Levels of cytokines in umbilical cord blood in small for gestational age preterm infants.

INTRODUCTION: Being born small for gestational age (SGA) can be a reference to intrauterine growth retardation (IUGR) and is associated with increased neonatal morbidity and mortality. In pregnancies complicated by IUGR placental insufficiency is thought to be one of the leading underlying pathogenetic mechanisms. As cytokines appear to be implicated in implantation and -placental development, imbalances in cytokine levels may contribute to pregnancy disorders i. e., IUGR. OBJECTIVE: Cord blood cytokine profiles were analyzed in order to characterize differences in cytokine profiles between SGA and appropriate for gestational age (AGA) preterm infants. METHODS: Cytokine concentrations were measured in venous cord blood of preterm infants delivered by caesarean section without previous labour activity and without signs of maternal or fetal infection. RESULTS: 93 preterm infants were enrolled, 29 SGA preterm infants (GA 31.0 (24.6-36.7) weeks; BW 1080 (315-2010) grams) and 63 AGA preterm infants (GA 33.3 (26.0-36.9) weeks; BW 1790 (760-3570) grams). In both groups multiple cytokines could be detected. Significant differences in cytokine levels between the groups were found for G-CSF, IL-12p40 and IL-8, while levels of IL-1a, IL-6, IL-10, IP-10, MCP-1, MCP-3, MIP-1a and TNF-a were not different. CONCLUSIONS: Alteration of cytokine levels in SGA preterm infants may be involved in the pathogenesis of reduced intrauterine growth as well as in the higher morbidity in these infants. Further studies are needed to get more comprehension of the complex function of cytokines in pregnancies complicated by IUGR.

Regenerative therapies in neonatology: clinical perspectives.

Regenerative therapy based on stem cells is applied as standard therapy in pediatric oncology. Furthermore, they are frequently used to treat immunodeficiency disorders of infants. For severe neonatal diseases, e. g. hypoxic-ischemic encephalopathy in term neonates or bronchopulmonary dysplasia in preterm infants, animal models have been established. According to some first preclinical results stem cell administration appears as a promising tool to improve the clinical outcome in high-risk infants. Provided the benefit of regenerative therapies can further be evaluated in appropriate preclinical neonate models, carefully controlled clinical trials to assess the significance of regenerative therapies, such as autologous stem cell administration, are indicated.

Serum cytokine levels in neonates with congenital diaphragmatic hernia.

Cytokines play an important role in immune regulation and fetal lung development. The systemic inflammatory response in newborns with congenital diaphragmatic hernia (CDH) has not been characterized so far. We compared various concentrations of cytokines in serum from newborns with CDH and in healthy term neonates. We analyzed cytokine patterns of CDH newborns under extracorporeal membrane oxygenation (ECMO) and mechanical ventilation (MV).38 newborns with CDH were included: ECMO group (n=13) and non-ECMO group (n=25). Healthy term neonates served as controls (n=13). Serum samples were obtained prospectively after birth and during therapy.Concentrations of IFN-α, IL-3,-6,-7,-8,-10, MIP-1α,-1ß and TNF-α in serum of newborns with CDH were higher than in umbilical cord blood of term neonates. Infants with severe CDH requiring ECMO therapy had higher postnatal IL-8,-10, and MIP-1α levels than newborns with milder disease in the non-ECMO treated group. IL-10 progressively decreased during the first 3 days following birth under ECMO. In contrast, the chemokine MIP-1α remained elevated during ECMO therapy compared to mechanically ventilated CDH newborns.The pattern of cytokines in the serum of newborns with CDH showed significant elevations compared to term neonates. Our findings indicate that CDH is associated with systemic inflammatory response immediately after birth. ECMO and MV show a similar increase of IL-1α and IP-10 in CDH newborns assuming a persistent pulmonary inflammatory reaction irrespective of the conducted treatment.

Three-dimensional in vitro reaggregates of embryonic cardiomyocytes: a potential model system for monitoring effects of bioactive agents.

To understand the physiological effects of substances used in drugs and therapies on heart muscle tissue, model systems that mirror the in vivo situation of living tissues are required. Therefore, the creation of 3-dimensional (3D) cell aggregates provides an improved and refined in vitro model as a link between cell-free or single cells and organs or whole organisms in vivo. Here we have characterized a stable contracting in vitro tissue model, which consists of embryonic chicken cardiomyocytes. For establishing a cell-based test system, the 3D in vitro cardiomyocyte spheres were characterized according to messenger RNA expression of special cardiac cell types and protein expression pattern of functional markers such as connexin-43. Finally, the in vitro spheroid model was used for investigating the effect of isoproterenol, a *-adrenergic receptor agonist, on the contractibility mediated by the ligand receptor interaction.

Novel tankyrase-related gene detected with meningioma-specific sera.

In many meningiomas, alterations of chromosome 22 can be found, and the NF2 (neurofibromatosis type 2) gene, in particular, is of great interest as a putative gene involved in meningioma. Because the NF2 gene is not mutated in all meningiomas, additional genes may be involved. Instead of looking for alterations directly at the DNA level, we used the immune response of meningioma patients to identify immunogenic antigens that may be associated with the disease. We screened a fetal brain cDNA expression library with sera pools from different patients bearing meningioma classified according to the three WHO grades, using the serological identification of antigens by recombinant expression cloning immunological screening method. Here, we report the finding of a new tankyrase-related protein. We found 16 overlapping clones with homologies to tankyrase when we screened the library with the common-type meningioma sera pool and 2 such clones when we screened the library with the atypical meningioma sera. The anaplastic meningioma sera did not identify any tankyrase-related clones. We tested some of the newly identified clones with 13 single sera, 6 of which (37.5%) reacted positively with the tankyrase-related clones. In addition, we screened the tankyrase-related clone with six sera pools from individuals without obvious disease. Although 1 of 24 (4.2%) normal sera reacted with the tankyrase-related clone, we found a striking difference in the frequency of reactivity to this clone by sera from patients bearing tumors corresponding to the three WHO meningioma grades; common-type sera was the most frequently reactive. Northern blot analysis demonstrates expression of the novel tankyrase gene in two common-type meningiomas from patients with immune response.