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Biomedical subjects

S Parmigiani

Publications and source records attributed to S Parmigiani.

At least 37 records · Page 2Linked to original sources

Prenatal exposure to endocrine disrupting chemicals: effects on behavioral development.

Numerous chemicals released into the environment by man are able to disrupt the functioning of the endocrine system by binding to hormonal receptors. Exposure to estrogenic endocrine disruptors during critical periods in fetal life can alter the development of reproductive organs, the neuroendocrine system and subsequent behavior. We present a series of studies on the effects of exposure during fetal life to low, environmentally relevant doses of two pesticides, o,p'DDT and methoxychlor, and of low doses of the synthetic estrogen, diethylstilbestrol on subsequent neuro-behavioral development in house mice. The main findings can be summarized as follows: (1) Mice prenatally exposed to methoxychlor showed changes in reflex development. Exposure to a very low dose of methoxychlor appeared to produce an increased reactivity during early postnatal life. (2) Methoxychlor exposed periadolescent mice showed a decreased reaction time exploring both a novel environment and a novel object. (3) The onset of male intrasex aggression appeared to be delayed in males prenatally exposed to low doses of methoxychlor, since exposed males showed low levels of aggressive interactions during early adolescence but not after they reached adulthood. (4) The rate of depositing urine marks in a novel environment was increased in males prenatally exposed to DES, and also to o,p'DDT and methoxychlor. (5) The proportion of both males and females attacking a same-sex conspecific was increased in mice prenatally exposed to low doses of DES and, marginally, to o,p'DDT. This effect appeared to be related to a decreased latency to attack. However, males prenatally exposed to o,p'DDT displayed a decreased intensity of aggression. The possible implications of perturbing the hormonal milieu during fetal development on the modulation of developmental turnpoints and future behavioral responses are discussed.

Animals↗

[High frequency oscillatory ventilation (HFOV) in the newborn. Study of 10 cases].

OBJECTIVE: To evaluate clinical effectiveness of high frequency oscillatory ventilation (HFOV) with a high-volume strategy in severe neonatal respiratory failure from different causes. PATIENTS AND METHODS: Infants with respiratory failure with oxygenation index (O.I.) > 10, independently from weight, gestation age, kind of respiratory disease, previous treatment with conventional mechanical ventilation (IPPV). Patients were treated with respirator Sensormedics 3100 A. Values of O.I. were recorded at start of HFOV and after 1/2, 6 and 24 hours. Also blood gases, arterial blood pressure and vital data were monitored. If HFOV failed infants were allowed to be shifted to IPPV. RESULTS: 10 infants were selected whose gestation age was comprised between 25-38 weeks and birth weight between 640-2620 grams. Mean value of O.I. at the beginning of HFOV was 31.5 +/- 25.1. In all cases but one O.I. decreased rapidly after HFOV and improvement was significant after 6 hours (10.7 +/- 6.3; p < 0.003) still improving after 24 hours (9.5 +/- 5; p < 0.002). The neonate that did not respond to HFOV had severe congenital valvular aortic stenosis and weighted 930 grams. Four infants died: 3 after response of respiratory failure to HFOV and 1 for cardiopathy. Side-effects were: i) edema in all infants that was treated with furosemide, and ii) transient decrease of sistemic blood pressure after start of HFOV in 6 infants that was treated easily with low-dosage dopamine infusion. No significant increase of the rate of complicating disease was observed in survived patients. CONCLUSION: HFOV with high-volume strategy was able to improve rapidly and significantly O.I. in severe neonatal respiratory failure without increasing complications in survivors. Edema was present in all infants and this might depend on the relatively tardy use of HFOV that required higher mean airway pressures. A more precocious intervention has to be considered in clinical practice.

High-Frequency Ventilation↗

Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery.

The development of laboratory rodent models for elicitation and measurement of a range of defensive behaviors raises the question of the relationship between defense in these animals and those of their wild congeners. To evaluate this relationship for mice, defensive responses to an anesthetized rat were compared for fourth-generation laboratory-bred wild mice and Swiss CD-1 (Swiss-Webster derived) laboratory mice in a Mouse Defense Test Battery. Wild mice showed enhanced levels of both freezing and flight, fleeing from distant approach of the predator in several situations and fleeing more quickly than the Swiss mice. However, Swiss mice did flee upon contact with the rat and also showed levels of several other defensive behaviors (risk assessment, defensive threat, and attack) that were often reliably higher than those of the wild mice. However, when wild mice were prevented from fleeing, their levels of defensive threat and attack were as high as, or at very short prey-predator distances higher than, those of the Swiss mice. These findings suggest that flight and freezing are the major defensive behaviors reduced in Swiss mice and that these reductions allow the appearance of higher levels of additional defensive behaviors in the laboratory animals. However, although Swiss mice do show lower levels of flight and freezing, their patterns of defensive behavior are sufficiently similar to those of wild mice that they provide adequate subjects for research on the biologic bases of defensive behavior. A final experiment indicated that when wild mice are familiarized with a chamber providing a place of concealment, they flee directly to this chamber on presentation of a rat, indicating that flight is a targeted response and not simply an abrupt increase in forward locomotion. Over 10 rat presentation trials with a blocked chamber entrance, however, this response declines.

Aggression↗

Interindividual variability in Swiss male mice: relationship between social factors, aggression, and anxiety.

In the present study we carried out a series of experiments in Swiss albino male mice to investigate a) the effects of previous social experience on the levels of anxiety in the elevated plus-maze (EPM) and b) whether the response of males in the EPM differs in relation to the different social status. In Experiment 1 we tested in the EPM male mice that received different social experience. Results showed that individually housing generally increased measures of anxiety in the EPM compared with the group-housing condition. Moreover, aggressive males, screened during dyadic encounters in a neutral cage, displayed the highest levels of anxiety relative to the other experimental conditions. In Experiment 2 male mice remained group-housed and were observed to record their social status. Results showed that those animals rated as socially dominant displayed a higher level of EPM anxiety relative to subordinates. From an ethological perspective our findings may be interpreted in terms of coping strategies, with aggressive/dominant animals typified by higher levels of risk assessment and open-arm avoidance than defensive/subordinate animals.

Aggression↗

An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice.

Psychoactive drugs (Fluprazine and Chlordiazepoxide--CDP) were used as probes to test both differences or similarities in neurochemical substrates (proximal causations) and adaptive significance (ultimate causations) of different forms of intraspecific aggression in wild mice and laboratory Swiss CD-1 counterparts. Fluprazine (1-5 mg/kg) inhibited maternal attack on female, but not on male intruders. Thus, phenotypically different attack behaviors (offence and defence respectively) which have different functions may be modulated by different neurochemical substrates. Intrasexual attack and infanticide which are phenotypically different, but share similar functions (i.e. competition for mates and resources) were equally inhibited by Fluprazine (2 mg/kg) both in males and females of wild and laboratory mice. This indicates that the neural substrates of these behaviors are related and similarly regulated in the two sexes. Fluprazine was used to test the prediction of the evolutionary model on fighting strategies in male-male asymmetric contests as far as fighting ability and resource value (mating and cohabitation with a female) are concerned. Fluprazine inhibited the intensity of fighting (i.e. more 'defensive' behavioral phenotype of attack) only in animals without previous positive fighting experience, suggesting that different behavioral strategies are based on different neurochemical modulation. Experience of attack also influenced the effects of CDP (2.5-5 mg/kg) in both lactating females and male resident mice. The reported proaggressive effects of benzodiazepines were observed only in animals with prior fighting experience in both cases. Thus the understanding of the effects of drugs on behavior demands consideration of the biological variability (e.g. genetic, previous experience and/or interindividual differences) and the adaptive significance of behavior in the experimental context. On this background ethopharmacology can be defined as an evolutionary approach to the study of a drugs effect on neurochemical mechanisms and functions of behavior.

Aggression↗

Effects of galanin and the galanin receptor antagonist galantide on plasma catecholamine levels during a psychosocial stress stimulus in rats.

The aim of this study was to investigate the role played by the neuropeptide galanin (GAL) in the regulation of sympathoadrenal function. We evaluated the effects of rat GAL (rGAL) and of the putative GAL receptor antagonist galantide (GLT) on epinephrine (E) and norepinephrine (NE) plasma levels in conscious freely moving male rats, during a psychosocial stress condition. Four groups of male rats were challenged by a stress stimulus, obtained by exposing the animals to a resident conspecific fighter (intruder model), following an intravenous injection with (1) rGAL + saline (SAL), (2) GLT + SAL, (3) rGAL + GLT, or (4) SAL + SAL. Plasma levels of both E and NE were also measured in an additional group of male rats not exposed to any stressor stimulus. The results (mean+/-SEM) showed that rats exposed to the stressor stimulus (intruder rats) exhibited a significant increase above baseline in circulating levels of both E (peak values of 834.13+/-115.13 pmol/l vs. basal values of 309.31+/-32.93 pmol/l; p < 0.01) and NE (peak values of 5,299.03+/-450.62 pmol/l vs. basal values of 2,798.24+/-311.56 pmol/l; p < 0.01) in comparison to control, nonstressed rats. The comparison of the areas under the curve response (AUC) among treatments in the intruder rats revealed that rGAL + SAL injections resulted in a further increase in E levels when compared to SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 25.38+/-5.52 nmol/ 1/20 min in SAL + SAL vs. rGAL + SAL treatment, respectively; p < 0.02). No significant changes in stress-induced E plasma levels were found following GLT + SAL treatment in comparison to SAL + SAL injections. When the intruder rats were submitted to rGAL + GLT injections, the increments in E levels were found to be higher than those observed following SAL + SAL treatment (AUC values: 8.26+/-0.64 vs. 36.00+/-13.76 nmol/ 1/20 min in SAL + SAL vs. rGAL + GLT treatment, p < 0.03); however, the values were not significantly different from those observed in rGAL + SAL-injected rats. No significant changes in stress-induced NE levels were found in either treatment group when compared to SAL + SAL-injected intruder rats. The results of this study demonstrate that rGAL administration leads to an increase in the E response to the stress stimulus without any effect on NE response. Galantide does not affect either the physiological stress-induced elevation of plasma catecholamines or the effects of rGAL on E plasma levels in response to stress. Therefore, GLT does not appear to behave as a GAL receptor antagonist in the regulation of sympathoadrenal function in rats.

Adrenal Glands↗

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses.

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship.

Animals↗

Differential effects of chlordiazepoxide on aggressive behavior in male mice: the influence of social factors.

The present study examined the influence of prior social experience on the effects of chlordiazepoxide (CDP; 5.0, 10.0 and 20.0 mg/kg) on intrasexual aggression in male mice. Prior to drug testing, animals were either individually housed or screened in dyadic encounters in a neutral cage. This novel method yielded four experimental groups comprising animals with different social experiences and different aggressive/defensive characteristics: 1) individually-housed males (I): 2) aggressive males (A); 3) counter-attacking males (C), which actively responded to but did not initiate attack; and 4) defeated males (D). Twenty-four hours after screening, animals were treated with CDP and subjected to a resident-intruder test with untreated intruders. Results indicated that the lowest dose of CDP (5 mg/kg) increased aggressive behaviour but only in A males. At higher doses (10-20 mg/kg), CDP reduced attacks towards intruders in A, C and I, but not D, males. In A and C males, the antiaggressive action of CDP was associated with a prosocial effect (increased social investigation), whereas in I males, reduced aggression was associated with an increase in fear-related behaviours. As these differential effects of CDP on intermale aggression cannot be fully explained by differences in behavioural baselines, present data highlight the importance of experiential background as a powerful variable in determining behavioural responses to benzodiazepines. Present findings therefore suggest that an understanding of drug effects on social behaviour demands consideration of biological variability in phenotype.

Aggression↗

Use of surfactant for prevention of respiratory distress syndrome in newborn infants in spontaneous breathing. A randomized multicentre clinical pilot-study.

OBJECTIVE: To evaluate the impact of administration of surfactant to premature infants in the delivery-room on respiratory distress syndrome (RDS) and short-term (28 days) mortality and outcome in a developing country where mechanical ventilators for infants were not available at the time of the study and neonatal mortality rate is extremely high. DESIGN: Babies with gestational age 28-33 wks were randomly assigned to receive porcine surfactant prophylaxis (200 mg/kg endotracheally) in the delivery-room or routine assistance in 4 hospitals in Romania. After randomization, supplemental oxygen and continuous airway positive pressure were allowed if available. No rescue treatment was allowed. Diagnosis of RDS was done by means of Silverman score > or = 3 within 24 hrs + requirement of supplemental oxygen > or = 40%. Other examinations were performed depending on local availability. RESULTS: 53 babies were analyzed, and 28 were given prophylaxis while 25 resulted controls. The two groups did not differ for gestational age and birth weight (mean values for prophylaxis and control infants respectively: 30.6 +/- 1.6 vs 30.2 +/- 1.7 wks and 1457 +/- 258 vs 1397 +/- 388 g.), nor for sex, type of delivery and Apgar score. Mortality 0-28 days was 42.8 vs 48% in the prophylaxis vs control group (p = ns), due prevalently to intracerebral haemorrhage in both groups. Babies given surfactant tended to die later than controls. The Silverman score resulted significantly reduced in the first 24 hours in the babies given prophylaxis vs the controls (p < 0.05) and values of PaO2/FiO2 ratio were almost constantly higher in the babies that received surfactant compared to the control infants during the first three days of life, even if the differences were not significant. CONCLUSION: Our data confirm that prophylaxis of RDS with surfactant in the delivery-room is able to improve the clinical conditions of the babies, however without the complete support of neonatal intensive care it does not resolve the problem of survival and unfavourable outcome in the babies with the lowest gestational ages. This kind of approach might anyhow facilitate the transport of the baby from a peripheral delivery-room to few equipped neonatal intensive care units to be created.

Analysis of Variance↗

Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial.

OBJECTIVE: To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS. METHODS AND PATIENTS: Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required. RESULTS: Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls. CONCLUSION: Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies.

Analysis of Variance↗

Evolution of respiratory mechanics in preterm babies after surfactant administration in the neonatal period.

OBJECTIVE: To evaluate the development of the lung of preterm infants given exogenous surfactant in the neonatal period versus control babies through the evolution of respiratory mechanics (RM) parameters. PATIENTS AND METHODS: Retrospective analysis of babies < or = 30 weeks' gestation admitted to our intensive care unit in the period 1990-94 in which RM parameters had been followed for the first two years of life. Babies were divided into two groups depending on the fact that they received endotracheal porcine surfactant 200 mg/kg for prophylaxis or rescue treatment of respiratory distress syndrome (RDS) (treatment group, No.37) or not (control group, No.41). Evaluation of RM were performed by means of PèDS at the post-conceptual age of 38-42 wks and/or 3-6 mth and/or 9-12 mth and/or 18-24 mth in spontaneous breathing after sedation with chloral hydrate and positioning of an oesophageal balloon. Chronic lung disease (CLD) was defined a posteriori as presence of polypnea at discharge independently from oxygen-therapy and from radiological findings, including also the most severe forms of bronchopulmonary dysplasia. RESULTS: The treatment and control group did not differ for birth weight and gestational age (1060 +/- 293 vs 1189 +/- 321 g. and 28.1 vs 28.3 +/- 1.5 wks respectively), however the babies of the treatment group had higher incidence of RDS, mechanical ventilation, nasal continuous positive airway pressure, and use of caffeine (p < 0.01 vs the control group). No difference was found in the incidence of CLD at discharge between the two groups. No difference was found between the treatment and the control group at the various times of the examinations concerning respiratory frequency, tidal volume, minute ventilation, dynamic compliance of the respiratory system (indexed both to body weight and length), and respiratory system resistances. The above cited parameters, except respiratory system resistances, showed significant changes from the first to the last evaluation (p < 0.01) in both groups, indicating a continuous improvement of the RM properties of the lung in the first two years of life. As regards respiratory system resistances, these were significantly reduced in the first two years of life in the treatment group (from 73.9 +/- 38.5 to 31.3 +/- 5.8 cmH2O/L/sec; p < 0.05), while there was no significant improvement in the control group (from 65.1 +/- 26.1 to 42.8 +/- 41.6 cmH2O/L/sec; p = ns). CONCLUSION: The use of surfactant both as prophylactic and rescue treatment of RDS seems able to guarantee the lung of the preterm infant to develop in a regular way, in spite of high incidence of respiratory diseases and unfavourable effects of respiratory therapies. This study also allows to have standard reference values of RM parameters for ex-preterm infants in the first two years of life to evaluate their lung development.

Analysis of Variance↗

Evaluation of reactive oxygen metabolites with micromethod in neonates: determination of standards of normality in full-term babies.

We have evaluated the value of reactive oxygen metabolites (ROMs) in 98 full-term neonates at 72 +/- 6 hours of life with a new colorimetric simple and rapid method (d-ROMs Test, Diacron s.r.l.) to establish the normal values for infants. The mean value of ROMs we have obtained in the total of the population was 127.9 +/- 39.2 U.Carr. We have then considered subgroups of infants on the basis of vaginal delivery vs cesarean section, and asphyxia vs non asphyxia during the delivery. We have found no difference within these groups and between the subgroups and the total population for the value of ROMs. We have preferred to consider as reference value for normality that of babies without intrapartum asphyxia, independently of the mode of delivery. This value is 125.2 +/- 27.6 U.Carr. The value of normality for full-term infants is lower than that reported for adults (between 250-300 U.Carr). This can be interpreted as a particular response of full-term baby to oxidative stress.

Asphyxia Neonatorum↗

Effects of chlordiazepoxide on maternal aggression in mice depend on experience of resident and sex of intruder.

Lactating mice respond differentially to intruders of differing sex, displaying defensive attack against the male and offensive attack against the female. Such a phenotypic dichotomy appears to have adaptive value in that unfamiliar males pose a much greater threat to the offspring than do females. The present study examined the effects of the benzodiazepine anxiolytic chlordiazepoxide (CDP) (2.5-10.0 mg/kg) on this differential response pattern in aggression-naive (nonscreened) (NS) and aggression-experienced (screened) (S) lactating female mice (Mus musculus domesticus) confronting intruders of either sex in a 10-min test. This procedure was used to evaluate the influence of both the type of opponent and previous aggressive experience on basal behavioural profiles and drug action. Results showed that both intruder sex and prior screening for attack modulated the behaviour of lactating females toward intruders. In turn, both variables strongly influenced CDP effects on maternal aggression. In particular, in S dams, CDP dose-dependently increased maternal attack against males but decreased attack against female intruders. Conversely, in NS dams, CDP decreased attack (and fear) against males but did not affect it against females. In both S and NS conditions, CDP modified the attack strategy of lactating females against the male, switching it from a defensive to an offensive pattern. Exploration, social investigation, eating, and immobility were differentially affected by the drug treatment, depending on screening and/or intruder sex condition. These differential effects of CDP between S and NS conditions, toward either male or female intruders, cannot be fully explained by differences in the baseline levels of these behaviours. Alternative hypotheses are discussed. These findings demonstrate that the effects of CDP on maternal attack behaviour depend on not only the drug but also the object of attack, and hence the function of attack and the prior experience of the attacker.

Aggression↗

Comparing different forms of male and female aggression in wild and laboratory mice: an ethopharmacological study.

The purpose of this study was to compare the effects of 2 mg/kg fluprazine (a serotonergic psychoactive drug with antiaggressive properties) on intrasexual attack, infanticide, and predation (on an insect larva) in males and females of wild and Swiss mice. The results showed that, in both stocks of mice, fluprazine significantly inhibited intrasexual and infanticidal attack in both sexes, but predatory attack was not altered by the drug treatment. Motivational and neural substrates underlying intrasexual attack and infanticide appear, thus, to be related to each other, and similarly modulated in both males and females. Conversely, predatory attack seems to be under a different neurohumoral control. The similar regulation of proximal mechanisms of aggressive behavior observed in wild and Swiss mice suggests a common neurobiology of aggression. For this reason, the outbred laboratory Swiss mice appear to be a reliable model for studies on causal and functional mechanisms of aggression.

Aggression↗

Prophylaxis of respiratory distress syndrome by treatment with modified porcine surfactant at birth: a multicentre prospective randomized trial.

The objective of this prospective, multicentre trial, carried out at 18 third level hospitals in Italy, was to evaluate efficacy of modified porcine surfactant (Curosurf), administered at birth to prevent the development of respiratory distress syndrome (RDS) in premature infants. 287 babies with a gestational age of 24-30 weeks were randomized to prophylactic treatment with Curosurf (80 mg/ml; dose 20 mg/kg) or to a control group receiving no surfactant treatment in the delivery-room. Babies in both groups were eligible for rescue treatment with surfactant (200 mg/kg) if they developed clinical symptoms of RDS and required mechanical ventilation. The main end-point was to obtain, in the prophylaxis group, a 30% reduction in the incidence of grade 3-4 RDS. Median gestational age was 28 weeks in both groups and mean birth weight 1010 and 1002 g, respectively for prophylaxis and control babies. There was a 32% reduction in the incidence of grade 3-4 RDS in the prophylaxis group (p < 0.05). This was associated with a significant reduction in mean maximum fraction of inspired oxygen (0.57 vs 0.66%; p < 0.01), a decreased incidence of pulmonary interstitial emphysema (7 vs 14%; p < 0.05) and a lowered mortality (21 vs 35%; p < 0.01). Combined unfavourable outcome (mortality + bronchopulmonary dysplasia and/or grade 3-4 intraventricular hemorrhage and/or grade 2-4 retinopathy of prematurity) was significantly lower in the prophylaxis than in the second group (41 vs 58%; p < 0.01). The favourable effects of prophylactic treatment were equally recorded in all the age groups, including the babies with the lowest gestational age (24-25 weeks). Multiple and logistic regression analysis confirmed that high gestational age and surfactant prophylaxis were, independently, associated with a lower degree of RDS (p = 0.0001 and p = 0.0008, respectively) and a lower mortality (p = 0.0001 and p = 0.0045, respectively). We conclude that prophylaxis with modified natural surfactant effectively prevents RDS in newborn babies between 24 and 30 weeks' gestation.

Biological Products↗

Urine marking and maternal aggression of wild female mice in relation to anogenital distance at birth.

A series of experiments were conducted with wild house mice to verify the effect of intrauterine position on females' anogenital distance at birth (AGD) and to examine the relationships between a female's AGD, used as a bioassay of androgen exposure during fetal life, and her social behavior and reproductive success in adulthood. Experiment 1 showed that cesarean-delivered females that developed in utero between two males (2 M females) have significantly longer AGD's than females positioned between two females (0 M females). We then categorized naturally delivered females shortly after birth as having a long, medium or short AGD. In adulthood, these females were tested for their behavior towards unfamiliar pups, their rate of urine-marking in response to a variety of social stimuli, postpartum aggression and success in protecting their litters in response to male and female intruders. Adult females with different AGD's at birth did not differ either in their behavior toward pups or in their rate of urine marking. Conversely, males housed across a wire mesh partition from a long-AGD female deposited a higher number of urine marks than those exposed to a short-AGD female. When tested after delivering a litter, long-AGD females displayed more tail-rattling (a component of agonistic behavior) towards intruders of both sexes in comparison to short-AGD females. These results are consistent with the hypothesis that females with a long AGD are exposed to higher levels of Testosterone during fetal life than females with a short AGD. Although not related to AGD, other measures of maternal aggression were affected by postpartum day, sex of intruders and a female's infanticidal potential while a virgin.

Aggression↗

Nest defense and survival of offspring in highly aggressive wild Canadian female house mice.

Nest defense behavior was examined in wild female house mice (Mus domesticus) that were derived from a stock initially trapped in Alberta, Canada. The first objective was to determine whether behavior toward pups prior to mating was related to the intensity of postpartum aggression in a variety of social situations. Therefore, prior to the experiments we screened virgin females for their behavior toward a newborn pup [60% of the females exhibited infanticide and 40% were noninfanticidal: 7% were parental (retrieved and hovered over the pup) and 33% ignored the pup]. Infanticidal and noninfanticidal females were then mated with males and used in four experiments. In Experiment 1 the females were housed individually prior to deliver, while in Experiment 2 the females were allowed to remain with their mates; in both situations all females successfully reared litters of similar sizes. Male and female intruders (that had all exhibited infanticide when previously tested with a pup) were placed separately into a test cage containing a lactating female during the first four days after delivery. Regardless of the presence of the stud male, previously infanticidal females were more aggressive (exhibited more attacks per min) toward both male and female intruders than were previously noninfanticidal females; infanticidal females also exhibited more of both forms of attack (offensive and defensive) and also attacked with greater intensity than did noninfanticidal females. The number of attacks toward intruders of both sexes increased for both infanticidal and noninfanticidal females between Day 1-4 postpartum, but very high rates of attack were observed on all days by the lactating females, including the day of delivery. In Experiments 3 and 4 only the most aggressive (previously infanticidal) females were tested. In Experiment 3, two unrelated, unfamiliar females were mated separately and then were housed together just prior to delivery, which was planned to occur 3-4 days apart. In 5 of the 15 cages, all pups disappeared on the day of delivery of the second female to deliver her litter. In the remaining 10 cages, it appeared that none of the pups produced by the 20 females were killed. Thus, in this experiment, 66% of pups survived to Day 4 postpartum. In Experiment 4, two previously infanticidal female siblings, which had been housed together since birth, were placed together with a stud male. In all 9 cages only one female became pregnant and delivered pups, but only 3 litters survived to Day 4 (no litters were observed being attacked during intruder tests).(ABSTRACT TRUNCATED AT 400 WORDS)

Aggression↗

Estrogenic pesticides: binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behaviour in male mice.

Numerous chemicals released into the environment by man are able to disrupt the functioning of the endocrine system by binding to estrogen receptors in estrogen-responsive cells. The ability of o,p'-dichlorodiphenyl trichloroethane (DDT) and methoxychlor to compete with estradiol for binding to estrogen receptors in MCF-7 cells (relative binding affinity; RBA) was examined in both serum-free medium and 100% serum; this is referred to as a relative binding affinity-serum modified access (RBA-SMA) assay. RBA's ranged from 0.04% for o,p'-DDT (which showed enhanced access to cells in serum relative to serum-free medium) to 0.004% for methoxychlor (which did not show enhanced access in serum). Based on these findings, these pesticides, along with diethylstilbestrol (DES) as a positive control, were fed to pregnant mice from days 11-17 of pregnancy. When the male offspring were examined in adulthood for their rate of urine marking in a novel territory (territorial behaviour), the rate of urine marking increased dramatically with low doses of DES (relative to controls) and then decreased significantly at the highest dose administered prenatally. Relative binding in MCF-7 cells accurately predicted the doses of o,p'-DDT and methoxychlor that produced the same results, providing support for the hypothesis that effects on behaviour were mediated by binding to estrogen receptors in the developing brain.

Animals↗