Small-bowel MRI in children and young adults with Crohn disease: retrospective head-to-head comparison of contrast-enhanced and diffusion-weighted MRI

Small-bowel MRI based on contrast-enhanced T1-weighted sequences has been challenged by diffusion-weighted imaging (DWI) for detection of inflammatory bowel lesions and complications in patients with Crohn disease.

[Fetal programming of cardiovascular disease: new causes and underlying mechanisms]

There exists an association between pathologic events occurring during early life and the development of cardiovascular disease in adulthood. For example, transient perinatal hypoxemia predisposes to exaggerated hypoxic pulmonary hypertension and preeclampsia predisposes the offspring to pulmonary and systemic endothelial dysfunction later in life. The latter finding offers a scientific basis for observations demonstrating an increased risk for premature cardiovascular morbidity in this population. Very recently, we showed that offspring of assisted reproductive technologies also display generalized vascular dysfunction and early arteriosclerosis. Studies in animal models have provided evidence that oxidative stress and/or epigenetic alterations play an important pathophysiological role in the fetal programming of cardiovascular disease.

[Pulmonary hypertension and lung edema at high altitude. Role of endothelial dysfunction and fetal programming]

High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease

Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Low prevalence of behavioural and emotional problems among Swiss paediatric patients with inflammatory bowel disease

Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables.

Maternal and fetal cord blood lipids in intrauterine growth restriction

Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses.

Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes

Atrial tissue expresses both connexin 40 (Cx40) and 43 (Cx43) proteins. To assess the relative roles of Cx40 and Cx43 in atrial electrical propagation, we synthesized cultured strands of atrial myocytes derived from mice with genetic deficiency in Cx40 or Cx43 expression and measured propagation velocity (PV) by high-resolution optical mapping of voltage-sensitive dye fluorescence. The amount of Cx40 and/or Cx43 in gap junctions was measured by immunohistochemistry and total or sarcolemmal Cx43 or Cx40 protein by immunoblotting. Progressive genetic reduction in Cx43 expression decreased PV from 34+/-6 cm/sec in Cx43(+/+) to 30+/-8 cm/sec in Cx43(+/-) and 19+/-11 cm/sec in Cx43(-/-) cultures. Concomitantly, the cell area occupied by Cx40 immunosignal in gap junctions decreased from 2.0+/-1.6% in Cx43(+/+) to 1.7+/-0.5% in Cx43(+/-) and 1.0+/-0.2% in Cx43(-/-) strands. In contrast, progressive genetic reduction in Cx40 expression increased PV from 30+/-2 cm/sec in Cx40(+/+) to 40+/-7 cm/sec in Cx40(+/-) and 45+/-10 cm/sec in Cx40(-/-) cultures. Concomitantly, the cell area occupied by Cx43 immunosignal in gap junctions increased from 1.2+/-0.9% in Cx40(+/+) to 2.8+/-1.4% in Cx40(+/-) and 3.1+/-0.6% in Cx40(-/-) cultures. In accordance with the immunostaining results, immunoblots of the Triton X-100-insoluble fraction revealed an increase of Cx43 in gap junctions in extracts from Cx40-ablated atria, whereas total cellular Cx43 remained unchanged. Our results suggest that the relative abundance of Cx43 and Cx40 is an important determinant of atrial impulse propagation in neonatal hearts, whereby dominance of Cx40 decreases and dominance of Cx43 increases local propagation velocity.