Ostreopsis cf. ovata, a benthic dinoflagellate often blooming along the Mediterranean coasts, has been associated with toxic events ranging from dyspnea to mild dermatitis. In late September 2009, an Ostreopsis cf.
View Article and Find Full Text PDFThe anthranilic acid diamides represent the most recent class of nonpeptide CCK(1) receptor (CCK(1)-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK(1)-R affinity and 15-fold for the human CCK(1)-R relative to the reference compound 12 (VL-0395).
View Article and Find Full Text PDFBovine and human serum albumins catalyze the aldol reaction of aromatic aldehyedes and acetone, with saturation kinetics and moderate and opposite enantioselectivity. The reaction occurs at the binding site in domain IIa, and is inhibited by warfarin. Kinetic data are consistent with an enamine mechanism.
View Article and Find Full Text PDFMetastasis of the inner auditory canal is a really rare event. Clinically, it usually presents with rapid worsening cranial nerve palsy. Authors present a review of the literature reporting clinical features, radiological findings, intraoperative aspects of an illustrative case.
View Article and Find Full Text PDFThe reduction of 1,3-diketones and β-hydroxyketones with NaBH(4) in aqueous acetonitrile is highly stereoselective in the presence of stoichiometric amounts of bovine or human albumin, giving anti 1,3-diols with d.e. up to 96%.
View Article and Find Full Text PDFClostridium difficile is the most commonly diagnosed cause of nosocomial diarrhea with increasing incidence and mortality among elderly and hospitalized patients. We report the first synthesis of the surface polysaccharide PS-II repeating unit and its nonphosphorylated analogue, with a linker for conjugation, via a (4 + 2) convergent approach from a common AB(D)C tetrasaccharide intermediate.
View Article and Find Full Text PDFIntestinal-type adenocarcinoma of the nasal cavities and paranasal sinuses is a relatively rare tumor. Standard therapeutic modalities include surgery followed by radiotherapy, sometimes with chemotherapy treatment. Despite these treatments, the outcome is poor due to frequent local recurrences constituting the main cause of death among patients; leptomeningeal carcinomatosis is not a frequent event, and its presence indicates short expected survival.
View Article and Find Full Text PDFAn efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale.
View Article and Find Full Text PDFBacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS.
View Article and Find Full Text PDFWe investigated the effects of the hydrogen sulfide (H₂S)-releasing derivatives of aspirin (ACS14) and salicylic acid (ACS21) in a rat model of metabolic syndrome induced by glutathione (GSH) depletion, causing hypertension and other pathological cardiovascular alterations. GSH depletion was induced in normal rats by the GSH-synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L day for seven days in the drinking water). Systolic blood pressure and heart rate were measured daily by the tail-cuff method, and plasma thromboxane B₂, 6-keto-prostaglandin F(2α), 8-isoprostane, GSH, insulin and glucose were determined at the end of the seven-day BSO schedule.
View Article and Find Full Text PDFThe novel quaternary ammonium salt (3R)-3-[[[(3-fluorophenyl)[(3,4,5-trifluorophenyl)methyl]amino]carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyclo[2.2.2]octane bromide (CHF5407) showed subnanomolar affinities for human muscarinic M1 (hM1), M2 (hM2), and M3 (hM3) receptors and dissociated very slowly from hM3 receptors (t(½) = 166 min) with a large part of the receptorial complex (54%) remaining undissociated at 32 h from radioligand washout.
View Article and Find Full Text PDFRecent advances in nanotechnology have allowed significant progress in utilising cutting-edge techniques associated with nanomaterials and nano-fabrication to expand the scope and capability of biosensors to a new level of novelty and functionality. The aim of this work was the development and characterisation of conductive polyaniline (PANI) nanostructures for applications in electrochemical biosensing. We explore a simple, inexpensive and fast route to grow PANI nanotubes, arranged in an ordered structure directly on an electrode surface, by electrochemical polymerisation using alumina nanoporous membranes as a 'nano-mould'.
View Article and Find Full Text PDFObjective: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years.
Methods: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed.
Results: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.
The dense glycan shield on the surface of human immunodeficiency virus type 1 (HIV-1) gp120 masks conserved protein epitopes and facilitates virus entry via interaction to glycan binding proteins on susceptible host cells. The broadly neutralizing monoclonal antibody 2G12 binds a cluster of high-mannose oligosaccharides on the gp120 subunit of HIV-1 Env protein. This oligomannose epitope is currently being considered for the design of a synthetic vaccine.
View Article and Find Full Text PDFStreptococcus agalactiae is the primary colonizer of the anogenital mucosa of up to 30% of healthy women and can infect newborns during delivery and cause severe sepsis and meningitis. Persistent colonization usually involves the formation of biofilm and increasing evidences indicate that in pathogenic streptococci biofilm formation is mediated by pili. Recently, we have characterized pili distribution and conservation in 289 GBS clinical isolates and we have shown that GBS has three pilus types, 1, 2a and 2b encoded by three corresponding pilus islands, and that each strain carries one or two islands.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2010
GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by reverse vaccinology, which has been shown to induce bactericidal antibodies in animal models. Here we show that this antigen induces protective immunity in humans and it is recognized by sera of patients after meningococcal disease. The protein binds heparin in vitro through an Arg-rich region and this property correlates with increased survival of the unencapsulated bacterium in human serum.
View Article and Find Full Text PDFA series of new thienyl ring containing analogues of nelfinavir and saquinavir with different substitution patterns were synthesized from suitable enantiopure diols. Their inhibitory activity against wild type recombinant HIV-1 protease was evaluated. In general thienyl groups spaced from the core by a methylene group gave products showing IC(50) in the nanomolar range, irrespective of the type and the substitution pattern of the heterocycle.
View Article and Find Full Text PDFA laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel beta-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or beta-(1,6)-branched (17mer-CRM197) beta-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-beta-(1,3)-glucan IgG, but no antibodies against beta-(1,6)-glucan, conferred protection to mice lethally challenged with C.
View Article and Find Full Text PDFPseudomonas aeruginosa infections constitute a widespread health problem with high economical and social impact, and the phosphorylcholine phosphatase (PchP) of this bacterium is a potential target for antimicrobial treatment. However, drug design requires high-resolution structural information and detailed biophysical knowledge not available for PchP. An obstacle in the study of PchP is that current methods for its expression and purification are suboptimal and allowed only a preliminary kinetic characterization of the enzyme.
View Article and Find Full Text PDFGroup B Streptococcus (GBS) causes serious infection in neonates and is an important target of vaccine development. Zwitterionic polysaccharides (ZPS), obtained through chemical introduction of positive charges into anionic polysaccharides (PS) from GBS, have the ability to activate human and mouse antigen presenting cells (APCs) through toll-like receptor 2 (TLR2). To generate a polysaccharide vaccine with antigen (Ag) and adjuvant properties in one molecule, we have conjugated ZPS with a carrier protein.
View Article and Find Full Text PDFPrevalence of symptomatic central nervous system (CNS) metastases among patients with breast cancer ranges from 5% to 16%, although autoptic studies have reported prevalence rates of up to 30%. Solid brain tumours are the most common presentation in the CNS (85-95%), and they tend to arise at the grey-white matter junction with a distribution that is proportional to the regional cerebral blood flow. Descriptions of solitary intra-ventricular metastasis are very rare; to date no cases from breast cancer have been reported in the literature.
View Article and Find Full Text PDFThe secretory activity of the two branched malpighian tubules (MTs) of the second-instar larva in Aeolothrips intermedius is described. MTs of adult thrips have the typical ultrastructure of excretory epithelium with apical microvilli containing long mitochondria and a rich system of basal membrane infoldings. In the second-instar larva just before pupation, the ultrastructure of MT epithelial cells is dramatically different, and there are numerous huge Golgi systems in the cytoplasm.
View Article and Find Full Text PDFPurpose: A morphofunctional approach to the management of brain tumours has been claimed to increase diagnostic accuracy. Among the proposed single-photon emission tomography (SPET) tracers, (99m)Tc-sestamibi is able to distinguish recurrent tumour from radio-necrosis and to identify early response or resistance to chemotherapy. Major drawbacks of sestamibi, that is, poor morphological resolution and the sites of physiological uptake, could be overcome by dual-modality, integrated systems.
View Article and Find Full Text PDFThe anthranilic acid diamides represent the more recent class of nonpeptide CCK(1) receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK(1) receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively.
View Article and Find Full Text PDFThis paper describes the development of a rapid and sensitive enzyme-linked electrochemical genosensor using a novel microfluidic-based platform. In this work, hybridization was performed on streptavidin-coated paramagnetic micro-beads functionalized with a biotinylated capture probe. The complementary sequence was then recognized via sandwich hybridization with a capture probe and a biotinylated signaling probe.
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