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Neonatal programming of body weight regulation and energetic metabolism.

Programming is an epigenetic phenomena by which nutritional, hormonal, physical psychological and other stressful events acting in a critical period of life, such as gestation and lactation, modifies in a prolonged way certain physiological functions. This process was preserved by natural selection as an important adaptive tool for survival of organisms living in nutritional impaired areas. So, malnutrition during gestation and lactation turns on different genes that provide the organism with a thrifty phenotype. In the case of an abundant supply of nutrients after this period, those organisms that were adapted to a low metabolic waste and higher energy utilization will be in a higher risk of developing metabolic diseases, such as obesity, hyperlipidemia, diabetes mellitus and hypertension. The kind of malnutrition, duration and intensity are important for the type of programming obtained. We discuss some of the hormonal and metabolic changes that occur in gestation or lactation, when malnutrition is applied to the mothers and their offspring. Some of these changes, such as an increase of maternal triiodothyronine (T(3)), leptin and glucocorticoids (GC) and decrease in prolactin are by itself potential programming factors. Most of these hormones can be transfer through the milk that has other important macronutrients composition changes in malnourished dams. We discuss the programming effects of some of these hormones upon body weight and composition, leptin, thyroid and adrenal functions, and their effects on liver, muscle and adipose tissue metabolism and the consequences on thermogenesis.

Adrenal Glands↗
PubMed1987

Prolonged exercise at a constant load on a bicycle ergometer: ratings of perceived exertion and leg aches and pain as well as measurements of blood lactate accumulation and heart rate.

To study changes over time during prolonged exercise on a bicycle ergometer at a constant load, 22 healthy males rated perceived exertion as well as aches and pain in the legs, and measurements were taken on blood lactate accumulation and heart rate (HR). The prolonged exercise was carried out at WOBLA (the power level eliciting a blood lactate concentration of 4 mmol X l-1). All four measured variables, ratings of perceived exertion, ratings of aches and pain in the legs, blood lactate accumulation, and HR, grew systematically according to negatively accelerating functions. HR showed more of a steady state, whereas all the other three variables grew continuously over time. Three subgroups were identified related to the blood lactate response after 15 min at WOBLA: elevated (greater than 5 mmol X l-1), intermediate (3.5-4.9 mmol X l-1), and low (less than 3.4 mmol X l-1). It was suggested that a major contribution to the discrepancies in blood lactate between the subgroups after 15 min was partly due to insufficient warming up, which was 5 min at 20 W as compared with the final power level (WOBLA), which differed between 140 and 260 W. After 15 min both rated perceived exertion and rated aches and pain in the legs were related to the corresponding blood lactates. It was suggested that rated perceived exertion and rated aches and pain in the legs partly reflected the degree of "anaerobic" metabolism measured as blood lactate.

Adult↗
PubMed2004

Surviving extreme lactic acidosis: the role of calcium lactate formation in the anoxic turtle.

During prolonged anoxia at low temperature, freshwater turtles develop high plasma concentrations of both lactate and calcium. At these concentrations the formation of the complex, calcium lactate, normally of little biological significance because of the low association constant for the reaction, significantly reduces the free concentrations of both lactate and calcium. In addition, lactate is taken up by the shell and skeleton to an extent that strongly indicates that calcium lactate formation participates in these structures as well. The binding of calcium to lactate thus contributes to the efflux of lactic acid from the anoxic cells and to the exploitation of the powerful buffering capacity of the shell and skeleton.

Acidosis, Lactic↗
PubMed1981

Hormonal and substrate responses during recovery from hypoglycaemia in man during beta 1-selective and non-selective beta-adrenergic blockade.

Recovery from acute hypoglycaemia induced by the injection of insulin has been examined in six human subjects under control conditions, under non-selective beta blockade (propranolol) and under selective beta 1 blockade (metoprolol). The normal blood glucose recovery was biphasic with an initial rapid and a slower subsequent phase of recovery. The early recovery mechanism was unaffected by either form of beta blockade, but with propranolol the late phase of recovery was significantly prolonged. Rises in blood lactate and plasma free fatty acids following hypoglycaemia were markedly reduced by propranolol but to a much lesser degree with metoprolol. The counterregulatory hormonal responses of glucagon, cortisol and growth hormone were augmented appropriately for the prolonged hypoglycaemia associated with propranolol. Non-selective beta adrenergic blockade with propranolol is associated with an impairment of the late phase of blood glucose recovery from hypoglycaemia. The possible mechanisms of this impairment are discussed.

Acetoacetates↗
PubMed1999

Metabolic and thermodynamic responses to dehydration-induced reductions in muscle blood flow in exercising humans.

1. The present study examined whether reductions in muscle blood flow with exercise-induced dehydration would reduce substrate delivery and metabolite and heat removal to and from active skeletal muscles during prolonged exercise in the heat. A second aim was to examine the effects of dehydration on fuel utilisation across the exercising leg and identify factors related to fatigue. 2. Seven cyclists performed two cycle ergometer exercise trials in the heat (35 C; 61 +/- 2 % of maximal oxygen consumption rate, VO2,max), separated by 1 week. During the first trial (dehydration, DE), they cycled until volitional exhaustion (135 +/- 4 min, mean +/- s.e.m.), while developing progressive DE and hyperthermia (3.9 +/- 0.3 % body weight loss and 39.7 +/- 0.2 C oesophageal temperature, Toes). On the second trial (control), they cycled for the same period of time maintaining euhydration by ingesting fluids and stabilising Toes at 38.2 +/- 0.1 degrees C. 3. After 20 min of exercise in both trials, leg blood flow (LBF) and leg exchange of lactate, glucose, free fatty acids (FFA) and glycerol were similar. During the 20 to 135 +/- 4 min period of exercise, LBF declined significantly in DE but tended to increase in control. Therefore, after 120 and 135 +/- 4 min of DE, LBF was 0.6 +/- 0.2 and 1.0 +/- 0.3 l min-1 lower (P < 0.05), respectively, compared with control. 4. The lower LBF after 2 h in DE did not alter glucose or FFA delivery compared with control. However, DE resulted in lower (P < 0.05) net FFA uptake and higher (P < 0.05) muscle glycogen utilisation (45 %), muscle lactate accumulation (4.6-fold) and net lactate release (52 %), without altering net glycerol release or net glucose uptake. 5. In both trials, the mean convective heat transfer from the exercising legs to the body core ranged from 6.3 +/- 1.7 to 7.2 +/- 1.3 kJ min-1, thereby accounting for 35-40 % of the estimated rate of heat production ( approximately 18 kJ min-1). 6. At exhaustion in DE, blood lactate values were low whereas blood glucose and muscle glycogen levels were still high. Exhaustion coincided with high body temperature ( approximately 40 C). 7. In conclusion, the present results demonstrate that reductions in exercising muscle blood flow with dehydration do not impair either the delivery of glucose and FFA or the removal of lactate during moderately intense prolonged exercise in the heat. However, dehydration during exercise in the heat elevates carbohydrate oxidation and lactate production. A major finding is that more than one-half of the metabolic heat liberated in the contracting leg muscles is dissipated directly to the surrounding environment. The present results indicate that hyperthermia, rather than altered metabolism, is the main factor underlying the early fatigue with dehydration during prolonged exercise in the heat.

Adult↗
PubMed1980

Induction by young of prolonged dioestrus in virgin rats behaving maternally.

The present investigation examined, by study of daily vaginal smears, whether the interaction of virgin female rats with young affected the oestrous cycle. Virgins behaving non-maternally or maternally were continuously exposed to young for extended periods. (1) All non-maternal virgins continued to cycle while 87% of maternal virgins ceased to cycle when exposed to young, and entered a series of prolonged dioestrous phases, each lasting about 14 days. Likewise, all maternal parous non-lactating controls exposed to young entered prolonged dioestrus. (2) The dioestrous phase induced by young in virgins was characterized by the decidual response. (3) Young aged 4-9 days were as effective as 10-15-day-old young for inducing and maintaining the dioestrus. (4) Confinement of young in a wire-mesh basket showed that body contact with young was essential to establish dioestrus. (5) Body contact with young was sufficient to induce dioestrus in maternal virgins with excised nipples. (6) Once established, the dioestrus could be maintained for about 12 days after removal of young as early as Day 4 of dioestrus in virgin and parous non-lactating females, but removal of young on Day 6 from post-partum lactating females resulted in a rapid resumption of cyclicity. (7) Prolonged suckling during a series of dioestrous phases induced lactation in 61% of maternal virgins, as well as in all parous control females.

Age Factors↗
PubMed1979

Lactation and fertility.

During the last decade there have been many reports indicating a decline in breast feeding practices in the urban areas of developing countries. This decline might have adverse effects on maternal and child health. A study of 1079 urban hospital attending women was undertaken to evaluate their breast feeding practices. Prolonged (mean duration of lactation 19.8 months) and successful lactation (failure of lactation occurred in only 3.5%) was common among this group. But a trend toward shorter duration of breast feeding was found among educationally and economically better off segment. There was very good correlation between mean duration of lactation, lactational amenorrhea, and interpregnancy interval. Therefore, it is possible that decrease in duration of lactation might result in shorter interpregnancy interval. The duration of lactation appeared to be "fixed" for each individual irrespective of age and parity. This in turn resulted in "fixed" duration of lactational amenorrhea and interpregnancy interval under conditions of unhindered lactation and uncontrolled fertility. Conception during lactational amenorrhea was low (7.7%) but once periods were reestablished lactation offered very little protection against conception.

Adolescent↗
PubMed1983

Pyruvate and lactate levels in oviducts of cycling, pregnant, and pseudopregnant mice.

Pyruvate and lactate were measured in oviducts during the first 5 days following ovulation in cycling, pregnant, and pseudopregnant mice, to determine how oviductal metabolism might change to promote the availability of these substrates to the early embryo. The postovulatory peak in ampullar pyruvate was most evident in the 12-h pregnant oviduct, 3.19 mmol . kg-1. This increase at +12 h was related to a decrease in lactate dehydrogenase (LDH) activity, compared to cycling animals, observed at this time. Although cycling animals showed a significant increase in isthmic pyruvate at +3 h, no change in isthmic pyruvate was observed in either mated group through the postovulatory period. Isthmic LDH activity was also unchanged in cycling or mated animals through this period. Ampullar lactate in both mated groups was elevated at 12 to 24 h after ovulation, a pattern similar to that seen in cycling animals. Isthmic lactate levels also increased after ovulation in all groups, but in the pregnant group the lactate remained elevated (25-28 mmol . kg-1) through 72 h, while concentrations in the cycling and pseudopregnant animals, returned to low levels (14-16 mmol . kg-1) by 48 h. The patterns of pyruvate and lactate, especially those in the pregnant animals, seem suited to providing these metabolites at levels near those required for optimal in vitro embryo growth. The +12 h ampullar pyruvate peak noted in mated animals implies a specific response to the mating stimulus. Prolongation of increased isthmic lactate levels only in pregnant animals suggests a response of the oviduct to the viable embryo.

Analysis of Variance↗
PubMed1996

Effect of sustained hyperadrenalinemia on exercise performance and lactate threshold in rats.

The effect of prolonged elevation of blood adrenaline concentration (sustained up to 60 h) on exercise performance and lactate threshold (TLA) was investigated in 24 rats on the basis of a incremental, multistage treadmill exercise test, performed before and after subcutaneous implantation of retard adrenaline tablets (15 mg), which release adrenaline at a constant rate of approx. 1.6 micrograms min-1. Blood samples for lactate (LA) determinations were taken from the rats' tails after each exercise stage. The results obtained indicate that hyperadrenalinemia within the physiologic range, sustained for 6 or 12 h, decreases exercise performance, measured as the maximal speed of running, increases blood LA concentration during submaximal and maximal exercise, and shifts TLA toward lower exercise intensities than in control or sham-operated rats. When adrenaline excess was maintained for 60 h the maximal running speed was still reduced, and exercise blood LA was even higher than during earlier stages of hyperadrenalinemia, but TLA returned to control values. In the rat, a moderate excess of circulating adrenaline, sustained up to 60 h, reduces maximal exercise performance, and causes marked elevations in submaximal and maximal blood lactate concentration. However, this is accompanied by lowering of TLA only in the early stages of hyperadrenalinemia (6 and 12 h), which suggests that shifts of TLA may occur independently of absolute levels of blood lactate during graded exercise.

Animals↗
PubMed1996

Lactation, nutrition, and postpartum amenorrhea in lowland Papua New Guinea.

Prolonged on-demand breast feeding is known to delay the resumption of postpartum ovarian cyclicity. At present, however, little is known about the factors that influence the effectiveness of breast feeding as a natural contraceptive. Here, I examine the effects of maternal nutritional status on the duration of postpartum amenorrhea in two socioeconomic groups of Au forager-horticulturalists of lowland Papua New Guinea. Although women in both groups continue to breast-feed their offspring for approximately three and one-half years, well-nourished wage-earning Au women experience their first postpartum menses just over one year earlier (median = 12.5 months) than their more poorly nourished traditional counterparts (median = 26.6 months). Probit analyses are used to demonstrate that, even after controlling for time since delivery, maternal age, parity, and supplementation of infants' diets, the duration of postpartum amenorrhea is significantly (p < 0.05) negatively associated with indexes of maternal fat mass. No association between indexes of maternal lean body mass and the duration of postpartum amenorrhea were found. The results of this study suggest that components of maternal nutritional status, in particular, adiposity, play an important role in influencing fecundity in human populations.

Amenorrhea↗
PubMed1999

The hypothalamic-pituitary-adrenal axis response to endotoxin is attenuated during lactation.

Pregnancy and lactation are times of prolonged physiological changes affecting the neuroendocrine and immunological systems. One well-characterized change is the neuroendocrine hyporesponsiveness to acute stressful stimuli. We have now designed studies to see whether there is an alteration in the response of the hypothalamic-pituitary-adrenal (HPA) axis to an immunological inflammatory challenge and to ascertain whether lactating animals show altered neural and endocrine responses to inflammatory stimuli. Lactating (day 9-12 postpartum) or virgin control Sprague-Dawley female rats were injected with either 200 microg of endotoxin (lipopolysaccharide, LPS ) or sterile saline given i.p. Trunk blood or jugular blood was collected from the animals at 2 h or hourly over 6 h after injection. Both plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations were significantly higher in saline treated lactating animals compared with the virgin group. LPS significantly elevated circulating levels of plasma ACTH and corticosterone in both virgin and lactating animals compared with saline controls, however, hormone responses to LPS were significantly reduced in lactating animals relative to virgin controls. Corticosterone-binding globulin concentrations were lower in lactating animals compared to virgin animals and LPS decreased concentrations in virgin, but not lactating rats. Analysis of cfos mRNA in the paraventricular nucleus (PVN) of the hypothalamus revealed that 2 h following injection there was a increase in cfos expression only in the virgin animals treated with LPS, compared to all other treatment conditions. Corticotropin-releasing hormone (CRH) mRNA expression was overall greater in virgin animals, but was increased to similar extent in both virgin and lactating animals treated with LPS. Primary arginine vasopressin (AVP) mRNA transcripts were increased 2 h following LPS injection, but a greater increase in expression was seen in virgin animals. These data demonstrate that there is a lower level of free circulating glucocorticoid in response to inflammatory stimuli and suggests that communication between the immune and endocrine systems may be altered during lactation.

Adrenocorticotropic Hormone↗
PubMed1985

Effect of prolonged gliclazide therapy in non-insulin dependent diabetic subjects.

The effect of prolonged gliclazide treatment on diabetic metabolic control was studied in 10 subjects with non-insulin dependent diabetes mellitus. Patients were examined before, after 15 days of treatment with diet alone and, again, after 60 days of treatment with diet plus gliclazide. Gliclazide did not restore the abnormality of blood glucose, free insulin and C-peptide response to an intensive stimulus of glucose load, although fasting and after-load blood glucose, fasting glycosylated haemoglobin, alanine and lactate significantly decreased after prolonged treatment with diet plus gliclazide, but not with diet alone. These findings support the assumption that the efficacy of prolonged treatment with gliclazide might be related to its extrapancreatic effects on glucose homeostasis.

Adult↗
PubMed1968

Induction of adenosine deaminase in Escherichia coli.

Supplementing the salts-glucose medium of Escherichia coli with adenine initiates induction of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), growth inhibition, and an increased potential for the net deamination of adenine. The extent and duration of these events are proportional to the initial adenine concentration and are dependent upon adenylate pyrophosphorylase and repression of histidine biosynthesis for maximal expression. The conversion of adenine to hypoxanthine, though limited in rate, occurs concurrently with induction and accounts for the progressively decreasing rate of deaminase induction, since hypoxanthine is a relatively ineffective inducer. The subsequent decrease in deaminase activity is due to dilution by continued cell division and by enzyme inactivation which occurs during the late-log and early-stationary phases. The partially purified deaminase is labile to a number of environmental conditions, particularly to phosphate buffers of pH 6.8 or less. A disproportionately slow rate of adenine deamination by cells utilizing lactate permits a more prolonged period of induction and, consequently, a greater quantity of enzyme to be synthesized; cell division, but not enzyme inactivation, reduces enzyme concentration. The adenosine deaminases of Aerobacter aerogenes and Salmonella typhimurium are not inducible.

Adenine↗
PubMed1986

Effects of lactate-induced panic attacks on brain stem auditory evoked potentials.

As the clinical symptomatology of panic attacks may be conceivably related to abnormal brain stem activity, the present study examined the effect of lactate-precipitated panic on brain stem auditory evoked potentials (BSAEPs). The subjects were 27 patients who met DSM-III criteria for panic disorder (Pd), agoraphobia with panic attacks (AgPa) or agoraphobia (Ag). Following drug washout, patients were tested in two separate sessions, in a double-blind randomised controlled design in which each session involved two sequentially ordered BSAEP collection periods - a baseline period with no infusion followed by an intravenous infusion of 5% dextrose in water or 1.0 M sodium lactate (5 ml/kg in 5% dextrose/water) over a 20-min period. Of the 27 patients, 17 were clear responders, reporting panic attacks and self-report changes under lactate similar to those occurring during spontaneous panic. Of the remaining 10 patients, 6 were pseudo-responders, reporting panic symptoms under both dextrose and lactate, and 4 were non-responders. In the clear responders, lactate did not alter electrical events of the BSAEP, but further analysis within the clear responders, comparing AgPa patients with Pd patients, yielded a significant effect with lactate resulting in a prolonged III-V inter-peak interval in the AgPa group. It is suggested that the increased III-V interval in the AgPa group may be reflective of hyperactivity of brain stem noradrenergic nuclei.

Anxiety↗
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↗
PubMed1987

Sodium valproate: effects on maternal behaviour in the mouse.

The behaviour of lactating mice in their home cages was examined by ethological procedures at 1, 7, 14 and 21 days postpartum. Early in lactation, maternal behaviour was more frequent in the light phase of the 24 hr cycle, whereas non-social activity occupied a greater amount of time during the dark phase. As the pups became older, maternal behaviour declined, and at 21 days the dams showed a marked increase of solitary immobility. Behavioural alterations produced by the administration of sodium valproate at 600 mg/l as drinking fluid during pregnancy and lactation (group SVP), and during lactation only, (group PN) were assessed. (Intake of drug amounted to 153 mg/kg during gestation and 186 mg/kg in lactation). Dams of group PN showed behavioural differences from controls in late lactation, pup nursing being prolonged at day 14 postpartum and the frequency of all categories of active behaviour, other than nursing and nestbuilding, was increased at day 21 postpartum in the dark phase of their daily cycle. There was not significant effect on categories of behaviour in dams of the SVP group. Overall, sodium valproate, at this dose, did not reduce maternal care.

Animals↗
PubMed1977

Biochemically assisted antibiotic treatment of lethal murine Staphylococcus aureus septic shock.

Evidence has been sought for life-prolonging effects of a variety of chemicals given subcutaneously 1 hr after intraperitoneal challenge of mice with 10(9) Staphylococcus aureus cells. The chemicals were chosen to replace chemicals found to be missing in the blood or carcass at death or to treat biochemical or visible abnormalities in sick mice near death from infection. Nafcillin given subcutaneously in adequate amounts cure S. aureus infection. In these experiments nafcillin treatment was delayed until 40% of the time from challenge to death in the controls. Chemicals were given in addition to nafcillin subcutaneously 20% of the time from challenge to death. Cortisol, Dilantic, epsilon-aminocaproic acid, glucose, nicotinamide, olive oil, phentolamine-propanalol, sodium bicarbonate, sodium lactate, and reserpine each prolonged life compared to saline treatment. When nafcillin was added, only cortisol, Dilantin, nicotinamide and reserpine were found to prolong life significantly compared to nafcillin-saline treatment Fatality rates were significantly reduced with cortisol and Dilantin when they were given in association with nafcillin compared to nafcillin-saline treatment.

Animals↗