14C-labelled lactate, and amounts of 14C from [1-14C]mannose incorporated into glucose and of 3H bound to C-2 of glucose, were measured. Glucose utilization was determined from yields of 3H2O from [5-3H]glucose. From the results using 14C, 32-43% of the hexoses phosphorylated to hexose 6-phosphate were estimated to have been dephosphorylated, i.e. cycled. Estimates of hexose cycling from 3H incorporation into glucose were similar. Differences in the ratios of 14C yields in CO2 and lactate indicated incomplete isotopic equilibration between glucose 6-phosphate and fructose 6-phosphate, making the estimates of cycling semi-quantitative. In the fasted state, a larger percentage of the hexose utilized went to lactate than in the fed state. Thus conversion of mannose into glucose in islets indicates the occurrence of glucose cycling in islets. Yields of 14C from [1-14C]mannose, compared with from [1-14C]glucose, provide an approach for quantifying the extent of this cycling. These data provide further evidence for extensive glucose cycling occurring in ob/ob islets in both the fed and the fasted state.

Animals↗

Ammonia and lactate: differential information on monitoring training load in sprint events.

Two hypotheses were tested concerning training relevance of ammonia in capillary blood compared with lactate after extensive and intensive high-paced runs. 1. There is a load threshold at which ammonia concentration deviates statistically significantly from the pre-load level, while lactate indicates already anaerobic metabolic processes at extensive training loads. Increased ammonia concentration is understood as the activation of type IIb fibers. 2. The increase in ammonia is primarily a consequence of increasing training load intensity. The hypotheses were tested in a field experiment with male sprinters n = 13. The experimental plan followed a design of repeated measures in a 4 x 4 Latin-square. The subjects completed four high-pace runs (300 m) at 82.5%, 85%, 87.5%, and 90% of the maximum running intensity (identified in a contest). The results confirmed our first hypothesis. Significant increase in ammonia concentration was not found until after four runs at an intensity of 87.5% or after one 300-m run at maximum running speed. In contrast to this, a glycolytic reaction became evident in one run at 82.5% of the maximum intensity. Lactate concentration exceeded the anaerobic threshold at this point. Definite instructions for training practice cannot be made at the present state of research.

Adenosine Monophosphate↗

Evaluation of the perinatal and postnatal effects of uranium in mice upon oral administration.

Perinatal and postnatal studies were performed in Swiss mice given uranium--as uranyl acetate dihydrate--at daily dosages of 0, 0.05, 0.5, 5, and 50 mg/kg from day 13 of pregnancy until weaning of the litters on day 21 post-birth. Postnatal development was monitored after 0, 4, and 21 d of lactation. At doses of 0, 0.05, 0.5, and 5 mg/kg.d, treatment with uranium had no significant effect on sex ratios, mean litter size, pup body weight, or pup body length throughout lactation. Significant decreases in the mean litter size on postnatal day 21, and in the viability and lactation indices were observed at the 50 mg/kg.d dose level. When comparing the "no observable effect level" (NOEL) for reproductive effects of uranium, with the concentrations of the metal usually ingested by men, a safety factor below 1,000 can be estimated.

Administration, Oral↗

Ischaemic heart disease, skeletal muscle fibres and exercise capacity.

Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma.

Adult↗

Phosphoenolpyruvate carboxylase of Escherichia coli. The role of lysyl residues in the catalytic and regulatory functions.

Phosphoenolpyruvate (PEP) carboxylase [EC 4.1.1.31] of E. coli was inactivated by 2,4,6-trinitrobenzene sulfonate (TNBS), a reagent known to attack amino groups in polypeptides. When the modified enzyme was hydrolyzed with acid, epsilon-trinitrophenyl lysine (TNP-lysine) was identified as a product. Close similarity of the absorption spectrum of the modified enzyme to that of TNP-alpha-acetyl lysine and other observations indicated that most of the amino acid residues modified were lysyl residues. Spectrophotometric determination suggested that five lysyl residues out of 37 residues per subunit were modified concomitant with the complete inactivation of the enzyme. DL-Phospholactate (P-lactate), a potent competitive inhibitor of the enzyme, protected the enzyme from TNBS inactivation. The concentration of P-lactate required for half-maximal protection was 3 mM in the presence of Mg2+ and acetyl-CoA (CoASAc), which is one of the allosteric activators of the enzyme. About 1.3 lysyl residues per subunit were protected from modification by 10 mM P-lactate, indicating that one or two lysyl residues are essential for the catalytic activity and are located at or near the active site. The Km values of the partially inactivated enzyme for PEP and Mg2+ were essentially unchanged, though Vmax was decreased. The partially inactivated enzyme showed no sensitivity to the allosteric activators, i.e., fructose 1,6-bisphosphate (Fru-1,6-P2) and GTP, or to the allosteric inhibitor, i.e., L-aspartate (or L-malate), but retained sensitivities to other activators, i.e., CoASAc and long-chain fatty acids. P-lactate, in the presence of Mg2+ and CoASAc, protected the enzyme from inactivation, but did not protect it from desensitization to Fru-1,6-P2, GTP, and L-aspartate. However, when the modification was carried out in the presence of L-malate, the enzyme was protected from desensitization to L-aspartate (or L-malate), but was not protected from desensitization to Fru-1,6-P2 and GTP. These results indicate that the lysyl residues involved in the catalytic and regulatory functions are different from each other, and that lysyl residues involved in the regulation by L-aspartate (or L-malate) are also different from those involved in the regulation by Fru-1,6-P2 and GTP.

Aspartic Acid↗