2014
Anniver sario FoRST
“10 anni a sostegno della ricerca scientifica termale”
Il 2013 ha segnato il decimo anniversario della nascita
della Fondazione. Motivo di orgoglio per la Federterme
che l’ha istituita nel 2003 e per tutte le aziende termali
italiane che attraverso il proprio contributo finanziano la
ricerca in ambito termale
Molti gli obiettivi raggiunti in questo decennio, forse
impensabili nel lontano 2003, ma sicuramente molto resta
ancora da fare.
Riassumendo brevemente, possiamo ricordare che la
Fondazione ha raccolto sino ad oggi circa 6 milioni di euro
di contributi dalle aziende termali, per investirne quasi
altrettanti per iniziative di ricerca.
I bandi lanciati sino ad oggi sono stati 16, per un totale di
67 progetti co-finanziati e una somma complessiva di
2.150 mila euro erogati agli enti di ricerca, per un totale di
fondi impegnati a favore della ricerca pari a 5 milioni di euro.
L’ultimo bando in ordine di tempo, è quello dedicato al tema
della riabilitazione in ambito termale, che evidenzia il
collegamento tra l’impegno di FoRST ed il Piano nazionale
per la riabilitazione termale, fortemente voluto dal Ministero
della Salute, che insieme all’INAIL, ha costituito un gruppo
tecnico di lavoro finalizzato a redigere i criteri per l’avvio
presso gli stabilimenti termali di una sperimentazione
clinica, per il trattamento dei pazienti in fase post-acuzie.
Ben 35 le pubblicazioni su riviste scientifiche impattate,
che oltre a coprire la quasi totalità degli ambiti scientifici di
riferimento, si sono arricchite di risultati superiori alle
aspettative, come recentemente avvenuto sui progetti di
ricerca sui solfuri portati avanti da gruppi di ricerca italiani
e statunitensi. Nello specifico i risultati ottenuti
dall’Università di Modena evidenzierebbero l’importanza
dell’idrogeno solforato nel rallentare la progressione dei
processi neurodegenerativi indotti dall’Alzheimer. L’equipe
del prof. Robert Gallo, dell’Università di Baltimora si è
invece dedicata allo studio del ruolo del solfuro di idrogeno
negli stati acuti dei processi infiammatori e la prevenzione
della loro cronicizzazione. L’interesse suscitato nei
ricercatori dai risultati preliminari degli studi, li ha convinti
ad approfondirne il significato; siamo pertanto in attesa di
conoscere quali saranno gli esiti delle nuove
sperimentazioni cliniche che partiranno a breve.
Di pari passo con le iniziative scientifiche, e rispondendo
anche ad una logica di “servizio” alle Aziende, FoRST ha
avviato nell’ultimo triennio una linea specifica di
promozione dei risultati delle ricerche finanziate, ma anche
in senso più generale sull’efficacia delle cure termali. Negli
incontri organizzati con la stampa specializzata i ricercatori
delle università co-finanziate hanno illustrato i risultati
pubblicati delle ricerche effettuate in tema di patologie,
reumatiche, otorinolaringoiatriche, gastroenterologiche ecc.
Ha, attivamente collaborato alla campagna radiofonica
realizzata da Federterme “occupando” spazi specifici
dedicati alle patologie più comunemente curate alle Terme
con dei “focus” particolari, come quelli dedicati ai bambini.
Le malattie respiratorie in età pediatrica hanno altresì
costituito uno dei leit-motiv guida del sito della Fondazione,
che oltre a proporsi quale utile banca dati per gli addetti al
settore, ha inteso proporsi anche quale strumento di
dialogo con i medici di base, le Scuole di Specializzazione
in Medicina termale, nonché i Direttori sanitari degli
stabilimenti termali, al fine di creare un circolo virtuoso, che
comprenda tutte le fase dell’erogazione delle prestazioni
termali, a partire dalla prescrizione del medico di famiglia.
E proprio ai medici di famiglia sono state rivolte le iniziative
sul territorio realizzate lungo tutto il 2013, finalizzate ad
integrarne la formazione con le nuove conoscenze che si
stanno acquisendo sul tema della ricerca in ambito termale.
Registriamo, infine, grande soddisfazione per il documento
Wold Health Organization Traditional Medicine Strategy
2014-2023, presentato dall’Organizzazione Mondiale
Sanità lo scorso novembre e che ha riconosciuto il pieno
ruolo delle terapie termali nell’ambito delle medicine
tradizionali e complementari. Una novità assoluta resa
possibile dai risultati degli studi realizzati da un gruppo di
lavoro composto da rappresentanti della FEMTEC
(Federazione Mondiale Termalismo e Climatismo) e della
nostra Fondazione, con la supervisione tecnica
dell’Organizzazione Mondiale della Sanità. L’auspicio è
quello di poter fornire un supporto appropriato alla richiesta
che sarà inviata alla Commissione Europea, di inserire la
Medicina Termale fra le materie oggetto di
programmazione in tema di ricerca scientifica, con la
conseguente allocazione di risorse dedicate.
Ma sul tema della ricerca scientifica, vogliamo spingerci
ancora oltre. Sono infatti in corso contatti con i poli
tecnologici di alcuni istituti universitari, al fine di individuare
un progetto di comune interesse nel campo
dell’innovazione tecnologica, o nell’ambito delle
modificazioni biotecnologiche dei principi attivi delle acque
o sul tema dello sviluppo di nuove tecnologie per la
somministrazione delle cure.
Come dicevamo all’inizio tanto resta ancora da fare, ma
in un’Italia segnata dalla fuga dei ricercatori in altri Paesi,
ci sentiamo orgogliosi del nostro sistema di imprese, che
continua a finanziare con i propri mezzi la ricerca
scientifica.
Il Presidente
Filippo Fernè
LA RICERCA SCIENTIFICA TERMALE
L’impostazione metodologica della Fondazione per la Ricerca Scientifica Termale (FoRST) è destinata a generare un significativo impulso alla ricerca scientifica di qualità nel settore termalistico.
L’adozione di criteri internazionalmente riconosciuti di giudizio scientifico sui progetti presentati (elenco pubblicazioni, impact factor e altri elementi bibliometrici
della produzione scientifica dei proponenti) e la revisione dei progetti esclusivamente da parte di esperti stranieri sono i cardini del recente adeguamento di
Fondazione agli standard scientifici internazionalmente riconosciuti per le agenzie di granting della ricerca.
Parallelamente, FoRST ha intrapreso un confronto con realtà termali di altri
Paesi europei per stabilire criteri comuni (ad esempio, le parole chiave per rendere omogenei i motori di ricerca sulla materia termale) e si propone un ampliamento su scala non solo europea di questo confronto scientifico tramite
organizzazioni internazionali di massimo livello per poter giungere nell’arco dei
prossimi 2-3 anni a linee guida condivise sui metodi, indicazioni e trattamenti
nell’ambito della medicina termale basati sulle evidenze.
Razionale allocazione dei fondi finalizzata alla ricerca scientifica di qualità ed internazionalizzazione sono le metodologie di FoRST destinate a creare la piattaforma su cui Federterme desidera proseguire il dialogo con le Istituzioni preposte
alla tutela della salute, alla prevenzione ed alla formazione sanitaria.
Una analisi più specifica della ricerca che FoRST ha finanziato in questi anni
(analisi ovviamente retrospettiva) rivela come la produzione scientifica sia stata
comunque di buon livello. In particolare è da segnalare che, in parallelo a studi
clinici atti a dimostrare il beneficio tangibile dell’approccio termale in varie patologie, siano finalmente stati implementati con ottimi risultati studi di scienze di
base, in cui l’acqua termale è stata sostituita nei saggi in vitro su cellule umane
con il principio attivo delle stesse (sali, donatori chimici di sostanze gassose): i
risultati sono stati pubblicati su riviste scientifiche di qualità, e la strada per una
valutazione scientifica seria basata sulla sperimentazione controllata in vitro
è stata tracciata.
Un altro aspetto da sottolineare è il finanziamento che la FoRST ha assegnato,
in collaborazione con AIRC all’Istituto Nazionale Tumori di Milano per studiare
l’azione termale su una ampia e ben controllata popolazione di fumatori al fine
di prevenire almeno in parte gli effetti cronici del fumo sulla mucosa bronchiale.
Questo progetto, basato su un rigoroso approccio sperimentale, ha come
punto di forza la popolazione dello studio ben controllata e statisticamente
assai significativa (diverse migliaia di soggetti) e implica la verifica della valenza
preventiva dell’acqua termale sulla precancerosi bronchiale.
Il punto di incontro fra una delle branche della medicina in cui tradizionalmente
l’uso delle acque termali ha avuto un suo preciso spazio e queste tematiche di
grande valenza riguardo alla prevenzione (con ovvie implicazioni sulla salute
pubblica) rappresenta il vero e nuovo punto di partenza della medicina termale
moderna.
Prof. Marco Vitale
Coordinatore del Comitato Scientifico FoRST
I PROGETTI E LE RISORSE
Sulla base di un Accordo sottoscritto fra
Federterme, il Ministero della Salute e
le Regioni, a partire dall’anno 2000 le
Aziende termali italiane hanno iniziato
ad accantonare lo 0,30% (0,40% nel
solo 2004) del fatturato SSN lordo
ticket presso un Fondo, appositamente
costituito presso Federterme, per la
realizzazione di iniziative di ricerca
scientifica in campo termale. Nel
gennaio 2003, al fine di consentire una
più corretta operatività nella gestione
dei fondi raccolti, è stata istituita da
Federterme, con l’assenso del
Ministero della Salute e delle Regioni,
la “Fondazione per la Ricerca
Scientifica Termale” - FoRST cui è stata
riconosciuta personalità giuridica nel
settembre 2003.
Dall’anno 2000 e sino al 31.12.2013, la
Fondazione ha raccolto circa 5,8
milioni di euro, impegnando in progetti
di ricerca più di 5 milioni di euro.
La Fondazione, amministrata da un
CdA misto pubblico-privato, ha lanciato
dal 2004 ad oggi ben sedici bandi di
ricerca, mettendo in moto 73 progetti e
cofinanziandone 61, di cui 35 pubblicati
su riviste impattate, 4 in corso di
pubblicazione e 40 conclusi.
A far data dal 1° gennaio 2010, così
come previsto dall’Accordo Nazionale
per il rinnovo delle tariffe per le
prestazioni termali a valere sul biennio
2008-2009, le Aziende Termali versano
lo 0,30% di loro spettanza direttamente
alla FoRST. Nell’ambito dell’Accordo
sopra citato Federterme e le Regioni si
sono impegnate a definire, in tempi
prefissati, una “scheda sanitaria” sulla
base di quella progettata dall’Istituto
Superiore di Sanità e realizzata con il
contributo
economico
della
Fondazione,
con
l’obiettivo
di
procedere alla sistematica rilevazione
dei dati clinici e sociali relativi ai
soggetti in cura termale e con
possibilità di ricavare su basi
statisticamente significative elementi
epidemiologicamente utili sia ai fini
della valutazione degli effetti della
terapia termale effettuata, sia ai fini di
carattere sanitario generale, in ordine
alla prevenzione e alla cura delle
malattie, nonché alla riabilitazione.
Gli ambiti nosologici
di riferimento dei bandi
sono i seguenti:
Reumatologia-Ortopedia
Otorinolaringoiatria
Broncopneumologia
Patologie dermatologiche
Patologie dell’apparato
digerente e urinario
Sistema cardiovascolare
Terapia della riabilitazione
con mezzo termale
Igiene e Microbiologia
nelle strutture termali
Farmacoeconomia
Innovazione tecnologica
FoRST IN CIFRE
€ 5.800.000
i fondi raccolti
67
dal 2000 al 2013
€ 5.000.000
il totale dei fondi
40
impegnati
a favore della ricerca
16
i bandi lanciati
dall’inizio dell’attività
35
i progetti di ricerca
cofinanziati
i progetti di ricerca
conclusi
i progetti di ricerca
pubblicati su riviste
impattate
PROGETTI PU B B LIC ATI
I E II B A N D O
[ANNI 2005-2006]
Progetti pervenuti: 98
Progetti cofinanziati: 29
Stanziati: € 1.400.000
Valore dei progetti: € 2.501.225
Importo dei cofinanziamenti: € 1.076.750
Erogati: € 487.428,11
SCIENZA DI BASE
€ 2.600.000 –
–
€ 2.400.000 –
–
€ 2.200.000 –
–
€ 2.000.000 –
–
€ 1.800.000 –
–
€ 1.600.000 –
–
€ 1.400.000 –
–
€ 1.200.000 –
–
€ 1.000.000 –
–
€ 800.000 –
–
€ 600.000 –
–
€ 400.000 –
–
€ 200.000 –
–
Stanziati
Valore
dei
progetti
Importo
dei
cofinanziamenti
Erogati
Tutti i progetti sono stati conclusi
N. 12 lavori pubblicati - (abstract in calce)
N. 8 revocati
SCIENZA DI BASE
Hydrogen sulfide prevents apoptosis of Exogenous Hydrogen Sulfide Induces
human PMN via inhibition of p38 and Functional Inhibition and Cell Death of
Cytotoxic Lymphocytes Subsets.
caspase 3.
Laura Rinaldi1 , Giuliana Gobbi1 , Maurizia Pambianco2 ,
Cristina Micheloni1 , Prisco Mirandola1 and Marco Vitale1,3
1 Department of Anatomy, Pharmacology & Forensic
Medicine, Human Anatomy Section, University of Parma,
Ospedale Maggiore, Parma, Italy;
2 Terme di Sirmione, Cell Biology Laboratory, Terme di
Sirmione, Brescia, Italy
3 ITOI-CNR, Bologna Unit, c/o Research Institute ‘CodivillaPutti’, IOR, Bologna, Italy
Hydrogen sulfide, together with carbon monoxide and nitric
oxide, is now considered a gasotransmitter able to induce
specific cellular responses. As hydrogen sulfide is a
component of several natural compounds known to be
effective in many inflammatory pathologies, particularly of the
respiratory tract, we studied its effects in vitro on the survival
and bactericidal activity of purified human neutrophils. We
found that (1) HS_ ions promote the survival of granulocytes,
but not that of lymphocytes or eosinophils, cultured in serumfree medium; (2) the pro-survival effect of HS_ is due to
inhibition of caspase-3 cleavage and p38 MAP kinase
phosphorylation; (3) the bactericidal activity of neutrophils is
not impaired by hydrogen sulfide. We conclude that HS_
promotes the short-term survival of neutrophils potentially
accelerating the resolution of inflammatory processes and
preventing the occurrence of new ones.
Laboratory Investigation (2006) 86, 391-397 © 2006 USCAP,
Inc
All rights reserved 0023-6837/06 $30.00
www.laboratoryinvestigation.org
Prisco Mirandola1 , Giuliana Gobbi1 , Ivonne Sponzilli1 ,
Antonio
Maurizia Pambianco2 , Chiara Malinverno1 ,
Cacchioli3 , Giuseppe De Panfilis4 , and Marco Vitale1
1 Department of Anatomy, Pharmacology & Forensic
Medicine, Human Anatomy Section, University of Parma,
Ospedale Maggiore, via Gramsci, Parma, Italy;
2 Terme di Sirmione, Cell Biology Laboratory, Terme di
Sirmione, Brescia, Italy;
3 Department of Animal Health, University of Parma, Italy;
4 Department of Surgery, Section of Dermatology, University
of Parma, Italy
The toxic effects of exogenous hydrogen sulfide on peripheral
blood lymphocytes have been investigated in detail. Hydrogen
sulfide is now considered as a gasotransmitter with specific
functional roles in different cell types, like neurons and
vascular smooth muscle. Here we show that exogenous
hydrogen sulfide induces a caspase-independent cell death of
peripheral blood lymphocytes that depends on their
intracellular glutathion levels, with a physiologically relevant
subset specificity for CD8+ cells and NK cells. Although
lymphocyte activation does not modify their sensitivity to HS-,
after 24 h exposure to hydrogen sulfide surviving lymphocyte
subsets show a dramatically decreased proliferation in
response to mitogens and a reduced IL-2 production. Overall,
our data demonstrate that HS- reduces the cellular cytotoxic
response of peripheral blood lymphocytes as well as their
production of IL-2, therefore deactivating the major players of
local inflammatory responses, adding new basic knowledge to
the clinically well known antiinflammatory effects of sulfur
compounds.
J. Cell. Physiol. 213: 826–833, 2007.
2007 Wiley-Liss, Inc. ORIGINAL ARTICLE 826 Journal of
Cellular Physiology
O TO R I N O L A R I N G O I AT R I C A
O TO R I N O L A R I N G O I AT R I C A
Effects of sulfurous, salty, bromic, iodic
thermal water nasal irrigations in
nonallergic chronic rhinosinusitis: a
prospective, randomized, double-blind,
clinical, and cytological study
Effectiveness of Ischia thermal water
nasal aerosol in children with seasonal
allergic rhinitis: a randomized and
controlled study
Ottaviano G, Marioni G, Staffieri C, Giacomelli L, MarcheseRagona R, Bertolin A, Staffieri A.
Otolaryngology Section, Department of Medical and Surgical
Specialties, University of Padova, Padova, Italy.
OBJECTIVES: Nasal irrigations are mentioned among the
adjunctive measures for treating several sinonasal conditions.
Hyperchromatic supranuclear stria (HSS) in the ciliated cells
(CCs) has recently been suggested as a potential cytological
marker of the anatomofunctional integrity of nasal mucosa.
The aim of this study was to compare the effects of nasal
irrigations with sulfurous, salty, bromic, iodic (SSBI) thermal
water or isotonic sodium chloride solution (ISCS) in patients
with nonallergic chronic rhinosinusitis, considering the
endoscopic, functional, microbiological, and cytological
evidence (including the ratio of HSS-positive CCs to total CCs
[the HSS+ rate]).
METHODS: In a prospective, randomized, double-blind
setting, 80 patients were recruited for nasal irrigations with
SSBI water or ISCS for 1 month.
RESULTS: An endoscopically assessed significant clinical
improvement was seen after both SSBI thermal water and
ISCS irrigations. Before treatment, Staphylococcus aureus
was isolated in 5 patients in the SSBI thermal water group and
4 in the ISCS group. After the nasal irrigations, there was no
sign of the bacteria in either group. Only the SSBI water
irrigations significantly reduced total nasal resistance, as
determined by rhinomanometry. Mild nasal irritation (6 cases)
and episodes of extremely limited epistaxis (5 cases) were
only reported after SSBI thermal water irrigations. Neither type
of nasal irrigation significantly increased the mean HSS+ rate
at cytological control after 1 month.
CONCLUSIONS: Both types of nasal irrigation improved the
endoscopic and microbiological features of patients with
nonallergic chronic rhinosinusitis, whereas only SSBI
irrigations significantly reduced total nasal resistance. Further
investigations are needed based on longer treatments and
follow-up periods to establish whether the HSS+ rate is useful
for monitoring clinical improvements in chronic rhinosinusitis
treated with nasal irrigations.
Am J Otolaryngol. 2010 May 25. Copyright © 2010. Published
by Elsevier Inc.
PMID: 20537762 [PubMed - as supplied by publisher
M. Miraglia Del Giudice1, F. Decimo1, N. Maiello1, S. Leonardi2,
G. Parisi3, M.Golluccio2, M. Capasso1, U. Balestrieri1, A.
Rocco1, L. Perrone1 and G. Ciprandi4
1 Pediatric Department “F.Fede”, II University of Naples,
Naples;
2 Pediatric Department, University of Catania;
3 UOC Pediatrics and Neonatology, ASL Na-2, PO “Anna
Rizzoli”, Lacco Ameno;
4 Azienda Ospedaliera Universitaria San Martino, Genova,
Italy
Allergic rhinitis is characterized by local inflammation. Nasal
lavage may be a useful treatment, however, there are few
studies on this topic. This study aims to evaluate the effects of
Ischia thermal water nasal irrigation on allergic rhinitis
symptoms and airway inflammation during the period of natural
exposure to Parietaria pollen in children with allergic rhinitis
and intermittent asthma. Forty allergic children were randomly
divided into two groups: the first group (Group 1) practiced
crenotherapy with thermal water aerosol for 15 days per
month, for three consecutive months, the control group (Group
2) was treated with 0.9% NaCl (isotonic) solution. In addition,
all children were treated with cetirizine (0.5 gtt./kg/day once
daily). Nasal symptom assessment, including Total Symptom
Score (TSS), spirometry, and exhaled nitric oxide (FeNO) were
considered before the treatment (T0), at the end of the
treatment (T1) and again 2 weeks after the end of the
treatment (T2). The study was registered in the Clinical
Trials.gov (NCT01326247). Thermal water significantly
reduced both TSS and FeNO levels and there was a significant
relationship between reduction of nasal symptoms and FeNO
values at the end of treatment with thermal water. In
conclusion, this study shows that nasal crenotherapy with the
hypermineral chloride-sodium water of Ischia was effective in
children with seasonal allergic rhinitis based on the sensitivity
to Parietaria. These results demonstrate that this natural
treatment may be effective in a common and debilitating
disease such as the allergic rhinitis.
Keywords: thermal water, nasal lavage, Ischia, allergic rhinitis,
children
Received April 14, 2011 – Accepted October 10, 2011
International Journal of Immunopathology and Pharmacology
Vol. 24, no. 4, 0-0 (2011)
Copyright © by BIOLIFE, s.a.s.
O TO R I N O L A R I N G O I AT R I C A
O TO R I N O L A R I N G O I AT R I C A
Smoking and chronic rhinitis: effects of
nasal irrigations with sulfurous-arsenicalferruginous thermal water: A prospective,
randomized, double-blind study
Crenotherapy modulates the expression
of proinflammatory cytokines and
immunoregulatory peptides in nasal
secretions of children with chronic
rhinosinusitis
Giancarlo Ottaviano, MD,PhDa, Gino Marioni, MDa, Luciano
Giacomelli, MDb, Fabio Biagio La Torre, MDa. Claudia Staffieri,
MDc, Rosario Marchese-Ragona, MDa, Alberto Staffieri, MDa
a) Department of Neurosciences, Otalaryngology Section,
Padova University, Padova, Italy
b) Department of Medicine Anatomic Pathology Section,
Padova University, Padova, Italy
c) Department of Neurosciences, Otalaryngology Section,
Treviso Branch, Padova University, Treviso, Italy
ABSTRACT PURPOSE: Smoking is a self-destructive
behavior that is known to induce remodeling of the lower
airways, leading to squamous metaplasia, but little is known
about its effects on the nose and paranasal sinuses. Nasal
irrigations are often mentioned as measures for treating
sinonasal inflammations. The purpose of our study was to
compare the effects of nasal irrigations with sulfurousarsenical-ferruginous thermal water or isotonic sodium chloride
solution in smokers with nonallergic chronic rhinosinusitis,
based on clinical and olfactory evidence.
MATERIALS AND METHODS: The present study was a
prospective, randomized, double-blind study performed in a
tertiary academic referral center. Seventy smokers with
nonallergic chronic rhinitis were enrolled. Nasal endoscopy,
rhinomanometry, nasal cytology, and odor threshold
measurements were performed in subjects randomized to
daily nasal irrigations with either thermal water or isotonic
sodium chloride solution for 1 month.
RESULTS: Immediately after the treatment, the thermal water
irrigations revealed a positive pharmacologic action, judging
from a tendency toward lower nasal resistances (P = .07) and
larger numbers of ciliated cells in the patients treated (P = .003).
Endoscopic findings in the thermal water group were still better
than in the control group a further 2 months later (P = .03).
CONCLUSIONS: Our results indicate that nasal irrigations with
thermal water had a good effect on endoscopic objective signs,
nasal resistances, and epithelial trophism.
Received 7 February 2012 - Epub 2012 Apr 20.
Am J Otolaryngol. 2012 Nov-Dec;33(6):657-62.
10.1016/j.amjoto.2012.03.002.
© 2012 Elsevier Inc. All rights reserved
doi:
Annalisa Passariello, MD, PhD, Margherita Di Costanzo, MD,
Gianluca Terrin, MD, PhD, Antonio Iannotti, MD, Pietro
Buono, MD, PhD, Umberto Balestrieri, MD, Gianni Balestrieri,
MD, Enrico Ascione, MD, Monica Pedata, MD, Francesco
Berni Canani, MD, and Roberto Berni Canani, MD, PhD
Abstract
Background: The effect of crenotherapy on major mucosal
markers of inflammation, TNF alpha, human beta-defensins 2
(hBD-2), and calprotectin, are largely unexplored in pediatric
chronic rhinosinusitis (CRS). The aim of this study was to
investigate the effects of crenotherapy with sulfate-sodiumchloride water on mucosal markers of inflammation in children
with CRS.
Methods: Children with CRS received 15-day crenotherapy
consisting of sulfate-sodium-chloride thermal water inhalations
by nasal aerosol (15 minutes/day). Concentrations of nasal
mucosal markers of inflammation (TNF alpha, hBD-2, and
calprotectin) were measured before and after crenotherapy.
Presence of specific symptoms (nasal obstruction, nasal
discharge, facial pain, sense of smell, and cough), value of
symptoms score sino-nasal 5 (SN5), quality of life (QoL) score
(1 [worse] to 10 [optimal]) were also assessed.
Results: After crenotherapy a significant reduction was
observed in TNF alpha (from 0.14 ± 0.02 to 0.08 ± 0.01; p <
0.001), calprotectin (from 2.9 ± 1.0 to 1.9 ± 0.5; p < 9.001); and
hBD-2 (from 2.0 ± 0.1 to 0.9 ± 0.6; p < 0.001) concentrations.
A significant (p < 0.05) reduction in number of subjects
presenting symptoms of nasal obstruction (100% versus 40%),
nasal discharge (33% versus 13%), facial pain (30% versus
10%), and sense of smell (60% versus 20%) was observed. A
significant improvement of SN5 (from 3.07 ± 0.76 to 2.08 ±
0.42; p < 0.001) was observed after the crenotherapy. QoL
also improved after crenotherapy (from 4.2 ± 1.1 to 6.6 ± 1.0;
p < 0.001).
Conclusion: Crenotherapy induced a down-regulation of nasal
mucosal inflammatory mediators in children with CRS.
Am J Rhinol Allergy. 2012 Jan-Feb;26(1):e15-9. doi:
10.2500/ajra.2012.26.3733.
D E R M ATO L O G I C A
GASTROENTEROLOGICA
Hydrogen sulfide impairs keratinocyte
cell growth and adhesion inhibiting
mitogen-activated
protein
kinase
signaling.
Functional and Histologic Assessment
of Rat Gastric Mucosa after Chronic
Treatment with Sulphurous Thermal
Water
Giuliana Gobbi1,2,Francesca Ricci1, Chiara Malinverno1,
Ceciloa Carubbi1, Maurizia Pambianco3, Giuseppe de Panfilis4,
Marco Vitale1,2 and Prisco Mirandola
Gabriella Coruzzia, Maristella Adamia, Cristina Pozzolia, Elvira
Solenghib, Daniela Grandib
1) Department of Anatomy, Pharmacology and Forensic
Medicine, University of Parma, Parma, Italy;
2) Center for Morphology and Body Composition (CMBC),
University of Parma, Parma, Italy;
3) Terme di Sirmione, Cell Biology Laboratory, Terme di
Sirmione, Brescia, Italy;
4) Department of Surgery, Dermatology Division, University of
Parma, Parma, Italy.
The effects of exogenous hydrogen sulfide (H2S) on normal
skin-derived immortalized human keratinocytes have been
investigated in detail. We show in vitro that exogenous
hydrogen sulfide reduces clonal growth, cell proliferation and
cell adhesion of human keratinocytes. H2S, in fact, decreases
the frequency of the putative keratinocyte stem cell
subpopulation in culture, consequently affecting clonal growth,
and impairs cell proliferation and adhesion of mature cells. As
a mechanistic explanation of these effects, we show at the
molecular level that (i) H2S reduces the Raf/MAPK
kinase/ERK signaling pathway; (ii) the reduced adhesion of
sulfur-treated cells is associated to the downregulation of the
expression of b4, a2 and a6 integrins that are necessary to
promote cell adhesion as well as anti-apoptotic and
proliferative signaling in normal keratinocytes. One specific
interest of the effects of sulfurs on keratinocytes derives from
the potential applications of the results, as sulfur is able to
penetrate the skin and a sulfur-rich balneotherapy has been
known for long to be effective in the treatment of psoriasis.
Thus, the relevance of our findings to the pathophysiology of
psoriasis was tested in vivo by treating psoriatic lesions with
sulfurs at a concentration comparable to that most commonly
found in sulfurous natural springs. In agreement with the in
vitro observations, the immunohistochemical analysis of
patient biopsies showed a specific downregulation of ERK
activation levels, the key molecular event in the sulfur-induced
effects on keratinocytes. KEYWORDS: flow cytometry;
western blot; MAPK; skin; NaHS.
Laboratory Investigation (2009), 1-13 © 2009 USCAP, Inc. All
Rights Reserved 0023-6837/09 $32,00
Sections of aPharmacology and bAnatomy, Department of
Human Anatomy, Pharmacology and Forensic Medicine,
University of Parma, Parma, Italy
Key Words
• Sulphurous thermal water
• Gastric acid secretion
• Sulphurous muscosal defense
• Ethanol
• Indomethacin
The effect of a chronic (4 weeks) administration of sulphurous
thermal water on gastric acid secretion and mucosal defense
was investigated in rats. Animals were randomized to receive
daily intake of tap water or of thermal water obtained from a
local spa center (Tabiano, Parma, Italy). Rats were followed
for one month as for water and food consumption, body weight
and general conditions. At the end of the watering period, the
following study protocols were carried out: (a) study of basal
and stimulated gastric acid secretion under general
anesthesia, and (b) study of the gastric mucosal resistance
against the damage induced by ethanol and indomethacin in
conscious rats. Basal acid secretion and the acid response to
pentagastrin or to histamine were similar in rats assuming
ordinary drinking water or thermal water. As for resistance to
gastric damage, histological, but not macroscopic, evaluation
revealed that rats which assumed thermal water were slightly
more resistant to the gastrolesive effect of ethanol (either
absolute or diluted). Again, when indomethacin was used as a
noxious stimulus, no difference was noted between the two
groups as for macroscopic damage; only a nonsignificant
reduction of damage was observed histologically in stomachs
of rats assuming thermal water. In conclusion, these results
indicate that chronic treatment of rats with thermal water, rich
in sulphur compounds, may have only minimal effects on the
rat gastric mucosa and did not significantly affect mucosal
defense mechanisms. The observed tendency to
gastroprotection would possibly need further investigation with
longer periods of administration.
Pharmacology 2010; 85:146-152 (DOI: 10.1159/000280603)
Copyright © 2010 S. Karger AG, Basel
GASTROENTEROLOGICA
Beneficial effect of sulphate-bicarbonate
-calcium water on gallstone risk and
weight control
Stefano Ginanni Corradini1, Flaminia Ferri1, Michela Mordenti1,
Luigi Iuliano2, Maria Siciliano1, Maria Antonella Burza1, Bruno
Sordi3, Barbara Caciotti3, Maria Pacini3, Edoardo Poli1, Adriano
De Santis1, Aldo Roda4, Carolina Colliva4, Patrizia Simoni5,
Adolfo Francesco Attili1
1) Gastroenterology Division, Department of Clinical Medicine,
Sapienza University of Rome, Viale dell’Università 37,
Rome 00185, Italy
2) Department of Medical Sciences and Biotechnology,
Vascular Medicine and Atherothrombosis Laboratory,
Sapienza University of Rome, Corso della Repubblica 79,
Latina 04100, Italy
3) Direzione Sanitaria Terme di Chianciano, Via delle Rose 12,
Chianciano Terme Siena 53042, Italy
4) Department of Pharmaceutical Science, Alma MaterUniversity of Bologna, Via Belmeloro 6, Bologna 40126,
Italy
5) Department of Clinical Medicine, Alma Mater-University of
Bologna, Via Massarenti 9 Bologna 40138, Italy
Author contributions: Ginanni Corradini S, Attili AF and De
Santis A designed research; Ginanni Corradini S, Ferri F,
Mordenti M, Siciliano M, Burza MA, Sordi B, Caciotti B, Pacini
M, Poli E and Iuliano L performed research; Roda A, Colliva
C, Simoni P contributed analytic tools; Ginanni Corradini S,
Ferri F, Mordenti M analyzed data and wrote the paper.
Supported by The Italian Thermal Scientific Research
Foundation and the Italian Ministery of Instruction University
and Research
Stefano Ginanni Corradini, MD, PhD, Gastroenterology
Division, Department of Clinical Medicine, Sapienza University
of Rome, Viale dell’ Università 37, Rome 00185, Italy.
E-mail: [email protected]
+39-6-49972086 Fax: +39-6-4453319
Abstract
AIM: To investigate the effect of drinking sulphate-bicarbonatecalcium thermal water (TW) on risk factors for atherosclerosis
and cholesterol gallstone disease.
METHODS: Postmenopausal women with functional dyspepsia
and/or constipation underwent a 12 d cycle of thermal (n = 20) or tap
(n = 20) water controlled drinking. Gallbladder fasting volume at
ultrasound, blood vitamin E, oxysteroys (7-ß-hydroxycholesterol
and 7-ketocholesterol), bile acid (BA), triglycerides, total/low density
lipoprotein and high density lipoprotein cholesterol were measured
at baseline and at the end of the study. Food consumption, stool
frequency and body weight were recorded daily.
RESULTS: Blood lipids, oxysterols and vitamin E were not
affected by either thermal or tap water consumption. Fasting
gallbladder volume was significantly (P < 0.005) smaller at the
end of the study than at baseline in the TW (15.7 ± 1.1 mL vs
20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL
vs 19.4 ± 1.5 mL). Total serum BA concentration was
significantly (P < 0.05) higher at the end of the study than at
baseline in the TW (5.83 ± 1.24 µmol) but not in the tap water
group (3.41 ± 0.46 µmol vs 2.91 ± 0.56 µmol). The increased
BA concentration after TW consumption was mainly accounted
for by glycochenodeoxycholic acid. The number of pasta (P <
0.001), meat (P < 0.001) and vegetable (P < 0.005) portions
consumed during the study and of bowel movements per day
(P < 0.05) were significantly higher in the TW than in the tap
water group. Body weight did not change at the end of the
study as compared to baseline in both groups.
CONCLUSION: Sulphate-bicarbonate-calcium water consumption
has a positive effect on lithogenic risk and intestinal transit and
allows maintenance of a stable body weight despite a high
food intake. Keywords: thermal water, gallstones, oxidative
stress, body weight, bile acid
Received: June 24, 2011 - Revised: September 9, 2011Accepted: December 31, 2011
Published online 2012 March 7. doi: 10.3748/wjg.v18.i9.930
World J Gastroenterol. 2012 March 7; 18(9): 930–937.
© 2012 Baishideng. All rights reserved.
R E U M ATO L O G I C A
R E U M ATO L O G I C A
Short- and long-term effects of spa therapy Short and long-term effects of mud-bath
in knee osteoarthritis
treatment on hand osteoarthritis: a
randomized clinical trial
Fioravanti A, Iacoponi F, Bellisai B, Cantarini L, Galeazzi M.
Rheumatology Unit, Department of Clinical Medicine and
Immunological Sciences, University of Siena, Siena, Italy.
OBJECTIVE: To assess both the short- and long-term
effectiveness of spa therapy in patients with primary knee
osteoarthritis in a prospective, randomized, single-blinded,
controlled trial.
DESIGN: Eighty outpatients were enrolled in this study; 40
patients were treated with a combination of daily local mud
packs and bicarbonate-sulfate mineral bath water from the spa
center of Rapolano Terme (Siena, Italy) for 2 wks, and 40
patients continued regular, routine ambulatory care. Patients
were assessed at baseline time; after 2 wks; after 3, 6, and 9
mos after the beginning of the study and were evaluated by
Visual Analog Scale for spontaneous pain, Lequesne index,
Western Ontario and McMaster Universities Index for
gonarthrosis, Arthritis Impact Measurement Scale-1, and
symptomatic drug consumption.
RESULTS: We observed a significant improvement of all
evaluated parameters at the end of the cycle of spa therapy,
which persisted throughout the whole of the follow-up period,
whereas in the control group no significant differences were
noted. This symptomatic effect was confirmed by the
significant reduction of symptomatic drug consumption.
Tolerability of spa therapy seemed to be good, with light and
transitory side effects.
CONCLUSIONS: The results from our study confirm that the
beneficial effects of spa therapy in patients with knee
osteoarthritis lasts over time, with positive effects on the painful
symptomatology and a significant improvement on functional
capacities. Spa therapy can represent a useful backup to
pharmacologic treatment of knee osteoarthritis or a valid
alternative for patients who do not tolerate pharmacologic
treatments.
Am J Phys Med Rehabil. 2010 Feb;89(2):125-32.
Antonella Fioravanti1, Sara Tenti1, Chiara Giannitti1, Nicola
Angelo Fortunati2, Mauro Galeazzi1
1) Rheumatology Unit, Department of Clinical Medicine and
Immunological Sciences, University of Siena, Viale
Bracci,1, 53100, Siena, Italy, e- mail: [email protected]
2) Spa Centre of Fonteverde Natural Spa Resort San
Casciano Terme, Siena, Italy
Abstract
The aim of this study was to evaluate both the short-term and
the long-term effectiveness of spa therapy in patients with
primary hand osteoarthritis (OA). This was a prospective
randomized, single blind controlled trial. Sixty outpatients with
primary bilateral hand OA were included in the study and
randomized to one of two groups. One group (n = 30) was
treated with 12 daily local mud packs and generalized thermal
baths with a sulfate-calcium-magnesium-fluorides mineral
water added to usual treatment. The control group (n = 30)
continued regular outpatient care routine (exercise, NSAIDs
and/or analgesics). Each patient was examined at baseline,
after 2 weeks, and after 3, 6, 9 and 12 months. Primary
outcome measures were global spontaneous hand pain on a
visual analogue scale (VAS) and the functional index for hand
osteoarthritis (FIHOA) score; secondary outcomes were health
assessment questionnaire (HAQ), duration of morning
stiffness, medical outcomes study 36-item short form (SF-36)
and symptomatic drugs consumption. Our results
demonstrated that the efficacy of spa therapy was significant
in all the assessed parameters, both at the end of therapy and
after 3 months; the values of FIHOA, HAQ and drugs
consumption continued to be significantly better after 6 months
in comparison with baseline. There were no significant
modifications of the parameters throughout the follow-up in the
control group. Differences between the two groups were
significant for all parameters at the 15th day and at 3 months
follow-up; regarding FIHOA, HAQ, and symptomatic drugs
consumption, the difference between the two groups persisted
and was significant at 6month follow-up. Tolerability of spa
therapy seemed to be good. In conclusion, our results confirm
that the beneficial effects of spa therapy in patients with hand
OA last over time.
Keywords: mud-bath treatment, spa therapy, hand
osteoarthritis, randomized clinical trial
Received: 16 October 2012 – Revised: 19 December 2012 Accepted: 20 December 2012
Published online: 14 January 2013
Int J Biometeorol. DOI 10.1007/s00484-012-0627-6 ©
ISB 2013
R E S P I R ATO R I A
Effects of Inhalation of Thermal Water
on Exhaled Breath Condensate in
Chronic Obstructive Pulmonary Disease
Gabriella Guarnieria, Silvia Ferrazzonia, Maria Cristina Scarpaa,
Alberto Lallib, Piero Maestrellia
a) Department of Environmental Medicine and Public Health,
University of Padova
b) Centro Studi Termali Pietro d’Abano, Montegrotto TermeAbano Terme, Padova, Italy
Key Words Lung function _ Normal saline _ Aerosol therapy
_Leukotriene B 4 _ ulmonary inflammation Inhalation of
thermal water (TW) is traditionally used as part of the treatment
of chronic obstructive pulmonary disease (COPD), but its
benefit and mechanisms are controversial.We previously
observed a reduced proportion of neutrophils in induced
sputum after treatment with TW. The aim of this study was to
determine whether inhalation of TW in COPD patients is
associated with biochemical changes of airway lining fluid,
including a reduction in the neutrophil chemoattractant
leukotriene B 4 (LTB 4). Thirteen COPD patients were
randomly assigned to receive a 2-week course of TW and
normal saline inhalation in a cross-over, single-blind study
design. Exhaled breath condensate (EBC) was collected
before and after treatments. LTB 4 concentrations in EBC were
determined by ELISA, and EBC pH was measured before and
after argon deaeration. No significant differences in LTB 4
concentrations in EBC were detected with either treatment. A
significant decrease in pH of non- eaerated EBC was observed
after a standard course of TW (median 7.45, interquartile range
6.93–7.66, vs. median 6.99, interquartile range 6.57–7.19; p =
0.05), which disappeared after argon deaeration. In
conclusion, there is no evidence that TW treatment affects LTB
4 concentration in EBC. The results of EBC pH measurements
suggest that TW inhalation induces an imbalance of volatile
components of the buffer system in airway lining fluid.
Clinical Investigations Respiration DOI: 10.1159/000227801
Copyright © 2009 S. Karger AG, Basel
III B A N D O [ A N N O 2 0 1 0 ]
Progetti pervenuti: 25
Progetti cofinanziati: 13
Stanziati: € 1.500.000
Valore dei progetti: € 2.686.000,00
Importo dei cofinanziamenti: € 1.195.000,00
Erogati: € 876.527,60
VA S C O L A R E
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Stanziati
Valore
dei
progetti
Importo
dei
cofinanziamenti
Erogati
N. 10 lavori pubblicati - (abstract in calce)
N. 3 revocati
VA S C O L A R E
Hydrogen sulfide is an endogenous Hydrogen sulfide down-regulates the
inhibitor of phosphodiesterase activity expression and release of osteoprotegerin
(OPG) by vascular endothelial cells
Mariarosaria Bucci, Andreas Papapetropoulos, Valentina
Vellecco, Zongmin Zhou, Anastasia Pyriochou, Charis Roussos,
Fiorentina Roviezzo, Vincenzo Brancaleone, Giuseppe Cirino
From the Department of Experimental Pharmacology, Faculty
of Pharmacy, University of Naples–Federico II, Naples, Italy
(M.B., V.V., F.R., V.B., G.C.); the Laboratory for Molecular
Pharmacology, Department of Pharmacy, University of Patras,
Greece (A. Papapetropoulos, A. Pyriochou), and the “G. P.
Livanos” Laboratory, Department of Critical Care and
Pulmonary Services, University of Athens, Greece (Z.Z., C.R.).
Erika Rimondi 1, Maria Grazia di Iasio 1, Arianna Gonelli 1,
Claudio Celeghini 2, Paola Secchiero 1, Giorgio Zauli 2,3
1 Department of Morphology and Embryology and LTTA
Centre, University of Ferrara, Ferrara, Italy
2 Institute for Maternal and Child Health, IRCCS “Burlo
Garofolo”, Trieste, Italy
3 Department of Morphology and Embryology, Human
Anatomy Section, University of Ferrara
OBJECTIVE: Recent studies have demonstrated that hydrogen
sulfide (H(2)S) is produced within the vessel wall from L-cysteine
regulating several aspects of vascular homeostasis. H(2)S
generated from cystathione γ-lyase (CSE) contributes to vascular
tone; however, the molecular mechanisms underlying the
vasorelaxing effects of H(2)S are still under investigation.
METHODS AND RESULTS: Using isolated aortic rings, we
observed that addition of L-cysteine led to a concentrationdependent relaxation that was prevented by the CSE inhibitors
DL-propargylglyicine (PAG) and β-cyano-l-alanine (BCA).
Moreover, incubation with PAG or BCA resulted in a rightward
shift in sodium nitroprusside-and isoproterenol-induced
relaxation. Aortic tissues exposed to PAG or BCA contained lower
levels of cGMP, exposure of cells to exogenous H(2)S or
overexpression of CSE raised cGMP concentration. RNA
silencing of CSE expression reduced intracellular cGMP levels
confirming a positive role for endogenous H(2)S on cGMP
accumulation. The ability of H(2)S to enhance cGMP levels was
greatly reduced by the nonselective phosphodiesterase inhibitor
3-isobutyl-1-methylxanthine. Finally, addition of H(2)S to a cellfree system inhibited both cGMP and cAMP breakdown.
CONCLUSIONS: These findings provide direct evidence that
H(2)S acts as an endogenous inhibitor of phosphodiesterase
activity and reinforce the notion that this gasotransmitter could be
therapeutically exploited. Keywords: endothelium - hypertension
- signal transduction - vascular muscle - vasodilation - cystathione
γ-lyase hydrogen sulfide - cAMP - cGMP - phosphodiesterase.
Osteoprotegerin (OPG) is a soluble member of the tumor
necrosis factor (TNF) receptor family, initially characterized for
its ability to inhibit the receptor activator of NfkB ligand (RANKL)stimulated formation of osteoclasts. OPG also interacts with
TNF-related apoptosis inducing ligand (TRAIL), a different
member of the TNF super-family whose extracellular domain
shares a 35% homology with RANKL. Several studies have
demonstrated that OPG is elevated in the serum/plasma of
patients affected by different types of cancer, but the potential
role of OPG with respect to cancer development/progression is
unknown. Among different potential cellular sources of circulating
OPG, endothelial cells represent a major source of OPG under
basal conditions as well as in response to inflammatory stimuli.
Hydrogen sulfide (H2S)-known for decades as a toxic gas—is
endogenously generated from cysteine, in reactions catalyzed
by cystathionine β-synthase(CBS) and cystathionine y-lyase
(CSE). Mounting data on endogenously generated H2S have
now included this gas in the family of gasotransmitters, together
with nitric oxide (NO) and carbon monoxide (CO), and its effects
are intensively investigated both at the cellular and molecular
level. On these bases, the aim of the present study was to
investigate in vitro the effect of H2S on the expression and
release of OPG by human vascular endothelial cells in the
absence or presence of the pro-inflammatory cytokine TNF-α
Published online July 15, 2010
Arterioscler Thromb Vasc Biol DOI: 10.1161/ATVBAHA.110.209783
Print ISSN: 1079-5642. Online ISSN: 1524-4636
Copyright © 2010 American Heart Association. All rights reserved.
Received: 9 April 2011 - Accepted: 19 April 2011
Published online 04 May 2011
Invest New Drugs DOI 10.1007/S10637-011-9675-8
© Springer Science+Business Media, LLC 2011
MICROBIOLOGICA
MICROBIOLOGICA
Hydrogen sulfide in thermal spring Molecular enrichment for detection of S.
waters and its action on bacteria of aureus in recreational waters
human origin
a
a
a
b
S. Giampaolia , F. Valeriani , G. Gianfranceschi , M. Vitali ,
M. Delfini c, M.R. Festa c, E. Bottari c, V. Romano Spica a
a) Unit of Public Health, University of Rome “Foro Italico”,
P.zza L. De Bosis, 6, 00135 Roma, Italy
b) Department of Public Health and Infectious Diseases,
“Sapienza” University, P.le Aldo Moro, 5, 00185, Rome, Italy
c) Department of Chemistry, “Sapienza” University, P.le Aldo
Moro, 5, 00185, Rome, Italy
Abstract
Hydrogen sulfide (H2S) is a molecule dissolved in many
thermal spring waters at variable concentration. The H2S
effects of thermal waters treatments have long been studied,
for dermatological and clinical treatments, but its role in
recreational waters was never investigated. The use of sulfur
spring waters in pools raises concerns related to disinfection
by oxidants. The aim of this work is to evaluate the survival
rate of microbial species in waters with different titers of H2S.
Four selected thermal waters collected from Italian springs,
belonging to different chemical categories, have been tested
in comparison to Tyrrhenian sea water and natural mineral
bottled water. Results show inhibition properties on bacterial
proliferation that seem related to H2S concentrations. To
further asses this phenomenon H2S was added to thermal and
natural mineral waters. The results strongly support a
bactericidal role of H2S in thermal spring waters used for
recreational purposes. These observations open up new
perspectives for a disinfectant role of H2S in pool treatment
and management.
Keywords: hydrogen sulphide, thermal spring water, pools,
bacteria, disinfection, hygiene
Received 19 October 2012 - Accepted 29 October 2012
Microchemical Journal. ©2012 Elsevier B.V. All rights reserved
F. Valeriani, S. Giampaoli, L. Buggiotti, G. Gianfranceschi and
V. Romano Spica
University of Rome ‘Foro Italico’,
P.zza L. De Bosis, 6, 00135 Roma, Italy
E-mail: [email protected]
Abstract
The identification of rapid methods for the control of
recreational water and of aquatic environments with similar
characteristics is necessary to provide adequate levels of
health safety for users. Molecular techniques have been
proposed in recent years as a viable alternative to traditional
microbiological methods, as they offer various advantages and
are less time consuming than traditional tests. An innovative
protocol based on molecular enrichment that allows the
identification of low concentrations of Staphylococcus aureus
in recreational water has been developed. The method is
based on the specific amplification of prokaryotic genomic
DNA by the usage of universal primers for 23S rDNA;
subsequently, a second amplification step is performed with
specific real-time polymerase chain reaction (PCR) primers
and probe. This approach shows sensitivity levels similar to
those observed with microbiological tests, with the additional
benefits of the specificity typical of nucleic acids techniques.
This methodology is easily applicable also to other
microbiological parameters, representing an important
milestone in hygiene monitoring by the detection of specific
pollution indicators.
Keywords: molecular enrichment, real-time PCR, recreational
water, staphylococcus aureus, 23S rDNA
Water Sci Technol. 2012;66(11):2305-10. doi: 10.2166/wst.2012.435
D E R M ATO L O G I C A
URINARIA
Hydrogen sulfide modulates the release Dietary habits in women with recurrent
of nitric oxide and VEGF in human idiopathic calcium nephrolithiasis
keratinocytes
1
1
1
Stefania Merighi, Stefania Gessi, Katia Varani, Debora Fazzi,
Pier Andrea Borea
Department of Clinical and Experimental Medicine,
Pharmacology Section and Interdisciplinary Center for the
Study of Inflammation, University of Ferrara, Via Fossato di
Mortara, 17/19, 44100 Ferrara, Italy.
Abstract
Hydrogen sulfide (H2S) is a novel signaling molecule with both
pro- or anti-inflammatory effect. The present study aimed to:
(i) characterize the in vitro effects of H2S on human
keratinocyte's proliferation and death; (ii) investigate the ability
of H2S to modulate VEGF and NO production; (iii) examine
the intracellular signaling pathways involved in VEGF and NO
modulatory effect. We found that exogenous application of
H2S (NaHS and GYY4137 as H2S donors) significantly
enhances NO through increase of iNOS, in a manner Aktdependent. The increment in NO down-regulates ERK1/2
activation thereby resulting in the decrease of VEGF release.
We suggest that H2S -releasing agents may be promising
therapeutics for chronic inflammatory disorders of the skin, i.e.
psoriasis, in which NO increases as well as anti-VEGF
treatments have been suggested to be novel effective
approaches.
Keywords: Akt, ERK ½, hydrogen sulphide, keratinocytes,
nitric oxide,VEGF
Pharmacol Res. 2012 Nov;66(5):428-36. doi:
10.1016/j.phrs.2012.07.002.
Received 11 May 2012 - Received in revised form 9 July
2012 - Accepted 9 July 2012 - Epub 2012 Jul 27.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Tiziana Meschi , Antonio Nouvenne , Andrea Ticinesi ,
Beatrice Prati 1, Angela Guerra 1, Franca Allegri 1, Federica
Pigna 1, Laura Soldati 2, Giuseppe Vezzoli 3, Giovanni Gambaro
4
, Fulvio Lauretani 5, Marcello Maggio 6 and Loris Borghi 1
1) Department of Clinical Sciences, University of Parma, Via
A. Gramsci 14, 43126 Parma, Italy
2) Department of Medicine, Surgery and Dentistry, University
of Milan, Milan, Italy
3) Nephrology Unit, S. Raffaele Hospital, Milan, Italy
4) Department of Internal Medicine and Medical Specialties,
Renal Program, Columbus-Gemelli University Hospital,
Catholic University, Rome, Italy
5) Geriatric Unit, Parma University Hospital, Parma, Italy
6) Department of Internal Medicine and Biomedical Sciences,
University of Parma, Parma, Italy
Abstract
Background: Nutrition has been widely recognized to influence
the risk of kidney stone formation. Therefore the aim of our
study was to assess: a) whether usual diet of women with
idiopathic calcium nephrolithiasis (ICN) living in Parma
(Northern-Italy) is different compared to healthy controls, b)
how their diet differs from Italian National guidelines and c)
whether it is related to nephrolithiasis clinical course.
Methods: 143 women with recurrent ICN (mean age 43 ± 13
ys) and 170 healthy women (mean age 42 ± 11 ys) were
enrolled. All women completed a food frequency questionnaire
for the last 60-days and a 3-day dietary diary analysed with a
dedicated software.
Results: Stone formers showed a higher consumption of
sausages, ham, meat and sweets than healthy controls (43.1%
vs 11.1%, 29.4% vs 13.9%, 21.6% vs 4.2%, 66.7% vs 18.1%,
p < 0.001). The 3-day diary analysis showed an intake of
calories, carbohydrates, lipids and non-discretionary sodium
about 10% higher than healthy controls (p < 0.001). Finally,
after dividing the population into 3 age groups (≤30, 31-40, >
40 years), the differences described above were amplified in
the class ≤30 years, where nephrolithiasis presented a more
serious course (shorter recurrence interval, greater stonerate). In this age group the intake of fruit and vegetables was
notably lower than guideline recommendations.
Conclusions: We conclude that the usual diet of women with
recurrent ICN is different from controls and characterized by
low intake of fruits and vegetables and higher consumption of
simple sugars and foods with high protein and salt content.
This dietary imbalance could play a role in the ICN
pathogenesis, especially in younger women. This work was
financed by grants from Italian Ministry of University and
Research as part of a larger project about the prevention of
kidney stones (PRIN 2005063822) and by Fondazione per la
Ricerca Scientifica Termale (FoRST). No potential conflict of
interest relevant to this paper was reported.
Keywords: Idiopathic calcium nephrolithiasis, Diet, Kidney
stones, Food frequency
Journal of Translational Medicine 2012, 10:63
doi:10.1186/1479-5876-10-63
URINARIA
Lifestyle Recommendations to Reduce
the Risk of Kidney Stones
Tiziana Meschi, MD, Antonio Nouvenne, MD, PhD, Loris
Borghi, MD*
Internal Medicine and Subacute Critical Care Clinic,
Department of Clinical Sciences, University of Parma,
Via A. Gramsci 14, 43126 Parma Italy
*Corresponding author. E-mail address: [email protected]
Kidney stones are a disorder that could be termed social
because of its vast diffusion and growing incidence in wealthy
industrialized countries.1 Many international studies have
shown that this condition affects just less than 10% of the
population, constituting an expense of approximately 2 billion
dollars a year in hospital admissions in the United States
alone.2 In some cases, it is the consequence of specific
hereditary or acquired diseases, such as cystinuria, primary
hyperoxaluria,
medullary
sponge
kidney,
primary
hyperparathyroidism,
and
infections
or
anatomic
malformations of the kidneys and urinary tract. However, the
most common form is idiopathic calcium nephrolithiasis (ICN),
with the formation of calcium oxalate stones, sometimes mixed
with calcium phosphate and with a prevalence of
approximately 80%. The distribution by sex shows the
frequency to be slightly higher in men.3 The pathogenesis of
ICN includes genetic and acquired factors that interact to
cause biochemical urinary abnormalities that lead to the
formation of kidney stones. A high rate of supersaturations of
calcium oxalate and/or calcium phosphate leads to the
formation of crystalline nests that can grow and join together
to form a stone. The urinary elements and compounds, both
inhibitors and activators, involved in the crystallization process
are known as lithogenic urinary risk factors. For calcium
oxalate, the lithogenic urinary risk factors are low urinary
volume (<2 L/d), hypercalciuria (>250 mg/d), hyperoxaluria
(>40 mg/d), hyperuricosuria (>600 mg/d), hypocitraturia (<320
mg/d), and hypomagnesuria (<50 mg/d). For calcium
phosphate, in addition to the above, the most important factors
are hyperphosphaturia (>1000 mg/d) and urinary pH. A pH
more than 7 favors the formation of kidney stones primarily
comprising phosphates, whereas a pH between 6 and 7
associated with a urinary volume of less than 1 L/d can
dangerously increase the supersaturation of calcium
phosphate and lead to the formation of mixed Ca-oxalate and
Ca-phosphate stones. Last, in the case of uric acid–induced
stone disease, another common form with a frequency of 10%
to 15%, the factors involved are hyperuricosuria and pH less
than 5.5. Of the various lithogenic urinary risk factors, the most
commonly observed in patients with ICN is hypercalciuria, with
a prevalence of approximately 50%. Regarding the age of
onset, there are 2 peaks: between 20 and 30 years and
between 50 and 60 years.4 The presence of a genetic
substrate does not, however, detract from the role of lifestyle:
dietary habits and lifestyle have a direct effect on the lithogenic
urinary risk factors and the pathogenesis of this condition. This
article examines the role of lifestyle in the prevention and
treatment of calcium and uric acid kidney stones. This article
specifically analyzes the relationship between (1) kidney
stones and dietary habits, (2) kidney stones and body weight,
(3) kidney stones and exercise, (4) kidney stones and stressful
life events, and (5) particular causes.
This work was supported by Fondazione per la Ricerca
Scientifica Termale (FoRST) grants.The authors have nothing
to disclose.
Keywords: idiopathic calcium nephrolithiasis, lifestyle, diet,
prevention, kidney stones
Urol Clin N Am 38 (2011) 313-320
doi: 10.1016/j.ucl.2011.04.002
0094-0143/11/$ - see front matter ©2011 Elsevier Inc. All rights
reserved.
NEUROLOGICA
SCIENZA DI BASE
Hydrogen sulfide slows down progression
of experimental Alzheimer's disease by
targeting multiple pathophysiological
mechanisms
Sulphurous thermal water increases the
release of the anti-inflammatory cytokine
IL-10 and modulates antioxidant enzyme
activity
Giuliani D, Ottani A, Zaffe D, Galantucci M, Strinati F, Lodi R,
Guarini S.
Prandelli C, Parola C, Buizza L, Delbarba A, Marziano M, Salvi
V, Zacchi V, Memo M, Sozzani S, Calza S, Uberti D, Bosisio D.
Department of Biomedical, Metabolic and Neural Sciences,
Section of Pharmacology and Molecular Medicine, University
of Modena and Reggio Emilia, Modena, Italy
Department of Molecular and Translational Medicine,
University of Brescia, Brescia, Italy.
Abstract
It has been previously reported that brain hydrogen sulfide
(H2S) synthesis is severely decreased in Alzheimer's disease
(AD) patients, and plasma H2S levels are negatively correlated
with the severity of AD. Here we extensively investigated
whether treatment with a H2S donor and spa-waters rich in
H2S induces neuroprotection and slows down progression of
AD. Studies with sodium hydrosulfide (a H2S donor) and
Tabiano's spa-water were carried out in three experimental
models of AD. Short-term and long-term treatments with
sodium hydrosulfide and/or Tabiano's spa-water significantly
protected against impairment in learning and memory in rat
models of AD induced by brain injection of β-amyloid1-40 (Aβ)
or streptozotocin, and in an AD mouse model harboring human
transgenes APPSwe, PS1M146V and tauP301L (3xTg-AD
mice). The improvement in behavioral performance was
associated with hippocampus was size of Aβ plaques and
preservation of the morphological picture, as found in AD rats.
Further, lowered concentration/phosphorylation levels of
proteins thought to be the central events in AD
pathophysiology, namely amyloid precursor protein, presenilin1, Aβ1-42 and tau phosphorylated at Thr181, Ser396 and
Ser202, were detected in 3xTg-AD mice treated with spawater. The excitotoxicity-triggered oxidative and nitrosative
stress was counteracted in 3xTg-AD mice, as indicated by the
decreased levels of malondialdehyde and nitrites in the
cerebral cortex. Hippocampus reduced activity of c-jun Nterminal kinases, extracellular signal-regulated kinases and
p38, which have an established role not only in
phosphorylation of tau protein but also in inflammation and
apoptosis, was also found. Consistently, decrease in tumor
necrosis factor-α level, up-regulation of Bcl-2, and downregulation of BAX and the downstream executioner caspase-3,
also occurred in the hippocampus of 3xTg-AD mice after
treatment with Tabiano's spa-water, thus suggesting that it is
also able to modulate inflammation and apoptosis. Our
findings indicate that appropriate treatments with H2S donors
and Tabiano’s spa-waters, and may be other spa-waters rich
in H2S content, might represent an innovative approach to
slow down AD progression in humans by targeting multiple
pathophysiological mechanisms.
Ricerca pubblicata su: Neurobiology of Learning and Memory 2013
Titolo originale: Hydrogen sulfide slows down progression of
experimental Alzheimer's disease by targeting multiple
pathophysiological mechanisms
Data di pubblicazione: 2013
Abstract
The beneficial effects of hot springs have been known for
centuries and treatments with sulphurous thermal waters are
recommended in a number of chronic pathologies as well as
acute recurrent infections. However, the positive effects of the
therapy are often evaluated in terms of subjective sense of
wellbeing and symptomatic clinical improvements. Here, the
effects of an S-based compound (NaSH) and of a specific
sulphurous thermal water characterized by additional ions
such as sodium chloride, bromine and iodine (STW) were
investigated in terms of cytokine release and anti-oxidant
enzyme activity in primary human monocytes and in saliva
from 50 airway disease patients subjected to thermal
treatments. In vitro, NaSH efficiently blocked the induction of
pro-inflammatory cytokines and counterbalanced the formation
of ROS. Despite STW not recapitulating these results, possibly
due to the low concentration of S-based compounds reached
at the minimum non-toxic dilution, we found that it enhanced
the release of IL-10, a potent anti-inflammatory cytokine.
Notably, higher levels of IL-10 were also observed in patients’
saliva following STW treatment and this increase correlated
positively with salivary catalase activity (r2 = 0.19, *p less than
0.01). To our knowledge, these results represent the first
evidence suggesting that S-based compounds and STW may
prove useful in facing chronic inflammatory and age-related
illness due to combined anti-inflammatory and anti-oxidant
properties.
Ricerca pubblicata su: International Journal Of Immunopathology
And Pharmacology
Titolo originale: Sulphurous thermal water increases the
release of the anti-inflammatory cytokine IL-10 and modulates
antioxidant enzyme activity
Data di pubblicazione: 2013
R E U M ATO L O G I C A
A multidisciplinary approach to study
the effects of balneotherapy and mudbath therapy treatments on fibromyalgia
Bazzichi L. 1, Da Valle Y. 2, Rossi A. 1, Giacomelli C. 1, Sernissi
F. 1, Giannaccini G. 2, Betti L. 2, Ciregia F. 2, Giusti L. 2,
Scarpellini P. 3, Dell'Osso L. 3, Marazziti D. 3, Bombardieri S. 1,
Lucacchini A. 2
1) Department of Clinical and Experimental Medicine,
Division of Rheumatology
2) Department of Pharmacy, and
3) Department of Clinical and Experimental Medicine,
Division of Psychiatry, University of Pisa, Pisa, Italy
Abstract
OBJECTIVES: To study the effects of both balneotherapy and
mud-bath therapy treatments in patients affected by primary
fibromyalgia (FM) using rheumatological, psychiatric,
biochemical and proteomic approaches.
METHODS:
Forty-one FM patients (39 females, 2 males), who fulfilled the
American College of Rheumatology criteria received a 2-week
thermal therapy programme consisting of therapy once daily
for 6 days/week. Twenty-one patients received mud-bath
treatment, while the other twenty balneotherapy. Pain,
symptoms, and quality of life were assessed. Oxytocin, brainderived neurotrophic factor (BDNF), ATP and serotonin
transporter levels during therapy were assayed. Comparative
whole saliva (WS) proteomic analysis was performed using a
combination of two-dimensional electrophoresis (2DE) and
mass spectrometry techniques.
RESULTS: We observed a reduction in pain, FIQ values and
improvement of SF36 in both groups of patients treated with
mud-bath or balneotherapy. The improvement of the outcome
measures occurred with different timing and duration in the two
spa treatments. A significant decrease in BDNF concentrations
was observed either after balneotherapy or mud-bath therapy
when assayed after twelve weeks, while no significant change
in oxytocin levels, ATP levels and serotonin transporter were
detected. Significant differences were observed for
phosphoglycerate mutase1 (PGAM1) and zinc alpha-2glycoprotein 1 (AZGP1) protein expression.
CONCLUSIONS: Our results showed that the thermal
treatment might have a beneficial effect on the specific
symptoms of the disease. In particular, while balneotherapy
gives results that in most patients occur after the end of the
treatment but which are no longer noticeable after 3 months,
the mud-bath treatment gives longer lasting results.
Ricerca pubblicata su: Clinical and Experimental rheumatology
Titolo originale: A multidisciplinary approach to study the
effects of balneotherapy and mud-bath therapy treatments on
fibromyalgia
Data di pubblicazione: 2013
IV B A N D O [ A N N O 2 0 1 2 ]
B a n d o i n Me di ci na Te r m ale Riabilitativa o Otorinolaringoiatrica
€ 1.000.000 –
Progetti pervenuti: 10
€ 900.000 –
€ 800.000 –
€ 700.000 –
Progetti cofinanziati: 6
€ 600.000 –
€ 500.000 –
Stanziati: € 500.000
€ 400.000 –
€ 300.000 –
Valore dei progetti: € 923.000,00
€ 200.000 –
€ 100.000 –
Importo dei cofinanziamenti: € 499.550,00
Stanziati
Valore
dei
progetti
Erogati: € 87.760,00
Importo
dei
cofinanziamenti
Erogati
N. 1 revocato
Ateneo
Titolo Ricerca
Area
Durata
(in mesi)
_______________________________________________________________________________________________________________________________________________________________
Università di Milano - Bicocca
Lymphopoiesis
in secondary
lymphoid tissue.
Ear, nose & throat
24
_______________________________________________________________________________________________________________________________________________________________
Università di Padova
The effects of thermal balneokinesitherapy in obese patients
with knee osteoarthritis.
Rehabilitation
24
_______________________________________________________________________________________________________________________________________________________________
IRCCS San Raffaele Pisana
Effectiveness of thermal water
nasal inhalation and irrigation
in rhinopharyngitis and sinusitis.
Ear, nose & throat
24
_______________________________________________________________________________________________________________________________________________________________
Università di Bari
Thermal water inhalationin
chronic upper respiratory
tract infections in elderly.
Ear, nose & throat
12
_______________________________________________________________________________________________________________________________________________________________
Università di Napoli Federico II
Effects of crenotherapy+
exercise rehabilitation
in patients with PAOD stage II b.
Rehabilitation
24
_______________________________________________________________________________________________________________________________________________________________
Università di Cagliari
Randomized controlled trial
of a thermal rehabilitation program
in axial spondyloarthritis.
Rehabilitation
24
_______________________________________________________________________________________________________________________________________________________________
I progetti di ricerca hanno preso avvio nel mese di luglio 2013
Conclusione prevista luglio 2015
BANDI PREMIO 2007 - 2012
A partire dal 2007 FoRST ha bandito annualmente
un premio per la ricerca medico-scientifica a
favore delle migliori pubblicazioni bio-mediche
di interesse per il settore termalistico. I lavori
scientifici proposti devono essere pubblicati su
riviste a diffusione internazionale indicizzate
(impact factor), in data non antecedente ai due
anni precedenti il bando.
Emanati a partire da febbraio 2008
Stanziati: € 55.000,00
Lavori pervenuti: 31
Lavori premiati: 18
E M ATO L O G I C A
Thermal balneotherapy induces changes
of the platelet serotonin transporter in
healthy subjects
Donatella Marazziti a, Stefano Baroni a, Gino Giannaccini a,
Mario Catena Dell’Osso a, Giorgio Consoli a, Michela Picchetti a,
Marina Carlini a, Gabriele Massimetti a, Serafina Provenzano b,
Antonio Galassi b
a Dipartimento di Psichiatria, Neurobiologia, Farmacologia e
Biotecnologie, University of Pisa, Italy
b Medical Direction, Montecatini spa, Italy
Il lavoro mette in evidenza come la sensazione di benessere
soggettivo di pazienti sottoposti a trattamento balneotermale
ozonizzato sia correlato all’incremento di serotonina,
neuromodulatore implicato in funzioni fisiologiche della psiche.
Sono stati studiati 18 soggetti sani, uomini e donne, di età fra
25-50 anni sottoposti a balneoterapia termale ozonizzata a cui
si sono misurati prima e dopo il trattamento i parametri ematici
piastrinici del Sert. Il trasportatore (Sert) della serotonina (5HT) è una proteina localizzata a livello dei terminali presinaptici
serotoninergici e rappresenta il principale meccanismo che
regola la concentrazione sinaptica d 5-HT attraverso un
meccanismo attivo di ricaptazione. La nostra ricerca ha
verificato modificazioni del SERT, attraverso la valutazione dei
parametri (Bmax e Kd) del binding della 3H-paroxetina in
membrane piastriniche di 18 soggetti sani prima (t0) e dopo
(t1) trattamento balneoterapico in acqua termale. I risultati
ottenuti evidenziano un aumento dell’affinità (l’inverso della
costante di dissociazione, Kd) del radioligando 3H-paroxetina
per il SERT, in tutti i soggetti dopo il trattamento (t1), che si
incrementava ulteriormente in quelli dopo una settimana (t2).
Queste modificazioni del SERT potrebbero giustificare la
sensazione soggettiva di benessere dopo la balneoterapia in
acqua termale, rilevata in tutto il campione in esame.
I risultati ottenuti nel nostro studio evidenziano modificazione
del SERT (trasportatore della serotonina, neuromediatore
maggiormente correlato alla sensazione di benessere
soggettivo) successiva ad un trattamento di balneoterapia
ozonizzata in acqua termale ipotonica salso-solfato- alcalina
di Montecatini, utilizzata per la cura delle vasculopatie
periferiche. L’aumento del Sert, indotto dal trattamento
termale, sembra responsabile della sensazione di benessere
manifestata dai pazienti inseriti nello studio. Lo studio,
eseguito in doppio cieco, avvalora l’importanza dell’ambiente
e del mezzo termale nei pazienti sottoposti a crenoterapia
aprendo nuovi orizzonti a trattamenti balneoterapici che
coinvolgono l’organismo sia nel soma che nella psiche.
Progress in Neuro-Psycopharmacology &
Psychiatry 31 (2007) 1436 –1439 ELSEVIER
Biological
R E S P I R ATO R I A
R E S P I R ATO R I A
Control of Legionella Pneumophila
Contamination
in
a
Respiratory
Hydrotherapy System with Sulfurous
Spa Water
Free radical-scavenging activity of
sulfurous water investigated by
electron paramagnetic resonance (EPR)
spectroscopy.
E. Leoni, MD, R. Sacchetti, MSc, F. Zanetti, MD, and P. P.
Legnani, MD
Pier Carlo Braga, Monica Dal Sasso, Maria Culici, Mario
Falchi, Alessandra Spallino, and Giuseppe Nappi
Department of Medicine and Public Health, Division of
Hygiene, University of Bologna, Italy (all authors)
Center of Respiratory Pharmacology, Department of
Pharmacology, School of Medicine, University of Milan,
Milan, Italy
Objective: To evaluate the effectiveness of different disinfection
treatments in a spa water system contaminated by Legionella
pneumophila and associated with a case of Legionella
pneumonia.
Design: During an 18-month period, the spa water was
analyzed by taking samples from the well, the recirculation line,
and the final distribution devices (nebulizers and nasal
irrigators). Various attempts were made to eradicate Legionella
organisms by chemical and thermal shock. The final protocol
consisted of heat shock treatment at 70° C – 75° C for 3 hours,
2 nights per week, followed by a lowering of the water
temperature to 30° C + 1° C for the use in the plant. In addition,
3 times a week superheated steam (at a pressure of 1
atmosphere) was introduced for 1 hour into the nebulization
machines.
Setting: A spa at which sulfurous water was used for
hydrotherapy by means of aerosol and nasal irrigation.
Patient: A 74-year-old woman with legionnaires disease.
Results. After the case of infection occurred, L. pneumophila
was isolated from the recirculation line at a concentration of
400,000 cfu/ L and from the nebulizers and nasal irrigators at
levels ranging from 3,300 to 1,800,000 cfu/L. The colonizing
organisms consisted of a mixture of L. pneumophila serogroup
1 (12%) and serogroup 5 (88%). The shock treatment with
chlorine dioxide and peracetic acid resulted in the eradication
of Legionella organisms from the recirculation line but not from
the water generated from the final distribution devices. After
the restructuring of the plant and the application of thermal
shock protocol, an evaluation after 12 months revealed no
evidence of Legionella contamination.
Conclusion: To prevent Legionella colonization, disinfection
treatment is effective if associated with carefully selected
materials, good circuit design, and good maintenance
practices.
Infection Control and Hospital Epidemiology July 2006,
Vol. 27, No. 7
Abstract
The aim of the study was to explore the antiradical activity of
sulfurous water, used for inhalatory therapy (characterized by
the presence of sulfhydryl [HS]) by means of electron
paramagnetic resonance (EPR) spectroscopy. The effects of
sulfurous water corresponding to the concentrations from 16
down to 0.25 μg/mL of HS were tested by means of Fenton
reaction (HO•), KO2–crown ether system (O2−•), and EPR of
Tempol and of Fremy's salt radical. All of these assays were
made using natural sulfurous water or degassed sulfurous
water (no detectable HS) or reconstituted sulfurous water
(degassed plus NaHS). The free radicals were significantly
inhibited by natural water with HS concentrations ranging from
16 to 1 μg/mL for HO•, Tempol, and Fremy's salt, and O2−•
was significantly inhibited from 16 and 2 μg/mL. The tests of
degassed water did not reveal any significant differences from
baseline values. The tests of reconstituted water led to
significant results overlapping those obtained using natural
water, thus confirming the importance of the presence of HS
group (reductive activity). The positive effects of the activity of
sulfurous thermal water is partially based on the patients’
subjective sense of well-being and partially on symptomatic
(or general) clinical improvements that are sometimes difficult
to quantify. These findings indicate that, in addition to their
known mucolytic activity and trophic effects on respiratory
mucosa, the HS groups in sulfurous water also have
antioxidant activity that contributes to the water's therapeutic
effects on upper and lower airway inflammatory diseases.
Keywords: antixodant activity, electron paramagnetic
resonance (EPR), spectroscopy, HS group, sulforous thermal
water.
Epub 2011 Dec 20.
Exp Lung Res. 2012 Mar;38(2):67-74.doi:
10.3109/01902148.2011.641668.
© Informa Healthcare USA, Inc.
R E U M ATO L O G I C A
R E U M ATO L O G I C A
Polyphasic characterization of a thermo - Combination treatment with etanercept
tolerant filamentous cyanobacterium and an intensive spa rehabilitation
isolated from the Euganean thermal muds program in active ankylosing spondylitis
(Padua, Italy)
1
1
1
1
1
Isabella Moro , Nicoletta Rascio , Nicoletta La Rocca , Katia
Sciuto 1, Patrizia Albertano 2, Laura Bruno 2 and Carlo Andreoli 1
1) Department of Biology; University of Padua,
Via Ugo Bassi 58/B, 35131Padua, Italy
2) Department of Biology; University of Roma
“Tor Vergata”, Via della ricerca scientifica,
00133 Roma, Italy
Abstract
In this paper we report a morphological, ultrastructural,
biochemical and molecular (16S rRNA, 16S–23S ITS, rbcL
and rpoC1 gene sequencing) survey on a very thin, nonheterocystous, filamentous cyanobacterium, isolated from
mats covering several mud maturation tanks of the Euganean
Thermal District, at temperatures ranging from 26 to 59°C.
Denaturing gradient gel electrophoresis results, obtained using
cyanobacterial primers targeting the 16S rRNA gene,
confirmed that this cyanobacterium is one of the commonest
taxa growing in the mud tanks. Comparison with Geitlerinema
sp. PCC 8501 (=Phormidium laminosum Gomont ex Gomont
strain OH-1-p Cl 1), a thin thermobiotic species isolated from
hot springs of Oregon and morphologically similar to our
isolate, led us to hypothesize that the Euganean and PCC
8501 strains are either very similar sister species or ecotypes
of the same species in a yet to be defined clade, clearly distinct
within the paraphyletic Leptolyngbya group.
Keywords: cyanobacteria, morphology, pigment composition,
thermal springs, ultrastructure, 16S rRNA, 16S–23S ITS, rbcL,
rpoC1
Received 12 February 2009 - Revised 30 October 2009 Accepted 6 November 2009
Eur. J. Phicol. DOI:10.1080/09670260903564391
M. Colina, G. Ciancio, R. Garavini , M Conti , F. Trotta and
M. Govoni
1 Presidio di Medicina Fisica e Riabilitazione delle Terme di
Castrocaro, Italy
The aim of this study is to determine the effects of a
combination treatment with etanercept and spa rehabilitation
versus etanercept alone on function, disability and quality of
life in a group of patients with active ankylosing spondylitis
(AS). Sixty patients with AS underwent etanercept as
suggested by ASAS/EULAR recommendations. As the clinical
and laboratory conditions improved, 30 patients accepted the
proposal of coupling the medical therapy with a 7-day
rehabilitation program in a thermal baths centre; the remaining
30 subjects continued to take the biologic agent alone. The
comparisons between the 2 groups were made after 3 and 6
months. The primary outcome was an improvement in BASFI.
The secondary outcome was an improvement in the visual
analogic scale of EuroQol (EQ-5Dvas). After 6 months a
statistically significant improvement in BASFI (p < 0.05) and
EQ-5DVAS (p < 0.05) scores was observed in both groups. The
mean change in EQ-5DVAS value showed a statistically
significant difference in favour of the combination therapy
group versus the monotherapy group (22 vs 32, p < 0.05). A
therapeutic regimen combining etanercept with an intensive
rehabilitation program contributes to disability reduction and
ameliorates quality of life for AS patients.
Keywords: ankylosing spondylitis, rehabilitation, etanercept,
BASFI, quality of life.
Received May 8, 2009 – Accepted September 24, 2009
International Journal of Immunopathoogy and Pharmacology
Vol. 22 no. 4, 1125-1129 (2009)
Copyright © by BIOLIFE, s.a.s.
R E U M ATO L O G I C A
R E U M ATO L O G I C A
The in-vitro percutaneous migration of Effects of Spa therapy on serum leptin
chemical elements from a thermal mud and adiponectin levels in patients with
for healing use
knee osteoarthritis
F. Tateo a, A. Ravaglioli b, C. Andreoli c, F. Bonina d, V. Coiro e,
S. Degetto f, A. Giaretta a, A. Menconi Orsini g, C. Puglia d, V.
Summa h
a Istituto di Geoscienze e Georisorse, CNR, Padova, Italy
b Istituto di Scienza e Tecnologia dei Materiali Ceramici, CNR,
Faenza, RA, Italy
c Dipartimento di Biologia, University of Padova, Padova, Italy
d Dipartimento di Scienze Farmaceutiche, University of
Catania, Catania, Italy
e Dipartimento di Medicina Interna e Scienze Biomediche,
University of Parma, Parma, Italy
f Istituto di Chimica Inorganica e delle Superfici, CNR,
Padova, Italy
g Circuito Termale Emilia-Romagna (COTER), Castel S.Pietro
Terme, BO, Italy
h Istituto di Metodologie di Analisi Ambientale, CNR, Potenza,
Italy
In-vitro experiments have been developed to ascertain
whether pelotherapy applications involve the transfer of
chemical elements from the healing mud to the human body,
across the skin. All the materials used for therapy (raw clay,
mineral water and healing mud obtained after maturation) have
been characterised from different points of view (mineralogy,
chemistry, exchange properties, radioactivity, grain size and
microbiology) in order to get an accurate knowledge of the
natural media used for therapy and to follow the development
of maturation in the spa centre.
A polymineralic silty clay with rather a common mineralogical
and chemical composition is used; the mud is matured in a
very saline mineral water, of marine origin, for 5 months. Under
these conditions the maturation process increases the
dispersion of clay particles and allows cation exchange
between clays and water, whereas neither microbiological nor
mineralogical changes are detectable. In absence of the
biologic indicators of mud maturity, the equilibration of clay with
mineral water represents an objective quantitative criterion. Invitro tests have been carried out by using the Franz-type
diffusion cells, which show that the transfer of chemical
elements across the skin is very well-developed, and also
involving many essential or possibly essential elements. The
amounts of chemical elements transferred were compared
with toxicological guidelines and with world-wide daily
requirement models. No concerns appear from the data,
whereas a significant supply of some elements results from a
typical application of thermal mud (20 min, full body). The
elements which have been considered in order to represent a
significant supply are Li, Sr, B, I, Rb, Br, Ba, Na, Cl, Se and
Ca, some of these are essential nutrients. The biological
effects of the main elements are briefly discussed. Keywords:
Pelotherapy Essential elements Percutaneous absorption
Applied Clay Science 44:83-94, 2009 © 2009 Elsevier B.V. All
rights reserved.
Antonella Fioravanti 1, Luca Cantarini 1, Maria Romana Bacarelli 1,
Arianna de Lalla 2, Linda Ceccatelli 2, Patrizia Blardi 2
1 Rheumatology Unit, Department of Medicine and
Immunological
Sciences,
University
of
Siena,
Viale Bracci, 1, 53100 Siena, Italy
e-mail: [email protected]
2 Center of Clinical Pharmacology, University of Siena, Siena,
Italy
Abstract Adipocytokine, including leptin and adiponectin, may
play an important role in the pathophysiology of osteoarthritis
(OA). Spa therapy is one of the most commonly used nonpharmacological approaches for OA, but its mechanisms of
action are not completely known. The aim ofthe present study
was to assess whether spa therapy modified plasma levels of
leptin and adiponectin in thirty patients with knee OA treated
with a cycle of a combination of daily locally applied mud-packs
and bicarbonate–sulphate mineral bath water. Leptin and
adiponectin plasma levels were assessed at baseline and after
2 weeks, upon completion of the spa treatment period. The
concentrations of leptin and adiponectin were measured by
ELISA. At basal time, plasma leptin levels were significantly
correlated with body mass index (BMI) and gender, but no
significant correlation was found with patient age, duration of
disease, radiographic severity of knee OA, VAS score or
Lequesne index. There was no correlation between plasma
adiponectin level and BMI, gender and age, duration of the
disease, radiographic severity of knee OA and VAS score. A
significant correlation of plasma adiponectin levels was found
only with the Lequesne index. At the end of the mud-bath
therapy cycle, serum leptin levels showed a slight but not
significant increase, while a significant decrease (P\0.05) in
serum adiponectin levels was found. However, leptin and
adiponectin concentrations after treatment were not correlated
with other clinical parameters. In conclusion, our data show
that spa therapy can modify plasma levels of the
adipocytokines leptin and adiponectin, important mediators of
cartilage metabolism. Whether this effect may play a potential
role in OA needs further investigations.
Keywords Osteoarthritis _ Leptin _ Adiponectin _Spa therapy
Received: 13 October 2009 / Accepted: 27 February 2010
/Published online: 18 March 2010
Rheumatol Int DOI 10.1007/s00296-010-1401-x
© Springer-Verlag 2010
R E U M ATO L O G I C A
R E U M ATO L O G I C A
Biomarkers of oxidation, inflammation
and cartilage degradation in ostearthritis
patients undergoing sulfur-based spa
therapies
A study on the efficacy of treatment with
mud packs and baths with Sillene mineral
water (Chianciano Spa Italy) in patients
suffering from knee osteoarthritis.
Serena Benedetti a*, Claudia Canino a, Gaetana Tonti a, Virginia
Medda a, Piergiorgio Calcaterra b, Giuseppe Nappi c, Fausto
Salaffi d, Franco Canestrari a
Antonio Fraioli a, Angelo Serio b, Gioacchino Mennuni a, Fulvia
Ceccarelli c, Luisa Petraccia a, Mario Fontana a, Marcello Grassi a,
Guido Valesini a
a Department of Biomolecular Sciences, Section of Clinical
Biochemistry, University of Urbino “Carlo Bo,” Urbino, Italy
b Thermal Center of Saturnia, Grosseto, Italy
c Study and Research Center of Thermal Medicine,
University of Milan, Milan, Italy
d Department of Rheumatology, Polytechnic University of
Marche, Ancona, Italy
a) Dipartimento di Clinica e Terapia Medica, UOC Medicina
Interna E, Terapia Medica e Medicina Termale, Scuola di
Specializzazione in Idrologia Medica,
Sapienza Università di Roma, Azienda Policlinico Umberto I,
V.le del Policlinico 155, 00161 Rome, Italy
e-mail: [email protected]
b) Università Campus Bio-Medico di Roma, Rome, Italy
c) Dipartimento di Clinica e Terapia Medica, UOC
Reumatologia, Scuola di Specializzazione in Reumatologia,
Sapienza Università di Roma, Azienda Policlinico Umberto I,
V.le del Policlinico 155, 00161 Rome, Italy
Objectives: To investigate the effects of sulfur-based spa
therapies on oxidation, inflammation and cartilage degradation
biomarkers in osteoarthritis (OA) patients.
Design and methods: Analyses were performed before therapy
(T0), after therapy (T1) and 1 month after its suspension (T2),
in OA subjects undergoing mud bath treatments in combination
(group A) or not (group B) with hydropinotherapy, and
compared with those of patients not subjected to spa therapies
(group C).
Results: No modifications in plasma/serum biomarker
concentrations were observed throughout the study in nontreated patients, while a significant reduction in oxidation,
inflammation and cartilage degradation parameters was
evidenced in patients of group A. Group B presented a
favorable biochemical profile at T1 but not at T2.
Conclusions: To ensure the long term preservation of the
chondroprotective effects of sulfur-based therapies, standard
mud bath treatments should be associated with
hydropinotherapy in order to maintain reduced oxidative,
inflammatory and degradative stimuli longer.
Keywords: Osteoarthritis, Oxidative stress, Spa therapy,
Sulfurous water, Antioxidant protection
Received 9 February 2010 – Received in revised form 3
May 2010 – Accepted 6 May 2010 – Available online 20 May
2010 Clinical Biochemistry 43 (2010) 973-978 DOI:
10.1016/j.clinbiochem.2010.05.004
© 2010 The Canadian Society of Clinical Chemists. Published
by Elsevier Inc. All rights reserved.
Abstract
Mud-bath therapy plays a primary role in the treatment and
prevention of osteoarthritis that has been recognised since
antiquity. Numerous studies have demonstrated its clinical
benefits and its effects on inflammatory mediators
(interleukins), the immune system, cenesthesic factors
(endorphins), and the diencephalic–pituitary–adrenal axis. This
study was conducted to assess the efficacy of mud-bath
therapy with mineral water from the Sillene Spring at Italy’s
Chianciano Spa in patients with osteoarthritis of the knee.
Patients (n = 61) were divided into two groups. Group A
underwent three cycles of mud-based spa therapy over a
year’s time, whereas group B did not. Clinical conditions, visual
analogue scale pain ratings, and Lequesne indexes of the two
groups were compared. We also compared these same
parameters in the patients of the two groups that were
following the therapy with drugs and in the patients of the
group A before and after spa treatment. The percentage of
patients with no symptoms or mild symptoms was higher in
group A than in group B. Within group A, this percentage was
higher after treatment than before spa therapy. Even in the
comparison between the patients of the two groups that were
following the therapy with drug, the results was that in group A
the percentage of patients with no symptoms or mild
symptoms was higher than in group B. Statistical analyses
based on various tests revealed that almost all these
differences were highly significant. No adverse effects were
observed in any of the patients in group A. In conclusion, the
mud-bath therapy performed at Chianciano Spa with Sillene
Spring water remarkably improved the clinical conditions of
patients with knee arthritis and significantly reduces the
frequency and severity of symptoms and the disability they
cause.
Keywords: spa therapy, mud-bath therapy, osteoarthritis, knee
osteoarthrits
Rheumatol Int (2011) 31:1333-1340
DOI 10.1007/s00296-010-1475-5
Received 21 November 2009 - Accepted 27 March 2010 Published online 14 April 2010
© Springer-Verlag 2010
R E U M ATO L O G I C A
R E U M ATO L O G I C A
Mechanisms of action of spa therapies in Short-term and long-term maturation of
rheumatic diseases: what scientific different clays for pelotherapy in an
evidence is there?
alkaline-sulphate mineral water (Rapolla,
Italy)
Antonella Fioravanti, Luca Cantarini, Giacomo Maria Guidelli,
Mauro Galeazzi
Rheumatology Unit, Department of Clinical Medicine
and Immunology, University of Siena,
Viale Bracci 1, 53100 Siena, Italy.
e-mail: [email protected]
Abstract
Spa therapy represents a popular treatment for many
rheumatic diseases. The mechanisms by which immersion in
mineral or thermal water or the application of mud alleviates
suffering in rheumatic diseases are not fully understood. The
net benefit is probably the result of a combination of factors,
with mechanical, thermal and chemical effects among the
most prominent ones. Buoyancy, immersion, resistance and
temperature all play important roles. According to the gate
theory, pain relief may be due to the pressure and
temperature of the water on skin; hot stimuli may influence
muscle tone and pain intensity, helping to reduce muscle
spasm and to increase the pain threshold. Mud-bath therapy
increases plasma β-endorphin levels and secretion of
corticotrophin, cortisol, growth hormone and prolactin. It has
recently been demonstrated that thermal mud-pack therapy
induces a reduction in the circulating levels of prostaglandin
E2 (PGE2), leukotriene B4 (LTB4), interleukin-1β (IL-1β) and
tumour necrosis factor-α (TNF-α), important mediators of
inflammation and pain. Spa therapy has been found to cause
an increase in insulin-like growth factor-1 (IGF1), which
stimulates cartilage metabolism, and transforming growth
factor-β (TGF-β). There is also evidence of the positive action
of mud-packs and thermal baths on the oxidant/antioxidant
system, with a reduction in the release of reactive oxygen
(ROS) and nitrogen (RNS) species. Overall, thermal stress
has an immunosuppressive effect. Many other non-specific
factors may also contribute to the beneficial effects observed
after spa therapy in some rheumatic diseases, including
effects on cardiovascular risk factors, and changes in the
environment, pleasant surroundings and the absence of work
duties.
Keywords: spa therapy, balneotherapy, mud-packs, rheumatic
diseases, mechanisms of action
Received: 7 April 2010 – Accepted: 13 November 2010 Published online 1 december 2010
Rheumatol Int (2011) 31:1-8
DOI 10.1007/s00296-010-1628-6
© Springer –Verlag 2010.
F. Tateo a, C. Agnini b, A. Carraro a, M.L. Giannossi c, S.
Margiotta c, L. Medici c, F.E. Finizio c, V. Summa c
a) Istituto di Geoscienze e Georisorse, Consiglio Nazionale
delle Ricerche (CNR) Padova, c/o Dipartimento di
Geoscienze, Università di Padova, Via Giotto 1, I-35137
Padova, Italy
b) Dipartimento di Geoscienze, Università di Padova, Via
Giotto 1, I-35137 Padova, Italy
c) Lab. Environmental and Medical Geology of IMAA-CNR
C.da Santa Loja, Tito scalo (Pz), Italy
Abstract
This study investigated in detail the mineralogical changes
within 8 little maturation ponds filled with different clay
materials placed in a spa center in southern Italy and kept
under the traditional environmental conditions used by the spa
itself. Both short- and long-term maturation periods were
investigated. Several changes were observed in all the
samples during the first month of maturation and also in the
following 2 months. A significant increase in soluble Na
occurred in all the samples. No significant variations in the
initial mineral assemblage were detectable either in the bulk
material and or in the clay fraction except for the crystallization
of neoformed Na-minerals. The amount and the type of silicate
minerals did not change in time, but the position and the width
of the basal reflection of expansible minerals changed due to
a gradual incorporation of new ions into the interlayer space.
During the first month a variation in the grain-size distribution
as well as a decrease in calcareous nannofossils can be
observed. A slight increase in Corg was also recorded during
the maturation. Some of the parameters which were more
sensitive to short maturation continued to adjust also during a
fairly longer time such as 15 months. The spacing and the
FWHM of the basal reflection of smectite and mixed layers
minerals and the crystallization of soluble salts were good
monitors of long-term maturation.
There were two tracks in the maturation period and were
related to particular indicators.
Typical indicators of this “first track”, mainly between months
1 and 2 of maturation were the grain size, the calcareous
nannofossils and the amount and the type of exchangeable
cations. The salt crystallization can be considered a suitable
indication of the “second track” of maturation within 6–9
months.
Keywords: maturation, pelotherapy, sulfate-alkaline water,
calcareous nannofossils, clay
Received 24 June 2010 Received in revised form 31 August 2010 Accepted: 2 October 2010 - Available online 12 October 2010
Applied Clay Science, Volume 50, Issue 4, December 2010,
Pages 503–511
© Published by Elsevier B.V.
O TO R I N O L A R I N G O I AT R I C A
O TO R I N O L A R I N G O I AT R I C A
The effects of sulfurous-arsenical- Antioxidant Effect of Sulphurous
ferruginous thermal water nasal Thermal Water on Human Neutrophil
irrigation in wound healing after Bursts: Chemiluminescence Evaluation
functional endoscopic sinus surgery
Pier Carlo Braga a, Giuseppe Sambataro b, Monica Dal Sasso a,
forchronic rhinosinusitis: a prospective Maria Culici a, Marina Alfieri a, Giuseppe Nappi c
randomized study
a
b
Alberto Staffieri, MD ,* Filippo Marino, MD , Claudia Staffieri,
MD a, Luciano Giacomelli, BD b, Emiliano D'Alessandro, MD b,
Silvia Maria Ferraro, MD a, Umberto Fedrazzoni, MD c, Gino
Marioni, MD a
a Department of Medical and Surgical Specialties, Section of
Otolaryngology, University of Padova, Padua, Italy
b Department of Medical/Diagnostic Sciences and Special
Therapies, Section of Anatomic Pathology, University of
Padova, Padua, Italy
c Levico Spa, Levico Terme, Trento, Italy
Purpose: Although several publications reported the benefits
of nasal irrigation in the managementof chronic rhinosinusitis
and in sinonasal postoperative care, the available data are
poorly controlled.
The aim of this prospective randomized study was to compare
the effects of sulfurous-arsenicalferruginous thermal water
nasal irrigation vs isotonic sodium chloride solution nasal
irrigation after functional endoscopic sinus surgery (FESS) for
chronic sinonasal disease considering the histomorphological
characteristics of mucosal repair after sinus surgery.
Materials and Methods: Eighty patients who consecutively
underwent FESS were randomly assigned (1:1) to
postoperative nasal irrigation with sulfurous-arsenicalferruginous thermal water or isotonic sodium chloride solution
for 6 months. Intraoperative and postoperative (1, 3, and 6
months) mean counts of lymphocytes, neutrophils,
eosinophils, plasma cells, histiocytes, and mast cells in
ethmoid biopsies were blindly determined by a pathologist.
Results: Fifty-six patients underwent at least 2 postoperative
biopsies. A statistically significant reduction of eosinophil count
was disclosed 6 months postoperatively only after sulfurousarsenicalferruginous solution nasal irrigation (P = .04). After
isotonic sodium chloride solution nasal irrigation, the mean
eosinophil count in 6-month postoperative biopsies did not
decrease. After both irrigation modalities, the mean mast cell
counts in 6-month postoperative biopsies were significantly
lower than in intraoperative biopsies (P b .05). Neutrophils,
lymphocytes, histiocytes, and plasma cell counts were not
significantly different between intraoperative vs 6-month
postoperative biopsies independently from irrigation modality.
Conclusions: Considering the important role of eosinophils in
allergic response, we should suggest sulfurousarsenicalferruginous solution nasal irrigation in particular,
which significantly reduces local eosinophil count, for allergic
patients after FESS for chronic rhinosinusitis.
Received 31 January 2007
American Journal of Otolaryngology–Head and Neck Medicine
and Surgery 29 (2008) 223–229
© 2008 Elsevier Inc. All rights reserved.
a Center of Respiratory Pharmacology, Department of
Pharmacology, School of Medicine, University of Milan,
b Department of Otolaryngology, School of Medicine,
University of Milan,
c Center of SPA Thermal Medicine, School of Medicine,
University of Milan, Italy.
The activities of the HS (sulfhydryl or thiolic) group in the
cysteine of glutathione or various low-weight soluble molecules
(thiolic drugs), such as N-acethylcysteine, mesna, thiopronine
and dithiotreitol or stepronine and erdosteine (prodrugs),
include its antioxidant activity in the airways during the release
of reactive oxygen or nitrogen species (ROS,RNS) by
neutrophils (PMNs) activated in response to exogenous or
endogenous stimuli. In addition to being administered by
means of thiolic molecules, the HS group can also be given by
means of the inhalation of sulphurous thermal water. The aim
of this luminol-amplified chemiluminescence (LACL) study was
to investigate the effect of sulphurous thermal water on the
release of ROS and RNS during the bursts of human PMNs.
The water significantly reduced the LACL of fMLP- and PMAactivated PMNs on average from 0.94μg/ml to 15.5μg/ml of
HS, even after the addition of L-Arg, a nitric oxide (NO) donor.
Similar findings have also been obtained in a cellfree system,
thus confirming the importance of the presence of HS group
(reductive activity). The positive effects of the activity of
sulphurous thermal waters has been partially based on the
patients’ subjective sense of wellbeing and partially on not
always easy to quantify symptomatic (or general) clinical
improvements. Our findings indicate that, in addition to their
known mucolytic activity and trophic effects on respiratory
mucosa, the HS groups present in the sulfureous thermal
water of this spring also have antioxidant activity that
contributes to the therapeutic effects of the water in upper and
lower airway inflammatory diseases.
Key words: Sulphurous thermal water; HS group; Antioxidant
activity; PMN; LACL; Cell-free system.
Respiration 2008;75:193-201 (DOI: 10.1159/000107976)
Copyright © 2007 S. Karger AG, Basel
INFIAMMAZIONE
GASTROENTEROLOGICA
Antioxidative effects of sulfurous Possible antioxidant role of SPA therapy
mineral water: protection against lipid with chlorine-sulphur-bicarbonate mineral
and protein oxidation
water
S Benedetti 1, F Benvenuti 1, G Nappi 2, NA Fortunati 3, L
Marino 3, T Aureli 3, S De Luca 2, S Pagliarani 1 and F
Canestrari 1
1 Istituto di Istologia e Analisi di Laboratorio, Università di
Urbino ‘Carlo Bo’, Urbino, Italy;
2 Centro di Studi e Ricerche in Medicina Termale, Università
di Milano, Milano, Italy
3 Terme di Saturnia, Grosseto, Italy
Objectives: To investigate the antioxidative properties of
sulfurous drinking water after a standard hydropinic treatment
(500 ml day-1 for 2 weeks). Subjects/Methods: Forty
apparently healthy adults, 18 men and 22 women, age 41–55
years old. The antioxidant profile and the oxidative condition
were evaluated in healthy subjects supplemented for 2 weeks
with (study group) or without (controls) sulfurous mineral water
both before (T0) and after (T1) treatment. Results: At T1, a
significant decrease (P<0.05) in both lipid and protein oxidation
products, namely malondialdehyde, carbonyls and AOPP, was
found in plasma samples from subjects drinking sulfurous
water with respect to controls. Concomitantly, a significant
increment (P<0.05) of the total antioxidant capacity of plasma
as well as of total plasmatic thiol levels was evidenced.
Tocopherols, carotenoids and retinol remained almost
unchanged before and after treatment in both groups.
Conclusions: The improved body redox status in healthy
volunteers undergoing a cycle of hydropinic therapy suggests
major benefits from sulfurous water consumption in reducing
biomolecule oxidation, possibly furnishing valid protection
against oxidative damage commonly associated with aging
and age-related degenerative diseases. Keywords: hydropinic
treatment; sulfurous mineral water; hydrogen sulfide; thiols;
oxidative markers; antioxidant profile
European Journal of Clinical Nutrition (2009) 63, 106–112;
doi:10.1038/sj.ejcn.1602892; published online 22 August
2007
M. Costantino 1,2 G. Giuberti 3, M. Caraglia 3, A. Lombardi 3, G.
Misso 3, A. Abbruzzese 3, F. Ciani 4, E. Lampa 2
1 CE.RI.S.T. Center of Thermal Researches and Studies Srl,
Naples, Italy;
2 Department of Experimental Medicine Pharmacological
Division II, University of Naples, Naples, Italy;
3 Department of Biochemistry and Biophysics “F. Cedrangolo”
II, University of Naples, Naples, Italy;
4 Department of Veterinary, University “Federico II”, Naples,
Italy
The aim of our research was to analyze the antioxidant role
and efficacy of thermal or salus per aquam (spa) therapy with
chlorine-sulphur-bicarbonate mineral water. The study has
been performed on 30 rats. The animals were randomized in
three groups, each of them composed by ten animals,
denominated A, B and C. The A group was the control group
and was not subjected to any specific treatment (placebo); the
B group has been treated with a standard cycle of hydropinics
treatment with mineral water of Therme of Stabia in
Castellammare (Naples, Italy) denominated STABIA; the C
group was treated with a standard cycle of hydropinics
treatment with mineral water of Therme of Stabia
Castellammare (Naples, Italy) denominated SULFUREA. After
two weeks of treatment all the rats were sacrificed and blood
was collected for the plasmatic determination of reactive
oxygen species (ROS). The results demonstrated a significant
(P<0.05) reduction of ROS in B (374 Carr. U + 73) and C group
(399 Carr. U + 62) treated with mineral waters if compared with
control group (571 + 69 Carr. U). In conclusion this study
suggests a possible antioxidant effect of chlorine-sulphurbicarbonate spa hydropinic treatment with a consequent
suitable intestinal physiology, with reduction of the functional
and organic modifications that can lead to pathological
disorders of the gastroenteric diseases in whole pathogenesis
the oxidative stress can develop an important role.
Keyword Spa therapy – Sulphur mineral water – Reactive
radicals of the oxygen – Free radicals –Oxidative stress Polyamines
Amino Acids (2009) 36: 161 – 165 DOI 10.1007/s00726-0080032-y
SCIENZA DI BASE
URINARIA
Has time come for a re-assessement of Effects of a low-salt diet on idiopathic
spa therapy? The NAIADE survey in Italy hypercalciuria in calcium-oxalate stone
formers: a 3-mo randomized controlled
S. Coccheri 1, G. Gasbarrini 2, M. Valenti 3, G. Nappi 4, F. Di Orio 5
trial1–3
1 Cardiovascular Department, University of Bologna, Via Ugo
Bassi, 13 - 40121 Bologna, Italy
e-mail: [email protected]
2 Department of Internal Medicine, Catholic University, Rome,
Italy
3 Unit of Epidemiology, University of L’Aquila, L’Aquila, Italy
4 Postgraduate School of Hydrology and Thermal Medicine,
University of Milan, Milan, Italy
5 Department of Medical Statistics and Public Health,
University of L’Aquila, L’Aquila, Italy
Abstract Goal of this study was to investigate whether
appropriately applied spa therapy in several indications could
be associated with a subsequent fall in the need for costly
health services and missed working days due to sick-leave.
The Naiade project was a multicenter observational,
longitudinal, questionnaire-based study comparing an “entry”
inquiry addressed to patients before an entry thermal cycle,
and a “return” inquiry after 1 year. Routine statistical methods
were used for comparisons. The study was carried out in 297
of the 340 certified Italian spa centers. Inquiries were managed
by the spa doctor(s), with the collaboration of family doctors,
and when necessary, hospitals, other health services, labour
offices and employers. After exclusion of regular customers
and of patients with acute disease phases or severe health
conditions, 39,943 patients divided into eight diseases
subgroups
(rheumatic,
respiratory,
dermatologic,
gynaecologic, otorhynologic, urinary, vascular and
gastroenteric) underwent entry inquiry and appropriate spa
treatment. Patients who returned for treatment after 1 year
(“index year”) were 23,680 (59.2%) and received return inquiry.
Outcomes considered were: frequency and duration of
hospitalisation periods; missed working days; regular use of
disease-specific drugs; and resort to “non-spa” rehabilitation
therapies. The data collected at return inquiry were compared
with those of entry inquiry. All the considered outcomes
appeared to be significantly reduced in the index year in seven
of the eight disease subgroups in comparison with the previous
year. In conclusion, disease-appropriate spa treatments were
followed by a reduction in the need of subsequent health
interventions in most disease subgroups. The health promoting
value of spa treatments should therefore undergo more
rigorous assessment with randomised controlled studies.
Keywords Spa treatments * Health resources * Hospital
admissions * Sick-leave * Drug consumption
Received: 4 July 2006/Revised: 18 June 2007/Accepted:
1 August 2007/Published online: 6 September 2007
Int J Biometeorol (2008) 52:231-237
DOI 10.1007/s00484-007-0117-4
© ISB 2007
Antonio Nouvenne, Tiziana Meschi, Beatrice Prati, Angela
Guerra, Franca Allegri, Giuseppe Vezzoli, Laura Soldati,
Giovanni Gambaro, Umberto Maggiore, and Loris Borghi
From the Departments of Clinical Sciences (AN TM BP AG FA
and LB) AND Clinical Medicine, Nephrology and Prevention
Sciences (UM), University of Parma, Parma, Italy; the
Nephrology Unit, San Raffaele Hospital, Milan, Italy (GV); the
Department of Sciences and Biomedical Technologies,
University of Milan, Milan, Italy (LS); and the Division of
Nephrology, Columbus-Gemelli Hospital, Catholic University,
Rome, Italy (GG).
ABSTRACT
Background: A direct relation exists between sodium and
calcium excretion, but randomized studies evaluating the
sustained effect of a low-salt diet on idiopathic hypercalciuria,
one of the main risk factors for calcium-oxalate stone
formation, are still lacking. Objective: Our goal was to evaluate
the effect of a low-salt diet on urinary calcium excretion in
patients affected by idiopathic calcium nephrolithiasis. Design:
Patients affected by idiopathic calcium stone disease and
hypercalciuria (.300 mg Ca/d in men and .250 mg Ca/d in
women) were randomly assigned to receive either water
therapy alone (control diet) or water therapy and a low-salt diet
(low-sodium diet) for 3 mo. Twenty-four-hour urine samples
were obtained twice from all patients: one sample at baseline
on a free diet and one sample after 3 mo of treatment. Results:
A total of 210 patients were randomly assigned to receive a
control diet (n = 102) or a low-sodium diet (n = 108); 13
patients (2 on the control diet, 11 on the low-sodium diet)
withdrew from the trial. At the follow-up visit, patients on the
low-sodium diet had lower urinary sodium (mean ± SD: 86 ±
43 mmol/d at 3 mo compared with 228 ± 57 mmol/d at
baseline; P < 0.001). Concomitant with this change, they
showed lower urinary calcium (271 ± 86 mg/d at 3 mo
compared with 361 ± 129 mg/d on the control diet, P = 0.001)
and lower oxalate excretion (28 ± 8 mg/d at 3 mo compared
with 32 ± 10 mg/d on the control diet, P = 0.001).
Urinary calcium was within the normal range in 61.9% of the
patients on the low-salt diet and in 34.0% of those on the
control diet (difference: +27.9%; 95% CI: +14.4%, +41.3%; P
< 0.001).
Conclusion: A low-salt diet can reduce calcium excretion in
hypercalciuric stone formers. This trial was registered at
clinicaltrials.gov as NCT01005082
Received September 3, 2009 - Accepted December 4, 2009
Published online December 30, 2009
Am J Clin Nutr 2010;91:565–70.
DOI: 10.3945/ajcn.2009.28614.
Printed in USA. © 2010 American Society for Nutrition
VA S C O L A R E
Effect of immersion in CO2-enriched
water on free radical release and total
antioxidant status in peripheral arterial
occlusive disease
G. Dogliotti 1, E. Galliera 1, E. Iorio 2, M. De Bernardi Di Valserra 3,
U. Solimene 1,4, M. M. Corsi 1,5
1 Department of Human Morphology and Biomedical
Sciences “Città Studi”, University of Milan, Italy
2 International Observatory for Oxidative Stress, Salerno,
Italy
3 Rabbi Fonti, Trento, Italy
4 Bioclimatology Study Center, University of Milan, Milan, Italy
5 Operative Unit of Clinical Pathology, IRCCS Policlinico San
Donato, Milan, Italy
Aim. The aim of this paper was to investigate the release of
oxygen free radicals in patients with peripheral occlusive
arterial disease and the effects of immersion of the legs and
feet in carbon dioxide (CO2)-enriched water.
Methods. Twenty-five patients with peripheral occlusive arterial
disease (Fontaine stage II) and 15 healthy controls were
treated by immersing the lower legs in either CO2 enriched or
normal spa water. Blood samples were collected in
heparinized tubes and total antioxidant status (TAS) and
reactive oxygen metabolites (ROMs) were measured after five
treatments a week for two weeks.
Results. d-ROM plasma levels decreased in patients with
peripheral occlusive disease after immersion in CO2-enriched
water (P<0.001), and in healthy controls (P<0.01), in line with
a significant increase in TAS (P<0.001).
Conclusion. CO2 -enriched water immersion had a positive
effect, reducing free radical plasma levels and raising the
levels of antioxidants, suggesting an improvement in the
microcirculation.
Key words: Free radicals - Reactive oxygen species - Arterial
occlusive diseases
Received October 5, 2009 – Accepted April 9, 2010
Int Angiol 2011;30:12-17
PREMIO 2013
On. MASSIMO VANNUCCI
A partire dall’anno 2013,
FoRST ha inteso dedicare all’On. Massimo Vannucci,
fautore della legge di riordino del settore termale e promotore
dell’Associazione parlamentare «Amici del Termalismo»
il premio previsto per le migliori pubblicazioni scientifiche
per la ricerca medico-scientifica in ambito termalistico
“Premio Massimo Vannucci 2013”
per la ricerca medico-scientifica in ambito termalistico
Il 17 dicembre 2013, presso la Sala Berlinguer
della Camera dei Deputati,
Filippo Maria FERNE’, Presidente della Fondazione FoRST
e Costanzo JANNOTTI PECCI, Presidente di Federterme,
hanno avuto il piacere di consegnare i premi ai ricercatori
vincitori del premio 2013:
dott.ssa K. Sciuto, dott.ssa A. Fioravanti,
prof. M.M. Corsi, prof.ssa A. Faga.
Sono intervenuti alla cerimonia:
Nadia Vannucci, sorella On. Massimo Vannucci
Luciano Arcangeli, Sindaco di Macerata Feltria
Marco Vitale, Coordinatore scientifico FoRST
Conclusione e saluti finali a cura dell’On. Stefano Fassina del Partito Democratico
Pubblicazioni che si sono aggiudicate
il premio On. Massimo Vannucci 2013
R E U M ATO L O G I C A
R E U M ATO L O G I C A
Polyphasic approach and typification Efficacy of balneotherapy on pain,
of selected Phormidium strains function and quality of life in patients
(Cyanobacteria)
with osteoarthritis of the knee
Katia Sciuto, Carlo Andreoli, Nicoletta Rascio, Nicoletta La
Rocca, Isabella Moro
Department of Biology, University of Padova, Italy
Abstract
Cyanobacteria (phylum Cyanophyta/Cyanobacteria, class
Cyanophyceae) are among the most widespread organisms
and are able to adapt themselves to different extreme
environments. These micro-organisms have an important
ecological role, given their ability to perform oxygenic
photosynthesis, and are employed in different fields based on
their ability to produce several bioactive compounds. Their
prokaryotic nature, the presence of many cryptic species, and
the coexistence of different nomenclature systems make the
taxonomic identification of cyanobacteria particularly difficult.
Moreover, for several species, the original reference strains
(holotypes) are lacking. Increasingly, authors are using a
polyphasic approach to characterize cyanobacteria, while
typification is a recent trend that is being used to solve the
problem of missing holotypes in other micro-organisms. Here
we focus on a filamentous cyanobacterium, isolated from the
Euganean Thermal District (Padova, Italy) and temporarily
named strain ETS-02, using a polyphasic approach that
includes morphological, ultrastructural, biochemical (pigment
and fatty acid content), physiological (nitrogen fixation), and
genetic (16S rRNA, 16S–23S ITS, cpcB-IGS-cpcA, rpoC1,
gyrB, rbcL, nifD loci) analyses. The description of Phormidium
cf. irriguum CCALA 759 as the epitype of Phormidium irriguum
was also used to complete the characterization of strain ETS02.
Ricerca pubblicata su: Cladisticts
Titolo originale: Polyphasic approach and typification of
selected Phormidium strains (Cyanobacteria)
Data di pubblicazione: 2012
Fioravanti A, Giannitti C, Bellisai B, Iacoponi F, Galeazzi M.
Rheumatology Unit, Department of Clinical Medicine and
Immunological Sciences, University of Siena, Siena, Italy.
[email protected]
Abstract
The aims of this study were to evaluate whether balneotherapy
with mineral sulphate-bicarbonate-calcium water could
determine substantial symptomatic improvement, and to detect
any changes in the quality of life (QoL) of patients with
symptomatic knee osteoarthritis (OA). This was a prospective
randomized, single blind controlled trial. Sixty outpatients with
primary bilateral knee OA, according to ACR criteria, were
included in the study and randomized to one of two groups:
group I (30 patients) was treated with a daily sulphatebicarbonate-calcium mineral water bath; group II (30 patients),
the control group, continued their regular outpatient care routine.
At baseline, after 15 days and after 12 weeks, patients were
evaluated by Visual Analogue Scale (VAS) for spontaneous
pain, Lequesne and Womac Index for gonarthrosis, SF-36,
Arthritis Impact Measurement Scale (AIMS) and symptomatic
drugs consumption. We observed a significant improvement
of all parameters at the end of the cycle of balneotherapy
which persisted throughout the follow-up period, whereas in
the control group no significant differences were noted. This
symptomatic effect was confirmed by the significant reduction
of symptomatic drugs consumption. The differences between
the two groups were significant for all considered parameters
already from the 15th day and persisted during follow-up.
Tolerability of balneotherapy seemed to be good, with light and
transitory side effects. Our results confirm that the beneficial
effects of balneotherapy in patients with knee OA last over
time, with positive effects on the painful symptomatology, a
significant improvement on functional capacities and QoL.
Balneotherapy can represent a useful backup to
pharmacological treatment of knee OA or a valid alternative
for patients who do not tolerate pharmacological treatments.
Ricerca pubblicata su: Int J Biometeorol 2012
Titolo originale: Efficacy of balneotherapy on pain, function and
quality of life in patients with osteoarthritis of the knee
Data di pubblicazione: 2012
D E R M ATO L O G I C A
O TO R I N O L A R I N G O I AT R I C A
Effects of thermal water on skin Carbon
dioxide-enriched
water
regeneration
inhalation in patients with allergic
rhinitis and its relationship with nasal
Faga A, Nicoletti G, Gregotti C, Finotti V, Nitto A, Gioglio L.
fluid cytokine/chemokine release.
Department of Plastic Surgery, University of Pavia - IRCCS
Fondazione S. Maugeri, Pavia, Italy
Abstract
An experimental study was carried out in an animal (New
Zealand white rabbit) wound model to evaluate any effects of
a hypotonic, bicarbonate-calcium-magnesium mineral water
(Comano thermal water) on skin regeneration, comparing the
healing rate of split-thickness skin graft donor sites treated with
the thermal water wet dressing versus a standard petrolatum
gauze dressing versus a saline solution wet dressing. The
study was performed in two steps; an overall of 22 animals
were enrolled in the study. The wound healing progress was
evaluated both by the surgeons and by the histologists. Sixtyfour punch biopsies were examined in all. The histological
samples were examined after staining with haematoxylin and
eosin, Masson's and orcein staining and under a transmission
electron microscope. The data were statistically analysed. The
Comano thermal water proved to improve skin regeneration,
not only by increasing keratinocyte proliferation and migration
but also favourably modulating the regenerated collagen and
elastic fibres in the dermis. We propose that the results of the
topical treatment with the thermal water could be due to the
favourable combination of a local wet environment with an antiinflammatory action and that the regenerative properties of
Comano thermal water observed in rabbits could also be
applied for human use.
Ricerca pubblicata su: International Journal Of Molecular
Medicine 2012
Titolo originale: Effects of thermal water on skin regeneration
Data di pubblicazione: 2012
Pagani D, Galliera E, Dogliotti G, De Bernardi di Valserra M,
Torretta S, Solimene U, Corsi MM, Pignataro L.
Department of Special Surgical Sciences, Fondazione IRCCS Cà
Granda-Ospedale Maggiore Policlinico, University of Milan, Italy
Abstract
Background and aims: Allergic rhinitis is characterized by
eosinophil infiltration and accumulation in the nasal mucosa
mainly due to IL-3, IL-5, and eotaxin activities. We undertook
this study to investigate a possible in vivo effect of carbon
dioxide-enriched water inhalation in patients with allergic rhinitis.
Methods: Twenty five consecutive patients inhaled carbon
dioxide-enriched water at Fonti di Rabbi Spa Centre (Trento,
Italy). Symptom scores for nasal obstruction, itching and
sneezing were obtained before and after treatment. Nasal
lavage was collected, and IL-3, IL-5, and eotaxin levels were
assessed using the quantitative sandwich enzyme
immunoassay technique. Cytometric analysis was performed
on samples to measure total cell count, CD45+ cells, and
percentages of polymorphonucleates and lymphocytes.
Results: There were statistically significant differences in
chemokine levels and in cell populations between patients and
healthy controls before treatment. After carbon dioxideenriched water inhalation, we observed statistically significant
improvements in symptom scores, chemokine levels, and
percentages of cell populations.
Conclusions: Our results seem to confirm the role of IL-3, IL5, and eotaxin in the pathophysiology of allergy and the
beneficial effect of carbon dioxide-enriched water inhalation in
patients affected by allergic rhinitis.
Received for publication February 14,2011; accepted June
20,2011 (ARCHMED-D-1100081)
Ricerca pubblicata su: Elsevier Inc.
Titolo originale: Carbon dioxide-enriched water inhalation in
patients with allergic rhinitis and its relationship with nasal fluid
cytokine/chemokine release.
Data di pubblicazione: 2011
B A N D O CONGIUNTO
Anni 2009-2013
A.I.R.C.
Associazione Italiana
per la Ricerca sul Cancro
FoRST
Fondazione per la Ricerca
Scientifica Termale
Hanno emesso un bando congiunto
per uno stanziamento complessivo
di 900 mila euro per il finanziamento del progetto:
“Efficacy of thermal treatment
for respiratory airways in heavy smokers”
Ente di ricerca: Istituto Tumori di Milano
Principal Investigator: prof. Ugo Pastorino
finalizzato a valutare l’eventuale valenza terapeutica
delle acque termali nel prevenire l’insorgenza
dei fattori di rischio nelle neoplasie polmonari
Progetto concluso – si attende la pubblicazione
COLLABORAZIONI CON ENTI DI RICERCA INTERNAZIONALI
“Analysis of the effects of H2S as a major component
of the thermal waters on endothelial functions
during Mycoplasma infection”
Dipartimento di Virologia Umana, dell’Università del Maryland equipe del prof.Robert Gallo
Progetto di ricerca di base
sugli effetti del solfuro di idrogeno (H2S)
sugli stati acuti dei processi infiammatori
e la prevenzione della loro cronicizzazione
Progetto concluso e in fase di pubblicazione - prevista una II fase dello studio
www.fondazioneforst.it
Contatti I Mappa del sito
Fondazione per la Ricerca Scientifica Termale
Chi siamo News ed Eventi FoRST per i Medici Come curarsi alle Terme La nostra Ricerca 5 per mille Link
LA FONDAZIONE
La Fondazione per la Ricerca Scientifica Termale ( FORST) promuove e sostiene l’attività di ricerca medico- scientifica in ambito termale.
I progetti di ricerca finanziati dalla Fondazione sono orientati a certificare gli effettivi benefici che l’utilizzo delle acque termali e delle risorse del
termalismo terapeutico sono in grado di assicurare. [segue]
AREA PUBBLICO
AREA MEDICI
AREA RICERCATORI
Come curarsi alle terme
FoRST per i medici
[Entra]
[Entra]
Possibilità di partecipazione
ai bandi per la ricerca online
[Entra]
AT T I V I T À E P R O G R A M M I P E R I L 2 0 1 4
• Progetto di ricerca con Campus Biomedico di Roma:
“Effetto dell’assunzione di acqua ad alto potere tampone e bassa tensione di CO2
sul profilo pH-impedenzometrico e sullo score dei sintomi in pazienti affetti
da malattia da reflusso gastroesofageo non erosiva e da dispepsia”
• V bando in materia di innovazione tecnologica
Stanziamento 300 mila euro
Ambiti di riferimento:
- Modificazioni biotecnologiche dei principi attivi delle acque
- Sviluppo di nuove tecnologie per la somministrazione delle cure.
Sono in corso contatti con poli tecnologici universitari per l’individuazione di un progetto di comune interesse.
• Progetto Hydroglobe: Femtec/FoRST/Oms
“Definition of a global framework for hydrotherapy”
Presentazione risultati
• Prosecuzione attività di comunicazione sui risultati delle ricerche co-finanziate
• Consolidamento rapporti con enti ed istituzioni europee ed internazionali per il
rafforzamento del sistema termale nazionale ed europeo
• Bando Premio 2014 On. Massimo Vannucci per uno stanziamento di 40 mila euro
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E S T R AT TO D E L L O S TAT U TO D I F o R S T
Articolo 2
SCOPI
2.1 La Fondazione prosegue le attività già svolte dal Fondo per la ricerca
scientifica termale e si propone lo scopo di promuovere e sostenere l’attività
di ricerca medico-scientifica in ambito termale, anche sulla scorta di quanto
previsto dalla Legge n. 323/2000.
In particolare si propone di confermare nel tempo, in rapporto all’evoluzione
epidemiologica, l’appropriatezza delle cure termali erogate con oneri a carico
del SSN, ai sensi dell’art. 4 comma 1 della Legge n. 323/2000.
2.2 Ai fini del comma precedente, la Fondazione, nei limiti e in conformità alle
norme di legge applicabili, può promuovere lo svolgimento di convegni, conferenze, programmi di studio e ricerca, intraprendere e promuovere l’attuazione di iniziative di carattere scientifico nel campo della progettazione e
promozione della realizzazione delle Opere dell’ingegno, assumere direttamente la gestione di iniziative nel campo della elaborazione di studi progettuali
e/o della promozione della realizzazione delle Opere dell’ingegno, sollecitare
e sostenere specifici progetti di ricerca di interesse del settore termale, intraprendere qualsiasi altra attività necessaria o utile ai fini del perseguimento dei
propri scopi istituzionali.
2.3 Rientrano, altresì, tra gli scopi della Fondazione la stampa e la diffusione,
mediante qualsiasi mezzo di comunicazione, anche di massa, ritenuto utile
allo scopo, di lavori, pubblicazioni e informazioni medico-scientifiche in materia
termale anche finalizzate alla maggiore conoscenza delle terapie termali e
della loro efficacia.
2.4 La Fondazione potrà prestare la propria collaborazione con Enti o Istituzioni, sia pubblici che privati, per il conseguimento degli scopi predetti ed effettuare ogni altra attività necessaria o utile ai fini del perseguimento dei propri
scopi istituzionali.
2.5 La presentazione dei progetti di ricerca, finanziabili attraverso il patrimonio
della Fondazione, dovrà avvenire da parte dei soggetti indicati e secondo le
modalità stabilite dal Regolamento.
2.6 Le finalità della Fondazione sono espletate su tutto il territorio della Comunità Europea.
2.7 Non possono far parte della Fondazione, né possono essere nominati Sostenitori, e se già nominati sono esclusi di diritto, coloro che si trovino in conflitto d’interessi o in situazione d’incompatibilità con la Fondazione.
L’esclusione viene dichiarata con deliberazione del Consiglio di Amministrazione.
E S T R AT TO D E L R E G O L A M E N TO D I F o R S T
OMISSIS
Articolo 6 - SOGGETTI LEGITTIMATI A PRESENTARE
E REALIZZARE PROGETTI DI RICERCA
Articolo 8 - MODALITÀ DI FINANZIAMENTO
8.1 La Fondazione, secondo le procedure di cui al seguente
art. 10, co-finanzierà una quota che in nessun caso potrà eccedere il 60% dell’intero importo previsto per la realizzazione
Sono soggetti legittimati a presentare e realizzare progetti di
del progetto di ricerca e comunque fino alla concorrenza di un
ricerca scientifica finanziabili dalla Fondazione:
importo massimo di cofinanziamento non superiore ad euro
a) Enti di Ricerca nazionali ed internazionali sia pubblici che
90.000,00 (novantamila) come da delibera del Comitato ese-
privati, le Università e le Aziende Sanitarie e Ospedaliere;
cutivo del 7 luglio 2011. La percentuale e l’importo massimo
b) gli IRCCS;
di cofinanziamento di cui sopra sono comprensivi dell’even-
c) le Regioni;
tuale ulteriore contributo per la pubblicazione dei risultati della
d) il Ministero della Salute;
ricerca su riviste scientifiche con fattore d’impatto citate in
e) l’Istituto Superiore di Sanità;
ISI/PubMed, il cui ammontare non potrà superare il 30% del-
f) l’INPS;
l’importo co-finanziato, di cui all’art.12, punto 2.
g) l’INAIL.
8.2 Fondazione stipulerà apposita Convenzione con gli Enti
Art. 7 - CRITERI DI INAMMISSIBILITÀ
E DI VALUTAZIONE DEI PROGETTI
beneficiari del co-finanziamento.
Fondazione è abilitata al versamento delle somme oggetto del
co-finanziamento unicamente nei confronti dei Soggetti firma-
7.1 Non verranno ritenuti ammissibili:
tari della Convenzione, i quali sono tenuti all’analitica rendi-
a) progetti la cui durata prevista sia superiore a quella indicata
contazione delle spese sostenute per la realizzazione del
in ogni singolo Bando;
progetto di ricerca, secondo i criteri riportati in ciascun bando
b) progetti che non prevedano un piano almeno annuale di
e allegati alla Convenzione di cui al comma precedente.
stato di avanzamento dei lavori;
8.3 In tutti i casi in cui venga erogato il finanziamento, i lavori
c) progetti di ricerca già avviati;
scientifici pubblicati ed i relativi risultati rimarranno nella libera
d) progetti di ricerca la cui conduzione scientifica risulti affidata
disponibilità della Fondazione.
a soggetti diversi da quelli indicati all’art.6, lett. a), b), c), d),
8.4 Nel caso in cui, in riferimento ad un medesimo Bando, ven-
e), f), g);
gano ritenuti idonei al finanziamento più progetti, di norma si
7.2 La valutazione dei progetti sarà effettuata secondo le se-
procederà all’erogazione della quota prevista partendo dal pro-
guenti modalità:
getto che avrà ottenuto il punteggio più elevato fino a concor-
Il Comitato Esecutivo della Fondazione per la Ricerca Scien-
renza dell’importo destinato al singolo Bando.
tifica Termale è incaricato dell’istruttoria, ed opera una prima
analisi dei progetti di ricerca per valutarne l’ idoneità formale.
OMISSIS
I progetti di ricerca dichiarati ammissibili verranno sottoposti
al parere di esperti internazionali di cui al successivo art.10,
che dovranno proporre per iscritto un punteggio sulla base dei
Articolo 12 - PROCEDURE DI EROGAZIONE
DEL CONTRIBUTO
criteri riportati nel bando.
Il Comitato Esecutivo, acquisiti i pareri del Comitato Scientifico
12.1 Il 70% del contributo complessivo che FoRST erogherà
e verificata la congruità del finanziamento richiesto, propone
all’Ente aggiudicatario sarà versato con le seguenti modalità:
la graduatoria finale alla valutazione del Consiglio di Ammini-
a. il 20% del contributo, ad avvenuta comunicazione di inizio
strazione.
attività ed in concomitanza alla sottoscrizione della Convenzione;
7.3 Sulla base dei risultati dell'istruttoria preliminare e della
b. il 30% del contributo dopo 12 mesi dalla comunicazione di
valutazione successiva circa gli aspetti di ordine tecnico –
inizio attività e previa presentazione di una relazione scientifica
scientifico e finanziario, il Consiglio di Amministrazione della
dettagliata dello stato di avanzamento del progetto nonché
Fondazione per la Ricerca Scientifica Termale approva con
della rendicontazione contabile delle spese sostenute;
propria delibera la graduatoria finale dei progetti, specificando
c. Il residuo 20% del contributo alla presentazione dei risultati
l’entità del finanziamento riconosciuto nonché le modalità e le
conclusivi della ricerca (relazione conclusiva) e della rendicon-
procedure per l’erogazione dello stesso.
tazione analitica delle spese sostenute, secondo i criteri ripor-
7.4 Le verifiche in itinere ed ex post vengono operate dal Co-
tati nell’allegato modello di rendicontazione (Allegato A).
mitato scientifico e dalla Commissione di rendicontazione.
12.2 Il 30% della cifra complessivamente riconosciuta verrà
infine erogato alla pubblicazione dei risultati della ricerca su riviste scientifiche con fattore d’impatto citate in ISI/PubMed.
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IL CONSIGLIO
DI AMMINISTRAZIONE
Presidente
Filippo Fernè *
Tesoriere
Rosanna Turchi *
Consiglieri d’Amministrazione
Enzo Baretella
Paolo Bonini *
Amato De Paulis
Aldo Ferruzzi
Leonardo Punzi
Marco Tagliaferri
Claudio Zucchi
Coordinatore del Comitato Scientifico
Marco Vitale
COLLEGIO DEI REVISORI DEI CONTI
Presidente
Bruno Mambriani
Sindaci
Mario Crosato
Alessandro Mollica
Segretario
Cristina Frezza
* Membri Comitato Esecutivo
Via Po, 22
00198 Roma
06.85300966
www.fondazioneforst.it