The DMT1 IVS4+44C>A polymorphism and the risk of iron deficiency anemia in children with celiac disease.

Background: Iron deficiency anemia in celiac disease is related to impaired duodenal mucosal uptake, due to villous atrophy. Iron enters the enterocytes through an apical divalent metal transporter, DMT1. Different DMT1 transcripts have been identified, depending on the presence of an iron-responsive element that allows DMT1 up-regulation during iron starvation.

Moyamoya syndrome in children with neurofibromatosis type 1: Italian-French experience.

Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children with neurofibromatosis type 1 (NF1). In this study, we clinically, radiologically, and genetically examined a cohort that was not previously described, comprising European children with NF1 and MMS. The NF1 genotyping had been registered.

PKCβII-mediated cross-talk of TRPV1/CB2 modulates the glucocorticoid-induced osteoclast overactivity.

In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts.

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation.

Context: Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/hypertrophy. Obesity inhibits the "browning" of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce antiobesity effect in mice.

Iron overload enhances human mesenchymal stromal cell growth and hampers matrix calcification.

Background: Iron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron overload including liver, heart, joints, endocrine glands, and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed.

Serum Hepcidin and Iron Absorption in Paediatric Inflammatory Bowel Disease.

Background And Aims: We sought to correlate hepcidin levels in inflammatory bowel disease [IBD] children with disease activity, inflammatory markers, and iron load test [ILT] and to compare IBD patients with coeliac and healthy patients.

Methods: Between December 2012 and June 2013, 145 subjects [50 IBD patients, 45 coeliac patients and 50 healthy controls] were included in the study. All patients underwent the following examinations: blood count, iron status, erythropoiesis parameters, serum hepcidin, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR].

The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche.

Background: The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement.

CB(2) and TRPV(1) receptors oppositely modulate in vitro human osteoblast activity.

In the current study, we have investigated the effect of CB2 and TRPV1 receptor ligands on in vitro osteoblasts from bone marrow of human healthy donors. A pivotal role for the endocannabinoid/endovanilloid system in bone metabolism has been highlighted. We have demonstrated a functional cross-talk between CB2 and TRPV1 in human osteoclasts, suggesting these receptors as new pharmacological target for the treatment of bone resorption disease as osteoporosis.

Association between cannabinoid receptor type 2 Q63R variant and oligo/polyarticular juvenile idiopathic arthritis.

Objectives: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features.

Method: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped.

Results: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.

Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels.

The pathogenesis of bone resorption in β-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with β-thalassemia major and its relationship with iron overload and iron chelation therapy. This study demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration.

Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with β-thalassemia major.

Iron overload in β-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.

ITP-QoL questionnaire for children with immune thrombocytopenia: Italian version validation's.

Background: The ITP-QoL is a disease-specific questionnaire for the assessment of health-related quality of life (HRQoL) in children with immune thrombocytopenia (ITP) and their parents. The aim of this study was to test the psychometric characteristics of the ITP-QoL in the Italian pediatric population in terms of validity and reliability.

Procedure: Children aged 8-16 years with acute or chronic ITP and their parents were recruited in Italy.

The cannabinoid receptor type 2 as mediator of mesenchymal stromal cell immunosuppressive properties.

Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive properties of human mesenchymal stromal cells have attracted much attention from immunologists, stem cell biologists and clinicians. Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated.

The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice.

Background And Purpose: Osteoporosis is a condition characterized by a decrease in bone density, which decreases its strength and results in fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved in the regulation of skeletal remodelling. The aim of this study was to investigate the possible modulation of bone mass mediated by the transient receptor potential vanilloid type 1 channel (TRPV1) in vivo and in vitro.

Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: tailoring better vaccination strategies.

Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes.

Congenital erythrocytosis associated with gain-of-function HIF2A gene mutations and erythropoietin levels in the normal range.

Hypoxia-inducible factor 2α (HIF-2α) plays a pivotal role in the balancing of oxygen requirements throughout the body. The protein is a transcription factor that modulates the expression of a wide array of genes and, in turn, controls several key processes including energy metabolism, erythropoiesis and angiogenesis. We describe here the identification of two cases of familial erythrocytosis associated with heterozygous HIF2A missense mutations, namely Ile533Val and Gly537Arg.

Association between a polymorphism in cannabinoid receptor 2 and severe necroinflammation in patients with chronic hepatitis C.

Background & Aims: The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection.

The 17-β-oestradiol inhibits osteoclast activity by increasing the cannabinoid CB2 receptor expression.

Bone is a highly metabolically active tissue and its formation and resorption is at the base of bone remodelling. The critical importance of a balanced bone remodelling is demonstrated by human diseases, i.e.

Neridronate improves bone mineral density and reduces back pain in β-thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel-arm, open-label study.

Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open-label study, 118 adults with β-thalassaemia and bone mineral density (BMD) Z scores ≤-2·0 were randomized 1:1-500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P < 0·001), and values were significantly higher than the control group at both time intervals.

The cannabinoid receptor type 2 Q63R variant increases the risk of celiac disease: implication for a novel molecular biomarker and future therapeutic intervention.

Celiac disease (CD) is a chronic inflammatory disease of the small bowel that occurs with the ingestion of gluten, found in several grains products. Although HLA-DQ2 variant is required for the gluten-derived peptide gliadin presentation by antigen-presenting cells to T-cells, non-HLA genetic factors account for the majority of heritable risk. Several genome-wide association studies have identified susceptibility loci for CD on chromosome 1.

CNR2 functional variant (Q63R) influences childhood immune thrombocytopenic purpura.

Immune thrombocytopenic purpura is an acquired autoimmune disorder that is the most common cause of thrombocytopenia in children. The endocannabinoid system is involved in immune regulation. We evaluated a common missense variant (CAA/CGG; Q63R) of the gene encoding the cannabinoid receptor type 2 (GeneID 1269) in 190 children with immune thrombocytopenic purpura and 600 healthy controls.

The endovanilloid/endocannabinoid system: a new potential target for osteoporosis therapy.

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis.

Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study.

Background: The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series.

Procedure: Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H.

EPO receptor gain-of-function causes hereditary polycythemia, alters CD34 cell differentiation and increases circulating endothelial precursors.

Background: Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined.

Methodology/principal Findings: We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G-->T change at nucleotide 1251 of exon 8.