Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Drug Delivery to the brain: in vivo evaluation on surface engeneered nanoparticles

Drug Delivery to the brain: in vivo evaluation on surface engeneered nanoparticle

Nanotech approaches to CNS delivery: nanoparticles surface modification to obtain long circulating polymeric drug carriers

Nanotech approaches to CNS delivery: nanoparticles surface modification to obtain long circulating polymeric drug carrier

Nanotech approaches to CNS delivery: nanoparticle surface modification to obtain long-circulating polymeric drug carriers

There is a broad interest in the development of nanoparticles (NPs) carrying on their surface carbohydrates such as sialic acids. It is known that these carbohydrates influence the biological and physical properties of biopharmaceutical proteins and living cells. Macromolecular compounds containing these carbohydrates showed an anti-recognition effect, exert an antiviral effect and also are able to be recognized by the cell surface of some kind of cancer cells. Thus, in the present research we performed two different approaches in order to obtain polymeric (poly(d,l-lactide-co-glycolide), PLGA) NPs surface decorated with the sialic acid N-acetylneuraminic acid (Neu5Ac). The first strategy that has been followed is based on the derivatization of the polyester PLGA with the thioderivative of Neu5Ac, starting material for the preparation of the NPs; the second is based on the synthesis of compounds potentially able to insert their lipophilic moiety into the underivatized PLGA NPs during their preparation, and to display their hydrophilic moiety (Neu5Ac) on their surface. The first approach allowed the obtainment of NPs surface decorated with Neu5Ac, as evidenced by ESCA spectroscopy and interaction with the lectin Wheat Germ Agglutinin. Moreover, a formulation of these NPs suitable for in vitro assays showed that they are phagocytosed by human monocytes with an apparently different mechanism with respect of those made of underivatized PLGA. The second strategy led to NPs in which their surface appears to be very different with respect to the NPs obtained following the first strategy, with the carboxylic groups of Neu5Ac markedly shielded. Thus, the new Neu5Ac-modified PLGA polyester represent a useful starting material for the preparation of NPs surface decorated with this sialic acid

Anatomical Study of the Application of a Galeo-Pericranial Flap in Oral Cavity Defects Reconstruction

Oral cavity defects occur after resection of lesions limited to the mucosa, alveolar gum, or minimally affecting the bone. Aiming at esthetical and functional improvements of intraoral reconstruction, the possibility of harvesting a new galeo-pericranial free flap was explored. The objective of this study was to assess the technical feasibility of flap harvesting through anatomical dissections and surgical procedure simulations. Ten head and neck specimens were dissected to simulate the surgical technique and evaluate the vascular calibers of temporal and cervical vessels. The procedure was therefore reproduced on a revascularized and ventilated donor cadaver. Anatomical dissections demonstrated that the mean cervical vascular calibers are compatible with superficial temporal ones, proving to be adequate for anastomosis. Perforating branches of the superficial temporal vascularization nourishing the pericranium were identified in all specimens. In conclusion, blood flow presence was recorded after anastomosing superficial temporal and facial vessels in the revascularized donor cadaver, demonstrating both this procedure's technical feasibility and the potential revascularization of the flap and therefore encouraging its potential in vivo application

Nanotechnology for the CNS drug delivery and targeting

In the last years, the application of "nanotechnology “to the field of “medicine” surely represented the most innovative strategy to cope with diseases and it coule be named as nanomedicine applied to difficult-to-treat diseases. As known, in this field of research, the most important goal to be reached is an increase in selectivity and specificity of drug action. Several results with stimulating findings in preclinical or clinical phases have been reached by using nanocarriers, delivering agents to targeted pathologies, and among them, it is known that neuro-pathologies represent a stimulating issue. In fact, the pharmaceutical treatment of Central Nervous System (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, non-invasive drug delivery systems for CNS are actively studied. The nano-technological approach consist of the use of nanosystems (colloidal carriers) which could be polymer-based (nanoparticles, Np) or solid lipid material made (solid lipid nanoparticles, SLNp) and lipid-based (liposomes, LP). In fact, the development of these new delivery systems started with the discovery that properly surface-engineered colloidal vectors, with a diameter around 200 nm, were shown to be able to cross the BBB without apparent damage, and to deliver drugs or genetic materials into the brain. During this talk, an overview will be presented considering the most recent literature results of nanomedicine applied to brain diseases, carried out with all the most popular kinds of nanoparticulate systems, focusing in particular on peptide-decorated nanosystems able to target the CNS

Immunonanosystems to CNS pathologies: State of the art

This chapter deals with an overall view of nanoparticulate systems opportunately engineered with antibodies for the delivery of active substance to the Central Nervous System. Concordantly to this aim, a brief introduction of the rationale undergoing the nanoparticulate approach to the brain targeting has been developed. Nanoparticles, liposomes and solid lipid nanoparticles, representing the most widely studied carriers for drug delivery and targeting, have been reviewed in their application to CNS targeting. In particular, antibody-mediated targeting represent one of the best choices in order to engineer and superficially modify the carriers, to finally target the therapeutic goal. Amongst the receptors to be usefully used for translocation into the CNS, the transferrin and insulin receptors seem to be the most selective systems for an active transcytosis of antibody-engineered nanosystems across the the Blood Brain Barrier

Nanoparticles for drug delivery to the CNS

Nanoparticles for drug delivery to the CN

Sialic acid as surface modifier of polymeric PLGA nanoparticles

Nanoparticles for drug delivery to CN

Polymeric nanoparticles for CNS drug delivery: strategies and perspectives

The application of nanotechnology to health raises high expectations for a more efficient and affordable healthcare. Even if several areas of medical care could benefit from the advantages that nanotechnology can offer, a selective CNS drug delivery and targeting could improve the therapy of brain diseases which have a tremendous negative impact not only on the patient himself but also on the whole society and linked social and insurance systems. Polymeric nanoparticles (Np) have been considered as strategic carriers for the brain delivery and targeting. Specific ligands on the surface allowed the Np to cross the Blood-Brain Barrier (BBB) carrying model drugs within the brain district after their i.v. administration in experimental animals. A new strategy for Np brain targeting by using a simil-opioid peptide−derived PLGA, obtaining Np showing both the ligands for CNS targeting and the marker of fluorescence on their surface was found (M-Np). After administration, the M-Np were found to be able to cross the BBB and the ability of these M-Np to act as drug carriers has been shown (Tosi et al., 2007). Moreover, the biodistribution of M-Np showed a localization into the CNS in a quantity (15% of the injected dose) about two orders of magnitude greater than that found with the other known Np drug carriers (Vergoni et al., 2009). Moreover, it is known that sialic acid receptors are present in several organs, including in the brain parenchyma. Thus, PLGA Np modified on their surface with a BBB-crossing ligand (simil-opioid peptide) and with a sialic acid residue (SA) were prepared (SA-M-Np). This double targeting (for BBB crossing and for the interaction with brain receptors) allowed to obtain novel targeted Np with a prolonged residence within the brain parenchyma, thus letting to reach a long-lasting brain delivery of drugs. Notwithstanding an increased accumulation of SA-covered Np in those organs showing SA-receptors (liver, kidney, lung), the pharmacological and biodistribution results are proofs of the ability of double-targeted Np to enter the brain allowing the drug to be released over a prolonged time. References•Tosi G. et al., Targeting the Central Nervous System. In vivo experiments with peptide derivatized nanoparticles loaded with Loperamide and Rhodamine 123, J. Control. Release 122 (2007) 1-9.•Vergoni AV et al., Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution. Nanomedicine: Nanotechnology, Biology and Medicine 5 (2009) 369-377