Effect of Fractionated Weaning on Hormonal Patterns and Weaning to Oestrus Interval in Primiparous Sows

The effect of weaning the 4–5 heaviest piglets in the litter on day 33 of lactation and the remainder 2 days later (fractionated weaning) on plasma levels of prolactin, Cortisol, oestradiol-17β (E2), progesterone (P4) and LH, as well as on the weaning to oestrus interval in primiparous sows was studied. Twelve crossbred sows were grouped into 6 pairs according to farrowing date and litter size. The litter of 1 sow in each pair (F) was weaned in 2 stages, and the other conventionally weaned at 35 days (C). Blood samples were collected via a permanent jugular vein catheter every 3 h from 9 am to 9 pm daily throughout the experimental period, and intensively at 15 min intervals for 12 h on the day of first and final weaning and for 6 h on the day after each weaning. All sows were slaughtered following their first post-weaning oestrus and the reproductive organs were macroscopically examined. Lactational oestrus was not observed in any of the sows. Sows from 5 out of 6 pairs showed oestrus within 8 days of weaning and post-mortem examination showed normal ovulation. There was a tendency for the F sows to have a shorter weaning to oestrus interval, as compared with the C sows (5 of 6 pairs, 4.8 days v 5.6 days). The plasma levels of prolactin around weaning were not significantly different between the 2 groups. Within 6 h after final weaning, the prolactin concentrations decreased gradually from 7.6 and 8.7 to 1.6 and 1.7 µg/l in the control and treatment groups, respectively. The plasma levels of Cortisol, showing a diurnal rhythm (with the lowest level at 6 and/or 9 p m), did on no occasion differ between the 2 groups. On the day of final weaning, no diurnal rhythm was observed, with Cortisol remaining high at 6 and 9 pm. The plasma levels of E2 and P4 were low until final weaning in both groups. After final weaning the E2 levels rose faster in the F sows than in the C sows, to 44.3 and 34.8 pmol/l, respectively, on day 2 (p < 0.01). No significant differences in levels of plasma LH and the number of LH pulses were observed between the groups. After final weaning the average and base levels of LH and the number of LH pulse(s) increased significantly.     

Plasma Thyroxine in the Sow During Pregnancy and Lactation and During Resumption of Ovarian Activity After Weaning

Total thyroxine in plasma was studied during pregnancy, lactation and during the post weaning period. The ovarian activity was monitored by progesterone determinations, and oestrous symptoms were recorded. In the two sows studied during pregnancy there was a distinct decrease in total thyroxine values in the last month of pregnancy, reaching a minimum about the time of farrowing. Total thyroxine values stayed low during lactation, but from about the time of weaning and during the following two weeks the concentrations increased rapidly. There was no difference in the thyroxine pattern in sows resuming ovarian activity within normal time (10 days) after weaning (72 sows) compared with sows with delayed resumption of ovarian activity (19 sows). The thyroxine level after weaning did not differ between sows with “silent 11631” and sows with overt oestrus. Primiparous and pluriparous sows had also similar thyroxine values after weaning. Sows weaned in January—June had a little higher thyroxine concentrations after weaning than sows weaned in July—December. There was a significant negative correlation between number of suckling piglets and thyroxine concentrations before weaning. Free thyroxine index was calculated in some selected samples. The results suggested that the changes observed in total thyroxine reflect changes in the free thyroxine concentrations.     

Modeling Free Energy Availability from Hadean Hydrothermal Systems to the First Metabolism

Off-axis Hydrothermal Systems (HSs) are seen as the possible setting for the emergence of life. As the availability of free energy is a general requirement to drive any form of metabolism, we ask here under which conditions free energy generation by geologic processes is greatest and relate these to the conditions found at off-axis HSs. To do so, we present a conceptual model in which we explicitly capture the energetics of fluid motion and its interaction with exothermic reactions to maintain a state of chemical disequilibrium. Central to the interaction is the temperature at which the exothermic reactions take place. This temperature not only sets the equilibrium constant of the chemical reactions and thereby the distance of the actual state to chemical equilibrium, but these reactions also shape the temperature gradient that drives convection and thereby the advection of reactants to the reaction sites and the removal of the products that relate to geochemical free energy generation. What this conceptual model shows is that the positive feedback between convection and the chemical kinetics that is found at HSs favors a greater rate of free energy generation than in the absence of convection. Because of the lower temperatures and because the temperature of reactions is determined more strongly by these dynamics rather than an external heat flux, the conditions found at off-axis HSs should result in the greatest rates of geochemical free energy generation. Hence, we hypothesize from these thermodynamic considerations that off-axis HSs seem most conducive for the emergence of protometabolic pathways as these provide the greatest, abiotic generation rates of chemical free energy.     

Relation of Childhood Home Environment to Cortical Thickness in Late Adolescence: Specificity of Experience and Timing

What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing.     

Co-administration of Creatine Plus Pyruvate Prevents the Effects of Phenylalanine Administration to Female Rats During Pregnancy and Lactation on Enzymes Activity of Energy Metabolism in Cerebral Cortex and Hippocampus of the Offspring

Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth weight and neonatal sequelae, especially microcephaly and intellectual disability. The mechanisms underlying the neuropathology of brain injury in maternal PKU syndrome are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by phenylalanine administration to female Wistar rats during pregnancy and lactation on some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Phenylalanine administration provoked diminution of body, brain cortex an hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic creatine kinase activities. Co-administration of creatine plus pyruvate was effective in the prevention of those alterations provoked by phenylalanine, suggesting that altered energy metabolism may be important in the pathophysiology of maternal PKU. If these alterations also occur in maternal PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric mothers.     

Haloperidol and Cerebral Metabolism in the Conscious Rat: Relation to Pharmacokinetics

The time course and distribution of alterations in cerebral metabolic activity after haloperidol administration were evaluated in relation to the pharmacokinetics of haloperidol and the topography of the dopaminergic system in the brain. Local cerebral glucose utilization was measured, using the 2-deoxyglucose technique, in awake rats after i.p. administration of the dopamine antagonist haloperidol (0.5 or 1 mg/kg). Haloperidol significantly reduced glucose utilization in 60% of 59 brain regions examined, but produced a large increase in the lateral habenula. The regional distribution of changes in glucose utilization was not closely related to the known anatomy of the brain dopaminergic system. The time course of the effect of haloperidol on cerebral metabolism was different for the two doses studied (0.5 and 1 mg/kg), and was not simply related to estimated brain concentrations of haloperidol. However, a linear relation between the metabolic effect and the time-integrated brain concentration was demonstrated. These results show that haloperidol has an effect on CNS metabolic activity that is more widespread than would be predicted from the topography of the dopaminergic system; this may be due to indirect propagation of the primary effects of haloperidol. The metabolic response to haloperidol depends on brain concentration and duration of exposure to the drug.     

Mother — Offspring Conflict in the Saharan Arrui,Ammotragus lervia sahariensis: Relation to Weaning and Mother's Sexual Activity

Behavioural conflict between mother and offspring was investigated in a captive population of the Saharan arrui (Ammotragus lervia sahariensis, Artiodactyla: Bovidae). The frequency of agonistic behaviours (mother's aggressiveness and calf's retreats) and unsuccessful suckling attempts, Hinde's proximity index and the distances between mother and calf have been analysed in relation to weaning and sexual activity of the mother. Mothers that conceive in the following mating season accelerate the weaning process of their current offspring; furthermore, high-ranking females wean their male calves earlier. Behavioural conflict occurs during the resumption of the mother's sexual activity; however, no conflict appears to happen during weaning.     

Lameness and Claw Lesions of the Norwegian Red Dairy Cattle Housed in Free Stalls in Relation to Environment,Parity and Stage of Lactation

Approximately 88% of Norwegian dairy cattle are housed in tie stalls. Free stall housing for all dairy cattle will be implemented within 20 years. This means that the majority of existing stalls will be rebuilt in the near future. Fifty-seven free stall herds of the Norwegian Red breed were randomly selected and 1547 cows and 403 heifers were trimmed by 13 claw trimmers during the late winter and spring of 2002. The claw trimmers had been taught diagnosing and recording of claw lesions. Environment, management- and feeding routines were also recorded. Fifty-three herds had concrete slatted alleys while 4 had solid concrete. Thirty-five herds had concrete as a stall base, while 17 had rubber mats, 2 had wood and 3 had deep litter straw beds. The prevalence of lameness was 1.6% in hind claws. Models for lameness and claw lesions were designed to estimate the influence of different risk factors and to account for the cluster effects within herd and claw trimmer. Detected risk factors for lameness were: parity three and above and narrow cubicles; for heel horn erosions: lactation stage around 5–7 months after calving and solid concrete alleys; for haemorrhages of the white line: lactation stage around 3–5 months after calving and solid concrete alleys; for haemorrhages of the sole: parity one, lactation stage around 5–7 months after calving and short cubicles, for white line fissures: slatted concrete alleys; for asymmetrical claws: parities two and above and for corkscrewed claws: solid concrete alleys. The prevalence of lameness in heifers was low, however 29% had one or more claw lesions. Heifers that were housed in pens or free stalls had more heel-horn erosions, haemorrhages of the sole and white-line fissures than heifers in tie stalls. As new free stalls are being built, it is important to optimise the conditions for claw health.     

Placental Transfer of a Fully Human IgG2 Monoclonal Antibody in the Cynomolgus Monkey,Rat, and Rabbit: A Comparative Assessment from during Organogenesis to Late Gestation

Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo‐fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approximately 0.5% maternal plasma concentration, MPC) was similar to the limited published human data for endogenous IgG. At this early gestational stage, IgG2X placental transfer was approximately 6‐fold higher in the rabbit (gd10). By the end of organogenesis, rat embryonic plasma concentrations (gd16) exceeded those in the cynomolgus monkey (gd50) by approximately 3‐fold. These data suggest that relative to the cynomolgus monkey, the rabbit (and to a lesser extent the rat) may overestimate potential harmful effects to the human embryo during this critical period of development. Beyond organogenesis, fetal IgG2X plasma concentrations increased approximately 10‐fold early in the second trimester (gd50–70) in the cynomolgus monkey and remained relatively unchanged thereafter (at approximately 5% MPC). Late gestational assessment was precluded in rabbits due to immunogenicity, but in rats, fetal IgG2X plasma concentrations increased more than 6‐fold from gd16 to gd21 (reaching approximately 15% MPC). In rats, maternal exposure consistent with that achieved by ICH S6(R1) high‐dose selection criteria resulted in embryonic plasma concentrations, reaching pharmacologically relevant levels during organogenesis. Furthermore, dose proportional exposure in both mothers and embryos indicated that this was unlikely to occur at the lower therapeutic dose levels used in humans     

Nitrogen Metabolism of Detached Kalanchoe Leaves in the Dark in Relation to Acidification, Deacidification, and Oxygen Uptake

Detached Kalancho leaves were placed in the dark and changesin the amounts of total soluble N, asparagine, glutamine, aminoN, ammonia, and titratable acid were followed during the periodsof acidification and deacidification. Abundant starch was presentthroughout the experiments. The amount of acid which accumulatedin the initial period was increased by placing the leaves in5 per cent. CO₂ and also by decreasing the temperature from25 to 10°. In neither case were the nitrogen fractions affectedin a similar way to the acid levels. No consistent relationshipcould be found between the amount or change in amount of acidand the amounts of the nitrogen fractions. Over prolonged periodsthe drifts in the amounts of the nitrogen fractions were verysimilar to those known in non-succulent leaves. It is concludedthat, despite the large amounts of free acid and starch present,the nitrogen metabolism of detached Kalancho leaves in the darkis similar to that of non-succulent leaves. A possible explanationis suggested for the incorporation of ¹⁴C from ¹⁴CO₂ into nitrogenoussubstances in Kalancho leaves during dark acidification. Changesin the amounts of glutamine, which seemed to be related to oxygenuptake rather than to acid fluctuations, were measured in comparableleaf samples showing different rates of oxygen uptake. The rateof oxygen uptake of leaves and leaf disks in the dark was controlledby placing them in an atmosphere of nitrogen, or 5, 20, or 100per cent, oxygen, by the addition of 10^–3 M. cyanide,or by varying the temperature. At the end of a given periodthe amount of glutamine was always greater in the samples whichhad shown the higher rate of oxygen uptake during this perod.This correlation was found irrespective of whether the amountof glutamine had increased or decreased. With the assumptionsthat glutamine production and consumption were proceeding simultaneouslyand that the rate of consumption was unaffected by the rateof oxygen uptake, the experimental values are consistent withthe hypothesis that the rate of glutamine production and therate of oxygen uptake were directly related. The possible significanceof these findings is discussed.     

Metabolism of Leucine and Alanine in Growing Rats Fed the Diets with Various Protein to Energy Ratios

In order to clarify the nutritional significance of metabolism of the carbon skeleton of individual amino acids, the metabolic fates of l-leucine-U-¹⁴C and l-alanine-U-¹⁴C were investigated in growing rats fed the diets with various protein calories percents (PC%) at 410 kcal of metabolizable energy.

The incorporation of ¹⁴C into body protein in 12 hr after the injection of leucine-¹⁴C was about 73% of the dose in the 0 and 5 PC% groups, though it decreased with increasing the levels of dietary protein from 10 to 30 PC%. The value of ¹⁴C recovery in body protein almost agreed with the net protein utilization (NPU) determined for the whole egg protein in a similar experimental condition. The ¹⁴C recovery in expired CO₂ and body lipid suggested that the carbon skeleton of leucine is well utilized as an energy source when the dietary carbohydrate is extensively replaced by protein.

While, the incorporation of ¹⁴C into body protein from alanine-¹⁴C was less than about 11% of the dose in all the dietary groups, and the majority of ¹⁴C was recovered in expired CO₂ and body lipid in a remarked contrast to leucine.

A similar pattern in urinary excretion of ¹⁴C was obtained for these amino acids, and the refracted rise of ¹⁴C from 10 PC% may give an indication for minimum protein requirements.     

Perinatal Exposure of Mice to the Pesticide DDT Impairs Energy Expenditure and Metabolism in Adult Female Offspring

Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.