Autori: Alaoui A., Charrouf Z., Pizza C., Carbone V., Malorni A., Piacente S
Titolo: Triterpenoid Saponins from the shell of Argania spinosa seeds
Abstract:
Two new oleanene saponins were isolated from the MeOH extract of the shell of Argania spinosa.They possess protobassic acid and 16alpha- protobassic acid as aglycons. The disaccharide moiety linked to C-3 of the aglycon is made up of two glucose units; the pentasaccharide moiety linked to C-28 is made up of arabinose, xylose, and three rhamnose units. Their structures were elucidated by 1D and 2D NMR experiments including (1)H-(1)H (DQF-COSY, 1D TOCSY, and 2D HOHAHA) and (1)H-(13)C (HSQC and HMBC) spectroscopy along with mass spectrometry.
Rivista: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY anno: 2002	volume n.: 50	pag. da: 4600	a: 4603
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Autori: Andrew C.R. Martin, Angelo M. Facchiano, Alison L. Cuff, Tina Hernandez-Boussard, Magali Olivier, Pierre Hainaut, Janet M. Thornton
Titolo: Integrating Mutation Data and Structural Analysis of the p53 Tumour-Suppressor Protein
Abstract:
TP53 encodes p53, which is a nuclear phosphoprotein with cancer-inhibiting properties. In response to DNA damage, p53 is activated and mediates a set of antiproliferative responses including cell-cycle arrest and apoptosis. Mutations in the TP53 gene are associated with more than 50% of human cancers, and 90% of these affect p53-DNA interactions, resulting in a partial or complete loss of transactivation functions. These mutations affect the structural integrity and/or p53-DNA interactions, leading to the partial or complete loss of the protein's function. We report here the results of a systematic automated analysis of the effects of p53 mutations on the structure of the core domain of the protein. We found that 304 of the 882 (34.4%) distinct mutations reported in the core domain can be explained in structural terms by their predicted effects on protein folding or on protein-DNA contacts. The proportion of "explained" mutations increased to 55.6% when substitutions of evolutionary conserved amino acids were included. The automated method of structural analysis developed here may be applied to other frequently mutated gene mutations such as dystrophin, BRCA1, and G6PD.
Rivista: HUMAN MUTATION anno: 2002	volume n.: 19	pag. da: 149	a: 164
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Autori: Basile A., Ferranti P., Mamone G., Manco I., Pocsfalvi G., Malorni A., Acampora A., Sannolo N.
Titolo: Structural analysis of styrene oxide/haemoglobin adducts by mass spectrometry: identification of suitable biomarkers for human exposure evaluation
Abstract:
The structural characterisation of adducts formed by the in vitro reaction of haemoglobin (Hb) with styrene oxide (SO), the most reactive metabolite of the industrial reagent styrene, was obtained by liquid chromatography/electrospray ionisation mass spectrometry (LC/ES-MS) analysis of modified tryptic peptides of human Hb chains. The reactive sites of human Hb towards SO were identified through characterisation of alkylated tryptic peptides by matrix-assisted laser desorption/ionisation with tandem mass spectrometry (MALDI-MS/MS). A procedure was set up based on this characterisation, allowing Hb modification to be assessed by monitoring SO/Hb adducts using HPLC with selected ion recording (SIR) mass spectrometry. By this methodology it was also possible to compare advantages and disadvantages of presently available strategies for the measurement of Hb adducts with SO. The results obtained could most plausibly lead to the optimisation of molecular dosimetry of SO adducts, and the analytical procedure described herein could be applied to the biological monitoring of styrene exposure in the workplace.
RAPID COMMUNICAIONS IN MASS SPECTROMEY anno: 2002	volume n.: 16	pag. da: 871	a: 878
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Autori: Bevilacqua C., Ferranti P., Garro G., Veltri C., Lagonigro R., Leroux C., Pietrola E., Addeo F., Pilla F., Chianese L., Martin P.
Titolo: Interallelic recombination is probably responsible for the occurrence of a new alpha(s1)-casein variant found in the goat species
Abstract:
The alphas1-casein (alphas1-Cas) locus in the goat is characterized by a polymorphism, the main feature of which is to be qualitative as well as quantitative. A systematic analysis performed in an autochthon southern Italy breed identified a new rare allele (M), which was characterized at both the protein and genomic level. The M protein displays the slowest electrophoretic mobility of the alphas1-Cas variants described so far. MS and automated Edman degradation experiments showed that this behavior was due to the loss of two phosphate residues in the multiple phosphorylation site (64SP-SP-SP-SP-SP-E-70E) consecutively to a Ser-->Leu substitution at position 66 of the peptide chain (64S-SP-L-SP-SP-E-70E). This was confirmed by sequencing a genomic DNA fragment encompassing exon 9 where the 8th codon (TCG) was shown to be mutated to TTG. Sequencing of amplified genomic DNA segments spanning the 5' and 3' flanking regions of each exon allowed us to identify 23 single nucleotide polymorphisms and two insertion/deletion events in the coding as well as the noncoding regions. A comparison of specific haplotypes defined for each of the alphas1-CasF, A and M alleles indicates that the M allele probably arises from interallelic recombination between alleles A and B2, followed by a C-->T transition at nucleotide 23 of the ninth exon. The region encompassing the recombination break point was putatively located between nucleotide 86 upstream and nucleotide 40 downstream of exon 8. Interallelic recombination therefore appears to be a possible means of generating allelic diversity at the alphas1-Cas locus, at least in the goat. The previously proposed molecular phylogeny must now be revised, possibly starting from two ancestral allelic lineages.
EUROPEAN JOURNAL OF BIOCHEMISTY anno: 2002	volume n.: 269	pag. da: 1293	a: 1303
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Autori: De Maria S, Metafora S, Metafora V, Morelli F, Robberecht P, Waelbroeck M, Stiuso P, De Rosa A, Cozzolino A, Esposito C, Facchiano A, Carteni M.
Titolo: Transglutaminase-mediated polyamination of vasoactive intestinal peptide (VIP) Gln16residue modulates VIP/PACAP receptor activity.
Abstract:
Previous data showing an increase of receptor binding activity of [R16]VIP, a vasoactive intestinal peptide (VIP) structural analogue containing arginine at the position 16 of its amino acid sequence, have pointed out the importance of a positive charge at this site. Here, the functional characterization of three VIP polyaminated adducts (VIPDap, VIPSpd, and VIPSpm), obtained by a transglutaminase-catalysed reaction between the VIP Gln16 residue and 1,3-diaminopropane (Dap), spermidine (Spd), or spermine (Spm), is reported. Appropriate binding assays and adenylate cyclase enzymatic determinations have shown that these VIP adducts act as structural VIP agonists, both in vitro and in vivo. In particular, their IC50 and EC50 values of human and rat VIP/pituitary adenylate cyclase activating peptide (PACAP)1 and VIP/PACAP2 receptors indicate that VIPDap is a VIP agonist, with an affinity and a potency higher than that of VIP, while VIPSpd and VIPSpm are also agonists but with affinities lower than that of VIP. These findings suggest that the difference in adduct agonist activity reflects the differences in the positive charge and carbon chain length of the polyamine covalently linked with the VIP Gln16 residue. In addition, the data obtained strongly suggest that the length of polyamine carbon chain could be critical for the interaction of the agonist with its receptor, even though possible hydrophobic interaction cannot be ruled out. In vivo experiments on murine J774 macrophage cell cultures have shown the ability of these compounds to stimulate the inducible nitric oxide synthase activity at the transcriptional level.
EUROPEAN JOURNAL OF BIOCHEMISTY anno: 2002	volume n.: 269	pag. da: 3211	a: 3219
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Autori: Esposito C, Paparo F, Caputo I, Rossi M, Maglio M, Sblattero D, Not T, Porta R, Auricchio S, Marzari R, Troncone R.
Titolo: Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ.
Abstract:
Coeliac disease (CD) is a multifactorial disorder which has an autoimmune component characterised by the occurrence of disease specific autoreactive antibodies against the enzyme tissue transglutaminase (tTG). The aim of this study was to investigate whether binding of antibodies to the enzyme influences tTG activity. METHODS: tTG activity was assayed in the presence of immunoglobulin A (IgA) and immunoglobulin G (IgG) purified from the serum of coeliac patients, CUB 7402 (an anti-tTG mouse monoclonal antibody), and human anti-tTG monoclonal antibodies derived from both intestinal lymphocytes from three patients with CD and from peripheral blood lymphocytes from healthy subjects. For our studies we used calcium treated and untreated recombinant human tTG. Furthermore, the effects of antibodies were determined by immunohistochemical detection of tTG activity in sections of human umbilical cord. RESULTS: IgG and IgA from CD patients inhibited tTG activity in vitro in a dose dependent manner, with a different rate of inhibition among patients. The monoclonal antibody CUB 7402 and human monoclonal antibodies displayed a dose dependent inhibitory effect towards the catalytic activity of the enzyme, both in vitro and in situ. Preincubation of tTG with CaCl(2) caused loss of the inhibitory effect due to CUB 7402 but not that caused by human monoclonal antibodies. CONCLUSIONS: Purified CD IgA, IgG, as well as human anti-tTG monoclonal antibodies inhibited the enzymatic activity of human tTG both in vitro and in situ.
Rivista:GUT anno: 2002	volume n.: 51	pag. da: 177	a: 181
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Autori: Facchiano A, Russo K, Facchiano AM, De Marchis F, Facchiano F, Ribatti D, Aguzzi MS, Capogrossi MC
Titolo: Identification of a novel domain of fibroblast growth factor- 2 controlling its angiogenic properties.
Abstract:
Fibroblast growth factor 2 (FGF-2) is a potent factor modulating the activity of many cell types. Its dimerization and binding to high affinity receptors are considered to be necessary steps to induce FGF receptor phosphorylation and signaling activation. A structural analysis was carried out and a region encompassing residues 48-58 of human FGF-2 was identified, as potentially involved in FGF-2 dimerization. A peptide (FREG-48-58) derived from this region strongly and specifically inhibited FGF-2 induced proliferation and migration of primary bovine aorta endothelial cells (BAEC) in vitro, and markedly reduced FGF-2-dependent angiogenesis in two distinct in vivo assays. To further investigate the role of region 48-58, a polyclonal antibody raised against FREG-(48-58) was tested and was found to block FGF-2 action in vitro. Human FGF-2 has three histidine residues, one falling within the region 48-58. Chemical modification of histidine residues blocked FGF-2 activity and FREG-(48-58) inhibitory effect in vitro, indicating that histidine residues, in particular the one within FREG-(48-58) region, play a crucial role in the observed activity. Additional experiments showed that FREG-(48-58) specifically interacted with FGF-2, impaired FGF-2-interaction with itself, with heparin and with FGF receptor 1, and inhibited FGF-2-induced receptor phosphorylation and FGF-2 internalization. These data indicate for the first time that region 48-58 of FGF-2 is a functional domain controlling FGF-2 activity.
Rivista: JOURNAL OF BIOLOGICAL CHEMISTRY anno: 2002	volume n.:	pag. da:	a:
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Autori: Giacco R., Clemente G., Riccardi G.
Titolo: Dietary fiber in treatment of diabetes: mith or reality?
Abstract:
Diabetes is a plurimetabolic disease characterized mainly by glucose metabolism abnormalities responsible of development of acute and long- term complications in diabetic patients. Long-term complications are quickly increasing, explaining the higher mortality for cardiovascular events observed in diabetic patients in respect to general population. It is well known that a poor blood glucose control is an important risk factor for the development of cardiovascular complications and dietary fiber, particularly the soluble type, play an important role on the control of plasma glucose concentrations and other risk factors associated to diabetes. Several and convincing evidences prove that: 1) dietary fiber in diabetic patients decreases postprandial plasma glucose, insulin and triglyceride concentrations and has a clinically relevant hypocholesterolemic effect; 2) it is possible to increase dietary fiber by consuming exclusively natural foods and to have a satisfactory compliance in free living diabetic patients also in the long term since side effects are minimal; 3) the beneficial metabolic effects of dietary fiber in both type 1 and type 2 diabetic patients are clinically relevant and long-lasting as showed by lower plasma glycosylated hemoglobin levels, reduced rate of hypoglycemias and improved cardiovascular profile.
Rivista: DIGESTIVE AND LIVER DISEASE anno: 2002	volume n.: 34	pag. da: 140	a: 144
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Autori: Iametti S., Rasmussen P., Frokiaer H., Ferranti P., Addeo F., Bonomi F.
Titolo: Proteolysis of bovine beta-lactoglobulin during thermal treatment in subdenaturing conditions highlights some structural features of the temperature-modified protein and yields fragments with low immunoreactivity
Abstract:
Bovine beta-lactoglobulin was hydrolyzed with trypsin or chymotrypsin in the course of heat treatment at 55, 60 and 65 degrees C at neutral pH. At these temperatures beta-lactoglobulin undergoes significant but reversible structural changes. In the conditions used in the present study, beta-lactoglobulin was virtually insensitive to proteolysis by either enzyme at room temperature, but underwent extensive proteolysis when either protease was present during the heat treatment. High-temperature proteolysis occurs in a progressive manner. Mass spectrometry analysis of some large-sized breakdown intermediates formed in the early steps of hydrolysis indicated that both enzymes effectively hydrolyzed some regions of beta-lactoglobulin that were transiently exposed during the physical treatments and that were not accessible in the native protein. The immunochemical properties of the products of beta-lactoglobulin hydrolysis were assessed by using various beta-lactoglobulin-specific antibodies, and most epitopic sites were no longer present after attack of the partially unfolded protein by the two proteases.
Rivista:EUROPEAN JOURNAL OF BIOCHEMISTRY anno: 2002	volume n.: 269	pag. da: 1362	a: 1372
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Autori: La Cara F. ,Immirzi B. ,Ionata E. ,Mazzella A. ,Portofino S. ,Orsello G. ,De Prisco P.P.
Titolo: Biodegradation of Poly-e-caprolactone/poly-b-hydroxibutyrate blend
Abstract:
poly-e-caprolactone (PCL), poly-b-hydroxibutyrate (PHB) and one of their blends have been incubated in presence of some microbial consortia isolated from plastic-contaminated environments. In the conditions used in this work, Both pure PCL and PHB samples were degradated with strong erosion of the amorphous zones. The PCL/PHB 70/30 blend showed, after only 20 days of incubation, that spheres of PCL were bordering with spaerulites of PHB indicating complete degradation. The crystallinity content of homopolymers and blend were investigated at different degradation times: whilst PCL crystallinity remains constant, both PHB and the blend PHB- phase crystallinity increased. Data from differential scanning calorimetry are well fitted with those obtained by scanning electron microscopy, gel permeation chromatography and weight loss analysis
Rivista:POLYMER DEGRADATION AND STABILITY anno: 2002	volume n.: 79	pag. da: 37	a: 43
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Autori: Luongo D, Mazzarella G, Della Ragione F, Maurano F, Rossi M.
Titolo: Down-regulation of ERK1 and ERK2 activity during differentiation of the intestinal cell line HT-29.
Abstract:
The role and regulation of signal transduction pathways in proliferation and differentiation of intestinal epithelial cells are still poorly understood. However, growing evidences have been recently accumulated demonstrating that mitogen-activated protein kinases (MAPKs) play a pivotal function in the normal development of intestine. We have investigated, in the intestinal cell line HT-29, the regulation (namely activity and phosphorylation degree) of MAP kinases ERK 1 (p44) and ERK 2 (p42) during differentiation. Addition of fetal calf serum to HT-29 undifferentiated resting cells caused a rapid phosphorylation of both ERKs and an increase of their specific kinase activity. Moreover, nuclear translocation of ERK 1 and ERK 2 occurred concurrently to their activation, leading to the conclusion that ERK 1 and ERK 2 are classically regulated when quiescent HT-29 cells are induced to proliferate. Butyrate addition to the intestinal cell line resulted in terminal differentiation and in a selective down-regulation of ERK 2 activity (and phosphorylation degree) without any effect on ERK 1. Conversely, when HT-29 cells were differentiated by repeated passages in a glucose-free medium, we observed a progressive dephosphorylation and inactivation of p42 and p44 kinases along with the failure of serum to activate both the enzymes. Our findings suggest that, during the differentiation of intestinal cells, remarkable changes occur in ERK 1 and ERK 2 control mechanisms leading to an unresponsiveness of MAP kinase pathway.
Rivista:MOLECULAR AND CELLULAR BIOCHEMISTY anno: 2002	volume n.: 231	pag. da: 43	a: 50
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Autori: Miraglia N, Genovese G, Acampora A, Malorni L, Sannolo N.
Titolo: A novel mass spectrometric technique for the evaluation of occupational exposure to methyl bromide
Abstract:
Rivista: JOURNAL OF MASS SPECTROMETRY anno: 2002	volume n.: 37811	pag. da: 1171	a: 1174
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Autori: Miraglia N. ,Basile A., Pieri M. , Acampora A., Malorni L., De Giulio B.,Sannolo N.
Titolo: Ion trap mass spectrometry in the structural analysis of haemoglobin peptides modified by epichlorohydrin and diepoxybutane
Abstract:
Ion trap mass spectrometry has been shown to be particularly suitable for the structural analysis of high molecular weight peptides directly fragmented in the mass analyser without needing further sub-digestion reactions. Here we report the advantages of using multi-stage ion trap mass spectrometry in the structural characterisation of haemoglobin alkylated with epichlorohydrin and diepoxybutane. Alkylated globins were digested with trypsin and the peptide mixtures were analysed by MS(3). This technique allows the sequential fragmentation of peptides under analysis, giving rise to MS(3) product ion spectra with additional information with respect to MS(2) mass spectra. The results obtained complete the previously reported structural characterisation of alkylated haemoglobin, demonstrating the potential of ion trap mass spectrometry.
Rivista: RAPID COMMUNICATIONS IN MASS SPECTROMETRY anno: 2002	volume n.: 16, 9	pag. da: 840	a: 847
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Autori: Nazzaro F. ,Sorrentino A. ,Malinconico M. ,Orlando P.
Titolo: Influenza dell'alginato immobilizzante sulla vitalitý e sul metabolismo di batteri lattici
Abstract:
E' stata valutata líinfluenza esercitata da alcuni tipi di alginati, utilizzati come matrici immobilizzanti, sulla vitalitý cellulare e su alcune funzioni metaboliche di due ceppi di batteri lattici (L. delbrueckii subs bulgaricus e L. rhamnosus GG) sottoposti a congelamento ed a liofilizzazione. La vitalitý Ë stata testata mediante conta su piastra; il metabolismo Ë statao valutato dalla resistenza dei ceppi su citati ai sali biliari ed al lisozima. I dati ottenuti dimostrano che gli arginati purificati da Dyctioma dicotoma e soprattutto da Fucus vesiculosus hanno un effetto protettivo più efficcace rispetto a due arginati commerciali ed evidenziano quindi come una migliore purificazione del materiale immobilizzante possa dar luogo, anche dopo congelamento e liofilizzazione, ad una migliore vitalitý e resistenza in alcune condizioni di stress quali la presenza di lisozima e sali biliari. Tali parametri diventano importanti per un possibile utilizzo dei ceppi immobilizzati nella preparazione di starters nellíindustria alimentare o come formulati probiotici nellíindustria farmaceutica.
Rivista: INDUSRIE ALIMENTARI anno: 2002	volume n.: XL	pag. da: 777	a: 781
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Autori: Nazzaro F. ,Tedesco I. ,Maurelli L. ,De Giulio B. ,Nappo A. ,Graziani M.P. ,Barone C. ,De Rosa M.
Titolo: Influenza di un pretrattamento di osmodisidratazione con trealosio su mele essiccate
Abstract:
Eí stata valutata líopportunitý di utilizzare il trealosio come agente osmodisidratante in un ciclo combinato di essiccamento di mele. I parametri valutati hanno riguardato il contenuto di acido ascorbico, il contenuto di polifenoli totali, líattivitý antiossidante totale e le variazioni del colore. I dati ottenuti confermano la bontý del trattamento applicato e fanno ben sperare per una maggiore applicazione del trealosio in campo alimentare per ottenere prodotti che mantengano le loro qualitý organolettiche e nutrizionali.
Rivista: -INDUSTRIE ALIMENTARI anno: 2002	volume n.: LXI	pag. da: 941	a: 946
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Autori: Piacente S, Carbone V, Plaza A, Zampelli A, Pizza C.
Titolo: Investigation of the tuber constituents of maca (Lepidium meyenii Walp.)
Abstract:
Lepidium meyenii, known in South America as maca, has received attention worldwide as a powerful energizer that improves physical and mental conditions and increases fertility. Because of these reports, we investigated the secondary metabolites of the tuber of maca. The methanol extract of the tuber of maca contained, in addition to free sugars and amino acids, the following: uridine, malic acid and its benzoyl derivative, and the glucosinolates, glucotropaeolin and m- methoxyglucotropaeolin. Because glucosinolates and their derived products have received increasing attention due to their biological activities, the occurrence of glucosinolate degradation products in the hexane extract was also investigated, and benzylisothiocyanate and its m-methoxy derivative were isolated. The two glucosinolates were semiquantified by HPLC, and benzylisothiocyanate was semiquantified by GC/MS. The methanol extract of maca tuber also contained (1R,3S)-1-methyltetrahydro-beta- carboline-3-carboxylic acid, a molecule which is reported to exert many activities on the central nervous system.
Rivista: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY anno: 2002	volume n.: 50	pag. da: 5621	a: 5625
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Autori: Rossi M, Maurano F, Luongo D, Fasano A, Uzzau S, Auricchio S, Troncone R.
Titolo: Zonula occludens toxin (Zot) interferes with the induction of nasal tolerance to gliadin.
Abstract:
Both nasal and oral administration of soluble protein antigens (Ags) induce tolerance, a phenomenon that has hampered mucosal vaccine design. To produce active immunity the use of adjuvants co-administered with soluble Ags is required. Cholera toxin (CT) and Escherichia coli heat- labile enterotoxin (LT) were found to be powerful mucosal adjuvants, but they are not suitable for clinical use because of their associated toxicity. Therefore, there is the need to develop alternative strategies to deliver Ag in order to induce immunoprotection. Among these innovative tools, a new toxin, Zonula occludens toxin (Zot), produced by phages in toxigenic strains of Vibrio cholerae, has been recently exploited for its adjuvant activity at the mucosal level. The present study was undertaken to further highlight the adjuvant properties of Zot. The ability of Zot to induce a mucosal response to gliadin was demonstrated per serum antibody production. In our established model of systemic tolerance to gliadin, induced by its nasal administration, we found a reduced production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) upon administration of gliadin alone. This immune suppression was reverted in mice receiving gliadin together with Zot. As previously shown, the down- regulation of Th1-like cytokines was found to be associated to a suppression of the T-cell proliferation, while such a suppression was completely reverted by Zot co-administration. In conclusion, these data confirm Zot as a good mucosal adjuvant, considering its ability to interfere with the suppression of specific cell mediated immunity, probably as a result of the increased dose and/or altered processing of Ag at mucosal level.
Rivista: IMMUNOLOGY LETTERS anno: 2002	volume n.: 81	pag. da: 127	a: 221
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Autori: Russo K, Ragone R, Facchiano AM, Capogrossi MC, Facchiano A.
Titolo: Platelet-derived growth factor-BB and basic fibroblast growth factor directly interact in vitro with high affinity.
Abstract:
Platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) are potent growth factors active on many cell types. The present study indicates that they directly interact in vitro. The interaction was investigated with overlay experiments, surface plasmon resonance experiments, and solid-phase immunoassays by immobilizing one factor or the other and by steady-state fluorescence analysis. The interaction observed was specific, dose-dependent, and saturable, and the bFGF/PDGF-BB binding stoichiometry was found to be 2:1. K(D)(1) for the first step equilibrium and the overall K(D) values were found to be in the nanomolar and in the picomolar range, respectively. Basic FGF/PDGF-BB interaction was strongly reduced as a function of time of PDGF-BB proteolysis. Furthermore, docking analysis suggested that the PDGF-BB region interacting with bFGF may overlap, at least in part, with the PDGF-BB receptor-binding site. This hypothesis was supported by surface plasmon resonance experiments showing that an anti-PDGF-BB antibody, known to inhibit PDGF-BB binding with its receptor, strongly reduced bFGF/PDGF-BB interaction, whereas a control antibody was ineffective. According to these data, the observed bFGF.PDGF-BB complex formation might explain, at least in part, previous observations showing that PDGF-BB chemotactic and mitogenic activity on smooth muscle cells are strongly inhibited in the presence of bFGF.
Rivista:JOURNAL OF BIOLOGICAL CHEMISTRY anno: 2002	volume n.: 277	pag. da: 1284	a: 1291
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Autori: Russo P., Siani A., Venezia A., Iacone R., Russo O., Barba G., D'Elia L., Cappuccio F., Strazzullo P.
Titolo: Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study
Abstract:
OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. DESIGN: Cross-sectional and longitudinal 1980-1995) survey of male workers in southern Italy. SETTING: Medical centre of the Olivetti factories. PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P<0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers(TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.
Rivista: JOURNAL OF HYPERTENSION anno: 2002	volume n.: 20	pag. da: 1785	a: 1792
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Autori: Salzano A. M., Carbone V., Pagano L., Buffardi S., De Rosa C., Pucci P
Titolo: Hb Vila Real [beta36(C2)Pro-->His] in Italy: characterization of the amino acid substitution and the DNA mutation
Abstract:
A rare high oxygen affinity hemoglobin variant was identified in a 22- year-old male patient from Napoli (Naples, Italy) affected by erythrocytosis. A detailed structural characterization of the variant hemoglobin was carried out, both at the protein and DNA levels essentially by mass spectrometric procedures and allele-specific amplification techniques. The amino acid substitution was determined by liquid chromatography tandem mass spectrometric analysis of the tryptic digest as beta36(C2)Pro-->His; the corresponding DNA mutation was identified as C-->A at the second position of codon 36 of the beta chain (CCT-->CAT). These variations identified the presence of Hb Vila Real, described only once before in a Portuguese woman. Haplotype analysis of DNA polymorphisms showed that the beta-globin gene of Hb Vila Real was associated with haplotype I.
Rivista: HEMOGLOBINanno: 2002	volume n.: 26(1)	pag. da: 21	a: 31
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Autori: Siani A., Cappuccio F., Barba G., Trevisan M., Farinaro E., Lacone R., Russo O., Russo P., Mancini M., Strazzullo P.
Titolo: The relationship of waist circumference to blood pressure: the Olivetti Heart Study
Abstract:
BACKGROUND: The association between overweight, high blood pressure (BP), and insulin resistance is well established, but the role of body fat distribution in this association has yet to be fully elucidated. The aim of this study was to investigate the role of central adiposity in the association between overweight, high BP, and insulin resistance. METHODS: A total of 1,079 men participated in the follow-up of the Olivetti Heart Study from 1994 to 1995. The present analysis includes 768 men, after the exclusion of 184 participants on pharmacological treatment for hypertension. In 65 men fasting blood glucose was >7 mmol/L; in 48, age was below or above 2 standard deviations from the mean of the population; and in 14 the data set was incomplete. Anthropometric indices of adiposity, metabolic variables (including fasting serum insulin and homeostasis model assessment HOMA] index of insulin sensitivity), and BP were measured. RESULTS: In univariate analysis, waist circumference was the anthropometric index that best correlated with BP (P < .001). In multiple regression analysis, waist circumference remained the strongest independent predictor of BP after adjustment for confounders. Significant increase of systolic (P value for trend analysis < .001) and diastolic (P < .001) pressure, heart rate (P = .003), fasting and postload serum insulin (P < .001), and HOMA index of insulin sensitivity (P <.001) were observed across age-adjusted quintiles of waist circumference. Greater degrees of central adiposity were associated with higher prevalence of elevated BP values and insulin resistance (P value < .001, chi2 for linear trend). CONCLUSIONS: In middle-aged men, a central distribution of body fat is associated with increased BP,independently of body mass index and insulin resistance, thus suggesting a keyrole of central adiposity in the full expression of the "metabolic syndrome."
Rivista: AMERICAN JOURNAL OF HYPERTENSIONanno: 2002	volume n.: 15	pag. da: 780	a: 786
Area progettuale del piano triennale prioritaria:     Salute dell'Uomo
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Autori: Solaja BA, Terzic N, Pocsfalvi G, Gerena L, Tinant B, Opsenica D, Milhous WK.
Titolo: Mixed steroidal 1,2,4,5-tetraoxanes: antimalarial and antimycobacterial activity
Abstract:
Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 microM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.
Rivista: JOURNAL OF MEDICINAL CHEMISTRY anno: 2002	volume n.: 45	pag. da: 3331	a: 3336
Area progettuale del piano triennale prioritaria:     Salute dell'Uomo
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Autori: Stiuso P., Libondi T., Facchiano A.M., Colicchio P., Ferranti P., Lilla S., Colonna G.
Titolo: Alteration in the ubiquitin structure and function in the human lens: a possible mechanism of senile cataractogenesis
Abstract:
High-performance liquid chromatography purification followed by mass spectrometry analyses highlighted that human senile cataractous lens includes a 8182 Da species which is absent in the normal lens, whereas a 8566/8583 Da species is present in both lenses. Western blot analysis identified both species as ubiquitin. The species at lower molecular weight is a shorter form due to the cleavage of the C-terminal residues 73-76. As it is the last amino acid of ubiquitin which is involved in the protein degradation mechanism, we suggest that this structure modification compromises the function of ubiquitin and consequently the physiologically occurring degradation of the lens proteins.
Rivista: FEBS LETTERS anno: 2002	volume n.: 531	pag. da: 162	a: 167
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