Congenital high airway obstruction syndrome

Congenital high airway obstruction syndrome (CHAOS) is a very rare fetal malformation caused by obstruction of fetal airway because of laryngeal or tracheal atresia, subglottic stenosis, laryngeal cyst or laryngeal web. The prenatal diagnosis is inferred from secondary changes such as enlarged, hyperechogenic lungs, ascites and/or hydrops, flattened or everted diaphragms, dilated distal airways and mediastinal compression. There are only few cases of long-term survival described in literature. We present the case of fetus with such secondary changes diagnosed during routine ultrasound evaluation in 20 weeks' gestation. There were no other abnormalities and the kariotype was normal. In 26 weeks' gestation fetal hydrops appeared and subsequent polyhydramnios occurred in 28 weeks' gestation. The patient was planned for EXIT procedure during labor in experienced in CHAOS cases center. In 29 weeks' gestation the premature rupture of membranes and regular uterine contractions occurred and we've performed cesarean section. A multidisciplinary team of neonatologists, laryngologists and pediatric surgeons made their efforts to save the newborn, but there was complete laryngeal atresia and tracheal agenesia and immediate tracheostomy was impossible. The most important about CHAOS are early diagnosis, detailed fetal assessment and an adequate postnatal intervention for establishing fetal airways.     

Pharmacological and Regional Characterization of [3H]LY278584 Binding Sites in Human Brain

Abstract: Binding of [³H]LY278584, which has been previously shown to label 5-hydroxytryptamine₃ (5-HT₃) receptors in rat cortex, was studied in human brain. Saturation experiments revealed a homogeneous population of saturable binding sites in amygdala ( K _D= 3.08 ± 0.67 n M, B _max= 11.86 ± 1.87 fmol/mg of protein) as well as in hippocampus, caudate, and putamen. Specific binding was also high in nucleus accumbens and entorhinal cortex. Specific binding was negligible in neocortical areas. Kinetic studies conducted in human hippocampus revealed a K _on of 0.025 ± 0.009 n M ⁻¹ min⁻¹ and a K _off of 0.010 ± 0.002 min⁻¹. The kinetics of [³H]LY278584 binding were similar in the caudate. Pharmacological characterization of [³H]LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5-HT₃ receptors. We conclude that 5-HT₃ receptors labeled by [³H]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5-HT₃ receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies.     

Deletion of IKK2 in haematopoietic cells of adult mice leads to elevated interleukin-6, neutrophilia and fatal gastrointestinal inflammation

The IκB kinase complex, consisting of IKK1, IKK2 and the regulatory subunit NEMO, is required for NF-κB signalling following the activation of several cell surface receptors, such as members of the Tumour Necrosis Factor Receptor superfamily and the Interleukin-1 Receptor. This is critical for haematopoietic cell proliferation, differentiation, survival and immune responses. To determine the role of IKK in the regulation of haematopoiesis, we used the Rosa26^Cre-ERT2 Cre/lox recombination system to achieve targeted, haematopoietic cell-restricted deletion of the genes for IKK1 or IKK2 in vivo. We found that the IKK complex plays a critical role in haematopoietic cell development and function. Deletion of IKK2, but not loss of IKK1, in haematopoietic cells led to an expansion of CD11b/Gr-1-positive myeloid cells (neutrophilia), severe anaemia and thrombocytosis, with reduced numbers of long-term haematopoietic stem cells (LT-HSCs), short-term haematopoietic stem cells (ST-HSCs) and multipotential progenitor cells (MPPs), increased circulating interleukin-6 (IL-6) and severe gastrointestinal inflammation. These findings identify distinct functions for the two IKK catalytic subunits, IKK1 and IKK2, in the haematopoietic system.Subject terms: Growth factor signalling, Interleukins, Myelopoiesis, Inflammatory diseases, Haematopoietic stem cells