The effect of zinc levels in fetal circulation on zinc clearance across the in situ perfused guinea pig placenta

Although zinc is essential for normal fetal growth and development, little is known about factors that influence its transfer across the placenta. The in situ perfused guinea pig placenta model was used to study the influence of the zinc concentration of fetal circulation on maternofetal placental zinc transfer. A placenta of the anaesthetized sow was perfused (on the fetal side) with a physiological perfusate via the umbilical vessels, with the fetus excluded. The sow was infused intravenously with 65zinc as a tracer of placental Zn clearance, and with antipyrine as an indirect indicator of maternal placental blood flow. Maternal plasma and placental effluent samples collected at intervals were counted for 65zinc by gamma counter, and the absorbance of nitrosated antipyrine was measured at 350 nm. Varying the mean zinc concentration in the perfusate from 0.176 to 1.87 mg/L had no effect on relative zinc clearance calculated as zinc clearance/antipyrine clearance (mean +/- SEM; 0.085 +/- 0.010 vs. 0.114 +/- 0.018; n = 6; p greater than 0.05). The results suggest that short-term changes in fetal zinc status do not influence placental zinc transfer.     

Evaluation of the capacity of the liver for phenazone biotransformation in patients with uremia on peritoneal dialysis

This work aimed at establishing whether liver ability to biotransformation of drugs expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing antipyrine kinetics with those obtained in 13 healthy individuals. At the time of investigations, standard clinical tests of liver function were normal and HBs antigen was absent in all patients. It was shown that peritoneally dialysed patients with end-stage renal failure had not significantly changed antipyrine elimination as compared with the group of healthy controls: t0.5 = 13.2 +/- 6.8 v. 11.8 +/- 8.1 h, plasma clearance = 50 +/- 30 v. 34 +/- 21 ml/min (x +/- SD). The obtained results indicate that antipyrine kinetics is within normal range in uraemic patients regularly dialysed suggesting cytochrome P-450 in microsomes not being markedly reduced.     

Chick growth rates in Charadriiformes: comparative analyses of breeding climate, development mode and parental care

The rate at which a young bird grows is highly diverse across taxa. We investigated the influences of ecological variables on growth rates of shorebirds, gulls and their allies (order Charadriiformes) using comparative analyses of 68 species. We investigated three hypotheses: (1) exposure to cold temperatures results in reduced growth rate due to the increased energy expenditure required for thermoregulation, (2) fast growth rates allow offspring to complete development in habitats with short periods of fair ecological conditions, and (3) parental feeding allows the offspring to grow faster than self-feeding offspring. Charadriiform species are suitable for testing these hypotheses, because they breed in diverse environmental conditions that include Arctic and Antarctic habitats, temperate zones and tropics, and in some species the offspring feed themselves (precocial) whereas in others they are fed by the parents (semi-precocial). First, we tested the influence of ambient temperature on growth rate and we found that species breeding in cold habitats had faster growth rates than species breeding in warm temperatures. The relationship between growth rate and ambient temperature was not significantly different between precocial and semi-precocial offspring. Second, we tested the influence of the length of the breeding season on growth rate, and we found that species with shorter breeding seasons had faster growth rates than species with longer breeding seasons. Finally, we show that precocial offspring grew slower than semi-precocial offspring, and this relationship remains significant when the influences of ambient temperature and breeding season length are statistically controlled. In conclusion, our work, using phylogenetically corrected models, confirms that ambient environment and developmental mode of young together influence the growth of Charadriiform chicks, and their effects are additive.     

Intravenous epoprostenol sodium does not increase hepatic microsomal enzyme activity in rats

Previous studies have indicated that epoprostenol may increase hepatic microsomal enzyme activity both in animals and humans. However, interpretation of the results of these studies may be confounded by the route of epoprostenol administration or small sample sizes. The primary objective of the present investigation was to evaluate the effects of epoprostenol (given as a continuous intravenous infusion) on hepatic microsomal enzyme activity in rats. Male Sprague Dawley rats (220–290 g) received infusions of either vehicle (glycine buffer, 1 mL/hr) or 0.2 μg/kg/min epoprostenol through a jugular vein cannula for 24 hr or 7 days. At the end of the infusion, a 25 mg/kg ix. bolus of antipyrine was administered and blood samples were collected over 6 hr. Serum antipyrine concentrations were determined by HPLC. Twenty-four hr post-infusion, hepatic microsomes were prepared, and cytochrome P-450 content was determined by difference spectroscopy. Cytochrome P-450 content and antipyrine clearance values determined from serum antipyrine concentration-time profiles were not significantly different between treatment groups. Antipyrine clearance [mean (SD)] in the 24-hr vehicle-treated group was 3.68 (0.49) mL/min/kg versus 4.35 (1.1)mL/min/kg in the epoprostenol-treated group. In the 7-day vehicle-treated rats, antipyrine clearance was 5.43 (1.0) mL/min/kg compared to 4.68 (0.61)mL/min/kg in epoprostenol-treated rats. A statistically significant effect of infusion duration was observed in the control group, i.e., antipyrine clearance in rats treated with vehicle for 7 days was significantly greater than that observed in rats treated with vehicle for 24 hr. However, the increase was less than 50%. These data suggest that when epoprostenol is administered as an intravenous infusion to rats, no significant alterations in hepatic microsomal enzyme activity occur. Based on these data, long term changes in heparic metabolism in response to chronic epoprostenol administration are nor expected.     

Impairment of human antipyrine metabolism by piroxicam

The pharmacokinetics of a single oral dose of antipyrine was determined in healthy young volunteers (18-28 years), both 3 days before piroxicam, ketoprofen, or naproxen administration and on the following day of their discontinuation. In all subjects treated with piroxicam (10, 20, and 40 mg daily) for 5 consecutive days, the rate of salivary antipyrine elimination slowed. Antipyrine half-life was prolonged and metabolic clearance was reduced significantly (p less than 0.01) proportional to the dose administered. After piroxicam was discontinued, both pharmacokinetic parameters of antipyrine returned toward normal. No significant modification in antipyrine half-life or metabolic clearance rate was demonstrated after pretreatment with ketoprofen (50, 100, and 200 mg daily) or naproxen (250 and 500 mg daily). The impairment on antipyrine disposition produced by piroxicam has been interpreted as a consequence of a reduction in the activity of hepatic microsomal drug-metabolizing enzymes, particularly the cytochrome P-450 system. These results suggest the possibility of drug accumulation and toxicity when certain other therapeutic agents are administered simultaneously with piroxicam. For the same reason, it is recommended to bear in mind the potential danger of long-term piroxicam therapy on the oxidative degradation of steroid hormones and other endogenous compounds that are metabolized by the mixed-function oxidase system.     

Familial aggregation of body mass index: a population-based family study in eastern Finland.

In this study, we investigated the familial aggregation of body mass index (BMI) in a sample of families with young offspring from eastern Finland. 15-year-olds were examined from 1996 to 1997, and their biological parents were examined from 1993 to 1994. 224 children were invited; 184 families participated, and 144 were included in the analysis with complete data. Significant positive correlations were found for mother-offspring pairs (correlation [r] = 0.31, p < 0.001, n = 140), father-offspring (r = 0.23, p = 0.017, n = 107), mother-daughter (r = 0.26, p = 0.044, n = 63) and mother-son (r = 0.36, p = 0.001, n = 77). Adjustment for confounding variables did not alter these results. There was a higher proportion of children in the highest quartile of BMI when the mother was obese (odds ratio [OR] = 3.0, 95 % CI = 1.4 - 6.7, n = 140) and when one or both parents were obese (OR = 2.8, 95 % CI = 1.0 - 8.0 when one parent was obese; OR = 4.6, 95 % CI = 1.1 - 20.0 when both parents were obese; n = 103). The study confirmed familial BMI aggregation. The consistent obesity relationship between mother and offspring may indicate the key role of the mother in primary obesity prevention.     

Brief report: Body water estimates in normally grown baboon neonates

Water contents of various body water compartments were estimated within nine hours of birth in 11 preterm and eight term baboon (Papio cynocephalus neonates. Estimated water contents of all body compartments (in ml) increased linearly with birthweight (r = 0.52 to 0.90, P ≦ 0.007) and with gestational age (r = 0.46–0.94, P ≤ 0.05). When body water estimates were expressed in proportion to bodyweight (in ml/kg), preterm neonates had significantly larger mean antipyrine space and intracellular water than their term peers. Mean corrected bromide space, interstitial water, plasma volume, blood volume, and red cell volume were similar in preterm and term neonates. Although there are minor differences in body water contents and distribution between baboon and human neonates, baboon data are sufficiently similar to human data to justify using the baboon fetus and neonate as a model for investigations of human development.     

Estimating final height from parental heights and sex in Taiwanese

We have developed a simple function for accurately estimating target height for use in evaluating growth and growth-promoting therapies in Taiwanese children. The heights of parents and their adult offspring born in the 1970s were determined in 1229 healthy families who accompanied another family member to our pediatric clinic. We directly measured the heights of the population-based cohort of adult offspring. The heights of their parents were based on self-report. Both the parents and their offspring were healthy. The increases in height between the two generations were 1.49-3.19 cm for boys and 2.03-2.61 cm for girls. These increases lie between those reported for Chinese children in Hong Kong (4.2-4.8 cm) and children in Sweden (0.7-1.0 cm). Final height was underestimated using the corrected midparental height method and was overestimated using the final parental height model developed from Swedish data. We developed a new linear model by fitting our data: boy height = 79.3 + 0.56 (midparental height); girl height = 35.2 + 0.76 (midparental height). The intercept and slope of the model are similar to those reported for Swedish girls but not to those reported for Swedish boys. Use of the new equations derived from our data may increase the accuracy of estimates of target height in Taiwanese children. The intermediate position of our fairly representative Taiwanese sample in both final height and generational increases in final height may reflect an intermediate stage between the Swedes and Hong Kong Chinese in the secular trend of heights.     

Experimental evidence that adult antipredator behaviour is heritable and not influenced by behavioural copying in a wild bird

Knowledge of the relative importance of genetics and behavioural copying is crucial to appraise the evolvability of behavioural consistencies. Yet, genetic and non-genetic factors are often deeply intertwined, and experiments are required to address this issue. We investigated the sources of variation of adult antipredator behaviour in the Alpine swift (Apus melba) by making use of long-term behavioural observations on parents and cross-fostered offspring. By applying an 'animal model' approach to observational data, we show that antipredator behaviour of adult Alpine swifts was significantly repeatable over lifetime (r = 0.273) and heritable (h(2) = 0.146). Regression models also show that antipredator behaviours differed between colonies and sexes (females were more tame), and varied with the hour and year of capture. By applying a parent-offspring regression approach to 59 offspring that were exchanged as eggs or hatchlings between pairs of nests, we demonstrate that offspring behaved like their biological parents rather than like their foster parents when they were adults themselves. Those findings provide strong evidence that antipredator behaviour of adult Alpine swifts is shaped by genetics and/or pre-hatching maternal effects taking place at conception but not by behavioural copying.     

Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study.

Plasma angiotensin I-converting enzyme (ACE) activity has been measured in a sample of 87 healthy families participating in a study of cardiovascular risk factors. The mean +/- SD levels of plasma ACE were 34.1 +/- 10.7, 30.7 +/- 10.4 and 43.1 +/- 17.2 units/liter in fathers (n = 87), mothers (n = 87) and offspring (n = 169), respectively. Plasma ACE was uncorrelated with age, height, weight, or blood pressure in the parents, but a negative correlation with age was observed in offspring (r = -.32). The age-adjusted familial correlations of plasma ACE were .038, .166, .323 and .303 for spouses, father-offspring, mother-offspring, and siblings, respectively. The results of the genetic analysis suggest that a major gene may affect the interindividual variability of plasma ACE, with different codominant effects in parents and offspring. According to this model, the major gene effect accounts for 4.8, 4.0, and 10.8 units/liter of the overall mean and for 29%, 29% and 75% of the variance of age-adjusted ACE in fathers, mothers, and offspring, respectively. The estimate of the probability of the less frequent allele is .26, and the major gene effect is approximately twice as great in high homozygotes than in heterozygotes and in offspring than in parents. The results of this study demonstrate the occurrence of a familial resemblance of plasma ACE activity in healthy families and suggest that this observation can be explained by the segregation of a major gene.     

Effects of zixoryn on pharmacokinetics of antipyrine in intact and sensitized guinea pigs]

The effect of zixoryn, a hepatic inductor of cytochrome P-450, on the pharmacokinetics of antipyrine in intact and sensibilized guinea-pigs was studied. It was found that sensibilization of albumin increased the half-time (T1/2), AUC and decreased the total body clearance (Clt) of antipyrine and the renal clearance (Clr) of metabolites in urine. The administration of zixoryn in sensibilized animals decreased T1/2 and AUC and increased the clearance of antipyrine and its metabolites.     

Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man

Eight healthy volunteers with a broad range in their ability to hydroxylate debrisoquine, a metabolic reaction which is under polymorphic genetic control, were given single oral doses of nortriptyline and antipyrine. There was a close correlation between an individual's ability to hydroxylate debrisoquine and nortriptyline (measured as plasma clerance of the drug) (Spearman r_s = 0.83; p = 0.01). This indicates that these two benzylic hydroxylations are controlled by similar if not identical genetic factors. In contrast to nortriptyline the clearance of antipyrine (assessed in saliva) was not positively related to the ability to hydroxylate debrisoquine.     

Familial longevity is marked by enhanced insulin sensitivity

Insulin resistance is a risk factor for various age-related diseases. In the Leiden Longevity study, we recruited long-lived siblings and their offspring. Previously, we showed that, compared to controls, the offspring of long-lived siblings had a better glucose tolerance. Here, we compared groups of offspring from long-lived siblings and controls for the relation between insulin and glucose in nonfasted serum (n = 1848 subjects) and for quantitation of insulin action using a two-step hyperinsulinemic-euglycemic clamp (n = 24 subjects). Groups of offspring and controls were similar with regard to sex distribution, age, and body mass index. We observed a positive bi-phasic linear relationship between ln (insulin) levels and nonfasted glucose with a steeper slope from 10.7mU L(-1) insulin onwards in controls compared to offspring (P = 0.02). During the clamp study, higher glucose infusion rate was required to maintain euglycemia during high-dose insulin infusion (P = 0.036) in offspring, reflecting higher whole-body insulin sensitivity. After adjustment for sex, age, and fat mass, the insulin-mediated glucose disposal rate (GDR) was higher in offspring than controls (42.5 ± 2.7 vs. 33.2 ± 2.7 micromol kg(-1) min(-1) , mean ± SE, P = 0.025). The insulin-mediated suppression of endogenous glucose production and lipolysis did not differ between groups (all P > 0.05). Furthermore, GDR was significantly correlated with the mean age of death of the parents. In conclusion, offspring from long-lived siblings are marked by enhanced peripheral glucose disposal. Future research will focus on identifying the underlying biomolecular mechanisms, with the aim to promote health in old age.     

Parent–offspring transaction: Mechanisms and the value of within family designs

This article is part of a Special Issue “Parental Care”. Parenting is best understood as a transactional process between parents and their offspring. Each responds to cues in the other, adapting their own behavior to that of their partner. One of the goals of parenting research in the past twenty years has been to untangle reciprocal processes between parents and children in order to specify what comes from the child (child effects) and what comes from the parent (parent effects). Child effects have been found to relate to genetic, pre and perinatal, family-wide, and child-specific environmental influences. Parent effects relate to stresses in the current context (e.g. financial strain, marital conflict), personality and ethnicity but also to adverse childhood experiences (e.g. parental mental health and substance abuse, poverty, divorce). Rodent models have allowed for the specification of biological mechanisms in parent and child effects, including neurobiological and genomic mechanisms, and of the causal role of environmental experience on outcomes for offspring through random assignment of offspring–mother groupings. One of the methods that have been developed in the human and animal models to differentiate between parent and child effects has been to study multiple offspring in the family. By holding the parent steady, and studying different offspring, we can examine the similarities and differences in how parents parent multiple offspring. Studies have distinguished between family average parenting, child-specific parenting and family-wide dispersion (the within family standard deviation). These different aspects of parenting have been differentially linked to offspring behavioral phenotypes.     

125I-radioimmunoassay for antipyrine

A radioimmunoassay (RIA) for the determination of antipyrine directly in plasma and saliva has been developed using 4-¹²⁵I-iodoantipyrine as the radioligand. The method showed excellent agreement (r=0.98) with a recently reported RIA for antipyrine using ³H-antipyrine as the radioligand. The interassay coefficient of variation for the ¹²⁵I-RIA did not exceed 7.6% and the mean recovery of antipyrine added to plasma or saliva was 101±1.73 (S.E.) over a range of 1.5 to 30 μg/ml. By virtue of its simplicity and low cost, the ¹²⁵I-RIA for antipyrine offers an attractive method for the routine determination of antipyrine levels and subsequent calculation of its half-life in man.     

Spontaneous sister chromatid exchange and chromosome aberration frequency in humans: the familial effect.

The possible effects of environmental and genetic factors on spontaneous frequencies of sister chromatid exchanges (SCEs) and cells with chromosome aberrations (CAs) in human lymphocytes were investigated by analysing 177 completed families (mother, father and at least one child). After removing the effects of methodological, biological and life-style factors by the use of multifactor analysis of variance (MANOVA), SCEs and CAs residuals were analysed by simple correlation analysis and principal component analysis. SCEs and CAs inter-familiar variability was higher than that found within families. A significant correlation was found between the average SCE frequencies shared by parents (the so-called 'midpoint parents', or 'midparent') and offspring (linear slope b=0.26+/-0.07, p<0.05), but also between mother and father (b=0.23+/-0.11, p<0.05) suggesting the presence of an effective environmental factor. The midparent-offspring correlation was found to be sustained by the mother-offspring relationship (b=0.28+/-0.08, p<0.05), being the father-offspring correlation not significant (b=0.16+/-0.11, p0.05). Concerning CAs, no statistically significant correlation between parents was found, but the strong relationship between mother and offspring was confirmed (b=0.468+/-0.11, p<0.001). The SCEs correlation between mother vs. offspring disappeared for older offspring (over 23 years old). The obtained findings strongly showed that the genetic make-up is barely detectable in the presence of domestic environment factors which are shown to play the major role in determining the interfamilial variability of SCE and CA in a general population. These results strengthen the suitability of the use of SCEs and CAs analysis in human cytogenetic surveillance for the detection of effective environmental factors.     

Prediction of expected genetic variation within groups of offspring for innovative mating schemes

Background

Experience from progeny-testing indicates that the mating of popular bull sires that have high estimated breeding values with excellent dams does not guarantee the production of offspring with superior breeding values. This is explained partly by differences in the standard deviation of gamete breeding values (SDGBV) between animals at the haplotype level. The SDGBV depends on the variance of the true effects of single nucleotide polymorphisms (SNPs) and the degree of heterozygosity. Haplotypes of 58 035 Holstein animals were used to predict and investigate expected SDGBV for fat yield, protein yield, somatic cell score and the direct genetic effect for stillbirth.

Results

Differences in SDGBV between animals were detected, which means that the groups of offspring of parents with low SDGBV will be more homogeneous than those of parents with high SDGBV, although the expected mean breeding values of the progeny will be the same. SDGBV was negatively correlated with genomic and pedigree inbreeding coefficients and a small loss of SDGBV over time was observed. Sires that had relatively low mean gamete breeding values but high SDGBV had a higher probability of producing extremely positive offspring than sires that had a high mean gamete breeding value and low SDGBV.

Conclusions

An animal’s SDGBV can be estimated based on genomic information and used to design specific genomic mating plans. Estimated SDGBV are an additional tool for mating programs, which allows breeders to identify and match mating partners using specific haplotype information.     

Offspring quality and tick infestation load in brood rearing great tits Parus major

Although the impact of nest-dwelling ectoparasites on nestlings in altricial birds is relatively well documented, little information is available on the fitness consequences of bird–ectoparasite systems with limited ectoparasite transmission between parents and their offspring. In this particular context we tested the hypothesis that parental infestation by a haematophageous field ectoparasite, the sheep tick Ixodes ricinus , in a hole-breeding passerine bird, the great tit Parus major , ultimately leads to the reduction of nestling quality. Observational data of a long-term study show that 15 days after hatching, nestlings' body condition (body mass corrected for body size) was negatively associated with the tick load of the mother, while no association was found with tick load of the father. A field experiment was conducted to test if adult infestation by ticks leads to a reduction in offspring quality. The field experiment consisted of a two by two factorial design: neither, one or both parents were infested with a high tick load (12 nymphs) when nestlings were eight days old. Four days after manipulation of the parents, the effect of the treatment on nestlings' health was assessed by measuring haematological and biochemical parameters. Body condition of nestlings was monitored from three days after hatching, until seven days after tick manipulation of the parents. Although parental tick manipulation resulted in successful tick feeding, nestlings' health parameters were not affected. We therefore suggest that the negative association between nestling condition and parental tick load does not reflect a causal effect of parasites, but either reflects a common environmental factor affecting parental infestation levels and offspring condition, or reflects parental quality. We propose different explanations why this association is expressed in female parents only.     

Genetic consequences of polygyny and social structure in an Indian fruit bat, Cynopterus sphinx. I. Inbreeding, outbreeding, and population subdivision

Population subdivision into behaviorally cohesive kin groups influences rates of inbreeding and genetic drift and has important implications for the evolution of social behavior. Here we report the results of a study designed to test the hypothesis that harem social structure promotes inbreeding and genetic subdivision in a population with overlapping generations. Genetic consequences of harem social structure were investigated in a natural population of a highly polygynous fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae), in western India. The partitioning of genetic variance within and among breeding groups was assessed using 10-locus microsatellite genotypes for 431 individually marked bats. Genetic analysis of the C. sphinx study population was integrated with field data on demography and social structure to determine the specific ways in which mating, dispersal, and new social group formation influenced population genetic structure. Microsatellite data revealed striking contrasts in genetic structure between consecutive offspring cohorts and between generations. Relative to the 1998 (dry-season) offspring cohort, the 1997 (wet-season) cohort was characterized by a more extensive degree of within-group heterozygote excess (F(IS) = -0.164 vs. -0.050), a greater degree of among-group subdivision (F(ST) = 0.123 vs. 0.008), and higher average within-group relatedness (r = 0.251 vs. 0.017). Differences in genetic structure between the two offspring cohorts were attributable to seasonal differences in the number and proportional representation of male parents. Relative to adult age-classes, offspring cohorts were characterized by more extensive departures from allelic and genotypic equilibria and a greater degree of genetic subdivision. Generational differences in F-statistics indicated that genetic structuring of offspring cohorts was randomized by natal dispersal prior to recruitment into the breeding population. Low relatedness among harem females (r = 0.002-0.005) was primarily attributable to high rates of natal dispersal and low rates of juvenile survivorship. Kin selection is therefore an unlikely explanation for the formation and maintenance of behaviorally cohesive breeding groups in this highly social mammal.     

Effects of age, sex and renal function on urinary insulin-like growth factor I (IGF-I) levels in adults.

Insulin-like growth factor I (IGF-I) levels in urine were measured in adults using specific RIA after extraction with acid-ammonium sulfate. Mean (+/- SD) total urine IGF-I values were 267.9 +/- 112.9 ng/day and 167.8 +/- 73.2 ng/g creatinine (Cr) in 17 normal young adults. There was a positive correlation (r = 0.785, P < 0.001) between IGF-I values in early morning urine and those of 24 h urine when they were corrected by urinary Cr. IGF-I values in early morning urine were ranged from 60 to 1,100 ng/gCr with a mean value of 309.6 ng/gCr in 178 normal adults aged 21-80 yr. There was a consistent trend towards higher urinary IGF-I values in males during aging and this trend did not reach statistical significance until the sixth and seventh decades. There was a positive correlation (r = 0.465, P < 0.005) between urinary IGF-I values and age in males but not in females. Although urinary IGF-I values were higher in females than in males of the second and third decades, no sex difference was found in older adults. Urinary IGF-I values were correlated reversely with 24 h Cr clearance (CCr) and positively with urinary beta 2-microglobulin (beta 2-MG) levels in patients with renal dysfunction. These findings indicate that urinary IGF-I levels are influenced by age, sex and renal function in adults.