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Rossana PANINI

Personale tecnico amministrativo
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2023 - CD271 activation prevents low to high-risk progression of cutaneous squamous cell carcinoma and improves therapy outcomes [Articolo su rivista]
Quadri, Marika; Tiso, Natascia; Musmeci, Francesco; I Morasso, Maria; R Brooks, Stephen; REGGIANI BONETTI, Luca; Panini, Rossana; Lotti, Roberta; Marconi, Alessandra; Pincelli, Carlo; Palazzo, Elisabetta
abstract

2021 - TERT promoter methylation and protein expression as predictive biomarkers for recurrence risk in patients with serous borderline ovarian tumours [Articolo su rivista]
Losi, Lorena; Botticelli, Laura; Garagnani, Lorella; Fabbiani, Luca; Panini, Rossana; Gallo, Graziana; Sabbatini, Roberto; Maiorana, Antonino; Benhattar, Jean
abstract

Epithelial ovarian neoplasms can be divided into three distinct clinicopathological groups: benign, malignant and borderline tumours. Borderline tumours are less aggressive than epithelial carcinomas, with an indolent clinical course and delayed recurrence. However, a subset of these cases can progress to malignancy and relapse, and death from recurrent disease can occasionally occur. Telomerase activation is a critical element in cellular immortalisation and cancer. The enzyme telomerase comprises a catalytic subunit (TERT) expressed in various types of cancers and regulated by promoter methylation mainly in epithelial tumours. The aim of this study was to investigate the promoter methylation status and the expression of TERT in 50 serous borderline tumours (SBTs) and their correlation with clinicopathological features and outcome. TERT methylation was analysed by bisulfite pyrosequencing and TERTexpression by immunohistochemistry. Methylation of TERT promoter was only observed in four SBTs. A good correlation with immunostochemistry was found: nuclear positivity for TERT expression was observed in the methylated cases, whereas no expression was detected in unmethylated tumours. One of these patients had a recurrence after 7 years and another patient died from the disease. SBTs with hypomethylated tumours and absence of TERTexpression showed a good clinical behaviour. Our study highlights the low presence of TERT methylation in SBTs, confirming that these tumours have a different biology than serous carcinomas. Furthermore, the concordance between TERT promoter methylation and TERT expression and their association with clinical outcomes leads to consider TERT alteration as a potential predictive biomarker for recurrence risk identifying patients who should undergo a careful and prolonged follow-up.

2003 - Effetti dell’insulina sui livelli di omocisteina plasmatica in pazienti con diabete mellito tipo ii con e senza intolleranza alla metionina [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; M. C., Rosa; G., Salvioli
abstract

Premessa- Una elevata prevalenza di iperomocisteinemia (HHcy) è stata osservata in pazienti con diabete mellito tipo II e malattia vascolare documentata; da qui l’ipotesi che la iperomocisteinemia possa contribuire alla mortalità generale nei pazienti diabetici. Il legame fra insulina e metabolismo dell'omocisteina (Hcy) non è stato ancora chiarito; in particolare, sono disponibili soltanto pochi dati circa gli effetti in vivo dell’insulina sul metabolismo dell' Hcy in presenza di quelle alterazioni (congenite e/o acquisite) del metabolismo degli aminoacidi solforati in grado di condizionare una condizione di HHcy (intolleranza alla metionina). Scopo- valutare in che modo la presenza di una condizione di intolleranza della metionina possa influenzare i livelli plasmatici di Hcy in risposta all'infusione dell'insulina in vivo in pazienti con diabete tipo II.Materiali e metodi - Abbiamo sottoposto 18 pazienti (gruppo A) con normale e 18 pazienti con anormale (iperomocisteinemia dopo carico, intolleranza alla metionina) risposta (gruppo B) al carico orale con metionina ad uno studio di clamp euglicemico. A tempo 0 ed a 30, 60 e 120 minuti dall’induzione di iperinsulinemia, abbiamo valutato i livelli circolanti di omocisteina (tHcy) e metionina (Met) (HPLC). Per valutare la causa di intolleranza della metionina, tutti i pazienti sono stati sottoposti a valutazione del rapporto omocisteina-cisteina a digiuno (indicatore di sospetta eterozigosi per deficit di CS), a valutazione genetica della mutazione C677T della MTHFR e al dosaggio sierico delle vitamine necessarie al corretto metabolismo dell’omocisteina [ vitamina B 6 ( PLP), vitamina B 12 e folati ]. Risultati - Dopo iperinsulinemia, i livelli di Met sono risultati ridotti (circa –30% a 120 minuti rispetto ai valori basali) in entrambi i gruppi, mentre la tHcy è risultata ridursi nel gruppo A (fino a - 6.6  3.6 % rispetto ai valori basali), ed aumentare nel gruppo B (fino a +29.05  8.3 % rispetto ai valori basali) . I livelli sierici di folati (7.45  2.8 contro. 4.82  2.5 nmol/L, p<0.05), Vit. B 12 (348  78 contro. 242  65 pmol/L, p< 0.05) e PLP (84.1  23.6 contro 50.6  32.4 nmol/L; p<0.01) sono risultati più alti nel gruppo A che nel gruppo B; i livelli di PLP sono risultati correlare significativamente con quelli della tHcy dopo carico (n=36; r=-.327, p<0.05); il gruppo A presentava inoltre una prevalenza inferiore di sospetta eterozigosi per CS [ 1/18 (11.1 %) contro 5/18(33.3%), p<0.05 ] e una ridotta prevalenza dell'allele mutato T della MTHFR [ 4/18 (22.2%) contro 11/18 (61.1%), p<0.01 ]. L’analisi di regressione logistica multipla con la variazione di Hcy sotto stimolo insulinico (evento A = riduzione; evento B = aumento) come variabile dipendente, ha indicato la carenza di folati e di PLP e la presenza dell'allele di MTHFR T come le variabili più significativamente predittive del tipo di risposta dell’Hcy all’iperinsulinemia.Conclusioni - La presenza di intolleranza alla metionina può influenzare l'effetto dell'insulina sull' omocisteina plasmatica in pazienti con diabete tipo 2. Per prevenire la possibilità di episodi acuti, ripetuti e potenzialmente dannosi, di iperomocisteinemia in questi pazienti in seguito alla assunzione di insulina, potrebbe essere utile la valutazione della presenza di una condizione di intolleranza della metionina (test orale alla metionina) e uno studio dello stato vitaminico Hcy-relato in tutti i pazienti diabetici da sottoporre alla terapia insulinica.

2003 - Relevance of different apolipoprtein content in homocysteine binding to plasma lipoproteins [Abstract in Rivista]
Ventura, Paolo; Panini, Rossana; M. C., Rosa; E., Gaetti; Salvioli, Gianfranco
abstract

Background and aims: In plasma, homocysteine (Hcy) circulates free or bound to proteins (Pb-Hcy). Our study sets out to assess the lipoprotein-Hcy (LP-Hcy) binding in vivo and the possible influence of different apolipoprotein content in this binding. Methods: In 34 healthy subjects fasting plasma lipoprotein (Sequential ultra-centrifugation) and correspondent apolipoprotein (apo A-I, apo A-II, apo C-II, apo C-III, apo B, apo(a) and apo E) content (Immunoturbidimetric assay), and Hcy (HPLC) bound to different plasma protein fractions were assessed; ten subjects underwent a methionine oral load in order to evaluate Pb-Hcy and LP-Hcy modifications after induction of hyperhomocysteinemia (HHcy). Results: Pb-Hcy (mean values 9.22±1.7 mol/L) resulted 78% of total plasma Hcy (mean values 11.8±1.8 mol/L). Pb-Hcy distribution between the different fractions was as follows (mol/L): VLDL= 0.25 ± 0.08 (2.7 %); LDL= 0.88 ± 0.22 (9.5 %); HDL =1.40 ± 0.36 (15.2 %), Lipoprotein-Free Protein Fraction (LPDS) = 6.7 ± 1.2 (72.6 %). Hcy/protein ratios (mol / g of protein) of each protein fraction were: VLDL= 0.32 ± 0.19, LDL= 0.43 ± 0.37, HDL= 0.26 ± 0.18, LPDS < 0.1, this suggesting a higher binding capacity for Hcy of VLDL and LDL. This data was confirmed by the higher increase in Hcy content in LDL and VLDL (+76 and +90%, respectively vs. +36% and +3.1 % for HDL and LPDS fractions) after HHcy. Lp-Hcy binding significantly correlated with the apo B content of VLDL and LDL and Apo A-I content of HDL. Conclusions: An important fraction of Hcy circulates bound to LP (about 27% of Pb-Hcy); VLDL and LDL show the highest binding capacity for Hcy; this may be due to content in Apo B, a possible high capacity binding site for Hcy (great availability of free cysteine and lysine residuals).

2003 - Rilevanza del diverso contenuto apolipoproteico nel legame dell’omocisteina alle lipoproteine [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; M. C., Rosa; E., Gaetti; Salvioli, Gianfranco
abstract

Premesse: Nel plasma l’omocisteina (Hcy) circola in forma libera e (per la maggior parte, circa il 70-80% del totale) legata alle proteine (Pb-Hcy). E’ ormai accettato il ruolo pro-aterogeno di moderatamente elevati livelli plasmatici di omocisteina; meno definita è la relazione esistente fra omocisteina e metabolismo lipidico, sebbene una relazione fra livelli di omocisteina (dotata di attività pro-ossidante) e ossidazione delle lipoproteine sia stata riportata da diversi autori.Scopo: valutare l’esistenza di un legame fra Hcy e lipoproteine (LP-Hcy) in vivo e la possibile influenza del differente contenuto apolipoproteico in tale legame.Materiali e metodi: 34 soggetti sani (età media 54 ± 8, 18 donne) sono stati sottoposti a determinazione del contenuto plasmatico delle principali lipoproteine (ultracentrifugazione sequenziale) e del loro corrispondente contenuto apoproteico (Apo A-I, apo A-II, apo C-II, apo C-III, apo-B, apo (a) e apo E) (immunoturbidimetria) e a dosaggio (HPLC con metodica fluorimetrica) dell’Hcy legata alle diverse frazioni lipoproteiche; inoltre, dieci soggetti sono stati sottoposti a carico orale con metionina (100 mg/kg in 200 cc di the), allo scopo di valutare variazioni “dinamiche” nel legame Pb-Hcy e LP-Hcy in seguito all’induzione di iperomocisteinemia (HHcy).Risultati: la quota di Hcy circolante legata a proteine (9.22 ± 1.7 mol/L) è risultata il 78% del totale (11.8 ± 1.8 mol/L). La distribuzione della quota di Hcy legata fra le diverse frazioni proteiche ottenute con ultracentrifugazione sequenziale è risultata la seguente (mol/L): VLDL= 0.25±0.08 (2.7%); LDL= 0.88± 0.22 (9.5%); HDL= 1.4 ± 0.36 (15.2%), Frazione plasmatica proteica senza lipoproteine (LPDS): 6.7± 1.2 (72.6%). Il rapporto fra Hcy legata e contenuto proteico di ciascuna frazione (mol Hcy / g di proteina) è risultato: VLDL =0.32± 0.19, LDL=0.43±0.37, HDL=0.26±0.18, LPDS <0.1: ciò suggerisce una maggiore capacità legante l’Hcy da parte di VLDL e LDL. Il dato è confermato dai risultati della prova “dinamica”: in corso di HHcy indotta da carico con metionina, l’aumento percentuale del contenuto in Hcy è risultato nettamente superiore nelle frazioni LDL e VLDL (rispettivamente del 90% e del 76% rispetto al contenuto di partenza) che in quelle HDL e LPDS (36% e 31%, rispettivamente). Il legame LP-Hcy correla in modo significativo, sia in condizioni basali che dopo carico con metionina con il contenuto in apo-B delle VLDL e delle LDL e di Apo A-I nelle HDL. Ciò può dipendere dalla peculiare struttura primaria di tali apoproteine (ricche di residui laterali liberi di cisteina e lisina, siti di legame preferenziale dell’omocisteina).Conclusioni: Una frazione significativa dell’omocisteina circola nel plasma legata a lipoproteine (circa il 27% della quota legata a proteine); fra queste le VLDL e le LDL mostrano la maggiore capacità legante per l’Hcy, probabilmente in relazione al loro contenuto in apo-B, proteina ricca in residui laterali sulfidrilici liberi e residui di lisina , possibili punti di reazione con gruppo sulfidrilico libero dell’Hcy.

2001 - Effect of N-acetylcysteine long term oral administration on plasma and urinary homocysteine and cysteine levels [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; G., Marchetti; Salvioli, Gianfranco
abstract

Background: A decrease of plasma homocysteine (Hcy) may represent a therapeutic promise for reducing the impact of atherosclerosis. N-acetyl-cysteine (NAC) at high dosage seems able to interfere with endogenous thiols [cysteine (Cys) and Hcy] by forming mixed disulphides undergoing a more efficient renal clearance. Aim : to assess the effect of NAC oral chronic administration (different doses) on plasma and urine levels of different forms of plasma Cys and Hcy. Methods: In 40 healthy (44±15 years, 22 F) we assessed fasting total and free (= not protein bound) forms of plasma and urinary levels of Hcy and Cys. After informed consent subjects were randomly assigned to group A (n= 13, no therapy), group B (n= 14, NAC 600 mg once daily per os) and group C (n= 14, NAC once daily 1800 mg per os) for a month. Results: Group C showed a significant reduction of total Hcy (10.68  2.8 vs. 13.64  3.56 mmol/L, p= .001) a not significant reduction of free Hcy (3.48  0.72 vs. 3.55  0.74 mol/L, p=.702) a significant reduction of total Cys (320  93 vs. 377  122 mol/L, p=.013) a not significant reduction of free Cys (147  26.5 vs. 162  40.6 mol/L, p= .294), a significant increase of free/bound Hcy and Cys ratio (33.2  3.21 vs. 26.5  3.7 %, p= .000 and 48  7.6 vs. 42  6.0 %, p=.045, respectively).Group B showed a significant reduction of total plasma Hcy (11.6 3.7 vs. 12.88  3.9 mol/L, p=0.031) but not significant modification of other thiols forms levels.After NAC therapy Group C showed also significant higher daily Hcy and Cys urinary levels (11.73.5 vs. 9.13.1 mmol/ mg urinary creatinine , p<0.01, 24773 vs. 22074 mmol/ mg urinary creatinine, p=0.011).Also group B showed higher, but not significant, Hcy and Cys urinary levels (11.24.2 vs 10.513.3 mol/ mg urinary creatinine, p=0.056 and 23949 vs 22955 mol/ mg urinary creatinine, p=0.055). No significant variations in plasma and urinary thiols were noticed in group A.Conclusions: A chronic (one month) oral NAC administration induces a decrease of the main circulating plasma thiols (Cys and Hcy) by increasing their renal excretion. This effect seems dose-dependent, being significant only at higher NAC dosage; the modification of plasma thiols forms (reduction of total and free forms but increase of free/total ratio) support the hypothesis of displacement by NAC of thiols from their plasma protein binding sites to form mixed disulphides, which in turns may undergo a higher renal clearance, resulting in an increase of urinary excretion.

2001 - Homocysteine Production and membrane oxidative stress in erythrocytes [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; Salvioli, Gianfranco
abstract

Background: Homocysteine (Hcy) seems to induce oxidative stress (H2O2 production). Hcy synthesis occurs in erythrocytes (RBC).Aims: To assess if Hcy production in RBC may contribute to membrane lipid peroxidation.Methods: 15 RBC samples from patients with normal plasma Hcy (7.8 ± 3.1 mol/L) (controls) and 15 from megaloblastic anemia patients, [with higher Hcy plasma levels (19.1 ± 6.3 mol/L , p<0.01 with respect to controls) and RBC folate and serum B12 levels significantly lower (145.6 ± 34.1 vs. 272.6 ± 61.3 g/L, p<0.01, and 152 ± 65.5vs.582.6±195.6 pmol/ml,p<0.01, respectively)] were incubated both at 4°C and at 37° C in a RPMI folate and B12-free medium, containing methionine 50 mol. In each sample supernatant we measured at 4, 8 and 24 h Hcy, malondialdehyde (MDA) (HPLC) (marker of lipid peroxidation) and LDH levels (marker of early membrane damage) Results: In 37°C incubation samples Hcy production resulted higher in samples from megaloblastic anemia, whereas a slight Hcy increase was observed during incubation at 4°C in both groups (see figure). Hcy production (incubation at 37°C) seems associated to an higher lipid peroxidation and membrane functional derangement (see table) and a significant correlation ( 4 h : r=.668, p<0.01; 8h : r=.774, p<0.01; 24h : r= .556, p<0.01) was found between RBC Hcy production and MDA levels in the supernatant from samples at 37° Conclusions: Hcy production by RBC contribute to oxidative stress of membrane lipids. Lipoperoxidation (higher MDA levels in the medium) and membrane damage (LDH levels) in vitamin-deficient RBC may account for higher frequency of haemolysis in patients with megaloblastic anemia.

2001 - Homocysteine erythrocyte production in patients affected by dementia [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; M., Uneddu; M., Modugno; Neri, Mirco; Salvioli, Gianfranco
abstract

Background: Patients affected by dementia Alzheimer type (DAT) or vascular dementia (VD) often exhibit mild hyperhomocysteinemia (HHcy); HHcy may be important in neuron damage: it is an early marker of vitamin deficit, (folate and vit. B12), often associated with cognitive decline; HHcy itself seems to exert a neurotoxic effect (activation of NMDA receptors and induction of cell death; excitotoxic effect by some metabolites) and it is also an indipendent risk factor for (cerebro)vascular disease. Red blood cells (RBC) have enzymatic activities for Hcy synthesis (methionine demethylation) and (probably) metabolism (remethylation to methionine), representing a possible model for studying abnormalities of Hcy metabolism.Aim: to assess the possible difference in RBC production between healthy elderly and elderly affected by Dementia syndrome.Methods: In 105 subjects affected by dementia (DSM-IV criteria) [55 by DAT (30 f, mean age 78±8 years) and 50 by VD (38 f, 81±5 years); DAT and VD diagnosis was made by NINCDS-ARDRA and NINDS-AIREN criteria and Hachinsky score] and 40 healthyelderly (controls; 22 f; mean aged 77±10 years) we assessed fasting plasma Hcy (HPLC) and serum vit. B12 and RBC folates (RIA) . A RBC sample from all subjects was incubated at 37° for 8 h in RPMI vitamin-free (Ht=26%) medium. In these samples we measured at time 0 e after 4 and 8 hour Hcy concentration (supernatant and RBC cytoplasm).Results: RBC from AD patients produce more Hcy (p<0.05 for all parameters in DAT e VD vs. controls, ANOVA, Tukey post hoc); in RBC from VD patients Hcy production is higher than from DAT, but not significantly (p=0.055) (see figure). Data are corrected for Hcy-related vitamin status.Conclusions: Our data are suggestive that AD patients have higher prevalence of transmethylathion abnormalities with respect to controls. This may have both indirect (role of methylation in normal neuron trophism) and direct (toxicity due to Hcy accumulation) physiologic relevance.

2001 - Methionine intolerance and plasma homocysteine after insulin infusion in type II diabetic patients [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; S., Emiliani; Salvioli, Gianfranco
abstract

Background-To establish whether transsulfuration impairment (methionine intolerance) may influence total plasma homocysteine (Hcy) in response to insulin infusion in type II diabetic patients (DB).Materials and Methods- DB with normal (group A, n=13) and abnormal (hyperhomocysteinemia, HHcy)) (Group B, n=17) response to oral methionine load underwent a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, Hcy and methionine (Met) plasma levels were assessed. All patients were assayed for fasting Homocysteine-Cysteine ratio (as marker of suspected heterozygosis for cystathionine--synthase deficit) and vitamin status [serum vitamin B6 (PLP), vitamin B12 and folate]. Results- After hyperinsulinemia, plasma methionine reduced (about –30% at 120 minutes vs. basal values) within both groups, whereas Hcy decreased in group A (up to –15.2  8.9 % at 120 minutes) and increased in group B (up to +30.6  10.9 % at 120 minutes). (see figure) PLP was higher in group A than in group B (94.2  42.6 vs. 54.6  32.4 nmol/L; p<0.01); group A showed a lower prevalence of suspected heterozygosis for cystathionine--synthase deficit (1/13 (7,7%) vs.13/17 (76.5%), p=0.000). Conclusions-Methionine intolerance may influence insulin effect on plasma Hcy. To prevent a possible acute HHcy due to insulin administration in case of transsulfuration impairment, it may be suggested to assess transsulfuration capacity in all patients due to be subjected to insulin therapy.

1998 - Increase of protein and lipid oxidation during hyperhomocysteinemia induced by methionine oral loading [Abstract in Rivista]
Ventura, Paolo; Panini, Rossana; C., Verlato; G., Scarpetta; Salvioli, Gianfranco
abstract

Introduction: Hyperhomocysteinemia (HHcy) is a well-defined risk factor for vascular disease by a not still well clear molecular mechanism. It is known a pro-oxidant effect of Hcy “in vitro” in presence of metal ions (Fe e Cu). To assay a similar effect in vivo, we studied plasma markers of lipid and protein oxidation during hyperhomocysteinemia induced by methionine oral load.Materials and methods: 16 subjects (aged 79  14 years; 16f), 14 of which underwent a methionine (100 mg/Kg) oral load were studied; in all patients we assayed total plasma HCY, malonaldehyde (MDA) and conjugates dienes (DIE), oxidized protein (PTOX) (carbonilic groups) in basal conditions and after 4, 6, 8 and 24 hours from the oral load. In the two subjects who did not take the methionine load (controls), were made the same assays with the same timing of the probands. In all subjects we assayed basal and after 8 hours from the methionine load total plasma antioxidant (ANTOX) capacity.Results: table shows values (mean  DS) of considered parameters in subjects who underwent the methionine loadParameterBasal4 h6 h8 h24 hHcy (nmol/ml)20.7  11.550.6  19.157.2  25.561.6  28.3 45.3  30.7PTOX (nmol/mg prot.)0.38  0.210.49  0.270.68  0.390.68  0.270.58  0.40DIE(nmol/ml)493  163562  181526  233590  202545  182MDA(nmol/ml)1.66  0.801.91  0.942.19  1.321.96  0.931.95  0.99ANTOX(nmol/ml)1.76 +/- 0.511.38 +/- 0.86 Conclusions: HHCY induces a correspondent increase of plasma oxidation makers. In absence of HHCY, no significant modifications were observed. This data, together with the reduction of ANTOX in correspondence of maximum plasma HCY increase, are suggestive of pro-oxidant effect of HHCY in vivo.

1998 - Is Hyperhomocysteinemia (HHcy) a nutritional marker of senile ementia ? [Abstract in Rivista]
Ventura, Paolo; Panini, Rossana; M. C., Pasini; C., Verlato; Salvioli, Gianfranco
abstract

Introduction: Correlations between nutritional status and cognitive impairment still need to be defined. Mild hyperhomocysteinemia (Hcy>15 nmol/ml)) is a good marker of multiple (and often subclinical) vitamin (B12, B6 and folic acid) deficits, often associated with neurological disturbances and poor performance on neuropsychological tests. Several studies have shown cognitive impairment (spatial copying and memory tests) in elderly patients with normal values of blood folates and serum Vit. B12 levels but mild hyperhomocysteinemia. Aim of this study is to evaluate, in healthy elderly (HE) and in patients with senile dementia Alzheimer type (AD), the prevalence and the relevance of HHcy versus other common nutritional parameters Materials and methods: 108 patients affected by AD (DSM IV criteria) were compared with 64 age matched healthy elderly (HE). All subjects underwent a nutritional (biochemical and anthropometric parameters) and Hcy plasma level assessment. Statistical analysis were performed by standard methods. Results: The prevalence of HHcy is higher in the AD group (75%) with respect of HE group (45%). HHcy is an associated factor of AD, as suggested by an Odds Ratio value of 5.58 (2.71 11.48; 95% C.I.). A statistically significant (p<0.05, t test for independent samples) difference for all nutritional parameters and for Hcy plasma levels was found between AD and HE group. Entering these parameters into a multiple logistic regression analysis, taking the presence or absence of dementia as the dependent variable, we obtained a model predicting dementia with a likelihood of 78.5% based on the table parameters. ParameterBRSignificanceHHcy0.800.22p<0.01Albumin-1.20-0.14p<0.02Haemoglobin-0.65-0.19p<0.01Lymphocyte count-0.013-0.14p<0.02Folic acid-0.48-0.19p<0.01 Conclusions: Our data show a high prevalence of HHcy in elederly patients with AD, suggesting its importance as a nutritional risk factor for cognitive impairment.

1998 - Preparazione e caratterizzazione del complesso tra acido iodesossicolico e 2-idrossipropil-beta-ciclodestrina [Abstract in Atti di Convegno]
Vandelli, Maria Angela; Panini, Rossana; Mucci, Adele; Schenetti, Luisa; Ruozi, Barbara; Forni, Flavio
abstract

Preparazione e caratterizzazione del complesso tra acido iodesossicolico e 2-idrossipropil-beta-ciclodestrina

1998 - Ursodeoxycholic acid complexation with 2-hydroxypropyl-beta-cyclodextrin increases ursodeoxycholic acid biliary excretion after single oral administration in rats [Abstract in Rivista]
Ventura, Paolo; Panini, Rossana; Montosi, Giuliana; Garuti, Cinzia; Vandelli, Maria Angela; G., Brunetti; Pietrangelo, Antonello; Salvioli, Gianfranco
abstract

Complexation of ursodeoxycholic acid (UDCA) with 2-hydroxypropyl-beta-cyclodextrin (HPbCD) (1:1 molar ratio) improves the water solubility and dissolution rate of UDCA and hence its bioavailability. We compared UDCA bile recovery (percentage of administered UDCA dose excreted in bile) after single oral (gavage) administration of UDCA in three different pharmaceutical forms in a bile fistula rat model. Male Sprague-Dawley rats were randomly assigned to 11 groups (6 rats per groups); the bile duct was cannulated after gavage to collect 4-h bile samples. Groups 1, 2 and 3 (fed 5, 10 and 50 mg/kg body weight UDCA/HPbCD complex, respectively) showed (mean values ± SD) 39.2 ± 5.9%, 25.7 ± 4.1% and 9.4 ± 3.1% UDCA bile recovery, respectively; in groups 4, 5 and 6 (fed UDCA suspension formulation containing 5, 10 and 50 mg/kg body weight, respectively) UDCA bile recovery was 33.2 ± 3.6%, 16.9 ± 4.7% and 6.3 ± 0.8%, respectively; groups 7, 8 and 9 (fed UDCA capsule formulation containing 5, 10 and 50 mg/kg body weight, respectively) showed 30.6 ± 9.0%, 21.7 ± 6.4% and 4.7 ± 1.8% UDCA recovery. Groups 10 and 11 (controls) were fed with HPbCD and saline, respectively. Results indicate a significantly (p<0.05) higher bile UDCA recovery in rats fed UDCA-HPbCD complex than in those fed UDCA suspension or UDCA capsule formulations at the same dose. In this model, oral UDCA/HPbCD complex increased UDCA biliary excretion making for greater UDCA enrichment of the bile acid pool than identical doses of common pharmaceutical formulations.

1997 - Correlation between plasma malonyldialdeide levels and paroxonase activity in healthy subjects and in patients with atherosclerotic disease [Abstract in Rivista]
G., Scarpetta; Ventura, Paolo; Panini, Rossana; Salvioli, Gianfranco
abstract

Paraoxonase (PON) is a calcium-dependent HDL-associated ester hydrolase catalizying hydrolysis of organophosphates. Its biological role is still unknown: experimental studies suggest a hydroperoxidasic activity on lipoperoxides formed during LDL-oxidation, thus acting as a protective agent against atherogenesis. We evaluated PON activity in healthy subjects (HS) and in patients with cardiovascular (CHD) and cerebrovascular (CVD) disease ; PON activity was correlated with plasma malonyldialdeide (MDA) levels, as markers of lipid peroxidation Materials and Methods: 33 HS (age 7012 yr), 45 CHD (age 818 yr) and 38 CVD (age 8011 yr) patients were studied. Serum PON and plasma MDA levels were measured spectrophotometrically. Statististical analysis was performed by ANOVA univariate for groups comparation and by Pearson r test for values correlation Results: PON activity (mol min-1 ml-1) is higher in HS (0.0750.03) than in CHD (0.0450.03) and CVD (0.0560.03) patients (p<0.05 HS vs. CHD and CVD; ns CHD vs. CVD). MDA (mol/ml) levels are lower in HS (0.0280.023) than in CHD (0.0630.012) and in CVD (0.0560.036) patients (p<0.05 in HS vs. CHD and CVD, ns in CHD vs CVD). Table shows correlation between PON activity and MDA plasma levels in the three studied groups are shown below. rsignificanceHS-.43 p<0.05CHD-.39 p<0.01CVD-.33 p<0.05Conclusions: PON activity is significatively higher in HS than in CHD and CVD patients; whereas there are no significant difference between CHD e CVD patients. In all groups there is statistically significant negative correlation between PON activity and lipid peroxides content (MDA levels) in plasma. Our results suggest a protective role of PON activity against atherogenesis occurring with higher levels of lipoperoxides.

1997 - Distribution of homocysteine in plasma lipoproteins [Abstract in Rivista]
Ventura, Paolo; Panini, Rossana; P., Paolello; G., Scarpetta; Salvioli, Gianfranco
abstract

Aim of study: Plasma Homocysteine (HCY) is free or bound to plasma proteins (PbHCY). A moderate increase of HCY is a risk factor for vascular disease, even though by mechanism not yet known: it may depend on oxidative HCY-induced modification of lipoproteins (LP). The present study aims to evaluate the LP-HCY binding in vivo. Materials and methods: 53 subjects (mean age 7120 yr) were studied. HCY was measured by HPLC method. Plasma lipoprotein fractions were separated by sequential ultracentrifugation. Single fraction purity was tested on agarose gel electrophoresis. HCY bound to single plasma protein fraction was calculated as difference between total and free HCY. Results: Pb-HCY (mean value: 19.4±2 nmol/ml) results on average about 80% of total plasma HCY (mean values 24.2±2.5 nmol/ml). Distribution (absolute and percentage mean values) of Pb-HCY (nmol/ml) among the different fractions and single fraction HCY/protein ratio (nmol of HCY/mg of protein) are shown in the table. FractionsPb-HCY % of Pb-HCYHCY/protein ratio VLDL1 ± 0.65.10.76 ± 0.4LDL1.5 ± 0.57.70.52 ± 0.3HDL1.9 ± 0.59.70.11 ± 0.1LFF*15.1 ± 277.5< 0.1*LFF= Lipoprotein free fraction (density > 1.21 g/ml) Conclusions: A fraction of plasma HCY circulates bound to LP (about 23% of Pb-HCY); if single Pb-HCY fraction values are considered in terms of ratio between Pb-HCY (nmol) and mg of protein, VLDL and LDL fractions show the highest “affinity” for HCY. These results might explain the damaging effect of HCY on the vessel wall.

1996 - Affinità dell'omocisteina per le lipoproteine [Abstract in Atti di Convegno]
Ventura, Paolo; Panini, Rossana; M. C., Pasini; Salvioli, Gianfranco
abstract

Il lavoro affronta in modo approfondito il legame dell'omocisteina alle lipoprpoteine

1996 - Problemi dell'iperomocisteinemia nell'anziano [Relazione in Atti di Convegno]
M. C., Pasini; Ventura, Paolo; Panini, Rossana; Salvioli, Gianfranco
abstract

Il lavoro riguarda i problemi dell'iperomocisteinemia nell'anziano affrontando gli aspetti fisiopatologici e le possibili conseguenzze cliniche