IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease.

Genetic defects of innate immunity impairing intestinal bacterial sensing are linked to the development of Inflammatory Bowel Disease (IBD). Although much evidence supports a role of the intestinal virome in gut homeostasis, most studies focus on intestinal viral composition rather than on host intestinal viral sensitivity. To demonstrate the association between the development of Very Early Onset IBD (VEOIBD) and variants in the IFIH1 gene which encodes MDA5, a key cytosolic sensor for viral nucleic acids.

Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3 like matrix AAA peptidase subunit 2 gene.

Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. In an attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19-year-old male that had been affected by isolated DOA since childhood.

Cardiac arrest in a toddler treated with propranolol for infantile Hemangioma: a case report.

Background: Propranolol has become the first-line treatment for complicated Infantile Hemangioma (IH), showing so far a good risk-benefit profile.

Case Presentation: We report the case of a toddler, on propranolol, who suffered cardiac arrest during an acute viral infection. She had a neurally-mediated syncope that progressed to asystole, probably because of concurrent factors as dehydration, beta-blocking and probably individual susceptibility to vaso-vagal phenomena.

Pathogenesis of migraine: role of neuromodulators.

The pathogenesis of migraine is still, today, a hotly debated issue. Recent biochemical studies report the occurrence in migraine of metabolic abnormalities in the synthesis of neurotransmitters and neuromodulators. These include a metabolic shift directing tyrosine metabolism toward the decarboxylation pathway, therein resulting in an unphysiological production of noradrenaline and dopamine along with increased synthesis of traces amines such as tyramine, octopamine, and synephrine.

Migraine with aura: conventional and non-conventional treatments.

Migraine with aura (MwA) is a primary headache that affects up 30% of migraine patients. Although the frequency of MwA attacks is usually low and the majority of migraine sufferers do not need prophylactic treatment(s), same particular patients do. This occurs when the neurological symptoms, that characterize the auras, determine anxiety to the migraine sufferers and when the frequency of MwA attacks is or becomes high.

Thymidylate synthetase allelic imbalance in clear cell renal carcinoma.

Purpose: To investigate the allelic status of the thymidylate synthetase (TYMS) gene, located at chromosome band 18p11.32, in renal cell carcinoma (RCC). TYMS is a key target of the 5-fluorouracil (5-FU)-based class of drugs, frequently considered in combination therapies in advanced RCC.

1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity.

Some nonsteroidal anti-inflammatory drugs has been shown to allosterically modulate the activity of gamma-secretase, the enzymatic complex responsible for the formation of beta-amyloid (Abeta). 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074) is a new gamma-secretase modulator, devoid of anticyclooxygenase (COX) and Notch-interfering activities in vitro. We evaluated the effects of chronic CHF5074 treatment on brain Abeta pathology in Tg2576 transgenic mice.

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells.

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3-10 muM) augments beta-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by G(i)/G(o) protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca(2+)](i)) levels sensitive to clotrimazole and nitrendipine (10-30 muM).

Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients.

To investigate whether peripheral immune abnormalities are associated with brain inflammation in multiple sclerosis, and whether differences in MRI activity are paralleled by changes in leukocyte composition, we conducted a prospective longitudinal study in patients at their clinical onset. Twenty patients presenting a first inflammatory event in the central nervous system suggestive of multiple sclerosis underwent, every 45 days for one year, immunophenotyping of 98 blood cell subsets together with brain MRI and clinical evaluation. Six patients showed intense MRI activity, six patients did not display MRI activity, while the remaining 8 patients had low (i.

Identification of an unusual naturally occurring apolar fatty acid amide in mammalian brain and a method for its quantitative determination.

Fatty acid amides (FAAs), such as the N-acylamides, N-acylethanolamides, N-acyldopamines and N-acylamino acids, are now emerging as an important new class of lipid-signalling molecules. This paper provides evidence, based on high-performance liquid chromatography/electrospray ionisation mass spectrometry (HPLC/ESI-MS/MS), gas chromatography/mass spectrometry (GC/MS) and 1H-NMR, of the occurrence in mouse and bovine brain extracts of a compound characterised by a mass spectrum attributable to a FAA not previously described, namely, the isopropyl-amide of stearic acid (SIPA). A highly sensitive GC/MS method was developed for quantification of naturally occurring SIPA and, also, for purposes of comparison, that of palmitoylethanolamide (PEA), a structurally related compound commonly determined in animal tissues.

Stearoylethanolamide exerts anorexic effects in mice via down-regulation of liver stearoyl-coenzyme A desaturase-1 mRNA expression.

Given the recent demonstration that oleoylethanolamide (OEA), a cannabinoid receptor-inactive N-acylethanolamine, decreases food intake by activating the nuclear receptor PPARalpha (peroxisome proliferator-activated receptor alpha) in the periphery, we here evaluated the effects of both saturated and unsaturated C18 N-acylethanolamides (C18:0; C18:1; C18:2) in mice feeding behavior after overnight starvation. Our results show stearoylethanolamide (SEA, C18:0) exerts, unlike other unsaturated C18 homologs, a marked dose-dependent anorexic effect evident already at 2 h after its intraperitoneal administration. In addition, oral administration of SEA (25 mg/kg) was also effective in reducing food consumption, an effect ascribed to the molecule itself and not to its catabolites.