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Biomedical subjects

M Di Renzo

Publications and source records attributed to M Di Renzo.

At least 19 recordsLinked to original sources
PubMed2006

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes.

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNgamma and TNFalpha production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.

Acute Disease↗
PubMed2005

Cytokines in acute coronary syndromes.

The aim of this study was to show the presence of an imbalance between pro-inflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, which are well known to possess pro-inflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity, in two groups of 30 patients affected by acute myocardial infarction (AMI) and unstable angina (UA), compared with two equivalent groups of patients with stable angina (SA) and of healthy volunteers. We found a significant increase of IFNgamma and TNFalpha production (p<0.01) and a significant decrease of IL-10 production (p<0.01) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes were found between AMI and UA patients and SA patients and controls. We conclude that a relevant imbalance in cytokine release is present in ACS, markedly favoring pro-inflammatory effects.

Acute Disease↗
PubMed2005

Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

Angina Pectoris↗
PubMed2005

Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6.

Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.

Aged↗
PubMed2005

Extracorporeal photopheresis affects interleukin (IL)-10 and IL-12 production by monocytes in patients with chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Extracorporeal photopheresis (ECP) has recently been introduced as an alternative treatment for cases of cGVHD refractory to conventional immunosuppressive treatment, but its mechanism of action is not yet clear. OBJECTIVES: To investigate in seven patients with cGVHD the effects of ECP on resistance of monocytes to apoptosis and on monocyte cytokine production. METHODS: We designed an in vitro model that could mimic the potential in vivo effect of reinfusion of peripheral blood mononuclear cells treated by ECP. The model was based on coculture of ECP-treated lymphocytes with untreated monocytes from the same patient. RESULTS: ECP did not accelerate spontaneous apoptosis of monocytes. However, ECP-treated monocytes produced increased amounts of interleukin (IL)-12. In contrast, IL-12 production by monocytes did not increase in cocultures, but IL-10 production was upregulated. CONCLUSIONS: These results suggest that reinfusion of large numbers of autologous apoptotic lymphocytes is significant for the therapeutic outcome of ECP through upregulation of IL-10, which is an immunosuppressive cytokine.

Adult↗
PubMed2005

Short-term and long-term effects of one-week treatment with intravenous iloprost in critical limb ischemia patients (Leriche-Fontaine stage III and IV).

AIM: Iloprost, usually administered through intravenous infusion for 6 hours per day for at least 21 days, is the main medical treatment for critical limb ischemia in patients unsuitable for surgical or endovascular approach. We evaluated the tolerance and the short-term and long-term effects of a single 1-week treatment in critical limb ischemia patients. METHODS: Twenty-nine patients in Leriche-Fontaine III and IV stage were treated with iloprost infusions for 16 hours per day for 7 days, achieving a maximal dose of 1.5 ng/kg/min. Tolerance and clinical assessment after treatment discontinuation and after 1 and 6 months were recorded; clinical evaluation (rest pain, trophic lesions), ankle/brachial pressure index (ABPI) and treadmill exercise test were performed before, immediately after treatment and after 1 and 6 months. RESULTS: No discontinuation of treatment occurred because of intolerance to iloprost. At the end of the treatment 69% of patients were responders, 55.2% at 1 month, 37.9% after 6 months. ABPI and treadmill maximum walking distance were improved by the treatment at every timepoint. After 6 months 10.3% mortality and 3.4% major amputation rates were recorded. There was a higher percentage of non-responders amongst women vs men, in diabetic patients vs non diabetic and in stage IV patients vs stage III. CONCLUSIONS: One-week treatment with iloprost is safe and effective in both Leriche-Fontaine stage III and IV patients. Clinical effects are persistent over time, often lasting up to the 6th month, similarly to the commonly used 28-day treatment, with clear implications in terms of patient's compliance and medical cost containment.

Aged↗
PubMed2004

Common variable immunodeficiency: a review.

Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome. The predominant manifestation is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, especially of the upper and lower respiratory airways, and is also associated with an increased incidence of autoimmune and neoplastic disorders. Most patients are diagnosed as adults and delay in the recognition of the disease is common. Several T and B cell defects have been described, although the underlying cause is still unknown.

Common Variable Immunodeficiency↗
PubMed2004

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

BACKGROUND: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation. METHODS: Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment. RESULTS: PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05). CONCLUSIONS: The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

Adult↗
PubMed2004

Mechanism of action of extracorporeal photochemotherapy in chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) affects 50% of long-term bone marrow transplant survivors and remains a cause of major long-term morbidity in these patients despite aggressive therapy. Extracorporeal photochemotherapy (ECP), considered as an effective treatment for patients with erythrodermic cutaneous T-cell lymphoma (CTCL), has recently been used successfully in the treatment of GvHD. One of the most intriguing aspects of ECP is its ability to induce two apparently opposite effects: activation of the immune system against neoplastic cells (as in CTCL) and downregulation of the activity of T-cell clones in autoimmune diseases (as in systemic sclerosis, systemic lupus erythematosus and pemphigus vulgaris) and autoallogeneic immune responses (as in GvHD and allograft rejection). Only a better and more complete understanding of the various mechanisms involved will enable this interesting new therapy to be made more effective and selective.

Apoptosis↗
PubMed2003

ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family.

Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.

Adult↗
PubMed2003

T cell activation and enhanced apoptosis in non-ST elevation myocardial infarction.

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Apoptosis↗
PubMed2002

Relationship between serum complement and different lipid disorders.

Inflammatory and lipid factors share an important role in atherosclerosis. Recent studies showed the concomitant presence and increase of complement components and lipids both in the atherosclerotic plaque and the circulating blood. The aim of this study was to examine the relationship between the complement system and lipid disorders. We evaluated the circulating complement terminal complex C5b-9, a clear sign of complement activation, in three groups of 30 patients the first with hypercholesterolemia, the second with hypertriglyceridemia (associated with low values of HDL-cholesterol), the third with low levels of HDL-cholesterol compared with an equivalent group of matched normolipemic subjects. We found a significant increase of sC5b-9 in each group of patients compared with controls. The mean sC5b-9 level in the hypercholesterolemic population was 366.2 +/- 141.2 ng/ml (P<0.01), 395.4 +/- 118.2 ng/ml in the hypertrygliceridemic group (P<0.01), 414.8 +/- 126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0 +/- 40.8. ng/ml in the control group. Regression analysis showed a significant direct correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse correlation between sC5b-9, HDL-chol (r=-0.74), and apo-A1 (r=-0.68); no significant relationship was found between sC5b-9 and cholesterol. We suggest that complement activation is associated with the various lipid disorders and is more important in those dyslipidemic conditions in which other factors may be involved. In particular, hypertriglyceridemia may be associated with endothelial and fibrinolytic disturbances, and the decrease of HDL may induce the failure of the regulatory proteins transported by the same HDL.

Adult↗
PubMed2002

Enhanced apoptosis of peripheral blood mononuclear cells in cardiac transplanted patients undergoing chronic immunosuppressive treatment.

Apoptosis plays a major role in tissue transplantation because intact T-cell-apoptosis pathways are required for the induction of tolerance to allografts. Moreover, immunosuppressive agents commonly used in clinical transplantation medicine promote lymphocyte apoptosis inhibiting the expression and production of cytokines involved in lymphocyte survival. The aim of our study was to evaluate peripheral blood mononuclear cells (PBMC) spontaneous apoptosis in patients undergoing chronic immunosuppressive treatment after cardiac transplantation. PBMC obtained from patients (n = 31) and controls matched for age and sex (n = 25) were cultured for 72 h and apoptosis was evaluated by quantification of fragmented DNA, staining with Hoechst 33258 dye and annexin V binding. We also investigated Fas expression and FasL mRNA expression as well as the ability of an IgM anti-Fas antibody to induce apoptosis. Finally, we evaluated IL2 production induced by PHA and the ability of IL2 to prevent apoptosis. In patients, PBMC underwent enhanced spontaneous apoptosis in comparison with controls. However, we could not find any difference between patients and normals as regards the expression of Fas and of FasL mRNA, even if the cross-linking of the Fas molecule induced apoptosis in PBMC from patients, whereas it failed to induce cell death in normals. We also found that IL2 production was significantly decreased in patients and that the addition of IL2 to the culture medium reduced PBMC spontaneous apoptosis. Our findings suggest that in cardiac transplanted patients PBMC undergo enhanced spontaneous apoptosis, which may contribute to prevent allograft rejection.

Adult↗
PubMed2002

[The psychologist and adults: pathology and pseudo-pathology in adolescence].

The difficulty an adult has in identifyng a pathology and distinguishing it from a pseudo-pathology in adolescence, is examined. Adults have the task of determining the uneasiness of the adolescent but very often they are conditioned by their own point of view. Moreover, it can often happen that parents consider a strange behaviour as pathologic symptoms and adolescents who have a good progress at school are not considered as problematic subjects, even if the present a withdrawal attitude both at home and outside. Pseudo-pathology today is presented as a confusion in educational styles, a lack of boundaries and roles, individual struggles for power which can even threaten the role of the therapeutist if the latter is not able to mediate between the past and the present both on a deep emotional level and in the review of theories and diagnostic pictures.

Adolescent↗
PubMed2001

A photoacoustic FTIRS study of the chemical modifications of human dentin surfaces: II. Deproteination.

This work focuses on the chemical alterations occurring on the dentin surface on treatment with sodium hypochlorite (NaOCl), a known deproteinating agent. In addition, sequential treatment with both acid and NaOCl are characterized. Modifications are evaluated using photoacoustic FTIR (PA-FTIRS), a surface-sensitive spectroscopy. Spectra of NaOCl-treated dentin samples show a slow and heterogeneous removal of its organic phase, leaving calcium hydroxyapatite and carbonate apatite unchanged. Spectra of this deproteinated surface resemble those of apatites synthesized at low temperatures and having very high-surface areas. A combined sequential 2-min treatment of dentin with both maleic acid and NaOCl indicates that this treatment can produce a surface region which is neither significantly demineralized nor deproteinated. This sequential treatment can be used to remove the smear layer and restore the dentin surface to its natural composition.

Acid Etching, Dental↗
PubMed2001

A photoacoustic FTIRS study of the chemical modifications of human dentin surfaces: I. Demineralization.

Acids are used to modify the structure and composition of dentin surfaces to improve bonds formed with resins. The purpose of this work is to investigate such chemical modifications using the surface-sensitive technique photoacoustic Fourier transform infrared spectroscopy (PA-FTIRS). Spectra of acid-treated samples (citric, maleic, nitric, and phosphoric at pH = 1.0) were recorded at various time intervals. Analysis of these spectra indicates a gradual increase in sample surface area with treatment time. A decrease of the bands associated with calcium hydroxyapatite (HAP) and carbonate apatite inherent to the mineral phase of dentin are also observed. A comparison of spectra of samples treated for 2 min with each acid also reveals that maleic and phosphoric acids remove more HAP than citric acid. We conclude that citric acid may cause the formation of precipitates at the etching front which inhibit etching.

Acids↗
PubMed2001

Enhanced T cell apoptosis in common variable immunodeficiency: negative role of the fas/fasligand system and of the Bcl-2 family proteins and possible role of TNF-RS.

CVI is a primary immunodeficiency characterized by a failure of B cell differentiation associated with an array of T cell defects, such as enhanced T cell apoptosis. In this study we investigated the mechanisms underlying CVI enhanced T cell death. We analysed both the expression of Fas using flow cytometry techniques and the expression of FasL mRNA using RT-PCR in CVI T cells. We could not find any significant differences between CVI and normal subjects with regard to Fas expression, although there was a subgroup of CVI patients with very high Fas expression which was accompanied by an up-regulation of FasL mRNA. However, attempts to induce Fas-mediated apoptosis in these high Fas expressing cells, as evaluated by propidium iodide staining and APO2.7 staining, were unsuccessful. We also investigated intracellular levels of Bcl-2, bcl-xl and bax in CD4(+) and CD8(+) CVI T cells, as well as the bax/Bcl-2 ratio, using flow cytometry techniques but could not detect any differences between CVI and normal subjects. Finally we analysed TNF-RI and TNF-RII mRNA expression in CD4(+) and CD8(+) CVI T cells using semiquantitative RT-PCR and found a significant increase in expression of both TNF-Rs in CD4(+) T cells from CVI patients. Our data suggest that the increased expression of both TNF-Rs on T cells may be one of the mechanisms responsible for the accelerated T cell apoptosis in CVI.

Adolescent↗