Journal of Drug Delivery Science and Technology, 2015
ABSTRACT The purpose of this study was to demonstrate that nanoparticles (NP), obtained by ionotr... more ABSTRACT The purpose of this study was to demonstrate that nanoparticles (NP), obtained by ionotropic crosslinking of reduced-MW chitosan (rCh) derivatives with reduced-MW hyaluronan (rHA), could be profitable vehicles for oral administration of beneficial doses of antioxidant constituents of red grape seeds extracts (GSE). NP have previously shown aptitude for internalisation by endothelial progenitor cells. Here they were seen by a fluorescence microscope migrating across excised rat intestine from mucosal to serosal side and permeating from the donor to the acceptor compartment of an Ussing chamber while carrying significant (15-20%) steadily associated fractions of initial antioxidant load. Freshly prepared NP dispersions were stabilised by lyophilisation. The NP dispersions were regenerated from the lyophilised products by adding water under gentle stirring. Lyophilisation-regeneration caused a significant NP size increase yet particles did not grow beyond the upper size limit of particles able to cross the intestinal barrier (500 nm).
Phlebology / Venous Forum of the Royal Society of Medicine, 2011
Visual and neurological disturbances have always been reported following liquid sclerotherapy (LS... more Visual and neurological disturbances have always been reported following liquid sclerotherapy (LS) for venous insufficiency. In 1993 Cabrera introduced foam sclerotherapy (FS) using a detergent sclerosant as Lauromacrogol 400 or sodium tetradecyl sulphate. Several authors have reported with FS an increased incidence of such transient visual disturbances and neurological complications. This has been associated with gas or air used to generate the sclerosing foam. The frequent association of the presence of a patent foramen ovale, a common condition in normal population, and such complications has led several authors to consider neurological and visual disturbances as paradoxical gas embolism. We are introducing a new pathogenetic hypothesis for sclerotherapy complications. Medical literature shows evidence of a clear relationship among cerebral and retinal vasospasm, migraine and intimal irritation. We think that the irritating sclerosant agent may stimulate a significant release of ...
International Journal of Biological Macromolecules, 2015
Different strategies have been developed to make the wound-healing process faster and less painfu... more Different strategies have been developed to make the wound-healing process faster and less painful. Recently, numerous studies demonstrated the ability of chitosan to accelerate wound healing. Aim of the present study has been to evaluate the effect of different chitosan derivatives to improve wound healing process. Quaternary ammonium-chitosan conjugates with low or high molecular weight (MW) and their thiolated derivatives effect were studied on human skin fibroblasts in terms of viability and migration (scratch wound assay). Results were compared both with basal medium (untreated cells) and with a positive control (chitosan chlorhydrate). After 24h both high and low MW chitosan derivatives were non-toxic up to 10μg/ml. The concentration of 10μg/ml was used for wound healing experiments. High-MW quaternary ammonium-chitosan conjugates bearing thiol groups on their chains were more effective in promoting cell migration than the non-thiolated conjugates and the chitosan chlorhydrate. Moreover, they significantly improve wound healing process compared to untreated cells. According to the present in vitro preliminary results, high MW thiolated quaternary ammonium-chitosan conjugates can be considered good candidates for the management of wounds.
The foam sclerotherapy technique has become one of the most commonly used treatments for superfic... more The foam sclerotherapy technique has become one of the most commonly used treatments for superficial venous insufficiency. Despite excellent results, few visual/neurologic disturbances have been recently reported; their pathogenesis is still debated but a correlation with endothelin-1 (ET-1) release from the treated vein has been proposed. The purpose of this work was to evaluate the ET-1 release after sclerotherapy and to investigate the effects of the anti-endothelin drug aminaphtone. As in vitro sclerotherapy model, an endothelial cell culture, mimicking vascular endothelium, was pretreated with aminaphtone and exposed to detergents. Cell survival and ET-1 release were measured. In in vivo experiments, 45 rats, fed with different aminaphtone-rich diets, were subjected to sclerotherapy, and the systemic ET-1 was measured. Aminaphtone cell exposure caused a statistically significant reduction in ET-1 release, both before and after in vitro sclerotherapy. Rats fed with aminaphtone showed a trend toward reduced mortality and a significant decrease of ET-1 release after sclerotherapy. This is the first study in which an anti-endothelin agent was able to cause a significant reduction of ET-1 release during sclerotherapy. Although clinical studies are required, these findings might advocate the use of anti-endothelin agents in prophylaxis of neurologic or visual disturbances after sclerotherapy.
Depression has been identified as a risk factor for an adverse prognosis and reduced survival in ... more Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim of this study was to evaluate the impact of depression on EPC levels in patients with ACS. Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34CD133KDR and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P < 0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and within each group patients with MDE again showed a significant decrease in circulating CD34CD133KDR EPCs compared with others (P <0.001). We showed that ACS patients with MDE have a reduced number of circulating CD34CD133KDR cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we propose that patients with MDE might be protected less than patients without MDE.
Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma a... more Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma argel. Stemmosides E--J are characterized by the occurrence of an uncommon 14 beta proton configuration while stemmosides E and F possess in addition a rare enolic function in C-16. On the other hand, stemmosides G-J display an unusual C-17 alpha side chain. Their structures were established by ESI-MS and NMR experiments. Moreover, the effect of these compounds on the VEGF-induced in Kaposi's sarcoma cell proliferation was tested. Results indicated that all the compounds reduced the cell proliferation in a dose dependent manner.
Journal of the American College of Cardiology, 2013
ABSTRACT Background: Depression and cardiovascular disease are two of the most common disorders i... more ABSTRACT Background: Depression and cardiovascular disease are two of the most common disorders in developed countries. In particular, depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). Moreover, the number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim was to evaluate the impact of depression on EPC levels in patients with ACS. Methods: Study population consisted of 88 non-consecutive ACS patients (20 females, 68 males; n=62 STEMI, age 58±11 years; n=26 NSTEMI, age 60±7 years), out of them, 44 had a diagnosis of current or previous mood or anxiety disorder (MDE) at the time of the inclusion in the study. Control groups were: 16 healthy subjects (5 females, 11 males, age 50±9 years) and 20 patients with current MDE without a history of cardiovascular diseases (8 females, 12 males, age 48±13 years). Circulating EPCs (CD133+/KDR+/CD34+) were evaluated by flow cytometry analysis. The presence of a current or previous MDE was evaluated using the Structured Clinical Interview for DSM-IV Diagnosis (SCID-I). Results: ACS patients with MDE showed a significant decrease in circulating EPC number compared to ACS patients without MDE (P<0.0001). The ACS study population was then subdivided into STEMI and NSTEMI patients, and inside each group again patients with MDE showed a significant decrease in circulating EPCs compared to others (P<0.0001). Finally, the change in EPC count correlated negatively with Hamilton Depression Rating Scale in patient with ACS (r = - 0.34, P= 0.0028). Conclusions: We showed that ACS patients with MDE have a reduced number of circulating EPCs compared to ACS patient without MDE, suggesting that the presence of MDE reduce the response of bone-marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we suppose that patients with MDE might be protected less than patients without MDE. Finally, our results suggest that individuals either with cardiovascular risk factors or with definite cardiovascular diseases, such as ACS, should be screened for depression.
Circulating endothelial progenitor cells (EPCs) play a significant role in neovascularization of ... more Circulating endothelial progenitor cells (EPCs) play a significant role in neovascularization of ischaemic tissues and in re-endothelization of injured blood vessels. Identification of compounds able to enhance EPC levels and improve their functional activity, noticeably compromised by risk factors for coronary heart disease, is of clinical interest. This study evaluates the effects of red wine on EPCs. After being isolated from total peripheral blood mononuclear cells, EPC phenotype was confirmed by the presence of double positive cells for DiLDL uptake and lectin binding and by expression of CD34, CD133 and VE-cadherin cell surface markers. Long-term culture in the presence of red wine (1 microl/ml), containing resveratrol (Resv) at physiological concentration (nM), determined a time-dependent amelioration of cell number (P < 0.05). The presence of red wine prevented the TNF-alpha-induced reduction of EPC number (P < 0.05) and this effect was accompanied by reduced p38-phosphorylation expression levels (P < 0.05) and increased NOx levels (P < 0.05) Indeed, pure Resv alone significantly improved the TNF-alpha reduced EPC number (P < 0.05). This evidence indicates novel beneficial effects of red wine and Resv in the positive modulation of EPCs levels.
Journal of Biochemical and Molecular Toxicology, 2010
Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor-α (TNF-α) reduced ... more Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor-α (TNF-α) reduced their number and biological activity. Yet, signal transduction events linked to TNF-α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in- flammation. Results demonstrated that incubation with fasudil starting from 50 μM but not Y27632 determined a dose-dependent improvement of EPC number during exposure to TNF-α (P < 0.05 vs. TNF-α alone). Analysis of the signal transduction pathway activated by TNF-α revealed that the increased expression of p-p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF-α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF-α) as well as the inhibitor of Erk1/2-specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF-α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D-DIGE and MALDI-TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin-related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway.
Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damage... more Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damaged blood vessels. Levels and functional activities of EPCs are noticeable altered by risk factors for coronary heart disease (CHD) and compounds that can prevent or ameliorate EPC dysfunction are currently of special clinical interest. Here, we evaluate the effects of red wine (RW) on EPCs in C57BL/6J mice subjected to physical exercise. FACS computed counting showed a significant increase of EPC number (P<0.05) in mice after short-term supplementation with RW. VEGF serum concentration was significantly increased by physical training in the presence or absence of RW supplementation (P<0.001). These in vivo observations support previous in vitro observation of the beneficial effect of RW in the modulation of EPC levels.
Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed... more Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS. Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations. Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p=.023), but not that of MDD (p=.721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD. Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.
European Journal of Pharmaceutics and Biopharmaceutics, 2012
To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) fro... more To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) from oxidative stress induced by hyperglycemia (HG) compared to red wine (RW) and prepare innovative pharmaceutical systems for the oral administration of red grape extract allowing the overcoming of its poor intestinal absorption. Human EPC were characterized by expression of cell surface markers. Cells were incubated with different concentrations of total polyphenols from grape components or RW in the presence or absence of HG. Cell viability, migration, adhesion, and reactive oxygen species (ROS) production were assayed. Intestinal permeation of polyphenols was studied in the absence or presence of a quaternary ammonium-chitosan conjugate (N⁺(60)-Ch). Grape components and RW increased EPC viability, adhesion and migration, and prevented the HG effect (P < 0.01). ROS production induced by HG was significantly reduced only by grape seed extract and RW (P < 0.01). N⁺(60)-Ch acted as an effective enhancer of polyphenol permeability across the excised rat intestine. Red grape components are a source of antioxidant compounds that ameliorate EPC viability and function, while preventing endothelial dysfunction. The use of polycationic chitosan derivatives can promote the absorption of polyphenols across intestinal epithelium, thus increasing their bioavailability and potential therapeutic value in atherosclerosis.
Journal of Drug Delivery Science and Technology, 2015
ABSTRACT The purpose of this study was to demonstrate that nanoparticles (NP), obtained by ionotr... more ABSTRACT The purpose of this study was to demonstrate that nanoparticles (NP), obtained by ionotropic crosslinking of reduced-MW chitosan (rCh) derivatives with reduced-MW hyaluronan (rHA), could be profitable vehicles for oral administration of beneficial doses of antioxidant constituents of red grape seeds extracts (GSE). NP have previously shown aptitude for internalisation by endothelial progenitor cells. Here they were seen by a fluorescence microscope migrating across excised rat intestine from mucosal to serosal side and permeating from the donor to the acceptor compartment of an Ussing chamber while carrying significant (15-20%) steadily associated fractions of initial antioxidant load. Freshly prepared NP dispersions were stabilised by lyophilisation. The NP dispersions were regenerated from the lyophilised products by adding water under gentle stirring. Lyophilisation-regeneration caused a significant NP size increase yet particles did not grow beyond the upper size limit of particles able to cross the intestinal barrier (500 nm).
Phlebology / Venous Forum of the Royal Society of Medicine, 2011
Visual and neurological disturbances have always been reported following liquid sclerotherapy (LS... more Visual and neurological disturbances have always been reported following liquid sclerotherapy (LS) for venous insufficiency. In 1993 Cabrera introduced foam sclerotherapy (FS) using a detergent sclerosant as Lauromacrogol 400 or sodium tetradecyl sulphate. Several authors have reported with FS an increased incidence of such transient visual disturbances and neurological complications. This has been associated with gas or air used to generate the sclerosing foam. The frequent association of the presence of a patent foramen ovale, a common condition in normal population, and such complications has led several authors to consider neurological and visual disturbances as paradoxical gas embolism. We are introducing a new pathogenetic hypothesis for sclerotherapy complications. Medical literature shows evidence of a clear relationship among cerebral and retinal vasospasm, migraine and intimal irritation. We think that the irritating sclerosant agent may stimulate a significant release of ...
International Journal of Biological Macromolecules, 2015
Different strategies have been developed to make the wound-healing process faster and less painfu... more Different strategies have been developed to make the wound-healing process faster and less painful. Recently, numerous studies demonstrated the ability of chitosan to accelerate wound healing. Aim of the present study has been to evaluate the effect of different chitosan derivatives to improve wound healing process. Quaternary ammonium-chitosan conjugates with low or high molecular weight (MW) and their thiolated derivatives effect were studied on human skin fibroblasts in terms of viability and migration (scratch wound assay). Results were compared both with basal medium (untreated cells) and with a positive control (chitosan chlorhydrate). After 24h both high and low MW chitosan derivatives were non-toxic up to 10μg/ml. The concentration of 10μg/ml was used for wound healing experiments. High-MW quaternary ammonium-chitosan conjugates bearing thiol groups on their chains were more effective in promoting cell migration than the non-thiolated conjugates and the chitosan chlorhydrate. Moreover, they significantly improve wound healing process compared to untreated cells. According to the present in vitro preliminary results, high MW thiolated quaternary ammonium-chitosan conjugates can be considered good candidates for the management of wounds.
The foam sclerotherapy technique has become one of the most commonly used treatments for superfic... more The foam sclerotherapy technique has become one of the most commonly used treatments for superficial venous insufficiency. Despite excellent results, few visual/neurologic disturbances have been recently reported; their pathogenesis is still debated but a correlation with endothelin-1 (ET-1) release from the treated vein has been proposed. The purpose of this work was to evaluate the ET-1 release after sclerotherapy and to investigate the effects of the anti-endothelin drug aminaphtone. As in vitro sclerotherapy model, an endothelial cell culture, mimicking vascular endothelium, was pretreated with aminaphtone and exposed to detergents. Cell survival and ET-1 release were measured. In in vivo experiments, 45 rats, fed with different aminaphtone-rich diets, were subjected to sclerotherapy, and the systemic ET-1 was measured. Aminaphtone cell exposure caused a statistically significant reduction in ET-1 release, both before and after in vitro sclerotherapy. Rats fed with aminaphtone showed a trend toward reduced mortality and a significant decrease of ET-1 release after sclerotherapy. This is the first study in which an anti-endothelin agent was able to cause a significant reduction of ET-1 release during sclerotherapy. Although clinical studies are required, these findings might advocate the use of anti-endothelin agents in prophylaxis of neurologic or visual disturbances after sclerotherapy.
Depression has been identified as a risk factor for an adverse prognosis and reduced survival in ... more Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim of this study was to evaluate the impact of depression on EPC levels in patients with ACS. Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34CD133KDR and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P < 0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and within each group patients with MDE again showed a significant decrease in circulating CD34CD133KDR EPCs compared with others (P <0.001). We showed that ACS patients with MDE have a reduced number of circulating CD34CD133KDR cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we propose that patients with MDE might be protected less than patients without MDE.
Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma a... more Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma argel. Stemmosides E--J are characterized by the occurrence of an uncommon 14 beta proton configuration while stemmosides E and F possess in addition a rare enolic function in C-16. On the other hand, stemmosides G-J display an unusual C-17 alpha side chain. Their structures were established by ESI-MS and NMR experiments. Moreover, the effect of these compounds on the VEGF-induced in Kaposi's sarcoma cell proliferation was tested. Results indicated that all the compounds reduced the cell proliferation in a dose dependent manner.
Journal of the American College of Cardiology, 2013
ABSTRACT Background: Depression and cardiovascular disease are two of the most common disorders i... more ABSTRACT Background: Depression and cardiovascular disease are two of the most common disorders in developed countries. In particular, depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). Moreover, the number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim was to evaluate the impact of depression on EPC levels in patients with ACS. Methods: Study population consisted of 88 non-consecutive ACS patients (20 females, 68 males; n=62 STEMI, age 58±11 years; n=26 NSTEMI, age 60±7 years), out of them, 44 had a diagnosis of current or previous mood or anxiety disorder (MDE) at the time of the inclusion in the study. Control groups were: 16 healthy subjects (5 females, 11 males, age 50±9 years) and 20 patients with current MDE without a history of cardiovascular diseases (8 females, 12 males, age 48±13 years). Circulating EPCs (CD133+/KDR+/CD34+) were evaluated by flow cytometry analysis. The presence of a current or previous MDE was evaluated using the Structured Clinical Interview for DSM-IV Diagnosis (SCID-I). Results: ACS patients with MDE showed a significant decrease in circulating EPC number compared to ACS patients without MDE (P<0.0001). The ACS study population was then subdivided into STEMI and NSTEMI patients, and inside each group again patients with MDE showed a significant decrease in circulating EPCs compared to others (P<0.0001). Finally, the change in EPC count correlated negatively with Hamilton Depression Rating Scale in patient with ACS (r = - 0.34, P= 0.0028). Conclusions: We showed that ACS patients with MDE have a reduced number of circulating EPCs compared to ACS patient without MDE, suggesting that the presence of MDE reduce the response of bone-marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we suppose that patients with MDE might be protected less than patients without MDE. Finally, our results suggest that individuals either with cardiovascular risk factors or with definite cardiovascular diseases, such as ACS, should be screened for depression.
Circulating endothelial progenitor cells (EPCs) play a significant role in neovascularization of ... more Circulating endothelial progenitor cells (EPCs) play a significant role in neovascularization of ischaemic tissues and in re-endothelization of injured blood vessels. Identification of compounds able to enhance EPC levels and improve their functional activity, noticeably compromised by risk factors for coronary heart disease, is of clinical interest. This study evaluates the effects of red wine on EPCs. After being isolated from total peripheral blood mononuclear cells, EPC phenotype was confirmed by the presence of double positive cells for DiLDL uptake and lectin binding and by expression of CD34, CD133 and VE-cadherin cell surface markers. Long-term culture in the presence of red wine (1 microl/ml), containing resveratrol (Resv) at physiological concentration (nM), determined a time-dependent amelioration of cell number (P < 0.05). The presence of red wine prevented the TNF-alpha-induced reduction of EPC number (P < 0.05) and this effect was accompanied by reduced p38-phosphorylation expression levels (P < 0.05) and increased NOx levels (P < 0.05) Indeed, pure Resv alone significantly improved the TNF-alpha reduced EPC number (P < 0.05). This evidence indicates novel beneficial effects of red wine and Resv in the positive modulation of EPCs levels.
Journal of Biochemical and Molecular Toxicology, 2010
Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor-α (TNF-α) reduced ... more Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor-α (TNF-α) reduced their number and biological activity. Yet, signal transduction events linked to TNF-α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in- flammation. Results demonstrated that incubation with fasudil starting from 50 μM but not Y27632 determined a dose-dependent improvement of EPC number during exposure to TNF-α (P < 0.05 vs. TNF-α alone). Analysis of the signal transduction pathway activated by TNF-α revealed that the increased expression of p-p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF-α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF-α) as well as the inhibitor of Erk1/2-specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF-α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D-DIGE and MALDI-TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin-related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway.
Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damage... more Circulating endothelial progenitor cells (EPCs) play a significant role in regeneration of damaged blood vessels. Levels and functional activities of EPCs are noticeable altered by risk factors for coronary heart disease (CHD) and compounds that can prevent or ameliorate EPC dysfunction are currently of special clinical interest. Here, we evaluate the effects of red wine (RW) on EPCs in C57BL/6J mice subjected to physical exercise. FACS computed counting showed a significant increase of EPC number (P<0.05) in mice after short-term supplementation with RW. VEGF serum concentration was significantly increased by physical training in the presence or absence of RW supplementation (P<0.001). These in vivo observations support previous in vitro observation of the beneficial effect of RW in the modulation of EPC levels.
Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed... more Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS. Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations. Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p=.023), but not that of MDD (p=.721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD. Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.
European Journal of Pharmaceutics and Biopharmaceutics, 2012
To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) fro... more To evaluate the ability of grape skin and seeds to protect endothelial progenitor cells (EPC) from oxidative stress induced by hyperglycemia (HG) compared to red wine (RW) and prepare innovative pharmaceutical systems for the oral administration of red grape extract allowing the overcoming of its poor intestinal absorption. Human EPC were characterized by expression of cell surface markers. Cells were incubated with different concentrations of total polyphenols from grape components or RW in the presence or absence of HG. Cell viability, migration, adhesion, and reactive oxygen species (ROS) production were assayed. Intestinal permeation of polyphenols was studied in the absence or presence of a quaternary ammonium-chitosan conjugate (N⁺(60)-Ch). Grape components and RW increased EPC viability, adhesion and migration, and prevented the HG effect (P < 0.01). ROS production induced by HG was significantly reduced only by grape seed extract and RW (P < 0.01). N⁺(60)-Ch acted as an effective enhancer of polyphenol permeability across the excised rat intestine. Red grape components are a source of antioxidant compounds that ameliorate EPC viability and function, while preventing endothelial dysfunction. The use of polycationic chitosan derivatives can promote the absorption of polyphenols across intestinal epithelium, thus increasing their bioavailability and potential therapeutic value in atherosclerosis.
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Papers by Francesca Felice