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A Fioravanti

Publications and source records attributed to A Fioravanti.

At least 19 recordsLinked to original sources
PubMed2005

Fluvastatin synergistically enhances the antiproliferative effect of gemcitabine in human pancreatic cancer MIAPaCa-2 cells.

The new combination between the nucleoside analogue gemcitabine and the cholesterol-lowering drug fluvastatin was investigated in vitro and in vivo on the human pancreatic tumour cell line MIAPaCa-2. The present study demonstrates that fluvastatin inhibits proliferation, induces apoptosis in pancreatic cancer cells harbouring a p21ras mutation at codon 12 and synergistically potentiates the cytotoxic effect of gemcitabine. The pharmacologic activities of fluvastatin are prevented by administration of mevalonic acid, suggesting that the shown inhibition of geranyl-geranylation and farnesylation of cellular proteins, including p21rhoA and p21ras, plays a major role in its anticancer effect. Fluvastatin treatment also indirectly inhibits the phosphorylation of p42ERK2/mitogen-activated protein kinase, the cellular effector of ras and other signal transduction peptides. Moreover, fluvastatin administration significantly increases the expression of the deoxycytidine kinase, the enzyme required for the activation of gemcitabine, and simultaneously reduces the 5'-nucleotidase, responsible for deactivation of gemcitabine, suggesting a possible additional role of these enzymes in the enhanced cytotoxic activity of gemcitabine. Finally, a significant in vivo antitumour effect on MIAPaCa-2 xenografts was observed with the simultaneous combination of fluvastatin and gemcitabine, resulting in an almost complete suppression and a marked delay in relapse of tumour growth. In conclusion, the combination of fluvastatin and gemcitabine is an effective cytotoxic, proapoptotic treatment in vitro and in vivo against MIAPaCa-2 cells by a mechanism of action mediated, at least in part, by the inhibition of p21ras and rhoA prenylation. The obtained experimental findings might constitute the basis for a novel translational research in humans.

5'-Nucleotidase↗
PubMed2005

Effect of hyaluronic acid (MW 500-730 kDa) on proteoglycan and nitric oxide production in human osteoarthritic chondrocyte cultures exposed to hydrostatic pressure.

OBJECTIVE: This study investigated the in vitro effects of hyaluronic acid (HA) of molecular weight (MW) 500-730 kDa on human articular chondrocytes cultivated for 48 h in the presence of interleukin-1beta (IL-1beta) with and without hydrostatic cyclical pressure. DESIGN: The effects of 10 and 100 microg/ml HA with and without IL-1beta were assessed in the culture medium of cells exposed to pressurization cycles in the form of sinusoidal waves (minimum pressure 1MPa, maximum pressure 5MPa) at a frequency of 0.25Hz for 3h, by the immunoenzymatic method on microplates for the quantitative measurement of human proteoglycans (PG) and by the Griess method for nitrites (NO). Morphological analyses were performed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). RESULTS: The presence of IL-1beta determines a significant decrease in PG and a significant increase in NO concentrations measured in the culture medium. When the cells are cultured in the presence of IL-1beta and HA at the two concentrations, a statistically significant restoration of PG and a decrease in NO levels are observed. Under pressurization conditions, we observed that the PG concentration in the medium of cells presented a very significant increase in all the conditions used in the study, except for IL-1beta alone. NO production decreased very significantly in the presence of IL-1beta+HA 10 and IL-1beta+HA 100. The results of metabolic evaluation are confirmed by morphological findings obtained by TEM and SEM. CONCLUSIONS: These in vitro studies confirm both the protective role of HA (MW 500-730 kDa), which counteracts the IL-1beta-induced effects, and the importance of pressure on chondrocyte metabolism and morphology.

Adjuvants, Immunologic↗
PubMed2005

Idarubicin and idarubicinol effects on breast cancer multicellular spheroids.

Despite extensive preclinical evaluation in several experimental models, no studies have determined the effect of idarubicin and its metabolite idarubicinol on multicellular spheroids, a model which mimics the microregions of solid tumors. The principal aim of the present study was to investigate the in vitro cytotoxicity of idarubicin and its metabolite idarubicinol on MCF-7 breast cancer cells growing as monolayers or multicellular spheroids and to evaluate the influence of the length of exposure on the cytotoxic effect of both drugs. Cytoxicity was evaluated on monolayer and spheroid cultures exposed to idarubicin and idarubicinol 0.01-1000 ng/ml for 24 h or treated for 6, 12, 24 and 48 h to 100 ng/ml of both drugs. The IC50 of idarubicin and idarubicinol were 3.3+/-0.4 and 3.6+/-0.7 ng/ml, respectively, on MCF-7 monolayers and 7.9+/-1.1 and 5.3+/-0.7 ng/ml in multicellular spheroids, respectively. The antiproliferative effects of 100 ng/ml idarubicin and idarubicinol on MCF-7 spheroids was characterized by a marked time-dependence, which was less evident on MCF-7 growing as monolayer. In conclusion, the present experimental data demonstrate, for the first time, that idarubicin and idarubicinol have significant cytotoxic activity against multicellular spheroids, comparable to the antiproliferative effects on monolayer cells. In contrast, spheroids displayed substantial resistance after short exposure times that was not present in the two dimensional cultures.

Antibiotics, Antineoplastic↗
PubMed2004

Bobble-head doll syndrome due to a suprasellar arachnoid cyst: endoscopic treatment in two cases.

OBJECT: We report two cases of bobble-head doll syndrome associated with a large suprasellar arachnoid cyst successfully treated with a minimally invasive endoscopic approach. METHODS: The clinical history, surgical treatment and results of two children, a 9-year-old boy and a 1-year-old girl, both presenting the clinical features of the bobble-head doll syndrome, are described. As a first procedure, a ventriculo-cystostomy was endoscopically performed in both patients, obtaining either resolution of the symptoms or notable cyst reduction. In the girl, a re-closure of the stoma, with cyst re-expansion, was observed after 18 months. She then underwent a second procedure, a ventriculo-cysto-cisternostomy, with a good result. After 3 years' follow-up, the neurological condition of both patients remains good with complete resolution of abnormal head movement. CONCLUSION: In our opinion, endoscopic treatment is the procedure of choice for this condition, as it involves few complications and gives good results.

Arachnoid Cysts↗
PubMed2004

Asymptomatic carriage of verocytotoxin-producing Escherichia coli O157 in farm workers in Northern Italy.

Faecal samples from 350 farm workers on 276 dairy farms and 50 abattoir employees from seven different operations were examined for the presence of Verocytotoxin-producing Escherichia coli 0157 (VTEC O157) by an O157-specific enzyme-linked fluorescent assay followed by immunoconcentration. VTEC O157 was isolated from four (1.1%) of the farm workers. A second stool sample was obtained from the positive farm workers as well as from their household contacts. VTEC O157 was isolated from the wife of one of them. The strains from the same household shared the same Verocytotoxin genes profile, phage type and pulsed-field gel electrophoresis pattern. The VTEC O157-positive subjects had neither intestinal symptoms at the moment of sampling nor a history of bloody diarrhoea or renal failure. Our study seems to confirm the hypothesis that farm residents often develop immunity to VTEC O157 infection, possibly due to recurrent exposure to less virulent strains of VTEC.

Abattoirs↗
PubMed2004

Simvastatin reduces MMP-3 level in interleukin 1beta stimulated human chondrocyte culture.

OBJECTIVES: Matrix metalloproteinases (MMPs) produced by chondrocytes play a role in the development of cartilage degradation in joint diseases. Moreover, inhibition of MMP secretion by macrophages accumulating in arteriosclerotic plaques would account for the plaque stabilising activity of statins in cardiovascular patients. Recently, simvastatin has been shown to inhibit both developing and established collagen induced arthritis in a murine model. We thus decided to investigate the effect of simvastatin on the production of MMP-3 from cultured interleukin (IL)1 stimulated human chondrocytes. METHODS: Cells from human cartilage, obtained from eight subjects with osteoarthritis undergoing surgery for total hip prostheses, were cultured in the presence of different concentrations of simvastatin (5, 10, and 50 micromol/l) with and without IL1beta (5 ng/ml). MMP-3 level was measured in the culture medium after 48 h of incubation. RESULTS: IL1beta stimulation of chondrocytes increased MMP-3 concentration in the cultures (from 0.69 (0.09) to 1.94 (0.12) ng/microg protein). Incubation with simvastatin was associated with a dose dependent reduction in MMP-3 increase, both in the presence (-15%, -17%, and -26% with 5, 10, and 50 micromol/l, respectively) and in the absence (-32% with 50 micromol/l) of IL1beta. The inhibiting effect of simvastatin was completely reversed by the addition of mevalonate (100 micromol/l) or farnesol (10 micromol/l). CONCLUSIONS: Our data show that simvastatin, by blocking HMGCoA-reductase and interfering in the prenylation processes, is able to inhibit MMP-3 production from cultured human chondrocytes that have been either unstimulated or stimulated with IL1beta, thus suggesting a possible additional mechanism for statins in counteracting chronic joint disease related cartilage damage.

Aged↗
PubMed2003

Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee.

OBJECTIVE: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index is a tested questionnaire to assess symptoms and physical functional disability in patients with OA of the knee and the hip. We adapted the WOMAC for the Italian language and tested its metric properties in 304 patients with symptomatic OA of the knee. METHODS: Three hundred and four consecutive patients, attending 29 rheumatologic outpatient clinic in northern, central, and southern Italy, were asked to answer two disease-specific questionnaires (WOMAC and Lequesne algofunctional index) and one generic instrument (Medical Outcomes Study SF-36 Health Survey-MOS SF-36). A sample of 258 patients was readministered the WOMAC 7-10 days after the first visit and the structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using intraclass correlation coefficients (ICCs), and construct and discriminant validity using Spearman's correlations, Wilcoxon rank sum test, and Kruskal-Wallis test. RESULTS: All WOMAC subscales (pain, stiffness, and physical function) were internally consistent with Cronbach's coefficient alpha of 0.91, 0.81, and 0.84, respectively. Test-retest reliability was satisfactory with ICCs of 0.86, 0.68, and 0.89, respectively. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, supporting the concepts of convergent construct validity. Very high correlations were also obtained between WOMAC scores and Lequesne OA algofunctional index. WOMAC physical function, but not WOMAC stiffness and pain subscales, was weakly associated with radiological OA severity (P=0.03). Also, WOMAC pain score was inversely correlated (P=0.01) with years of formal education. Examination of discriminant validity showed that the scores on the WOMAC and SF-36 followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. CONCLUSION: The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.

Aged↗
PubMed2003

Sonographic study of calcaneal entheses in erosive osteoarthritis, nodal osteoarthritis, rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: To establish by ultrasonography (US) the frequency of calcaneal entheses involvement in erosive osteoarthritis (EOA), nodal osteoarthritis (NOA), RA and PsA, and to compare these results in order to aid clinicians in the differential diagnosis among these diseases. A comparison between US results and radiography was also made. METHODS: The heels of 56 consecutive outpatients with EOA, 209 with NOA, 158 with RA and 125 with PsA were studied by US and radiography. A control group of 50 subjects was examined by US. RESULTS: US showed no significant difference in inferior calcaneal enthesophytosis among the four diseases. The frequency of posterioinferior enthesophytosis was lower in RA (34%) in comparison with the other diseases (57% in EOA, 47% in NOA, 49% in PsA). Achilles enthesitis was found in 8% of PsA and in 2% of RA. Retrocalcaneal bursitis was found in 18% of RA and in 6% of PsA. Posterior erosions were present in 12% of RA and 5% of PsA. Inferior erosions were present in 6% of RA and in 1% of PsA. Plantar fasciitis was found in 26% of RA, in 37% of PsA, and in 15% of NOA and 12% of EOA. Subcalcaneal panniculitis was observed in 10% of RA and in 1% of PsA. In the control group, only posterioinferior and inferior enthesophytosis (22% and 18% respectively) were found. Kappa statistics show excellent agreement between US and radiography in detecting posterioinferior (kappa = 0.89) and inferior enthesophytosis (kappa = 0.83), and entheseal erosions (kappa = 0.86). CONCLUSIONS: The calcaneal lesions that could be found in EOA are similar to those observed in NOA. The frequency of calcaneal enthesophytosis is similar in EOA, NOA, and PsA, but inflammatory lesions of calcaneal entheses and of the adjacent bursae are more frequent in RA and in PsA. In terms of heel involvement, EOA seems to be similar to NOA. US shows an excellent concordance with radiography in detecting entheseal cortical bone abnormalities.

Adult↗
PubMed2003

Clinical efficacy and cost-effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project.

AIM: The "Naiade" Project was carried out in execution of the Decree of December 1994 by the Italian Ministry of Health, with the objective of defining the therapeutic role of spa therapy in the various sectors of medicine. In this study the authors refer to the results obtained in osteoarthritis (OA). METHODS: The OA study included the observation of patients for 2 consecutive years, with the compilation of a series of clinical and socio-economic data. The initial sample was of 11437 patients suffering from primary and secondary OA, and in the 2(nd) year the total number of assessable patients was 6111 (53.4%). All patients underwent 1 annual cycle of balneotherapy and mud packs therapy for 2 consecutive years. The thermal treatments were carried out in 98 Italian spas with sulphurous water, sodium chloride-bromide-iodide water, sulphate water, and bicarbonate water. Analysis of the data collected confirmed the clinical efficacy of spa treatments for OA, particularly for localisations in the cervical and lumbar spine. The benefits of these treatments and the persistence of the therapeutic effects over time were clearly demonstrated by the collection of some socio-economic indicators relative to the year before each cycle of thermal therapy. RESULTS: In fact, the analysis of these indicators showed a significant reduction in recourse to additional treatments (hospital admissions, physical and pharmacological therapies) and absence from work. CONCLUSION: The obtained data was particularly interesting for the number of samples examined, the follow-up over a period of 2 years, and the collection of clinical and, especially, socio-economic parameters. The results of the Naiade Project confirmed the value of spa therapies in the treatment of OA.

Balneology↗
PubMed2001

Capillaroscopic findings in erosive and nodal osteoarthritis of the hands.

Osteoarthritis of the hands is a very common disease that can present a large number of different clinic pictures, such as nodal (NOA) and erosive (EOA) forms. EOA in particular is a rare subset of hand osteoarthritis characterised by faster destructive changes involving the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints. In the early stages of the disease the differential diagnosis from other arthritides, such as rheumatoid or seronegative arthritis, may pose a challenge. Nailfold capillaroscopy is a non-invasive technique that allows the in vivo study of the microvascular environment. In this study the authors have compared the capillaroscopic microvascular patterns in 56 patients with EOA, in 46 patients with NOA, and in 50 normal controls. The abnormalities that could be found in EOA patients were similar to those described by some authors in patients with psoriatic arthritis. The authors discuss the significance of these abnormalities and the possible relationship between EOA and psoriatic arthritis.

Aged↗
PubMed2001

[Articular involvement in the course of primary hypogammaglobulinemia].

The Authors describe the main features of the most common forms of primary hypogammaglobulinaemia (PH) focusing on the articular involvement. Patients with Bruton's agammaglobulinemia (BA) and common variable immune deficiency (CVID) are predisposed to develop septic arthritis (including arthritis due to atypical microorganisms such as mycoplasma), arthralgia and symmetrical (usually non-erosive) polyarthritis. In BA and CVID complicated by recurrent infections, amyloidosis, which may be itself a cause of arthropathy, can occur. In addition, patients with CVID and selective IgA deficiency show an increased prevalence of juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and primary biliary cirrhosis, while patients with selective IgA deficiency are prone to developing seronegative spondylarthropathies, including ankylosing spondylitis. The mainstay of treatment for BA and CVID is replacement therapy with human immunoglobulins. Septic arthritis should be promptly treated with antibiotics, whereas other types of arthritis usually respond well to non-steroidal antiinflammatory medications. In contrast, the second line agents commonly used to treat rheumatoid arthritis do not appear to be beneficial in patients with PH-associated arthritis.

Agammaglobulinemia↗
PubMed2001

[Rheumatoid arthritis. Recent findings and new pathogenic concepts].

The etiology of rheumatoid arthritis (RA) is still unknown, and many uncertainties regarding its pathogenetic mechanisms persist. During the past decade, various hypotheses have been advanced, yet none of these has been able to explain the complexity of the disease. In light of the most recent research, a sub-division of the pathogenesis of RA, in four phases, has been proposed. The first phase is that of tissue damage, induced by unknown infective or traumatic factors with the liberation of possible arthrogenic antigens that are presented to the immune system. In the second phase the immune and inflammatory mechanisms should begin to function and, if they are effective, they should determine the resolution of the process; the failure of these mechanisms would create a further amplification of the immuno-inflammation response (the third phase). The fourth phase would then be a chronic inflammatory with progressive articular destruction, as well as anatomical and functional damage. This evolution, in response to common pathogenic agents, is dependent upon a particular hereditary genetic asset (not only the HLA system) that is able to control the production of citokines and also upon the neuroendocrine system. The final outcome of the process is, therefore, determinated by multiple interference between the inflammatory/immune system and other systems that also interact with it (the integrated pathogenetic hypothesis). This hypothesis reflects the complexity of the immune/inflammatory system that must be considered to be an acting part of an integrated network of diverse systems. A better knowledge of these interactions needed for the discovery of potential new therapies for RA.

Arthritis, Rheumatoid↗
PubMed2000

N-acetylcysteine increases apoptosis induced by H(2)O(2) and mo-antiFas triggering in a 3DO hybridoma cell line.

N-Acetylcysteine (NAC) has been used as an antioxidant to prevent apoptosis triggered by different stimuli in different cell types. It is common opinion that cellular redox, which is largely determined by the ratio of oxidized and reduced glutathione (GSH), plays a significant role in the propensity of cells to undergo apoptosis. However, there are also contrasting opinions stating that intracellular GSH depletion or supplemented GSH alone are not sufficient to lead cells to apoptosis or conversely protect them. Unexpectedly, this study shows that NAC, even if it maintains the peculiar characteristics of an agent capable of reducing cell proliferation and increasing intracellular GSH content, increases apoptosis induced by H(2)O(2) treatment and mo-antiFas triggering in a 3DO cell line. We found that 24 h of NAC pre-treatment can shift cellular death from necrotic to apoptotic and determine an early expression of FasL in a 3DO cell line treated with H(2)O(2).

Acetylcysteine↗
PubMed2000

Effects of chondroitin sulfate and interleukin-1beta on human chondrocyte cultures exposed to pressurization: a biochemical and morphological study.

Objective This study investigated the in vitro effects of chondroitin sulfate (CS) on human articular chondrocytes cultivated in the presence or in the absence of interleukin-1beta (IL-1beta) during 10 days of culture with and without pressurization cycles. Design The effects of CS (10 and 100 microg/ml) with and without IL-1beta were assessed in the culture medium of cells exposed to pressurization cycles in the form of synusoidal waves (minimum pressure 1 Mpa, maximum pressure 5 Mpa) and a frequency of 0.25 Hz for 3 h by immunoenzymatic method on microplates for the quantitative measurement of human proteoglycans (PG). On the 4th and 10th day of culture the cells were used for morphological analysis by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results The presence of IL-1beta determines a significant decrease in PG concentration measured in the culture medium. When the cells are cultured in the presence of IL-1beta and CS, a statistically significant restoration of PG levels is observed. Under pressurization conditions, we observed that PG concentration in the medium of cells presents a significant increase at baseline conditions, in the presence of IL-1beta+CS10 and IL-1beta+CS100, but not with IL-1beta alone. The results concerning metabolic evaluation are confirmed by the morphologic findings obtained by TEM and SEM. Conclusions These in vitro studies confirm the protective role of CS, which counteracts the IL-1beta induced effects and they confirm the importance of pressure on chondrocyte metabolism and morphology.

Aged↗
PubMed1999

Cytogenetic investigation of chordomas of the skull.

We report the first cytogenetic investigation of cranial chordoma. Three cranial chordomas were examined, two of which could be further histopathologically classified as chondroid chordomas. In addition, we have included a case of chordoma of a cervical vertebra to compare the cytogenetic abnormalities. Diagnosis was made at histological and immunohistochemical levels. The three cases of cranial chordoma showed a normal karyotype, while one vertebra showed 46,XY,t(6;11)(q12;q23). Chordomas, particularly those containing cartilage, have to be distinguished from chondrosarcomas of the skull base. Such a distinction is normally based on expression of epithelial markers which usually are lacking in chondrosarcoma. Cytogenetic investigation may eventually prove to be useful in the distinction of the two lesions, if chromosome anomalies are consistently absent in chordoma, although some chondrosarcomas may also present a normal karyotype. Such a distinction has clinical implications because chondroid chordomas show better survival, whereas chondrosarcomas show a propensity to infiltrate the surrounding tissues.

Adult↗