Increased duodenal expression of miR-146a and -155 in pediatric Crohn’s disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast cells. METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well. RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β treatment did not influence the expression of miR-122. CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-β plays an important role in the regulation of the expression of these miRs.     

G-protein coupled receptor kinase-like immunoreactivity in the snail, Helix pomatia, neurons

GPRCs are regulated via phosphorylation by different protein kinases including GRKs and PKA and PKC. The purpose of this study was to determine the presence and physiological role of GRKs in the tissues of the snail, Helix pomatia. Here we report that immunoblotting of brain homogenate with anti-GRK2/3 antibody prepared from mammalian tissue can be detected in snail GRK-like immunoreactivity. The GRK2/3 immunoreactivity was found at approximately 80 kDa in a variety of cells, including salivary duct, salivary gland and eye. Intracellular injection of the anti-GRK2/3 prevented the neuron from desensitization and agonist-induced activation augmented the phosphorylated GRKs in the membrane fraction suggesting that GRKs may have a functional role in the neuropeptide receptor desensitization in snail.     

Glutamatergic innervation of growth hormone-releasing hormone-containing neurons in the hypothalamic arcuate nucleus and somatostatin-containing neurons in the anterior periventricular nucleus of the rat

Growth hormone-releasing hormone (GHRH) and somatostatin are the two main hypothalamic neurohormones, which stimulate or inhibit directly hypophysial growth hormone (GH) release. Majority of the GHRH neurons projecting to the median eminence is situated in the arcuate nucleus and the somatostatin neurons in the anterior periventricular nucleus. Data suggest that the excitatory amino acid glutamate may play an important role in the control of hypothalamic neuroendocrine neurons and processes including the control of GH. There is a dense plexus of glutamatergic fibres in the hypothalamic arcuate and anterior periventricular nucleus. The aim of the present studies was to examine the relationship of these fibres to the GHRH neurons in the arcuate nucleus and to somatostatin neurons in the anterior periventricular nucleus. Double-labelling immuno-electron microscopy was used. Glutamatergic structures were identified by the presence of vesicular glutamate transporter 2 (VGluT2) (a selective marker of glutamatergic elements) immunoreactivity. A significant number of VGluT2-immunoreactive boutons was observed to make asymmetric type of synapses with GHRH-immunostained nerve cells in the arcuate and with somatostatin neurons in the anterior periventricular nucleus. A subpopulation of somatostatin-immunoreactive neurons displayed also VGluT2 immunoreactivity. Our findings provide direct neuromorphological evidence for the view that the action of glutamate on GH release is exerted, at least partly, directly on GHRH and somatostatin neurons releasing these neurohormones into the hypophysial portal blood.     

Utility of combined high-resolution bone SPECT and MRI for the identification of rheumatoid arthritis patients with high-risk for erosive progression

Objectives

To evaluate the utility of sequentially acquired, post hoc fused, magnetic resonance imaging (MRI) and multi-pinhole single photon emission computed tomography (MPH-SPECT) with technetium-99m-labeled disphosphonates (Tc99m-DPD) for the identification of finger joints with later erosive progression in early rheumatoid arthritis (ERA) patients.

Methods

Ten consecutive ERA patients prospectively underwent MPH-SPECT and MRI of metacarpophalangeal (MCP) joints prior to and after 6 months methotrexate therapy. Tc99m-DPD uptake was measured at proximal and distal MCP sites using regional analysis. The course of joint pathologies was scored according to the Rheumatoid Arthritis MRI Score (RAMRIS) criteria.

Results

The frequency of increased Tc99m-DPD uptake, synovitis and bone marrow edemadecreased under MTX therapy; but the number of bone erosions increased. Joints with progressive and new erosions on follow-up had a higher baseline Tc99m-DPD uptake (2.64 ± 1.23 vs. 1.43 ± 0.91) (p = 0.02).

Conclusions

Joints with erosive progression are characterized by an early increased Tc99m-DPD uptake, even in absence of MRI bone pathologies. Tc99m-DPD MPH-SPECT might thus be of additional value to morphological MRI for the identification of RA patients with a high risk for erosive progression.     

Magnesium in Animal Nutrition

Magnesium (Mg) supplementation remarkably improves the digestibility of feed. In cows and sows, it has improved the reproduction and shortened the service period. In broilers it increased weight gain, and it has increased egg production of laying hens. In addition, increasing Mg intake benefits the quality of breeding eggs and improves hatching yield. However, increasing Mg intake has not altered visceral composition of embryos, although brain and liver might have the capacity to store Mg at intake above the requirement.     

Effects of Penta‐O‐galloyl‐β‐D‐glucose on Human Neutrophil Function: significant Down‐Regulation of L‐selectin Expression

Penta‐O‐galloyl‐β‐D‐glucose (PGG) occurrs in high concentrations in medicinal herbs such as Rhus chinensis, Paeonia suffruticosa, Acer truncatum and Terminalia chebula, which demonstrate anti‐inflammatory activity. We investigated the effect of PGG on stimulated and non‐stimulated neutrophils in processes which included reactive oxygen species generation (ROS), metalloproteinase‐9 and interleukin‐8 secretion (IL‐8), β₂ integrin (CD11b) and L‐selectin (CD62L) expression and apoptosis. In concentrations of 5 μM–20 μM, PGG demonstrated statistically significant inhibition of ROS generation, IL‐8 secretion and β₂ integrin expression in stimulated neutrophils. The inhibition of L‐selectin expression by PGG resulted in prevention in neutrophils’ endothelial attachment. The result obtained may explain the anti‐inflammatory activity of this compound and underline the contribution of PGG in the activity of PGG rich plant extracts. Copyright © 2012 John Wiley & Sons, Ltd.     

Welfare standards in hospital mergers

There is a broad literature on the consequences of applying different welfare standards in merger control. Total welfare is usually defined as the sum of consumer and provider surplus, i.e., potential external effects are not considered. The general result is then that consumer welfare is a more restrictive standard than total welfare, which is advantageous in certain situations. This relationship between the two standards is not necessarily true when the merger has significant external effects. We model mergers on hospital markets and allow for not-profit-maximizing behavior of providers and mandatory health insurance. Mandatory health insurance detaches the financial and consumption side of health care markets, and the concept consumer in merger control becomes non-evident. Patients not visiting the merging hospitals still are affected by price changes through their insurance premiums. External financial effects emerge on not directly affected consumers. We show that applying a restricted interpretation of consumer (neglecting externality) in health care merger control can reverse the relation between the two standards; consumer welfare standard can be weaker than total welfare. Consequently, applying the wrong standard can lead to both clearing socially undesirable and to blocking socially desirable mergers. The possible negative consequences of applying a simple consumer welfare standard in merger control can be even stronger when hospitals maximize quality and put less weight on financial considerations. We also investigate the implications of these results for the practice of merger control.