Second Week Of Life Research Articles

Cryptosporidium outbreak in calves on a large dairy farm: Effect of treatment and the association with the inflammatory response and short-term weight gain

Cryptosporidium spp. infections in neonatal dairy calves can cause diarrhoea and, in rare cases, death. The infection is usually self-limiting, but halofuginone lactate (HL) can be used prophylactically. Calves (n=144) in the study were born during a 2-month period on one farm. A total of 901 serum and 767 faecal samples were collected. Based on HL treatment, the calves were divided into 3 groups: I) not treated, II) treated incorrectly (treatment started >48h after birth, or lasted <7days), and III) treated correctly (started <48h after birth, and lasted ≥7days). Over the 3-month observation period, 14.6% (n=21) of the calves died, of which most (67%) had not been treated with HL. Correctly performed treatment of cryptosporidiosis significantly delayed the onset of oocysts shedding (P<0.001) and reduced haptoglobin (HP) and serum amyloid A (SAA) concentrations in the second week of life. HP concentration and HL treatment were negatively associated with weight gain at 3months of age. Cryptosporidium positive faecal samples were significantly (P<0.001) more likely to be diarrhoeic but Giardia or Eimeria positive samples were not. Correct prophylactic treatment with HL delayed the shedding of Cryptosporidium oocysts and improved survival, but was negatively associated with weight gain. Incorrect treatment had a low impact on mortality and resembled no treatment regarding the proportion of calves shedding oocysts. Acute phase response (APR) in the second week of life seemed to be positively associated with shedding high amounts of Cryptosporidium oocysts.

PRACTICAL FEATURES OF EARLY ENTERAL FEEDING OF VERY LOW BODY WEIGHT INFANTS

Introduction. The optimal rate of advance enteralfeeding for very low birth weight infants (less than 1500 g)is a significant problem in nursing of preterm.Objective. To study the tolerance of feedingadvancement in very low birth weight infants.Materials and methods. An advancement of enteralfeeding of 142 very low birth weight preterm infants, whichwere born in the Perinatal Center of Kyiv was investigated.Results. Above 28% of infants has achieved thecomplete enteral feeding by day 8-11 (an average increaseof enteral feeding started from 10 ml/kg /day up to 21,3ml /kg/day). There is a direct correlation between the average increase of enteral feeding and weight gain in 1 month(r=0.56). An average increase in the volume less than15 ml /kg /day significantly increases the risk of feedingintolerance after 8 days of life (RR=6.8). There is a directcorrelation (r = 0.4) between the day of initiation ofbreastfeeding and periods of feeding intolerance.Conclusions The progressive advancement of enteralfeeding from 10 ml/kg/d to 20 ml/kg/d leads to the morerapid achievement of full enteral feeding, reduce theinfusion therapy, decrease using of antibiotic therapy,decrease in weight loss and improve better weight gain at1 month. The low average rate of increase of the enteralfeeding volume in the second week of life contributes tothe more frequent occurrence of late feeding intolerance.

The post-natal development of intraocular pressure in normal domestic cats (Felis catus) and in feline congenital glaucoma

Intraocular pressure (IOP) is the most consistent risk factor for progressive vision loss in glaucoma. Cats with recessively inherited feline congenital glaucoma (FCG) exhibit elevated IOP with gradual, painless progression of glaucoma similar to humans and are studied as a model of glaucoma in humans and animals. Here, post-natal development of IOP was characterized in normal domestic cats and in cats with FCG caused by a homozygous LTBP2 mutation. Rebound tonometry (TonoVet®, ICare Oy, Finland) was used to measure IOP non-invasively, 2–3 times weekly in 63 FCG and 33 normal kittens, of both sexes, from eyelid opening until 3–6 months of age. IOPs in the left and right eyes of both FCG and normal kittens were compared by paired t-test and linear regression. One-way ANOVA and Tukey-Kramer post-tests were used to compare IOP of cats grouped by age and disease status. A p-value <0.05 was considered significant. In the second week of life, mean IOP was 7.16 mmHg (SD = 1.3) in normal kittens and 8.72 mmHg (SD = 1.4) in kittens with FCG. Mean IOP at age 10 weeks was significantly higher in FCG (19.8 mmHg; 95% CI = 17.7, 21.9 mmHg) than in normal kittens (13.2 mmHg; 95% CI = 11.9, 14.5 mmHg). At 3 months of age, IOP in normal cats reached adult values while IOP in FCG cats continued to increase through at least six months of age. These results provide ranges for normal IOP values in young kittens and confirm that IOP is significantly higher than normal by 10wks of age in this spontaneous feline glaucoma model.

Language disorders in children with congenital hypothyroidism

IntroductionCongenital hypothyroidism (CH) represents one of the most common preventable causes of mental retardation. If fetal hypothyroidism develops, untoward effects may be shown in certain organ systems, including the central nervous system. CH may be associated with hearing and language impairment. It is possible that this impairment may worsen with delay of therapy. Problems in language, auditory processing, and reading may persist in hypothyroid children, particularly if their treatment with l-thyroxin is delayed into the third week of life.The aim of this study is to estimate the extent of language disorder and detect the factors influencing language acquisition in children with CH.Patients and methodsThis study included 60 children. The study group included 40 children who complained of CH. The age range of this group was 3–8 years. The children of the study group were divided according to the level of thyroid stimulating hormone (TSH) and T4 into two subgroups. The G1 subgroup included children with controlled CH and subgroup G2 included children with uncontrolled hypothyroidism. The results of the study group were compared with those of another group (control group), which included 20 children; both groups were matched for age and sex. The children of both groups were subjected to the protocol of language assessment.Results and conclusionThe current study showed that the children with uncontrolled CH show delayed language, mental, social age, and intelligence quotient in comparison with children with controlled hypothyroidism and normal children.There is a need for the diagnosis and treatment of children with CH as soon as possible after birth, preferably no later than the second week of life. It is also important to screen hypothyroid children for hearing problems and to provide remediation in language and reading.

PP-32 Do plasma amino acid levels reflect arginine metabolism in parenteral nutrition (pn) dependent very preterm infants?

Background Arginine plays an important role in several metabolic pathways as well as being a substrate for pro-tein synthesis. Arginine metabolism involves multi-com-partment processes that vary according to cell type/body organ. Enterocytes are a major site for arginine synthesis. The key amino acid (AA) metabolites of arginine synthesis pathways in the enterocytes of very preterm infants (VPIs) include glutamine, glutamate and proline with interme-diates ornithine and citrulline. The key arginine degrada-tion AA metabolite in the liver is ornithine. In contrast to these metabolically active AAs, histidine is presumed to be a metabolically inert AA and hence probably a useful indicator of non-metabolic factors (e.g. renal elimination). Newborn infants are dependent on enteral milk proteins for the AAs required for enterocyte arginine synthesis. However VPIs are dependent on parenteral nutrition (PN) and therefore parenteral AA for the first 2 weeks of life un-til milk feeds are established. Methods Secondary analysis was performed on the plasma AA data collected during a previously published randomised controlled trial.1 Plasma AA were collected in the second week of life in infants randomised to receive either 3.2 g/kg/d (standard) or 4.3 g/kg/d (high dose) par-enteral AA.2 A Spearman’s correlation analysis was run on the plasma data for the AA subgroups involved in argi-nine metabolic pathways to assess their relationship with arginine in the VPI population. The data also underwent multivariate regression analysis (combining both groups) to test if any of these AA significantly predicted plasma arginine levels. Results Plasma AA levels were performed on median (IQR) day 9 (8-10) in both groups. Mean (95% confidence intervals) plasma arginine levels were 41 (25-57) and 35 (22-46) micromol/litre in the high and standard AA dose groups respectively (p=0.21) well below the reference range minimum (57µmol/L). Data analysis showed that arginine had the strongest positive correlation with or-nithine, r=0.602, n=107, p Conclusion Plasma ornithine, glutamate and histidine are significant predictors of plasma arginine in PN depen-dent VPIs. This indicates that there are both metabolic and non-metabolic factors that play a role in determination of plasma arginine levels.

CLOACAL AND SURFACE TEMPERATURES OF BROILERS SUBJECT TO THERMAL STRESS

ABSTRACT : The cloacal and surface temperatures are important physiological parameters to quantify the thermal comfort of animals, its variations may occur as a function of thermal variables. In this context, the goal of the present study was to evaluate the cloacal (t clo ) and surface (t sur ) temperatures of Cobb ®500 broilers, in the second week of life, subjected to different air dry-bulb temperature (24, 27, 30 and 33 °C) and stress durations (1, 2, 3 and 4 days). The experiment was carried out in four climate-controlled wind tunnels. Air relative humidity and air velocity were set at 60% and 0.2 m s -1 , respectively. The t clo and t sur were measured daily through digital thermometer and thermographic camera, respectively. Analysis of variance and Scott Knott mean test at 5% probability were applied to the data. The results indicate that the stress by low air temperature (24 and 27 °C) resulted decreased of t clo and t sur (p 0.05, Scott-Knott test) compared to the control treatment (30 °C). Acclimation of broilers to thermal stress occurred from the second day of stress.

P24.08: Prenatal sonographic diagnosis of congenital arachnoid cyst: clinical outcomes in a tertiary care centre

To investigate the prenatal ultrasonographic(US) findings which are associated to abnormality and neonatal outcome of 21 fetuses with congenital arachnoid cysts(CAC) diagnosed antenatally. A retrospective study of all cases which were prenatally and postnatally diagnosed as CACs was performed in patients referred to the Severance Hospital from November 2005 to December 2016. 17 CAC fetuses were identified by US at the median gestational age of 30 weeks (range 24-38). Of the 17 probable CAC, 11 (64.7%) cases were diagnosed with CAC and 6 cases were confirmed with other diagnosis based on MRI finding. 4 cases were misdiagnosed as other different disease based on prenatal US. 3 (75%) of the 4 misdiagnosed cases were confirmed postnatally as posterior fossa CAC and 1 case was confirmed as intraventricular arachnoid cyst. In terms of location, 7 (46.7%) had CAC in posterior fossa. Of the 15 confirmed CAC, only one case presented agenesis of the corpus callosum and two cases presented secundum atrial septal defect and ventricular septal defect. None of the 15 cases was confirmed as chromosomal abnormality. For 6 cases, conservative management was done, while other 9 babies, fenestration of CAC was performed. In 4 of the 9 cases, surgery was performed in the second week of life (day 6 to 12). Because of enlarged CAC with aggravated symptoms, 4 needed subsequent cystoperitoneal shunt. Depending on the location of CAC, it can be diagnosed incorrectly as other disease with similar US finding. According to our study and previous literature, the prognosis of CAC depends on the presence of the corpus callosum or other congenital malformations, and the progression of ventriculomegaly. Therefore, if CAC is suspected, it is necessary to conduct the detailed US screening for congenital malformation. Also, there is a need for proper consultation for parents with regard to the possibility of surgery after delivery.

Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat model of epilepsy: implications for understanding presymptomatic epileptogenesis, predictive diagnosis, and targeted treatments

Epilepsies affect about 4% of the population and are frequently characterized by a prolonged “silent” period before the onset of spontaneous seizures. Most current animal models of epilepsy either involve acute seizure induction or kindling protocols that induce repetitive seizures. We have developed a rat model of epilepsy that is characterized by a slowly progressing series of behavioral abnormalities prior to the onset of behavioral seizures. In the current study, we further describe an accompanying progression of cytoarchitectural changes in the hippocampal formation. Groups of male and female SD rats received serial injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the second week of life. Postmortem hippocampal tissue was obtained on postnatal days 29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN, and calbindin expression. The data revealed no significant changes on postnatal day (PND) 29 but a significant increase in hilar NeuN-positive cells in some regions on PND 64 and 90 that were identified as ectopic granule cells. Further, an increase in GFAP positive cell counts and evidence of reactive astrogliosis was found on PND 90 but not at earlier time points. We conclude that changes in cellular expression, possibly due to on-going non-convulsive seizures, develop slowly in this model and may contribute to progressive brain dysfunction that culminates in a seizure-prone phenotype.

Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus

AbstractNeurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS‐expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS‐immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα‐immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFPVglut2, EYFPVgat, and GFPGad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes.

Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFPVglut2 , EYFPVgat , and GFPGad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes.

A pioneering study: oral clarithromycin treatment for feeding intolerance in very low birth weight preterm infants

Purpose: To examine the prokinetic effect of clarithromycin in very low birth weight (VLBW) preterm infants. Materials and methods: VLBW preterm infants who have not achieved half of the full enteral feeding in the second week of life were enrolled in the study. The infants enrolled in the study were randomized. Twenty infants received oral clarithromycin (7.5 mg/kg, twice a day) and 20 control infants did not receive any treatment. Results: Full enteral feeding was attained earlier in the clarithromycin group than in the control group [7 (6–9) versus 9 (9–11) days, respectively; p < .001]. Duration of parenteral nutrition and number of withheld feeds were significantly lower in the clarithromycin group (p = .013 and p < .001, respectively). Parenteral nutrition-associated cholestasis (n = 1 versus 3, p = .1) and length of hospital stay (50 versus 59 median days, p = .1) tend to be lower in the clarithromycin group without any statistical significance. We observed no adverse effect of clarithromycin therapy. Conclusions: Clarithromycin treatment in VLBW preterm infants resulted in better toleration of enteral feeding. Larger randomized controlled trials are needed to establish routine use of clarithromycin in the treatment of feeding intolerance.

A Challenging Case of Severe Infantile Cholestasis in Alpha-1 Antitrypsin Deficiency

Jaundice in the newborn period can be physiologic and is often due to benign causes. Jaundice due to conjugated hyperbilirubinemia extending beyond the second week of life may be an early sign of several cholestatic or metabolic liver diseases, and it requires logical and timely analysis so that specific treatments can be initiated. Alpha-1 antitrypsin deficiency is the most common genetic cause of pediatric liver disease and transplantation, and it must be considered when evaluating cholestatic infants. Here, we present an unusual case of alpha-1 antitrypsin deficiency with severe infantile cholestasis and rapid decompensation in the first 4 months of life, where in-depth but timely diagnosis was crucial for the appropriate intervention to take place.

Modified Hybrid Procedure in Hypoplastic Left Heart Syndrome: Initial Experience of a Center in Northeastern Brazil.

IntroductionAlthough it only corresponds to 2.5% of congenital heart defects, hypoplastic left heart syndrome (HLHS) is responsible for more than 25% of cardiac deaths in the first week of life. Palliative surgery performed after the second week of life is considered an important risk factor in the treatment of HLHS.ObjectiveThe aim of this study is to describe the initial experience of a medical center in Northeastern Brazil with a modified off-pump hybrid approach for palliation of HLHS.MethodsFrom November 2012 through November 2015, the medical records of 8 patients with HLHS undergoing hybrid procedure were retrospectively evaluated in a tertiary private hospital in Northeastern Brazil. The modified off-pump hybrid palliation consisted of stenting of the ductus arteriosus guided by fluoroscopy without contrast and banding of the main pulmonary artery branches. Demographic and clinical variables were recorded for descriptive analysis.ResultsEight patients were included in this study, of whom 37.5% were female. The median age and weight at the time of the procedure was 2 days (p25% and p75% = 2 and 4.5 days, respectively) and 3150 g (p25% and p75% = 3077.5 g and 3400 g, respectively), respectively. The median length in intensive care unit stay was 6 days (p25% and p75% = 3.5% and 8 days, respectively). There were no in-hospital deaths. Four patients have undergone to the second stage of the surgical treatment of HLHS.ConclusionIn this series, the initial experience with the modified off-pump hybrid procedure showed to be safe, allowing a low early mortality rate among children presenting HLHS.

A Critical Period in Purkinje Cell Development Is Mediated by Local Estradiol Synthesis, Disrupted by Inflammation, and Has Enduring Consequences Only for Males.

Identifying and understanding critical periods in brain development is essential to decoding the long-term impact of widespread, poorly defined, and frequently occurring insults such as inflammation. Using the laboratory rat Rattus norvegicus, we have discovered a narrowly constrained critical period in Purkinje neuron development subject to dysregulation by inflammation. The onset and offset of heightened vulnerability are attributed to a tightly orchestrated gene expression profile present only during the second postnatal week and not the first or third weeks. Genes expressed during this time code for enzymes and receptors which are critical not only for prostaglandin production and activity but also for estradiol production via the aromatase enzyme and estradiol action via the α isoform of the estrogen receptor. The two synthetic pathways are connected by prostaglandin E2 (PGE2) activation of the aromatase enzyme, as we reported previously (Dean et al., 2012b) and confirm here. Dysregulation of the PGE2-estradiol pathway during the second week by treatment with PGE2 or lipopolysaccharides produces enduring consequences as a result of reduced growth of Purkinje dendritic trees and impaired juvenile social play behavior, but only in males. The deleterious consequences of inflammation locally in the cerebellum are prevented by peripheral treatment with the cyclooxygenase inhibitor nimesulide or the aromatase inhibitor formestane. These findings highlight a novel regulatory pathway that creates a critical period in brain development vulnerable to dysregulation by inflammation. The cerebellum is increasingly appreciated for its role in social, emotional, and cognitive behaviors. It is consistently and severely affected in neuropsychiatric disorders originating during development, such as autism spectrum disorder and schizophrenia. We have identified a critical period in rat development during the second week of life that is dysregulated by inflammatory insults. An intrinsic program of gene expression determines the critical period. The enduring consequences of inflammation during the second postnatal week are stunted dendrites of the cerebellum's principal neurons, Purkinje cells, and impairments in later social behavior. These changes are not evident if inflammation occurs during the first or third week, highlighting the importance of fine-grained analyses of developmental processes and the factors that influence them.

PERIVENTRICULAR LEUKOMALACIA IN A PRETERM NEONATE WITH EARLY ONSET CAPNOCYTOPHAGA SEPSIS

Capnocytophaga sputigena is a slow-growing, capnophilic, gram negative, anaerobic, fusiform bacilli residing in oropharyngeal cavity of mammals. In humans, it causes localized periodontal infections and sporadic invasive infections in immunocompromised persons. Infrequently, it does cause chorioamnionitis and perinatal infections and is generally of lower morbidity risk in fetus and neonates. We describe a rare case report of early-onset neonatal Capnocytophaga sepsis with culture negative meningitis in preterm infant who developed early cystic periventricular leukomalacia in second week of life. Though neonatal Capnocytophaga infection is probably under-reported due to its fastidious nature and subclinical infection in mother, this case reminds that Capnocytophaga may be responsible for some occult cases of early neonatal septicemia, and that the organism may be more virulent in premature neonates with possibility of development of periventricular leukomalacia and neurological morbidities. Key words: Capnocytophaga species, Neonatal Infection, Periventricular Leukomalacia

Neonatal domoic acid alters in vivo binding of [11C]yohimbine to α2-adrenoceptors in adult rat brain.

Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset. We investigated the role of α2-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model of epilepsy. We injected male Sprague-Dawley rats daily from postnatal day 8-14 with saline or one of two sub-convulsive doses, 20μg/kg (DOM20) or 60μg/kg (DOM60) DOM, an AMPA/kainate receptor agonist. The rats were observed in open field, social interaction and forced swim tests at day 50, 75 and 98, respectively. At ~120days of age, four rats per group were injected and scanned with [11C]yohimbine, an α2-adrenoceptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner to measure α2-adrenoceptor binding. DOM60-treated rats spent more time in the periphery during the open field test and had a significant 26-33% reduction in [11C]yohimbine binding in the hypothalamus, hippocampus and orbital prefrontal cortex compared to saline-treated rats. On the other hand, DOM20 rats had a significant 34-40% increase in [11C]yohimbine binding in the hypothalamus, amygdala and entorhinal cortex compared to saline-treated rats, with no obvious behavioural differences. The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long-term changes in α2-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype.

Influence of raw material on the occurrence of tail-biting in undocked pigs

The aim of this study was to reveal the effects of raw material provision on tail-biting outbreaks in long-tailed pigs. Two different substrates, dried corn silage (SG, n=245) and alfalfa hay (AG, n=245) were provided for the pigs twice per day from the second week of life until the end of rearing. The control of long-tailed pigs (CG, n=231) were kept without the provision of additional raw material. Each tail was scored regarding tail lesions/tail losses once per week with a four-point score (0=no damage/original length, 3=severe damage/total loss). Weight was collected at the beginning and at the end of rearing. The effect of week after weaning, the batch and the interaction between treatment group and batch had highly significant influences on tail lesions (p<0.001). The main concentration of behavioural disorder took place in the rearing phase. Tail-biting started on average two to three weeks after weaning, followed by tail losses one to two weeks later. The effect of batch had a highly significant influence on tail losses at the end of rearing (p<0.001). The number of tail losses decreased with the number of batches and ranged from 98.6% in batch one to 8.5% in batch ten. This can be explained by enhanced and more precise animal observation by stable staff and points out the learning process in the course of the study. At the end of rearing, piglets of all batches had lost their tails to the greatest extent in CGs (48.7%), followed by AGs (45.2%) and SGs (41.3%). There was no clear trend in total weight gain regarding the level of tail lesions and tail losses. Corn silage stayed attractive for the piglets during the whole observation period, whereas the acceptance of the alfalfa hay decreased towards the end of rearing. The daytime, the batch and the day after weaning, as well as the interaction between treatment group and day after weaning had highly significant influences on the overall activity behaviour during rearing (p<0.001). To summarise, the rearing of long-tailed pigs requires intensive animal observation and direct intervention in case of tail-biting outbreaks. A provision of raw material on the floor of the piglet nest (suckling period) and in a piglet bowl (rearing period) from the second week of life until the end of rearing cannot prevent tail-biting during rearing, but reduces the occurrence of the behavioural disorder in long-tailed pigs.

Epithelial-mesenchymal transition of the retinal pigment epithelium causes choriocapillaris atrophy.

Epithelial-to-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is commonly observed at sites of choroidal neovascularization in patients suffering from age-related macular degeneration. To learn in an experimental model how RPE EMT affects the biology of the choroidal vasculature, we studied transgenic mice (βB1-TGF-β1) with ocular overexpression of transforming growth factor-β1 (TGF-β1). RPE EMT was detectable at postnatal day (P)1 and included marked structural and functional alterations such as loss of the outer blood-retina barrier and reduced mRNA expression of the RPE-characteristic molecules Rlbp1, Rpe65, Rbp1 and Vegfa. Moreover, vascular endothelial growth factor (VEGF) was not detectable by immunohistochemistry at the RPE/choroid interface, while RPE cells stained intensely for α-smooth muscle actin. The choriocapillaris, the characteristic choroidal capillary network adjacent to the RPE, developed normally and was not obviously changed in embryonic transgenic eyes but was absent at P1 indicating its atrophy. At around the same time, photoreceptors stopped to differentiate and photoreceptor apoptosis was abundant in the second week of life. Structural changes were also seen in the retinal vasculature of transgenic animals, which did not form intraretinal vessels, and the hyaloid vasculature, which did not regress. In addition, the amounts of retinal HIF-1α and its mRNA were markedly reduced. We conclude that high amounts of active TGF-β1 in the mouse eye cause transdifferentiation of the RPE to a mesenchymal phenotype. The loss of epithelial differentiation leads to the diminished synthesis of RPE-characteristic molecules including that of VEGF. Lack of RPE-derived VEGF causes atrophy of the choriocapillaris, a scenario that disrupts photoreceptor differentiation and finally results in photoreceptor apoptosis. Lack of retinal vessel formation and of hyaloid vessel regression might be caused by the decrease in the metabolic requirements of the neuroretina leading to low amounts of retinal HIF-1α. In summary, our data indicate that failure of RPE differentiation may well precede and cause atrophy of the choriocapillaris. In contrast, RPE EMT is not sufficient to cause choroidal neovascularization.

Consummatory succesive positive contrast produced by the downshift of an aversive solution in infant rats.

Subjects trained in successive positive contrast are usually given an appetitive stimulus of relatively low quality during a pre-shift, followed by exposure to a significantly greater quality of the same stimulus. Enhanced responsiveness to the high-quality stimulus during the post-shift phase, compared to a control group that receives the superior reward in both phases, is taken as an index of successive positive contrast. Successive positive contrast reports are rare, probably due to performance limitations inherent to the experimental protocols available. We exposed infant rats (14 days old at the start of training) to .1% or .01% quinine during 4, 10 min, trials (pre-shift phase). All animals were then given two trials of exposure to .01% quinine (post-shift phase). During the pre-shift the level of intake was greater in pups stimulated with the relatively less aversive .01% quinine solution. These animals also exhibited, compared to those stimulated with .1% quinine, lower emission of the aversive response paw treading. During the post-shift phase, the group that had been exposed to .1% quinine exhibited significantly greater intake of .01% quinine, along with a reduction in the emission of paw treading and an enhancement in paw licking, an ingestive, appetitive response. Altogether, the evidence is suggestive of the emergence of consummatory successive positive contrast during the second week of life of the rat. To our knowledge, this is the first evidence of positive contrast using an aversive solution.

Uro‐genital Development in Juvenile Sprague‐Dawley Rats: a Histomorphologic and Immunohistochemical Study

Preclinical juvenile toxicity studies are crucial in the development of new drugs intended to be administered to children. While the normal histomorphological features of the uro‐genital systems in mature rats have been described, the physiological developmental changes occurring in neonatal and juvenile rats remain incompletely characterized. As the rat is the most commonly used species in toxicology studies, it is pivotal to further understand the normal tissue remodeling events, including apoptosis and cell proliferation occurring during the juvenile phase, in order to prevent mistaking these changes for pathological lesions. The objective of this study was to describe the key histomorphologic postnatal events occurring in the uro‐genital system of Sprague‐Dawley rats from birth to postnatal day (PnD) 30, with a special focus on cell proliferation and apoptosis. Formalin‐fixed and paraffin‐embedded kidneys, urinary bladder, ovaries, testes, epididymis, uterus and vagina were obtained from 51 Sprague Dawley rats divided in 13 timepoints according to age (PnD 1, 2, 4, 6, 8, 10, 14, 17, 21, 24, 26, 28, and 30). Whenever possible, equal numbers of females and males were used in each group. The ratios of the testes and kidney weights relative to the body weight was calculated for each timepoint, reaching a maximum value between PnD10 and PnD15 and on PnD30, respectively. Immunohistochemistry staining was performed to highlight apoptosis (caspase‐3) and cell proliferation (Ki‐67) when relevant. Hematoxylin and eosin slides revealed an increased cellularity in the kidney at PnD1 with the presence of a distinct nephrogenic zone in the outer one‐fourth of the cortex and contained different stages of developing nephrons. Nephrogenesis was characterized by abundant cell death and mitoses progressing from the outer cortex to the medulla, and ceased mostly by PnD14, as only few mitoses were observed at the cortico‐medullary junction at PnD21. At PnD1, the cuboidal epithelium lining the luminal surface of the urinary bladder consisted of two distinct cell layers and became 3 to 4 layers thick by PnD21. On PnD1, the ovarian parenchyma was hypercellular and diffusely composed of pockets of oocytes enveloped in stromal cells and, by PnD 26, a sharply demarcated cortico‐medullary separation was noticeable. The first uterine glands became visible around PnD14, whereas scattered apoptotic epithelial cells were still present up to PnD26. The vaginal epithelium showed multifocal mucification mixed with few apoptotic cells starting on PnD24. At PnD1, the seminiferous tubular epithelium was 1 to 2 layers thick, composed of spermatogonia and sertoli cells, and a seminiferous lumen was rarely noticeable. Pachytene spermatocytes were observed around the second week of life, while round spermatids were first visible on PnD26. This study showed that the urogenital system of Sprague‐Dawley rats is immature at birth and that different organs develop at various rates during the first month of age. Programmed cell death and cell proliferation coexist and should not be misinterpreted as drug‐related effects in toxicologic studies.Support or Funding InformationMitacs