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Biomedical subjects

S Fedi

Publications and source records attributed to S Fedi.

At least 55 records · Page 3Linked to original sources

Evaluation of clotting and fibrinolytic activation after protracted physical exercise.

The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean length of time run 2.45+/-0.15 hours) 12 well-trained long-distance male runners (mean age: 35+/-7, range 25-47 years) were investigated. Blood samples were drawn in the morning on the day before the performance, immediately after the race, and 24 hours and 48 hours after the end of run. With respect of baseline, immediately after the race, a significant decrease of fibrinogen (-25%) and significant increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex (+848%) were observed. A significant acceleration of euglobulin lysis time (-41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%), plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and plasma fibrinogen degradation products (+1200%) were also found. Only a slight, yet not significant, decrease in plasminogen activator inhibitor type 1 activity was observed. One day after the end of marathon different parameters were still unchanged. Forty-eight hours after the competition all parameters investigated returned to baseline values. These results indicate a persistence of clotting as well as fibrinolysis activation up to 24 hours after the end of the race.

Adult↗

Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients.

Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD. We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT). TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml). Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p<0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p<0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 microg/l; range 1.7-21.0 microg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p<0.001) than those found in control subjects (TAT median 2.3 microg/l; range 1.4-4.2 microg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l). As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.

Adult↗

D-dimer plasma levels during normal pregnancy measured by specific ELISA.

A progressive increase in D-dimer plasma levels together with an increase in fibrinogen has been previously reported during normal pregnancy. However, significantly different D-dimer levels have been observed in different assays, due to different specificity of the antibodies employed. The aim of this study was to verify the increase in fibrin degradation product levels during normal pregnancy, using a recently introduced specific D-dimer ELISA. We determined D-dimer (ELISA) and fibrinogen (clotting method) plasma levels in 63 normal pregnant women, during three different periods of pregnancy (A, 7-20 weeks; B, 21-30 weeks; C, > 30 weeks). During period A, D-dimer plasma levels (range 2-103 ng/ml) showed an insignificant increase compared with a control group of non-pregnant women (range 2-73 ng/ml). During periods B and C, we observed an increase in D-dimer level (P < 0.0001) compared with period A, with a significant correlation between D-dimer levels and gestational age (P < 0.0001). Period A fibrinogen levels (range 3.24-6.43 g/l) were significantly higher (P < 0.0001) than in controls (range 2.31-4.71 g/l), with a further increase in periods B and C. In conclusion, we confirmed a progressive increase in plasma concentrations of fibrin degradation product during normal pregnancy, but D-dimer levels were significantly lower than those reported in the literature for other ELISAs.

Adult↗

Evidence for signaling between the phytopathogenic fungus Pythium ultimum and Pseudomonas fluorescens F113: P. ultimum represses the expression of genes in P. fluorescens F113, resulting in altered ecological fitness.

There is increasing evidence that communication between members of the same species, as well as members of different species, is important for the survival of microorganisms in diverse ecological niches, such as the rhizosphere. To investigate whether the phytopathogen Pythium ultimum could alter gene expression in the biocontrol strain Pseudomonas fluorescens F113, which protects the roots of sugar beet from the fungus, a screening system was developed to detect differential expression of bacterial genes in the presence of P. ultimum. The transposon Tn5, containing a promoterless lacZ reporter gene, was used to generate a library of transcriptional gene fusions in P. fluorescens F113. By this screening procedure, five P. fluorescens F113 gene clusters were identified and shown to be repressed in the presence of P. ultimum. The ecological fitness of three of the five reporter mutants in the rhizosphere of seed-inoculated sugar beet was lower than that of the wild type. Furthermore, all five mutants were impaired in their ability to subsequently colonize the rhizosphere of uninoculated sugar beet sown repeatedly in the same soil. With the exception of reporter mutant SF10, which was impaired in nitrogen metabolism, the reporter mutants had growth requirements and biocontrol abilities similar to those of the wild type. This is the first reported case of a fungus repressing the expressing of bacterial genes.

Ecology↗

Blood clotting activation during normal pregnancy.

Pregnancy is considered as a hypercoagulable state and an increased incidence of thromboembolic phenomena has been reported in pregnant women. Relevant changes in the hemostatic mechanism have been reported during physiological pregnancy: briefly, increased levels of coagulation factors, enhanced thrombin generation and suppression of fibrinolysis are commonly found in women with uncomplicated pregnancy. We recently described progressive increases in fibrinogen and D-dimer plasma levels during normal pregnancy. The increase in D-dimer levels makes difficult their interpretation for the exclusion of thromboembolic phenomena in pregnancy. The behavior of prothrombin fragment 1+2 (F1+2) levels during physiological pregnancy is scarcely known. The aim of this preliminary study was to establish range values of F1+2 plasma levels for different periods of normal pregnancy.

Adult↗

Platelet and blood clotting activation in patients with mitral valve prolapse.

In patients with mitral valve prolapse (MVP) a high incidence of valvular abnormalities with a history of previous cerebrovascular disease has been reported and an embolic mechanism has been proposed. Aim of this study is the study of platelet and coagulation activation in patients with MVP. Fifty-four patients affected by MVP (mean age 46 +/- 15 yrs, 22 males, 32 females) and 50 control subjects, age- and sex-matched, were tested for platelet activation [P-selectin and GpIIb-IIIa platelet surface expression at rest and after stimuli by flow cytometric analysis, Beta-Thromboglobulin (TG) and Platelet Factor 4 (PF4) plasma levels by ELISA, platelet-rich-plasma (PRP) and whole blood spontaneous platelet aggregation (SPA)] and for activation of blood coagulation (Prothrombin activation fragment F1+2 plasma levels by ELISA). P-selectin, GpIIb-IIIa expression, Beta-TG, PF4 and SPA were found similar in MVP patients and in controls. However, in patients with severe mitral regurgitation (MR) the percentage of activated platelets which express P-selectin after stimuli was slightly but significantly (p < 0.05) lower in comparison to MVP patients without or with mild to moderate MR and to controls. Moreover, in patients with severe MR F1+2 levels (median 1.6 nmol/L, range 0.6-2.6 nmol/L) were significantly higher (p < 0.001) than both in controls (median 0.95 nmol/L, range 0.2-1.4 nmol/L) and in patients without or with mild to moderate MR (median 1.0 nmol/L, range 0.4-2.3 nmol/L). Our findings suggest that MVP is not responsible per se for blood clotting activation, but in patients with severe mitral insufficiency an increase in thrombin generation can occur. These alterations in hemostatic system may represent a mechanism by which MR increases the risk of thromboembolic events in patients with MVP.

Adenosine Diphosphate↗

Antiphospholipid antibodies and pregnancy disorders in women with insulin dependent diabetes.

Insulin dependent diabetes (IDD) is considered to be an immune endocrinopathy as in such patients a disorder of the immune system is involved; however, up to now no data are available on the occurrence of antiphospholipid antibodies (aPL) in IDD pregnant women and on possible correlation between the presence of aPL and the high fetomaternal morbidity reported in these patients. The presence of lupus anticoagulant (LA) and of anticardiolipin antibodies (ACA) was monthly evaluated. In 35 IDD pregnant women referring within the 7 degrees week of pregnancy to the High Risk Pregnancy Medical Unit. Levels of D-dimer, fibrin degradation product, were also assayed. Twelve IDD pregnant women resulted to be aPL positive with a markedly high prevalence of positivity (34%). aPL positive did not significantly differ from aPL negative women in age, duration and severity of diabetes and in metabolic control throughout pregnancy. Pregnancy induced hypertension (PIH) and intrauterin growth retard (IUGR) were observed in 6/12 aPL positive and in only 2/23 aPL negative patients (p < 0.02). A pathological increase in D-dimer levels occurred in 6/12 aPL positive patients and in none aPL negative (p < 0.03). The high frequency of aPL positivity and its strict relation to pregnancy complications strongly support a major role for an autoimmune pathogenetic mechanism in the occurrence of feto-maternal morbidity in IDD pregnant women. The identification of this subgroup at risk for complications may be clinically relevant.

Analysis of Variance↗

Hemostatic abnormalities in inflammatory bowel disease.

Patients affected by inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Aims of this study were to investigate hemostatic system and the presence of antiphospholipid antibodies (aPL) in IBD patients. Forty-one patients affected by Crohn's disease (CD) and 19 by ulcerative colitis (UC) were studied, compared to 40 healthy control subjects. Platelet count (PLT), PT, aPTT, fibrinogen (Fib), prothrombin fragment F1+2, antithrombin (AT), protein C (PC), protein S (PS), factor XIII (FXIII), plasminogen (PLG), plasminogen activator inhibitor (PA1), spontaneous platelet aggregation in platelet-rich plasma (PRP-SPA) and in whole blood (WB-SPA), and antiphospholipid antibodies (aPL) were evaluated. PLT, Fib, F1+2 and WB-SPA were significantly increased in IBD patients (p at least <0.05) both in active and inactive phases; aPL positivity was more frequent (p<0.05) and FXIII was significantly decreased (p<0.05) in comparison to control subjects. The thrombophilic state of IBD patients is not related to the degree of activity of the disease or to previous thrombotic events; aPL express the immunological alterations connected with IBD and are not the main cause of thrombotic events.

Adolescent↗

Construction of a modified mini-Tn5 lacZY non-antibiotic marker cassette: ecological evaluation of a lacZY marked Pseudomonas strain in the sugarbeet rhizosphere.

In order to monitor the fate of genetically manipulated fluorescent pseudomonads following release into the environment, a lacZY transposable cassette, lacking antibiotic resistance genes, was constructed using a pUT suicide plasmid delivery system. The resulting plasmid, pUTLacZY, can be easily used to generate lacZY marked pseudomonads without having to use antibiotic resistance determinants. The lacZY transposon generates random, stable transcriptional/translational fusions on integration into the target genome. Pseudomonas fluorescens strain F113 was marked with lacZY and was unaltered with respect to ecological fitness in the rhizosphere. Although lateral gene transfer of the chromosomally integrated lacZY marker could be detected in vitro, it was not detected in rhizosphere microcosms.

Conjugation, Genetic↗

Improved delivery of biocontrol Pseudomonas and their antifungal metabolites using alginate polymers.

Alginate polymer was evaluated as a carrier for seed inoculation with a genetically modified strain Pseudomonas fluorescens F113LacZY, which protects sugar-beet against Pythium-mediated damping-off. F113LacZY survived in alginate beads at 5 log10 CFU/bead or higher counts for 8 weeks of storage, regardless of the conditions of incubation. In plant inoculation experiments, colonisation of the growing area of the root by F113LacZY, derived from alginate beads placed in the soil next to the seed or from an alginate coating around the seeds, was improved compared with application of just free cells of the strain. F113LacZY trapped in alginate beads was an effective producer of antifungal phloroglucinols as indicated by direct HPLC quantification of phloroglucinols and in vitro inhibition of both the indicator bacterium Bacillus subtilis A1 and the pathogenic fungus Pythium ultimum. Alginate polymer represents a promising carrier for the delivery of biocontrol inoculants for root colonisation and production of antifungal metabolites.

Alginates↗

Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus.

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet. Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasminogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL (p < 0.01) and to controls (p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.

Adult↗

Fibrinogen and factor VIIag in healthy adolescents: the Floren-teen (Florence teenager) Study.

At least five studies based on more than twenty thousand healthy subjects indicated that fibrinogen is an independent risk factor for cardiovascular events; less clear-cut is the relation between factor VII and risk for arterial thrombotic disorders, which was demonstrated in two of the three studies investigating this association. However, no study has investigated the behaviour of fibrinogen and factor VII in an adolescent population. In a study of Preventive Medicine and Education Program, fibrinogen (clotting method) and factor VIIag (ELISA), in addition to other metabolic parameters, life-style and familial history, were investigated in 451 students (313 females and 138 males, age 15-17 years) from two high schools of Florence. Fibrinogen levels were significantly higher in women than in men, whereas factor VIIag levels did not significantly differ. Both fibrinogen and factor VIIag significantly correlated with total cholesterol (p < 0.05) while only fibrinogen correlated with body mass index (p < 0.01). Factor VIIag was significantly correlated with systolic blood pressure (p < 0.001). This study provides information on coagulation risk factors in a population of adolescents which may be of importance in planning coronary heart disease prevention programs.

Adolescent↗

D-Dimer in intra-uterine growth retardation and gestational hypertension.

Pregnancy is sometime related to thromboembolic complications (1) and alterations in different hemostatic parameters have been reported in pregnancy (2-4). In particular, a progressive increase in fibrinogen and D-dimer levels occurs during normal pregnancy (5-9). D-dimer levels may be predictive for some complications such as preeclampsia (10) and they have been also reported to be useful for diagnosis of abruptio placentae (6). However, it remains to be established if common ELISA for D-dimer are able to discriminate pathologic samples in conditions such as intrauterine growth retardation (IUGR) or gestational hypertension (GH). Aim of the present study has been to evaluate the behavior of D-dimer in pregnant women with IUGR and GH.

Adult↗

D-dimer concentrations during normal pregnancy, as measured by ELISA.

In pregnant women a number of changes in blood clotting and fibrinolysis proteins have been reported so indicating the existence of a state of hypercoagulability. In addition to fibrinogen and antithrombin III (AT), D-dimer is frequently checked during pregnancy, in particular during at risk pregnancy, but the exact pattern of D-dimer modifications during uncomplicated pregnancy is not definitively described. The aim of this study was to establish the range values in three different periods of uncomplicated pregnancy (A: 1-20 wks; B: 21-30 wks; C: 31-40 wks). We measured plasma levels of D-dimer, clottable fibrinogen and AT in 108 consecutive normal pregnant women aged 16 to 42 years. In period A, the range of D-dimer values was 43-211 ng/mL, not different from controls, while fibrinogen levels were significantly higher (p < 0.05) than in matched non pregnant women. Mean D-dimer levels were higher in periods B (p < 0.05) and C (p < 0.05) vs period A. Similarly, mean fibrinogen levels were found more elevated in periods B and C vs period A (p < 0.05). A significant correlation was found between fibrinogen and D-dimer levels (p < 0.001). No differences in AT levels were found among the three periods of pregnancy. The results of this study indicate that levels of D-dimer up to 685 micrograms/L may be reached at the end of physiological pregnancy. This fact should be taken into account in the evaluation of hemostatic studies performed in uncomplicated and complicated pregnant women.

Adolescent↗

Substance P-induced fibrinolysis in the forearm of healthy humans.

Physiological saline with or without substance P (50 ng/ml) was infused into the humeral artery in 6 healthy males. Indices of fibrinolytic activity (whole blood diluted lysis time, euglobulin lysis time, lysis areas in non-heated fibrin plates produced by plasma or euglobulin precipitate, plasminogen plasma levels, alpha 2-macroglobulin, C1-inhibitor, and alpha 2-antiplasmin) were evaluated in the homolateral antecubital vein before and after 5 min of substance P or saline infusion. After substance P the fibrinolytic activity increased, as can be seen from the shortening of lysis times (p < 0.01) and enlargement of the lysis areas (p < 0.01). A reduction of plasminogen plasma levels (p < 0.01), associated with a decrease in alpha 2-antiplasmin (p < 0.01), was also found. Alpha 2-macroglobulin and C1-inhibitor were instead unaltered by the peptide. The saline infusion, on the other hand, was unable to modify any of the examined indices. We concluded that exogenous substance P given intra-arterially increases fibrinolytic activity in locally-sampled venous blood through a mechanism which remains to be elucidated.

Adult↗

Acute phase proteins in alcoholics with or without liver injury.

Acute phase proteins behaviour has been examined in chronic alcoholics to verify the hypothesis that chronic alcohol consumption stimulates the hepatic synthesis of acute phase proteins. Certain acute phase proteins were studied in two groups of alcoholics, one with and one without liver damage, and in a third group of healthy volunteers. The results show that the acute phase proteins were similar in the two groups of alcoholics, but differed when compared to the control group. The authors have concluded from these results, that chronic alcohol consumption causes a serum increase of: mucoproteins (p less than 0.001), alpha 1 acid glycoprotein (p less than 0.05), haptoglobin (p less than 0.05) and fibrinogen (p less than 0.02). Such increases are independent from the existence of liver damage.

Acute-Phase Proteins↗

Comparison of some serum copper parameters in trained runners and control subjects.

The serum copper parameters were evaluated in 41 male trained runners and in a control group of 24 male subjects engaged in normal physical activity. In the runner group lower serum copper concentrations, lower serum ceruloplasmin biological activity, and higher serum ceruloplasmin levels were found compared with the control group. Reduced serum copper levels may affect the ceruloplasmin biological activity, even if the serum ceruloplasmin levels are higher. The results suggest that more attention should be paid to serum copper and ceruloplasmin in athletes.

Adolescent↗