Third Week Of Life Research Articles

Analysis of Ultrasonic Vocalizations Emitted by Infant Rodents

Altricial rodent pups emit ultrasonic vocalizations (USVs), which are whistle-like sounds with frequencies between 30 and 90 kHz. These signals play an important communicative role in mother-offspring interaction because they elicit in the dam a prompt response as concerning care-giving behaviors. To investigate neurobehavioral development, the analysis of the number of USVs presents several advantages: (1) USVs are one of the few responses produced by very young rodents that can be quantitatively analyzed and elicited by quantifiable stimuli; (2) USV emission follows a clear ontogenetic profile from birth to the second to third week of life, thus allowing longitudinal analysis during very early post-natal ontogeny. The reported role played by several receptor agonists and antagonists in modulating the USV rate makes this measure highly informative in investigating the effects of toxicants and, more generally, psychoactive compounds on the development of selected brain systems.

The Very Large G-Protein-Coupled Receptor VLGR1: A Component of the Ankle Link Complex Required for the Normal Development of Auditory Hair Bundles

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

Phytase effects on the efficiency of utilisation and blood concentrations of phosphorus and calcium in Pekin ducks

1. The objective was to study the effects of a supplementation of a 6-phytase derived from the Peniophora lycii gene in the White Pekin duck. 2. In two balance studies, low-phosphorus (P) diets consisting mainly of maize, solvent extracted soybean meal and solvent extracted sunflower meal were supplemented with phytase up to concentrations of 1500 U/kg (Study 1) or 2000 U/kg (Study 2). Each diet (phytase level) was fed to 8 to 10 individually penned ducks. The intake and excretion of each animal was measured for 5 consecutive days when ducks were in their third week of life. Responses were described by nonlinear regression. 3. Although the basal diets from the two studies were similar in ingredient composition, efficiencies of P utilisation (P accretion/P intake × 100) for the unsupplemented basal diets were 39% in Study 1 and 30% in Study 2. Phytase supplementation significantly improved P utilisation up to levels of about 55% in both studies. A plateau in P utilisation with an increase in phytase supplementation was achieved in Study 2, but not in Study 1. The enzyme was more efficient in Study 2 than in Study 1 at low rates of supplementation. Utilisation of calcium (Ca) was significantly improved by phytase supplementation. Accretions of P and Ca increased at a constant ratio. 4. In a 5-week growth study, diets with an intentionally marginal P level were used. Diets were fed either unsupplemented or supplemented with 1000 or 10 000 U/kg of phytase. Eight pens of 10 sex-separated ducks each (4 pens per sex) were allocated to each dietary treatment. 5. Phytase significantly improved the growth of ducks of both sexes between d 1 and 21, but not between d 22 and 35. Feed conversion rate was not affected by treatment. Blood serum phosphate concentrations, but not calcium, were significantly increased by phytase supplementation. Blood concentrations of creatinine, aspartate aminotransferase and lactate dehydrogenase remained unaffected while alanine aminotransferase was significantly reduced by phytase supplementation. 6. It was concluded that the efficacy of a microbial phytase varies even under similar experimental conditions. Differences in intrinsic phytase activity of maize/soybean meal-based diets may be responsible for this. The 6-phytase used has the potential to improve the utilisation of plant P in duck feeding. A plateau in response was reached above 1500 U/kg.

Localized persistent pulmonary interstitial emphysema

A 3-week-old premature female infant was referred to our institution with progressively worsening respiratory distress. She was born at 29 weeks’ gestational age with radiologic evidence of mild respiratory distress syndrome. She required only minimal supplemental oxygen until her third week of life, when she developed worsening respiratory distress requiring mechanical ventilation. A new chest radiograph (Fig. 1) demonstrated hyperinflation of the left hemithorax with coarse reticular markings throughout the left lung. Computed tomography (CT; Fig. 2) revealed innumerable cystic spaces of varying sizes occupying the entirety of the left upper lobe, with no appreciable normal lung parenchyma interposed. She failed to wean from mechanical ventilation and underwent an urgent left thoracotomy. The entire upper lobe was grossly involved with cystic lung pathology (Fig. 3). This was treated by an uncomplicated left upper lobectomy, and the patient was weaned from mechanical ventilation over the next 3 days. The histopathology (Fig. 4) demonstrated cyst-like cavities lined by an irregular layer of cells within the lung parenchyma. These cells were mostly mononuclear admixed with foreign body–type multinucleated giant cells. The cysts were interspersed with essentially normal-appearing pulmonary tissue. Occasional air spaces were questionably dilated, particularly at the periphery of the lung beneath the pleural surface. However, widespread emphysematous changes were not apparent; neither was there any significant intraalveolar or interstitial inflammatory cell infiltrate. These findings were diagnosed as localized persistent pulmonary interstitial em

The effects of proinflammatory cytokines on the formation of behavior in early postnatal ontogenesis

Studies were performed to investigate impairments to the formation of behavior arising as a result of increases in the proinflammatory cytokine interleukin-1beta in early postnatal ontogenesis. The cytokine was given at pyrogenic or subpyrogenic doses for one week (the first, second, or third week of life). Behavior was assessed at prepubertal age and in the adult state in the open field and elevated cross maze tests. The greatest changes were seen in adolescent rats given interleukin-1beta during the first or third weeks of life. Impairments were seen after administration of pyrogenic and subpyrogenic doses of cytokine and were identical in females and males. Changes consisted of partial substitution of acts, increases in motor activity and decreases in investigative activity. After sexual maturation, these behavioral impairments were no longer seen.

Mechanism of Vitamin D Receptor Action

Studies in humans and in animal models have demonstrated that the receptor-dependent actions of 1,25-dihydroxyvitamin D are required for normal skeletal growth and maturation. Investigations were undertaken to address which consequences of vitamin D receptor deficiency are a direct result of impaired receptor-dependent hormone actions versus being due to metabolic changes. Vitamin D receptor (VDR) knockout mice were therefore generated. Investigations were performed in mice with abnormal mineral ion homeostasis, as well as in mice in which the development of abnormal mineral ion homeostasis was prevented by dietary means. VDR null mice had hypocalcemia, hyperparathyroidism, and hypophosphatemia in the first month of life. Rickets and osteomalacia are observed as well. Institution of a high-calcium, high-phosphorus, lactose-supplemented diet by the third week of life prevents abnormalities in mineral ion homeostasis. The bones of the VDR null mice with normal mineral ion homeostasis are indistinguishable from those of their wild-type littermates. The rachitic changes in the growth plates are also prevented by maintenance of normal mineral ion homeostasis. Investigations into the pathophysiological basis for the growth plate abnormalities in the VDR null mice with abnormal mineral ion homeostasis demonstrated that impaired apoptosis of hypertrophic chondrocytes due to hypophosphatemia was the cause of rachitic changes. Studies investigating the cause of the alopecia demonstrate novel ligand-independent VDR actions in the keratinocyte. The skeletal effects of VDR ablation are therefore indirect and reflect absence of ligand-dependent receptor actions in the intestine. In contrast, the cutaneous phenotype of VDR ablation is a direct consequence of absence of ligand-independent VDR actions in epidermal keratinocytes.

Awareness of Wilson-Mikity Syndrome: A Rare Complication of Chorioamnionitis

Summary Objective Wilson-Mikity syndrome is a rare neonatal morbidity of chorioamnionitis. It is characterized by insidious onset of progressive respiratory distress and may eventually lead to diffusely emphysematous lung changes. We report a mother who suffered from chorioamnionitis and who delivered a premature infant with Wilson-Mikity syndrome that was confirmed after delivery. Case Report A 33-year-old woman received tocolytic therapy from 19 weeks of gestation. Preterm premature rupture of membranes occurred at 24 weeks of gestation. Amniotic fluid culture yielded pseudomonas infection at 26 weeks of gestation. Despite supplementary tocolytics and a third-generation cephalosporin, a premature female infant was delivered vaginally at 26 weeks of gestation. Deteriorating respiratory symptoms and early chronic lung changes on chest radiography were found from the early third week of life. Wilson-Mikity syndrome was diagnosed based on the clinical and radiologic manifestations. The baby's respiratory condition improved under combination therapy with antibiotics, a bronchodilator, a steroid, and a synthetic surfactant, but she was hospitalized because of feeding problems. Conclusion The obstetrician must be aware of Wilson-Mikity syndrome as a rare complication of chorioamnionitis. This entity should raise concerns about decision making and counseling for patients with suspicious chorioamnionitis, such as requirement for tocolysis or intended preterm birth.

Role of premature leptin surge in obesity resulting from intrauterine undernutrition

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

Effect of Halofuginone Lactate on the Occurrence of Cryptosporidium parvum and Growth of Neonatal Dairy Calves

Thirty-one Holstein bull calves were purchased at birth from 3 dairy farms in Eastern Ontario. Each calf was assigned at random to oral treatment with either 5mg of halofuginone lactate in 10.0mL of aqueous carrier solution (Halocur, base comprised 10mg of benzoic acid, 100mg of lactic acid, and 0.3mg of tartrazine) or 10mL of placebo (Halocur base minus the active ingredient, halofuginone lactate) administered 15 to 30min after morning milk feeding for the first 7 d of life. Intakes of milk, calf starter, and water, and fecal consistency score were recorded daily for 56 d. Calf weights were recorded weekly for 56 d. Fecal samples were taken from all calves at approximately 2, 7, 14, 21, and 28 d of age for isolation of Cryptosporidium parvum oocysts. Logistic and linear regression analyses were used to assess the effect of treatment on the incidence of diarrhea and C. parvum infection status. The odds of C. parvum shedding among calves in the halofuginone lactate-treated group was 70% lower than the odds of shedding among calves in the placebo group. In calves treated with halofuginone lactate, no oocyst shedding occurred until 2 wk of age, whereas 12.5% of calves in the placebo group began shedding oocysts during wk 1. From all ages of placebo-treated calves, 31 of 73 samples (42.5%) were positive for C. parvum, whereas only 15 of 67 samples (22.4%) from all ages of halofuginone lactate-treated calves tested positive. The largest number of C. parvum-positive samples occurred in the third week of life. There was a significant delay of 3.1 d in the incidence of diarrhea among calves treated with halofuginone lactate. Intake of milk and starter, body weight gains, and age at weaning were not significantly different between treatment groups.

The identification of a R201H mutation in KCNJ11, which encodes Kir6.2, and successful transfer to sustained-release sulphonylurea therapy in a subject with neonatal diabetes: evidence for heterogeneity of beta cell function among carriers of the R201H mutation

To the Editor Diabetes caused by severe mutations in beta cell genes is usually diagnosed as neonatal diabetes [1] or MODY [2]. Activating mutations in KCJN11, the gene encoding the ATP-sensitive potassium channel subunit Kir6.2, have been described in very-early-onset diabetes ( A) was found in a single patient. This child was born at 40 weeks’ gestation and weighed 2,450 g. He was diagnosed with diabetes during the third week of life based on a plasma glucose of 35–50 mmol/l, without ketoacidosis, which was measured when he presented with pneumonia and bilateral acute otitis media. The patient was treatedwith insulin, with a dose of 0.7–1.0 U/kg used initially and subsequently decreased. At 9 years, 11 months he weighed 27.5 kg and his daily insulin requirement was 7 U (0.25 U/kg) as a single morning injection of intermediate-acting insulin. Despite little modification to his diet he rarely experienced hyperglycaemia above 11 mmol/l, and had an HbA1c level of 6.6%. These observations suggested endogenous beta cell function, which was confirmed by a fasting plasma C-peptide of 443 pmol/l (glucose 6.7 mmol/l) and an increase in plasma insulin concentration of 70 pmol/l during an IVGTT (Fig. 1). As patients with Kir6.2 diabetes may respond to sulphonylureas, we assessed whether this patient could successfully transfer to sulphonylurea tablets [3, 4]. Glipizide gastrointestinal therapeutic system (GITS), a controlledrelease sulphonylurea, was introduced [5]. A dose of 5 mg was administered for 2 days, then 10 mg; insulin was simultaneously slowly withdrawn over a period of 5 days. As the patient experienced a few mild hypoglycaemic episodes during the first 2 days after the discontinuation of insulin the glipizide GITS dose was decreased to 5 mg. While on this dose, a day profile of his capillary glucose concentrations revealed that they were between 4 and 6 mmol/l; a result confirmed by a 72-h record obtained using a continuous glucose monitoring system (Medtronic, Northridge, CA, USA). The IVGTT was repeated 3 weeks after a stable glipizide dose was achieved. At this time the patient’s fasting glucose level was 5.4mmol/l, and his C-peptide level was 347 pmol/l. T. Klupa and E. L. Edghill contributed equally to this work

Developmental expression and function of aldehyde reductase in proximal tubules of the kidney

Aldehyde reductase reduces a wide variety of toxic and physiological aldehydes with a marked preference for negatively charged substrates such as glucuronate. Reduction of glucuronate to gulonate is a step in inositol catabolism, a process specific to the kidney cortex. Administration of the aldehyde reductase inhibitor AL-1576 to mice increases urinary output of glucuronate and decreases output of vitamin C. Aldehyde reductase mRNA with a 319-bp 5'-untranslated region is expressed ubiquitously in murine tissues. A new isoform with a short 64-bp 5'-untranslated region is found predominantly in the kidney, resulting in 10-fold higher enzymatic activity observed in this organ compared with other tissues. A moderate level of the new transcript is found in liver, intestine, and stomach, whereas brain, heart, lung, spleen, ovary, and testis have low to insignificant levels. The short transcript is absent during embryonic development and is first observed in the murine kidney on postnatal day 6. The abundance of the short transcript and enzyme activity increase sigmoidally with age; the sharpest increase occurs during the third week of life. As shown by immunohistochemistry, aldehyde reductase expression is limited to the proximal tubules and parietal epithelium of Bowman's capsule. In the mouse, the intensity of staining in tubules increases with age, suggesting that induction of aldehyde reductase expression is part of renal tubular maturation. The human kidney also exhibits proximal tubular localization and the two mRNA transcripts of aldehyde reductase. Immunoreactive protein is present in the 9-wk-old fetal kidney, indicating that the induction of aldehyde reductase in humans occurs early in development.

Sex differences in the long-term effect of preweanling isolation stress on memory retention

Social experiences during development can powerfully modulate later neuroendocrine and behavioral system. In the present study, male and female rat pups experienced daily bouts of social isolation for 6 h per day or control conditions during the third postnatal week. Performance on a 12-arm radial maze with 8 arms consistently baited with food reward was examined in adulthood. During the social isolation, both male and female pups exhibited a significant increase in plasma corticosterone levels. When tested on the radial arm maze as adults, the performance of female rats that had experienced social isolation during development was not affected; however, male rats in the isolation condition initially exhibited impairments in working memory but not reference memory. Despite achieving comparable asymptotic levels of performance on the maze, male rats that experienced social isolation during the third week demonstrated disruption in working memory retention when radial arm maze trials were interrupted after the fourth arm choice. Thus, while male rats that experience social isolation during the third week of life eventually perform comparably to controls on the standard radial arm maze task, their ability to retain information over a delay remains impaired. These findings highlight an important sex difference in the long-term effects of stress during this period of late preweanling development.

La galactosémie congénitale : une révélation singulière

Congenital galactosaemia reveals usually in the second and third weeks of life with a severe liver dysfunction. We report on a case of congenital galactosaemia with, on the one hand, an early onset liver failure, without any free interval, and on the other hand, an hemophagocytic syndrome as a severe secondary outbreak with pulmonary haemorrhage. Appropriate diet led to normalisation of liver function. Hemophagocytosis, probably linked to an associated Klebsiella Pneumoniae sepsis, had a favourable outcome after antibiotic and corticosteroid therapy.

Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy

The succinic semialdehyde dehydrogenase (SSADH) null mouse represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both γ-hydroxybutyric acid (GHB) and γ-aminobutyric acid (GABA) in brain, blood, and urine. GHB is known to induce absence-like seizures and absence seizures have been reported to occur in children with SSADH deficiency. We tested the hypothesis that the phenotype of the SSADH −/− mouse shows absence-like seizures because of the inordinately high levels of GHB in the brain of this mutant animal. Sequential electrocorticographic (ECoG) and prolonged video ECoG recordings from chronically implanted electrodes were done on SSADH −/−, SSADH +/−, and SSADH +/+ mice from postnatal day (P) 10 to (P) 21. Spontaneous, recurrent absence-like seizures appeared in the SSADH −/− during the second week of life and evolved into generalized convulsive seizures late in the third week of life that were associated with an explosive onset of status epilepticus which was lethal. The seizures in SSADH null mice were consistent with typical absence seizures in rodent with 7 Hz spike-and-wave discharge (SWD) recorded from thalamocortical circuitry, the onset/offset of which was time-locked with ictal behavior characterized by facial myoclonus, vibrissal twitching and frozen immobility. The absence seizures became progressively more severe from P14 to 18 at which time they evolved into myoclonic and generalized convulsive seizures that progressed into a lethal status epilepticus. The absence seizures in SSADH −/− were abolished by ethosuximide (ETX) and the GABA BR antagonist CGP 35348. The seizure phenotype in the SSADH −/− recapitulates that observed in human SSADH deficiency. Hence, SSADH −/− may be used to investigate the molecular mechanisms that underpin the pathogenesis of absence and generalized tonic-clonic seizures associated with SSADH deficiency. As well, the SSADH −/− may represent a unique animal model of the transition from absence to myoclonic and generalized convulsive seizures that is observed in up to 80% of patients with juvenile absence epilepsy.

Isolation stress during the third postnatal week alters radial arm maze performance and corticosterone levels in adulthood

Stressful experiences during development cause long-lasting changes in neuroendocrine systems as well as lasting changes in behavior. The present study examines the long-term consequences of daily periods of social isolation during the third postnatal week on radial arm maze performance in adulthood. Male rat pups were either isolated for 6 h per day between postnatal days 15–21 or remained in the home cage. This manipulation caused a significant increase in plasma corticosterone during the isolation period. As adults, these animals were tested on a 12-arm radial arm maze. Rats that experienced social isolation during development made more working memory errors during initial acquisition but reached an asymptotic level of performance comparable to controls. The pattern of reference memory errors across testing was comparable to the pattern of working memory errors, though the difference between isolated and control animals was not significant. Blood samples taken in adulthood revealed that social isolation during development results in an long-term elevation in plasma corticosterone levels. These findings indicate that isolation stress during the third week of life leads to lasting impairments in cognition and HPA axis activity and suggest a potential alteration in hippocampal function.

Molecular and cellular correlates of the developmental acquisition of mechanisms modulating ingestive behavior

Postnatal development in most mammals is accompanied by the acquisition of controls of ingestion. In rodents, the initial and default controller appears to be gastric stretch. In the second week of life, rat pups acquire the ability to sense the presence of nutrients within the gut and appropriately modulate ingestion. In the third week of life, rat pups start to become weaned from the dam's milk and begin independent ingestion. There have been strong indications that neuropeptide Y is a stimulator of ingestion in adults, although there was very little information in pups. Dr. Gerard Smith initiated a series of studies that provide strong evidence to indicate that hypothalamic neuropeptide Y (NPY) neurons are strong candidates for providing the ability of preweaning rat pups to modulate ingestion according to caloric intake. Moreover, the studies also suggest that the overactivity of hypothalamic NPY neurons presage the onset of hyperphagia in syndromes associated with defects in leptin signaling.

Gene expression of OGFr in the developing and adult rat brain and cerebellum

The native opioid peptide, [Met 5]-enkephalin (termed opioid growth factor (OGF)), is a tonically active negative growth factor targeted to cell proliferation in the developing nervous system. OGF action is mediated by the OGF receptor (OGFr). The present study investigates gene expression of OGFr in the developing and adult brain and cerebellum of the rat using Northern blot analysis and normalization to GAPDH. OGFr was detected in whole brain at embryonic day 20 and birth, and was at least twofold greater than neonatal levels during the first week of life. From postnatal day 15 onwards to adulthood, levels of OGFr mRNA in the whole brain were detectable but less than those at birth. OGFr mRNA in cerebellum was found on embryonic day 20, and remained relatively constant until postnatal day 12 when a sharp increase was recorded. In the third week of life and continuing into adulthood, cerebellar OGFr mRNA was detected at levels comparable to those in postnatal week 1. These results show that message for OGFr is developmentally regulated prior to and after birth, is ubiquitously expressed during development, and is present in the adult brain and cerebellum even though OGF receptor binding is not recorded.

Cardiac features in the presymptomatic period in a neonate with anomalous left coronary artery arising from the pulmonary trunk

We describe a neonate presenting with a cholestatic jaundice due to Alagille syndrome. On echocardiography as part of the diagnostic work-up, we noted a slight dilation of the normally functioning left ventricle at the initial examination in the third week of life. Over the next 2 weeks, serial echocardiograms showed slowly progressive dilation and dysfunction of the left ventricle, together with a persistent mild elevation of levels of cardiac Troponin-I in the serum. These findings, unrelated to the underlying Alagille syndrome, prompted cardiac catheterisation, which confirmed that the main stem of the left coronary artery was originating from the pulmonary trunk. Surgery was successfully performed still in the presymptomatic period. The association of Alagille syndrome with anomalous left coronary artery arising from the pulmonary trunk is most unusual. We emphasise the cardiac findings prior to detection of the anomalous origin of the coronary artery.

Reference Intervals and Age‐related Changes for Platelet Count, Mean Platelet Volume and Plateletcrit in Healthy Pre‐weaning Piglets in Italy

Platelet count (PLT) mean platelet volume (MPV) and plateletcrit (PCT) were determined for 117 Landrace x Large White piglets aged 3-21 days; counts were performed with an automated blood cell counter (ABX Pentra 120). Reference values were estimated following the guidelines of the International Federation of Clinical Chemistry (IFCC) and the International Committee for Standardization in Haematology (ICSH). The calculated central 95% reference limits for PLT was 49.9-516.2 x 10(9)/1, for MPV 6.71-9.91 fl and for PCT 0.009-0.395%. When observations are divided into three age groups (about 1 week each) there is an increase in mean PLT count and PCT in 2-week piglets, and a decrease in MPV from the first to the third week of life. These reference values provide guidelines for interpreting for experimental and clinical observations, as well as for monitoring of the health status of similar aged piglets determined using automated impedance-light focusing methodology.

Limitations of ultrasonography for diagnosing white matter damage in preterm infants

Objectives: To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. Design:...