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Biomedical subjects

E Conte

Publications and source records attributed to E Conte.

At least 19 recordsLinked to original sources

Ribavirin up-regulates IL-12 p40 gene expression and restores IL-12 levels in Leishmania-treated PBMCs.

Ribavirin, a nucleoside analogue that interferes with viral mRNA synthesis and inhibits the replication of RNA and DNA viruses, has been recently proposed as an effective immune response modulator. In the present report, we studied the effect of ribavirin on IL-12 p40 gene expression in peripheral blood mononuclear cells (PBMCs) of healthy subjects. We also studied ribavirin effects on PBMCs activated with lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) and treated with Leishmania donovani antigens. We provide evidence that ribavirin was able to up-regulate IL-12 p40 gene expression and to restore levels of IL-12 p40 gene expression and IL-12 secretion in fully activated PBMCs that were strongly inhibited by L. donovani antigens. Because effective management of leishmanial disease is usually associated with a prevalent T-helper 1 immune response with elevated production of IL-12,our preliminary results may be of particular interest, provided that they will be confirmed by further in vitro and in vivo studies, when considering a possible use of ribavirin as adjuvant in severe leishmanial disease.

Adolescent↗

Pesticides re-entry dermal exposure of workers in greenhouses.

This research has the aim to evaluate the risk of pesticide dermal exposure for workers in greenhouses. We considered the following crops: tomato, cucumber and strawberry, largely spread in Bracciano lake district. The pesticides monitored were: tetradifon on strawberry: metalaxyl, azoxystrobin and fenarimol on cucumber; acrinathrin, azoxystrobin and chlorpyrifos ethyl on tomato. The dermal exposure was evaluated by Dislodgeable Foliar Residue (DFR) measurements employing transfer coefficients got from literature. For risk evaluation, we have compared the dermal exposures with Acceptable Operator Exposure Levels (AOEL). The re-entry time were obtained intercepting the dose decay curves with AOEL values. The re-entry times result higher than two days in the cases of chlorpyrifos on tomato (re-entry time: 3 days), azoxystrobin on tomato (4 days), and tetradifon on strawberry (8 days). The need of measuring specific transfer coefficients is pointed out.

Agriculture↗

Presence of plant protection products in three agricultural areas of Regione Lazio.

Aim of the research was to verify the impact of plant protection products on three significant agricultural areas of Regione Lazio: Maccarese, Cisterna di Latina, Sabaudia-Terracina. This research studied the presence of some active ingredients, indicated by technicians as distributed, on soil, water, crop and air samples, the last one in greenhouse; the analysis, carried out by multi-residue methods, allowed to investigate also on a large amount of active ingredients not indicated by technicians. The determinations have been obtained, using internal standards, by GC-NPD, GC-ECD, HPLC-UV, HPLC-DAD, with different columns, conditions and wavelength of adsorption. Taking into account the results we could to assert that only a small part of the molecules searched were found in the samples and that they are typical for the crops and the environment treated. In greenhouse, more persistence was founded in wood greenhouse, treated from the outside, probably for the release of a.i. in time from wood and for a better distribution. The active ingredients more frequently founded must be controlled to avoid possible accumulation or leaching, especially for herbicides in the areas of Maccarese and Cisterna di Latina. Furthermore, the molecule on which more attention must be done when applied, are: linuron on carrots, penconazole on zucchini and cymoxanil, often used inappropriately, particularly on minor crops, like red-radish. Although the number of sampling was limited, it has been possible to outline the situation in the three zones considered, for directing choices, that could be more sensible at sanitary spin-off and at the environment.

Air Pollutants↗

Pesticide residues in grapes and wine in Italy.

Two hundred and one pesticides comprising 84 fungicides, 88 insecticides and 29 herbicides are registered in Italy for use on grapes. Recently, the maximum residue limits (MRLs) for 16 fungicides and five insecticides were established for wine. However, literature data shows that some MRLs for wine are not consistent with the corresponding values for grapes. In Italy, the Ministry of Health has the responsibility for checking pesticide contamination in fruit and vegetables in general distribution (i.e. grocery shops, food stores). From 1996 to 1999, out of 1532 grape samples analysed, levels of 1.0, 0.9, 1.8 and 1.9% in each year respectively were contaminated. As part of the National Residue Monitoring Programme, the Ministry of Agriculture carried out investigations of samples collected directly from the field (therefore of a known pesticide treatment history) in order to find the causes of the observed irregularities and to identify preventative measures. In 1996, 1998 and 1999, out of 481, 1195 and 1949 grape samples analysed, 7.9, 6.5 and 2.5% respectively were contaminated, while no residues were detected in 259 wine samples. The National Observatory on Pesticide Residues collects data from analyses performed by highly reliable, non-institutional laboratories on samples from farming cooperatives or individual forms, food companies, wholesale and retail markets. Of the 846 grapes samples and 190 wine samples collected in 1998 and 1999, a total of 6.1 and 2.1% respectively of grapes and 0% for all wine samples were found to contain residues.

Humans↗

Role of interferon regulatory factor 1 in monocyte/macrophage differentiation.

Interferon regulatory factor-1 (IRF-1) has been recognized as an important tumor suppressor and growth regulatory transcription factor, which is also involved in cell differentiation. In this study we investigated the role of IRF-1 in phorbol 12-myristate 13-acetate (PMA)-induced monocyte/macrophage differentiation of human monoblastic U937 cells. For this purpose U937 cells were stably transfected with a vector overexpressing IRF-1 antisense mRNA (U937 IRF-1A cells) and with the SV-40 empty vector (U937-SV40 e.v. cells). We report here that U937 and U937-SV40 e.v. cells differentiated into macrophage-like cells upon PMA stimulation and showed IRF-1 up-regulation. On the contrary, U937 IRF-1A cells stimulated with PMA kept an undifferentiated phenotype and proliferated actively. A direct correlation between induction of IRF-1 and up-regulation of IRF-1 gene targets such as ornithine decarboxylase (ODC) and WAF-1/CIP-1 was also observed in U937 cells. On the other hand U937 IRF-1A cells down-regulated ODC and did not express WAF-1. Results show that IRF-1 plays a pivotal role in PMA-induced monocyte/macrophage differentiation.

Cell Differentiation↗

Early aggressive treatment of unstable angina without on-site cardiac surgical facilities: a prospective study of acute and long-term outcome.

BACKGROUND: The early invasive diagnostic approach with extensive use of myocardial revascularization in patients with unstable angina is a matter of debate. Both the advantages of this strategy and the choice of the best candidates are controversial. The widespread applicability of this approach in Italian hospitals is also questionable, due to limited availability of facilities for interventional cardiology. METHODS: A prospective, observational study was done on a cohort of consecutive patients, who were admitted with a diagnosis of unstable angina and treated with an early aggressive approach at a center with interventional cardiology facilities without cardiac surgery. The aim of the study was to evaluate both the immediate and long-term clinical outcome of patients and the efficiency of our therapeutic approach. RESULTS: Two-hundred and two patients were enrolled and 85% were in Braunwald class III. Coronary angiography was performed in 171 patients (85%) at 2.1 +/- 2.4 days after admission: it showed one-, two- and three-vessel disease in 40, 29 and 22% of cases, respectively; 9% of patients had no severe coronary lesion. Left ventricular ejection fraction was 0.58 +/- 0.13. Medical treatment, coronary by-pass surgery and percutaneous myocardial revascularization were chosen in 36, 24 and 40% of cases, respectively. Coronary angioplasty was performed in our center in 58 (73%) of 80 patients at 6.8 +/- 5.6 days after admission and stents were used in 42 cases (74%). Overall hospital stay was 10.4 +/- 4 days. Cumulated adverse events (death and non-fatal myocardial infarction) occurred in 2.5 and 7% of patients during the initial admission and in the following year, respectively. CONCLUSIONS: An early aggressive approach to patients with unstable angina is feasible in a hospital with interventional cardiology in the absence of cardiac surgical facilities. The immediate favorable clinical results of this strategy in an intermediate-risk cohort seem to persist at one-year follow-up.

Adrenergic beta-Antagonists↗

[Primary angioplasty in acute inferior myocardial infarct with anterior ST-segment depression: the long-term follow-up].

BACKGROUND: Concomitant anterior ST-segment depression is a marker of severe prognosis in inferior myocardial infarction. PATIENTS AND METHODS: Prospective observational study in patients with inferior acute myocardial infarction and ST-segment depression > or = 4 mm in the anterior leads, who were treated with primary angioplasty. Angiography was performed at hospital discharge and at six months, and a clinical follow-up was obtained at one year after the infarction. RESULTS: Sixty-three patients were included in the study. Pre-hospital and in-hospital delay were 147 +/- 70 minutes (20-355) and 54 +/- 11 minutes (18-80), respectively. Angioplasty was successful in all patients and 48 stents were implanted in 36 patients (57%). Angiography was performed at hospital discharge in 55 patients (87%) and showed a TIMI grade 3 coronary flow in the infarct-related artery in all cases. The left ventricular ejection fraction was 0.55 +/- 0.09 (0.4-0.8). One patient (1.6%) died before discharge, two (3.2%) had ischemic complications (one had non-fatal reinfarction, another had recurrent angina at rest), and three (4.9%) had local vascular complications. At the six-month follow-up, none of the patients had died. One had suffered reinfarction (1.6%) and another had been readmitted for recurrence of angina at rest (1.6%); none had symptoms of stable angina. The ejection fraction was 0.56 +/- 0.12 and eight patients (14%) showed angiographic restenosis. At twelve months, two patients had died (1.6%) and five (8%) had required readmission to hospital. CONCLUSIONS: Primary angioplasty yielded favorable results in this group of patients. Our data confirm the efficacy of primary angioplasty for the treatment of acute myocardial infarction, with a low rate of clinical (3.2%) and angiographic (14%) restenosis at six months, and a high rate (87%) of event-free survival at one year follow-up.

Adult↗

Nuclear factor-kappaB activation in human monocytes stimulated with lipopolysaccharide is inhibited by fibroblast conditioned medium and exogenous PGE2.

The nuclear factor kappaB (NF-kappaB) is thought to be crucially involved in the gene activation of several cytokines, including tumor necrosis factor alpha (TNF). Previously, we showed that fibroblast conditioned medium (FCM) is able to inhibit both TNF mRNA accumulation and protein release in peripheral blood-derived human monocytes (PBM) stimulated with lipopolysaccharide (LPS). In this study we have investigated the effect of FCM on the LPS-induced DNA-binding activity of NF-kappaB, by means of electrophoretic shift assay (EMSA). We provide evidence that FCM strongly inhibits the LPS-induced NF-kappaB activation in PBM. Furthermore, we show that exogenous PGE2 mimics the NF-kappaB inhibitory effect of FCM. On the other hand, FCM produced in the presence of indomethacin does not inhibit NF-kappaB activation by LPS. Our results lend further support to the hypothesis that inflammatory and immune responses of monocytes/macrophages may be modulated at the molecular level by signals originating from tissue structural cells such as fibroblasts.

Anti-Inflammatory Agents, Non-Steroidal↗

Improved cell adhesion to ion beam-irradiated polymer surfaces.

A very strong improvement of the cell adhesion, spreading and proliferation was observed for ion beam irradiated surfaces of polyethersulphones and polyurethane. The improvement shows a characteristic ion fluence-dependence with a threshold around 1 x 10(15) ions cm-2. We have compared this improvement of surface cytocompatibility with the various ion-induced chemical and physical modifications of the polymeric surfaces, taking into account their characteristic fluence-dependence. The irradiation induced a severe compositional and chemical modification of the polymeric surfaces as detected by X-ray photoelectron spectroscopy. Contact angle measurements showed that the surface free energy was strongly modified by ion irradiation. The fluence-dependent formation of a hydrogenated amorphous carbon phase was demonstrated by Raman spectroscopy. Our findings indicate that neither the simple modification of the functional groups nor the mere elemental composition nor the modification of the surface free energy can explain the observed fluence-dependence of the cell adhesion enhancement. On the contrary, we show that this enhancement correlates with the formation of a highly specific ion-induced 'unsaturated' a-C:H phase. According to these findings, we suggest that the formation of a substantial amount of hydrogenated amorphous carbon phases is the major factor promoting the cytocompatibility of ion irradiated polymer surfaces.

Astrocytoma↗

Postoperative enteral feeding does not prevent intestinal bacterial translocation, but reduces the rate of pulmonary infections in pigs undergoing total orthotopic small bowel transplantation.

OBJECTIVE: To assess the effects of a non-elemental liquid diet on nutritional state, composition of bowel flora, intestinal translocation, and pulmonary infections after small bowel transplantation in pigs. DESIGN: Prospective randomised experiment. SETTING: Teaching hospital, Italy. MATERIAL: 32 female Large White pigs. INTERVENTIONS: Group 1 (n = 6) underwent small bowel transplantation, were treated with immunosuppression, and fed on commercial chow. Group 2 (n = 6) were treated similarly except that they were fed with an enteral feed through a tube gastrostomy starting on day 4 postoperatively. Group 3 (n = 6) were treated similarly to group 1 except that they had no immunosuppression, and Group 4 (n = 6) underwent orthotopic small bowel autotransplantation; 8 further pigs underwent a sham operation only to act as controls. MAIN OUTCOME MEASURES: Signs of rejection, graft-versus-host-disease, luminal bacterial overgrowth, bacterial translocation, pneumonia, and the pigs' nutritional state. RESULTS: All animals in group 3 showed signs of acute rejection. There was appreciable overgrowth of aerobic and anaerobic bacteria in all three groups after allotransplantation compared with controls. The counts of anaerobic bacteria were significantly lower in group 2 (enterally fed animals) compared with those given free access to commercial chow [mean (SD) 2.81 (1.39) log CFU/cm2 compared with 4.80 (1.65), p = 0.047]. Bacterial translocation developed to a similar degree after autografts and allografts and pneumonia developed in fewer animals after enteral feeding (1/6) than after conventional feeding (5/6) but the difference was not significant (p = 0.08, odds ratio 25.0, 95% confidence interval of odds ratio 1.20 to 521.13). Enterally fed animals also lost less weight than conventionally fed animals [2.32 (1.23) kg compared with 4.53 (1.74), p = 0.016]. CONCLUSIONS: Enteral feeding for up to a month slightly reduced the rate of pneumonia and resulted in a better nutritional state in pigs after small bowel transplantation. It had no effect on luminal bacterial overgrowth or translocation.

Animals↗

Human lung fibroblasts inhibit tumor necrosis factor-alpha production by LPS-activated monocytes.

Mononuclear phagocytes are important regulators of normal immune, inflammatory, and fibrotic responses. These functions are mediated through the production of several cytokines, including tumor necrosis factor-alpha (TNF-alpha), which regulate the activity of inflammatory and tissue structural cells such as fibroblasts. It is increasingly evident that fibroblasts are also capable of releasing a number of cytokines and soluble factors that can, in turn, interact with monocytes and thereby modulate the inflammatory process. In this study we provide evidence that human lung fibroblasts, through the release of soluble factors such as prostaglandin E2 (PGE2), inhibit both TNF messenger ribonucleic acid (mRNA) accumulation and TNF-alpha protein release by lipopolysaccharide (LPS)-activated human peripheral blood monocytes (PBM). Reverse transcriptase-polymerase chain reaction (RT-PCR) results showed that fibroblast-conditioned medium (FCM) caused a 50% reduction of the TNF-alpha transcript accumulation in LPS-stimulated monocytes. Furthermore, FCM induced a significant decrease in the release of TNF-alpha by LPS-activated PBM. This effect was dependent on the concentration of the FCM and the number of fibroblasts producing it. The maximal effect was seen with monocytes cultured in 100% FCM produced by 2 x 10(6) fibroblasts. This indicated that one or possibly more soluble factors released by fibroblasts were responsible for the effect. Considering that exogenous PGE2 can inhibit TNF-alpha production by PBM, and that fibroblasts are a good source of PGE2, we determined the content of PGE2 in the FCM used in our experiments. We found a good correlation (r = 0.949) between the amount of PGE2 produced by fibroblasts and the degree of TNF-alpha inhibition exerted. In addition, the inhibitory effect of FCM was mimicked by the addition to PBM cultures of exogenous PGE2 in amounts similar to those spontaneously released by fibroblasts in FCM. All of these data suggest a molecular and cellular interaction between PBM and fibroblasts that could contribute to those modulatory mechanisms involved in the self-limitation of the fibrotic process.

Cells, Cultured↗

[The use of a check list for quality assurance of the treatment of acute myocardial infarction in the coronary care unit].

UNLABELLED: The implementation of Quality Assurance programs for the treatment of acute myocardial infarction in the Cardiac Intensive Care Unit may be specially important. In fact several therapeutic options are available in these patients, and delay in treatment must be as short as possible. A Quality Assurance program has been started in our center with a registry of all patients admitted within 24 hours of onset of acute myocardial infarction. PATIENTS AND METHODS: The following data were recorded: 1) indicators of Organization: pathway to admission, pre-hospital and in-hospital delay; 2) Process Indicators: duration of hospital stay, initial choice of therapy (conservative, intravenous lysis, primary angioplasty), and further diagnostic and interventional procedures; 3) Outcome Indicators: mortality and complications during admission, and 6-12 months follow-up. RESULTS: Since february 1994 to August 1995, 211 consecutive patients were included in the registry; 156 were male, mean age 66 years. Mean pre-hospital delay was 286 minutes. Admission was decided by a physician in 99 cases and by the patient him/herself in 112 cases; pre-hospital delay was 390 min. In the former group, and 194 min. In the latter (p < .001). Mean in-hospital delay was 61 minutes. Conservative treatment, intravenous lysis, and primary angioplasty were chosen by the attending cardiologist in 89 patients (group A), 69 patients (group B), and 53 patients (group C) respectively. The latter group included patients with highest risk on the basis of clinical and electrocardiographic characteristics. In-hospital mortality was 17, 7 and 9% In the 3 groups, respectively. An echocardiogram and coronary angiography were performed before discharge in 81% and 57% of patients, respectively. The mean duration of hospital stay was 11 days, irrespective of the initial therapeutic choice. CONCLUSIONS: A registry for patients with acute myocardial infarction provides information which is essential in the evaluation of therapeutic protocols; it may also help in improving the cooperation between the Emergency Department, the attending cardiologists, and the family physicians.

Aged↗

A phase II trial of vinorelbine and thiotepa in metastatic breast cancer.

BACKGROUND: Vinorelbine as single-agent has achieved an overall response rate of > 20% as second-line treatment and 40%-50% as first-line treatment. The aim of this study was to evaluate the activity and toxicity of the combination of vinorelbine and thiotepa as second-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-three patients (31: anthracycline-based chemotherapy, 16: high-dose epirubicin) were given vinorelbine 30 mg/m2 and thiotepa 12 mg/m2 d 1 and 8 every 21 days. RESULTS: Among the 32 evaluable patients two complete responses and seven partial responses were observed, for an overall response rate of 28% (C.I. 12-44). The median duration of response was 9 months and the median time to progression 6 months. Significant toxicity was primarily leukopenia (72%); anemia was also frequent (48%) as well as local phlebitis (39%). CONCLUSION: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines.

Adult↗