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Biomedical subjects

R Marcucci

Publications and source records attributed to R Marcucci.

At least 19 recordsLinked to original sources
PubMed2007

Endogenous risk factors for deep-vein thrombosis in patients with acute spinal cord injuries.

STUDY DESIGN: Case-control study. AIM OF THE STUDY: Investigate the presence of additional endogenous risk factors of deep-vein thrombosis (DVT). SETTING: Regional Spinal Unit of Florence, Italy. METHODS: A total of 43 patients with spinal lesion and a history of DVT during the acute stage of their neurological impairment (Group A) were comprehensively evaluated and the blood concentrations of the following risk factors, that are presumably associated with DVT, were determined: antithrombin III (ATIII), protein C (PC), protein S (PS), factor V Leiden, gene 200210A polymorphism, homocysteine (Hcy), inhibitor of plasminogen activator-1 (PAI-1) and lipoprotein A (LpA). The control group (Group B) consisted of 46 patients matched to Group A for sex, age, neurological status and prophylactic treatment during the acute stage, with no history of DVT. Statistical analysis was performed using the Mann-Whitney and Fisher's exact tests. RESULTS: Of the individuals in Group A, 14% had no risk factor and 86% had at least one; however, in Group B 54% had no endogenous risk factors and 46% had at least one. None of the individuals in either group had a deficit in their coagulation inhibitors (ATIII, PC and PS), and the LpA level was equivalent in the two groups. The levels of Hcy and PAI-1 were significantly higher in Group A. CONCLUSIONS: Increases in the levels of plasma Hcy and PAI-1 are demonstrated to be independent risk factors for developing a DVT.

Adult↗
PubMed2006

Chronic kidney disease is still present after renal transplantation with excellent function.

According to a k/DOQI work group, chronic kidney disease (CKD) can be present also in subjects with glomerular filtration rate (GFR) >90 mL/min or a serum creatinine (sCr) below 1.3 mg/dL. The aim of this study was to document the prevalence of clinical or biologic abnormalities among 190 cadaveric renal transplant patients with excellent and stable renal function at 6 months after transplantation as well as 5 years later. The recipients were 82 women and 108 men of mean age at transplantation of 44.56 +/- 11.73 years. All patients were on Neoral-based immunosuppression with at least 5-year follow-up. Mean sCr was 1.18 +/- 0.2 mg/dL. Mean GFR was 78.57 +/- 27.06 mL/min. Systolic blood pressure was >130 mm Hg in 56.6%, although 78.3% of patients were on antihypertensive therapy; 34.3% were anemic; 75.4% had serum cholesterol >200 mg/dL; 62.2% had serum triglyceride levels >170 mg/dL. Serum intact parathyroid hormone >100 pg/mL was observed in 38% of patients and 43% were on vitamin D supplementation, and 11.4% had developed posttransplant diabetes mellitus. With respect to controls, von Willebrand factor was higher in 81.2% (P < .0001; RR = 11); serum homocysteine levels in 75% (P < 0.001; RR = 7.61); PAI-1 in 37.5% (P = .0009; RR = 4). At 5 years posttransplantation we observed an overall improvement in these abnormalities. The vast majority of renal transplant patients with excellent graft function belong to stage 1 of CKD being affected by hypertension, dyslipidemia, anemia, and residual hyperparathyroidism. Markers of endothelial dysfunction were largely abnormal, a condition that could predispose to cardiovascular events.

Adult↗
PubMed2006

Markers of hypercoagulability and inflammation predict mortality in patients with heart failure.

BACKGROUND AND AIMS: Plasma levels of inflammatory markers are increased in chronic heart failure (HF) and are also subclinical indicators of future HF. Inflammation is strictly correlated with clotting activation, but the association between inflammation, hypercoagulability and prognosis in HF has not been previously reported. METHODS AND RESULTS: Markers of inflammation (interleukin-6; IL-6, and C-reactive protein; CRP) and hypercoagulability (D-dimer; DD, and thrombin-antithrombin III complex; TAT) were prospectively assessed in 214 subjects with New York Heart Association (NYHA) functional class II-IV HF. During a median follow-up of 8.5 months, 32 patients had an event: 13 died and 19 were hospitalized because of worsening of HF. IL-6, DD and TAT levels were all significantly associated with increased risk of death after adjustment for other known HF prognostic factors (age, gender, traditional cardiovascular risk factors, NYHA class, systolic left ventricular function, renal failure, hemoglobin, serum sodium) in a Cox multivariate proportional hazard model (P = 0.003, P = 0.01 and P = 0.02, respectively). When these markers were added simultaneously to the known prognostic factors in a new Cox multivariate model, only DD levels were significant predictors of mortality (hazard ratio [95% confidence interval; CI]: 11 [2.7-45.1], P = 0.001). The Kaplan-Meier curve revealed a significantly better outcome in patients with DD below 450 ng mL(-1). NT-pro-BNP was the only significant predictor of rehospitalization (HR [95% CI]: 5.3 [2.0-13.8], P < 0.001). CONCLUSION: Hypercoagulability and inflammation, as assessed by DD, TAT and IL-6 levels, are associated with an increased mortality risk in HF.

Aged↗
PubMed2005

Protein Z plasma levels in different phases of activity of coronary atherosclerosis.

We previously reported that low protein Z plasma levels are associated with acute coronary syndromes (ACS). Aim of the present study was to evaluate protein Z levels in different phases of activity of coronary atherosclerosis. Protein Z plasma levels were measured in 166 (131 male and 35 female) patients consecutively admitted to the University of Florence with a diagnosis of ACS (group A), 166 (131 male and 35 female) patients selected by age and gender in relation to group A from those with a clinical history of ACS who remained symptom- and/or event-free over the last year before the investigation (group B); and 332 (262 male and 70 female) controls comparable for age and gender with the other two groups. None had liver or renal dysfunction nor showed a positivity for antiphospholipid antibodies or for factor V Leiden mutation. Patients under warfarin therapy were excluded. Mean protein Z plasma levels were found to be significantly (P < 0.0001) lower in group A (1475 +/- 684.1 ng mL(-1)) and group B (1327.6 +/- 690.7 ng mL(-1)) as compared with control group (1650.1 +/- 634.5 ng mL(-1)), while no significant differences existed between the two groups of patients (P = 0.06). A logistic regression analysis, performed after the division of the study population into quartiles of protein Z levels and adjusted for all possible confounders, showed a significant increased risk of ACS for the lowest (<1213 ng mL(-1)) as compared with the highest quartile of protein Z in both groups of patients [group A odds ratio (OR): 2.7, 95% CI 1.3-5.5, P = 0.007; group B OR: 3.2, 95% CI 1.1-8.9, P = 0.02). In conclusion, these results strengthen our previous data on low protein Z plasma levels in ACS and indicate a possible dose-response effect of decreasing protein Z plasma levels on the coronary atherosclerotic disease.

Adult↗
PubMed2005

PAI-1 and homocysteine, but not lipoprotein (a) and thrombophilic polymorphisms, are independently associated with the occurrence of major adverse cardiac events after successful coronary stenting.

OBJECTIVE: To evaluate the role of factor V Leiden, prothrombin G20210A polymorphism, plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism, PAI-1, homocysteine, and lipoprotein (a) (Lp(a)) in the occurrence of major adverse cardiac events (MACE) in patients with acute coronary syndromes who underwent coronary stenting. DESIGN: 520 patients (375 men and 145 women) with acute coronary syndromes and 520 age and sex matched controls were enrolled. MACE were recorded for 109 patients. Heterozygosity for factor V Leiden, prothrombin G20210A polymorphism, and 4G/5G polymorphism did not significantly differ between patients with and without MACE. A significantly higher percentage of patients with increased homocysteine (28% v 19%, p < 0.001) and PAI-1 concentrations (25% v 16%, p < 0.001) had MACE with respect to those who did not. In Kaplan-Meier survival analysis, the overall risk of MACE was significantly higher among patients with increased PAI-1 (p = 0.006) and homocysteine concentrations (p = 0.04). Cox regression analysis adjusted for age, sex, traditional cardiovascular risk factors, renal function, systolic left ventricular function, the number of stenosed vessels, and history of percutaneous coronary intervention or coronary artery bypass grafting showed that homocysteine (odds ratio 7.5, 95% confidence interval (CI) 1.1 to 57.7, p < 0.05) and PAI-1 concentrations (odds ratio 5.3, 95% CI 1.2 to 23.8, p < 0.05) within the fifth quintile (with respect to the first) were significant and independent risk factors for the future occurrence of MACE. CONCLUSIONS: Increased PAI-1 and homocysteine concentrations are independent risk factors for MACE after successful coronary stenting, whereas Lp(a) and thrombophilic polymorphisms are not predictive.

Adult↗
PubMed2005

Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the 'Florence' diet is not Mediterranean.

OBJECTIVE: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels. DESIGN: Cross-sectional. SETTING: Population-based study. SUBJECTS: A sample of 520 clinically healthy subjects (211 males, 309 females) with a mean age of 46 y, living in Florence area, Italy. INTERVENTIONS: Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. Fasting blood samples were drawn for assessment of lipid profile, homocysteine and circulating vitamins. RESULTS: Contribution from total fats was over 30% in about 70% of subjects and intake of saturated fatty acids (SFA) was above the recommended values in at least 40% of the study population. Furthermore, almost the whole (99.6%) population reported low intake of polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present in over 40% of the study population, whereas abnormal values of LDL-cholesterol were observed in about 30%. High levels of homocysteine were found in 11.7% of the study population. An extremely high percentage of subjects reported low intake of vitamins, especially with regard to folic acid (89%), vitamin B(6) (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating levels of vitamin B(12) and folic acid, and intake of alcohol and vitamin C resulted in being independently associated with homocysteine plasma levels. CONCLUSIONS: In a typical Mediterranean country, general outlines of Mediterranean diet are not completely followed, especially concerning total fats, SFA, PUFA and vitamins' intake. SPONSORSHIP: Ministero della Salute (Italy) - 'Progetto per la Salute e la Prevenzione di Malattia' 2001-2003.

Cardiovascular Diseases↗
PubMed2005

Relevance of post-methionine homocysteine and lipoprotein (a) in evaluating the cardiovascular risk in young CAD patients.

BACKGROUND: Aims of our study were to evaluate the prevalence of high lipoprotein (a) [Lp(a)] and homocysteine levels - both in the fasting state (FHcy) and post-methionine (PMHcy) - in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia. MATERIALS AND METHODS: We studied 140 patients with angiographically documented CAD (24 women </= 55 years and 116 men </= 50 years) and 140 healthy subjects as controls. RESULTS: Both FHcy [13.2 (5.4-45.8) vs. 9.0 (5.1-24) micromol L(-1)); P < 0.0001] and PMHcy [(39.4 (9.0-66.4) vs. 25.2 (16.4-33.9); P < 0.0001] were significantly higher in patients than in controls. Lp(a) levels were significantly higher in patients than in controls (200 (3-1486) mg L(-1) vs. 97 (10-412) mg L(-1); P < 0.0001). At the multivariate analysis, adjusted for the classical cardiovascular risk factors and creatinine levels, the OR (95% CI) for CAD at young age significantly increased in the fourth quartile of the distribution of FHcy, PMHcy and Lp(a) levels [FHcy: 14.9 (4.1-58), P < 0.0001; PMHcy: 19.2 (4.0-86.3); P < 0.0001; Lp(a): 19.6 (4.7-78.6): < 0.0001]. Vitamin deficiencies were detected in 28/140 (20%) patients. The prevalence of the homozygous C677T (+/+) methylenetetrahydrofolatereductase genotype was higher, but not significantly different, in patients (22.8%) than in controls (18.6%). The allele frequency of the 844ins68 insertion variant in the cystathionine beta-synthase gene was 0.08 in the control group and 0.06 in the patient group. CONCLUSIONS: Results of the present study indicate the usefulness of including fasting and post-methionine Hcy, and Lp(a) determination in the diagnostic panels of young CAD patients, in order to obtain a better assessment of their cardiovascular risk profile.

Adult↗
PubMed2005

Thrombophilic risk factors in patients with severe carotid atherosclerosis.

Carotid stenosis and atrial fibrillation are the strongest risk factors for ischemic stroke. Ongoing prevention efforts include the identification of novel factors that increase the risk for carotid atherosclerosis. The aim of this study was to determine the thrombophilic risk profile of patients with severe carotid stenosis by evaluating a number of genetic and metabolic risk factors [factor (F)II G20210A, factor V Leiden, MTHFR C677T polymorphisms, anticardiolipin antibodies (aCL), lipoprotein(a) (Lp(a)), and homocysteine (Hcy)]. The study population consisted of 615 patients [(410 M/205 F; median age 73 (26-94) years] with severe (> 70%) carotid stenosis, and 615 apparently healthy subjects [(410 M/205 F; age 73 (31-92) years]. On multivariate analysis, independent risk factors were elevated Hcy [odds ratio (OR) 7.6, 95% confidence interval (CI) 4.8, 11.8] and Lp(a) levels (OR 2.9, 95% CI 2.1, 3.9), the presence of aCL (OR 5.7, 95% CI 3.1, 10.4) and heterozygosity for FII G20210A polymorphism (OR 2.8, 95% CI 1.3, 5.9). In the subgroup of women, independent risk factors for severe carotid atherosclerosis were: high levels of Hcy and Lp(a) and the presence of aCL, whereas hyperhomocysteinemia, elevated Lp(a) levels, aCL, FII G20210A and MTHFR 677TT polymorphisms remained independent risk factors in the subgroup of men. The results of the present study demonstrate that the prevalence of the thrombophilic risk factors is increased in patients with severe carotid atherosclerosis.

Adult↗
PubMed2005

Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss.

BACKGROUND: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100,000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded. OBJECTIVES: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). PATIENTS AND METHODS: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%). RESULTS AND CONCLUSIONS: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

Adult↗
PubMed2005

Cardiovascular risk factors in severe chronic renal failure: the role of dietary treatment.

BACKGROUND: Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF). METHODS: Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid. RESULTS: Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p < 0.005) with a reduction of LDL cholesterol (p < 0.01) and an increase of apoA1/apoB ratio (p < 0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p < 0.05) with lower TBARS concentrations (p < 0.01) and a significant reduction of total homocysteine (p < 0.002), Lp(a) (p < 0.002) and CRP levels (p < 0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p < 0.001) and OxLDL (p < 0.006) were associated to a risk of CRP > 0.3 mg/dl. CONCLUSIONS: These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Adult↗
PubMed2004

Role of hyperhomocysteinemia in aortic disease.

A growing body of evidence has shown a strong association between elevated plasma homocysteine (Hcy) levels with vascular disease and thrombotic complications. Data available in literature also suggest a role of hyperhomocysteinemia in abdominal and thoracic aortic diseases. In particular, Hcy was investigated in patients with Marfan syndrome and it was demonstrated that Hcy levels were associated with the risk of severe cardiovascular manifestations or dissection. Hcy was significantly higher also in patients with abdominal aortic aneurysms and was associated with the size of aneurysms. It remains to be elucidated if this association is causal or simply an effect of the disease. A number of mechanisms may be evoked to explain these findings. Studies in animal models demonstrated that hyperhomocysteinemia could induce marked remodelling of the extracellular matrix of the arterial wall by inducing elastolysis through the activation of metalloproteinases. In addition, Hcy may directly affect fibrillin-1 or collagen by interfering with intra- and/or inter-molecular disulfide bonds through disulfide exchange, or binding to free sulphydryl groups. Further studies are needed to confirm the role of Hcy in aortic disease and the usefulness of including Hcy determination in the clinical evaluation of these patients.

Aged↗
PubMed2003

Emerging risk factors for ischemic stroke.

The strongest evidence of a relationship between homocysteine (Hcy) and risk of cerebrovascular disease has been provided by six prospective studies. The vascular risk was shown to be dose dependent for both fasting and postmethionine Hcy levels and statistically independent of traditional cardiovascular risk factors, although there was a multiple effect in the presence of smoking and hypertension. Recently, it was demonstrated that not only hyperHcy but also MTHFR polymorphism is an independent risk factor for dissection. Finally, preliminary data suggest that hyperHcy is a risk factor for the occurrence of cerebrovascular events (transient ischemic attack/stroke) in patients with atrial fibrillation. On the basis of these results, several intervention trials are ongoing to determine whether lowering Hcy levels with vitamin supplementation will reduce the recurrence of stroke.

Biomarkers↗
PubMed2003

ACE DD genotype: an independent predisposition factor to venous thromboembolism.

BACKGROUND: The renin angiotensin system affects haemostasis through different mechanisms; data on the possible role of angiotensin-converting enzyme I/D polymorphism in the pathogenesis of deep venous thrombosis are conflicting, and no information is available regarding the A1166C polymorphism of the angiotensin type 1 receptor gene. In order to investigate this issue, angiotensin-converting enzyme and AT1R polymorphisms were genotyped in 336 consecutive venous thromboembolism patients and 378 controls. MATERIALS AND METHODS: Haemostasis-related risk factors have been evaluated by routine tests. Factor V Leiden, Factor II (G20210A), angiotensin-converting enzyme (I/D), and angiotensin type 1 receptor (A1166C) polymorphisms have been identified by molecular analysis. RESULTS: We documented a significant association between angiotensin-converting enzyme DD genotype and venous thromboembolism (OR=2.19 95%CI 1.51-3.17 adjusted for acquired and haemostasis-related risk factors, P<0.0001); in patients with haemostasis-related risk factors, angiotensin-converting enzyme DD genotype modified the risk of venous thromboembolism in hyperhomocysteinaemic and Factor V Leiden patients and was associated with the risk of recurrent venous thromboembolism (OR=1.83 95%CI 1.06-3.17 P=0.03). In patients without haemostasis-related risk factors the angiotensin-converting enzyme DD genotype was still an independent predictor of venous thromboembolism (OR=3.29 95%CI 2.17-4.98 adjusted for acquired risk factors, P<0.0001). No significant association between the angiotensin type 1 receptor CC genotype and venous thromboembolism was found. CONCLUSIONS: This study shows that angiotensin-converting enzyme DD genotype represents a susceptibility marker of thrombosis in subjects apparently without predisposing factors and traditional thrombophilic alterations, and increases the risk of venous thromboembolism in subjects in whom a thrombogenic condition occurs. Moreover, angiotensin-converting enzyme DD genotype may be considered a new predisposing factor to venous thromboembolism recurrence.

Adolescent↗
PubMed2001

High cysteine levels in renal transplant recipients: relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism.

BACKGROUND: Long-term survival of renal transplant recipients seems to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. Preliminary data available in the literature found high levels of cysteine (Cy) as a risk factor for deep venous thrombosis independently of high homocysteine (tHcy) levels, but no data are available about Cy levels in renal transplant recipients. METHODS: To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant recipients and 66 age- and sex-matched normal subjects as controls. RESULTS: Cy, tHcy, and PAI-1 levels were significantly higher in renal transplant recipients with respect to controls (Cy: 254 micromol/L [117-466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1 micromol/L [2.0-24.0], P<0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0-18.0], P<0.00001). High Cy levels were detected in 35.8% of patients. Hyperhomocysteinemia, both in the fasting state and postmethionine loading test, was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the fourth quartile with respect to the other quartiles were markedly increased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0 micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting tHcy levels correlated well with PAI-1 (r=0.65; P<0.0001) but not with Cy levels (r=0.10; P=0.4). The prevalence of the MTHFR 677TT genotype in renal transplant recipients was not significantly higher in patients than in controls (mutant allele frequency: 0.48 in patients and 0.47 in controls) and was associated with significantly higher fasting and postmethionine tHcy levels both in controls and patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 micromol/L [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy levels showed a small decrease that did not reach statistical significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/L [168-300]; P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of decrease of tHcy levels with respect to the other genotypes. CONCLUSION: In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy levels, and the amount of decrease seems to be influenced by the MTHFR genotype.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Splicing of constitutive upstream introns is essential for the recognition of intra-exonic suboptimal splice sites in the thrombopoietin gene.

The human thrombopoietin (TPO) gene, which codes for the principal cytokine involved in platelet maturation, shows a peculiar alternative splicing of its last exon, where an intra-exonic 116 nt alternative intron is spliced out in a fraction of its mRNA. To characterize the molecular mechanism underlying this alternative splicing, minigenes of TPO genomic constructs with variable exon-intron configurations or carrying exclusively the TPO cDNA were generated and transiently transfected in the Hep3B cell line. We have found that the final rate of the alternative intron splicing is determined by three elements: the presence of upstream constitutive introns, the suboptimal splice sites of the alternative intron and the length of the alternative intron itself. Our results indicate that the recognition of suboptimal intra-exonic splice junctions in the TPO gene is influenced by the assembly of the spliceosome complex on constitutive introns and by a qualitative scanning of the sequence by the transcriptional/splicing machinery complex primed by upstream splicing signals.

Alternative Splicing↗
PubMed2001

The role of cysteine and homocysteine in venous and arterial thrombotic disease.

Hyperhomocysteinemia is a risk factor for arterial and venous thrombosis, whereas few data are available on the total cysteine (tCy) levels in thrombophilic patients. We studied 82 patients with a previous myocardial infarction (MI; group 1), 68 patients with a previous deep venous thrombosis (group 2), and 100 control subjects (group 3). We assayed total homocysteine (tHcy) and tCy levels by high-performance liquid chromatography with fluorimetric detection. The odds ratios (ORs) for high levels of tCy and tHcy in venous thrombosis and MI were markedly increased in group 1 (fasting tCy: OR, 3.6; 95% confidence interval [CI], 1.6-11.2; postmethionine tCy: OR, 0.97; CI, 0.3-4.0; fasting tHcy: OR, 8.3; CI, 3.9-18.6; postmethionine tHcy: OR, 12.5; CI, 6.8-27.2) and in group 2 (fasting tCy: OR, 2.9; CI, 1.1-7.8; postmethionine tCy: OR, 0.86; CI 0.2-2.6; fasting tHcy: OR, 8.0; CI 3.6-18.0; postmethionine tHcy: OR, 11.0; CI, 6.0-22.1). Our data suggest that plasma tCy levels are a risk factor for venous thrombosis and MI independently of tHcy levels and that it may be appropriate to study both variables simultaneously to thoroughly study the methionine metabolism.

Adult↗
PubMed2001

Comparison of three methods for total homocysteine plasma determination.

Hyperhomocysteinemia is a well established risk factor for atherothrombotic disease, and the request for homocysteine determinations and the number of laboratories that need to perform this assay to assess individual risk profile is increasing. Different methods to evaluate homocysteine plasma levels are at present available. In the present study three methods, an in-house high-pressure liquid chromatographic (HPLC) method (considered as reference method) and two commercial immunoassays, an enzyme-linked immunoassay (EIA) and an automated fluorescence polarization immunoassay (FPIA), were used to measure homocysteine plasma levels in 100 samples. The median of homocysteine plasma levels obtained by HPLC was 9.0 micromol/L (range 4.2-23.0); the median of values obtained by EIA and FPIA were 10.6 micromol/L (range 3.3-21.5) and 9.6 micromol/L (4.8-20.2), respectively. The FPIA method showed the lowest within-run and between-run coefficients of variation (3.6% and 4.1%, respectively). There was a significant correlation between EIA and HPLC (r=0.81; p<0.0001), and between FPIA and HPLC (r=0.85; p<0.0001). The Bland-Altman analysis showed that FPIA agreed best with HPLC; EIA displayed a relatively wide scatter of difference data points. The present results indicate that the technological characteristics of the FPIA assay make this method suitable for the determination of Hcy in clinical laboratories.

Bias↗