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PubMed1990

Muscle carnitine metabolism during incremental dynamic exercise in humans.

The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75% of their maximal oxygen uptake (VO2 max) and to fatigue at 100% of VO2 max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (means +/- SE) 15.9 +/- 1.7 mmol kg-1 d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9 +/- 0.6 and 4.6 +/- 0.5 mmol kg-1 d.wt after exercise at 75 and 100% of VO2 max respectively. Acetylcarnine content at rest was 6.9 +/- 1.9 mmol kg-1 d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of VO2 max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle.

Acetyl Coenzyme A↗

PubMed1979

Change from homo- to heterolactic fermentation by Streptococcus lactis resulting from glucose limitation in anaerobic chemostat cultures.

Lactic streptococci, classically regarded as homolactic fermenters of glucose and lactose, became heterolactic when grown with limiting carbohydrate concentrations in a chemostat. At high dilution rates (D) with excess glucose present, about 95% of the fermented sugar was converted to l-lactate. However, as D was lowered and glucose became limiting, five of the six strains tested changed to a heterolactic fermentation such that at D = 0.1 h(-1) as little as 1% of the glucose was converted to l-lactate. The products formed after this phenotypic change in fermentation pattern were formate, acetate, and ethanol. The level of lactate dehydrogenase, which is dependent upon ketohexose diphosphate for activity, decreased as fermentation became heterolactic with Streptococcus lactis ML(3). Transfer of heterolactic cells from the chemostat to buffer containing glucose resulted in the nongrowing cells converting nearly 80% of the glucose to l-lactate, indicating that fine control of enzyme activity is an important factor in the fermentation change. These nongrowing cells metabolizing glucose had elevated (ca. twofold) intracellular fructose 1,6-diphosphate concentrations ([FDP](in)) compared with those in the glucose-limited heterolactic cells in the chemostat. [FDP](in) was monitored during the change in fermentation pattern observed in the chemostat when glucose became limiting. Cells converting 95 and 1% of the glucose to l-lactate contained 25 and 10 mM [FDP](in), respectively. It is suggested that factors involved in the change to heterolactic fermentation include both [FDP](in) and the level of lactate dehydrogenase.

Acetates↗

PubMed1987

Compartmentation of carbohydrate metabolism in vascular smooth muscle.

In vascular smooth muscle, oxidative phosphorylation and glycolysis are independently regulated. Previous studies indicated that the independent regulation of these pathways was related to a compartmentation of carbohydrate metabolism. To further study carbohydrate metabolism, glucose transport and the incorporation of radiolabel from glucose into glycogen and lactate were measured after the oxidative and glycolytic pathways were independently altered. Ouabain stimulated mechanical activity, oxygen consumption, and glycogenolysis, whereas lactate production was decreased. Although glycogenolysis was substantial, glucose was the only substrate for lactate, indicating that intermediates derived from glycogen do not mix with those from glucose uptake. Thus glycogenolysis and glycolysis are carried out by independent enzymatic pathways. Insulin-stimulated lactate production and glucose transport without affecting the other parameters. Again, lactate was produced only from glucose. Phenytoin decreased isometric tension and oxygen consumption, whereas stimulating lactate production and glycogenolysis. Glycogen was the primary substrate for the lactate produced. Our findings indicate that the compartmentation of substrate utilization is ascribable to the coordination of glycogenolysis with increases in oxygen consumption and the coupling of glycolysis to the Na-K-adenosine triphosphatase. The coupling of independent energy providing pathways to specific endergonic processes indicates a mechanism by which cellular energetic efficiency may be optimized.

Animals↗

PubMed1976

Biotin status and lipid metabolism in adult obese hypercholesterolemic inbred rats.

A statistically significant inverse association was generally found between plasma total lipid, cholesterol, or phospholipid and biotin status of 300-day-old male inbred BHE (IN-BHE) rats. Plasma, liver, and carcass lipid of both sexes generally had a significant direct association with liver lactate dehydrogenase activity; an inverse association in males resulted with improved biotin status. Elevated plasma lactate indicative of anaerobic glycolysis was found. It is proposed that an increased reductive environment - a consequence of accumulated NADH - could account for enhanced triglyceride synthesis and that this effect could explain the obesity in the IN-BHE rats. After the injection of 300 mug of biotin, plasma levels of lactate and pyruvate fell in male rats, indicating a stimulatory effect of biotin upon the oxidative pathways in these animals.

Animals↗

PubMed1988

Oxytocin and vasopressin gene expression in the hypothalamo-neurohypophyseal system of the rat during the estrous cycle, pregnancy, and lactation.

To study the state of hypothalamic expression of the oxytocin (OT) and vasopressin (VP) genes in different conditions of the female rat, OT and VP mRNA levels were determined during the estrous cycle, pregnancy, and lactation. OT and VP mRNA levels of the supraoptic nucleus were quantified by Northern blot and dot-blot analysis. OT and VP contents of the pituitary gland were determined by RIA. During the estrous cycle, OT mRNA levels of the supraoptic nucleus were significantly increased 1.5- to 2-fold at estrous relative to the other periods of the cycle. No significant cyclic variation was observed in VP mRNA levels. The OT content of the pituitary gland was significantly decreased at estrus and also the VP contents showed a cyclic variation with the lowest levels occurring at estrus and metestrus. At the last day of gestation a 3- and 2-fold increase of OT mRNA and VP mRNA, respectively, was measured, but no changes were observed at gestational day 12, 15, and 18. In rats lactating for 15 days, OT and VP mRNA levels were approximately 3-fold higher than during the estrous cycle. Concomitantly the OT and VP contents of the pituitary gland were decreased by approximately 50%. It is concluded that both OT and VP gene expression are stimulated just before birth and during lactation indicating that both genes are sensitive to common factors. A dissociation of the regulation of the OT and VP genes occurs in the estrous cycle.

Animals↗

PubMed1988

In vivo lactate kinetics at rest and during recovery from exhaustive exercise in coho salmon (Oncorhynchus kisutch) and starry flounder (Platichthys stellatus).

A bolus injection of [14C]lactate was used to measure lactate turnover rates at rest and during recovery from exhaustive exercise in coho salmon (Oncorhynchus kisutch) and starry flounder (Platichthys stellatus). At rest, lactate turnover rate in salmon was almost double that in flounder (1.33 versus 0.76 mumol min-1 kg-1), which reflected the higher blood lactate level in salmon (1.00 versus 0.12 mmol l-1). From 2 to 4 h after exercise, when blood lactate levels were at their peak and constant, turnover rates were elevated in both species, though to a greater extent in salmon than in flounder (11.88 versus 2.27 mumol min-1 kg-1). Lactate concentration and turnover rate were linearly correlated in both species. The higher turnover rate in salmon was solely a consequence of the higher blood lactate levels since, at similar blood lactate concentrations, turnover rates in flounder and salmon were the same. Therefore, the lower blood lactate levels in flounder after exercise were not a consequence of higher turnover. In neither species was the turnover rate adequate to account for the rate of lactate clearance from the muscle, suggesting a large portion was retained within the muscle and metabolized in situ. Furthermore, following injection of [14C]lactate, greater than 80% of the total blood activity was recovered as lactate, indicating that little label was incorporated into other products (e.g. glucose). These data suggest that the Cori cycle plays a minimal role in the metabolism of lactate in salmon and flounder. Furthermore, at least in flounder, there was no correlation between the kinetics of lactate clearance and O2 consumption, suggesting that the classical concept of 'O2 debt' is not applicable in this species.

Animals↗

PubMed1987

Mammary resistance: a possible controlling factor in milk ejection.

At 8 and 13 days post partum, rats have the same total milk availability; yet, in response to suckling they release a greater amount of milk on day 13 than on day 8. Increased sensitivity to suckling in the more advanced lactators may result from a greater release of oxytocin or from changes in the mammary glands as lactation advances. The present study explores this latter possibility in anaesthetized dams at 8-9 and 13-15 days of lactation. Milk release and intramammary pressure were measured in anaesthetized dams in response to various doses of oxytoxin. Milk release was determined from the body weight gain of pups which had been fasted for 5 h before suckling on dams which had been isolated for 5 h. This parameter was significantly greater in 13- to 15-day lactators than in 8- to 9-day lactators over the range of oxytocin doses examined. In contrast, intramammary peak pressure and its dissipation time were significantly larger in the 8- to 9-day lactators than in the 13- to 15-day lactators. The compliance of the mammary glands was indirectly assessed at the two stages of lactation. When a constant pressure pulse was introduced into a cannulated gland, the resulting pressure peak was significantly greater in 8-day than in 13-day lactators, indicating a greater resistance in the former. Taken together, these results indicate that when endogenous oxytocin is inhibited (by anaesthesia) the greater milk release observed at the later stage of lactation in response to various doses of oxytocin may be due to a decline in mammary resistance as lactation progresses.

Animals↗

PubMed1990

Metabolic responses to euglycaemic hyperinsulinaemia in lactating and non-lactating sheep in vivo.

Glucose utilization and production and changes in concentrations of plasma metabolites were studied in lactating and non-lactating sheep in response to three levels of insulin infusion whilst maintaining euglycaemia. Glucose utilization and production responded to insulin infusion similarly in both lactating and non-lactating ewes but, as circulating concentrations of insulin were lower in lactating animals, these parameters appeared more sensitive to plasma concentrations of insulin in lactating sheep. Changes in plasma concentrations of glycerol and free fatty acids during lactation indicated reduced sensitivity to insulin in adipose tissue and changes in plasma concentrations of amino acids were also less during lactation, suggesting reduced sensitivity of protein synthesis to insulin. Changes in plasma concentrations of urea and beta-hydroxybutyrate during lactation were similar to those in non-lactating animals, indicating similar insulin sensitivity of hepatic metabolism. It is concluded that during lactation ovine adipose tissue and muscle are more resistant to increased concentrations of insulin but that the sensitivity of the sheep liver is unchanged or increased. The rate of removal of insulin from the circulation was higher in lactating animals.

Animals↗

PubMed1991

Patterns of plasma sex hormone-binding globulin, thyroxine and thyroxine-binding globulin in relation to reproductive state and hibernation in female little brown bats.

A sex hormone-binding globulin (SHBG), which bound both oestradiol and dihydrotestosterone, was studied in the plasma of adult female little brown bats throughout the annual reproductive cycle. This protein was present at low baseline levels from September to May inclusive, months which correspond to the periods of hibernation, ovulation and early pregnancy. During the second half of pregnancy in June, SHBG levels increased 15- to 30-fold and remained increased throughout lactation and anoestrus/prooestrus (July-August). Although SHBG was increased during late pregnancy, the fact that levels were also high during and after lactation indicates that this protein is not specific to pregnancy. Plasma concentrations of thyroxine (T4) and the percentage binding of T4 to thyroxine-binding globulin (TBG) also showed marked seasonal variations, with T4 levels exhibiting a biphasic seasonal pattern. A major peak in plasma concentrations of T4 occurred around the time of spring arousal from hibernation and subsequent ovulation, while a second peak of lesser magnitude was measured in August, corresponding to the time of pro-oestrus and the onset of mating. The percentage binding of T4 by TBG was increased during the summer months in parallel with the increase in SHBG concentrations. Electrophoretic analysis of plasma T4 binding revealed a single peak of TBG activity throughout most of the year; however, during the early lactational period TBG was resolved as a double peak, suggesting the presence of a molecular variant during this reproductive stage.

Animals↗

PubMed1989

Effects of copper and molybdenum supplements on the copper and selenium status of pregnant ewes and lambs.

The aim of this work was to investigate whether Cu, alone or in combination with Mo, reduces the Se status of sheep. Thirty-six Hampshire ewes were separated prior to mating into four treatment groups of nine sheep each. The four groups consisted of 1) basal (alfalfa hay or legume-grass low-moisture silage, corn, oats), 2) basal plus 10 mg Cu/kg diet, 3) basal plus 10 mg Mo/kg and 4) basal plus Cu and Mo (each 10 mg/kg). Copper and Mo were added to both ewe and lamb diets. Treatments continued until lambs were weaned at 10 wk postpartum. The basal ewe diet contained, in mg/kg, 5.6 Cu, .05 Se and 1.0 Mo. The basal lamb diet contained, in mg/kg, 6.1 Cu, .07 Se and less than 1.0 Mo. Sulfur concentrations in the ewe and lamb diets were .24% and .20%, respectively. Copper supplements increased, and Mo supplements decreased, the concentration of Cu in the livers of ewes and lambs (P less than .05). Despite this, there were no effects of treatment on Se concentration or glutathione peroxidase activity in blood or tissues. Selenium levels in plasma of all ewes declined throughout pregnancy and lactation, indicating that .05 mg/kg Se was insufficient for the maintenance of Se status during pregnancy in Hampshire ewes. Copper and Se levels (mg/kg fresh weight) in the liver of lambs at weaning for Treatments 1 through 4 were 48 and .13, 158 and .10, 11 and .11, and 136 and .13, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1985

Metabolic and functional effects of phosphoenolpyruvate and adenosine triphosphate on rat hearts subjected to global ischemia.

The effect of phosphoenolpyruvate (PEP) and adenosine triphosphate (ATP) administered during ischemia was investigated, using the paracorporeal rat heart model. During 15 min of global ischemia the hearts were perfused twice with PEP and ATP (supplemented) or with NaCl only (non-supplemented). In hearts that were freeze-clamped after the ischemic period (group A), the myocardial content of high-energy phosphates showed only minor differences between hearts with and without supplemention. In the supplemented hearts there was increased myocardial content of pyruvate and, to some extent, of lactate, indicating that PEP was metabolized to pyruvate and partly to lactate. In groups B and C the hearts were reperfused for 40 min before freeze-clamping. The non-supplemented hearts showed higher energy content and better left ventricular performance and, concomitantly, the creatine kinase isoenzyme MB (CK-MB) efflux was less than for the supplemented hearts. A clear inverse relationship between left ventricular performance and CK-MB efflux indicated that CK-MB served as a marker of cell integrity. These results contrasted with previus finding of an unequivocally positive effect from PEP and ATP administration. Possible explanations are discussed.

Adenosine Triphosphate↗

PubMed1975

Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle.

Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1978

Effects of activated carbon, phenobarbital, and vitamins A, D, and E on polybrominated biphenyl excretion in cows.

Twelve cows environmentally contaminated with polybrominated biphenyl residues were in a balanced two-period changeover experiment. The treatments were activated carbon and sodium phenobarbital; sodium phenobarbital and injections of vitamins A, D, and E; activated carbon, phenobarbital, and vitamins A, D, and E; and control. A standard roughage and concentrate diet was fed. Average initial concentrations of polybrominated biphenyls in the milk fat ranged from 92 to 236 ppm. The experimental treatments did not affect significantly excretion of polybrominated biphenyls in milk and feces or the apparent half-life of residues in milk fat averaged 60 days but ranged from 36 to 301 days. The longer half-life in early lactation than in later lactation indicated an effect of change of body weight on half-life. Milk was the major route of excretion, averaging 6.5 times that of fecal excretion. Polybrominated biphenyl in milk fat, body fat, blood, and feces followed parallel concentrations troughout the study.

Adipose Tissue↗

PubMed1985

Supplementation of dairy cow diets with ammonium salts of volatile fatty acids.

The objective was to determine the efficacy of a blend of ammonium salts of the volatile fatty acids, isobutyric, 2-methylbutyric, isovaleric, and valeric as a supplement to diets for dairy cows. Treatments of 0 (control) or 120 (supplemented) g/cow of the blend were fed daily from approximately 3 wk prepartum through a complete lactation. Five trials were conducted concurrently with a total of 116 multiparous Holstein cows. Dietary ingredients or combinations of ingredients differed in each of the trials. Diets contained either 1) corn gluten meal and urea, 2) soybean meal, or 3) cottonseed meal as the primary grain source of crude protein. The forage portion of the diets contained corn silage in combination with one or more of the following: alfalfa hay, alfalfa haylage, or wheat silage. Cows fed the supplement produced more milk and fat-corrected milk than the control cows for the 305-d lactation on four of the five diets, resulting in an average increase of 1.7 kg/d or 7%. Feed intake of cows on the supplemented diet was generally similar or lower than intake of the control cows throughout lactation, indicating that increased milk yield was associated with improved feed utilization. Percent milk fat was similar for cows on the supplemented diet, but fat yield was higher. Percent milk protein was lower for supplemented cows, but protein yield was about the same for both treatments because of higher milk yield. Health and reproduction were similar for all cows.

Animal Feed↗

PubMed1976

Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury.

Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (C1-) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in C1- levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.

Animals↗

PubMed1992

Myocardial extraction of lactates, non-esterified fatty acids and their fractions in patients with dilated cardiomyopathy at rest and after the cold pressor test.

UNLABELLED: A decrease in the myocardial extraction or excretion of lactates indicates its hypoxia. The authors analyzed changes in the extraction of lactates, non-esterified fatty acids (NEFA) and their fractions: C 14:0, C 16:0, C 16:1, C 18:1, C 18:2 in a group of 15 patients with dilated cardiomyopathy (DC) and in 10 controls at rest and after the cold pressor test (CPT). At rest, 5 patients with DC produced lactates or extracted less than 10%. During CPT, production of lactates was observed in another four patients (mean values: 17.9 +/- 32.6% vs 24.5 +/- 5.2%, ns). NEFA extraction was found in the DC group: 18.4 +/- 20.6% vs. 13.9 +/- 33.3% /p < 0.05/). The acids involved were C 14:0, C 16:0, C 16:1 and C 18:0. In the controls, NEFA extraction did not change significantly: 12.1 +/- 8.6% vs 29.7 +/- 33.2%. CONCLUSIONS: 1. In part of patients with DC, production of lactates was found. The degree of lactate excretion increased due to CPT; 2. In DC, adrenergic stimulus (CPT) impairs the myocardial utilization of NEFA. This applied mainly to myristic acids, palmitic acid, palmitooleic acid and stearic acid; 3. This phenomenon probably is a result of profound functional and morphological damage to the mitochondrial system in DC.

Adult↗

PubMed1992

[Inhibition of initial puerperal and postabortion lactation using oral prostaglandin E2 (Dinoprostone)].

Authors present their experience in oral administration of Prostaglandin E2 (Dinoproston, Upjohn) during postpartal and postabortal period (à 0.5 mg after legal pregnancy interruption) in suppression of lactation. Indications for postpartal lactation suppression were such as: stillbirth, postpartal neonatal death and maternal negative attitude towards breast feeding. The patients in whom the suppression of lactation was applied were of generative age (18-40 years) either primiparas or multiparas. All were delivered vaginally with no extra intrapartal or postpartal complications being the same in legal pregnancy interruptions which were performed by application of intravaginal, intracervical and intramuscular Prostaglandin preparations. The patients were administered 1 tbl od 0.5 mg Dinoproston preparation every 6-7 hours, 48 h after the delivery, i.e. 2 tbl in total (after meal). This method of lactation suppression was applied in 50 patients during 1990. Satisfactory results were achieved in all cases, while negative side effects and complications were not noted. Oral administration of PGE2 was found very efficient in postpartal and postabortal lactation suppression while compared with previously applied methods such as Estrogen-Testosterone preparation, i.e. small doses of Bromergon applied during 10-14 days. Oral administration of PG2 is more efficient and in a certain way more comfortable in relation to the previously applied methods.

Abortion, Induced↗

PubMed1992

[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).

Animals↗