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Biomedical subjects

E Sacchi

Publications and source records attributed to E Sacchi.

At least 19 recordsLinked to original sources
PubMed2004

Gamma dose rate calculation and mapping of piemonte (North-West Italy) from gamma spectrometry soil data.

In this study the air gamma dose rate map of Piemonte, a region in the North-West of Italy, was produced from gamma spectrometry soil data. Soil samples collected in 110 different sites of Piemonte were analysed with Hyperpure Germanium (HPGe) detectors (30% relative efficiency), which allow the evaluation of the activity concentrations of natural radionuclides and (137)Cs. Then, using the available mathematical models, the gamma absorbed dose rate in air due to radionuclides was calculated. The contribution of the cosmic radiation to the total absorbed dose rate, which depend on the site altitude was also evaluated and added to the soil contribution. Finally, the map of the whole region was obtained by fitting the dose rate values of the different sites with kriging algorithms.

Algorithms↗
PubMed2004

Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementation in Type 2 diabetic patients.

Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age +/- SD, 62.1 +/- 6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5th and 10th week) and after (30th week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5th and the 10th week from baseline followed by an increase at the 30th week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the 10th week, while a decrease in 5G/5G PAI-1 was observed from the 5th week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects.

Antioxidants↗
PubMed2001

Multivariate statistical and GIS-based approach to identify heavy metal sources in soils.

The knowledge of the regional variability, the background values and the anthropic vs. natural origin for potentially harmful elements in soils is of critical importance to assess human impact and to fix guide values and quality standards. The present study was undertaken as a preliminary survey on soil contamination on a regional scale in Piemonte (NW Italy). The aims of the study were: (1) to determine average regional concentrations of some heavy metals (Cr, Co, Ni, Cu, Zn, Pb); (2) to find out their large-scale variability; (3) to define their natural or artificial origin; and (4) to identify possible non-point sources of contamination. Multivariate statistic approaches (Principal Component Analysis and Cluster Analysis) were adopted for data treatment, allowing the identification of three main factors controlling the heavy metal variability in cultivated soils. Geostatistics were used to construct regional distribution maps, to be compared with the geographical, geologic and land use regional database using GIS software. This approach, evidencing spatial relationships, proved very useful to the confirmation and refinement of geochemical interpretations of the statistical output. Cr, Co and Ni were associated with and controlled by parent rocks, whereas Cu together with Zn, and Pb alone were controlled by anthropic activities. The study indicates that background values and realistic mandatory guidelines are impossible to fix without an extensive data collection and without a correct geochemical interpretation of the data.

Environmental Monitoring↗
PubMed2001

HELLP syndrome and factor V Leiden.

The association of thrombophilia and obstetrical complications is documented and well consistent with the hypothesis of an insufficient placental perfusion due to fibrin deposition as a major underlying pathophysiological mechanism. Factor V Leiden is one of the most frequent thrombophilic mutations. A high prevalence of this mutation has recently been reported in a group of 21 German women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. In this respect, we studied the prevalence of factor V Leiden in 18 women who were consecutively diagnosed at our Department of Obstetrics and Gynaecology as having HELLP syndrome, between 1995 and 1999. Women were tested either at the time of diagnosis or months or years after delivery for coagulation parameters, protein C (PC), protein S (PS), antithrombin III, lupus-like anticoagulant, anticardiolipin antibodies (ACA), activated protein C (APC) resistance and detection of the G1691A mutation (factor V Leiden). In all women, the parameters studied were normal and in none of the investigated cases was the G1691A mutation found. HELLP being a severe form of preeclampsia, we think that the reported association between factor V Leiden and HELLP may reflect the well-known association with preeclampsia.

Adult↗
PubMed2000

Inflammatory bowel diseases are not associated with major hereditary conditions predisposing to thrombosis.

Patients with inflammatory bowel diseases (IBD) are at increased risk for thromboembolic complications. Our aim was to evaluate whether the increased risk for thrombosis in IBD could be due to a genetic association of IBD with hereditary prothrombotic conditions. In all, 102 IBD patients (51 with ulcerative colitis and 51 with Crohn's disease) with no history of thrombosis and 204 matched normal subjects were enrolled. DNA specimens were evaluated by PCR and restriction fragment length polymorphism for factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) and prothrombin gene mutations. In IBD patients and matched controls the observed allele frequencies were similar, being 1.5% and 1.2% for factor V Leiden gene mutation, 1.1% and 0.7% for prothrombin gene mutation, and 45.1% and 47.4% for MTHFR gene mutation, respectively. These rates also were not significantly different when patients were analyzed according to age and sex distribution, diagnosis, and extension and clinical type of disease. In conclusion, our study shows no association between IBD and the most frequent hereditary prothrombotic conditions. Other factors should be evaluated in order to understand the mechanisms underlying the thrombotic risk of IBD.

Adult↗
PubMed2000

A novel polymorphism in intron 1a of the human factor VII gene (G73A): study of a healthy Italian population and of 190 young survivors of myocardial infarction.

We have identified a novel polymorphism located in intron 1a of the human factor VII gene, caused by the nucleotide change G to A at position + 73. In a population of 128 healthy individuals from northern Italy, the variant A73 allele had a frequency of 0.21, whereas the frequency of the previously reported 10 bp insertion allele located at -323 in the promoter region was 0.17 and that of the Q353 allele in the catalytic region of the factor VII gene was 0. 20. In 75% of the healthy individuals, the A73 allele was present together with the 10 bp insertion and the Q353 alleles, indicating a strong linkage disequilibrium. The concomitant presence of A73 with both the 10 bp and the Q353 alleles was associated with the lowest factor VII levels, measured as coagulant activity, activated factor VII and factor VII antigen. The G73A polymorphism was also evaluated in 190 survivors of myocardial infarction who had experienced the event before the age of 45 years and in 179 individuals with a negative exercise test matched with patients for sex, age and geographical origin. Patients carrying the A73 allele associated with lower factor VII levels tended to have a lower risk of myocardial infarction (adjusted odds ratio 0.54; 95% confidence intervals 0.29-0.99). In conclusion, we found a novel variant allele in intron 1a of the human factor VII gene that is often associated in healthy individuals with the 10 bp and Q353 alleles in the promoter and catalytic region of the same gene. This intronic mutation, alone or in association with other factor VII gene polymorphisms, might confer protection against myocardial infarction in the young.

Adolescent↗
PubMed1998

High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.

BACKGROUND: Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and nongenetic risk factors (such as the use of oral contraceptive agents). We compared the prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80 patients with deep-vein thrombosis of the lower extremities, and 120 healthy controls. The G1691A mutation in the factor V gene and the G20210A prothrombin-gene mutation, which are established genetic risk factors for venous thrombosis, were studied. We also assessed the use of oral contraceptives and other risk factors for thrombosis. RESULTS: The prevalence of the prothrombin-gene mutation was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to 31.0) and was similar to that in patients with deep-vein thrombosis (18 percent). Similar results were obtained for the mutation in the factor V gene. The use of oral contraceptives was more frequent among women with cerebral-vein thrombosis (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61 percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women who were taking oral contraceptives and who also had the prothrombin-gene mutation (seven patients with cerebral-vein thrombosis but only one control), the odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence interval, 31.0 to 711.0). CONCLUSIONS: Mutations in the prothrombin gene and the factor V gene are associated with cerebral-vein thrombosis. The use of oral contraceptives is also strongly and independently associated with the disorder. The presence of both the prothrombin-gene mutation and oral-contraceptive use raises the risk of cerebral-vein thrombosis further.

Adolescent↗
PubMed1997

A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype.

Factor V gene polymorphisms were investigated to detect components that may contribute to the activated protein C (APC) resistance phenotype in patients with venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by six polymorphisms and its frequency was found to be similar in normal subjects coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was originated by ancestral mutational events. The relationship between the distribution of normalized APC ratios obtained with the functional assay and haplotype frequency was analyzed in patients heterozygous for factor V R506Q (factor V Leiden). The HR2 haplotype was significantly more frequent in patients with ratios below the 15th percentile than in those with higher ratios or in normal controls. Moreover, the study of 10 patients with APC resistance in the absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2 homozygotes. The HR2 haplotype was associated with significantly lower APC ratios both in patients with venous thromboembolism and in age- and sex-matched controls. However, the two groups showed similar HR2 haplotype frequencies. Plasma mixing experiments showed that an artificially created double heterozygote for the factor V R506Q mutation and the HR2 haplotype had an APC ratio lower than that expected for a simple R506Q heterozygote. Time-course experiments evaluating the decay of factor V in plasma showed the normal stability of the molecule encoded by the factor V gene marked by the HR2 haplotype, which ruled out the presence of a pseudo-homozygous APC resistance mechanism. Our results provide new insights into the presence of factor V genetic components other than the factor V R506Q that are able to contribute to the APC resistance phenotype in patients with venous thromboembolism.

Alleles↗
PubMed1997

Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians.

Gene polymorphisms associated with the plasma levels of fibrinogen, factor VII, and plasminogen activator inhibitor 1 (PAI-1)-hemostasis proteins that help to predict the risk of atherothrombotic disease-were compared in 124 healthy individuals > or = 100 years old and 130 young, healthy individuals to identify genetic influences on extreme longevity. We investigated the restriction fragment length polymorphism G/A-455 located in the promoter of the beta-fibrinogen gene, the guanine insertion/deletion polymorphism 4G/5G in the promoter of the PAI-1 gene, and the R353Q substitution polymorphism in exon 8 of the factor VII gene. Alleles and genotypes associated with elevated plasma levels of fibrinogen and factor VII were found with similar frequencies in centenarians and in the comparison group. However, in centenarians there was a significantly higher frequency of the 4G allele and of the homozygous 4G4G genotype associated with high PAI-1 levels. Since high PAI-1 is considered a predictor of recurrent myocardial infarction in young men, it is intriguing that the corresponding genetic marker is more frequent in centenarians who have escaped major age-related atherothrombotic disease and reached the extreme limits of human life. Homozygosity for the 4G allele, despite its association with impaired fibrinolysis, is compatible with successful aging.

Aged↗
PubMed1996

Plasma factor VII levels are influenced by a polymorphism in the promoter region of the FVII gene.

Genetic factors play a role in determining the variability of plasma factor VII (FVII) levels in healthy individuals. There is also evidence that high serum lipids are associated with high FVII levels in plasma. In the promoter region of the human FVII a DNA polymorphism has been described, originating from a decanucleotide insert present in the less frequent allele. This biallelic system, reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be detected by a DNA enzyme immunoassay of PCR products. We evaluated the association between the polymorphic alleles and the levels of FVII:Ag and FVII:C in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences for FVII:Ag and FVII:C were found in individuals with triglycerides above 250 mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to triglycerides only in individuals without the insert (P < 0.01); there was no significant relationship in those carrying the allele with the insert (A/a; P = 0.43 and 0.08). Our findings of genotype-associated differences in FVII levels and interactions with triglycerides are similar to those obtained with the amino acid dimorphism at position 353 of the factor VII protein.

Adult↗
PubMed1995

Protein S mRNA in patients with protein S deficiency.

A protein S gene polymorphism, detectable by restriction analysis (BstXI) of amplified exonic sequences (exon 15), was studied in seven Italian families with protein S deficiency. In the 17 individuals heterozygous for the polymorphism the study was extended to platelet mRNA through reverse transcription, amplification and densitometric analysis. mRNA produced by the putative defective protein S genes was absent in three families and reduced to a different extent (as expressed by altered allelic ratios) in four families. The allelic ratios helped to distinguish total protein S deficiency (type I) for free protein S deficiency (type IIa) in families with equivocal phenotypes. This study indicates that the study of platelet mRNA, in association with phenotypic analysis based upon protein S assays in plasma, helps to classify patients with protein S deficiency.

Alleles↗
PubMed1993

Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay.

Nine thrombophilic patients who had had previous diagnoses of functional protein S deficiency were reinvestigated. The functional protein S assays gave dose-response curves that were not parallel to those of the reference plasma. The same pattern was true for approximately half of the first-degree relatives of the propositi. When protein S was extracted from the plasma of the patients by immunoabsorption, it had a normal ratio of functional activity to immunologic concentration. Restriction fragment length polymorphism analysis, informative in one family, showed no linkage between the protein S gene marker and the abnormal behavior of the protein S functional assay. All the propositi and 23/36 first-degree relatives were resistant to the prolongation of activated partial thromboplastin time induced by activated protein C. Furthermore, there was striking concordance in all patients and relatives between the abnormal pattern of the protein S functional assay and resistance to activated protein C. We conclude that a plasma-based functional protein S assay is sensitive to activated protein C resistance and this may lead to spuriously low results in the assay. In agreement with the results of others, this study indicates that resistance to activated protein C is a frequent hemostatic defect in selected thrombophilic populations.

Base Sequence↗
PubMed1993

The genetic defect of type I von Willebrand disease "Vicenza" is linked to the von Willebrand factor gene.

Type I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF contrasting with a mild bleeding tendency. The pathophysiology of this subtype is still unknown. The presence of supranormal multimers in the patients' plasma could be due to a mutation in the vWF molecule which affects post-translational processing, or to a defect in the cells' processing machinery, independent of the vWF molecule. In order to determine if type I vWD Vicenza is linked to the vWF gene, we studied six polymorphic systems identified within the vWF gene in two apparently unrelated families with type I vWD Vicenza. The results of this study indicate a linkage between vWF gene and the type I vWD Vicenza trait. This strongly suggests that type I vWD Vicenza is due to a mutation in one of the vWF alleles, which results in an abnormal vWF molecule that is processed to a lesser extent than normal vWF.

Alleles↗
PubMed1993

Carrier detection and feasibility of prenatal diagnosis of hemophilia B by multiplex polymerase chain reaction.

Since direct diagnosis based on detection of factor IX mutations by direct sequencing is currently performed in a few laboratories only, restriction fragment length polymorphisms are still useful for carrier detection and prenatal diagnosis of hemophilia B. We analyzed 29 women from 20 families at risk of hemophilia B with three intragenic (MnlI, DdeI, TaqI) and two extragenic (HhaI, BamHI) restriction fragment length polymorphisms, all by the polymerase chain reaction. This analysis confirmed 10 possible carriers and excluded 16 as carriers. The diagnosis was made in 17 of the 20 families (85%). The combination of three polymorphisms indicated that MnlI/DdeI/HhaI and TaqI/DdeI/HhaI were the most informative (15/20 families, 75% and 14/20 families, 70%). For carrier detection with the most useful polymorphism combination (TaqI/DdeI/HhaI) we devised a multiplex polymerase chain reaction that uses two or three sets of primers, allowing carrier diagnosis in one step with 99% reliability. Our results indicate that the combination of five restriction fragment length polymorphisms makes carrier detection and prenatal diagnosis possible for 85% of families at risk of hemophilia B, with 99% reliability. With multiplex polymerase chain reaction such diagnoses can be obtained faster.

Base Sequence↗