Biomedical subjects

F Ricci

Publications and source records attributed to F Ricci.

At least 19 recordsLinked to original sources

PubMed2007

Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts.

A high incidence of relapses following induction chemotherapy is a major hindrance to patient survival in acute myelogenous leukemia (AML). There is strong evidence that activation of the phosphoinositide 3 kinase (PI3K)/Akt signaling network plays a significant role in rendering AML blasts drug resistant. An important mechanism underlying drug resistance is represented by overexpression of membrane drug transporters such as multidrug resistance-associated protein 1 (MRP1) or 170-kDa P-glycoprotein (P-gp). Here, we present evidence that MRP1, but not P-gp, expression is under the control of the PI3K/Akt axis in AML blasts. We observed a highly significant correlation between levels of phosphorylated Akt and MRP1 expression in AML cells. Furthermore, incubation of AML blasts with wortmannin, a PI3K pharmacological inhibitor, resulted in lower levels of phosphorylated Akt, downregulated MRP1 expression, and decreased Rhodamine 123 extrusion in an in vitro functional dye efflux assay. We also demonstrate that wortmannin-dependent PI3K/Akt inhibition upregulated p53 protein levels in most AML cases, and this correlated with diminished MRP1 expression and enhanced phosphorylation of murine double minute 2 (MDM2). Taken together, these data suggest that PI3K/Akt activation may lead to the development of chemoresistance in AML blasts through a mechanism involving a p53-dependent suppression of MRP1 expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

The "in situ" expression of human leukocyte antigen class I antigens is not altered by cryopreservation in human arterial allografts.

This study was aimed to establish whether the cryopreservation procedure we currently use in clinics can modify arterial homograft antigenicity. To this purpose, we performed an immunohistochemical study on fresh and cryopreserved human arterial homografts to visualize the expression of HLA class I heavy and light chains "in situ" by using the HC-10 and Namb-1 monoclonal antibodies. Human femoral arteries and thoracic aortas were harvested from 18 heart-beating donors and sampled before and after cryopreservation. Arterial segments were frozen in liquid nitrogen vapors in a controlled rate freezing system. After thawing, samples were processed for routine immunohistochemistry. To standardize immunostaining, flow-cytometry indirect immunofluorescence analysis was performed on HUVEC; immunohistochemistry of human ovarian cortical vessels was performed as an additional positive control. Negative controls were performed by omitting tissue incubation with primary antibodies. HLA-class I antigens were markedly expressed by endothelial cells lining surface intima and adventitial vasa vasorum; a moderate expression was found in medial smooth muscle cells. Except for the surface unreactivity caused by loss of endothelium, results from cryopreserved arterial allografts were strictly comparable to those observed in fresh, unfrozen tissues. These results support the view that cryopreserved arterial allografts are immunogenic as their fresh counterparts; apart from smooth muscle cells which retained a moderate expression of HLA class I antigens following cryopreservation, our study suggests that the highly HC-10 positive endothelial cells we found to line the rich adventitial network of vasa vasorum are expected to be one of the major targets of the serological response in the recipient.

Adult↗

PubMed2006

Stress proteins expression in rat kidney and liver chronically exposed to aluminium sulphate.

Aluminium (Al) is the third most widespread metal in the environment. It is toxic for the brain, bone and haematological system but unfortunately very little data exist for other organs. Stress proteins are induced or enhanced against metal toxicity with an essential role in the recovery of organules and other cellular proteins. This immunohistochemical study was performed to analyze the distribution of three stress proteins (HSP25, HSP72, GRP75) in rat kidney and liver orally exposed to Al sulphate daily for 3 and 6 months. Al-induced alterations were further studied by histopathology (H-E, PAS, Perl's, Masson) and ultrastructural morphometry. In the kidney: HSP25 was enhanced in proximal tubules after 6 months Al-exposure when abnormal brush borders were observed; HSP72 was induced in proximal tubules only after long Al-treatment; GRP75 was raised in midcortical area sometimes within nuclei. Furthermore, lysosomal and lipofuscins densities increased in the juxtamedullary tubules after 3 months Al exposure with respect to controls. In the liver: Perl's-positive deposits and fibrosis became evident after Al treatment. HSP25 was very weak; HSP72 focal in pericentral hepatocytes at 3 months and induced also in Kupffer cells at 6 months; GRP75 diffuse in periportal hepatocytes and non parenchymal cells at 6 months. Prolonged Al exposure stimulated stress proteins strictly organ-dependently in the rat. Their distribution in kidney and liver seems related to cumulative sublethal effects induced by metal and could be a sensitive index of Al susceptibility of these organs.

Aging↗

PubMed2006

Exposure to aluminium changes the NADPH-diaphorase/NPY pattern in the rat cerebral cortex.

Aluminium (Al) impairs the glutamate-nitric oxide-cGMP pathway and reduces the number of nitroxidergic neurons in the rat somatosensory cortex. To understand better the effect of the time of exposure, we monitored the effect of aluminium administration on nitroxidergic neurons, identified by NADPH-diaphorase (NADPH-d) or by nitric oxide synthase (NOS) staining, after 0.5, 1, 2, 3, 6 and 12 months of aluminium administration. Since neuropeptide Y (NPY) is known to be colocalised with nitric oxide synthase in cortical neurons, the aim of this work was to study the effects of Al administration on the cortical expression of NADPH-d, nNOS, and NPY. NADPH-d or NOS positive neurons were found scattered in the cortex where they constituted about 1% of all neurons. Double staining using NADPH-d and NPY showed that almost all nitroxidergic neurons were co-localised with NPY neurons (NADPH-d/NPY double stained neurons) whereas some neurons were stained only with NPY (NPY single stained neurons) ; these were more numerous than NADPH-d/NPY double stained neurons. Al significantly reduced NADPH-d and nNOS positive neurons in the cerebral cortex time dependently, with the greatest effect appearing after 3 months. Also measured was the integrated optical density (IOD) of nNOS positive neurons showing a significant decrease of NOS immunostaining even in the remaining NOS positive neurons. The double staining experiment exhibited a decrease in NADPH-d/NPY double stained neurons with an apparent increase in NPY single stained neurons; these then decreased after 6-12 months. On the whole, the results confirm that Al impairs nitroxidergic pathways time dependently; moreover, the transient increase in NPY single stained neurons from 1 to 3 months suggests that there is an intraneuronal down-regulation of NOS, without affecting neuronal viability. In addition, the decrease in the NPY system found at 6 and 12 months may indicate that Al affected nitroxidergic and NPY systems at different times.

Administration, Oral↗

PubMed2005

Acetylcholinesterase sensor based on screen-printed carbon electrode modified with prussian blue.

Acetylcholinesterase (ChE) sensor based on Prussian blue (PB) modified electrode was developed and tested for the detection of organophosphorus and carbamic pesticides. The signal of the sensor was generated in PB mediated oxidation of thiocholine recorded at +200 mv in DC mode. ChE from electric eel was immobilized by cross-linking with glutaraldehyde in the presence of bovine serum albumin (BSA) on the surface of screen-printed carbon electrode covered with PB and Nafion. The content of the surface layer (specific enzyme activity, Nafion and BSA amounts) was optimized to establish high and reliable response toward the substrate and ChE inhibitors. The ChE/PB sensor makes it possible to detect Aldicarb, Paraoxon and Parathion-Methyl with limits of detection 30, 10 and 5 ppb, respectively (incubation 10 min). The feasibility of practical application of the ChE/PB sensor developed for the monitoring of degradation of the pesticides in wine fermentation was shown. To diminish matrix interferences, the electrolysis of the grape juice with Al anode and evaporation of ethanol were suggested, however the procedures decrease the sensitivity of pesticide detection and stability of the sample tested.

Acetylcholinesterase↗

PubMed2005

Prevalence of blindness and low vision in an Italian population: a comparison with other European studies.

AIM: The scientific literature contains recent data on the prevalence of blindness and low vision for a few European countries, but most of these studies have been focused exclusively on the elderly sector of the populations. The purpose of the present study was to provide age-specific estimates of the prevalence and causes of visual loss in an Italian population aged 40 years and over. METHODS: In total, 847 of the 1,200 citizens >40 years of age (70.6%) in the island community of Ponza underwent complete standardized ophthalmological examinations. Visual acuity (VA) was measured using a standard logarithmic chart. World health organization (WHO) definitions of blindness and low vision were adopted (respectively, VA>1.3 logMAR or a visual field <10 degrees around central fixation, and VA >0.5 to 1.3 logMAR or a visual field <20 degrees around central fixation). Prevalence rates based on presenting VAs were also calculated. RESULTS: The overall best-corrected prevalence rates were 0.6% (presenting, 0.8%) for better eye blindness, 2.1% (presenting, 6.7%) for better eye low vision, 1.8% (presenting, 2.6%) for monocular blindness, 5.0% (presenting, 11.2%) for monocular low vision. Cataract, glaucoma, degenerative myopia, and AMD were the main causes of better eye visual loss. CONCLUSION: Age-specific prevalence rates in Ponza are fairly consistent with those for other European countries with similar socio-economic conditions and public healthcare systems. A substantial percentage of visual losses remains uncorrected despite the availability of potentially curative therapy. Greater emphasis needs to be placed on educating the public regarding the importance of good vision.

Adult↗

PubMed2005

A novel continuous subcutaneous lactate monitoring system.

A novel continuous lactate monitoring system has been developed modifying the GlucoDay portable medical device (A. Menarini Diagnostics), already present in the European market, and used to continuously measure glucose levels. Lactate oxidase based biosensors have been developed immobilising the enzyme on nylon net and placing it on a Pt electrode. The biosensor was connected to the portable device provided with a micro-pump and coupled to a microdialysis system. It is capable to record subcutaneous lactate every 3 min. In vitro analytical results confirmed that the sensors respond linearly in the interval of concentration between 0.1 and 10 mmol/L, covering the whole physiological range. During prolonged monitoring periods, the response of the biosensors remained stable, showing a limited drift of 8%, within 60 h. Stability tests are still on route. However, preliminary results have shown a shelf life of about 10 months. In vivo experiments performed on healthy rabbits have demonstrated the good accuracy and reproducibility of the system. A correlation coefficient equal to 0.9547 (N=80) was found, which represents a good correlation between the GlucoDay and the laboratory reference analyser. A 16 h in vivo monitoring on a healthy volunteer has been also performed.

Animals↗

PubMed2005

Novel planar glucose biosensors for continuous monitoring use.

Novel planar glucose biosensors to be used for continuous monitoring have been developed. The electrodes are produced with the "screen printing" technique, and present a high degree of reproducibility together with a low cost and the possibility of mass production. Prior to enzyme immobilisation, electrodes are chemically modified with ferric hexacyanoferrate (Prussian Blue). This allows the detection of the hydrogen peroxide produced by the enzymatic reaction catalysed by GOD, at low applied potential (ca. 0.0 V versus Ag/AgCl), highly limiting any electrochemical interferences. The layer of Prussian Blue (PB) showed a high stability at the working conditions (pH 7.4) and also after 1 year of storage dry at RT, no loss of activity was observed. The assembled glucose biosensors, showed high sensitivity towards glucose together with a long-term operational and storage stability. In a continuous flow system, with all the analytical parameters optimised, the glucose biosensors detected glucose concentration as low as 0.025 mM with a linear range up to 1.0mM. These probes were also tested over 50-60 h in a continuous flow mode to evaluate their operational stability. A 0.5 mM concentration of glucose was continuously fluxed into a biosensor wall-jet cell and the current due to the hydrogen peroxide reduction was continuously monitored. After 50-60 h, the drift of the signal observed was around 30%. Because of their high stability, these sensors suggest the possibility of using such biosensors, in conjunction with a microdialysis probe, for a continuous monitoring of glucose for clinical purposes.

Biosensing Techniques↗

PubMed2005

Sensor and biosensor preparation, optimisation and applications of Prussian Blue modified electrodes.

Being one of the most commonly used electrochemical mediators for analytical applications, Prussian Blue has found a wide use in the biosensor field during the last years. Its particular characteristic of catalysing hydrogen peroxide reduction has been applied in the construction of a large number of oxidase enzyme-based biosensors for clinical, environmental and food analysis. By modifying an electrode surface with Prussian Blue, it is in fact possible to easily detect hydrogen peroxide at an applied potential around 0.0 V versus Ag/AgCl, thus making possible coupling with oxidase enzymes while also avoiding or reducing electrochemical interferences. Papers dealing with glucose, lactate, cholesterol and galactose biosensors that are based on the use of Prussian Blue have recently appeared in the most important analytical chemistry journals. Another recent trend is the use of a choline probe based on choline oxidase for pesticide determination to exploit the inhibition of acetylcholinesterase by these compounds. In addition, the use of Prussian Blue in the development of biosensors for food analysis has captured the interest of many research groups and led to improved methods for the detection of glutamate, galactose, alcohol, fructosyl amine, formate, lysine and oxalate. This review will focus on the biosensing aspects of Prussian Blue-based sensors giving a general overview of the advantages provided by such mediator as well as its drawbacks. A comprehensive bibliographic reference list is presented together with the most up to date research findings in this field and possible future applications. The commercial potential of sensors based on this mediator will also be discussed.

Biosensing Techniques↗

PubMed2005

Antiapoptotic role of p38 mitogen activated protein kinase in Jurkat T cells and normal human T lymphocytes treated with 8-methoxypsoralen and ultraviolet-A radiation.

A combination of 8-methoxypsoralen and ultraviolet-A radiation (320-400 nm) (PUVA) is used for the treatment of T cell-mediated disorders, including chronic graft-versus-host disease, autoimmune disorders, and cutaneous T-cell lymphomas. The mechanisms of action of this therapy, referred to as extracorporeal phototherapy, have not been fully elucidated. PUVA is known to induce apoptosis in T lymphocytes collected by apheresis, however no information is available concerning the underlying signaling pathways which are activated by PUVA. In this study, we found that PUVA treatment of Jurkat cells and human T lymphocytes up-regulates the p38 MAPK pathway but not the p42/44 MAPK or the SAPK/JNK signaling networks. The use of a pharmacological inhibitor selective for the p38 MAPK pathway, SB203580, allowed us to demonstrate that this network exerts an antiapoptotic effect in PUVA-treated Jurkat cells and T lymphocytes from healthy donors. Moreover, the effect of SB203580 was not due to a down-regulation of the Akt survival pathway which was not activated in response to PUVA. These results may suggest that p38 MAPK-dependent signaling is very important for the regulation of survival genes after exposure to PUVA. Since the therapeutic effect of PUVA seems to depend, at least in part, on apoptosis, further studies on the apoptosis signaling networks activated by this treatment might lead to the use of signal transduction modulators in combination with PUVA, to increase the efficacy of this form of therapy.

Apoptosis↗

PubMed2005

Short- and long-term haematological surveillance of healthy donors of allogeneic peripheral haematopoietic progenitors mobilized with G-CSF: a single institution prospective study.

Healthy allogeneic donors, who were treated with G-CSF and underwent peripheral blood haematopoietic precursor collection at our Institution, were enrolled in a short- and long-term haematological surveillance protocol for a 5--7--year period. To date, 94 donors have been assessed with a mean follow-up of 30 months (4--84); for 30 subjects, the follow-up is >or=48 months. During G-CSF administration, 23/94 donors showed a significant platelet count decrease from the baseline. Pre-apheresis platelet decrement correlated with the total G-CSF dose administered, baseline platelet level and donor age. Normal platelet counts returned within 4--8 months. PMN and/or lymphocyte lower values were observed in 55/94 donors 2 weeks after G-CSF administration, with mean drops from the baseline of 40 and 36% for PMN and lymphocytes, respectively. The PMN decrease correlated inversely with donor age, as younger donors were more affected than older ones, whereas the lymphocyte decrease correlated directly with the total blood volumes processed in the apheresis courses, in particular for donors subjected to large volume leukaphereses. Long-term observation showed moderate neutrophil reduction (25% count drop from the baseline) in four of the 30 donors observed for four years or more. 14 donors showed persistent, slight lymphocytopenia (mean drop of 13%) until the third year, with recovery in the fourth year of follow-up.

Adult↗

PubMed2005

Incidence of visual loss in the Ponza Eye Study, Italy.

AIM: To study the incidence of visual loss over a 12-year period in the survivors of an original cohort aged 40 years or older at baseline. METHODS: Visual acuity (VA) was measured by means of a standardized logMAR chart. World Health Organization definition of blindness and low vision was adopted (respectively, best-corrected VA >1.3 logMAR or a visual field <10 degrees around central fixation, and best-corrected VA >0.5-1.3 logMAR or a visual field <20 degrees around central fixation). Moreover, binocular visual loss incidence (VA>0.5 logMAR) was calculated in a 'healthy' group who had uncorrected VA of 0.0 logMAR or better in both eyes at baseline and absence of eye diseases. RESULTS: Of the 584 eligible survivors, 411 (70.7%) had a 12-year follow-up visit. The overall incidence figures were as follows: best-corrected binocular blindness (0.7%), binocular low vision (3.9%), monocular blindness (2.7%), and monocular low vision (5.0%), respectively. The results for presenting VAs were 1.2, 9.5, 4.2, and 15.3%. Figures for uncorrected, best-corrected, and presenting binocular visual loss incidence in the 'healthy' group were respectively 12.7, 0.9, and 3.7%. CONCLUSION: The discrepancy between the ideal and real situations that emerges from this study has important implications for health-care planning. Over a period of 12 years, a substantial percentage of 'healthy' subjects will have to seek medical care. Incident visual loss was caused mainly by untreated cataract, glaucoma, myopia, and age-related macular degeneration.

Adult↗

PubMed2005

Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine.

The GABAB agonist baclofen (BCF) has recently been reported to block the expression of sensitization to the locomotor effect of amphetamine (AMPH), and to reverse it after repeated administration. The present study was undertaken to investigate whether baclofen could also prevent the development of sensitization to the psychostimulant. Chronic AMPH treatment (1.5 mg/kg i.p. for 10 days) led to an increased locomotor response to AMPH (1.5 mg/kg) when the animals were challenged 3 and 30 days after the end of repeated treatment. Chronic co-administration of BCF (2 mg/kg, i.p.) and AMPH blocked the development of sensitization to the stimulant effect of AMPH. An ancillary experiment excluded that a 'state-dependency' hypothesis could account for the effect of baclofen. Furthermore, a previous repeated treatment with baclofen alone had no influence either on the acute AMPH effect or on the subsequent development of sensitization to AMPH. In conclusion, the results confirm that GABAB receptors play an important role in the acquisition of AMPH behavioural sensitization and further support a potential use of GABAB agonists in the treatment of psychostimulant addiction.

Amphetamine↗

PubMed2005

Febrile nonhaemolytic transfusion reaction caused by antibodies against human platelet antigen 5a.

Anti-human platelet antigens (HPA) alloantibodies are seldom involved in febrile nonhaemolytic reactions (FNHTRs). We describe a case in which anti-HPA-5a alloantibodies are related to an FNHTR. We studied the specificity of the alloantibodies by flow cytometry, ELISA and MACE. Typing of donors and the patient was performed by sequence-specific polymerase chain reaction. The alloantibodies were found reactive with HPA-5a antigens. The patient was HPA-5b/b, whereas the donor of the platelet apheresis involved in the FNHTR was HPA-5a/a. Despite the low frequency of anti-HPA-5a antibodies, they might be responsible for FNHTR.

Adult↗

PubMed2005

Pre-operative assessment of extramural invasion and sphincteral involvement in rectal cancer by magnetic resonance imaging with phased-array coil.

OBJECTIVE: Pre-operative staging of rectal cancer should identify patients with extrarectal spread, who might benefit from pre-operative radiotherapy, and patients with minimal sphincteral involvement, who can avoid permanent colostomy. The aim of this study was to assess the accuracy of Magnetic Resonance Imaging (MRI) to predict tumour stage and sphincter status. PATIENTS AND METHODS: Thirty-three patients with a rectal tumour were pre-operatively assessed by MRI with a phased-array coil. Imaging results were correlated with the final pathological findings. RESULTS: The overall accuracy of pre-operative staging with MRI was 88% (k = 0.75) for extramural tumour invasion and 59% (k = 0.26) for lymph node metastases. MRI correctly evaluated the infiltration of the anal sphincters in 87% of patients (7 of 8 patients with low rectal tumour). CONCLUSION: MRI provides the surgeon with valuable information regarding extramural tumour spread and sphincteral involvement, enabling appropriate selection of patients for pre-operative adjuvant therapy or sphincter-saving surgery.

Adult↗

PubMed2005

Morpho-functional alterations in testicular and nervous cells submitted to modelled microgravity.

Humans, as well as other life forms, have developed on earth under the terrestrial gravitational field. Questions concerning the effect of the gravity vector changes on the animal physiology have begun to emerge only in the last decades. Physiological alterations were observed during space flights, but space-born investigations at cellular levels are still very limited. Earth-bound simulations of low gravity obtained with the 3-dimensional Random Positioning Machine are extensively utilized to explore the effects of microgravity on cell function. After only a few minutes, weightlessness affected the cytoskeleton of lymphocytes, astrocytes, neurons and testicular cells, disorganizing microtubules, intermediate filaments and microfilaments. Cell division was impaired, mitochondria were disrupted and apoptotic phenomena occurred. Expression of proteins involved in transmembrane ion and water transport were also affected. In the Leydig cells the key enzymes (3beta- and 17beta-hydroxysteroid dehydrogenases) leading to testosterone synthesis were depressed. However, after 20 h of clinorotation the cells were able to synthesize heat shock proteins that initiated protection and recovery. The cytoskeleton was again well organized, normal mitosis occurred and the percentage of apoptotic cells returned to the range of 5%, similar to the control cultures. Ion and water transmembrane proteins and steroid dehydrogenases returned to normal levels. Long-term experiments showed that low gravity induced only transient alterations in the cultured cells, which were able to adapt to the gravity vector changes and to regain normal activity. These data may explain the physiological adaptation occurring in astronauts during and after space flights.

Animals↗

PubMed2004

The influence of the Po River discharge on phytoplankton bloom dynamics along the coastline of Pesaro (Italy) in the Adriatic Sea.

In recent years, eutrophic phenomena have frequently been reported in the Italian coastal waters of the northern Adriatic Sea. The aim of the present study was to determine that the phytoplankton blooms occurring along the Italian coastline in the area of Pesaro are caused by the Po River waters. In fact between October and December 2000 the nutrient load flushed into the sea from local rivers is not significant (phosphorus 10 tons and nitrogen 110 tons), instead N and P load from the Po River are: 650 and 8969 tons. The bloom episodes occurred during this period, at which time hypoxia developed on the sea bottom. The phytoplankton cell concentrations were 40.0 x 10(6) cells L(-1), and a significant presence of diatoms was observed. This issue is important in analysing the anthropogenic disturbances and environmental changes. The eutrophic seawater conditions were also analysed using the eutrophic index.

Diatoms↗

PubMed2004

The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine.

Immunotoxins are chimeric proteins consisting of a toxin coupled to an antibody. To date, several clinical trials have been conducted, and some are still ongoing, to evaluate their anti-tumor efficacy. In this view, we chemically constructed an anti-CD20 immunotoxin with the mAb Rituximab and the type 1 ribosome-inactivating protein (RIP) saporin-S6, designed for B cells non-Hodgkin's lymphoma (NHL) therapy. This immunotoxin showed a specific cytotoxicity for the CD20+ cell lines Raji and D430B, evidenced by inhibition of protein synthesis, evaluation of apoptosis and clonogenic assay. Upon conjugation, saporin-S6 increased its toxicity on target cells by at least 2 logs, with IC(50) values of 0.1-0.3 nM. The percentage of AnnexinV+ cells was over 95% in both cell lines treated with 10 nM immunotoxin. A complete elimination of Raji clones was reached with the 10 nM immunotoxin, whereas a mixture of free RIP and mAb gave about 90% of clonogenic growth. Rituximab/saporin-S6, at 10 nM concentration, also induced apoptosis in 80% of lymphoma cells from NHL patients. Moreover, sensitivity of Raji to Rituximab/saporin-S6 was augmented when cells were coincubated with Fludarabine. The synergistic toxic effect of the two drugs led to a total elimination of the neoplastic population.

Antibodies, Monoclonal↗