Efficacy and Tolerability of a New Formulation in Rectal Ointment Based on Zn-L-Carnosine (Proctilor®) in the Treatment of Haemorrhoidal Disease

Haemorrhoidal disease (HD) shows high prevalence in western countries, reaching 4.4% per year in the US. Topical preparations are the first-line treatments, which are readily available as "over-the-counter" (OTC) products, often containing a nonstandardised mixture of "natural" remedies, or anaesthetics or cortisol;those latter are not free from undesirable effects. The Zinc-L-Carnosine is a cytoprotective compound, promoting mucosal repair in the gastrointestinal tract and also in mucosal repair, following radiation injuries to the rectum as well as in ulcerative colitis. Our aim was to study the efficacy of Zinc-L-Carnosine in relieving acute symptoms of HD, testing a preparation in the rectal ointment, Proctilor (R), in patients complaining of bleeding or thrombosed piles. In a multicentre open trial, 21 patients older than 18 years of age were enrolled. The symptoms of HD were graded according to the Haemorrhoidal Disease Symptoms Score (HDSS) in association with the Short Health Scale (SHS) to assess the influence of HD on quality of life. The pain was assessed with the VAS score, bowel habit by means of the Bristol scale. The patients were evaluated at enrolment (T0) and 2 (T1) and 4 (T2) weeks of treatment with Proctilor (R) rectal ointment. There were 10 men and 11 women; mean age, 49 years. Pain, bleeding, and thrombosis were all significantly reduced after treatment; the mean VAS score decreased from 4.71 +/- 3.05 at T0 to.52 +/- 0.87 and.05 +/- 0.22 at T1 and T2, respectively; (mean +/- SD; p < 0.001 in both cases). Similarly, the HDSS score showed to be significantly reduced between T0, T1 (8.05 +/- 4.55 vs. 1.14 +/- 1.01), and T2 (8.05 +/- 4.55 vs. 24 +/- 0.44) (mean +/- SD; p < 0.001 in both cases). Quality of life showed to be improved as the SHS score decreased significantly with treatment (7.90 +/- 4.17 at T0 vs. 4.24 +/- 0.44 at T1 vs. 4.05 +/- 0.22 at T2; mean +/- SD; p < 0.001 in both cases). The Bristol score of defecation remained substantially unchanged. No side effects or discontinuation of treatment were reported. Results of our investigation suggest a role of Proctilor (R) rectal ointment in treating symptomatic HD with good results and an excellent safety profile. However, our preliminary results encourage further studies on a larger number of patients to confirm the role of Zinc-L-Carnosine in the rectal ointment for the topical treatment of HD

A novel splicing mutation in the ABCA1 gene, causing Tangier disease and familial HDL deficiency in a large family.

International audience; Tangier disease is a rare disorder of lipoprotein metabolism that presents with extremely low levels of HDL cholesterol and apoprotein A-I. It is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. Clinical heterogeneity and mutational pattern of Tangier disease are poorly characterized. Moreover, also familial HDL deficiency may be caused by mutations in ABCA1 gene. ATP-binding cassette transporter A1 (ABCA1) gene mutations in a patient with Tangier disease, who presented an uncommon clinical history, and in his family were found and characterized. He was found to be compound heterozygous for two intronic mutations of ABCA1 gene, causing abnormal pre-mRNAs splicing. The novel c.1510-1G > A mutation was located in intron 12 and caused the activation of a cryptic splice site in exon 13, which determined the loss of 22 amino acids of exon 13 with the introduction of a premature stop codon. Five heterozygous carriers of this mutation were also found in proband's family, all presenting reduced HDL cholesterol and ApoAI (0.86 ± 0.16 mmol/L and 92.2 ± 10.9 mg/dL respectively), but not the typical features of Tangier disease, a phenotype compatible with the diagnosis of familial HDL deficiency. The other known mutation c.1195-27G > A was confirmed to cause aberrant retention of 25 nucleotides of intron 10 leading to the insertion of a stop codon after 20 amino acids of exon 11. Heterozygous carriers of this mutation also showed the clinical phenotype of familial HDL deficiency. Our study extends the catalog of pathogenic intronic mutations affecting ABCA1 pre-mRNA splicing. In a large family, a clear demonstration that the same mutations may cause Tangier disease (if in compound heterozygosis) or familial HDL deficiency (if in heterozygosis) is provided

ARMONIA Project: Transfrontier Strategy in the Management of Earthquakes

The ARMONIA project between Italy and Austria, represents a cross-border strategy for prevention and management of seismic risk through real-time production of shaking and damage scenarios using integration and processing of data from seismic and accelerometer monitoring networks. Partners are developing an innovative seismic monitoring system to have an immediate evaluation of the damages distribution and to plan interventions immediately after the occurrence of a destructive earthquake. The first year of ARMONIA project was focused on the reinforcement and improvement of cross border existing free-field accelerometric network and implementation of a dense monitoring network of "significant" buildings through the creation of a dense monitoring network of sensible target buildings in near fault high risk areas along the cross-border territory between Italy and Austria. New instrumentation has been tested and new sites have been selected by following common protocols. This allows to enhance the effectiveness in a transnational prospective, in order to obtain the required quality of the data together with the maximum distribution of the instruments in the territory and provides high level of efficiency adding important information in case of emergency

Peptide-Based Soft Hydrogels Modified with Gadolinium Complexes as MRI Contrast Agents

Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, bioimaging, and fabrication of biosensors). Here we report the synthesis, the structural characterization and the relaxometric behavior of two novel supramolecular diagnostic agents for magnetic resonance imaging (MRI) technique. These diagnostic agents are obtained for self-assembly of DTPA(Gd)-PEG8-(FY)3 or DOTA(Gd)-PEG8-(FY)3 peptide conjugates, in which the Gd-complexes are linked at the Nterminus of the PEG8-(FY)3 polymer peptide. This latter was previously found able to form selfsupporting and stable soft hydrogels at a concentration of 1.0% wt. Analogously, also DTPA(Gd)PEG8-(FY)3 and DOTA(Gd)-PEG8-(FY)3 exhibit the trend to gelificate at the same range of concentration. Moreover, the structural characterization points out that peptide (FY)3 moiety keeps its capability to arrange into β-sheet structures with an antiparallel orientation of the β-strands. The high relaxivity value of these nanostructures (~12 mM−1·s−1 at 20 MHz) and the very low in vitro cytotoxicity suggest their potential application as supramolecular diagnostic agents for MRI

Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis

Erythropoietin (EPO) is of great interest as a therapy for many of the central nervous system (CNS) diseases and its administration is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Endogenous EPO is induced by hypoxic/ischemic injury, but little is known about its expression in other CNS diseases. We report here that EPO expression in the spinal cord is induced in mouse models of chronic or relapsing-remitting EAE, and is prominently localized to motoneurons. We found a parallel increase of hypoxia-inducible transcription factor (HIF)-1 alpha, but not HIF-2 alpha, at the mRNA level, suggesting a possible role of non-hypoxic factors in EPO induction. EPO mRNA in the spinal cord was co-expressed with interferon (IFN)-gamma and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glial cells. Given the known inhibitory effect of EPO on neuroinflammation, our study indicates that EPO should be viewed as part of the inflammatory/anti-inflammatory network in MS

Report of the outcome of the comparative study for the deep Argo quality control processing

Report of the most appropriate methods and tools in the quality control of deep Argo float

Report on the suitability of the actual reference data sets for deep Argo DMQC

This report provides an assessment of the availability and quality of the CTD reference data for Argo for the regions of deployments of the deep European Argo fleet