Renal effects of adenosine A1-receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine in hypoxemic newborn rabbits.

The key role of intrarenal adenosine in mediating the hypoxemic acute renal insufficiency in newborn rabbits has been well demonstrated using the nonspecific adenosine antagonist theophylline. The present study was designed to define the role of adenosine A1 receptors during systemic hypoxemia by using the specific A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function parameters were assessed in 31 anesthetized and mechanically ventilated newborn rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis (+44%) and GFR (+19%), despite a significant decrease in renal blood flow (RBF) (-22%) and an increase in renal vascular resistance (RVR) (+37%). In hypoxemic conditions, diuresis (-19%), GFR (-26%), and RBF (-35%) were decreased, whereas RVR increased (+33%). DPCPX administration hindered the hypoxemia-induced decrease in GFR and diuresis. However, RBF was still significantly decreased (-27%), whereas RVR increased (+22%). In all groups, the filtration fraction increased significantly. The overall results support the hypothesis that, in physiologic conditions, intrarenal adenosine plays a key role in regulating glomerular filtration in the neonatal period through preferential A1-mediated afferent vasoconstriction. During a hypoxemic stress, the A1-specific antagonist DPCPX only partially prevented the hypoxemia-induced changes, as illustrated by the elevated RVR and drop in RBF. These findings imply that the contribution of intrarenal adenosine to the acute adverse effects of hypoxemia might not be solely mediated via the A1 receptor.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland.

BACKGROUND: Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland. METHODS: IRT was measured using AutoDELFIA Neonatal IRT-Kit in stored NBS cards. RESULTS: Between 2006 and 2009, 66 children with CF were reported, 4 of which were excluded for various reasons (born in another country, NBS at 6 months, no informed consent). 98% (61/62) had significantly higher IRT compared to matched control group. There was one false negative IRT result in an asymptomatic child with atypical CF (normal pancreatic function and sweat test). CONCLUSIONS: All children but one with atypical CF would have been detected with the planned two step protocol.

Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Résumant mon travail de thèse, l'article qui suit décrit un nouveau modèle animal servant à étudier l'impact combiné d'une ventilation mécanique (VM), d'une oxygénothérapie et d'une inflammation sur des poumons immatures. Cette étude permet, pour la première fois, de mesurer l'expression de gènes à distance d'une VM pour en analyser la cinétique. La VM représente un traitement intégral dans la prise en charge de prématurés. Sauvant des vies, elle est cependant non-physiologique et décrite comme nocive à court et à long terme, empêchant le bon développement pulmonaire. Nombreuses études se sont intéressées à l'impact immédiat de la VM sur les poumons, mais il n'existe à ce jour aucun modèle de rongeur pour en analyser les effets tardifs. Par analogie avec la clinique, nous avons créé un modèle avec un animal dont le stade développemental pulmonaire est comparable aux prématurés humains et consistant en une oxygénothérapie, une VM modérée avec intubation non chirurgicale, similaire à la pratique quotidienne, et un contexte inflammatoire mimant celui de chorioamnionite dans lequel bien des prématurés naissent. Nous avons ensuite réalisé une extubation pour permettre une période de rétablissement, puis fait des analyses et sur le plan structurel par histologie conventionnelle et en 3D, et sur le plan biologique, par analyse de l'expression de gènes et de protéines. Ce travail a permis de valider ce nouveau modèle comme outil de recherche pour réaliser des mesures à distance d'une VM chez des rats nouveau-nés. Comparant ces mesures à celles prises à la fin de la VM, nous observons: une augmentation initiale et transitoire des médiateurs impliqués dans la cascade inflammatoire dont le corrélat histologique est une maladie inflammatoire pulmonaire et, tardivement, une altération plus développementale de la structure pulmonaire avec diminution de l'alvéolarisation. Ceci pourrait être en partie dû à une expression asynchrone de gènes décrits comme importants pour la formation des alvéoles (matrix metalloproteinase 9, elastine). Offrant une nouvelle approche pour la recherche pulmonaire chez les rongeurs, ce modèle servira comme futur outil pour approfondir nos connaissances de la physiopathologie conduisant aux altérations structurelles retrouvées dans les poumons d'anciens prématurés soumis à une VM (dysplasie broncho-pulmonaire), pour tester l'influence de certains traitements (p.ex. surfactant) et pour étudier les effets de la VM en l'appliquant à des modèles transgéniques.

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Implications of newborn hearing screening: counseling parents of newborns with hearing loss

This paper reviews parental reactions to their newborn newly diagnosed with a hearing loss.

Auditory brainstem response with alternative transducers: implications for newborn hearing screening

This paper studies the efficacy of a bone-conducted transducer compared to a traditional air conduction transducer for auditory brainstem response screening of newborns.

Fructose in fetal cord blood and its relationship with maternal and 48-hour-newborn blood concentrations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 +/- 0.9 days; 2369 +/- 491 g) were randomly assigned to receive saline (placebo, P) or the AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland

Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland.

Acceptance of two liquid vitamin D₃ formulations among mothers with newborn infants: a randomized, single-blind trial

In Switzerland, children are prescribed 7.5-12.5 μg per day of vitamin D(3) dissolved in alcohol, but many families do not adhere to the recommendation. The aim of the trial was to compare the acceptance of vitamin D(3) dissolved in alcohol or in medium-chain triglycerides among mothers of Swiss newborn infants. The acceptance was tested in 42 healthy newborn infants (20 girls and 22 boys) aged between 2 and 7 days. Their neonatal body weight ranged between 2.225 and 4.150 kg, and the gestational age between 36 1/7 and 41 3/7 weeks. The blinded mothers rated the facial reaction of their children by pointing on a facial hedonic scale. Thirty eight of the 41 mothers, who brought the comparison to completion, assigned a better score to the oily preparation with no difference in the remaining three cases (P < 0.0001). The acceptance for the oily preparation was significantly better both among mothers whose babies were initially presented the alcoholic preparation and among mothers whose babies were initially presented the oily preparation. Furthermore, the acceptance for the oily preparation was better irrespective of gender of the infant or parity of the mother. In conclusion, from the perspective of mothers, Swiss newborn infants prefer the taste of the oily vitamin D(3) preparation over the alcoholic preparation.

Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation-free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes.

Humoral immune reaction of newborn calves congenitally infected with Neospora caninum and experimentally treated with toltrazuril

Neospora caninum is widely recognized as one of the most important infectious organisms causing abortion and stillbirth in cattle. This parasite causes severe economical losses worldwide. Infection is mostly passed vertically from mother to calf during pregnancy. Under certain circumstances, an infection can lead to abortion, but in most cases it results in a chronically infected calf, which itself will represent the next endogenously infectious generation. So far, no reliable therapeutic or metaphylactic tool has been developed. One possibility to control the problem may consist of treating newborn calves that became vertically infected by a persistently infected mother. This may allow parasite-free offspring. The aim of the present study was to address the questions: (1) can serology be used to assess efficiency of treatment in toltrazuril-medicated animals? and (2) is a strategic prevention measure possible by means of producing N. caninum-free calves from positive cows? Calves from Neospora-seropositive cows and heifers were randomly split into two different medication groups: 36 calves were medicated with toltrazuril and 36 calves obtained a placebo. Medication (20 mg toltrazuril per kg bw) was administered three times, every second day, within the 7 days post natum. Three months after medication, there was no difference in antibody reactivity between the two groups. At later time points (4-6 months), however, significant differences were found, as explained by a strong humoral immunity after chemotherapeutical affection of parasites, while the placebo-treated animals only responded weakly to the persistent infection. In summary, we concluded that (1) serology was not an entirely appropriate tool to answer our initial question and (2) toltrazuril has the potential to eliminate N. caninum in newborn calves. As a consequence, we plan to follow up toltrazuril-medicated calves clinically and serologically over a longer period and investigate if they give birth to Neospora-free calves.

A COMPARISON OF NEONATAL MORTALITY BETWEEN HOSPITALS WITH LEVEL III NEWBORN INTENSIVE CARE UNITS AND ALL OTHER HOUSTON HOSPITALS

A number of medical and social developments have had an impact on the neonatal mortality over the past ten to 15 years in the United States. The purpose of this study was to examine one of these developments, Newborn Intensive Care Units (NICUs), and evaluate their impact on neonatal mortality in Houston, Texas.^ This study was unique in that it used as its data base matched birth and infant death records from two periods of time: 1958-1960 (before NICUs) and 1974-1976 (after NICUs). The neonatal mortality of single, live infants born to Houston resident mothers was compared for two groups: infants born in hospitals which developed NICUs and infants born in all other Houston hospitals. Neonatal mortality comparisons were made using the following birth-characteristic variables: birthweight, gestation, race, sex, maternal age, legitimacy, birth order and prenatal care.^ The results of the study showed that hospitals which developed NICUs had a higher percentage of their population with high risk characteristics. In spite of this, they had lower neonatal mortality rates in two categories: (1) white 3.5-5.5 pounds birthweight infants, (2) low birthweight infants whose mothers received no prenatal care. Black 3.5-5.5 pounds birthweight infants did equally well in either hospital group. While the differences between the two hospital groups for these categories were not statistically significant at the p < 0.05 level, data from the 1958-1960 period substantiate that a marked change occurred in the 3.5-5.5 pounds birthweight category for those infants born in hospitals which developed NICUs. Early data were not available for prenatal care. These findings support the conclusion that, in Houston, NICUs had some impact on neonatal mortality among moderately underweight infants. ^