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Biomedical subjects

M Vincenti

Publications and source records attributed to M Vincenti.

At least 19 recordsLinked to original sources
PubMed2006

RelA is required for IL-1beta stimulation of Matrix Metalloproteinase-1 expression in chondrocytes.

OBJECTIVE: Interleukin-1beta (IL-1beta) stimulates collagenase-1 (Matrix Metalloproteinase-1 (MMP-1)) expression in articular chondrocytes, leading to cleavage of type II collagen and irreversible cartilage degradation. The nuclear factor-kappa B (NF-kappaB) pathway is potently activated in IL-1beta-stimulated cells and has been implicated as an intermediate in MMP-1 gene expression. However, the roles of individual NF-kappaB family members during IL-1beta-induced MMP-1 gene expression have not been defined. RESULTS: To address the relationship between the NF-kappaB pathway and MMP-1 gene activation in chondrocytes, primary cultured human articular chondrocyte cultures (HAC) and SW-1353 cells were stimulated with IL-1beta over a 24-h time course and MMP-1, NF-kappaB1, NF-kappaB2 and RelA gene expression was assayed. IL-1beta-induced MMP-1 expression was comparable in HAC and SW-1353 cells both temporally and quantitatively. MMP-1 gene expression was mirrored by increases in NF-kappaB gene expression, and inhibition of NF-kappaB nuclear translocation with dominant-negative IkappaBalpha reduced IL-1beta-dependent MMP-1 gene expression. IL-1beta activated the NF-kappaB pathway in chondrocytes, both through phosphorylation and transient degradation of IkappaBalpha, as well as through sustained phosphorylation of RelA. Small inhibitory RNAs (siRNA) specific for RelA resulted in significant reduction of MMP-1 mRNA, whereas siRNA for NF-kappaB1 and NF-kappaB2 augmented IL-1beta-induced MMP-1 expression. CONCLUSIONS: Our data demonstrate that IL-1beta activation of the NF-kappaB pathway is required for IL-1beta induction of MMP-1 in chondrocytes and that RelA can work independently of NF-kappaB1 or NF-kappaB2 to activate this gene expression program.

Aggrecans↗
PubMed2006

Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis.

An analytical procedure was developed for the fast screening of 16 diuretics (acetazolamide, althiazide, amiloride, bendroflumethiazide, bumetanide, canrenoic acid, chlorthalidone, chlorthiazide, clopamide, ethacrynic acid, furosemide, hydrochlorthiazide, hydroflumethiazide, indapamide, triamterene, trichlormethiazide) and a masking agent (probenecid) in human urine. The whole method involves three analytical steps, including (1) liquid/liquid extraction of the analytes from the matrix, (2) their reaction with methyl iodide at 70 degrees C for 2 h to form methyl derivatives, (3) analysis of the resulting mixture by fast gas chromatography/electron impact mass spectrometry (fast GC/EI-MS). The analytical method was validated by determining selectivity, linearity, accuracy, intra and inter assay precision, extraction efficiencies and signal to noise ratio (S/N) at the lowest calibration level (LCL) for all candidate analytes. The analytical performances of three extraction procedures and five combination of derivatization parameters were compared in order to probe the conditions for speeding up the sample preparation step. Limits of detection (LOD) were evaluated in both EI-MS and ECNI-MS (electron capture negative ionization mass spectrometry) modes, indicating better sensitivity for most of the analytes using the latter ionization technique. The use of short columns and high carrier gas velocity in fast GC/MS produced efficient separation of the analytes in less than 4 min, resulting in a drastic reduction of the analysis time, while a resolution comparable to that obtained from classic GC conditions is maintained. Fast quadrupole MS electronics allows high scan rates and effective data acquisition both in scan and selected ion monitoring modes.

Diuretics↗
PubMed2001

Diastereoselective formation of host-guest complexes between a series of phosphate-bridged cavitands and alkyl- and arylammonium ions studied by liquid secondary-ion mass spectrometry.

The reactions occurring between a new class of cavitands that carry up to four dioxaphosphocin binding units and alkyl- and arylammonium ions was investigated by liquid secondary-ion mass spectrometry (LSIMS). As the cavitands existed as distinct diastereomers with different spatial orientation of their binding groups, these geometrical differences proved to have a dramatic influence on their chemical properties, including their ability to form host-guest complexes. In practice, only the cavitands that carry at least three P=O groups oriented toward the inside of the cavity were demonstrated to be strong ligands toward organic ammonium ions, whereas those with only two converging binding groups (either adjacent or opposite in the cavitand structure) still formed host-guest complexes, but they were much weaker. Adjacent binding sites proved to be more effective in interacting with organic ammonium ions than those lying in opposite positions. The isomers with no converging P=O groups did not act as molecular receptors. Even the isomer with one group oriented toward the inside of the cavity did not form host-guest complexes, as the absence of synergistic hydrogen bonding made the interaction from inside the cavity energetically equivalent (or even less favorable) to the outside binding. The presence in the cavitand structure of substituents with an electron-donating character proved to increase the proton affinity of the P=O binding groups and, consequently, their binding energy. The strong proton affinity of the cavitands led to the formation of stable host-guest complexes, as confirmed by the collisionally activated dissociation experiments. Effects of steric hindrance were weak, at least for the cavitands with three converging P=O groups. This confirmed that the cavity has a wide and readily accessible opening. The relative complexation constants were measured for the various guests, yielding scales of relative affinity toward each cavitand. These relative constants may represent thermodynamic values referred to the matrix used in LSIMS experiments, namely 3-nitrobenzyl alcohol (NBA), provided that kinetically controlled selvedge processes are negligible. Absolute complexation constants could not be obtained on account of the unknown pH and the protonation constant in the NBA matrix.

Journal Article↗
PubMed2001

Formation of nitrophenols upon UV irradiation of phenol and nitrate in aqueous solutions and in TiO2 aqueous suspensions.

The formation of nitrophenols was studied as a consequence of ultra violet (UV) irradiation of aqueous solutions of phenol and nitrate in the range of pH 1-12. The study was performed both in homogeneous phase and in the presence of water-suspended TiO2. The effects of pH, dissolved oxygen and 2-propanol as .OH scavenger have been evaluated. A reaction mechanism is proposed, based on the experimental results.

Free Radical Scavengers↗
PubMed2001

Advanced ovarian cancer in the elderly: results of consecutive trials with cisplatin-based chemotherapy.

From 1982 through 1996, 547 untreated advanced ovarian cancer patients were entered onto Gruppo Oncologico Nord-Ovest (GONO) consecutive randomized trials including cisplatin-based chemotherapy. End points of analysis included the influence of age on prognosis, toxicity, clinical/surgical response rates, progression-free survival and survival. Of the entire study group, 116 patients were 65 years of age or older at diagnosis. WHO main toxicity (any grade) consisted of: emesis (93% of patients), myelotoxicity (leukopenia in 52%, anemia in 51% and thrombocytopenia in 17% of patients), nephrotoxicity in 13% of patients and neurotoxicity in 10% of patients. No significant difference in toxicity was evident between patients > or = or <65 years. Refusal of CT and early (< or =2 courses) interruption of CT due to toxicity were more frequent in elderly patients (3.4 vs. 1.4%; 3.4 vs. 0.7%, respectively). After a median follow-up of 71 months no difference was observed in survival and progression-free survival between younger and older patients. Cox multiple regression analysis of the entire study population demonstrated that age >65 years per se was not a negative prognostic factor.

Adult↗
PubMed1999

Formation of N-(2-hydroxyethyl)valine due to exposure to ethylene oxide via tobacco smoke: A risk factor for onset of cancer.

Human exposure to ethylene oxide (EtO) occurs mainly through inhalation of occupational polluted air and tobacco smoke. EtO is able to react with DNA and proteins producing some molecular adducts. One of these, resulting from reaction between EtO and valine in hemoglobin, is N-(2-hydroxyethyl) valine (HOEtVal). This adduct represents a biological effective dose marker, the level of which correlates linearly with the alkylating activity occurring in DNA. The aim of the present study was to measure HOEtVal in 146 urbanized adult and healthy subjects, nonoccupationally exposed to EtO, and to correlate it with smoke habits. HOEtVal showed a direct positive relationship to tobacco smoke exposure quantified by questionnaire, urinary cotinine (r=0.64509), and the number of cigarettes (r=0. 6308) actively or passively smoked. Results relative to HOEtVal and urinary cotinine in adults distinguish well between active and passive smokers but do not allow distinguishment between passive smokers and nonsmokers. Nevertheless, several authors demonstrated a very good capacity of cotinine to discriminate inside groups of adolescents passive smokers. Therefore, the future objective of the present study is a closer inspection of the two biomarkers with respect to passive exposure to tobacco smoke considering a large group of adolescents. Finally, the correlation between urinary cotinine and HOEtVal increases knowledge about early steps of the carcinogenic process due to active exposure to tobacco smoke.

Adolescent↗
PubMed1999

The effects of mefloquine treatment in pregnancy.

We investigated the relationship between mefloquine antimalarial treatment and the outcome of pregnancy in Karen women living in an area along the western border of Thailand where multidrug-resistant Plasmodium falciparum infections are common. Of 3,587 pregnancies investigated, 208 (5.8%) were exposed to mefloquine, 656 (18.3%) to quinine only, and 909 (25.3%) to other antimalarials, and 2,470 (68.9%) had no documented malaria. There were 61 stillbirths and 313 abortions. Women who received mefloquine treatment during but not before pregnancy had a significantly greater risk of stillbirth than did women treated with quinine alone (odds ratio [OR], 4.72; 95% confidence interval [CI], 1.7-12.7), women exposed to other treatments (OR, 5.10; 95% CI, 2-13.1), and women who had no malaria (OR, 3.50; 95% CI, 1.6-7.6) (P < .01). This association remained after adjustment for all identified confounding factors. Mefloquine was not associated with abortion, low birth weight, neurological retardation, or congenital malformations. Mefloquine treatment during pregnancy was associated with an increased risk of stillbirth.

Abnormalities, Drug-Induced↗
PubMed1999

Relationship between circadian rhythm of vinorelbine toxicity and efficacy in P388-bearing mice.

The relevance of chronopharmacology for improving tolerability and antitumor efficacy of the antimitotic drug vinorelbine was investigated in female B6D2F1 mice standardized with 12 h of light and 12 h of darkness. A single i.v. vinorelbine dose (26 mg/kg) was given to 279 mice at 7, 11, 19, or 23 hours after light onset (HALO). Bone marrow necrosis and leukopenia were nearly twice as large in the mice injected at 7 HALO as compared with those treated at 19 HALO (ANOVA: p <.001 and p = 0.004, respectively). The relevance of vinorelbine dosing time for antitumor efficacy was assessed in 672 P388 leukemia-bearing mice. Vinorelbine was injected as a single dose (20, 24, 26, or 30 mg/kg) or weekly (20, 24, 26, or 28 mg/kg/injection x 3) at one of six circadian times, 4 h apart. A significant correlation between single dose and median survival time was limited to vinorelbine administration at 19 or 23 HALO. An increase in the vinorelbine weekly dose shortened median survival time in the mice treated at 7 HALO (20 mg/kg: 29 days; 24 mg/kg: 17 days; and 26 mg/kg: 6 days) but significantly improved it in those treated at 19 HALO (20 mg/kg: 28.5 days; 24 mg/kg: 32 days; and 26 mg/kg: 36 days). The study demonstrates the circadian rhythm dependence of maximum tolerated dose and the need to deliver maximum tolerated dose at the least toxic time to achieve survival improvement through chronotherapy. This may be obtained with an evening administration of vinorelbine in cancer patients.

Animals↗
PubMed1998

Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy.

To evaluate toxicity and efficacy of chemotherapy in elderly patients (> or = 65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m2 i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m bolus plus leucovorin (LV) 500 mg/m2 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m2 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11-29) of elderly patients (15/82) in comparison with 23% (95% CL 17-32) of patients < 65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates.

Administration, Oral↗
PubMed1997

Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion.

The aim of this study was to examine in detail the incidence and severity of hand-foot syndrome in advanced colorectal cancer patients receiving 5-fluorouracil (5-FU) and leucovorin (L-LV) chemotherapy. 70 advanced colorectal cancer patients (pts) were given weekly 24 h continuous 5-FU (2600 mg/m2) infusion plus L-LV (100 mg/m2 i.v., 50 mg orally). The toxicity, in particular HFS, was analysed, correlated to the main pts characteristics and compared to the other observed side-effects. HFS occurred in 36/70 pts (51%): grade 1 in 16 pts, grade 2 in 16 pts, grade 3 in 3 pts and grade 4 in 1 pt. It occurred after a median number of nine courses. In one case, chemotherapy was interrupted for this toxicity, and in another 5 pts drug reduction and/or treatment delay were undertaken. Changes in the therapeutic programme because of diarrhoea or mucositis were more frequent, even though these toxicities were generally mild in our series of pts. HFS was significantly correlated to previous exposure to chemotherapy (P = 0.00003). HFS was a frequent side-effect of high-dose, short-term continuous 5-FU infusion, but the impact on quality of life of pts and on the correct delivery of the planned chemotherapy was limited.

Adult↗
PubMed1996

Abnormally large von Willebrand factor multimers in Henoch-Schönlein purpura.

Allergic vasculitis phenomena seem to be involved in Henoch-Schönlein purpura (HSP). Elevated plasma levels of von Willebrand factor (vWf) are a well recognized feature of vasculitis and have been taken as an indication of in vivo endothelial cell damage. Plasma factor VIII:C and vWf levels and vWf multimeric pattern were studied in 8 patients with HSP, during active disease and twice during the remission (3 and 9 months later). Plasma vWf multimeric composition was evaluated using low resolution gels which better resolve large vWf multimers. During active disease plasma factor VIII:C, vWf:Ag, and vWf:RCoF were normal in 5% of patients and increased in three, but in each patient, platelets appeared to aggregate at doses of ristocetin lower than in normals. Furthermore, all patients demonstrated the presence of abnormally large vWf multimers usually found only in platelets and endothelial cells. Three and 9 months later, during remission, in spite of the normalization of factor VIII:C and vWf levels, the abnormal multimers were still detectable, as well as hyper-responsiveness to ristocetin. These findings confirm that damage and/or perturbation of endothelial cells is associated with HSP. Moreover, the persistence of abnormality in the vWf multimeric pattern, when the disease is inactive, suggests that the mechanisms involved operate through the entire clinical course.

Adolescent↗
PubMed1995

Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: a phase I study.

BACKGROUND: There is evidence that continuous infusion allows the delivery of higher doses of a drug while reducing the incidence of neurologic and renal toxicity. To verify prior to phase II testing the feasibility of ambulatory treatment with high-dose ifosfamide/mesna by continuous infusion in adult solid tumours, the maximum tolerated dose (MTD) and the non-haematological dose-limiting toxicities for the achievement of 2 courses of therapy were determined. PATIENTS AND METHODS: Thirty-two patients with advanced solid tumours were given continuous-infusion ifosfamide, from 9 to 16 g/m2, over 4 consecutive days, with equidose mesna uroprotection and granulocyte colony-stimulating-factor support; courses were repeated every 3 weeks. Total dose/course was escalated by 1 g/m2, in cohorts of 3 to 5 patients until the MTD was determined. RESULTS: At 16 g/m2, the dose-limiting toxicity was renal, with 2 of the 5 patients treated developing renal failure. Haematological toxicity was dose-related and significant at higher dosages, but generally surmountable. Ifosfamide at 15 g/m2/course with mesna uroprotection was identified as the MTD. CONCLUSIONS: The present study shows that high-dose continuous-infusion ifosfamide, administered by portable infusion pumps, is feasible in an ambulatory regimen, with acceptable non-haematological toxicity and good patient compliance.

Adult↗
PubMed1994

Abnormal erythrocyte and renal frusemide-sensitive sodium transport in idiopathic calcium nephrolithiasis.

1. Anomalous transmembrane anion transport has been observed in erythrocytes of patients with idiopathic calcium nephrolithiasis. 2. To verify whether cation transport is also abnormal, we investigated the frusemide-sensitive Na+ efflux from Na(+)-loaded erythrocytes and the natriuretic response to acute intravenous frusemide administration in calcium oxalate renal stone formers. 3. Frusemide administration induced a statistically significant smaller increase in the fractional excretion of Na+ in patients than in control subjects. Abnormal kinetic properties of erythrocyte Na(+)-K(+)-2Cl- cotransport were observed in approximately 60% of stone formers. The Km for Na+ of Na(+)-K(+)-2Cl- co-transport correlated with urinary Ca2+ excretion. 4. The abnormal kinetic properties of Na(+)-K(+)-2Cl- co-transport may be relevant for stone formation, hampering renal Ca2+ reabsorption in the distal nephron and determining critical physicochemical conditions for calcium/oxalate crystallization.

Adult↗
PubMed1994

Efficacy of recombinant alpha-interferon 2a and 13-cis-retinoic acid in the treatment of squamous cell carcinoma.

BACKGROUND: Recent in vitro and in vivo studies hypothesize a synergistic effect of 13-cis-Retinoic Acid (13cRA) and recombinant alpha-IFN 2a (alpha-IFN) in the treatment of squamous cell carcinoma (SqCC). PATIENTS AND METHODS: 35 patients with SqCC in several sites were treated with 13cRA (0.6-1 mg/kg/day) combined with alpha-IFN (6 x 10(6) I.U./day), continuously for 3 months. RESULTS: We observed an objective response in 41% of cases (13/32 evaluable patients) with 5 complete and 8 partial responses. Toxicity was mild and always rapidly reversible, with no haematological side effects. CONCLUSIONS: These preliminary data confirm the feasibility and effectiveness of the combination of 13cRA and alpha-IFN in the therapy of SqCC, also in pre-treated patients, with acceptable toxicity and good compliance.

Adult↗
PubMed1993

Determination of plasma tocopherols by high-performance liquid chromatography with coulometric detection.

An HPLC procedure has been developed for tocopherol determination with coulometric detection in human serum samples. Eluent optimization and foreign peak identification (bilirubin) by mass spectrometry are described. An extraction procedure gave yields around 98% with 1.3% coefficient of variation, and the calibration ranged from 0.1 to 200 mg/l with a correlation coefficient of 0.999. The detection limit achieved for vitamin E was 60 pg (3 ng/ml).

Artifacts↗
PubMed1993

Abnormal urate transport in erythrocytes of patients with idiopathic calcium nephrolithiasis: a possible link with hyperuricosuria.

1. The demonstration of an inheritable anomaly of erythrocyte oxalate transport in 'primary' calcium nephrolithiasis suggested that this disease might be a generalized metabolic disorder characterized by a defect in cellular anion transport. 2. To determine whether this anomaly is restricted to oxalate alone, we studied erythrocyte transmembrane urate self-exchange in calcium-oxalate renal stone formers in whom urinary excretion of uric acid is frequently increased. 3. Abnormal urate self-exchange was found in 30% of the patients. The urate self-exchange rate constant was correlated with 24 h urinary excretion of uric acid; the erythrocyte anomaly was also associated with the frequency of hyperuricosuria and a more intense disease activity. Transmembrane urate self-exchange was inhibited by stilbene and heparan sulphate. Morphazinamide administration did not reduce urinary urate excretion in patients with abnormal urate erythrocyte self-exchange. 4. These findings suggest that hyperuricosuria during calcium-oxalate renal stone disease might be due to a cellular defect in urate transport, and further support the hypothesis that idiopathic nephrolithiasis is a metabolic disorder characterized by a defect in cellular anion transport.

Biological Transport↗