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Biomedical subjects

C Cortese

Publications and source records attributed to C Cortese.

At least 37 records · Page 2Linked to original sources
PubMed1999

Influence of the human paraoxonase polymorphism (PON1 192) on the carotid-wall thickening in a healthy population.

BACKGROUND: Serum paraoxonase (PON1) is a high-density lipoprotein-bound enzyme that can prevent oxidation of low-density lipoprotein and thus exert an anti-atherogenic effect. A polymorphism at codon 192 (Gln/Arg) of the PON1 gene gives rise to two isoforms that differ in substrate-dependent activity. OBJECTIVE: To determine any independent contribution of this polymorphism to the variability of intimal-medial thickness (IMT) of the common carotid artery for a sample of asymptomatic adult subjects from southern Italy by ultrasonography. METHODS: We studied 196 unrelated asymptomatic subjects (mean age 55.1 years), drawn from participants in a cardiovascular-disease-prevention campaign. Plasma levels of lipids and glucose were measured by routine methods. PON1 polymorphism was determined by polymerase chain reaction. IMT was measured from high-resolution B-mode echo-Doppler ultrasonography images. RESULTS: Prevalences of alleles A (Gln) and B (Arg) were 0.68 and 0.32, respectively. We found no significant difference with regard to plasma levels of lipids and glucose and other variables among the PON1 genotypes, although subjects with BB had higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. Common carotid artery IMT was slightly greater in subjects with BB, although no significant association between PON1 genotypes and common carotid artery IMT was found, even after adjustment for confounding variables. CONCLUSIONS: Our findings demonstrate that there is no significant association between PON1 gene polymorphism at codon 192 and common carotid artery IMT for an Italian population. However, the fact that we found slightly greater IMT in subjects with genotype BB would suggest that the study should be performed again with a larger sample.

Adult↗
PubMed1999

Evaluation of common carotid hemodynamic forces. Relations with wall thickening.

The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityxblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressurexinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6+/-3.3 dynes/cm(2) (mean+/-SD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4+/-0.6x10(4) dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (r=0.55, P<0. 0001) and directly associated with circumferential wall tension (r=0. 43, P<0.0001). Shear stress and circumferential wall tension were inversely correlated (r=0.66, P<0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors.

Adult↗
PubMed1998

Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease.

A common mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene results in elevated homocysteine levels and, presumably, in increased atherosclerotic risk. We evaluated serum homocysteine levels, MTHFR genotype, and a panel of variables in a sample of 155 middle-aged Italian subjects (mean age 38.1 years). Biometrical, hematological, and biochemical variables (including serum folate and vitamin B12) and lifestyle characteristics were investigated. MTHFR genotype was studied by polymerase chain reaction. The frequency of the genotype Val/Val (homozygosity for the mutant allele) was 16.13%. The Val/Val genotype was associated with increased levels of homocysteine; no differences among genotypes were seen in individuals with folate or vitamin B12 levels at or above the median values. In multivariate analysis, MTHFR genotype was an independent predictor of homocysteine levels in both biochemical and non biochemical regression models. Sex and diastolic blood pressure emerged as non biochemical variables independently associated with homocysteine. Apart from cofactors, uric acid was the only biochemical variable independently associated with homocysteine, particularly in subjects with Val/Val genotype. The observed parallel increases in homocysteine and uric acid levels in subjects with thermolabile MTHFR warrant further investigation.

Adult↗
PubMed1998

Apolipoprotein E genotype and cholesterogenesis in polygenic hypercholesterolemia.

We studied 22 normal-weight patients with polygenic hypercholesterolemia (PH), of which 11 (two males and nine females) had the apolipoprotein (apo) E3/4 genotype and 11 (one male and 10 females) the E3/3 genotype. The two groups were comparable for age, body mass index, total and low-density lipoprotein (LDL) cholesterol levels. The diagnosis of PH was made on the basis of clinical assessment, the criteria being type IIa hypercholesterolemia without tendon xanthomas and/or family history and clinical criteria indicative of familial hypercholesterolemia and/or familial combined hyperlipidemia. To avoid the influence of the habitual individual diet on cholesterogenesis, daily urinary mevalonic acid (MVA) excretion, an index of whole-body cholesterol synthesis, was evaluated in the steady-state condition while patients were on a low-fat, low-cholesterol diet for at least 3 months. Urinary MVA excretion rates were 2.52 +/- 0.8 micromol/24 h in E3/4 patients, significantly higher (P < .001) than in E3/3 patients (1.38 +/- 0.6 micromol/24 h). This is the first evidence of a higher rate of cholesterogenesis in PH patients carrying the epsilon4 allele versus the epsilon3 allele under a standardized lipid-lowering diet. We conclude that the higher rate of cholesterogenesis in PH patients with the epsilon4 allele might partly explain the interindividual differences in response to treatment with cholesterol synthesis inhibitors such as statins.

Alleles↗
PubMed1998

Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online.

Mutations in the low density lipoprotein (LDL)-receptor gene cause familial hypercholesterolemia (FH), an autosomal dominant disease associated to an increased risk of premature atherosclerosis. We describe two novel mutations found in Italian families and consisting in minor gene rearrangements. The first one (FH-Pisa) is a tetranucleotide insertion occurring in exon 8, which causes a frameshift and a premature stop codon. The second one (FH-Chieti3) occurs at the 3'-end of exon 4 and consists in a trinucleotide deletion replaced by a six-base insertion, so that the reading frame is maintained with a glutamic acid-to-cysteine substitution at codon 207 and the insertion of a lysine at codon 208. Both mutations occur in regions of the LDL-receptor gene which can be considered hotspots for minor rearrangements.

Amino Acid Substitution↗
PubMed1998

Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine.

We describe a 6-min HPLC method to measure the total concentrations of the most important thiols in plasma and urine--cysteine, homocysteine, cysteinylglycine, and glutathione--as well as the concentrations in plasma and urine, respectively, of cysteamine and 2-mercaptopropionylglycine, two compounds used to treat disorders of cysteine metabolism. Precolumn derivatization with bromobimane and reversed-phase HPLC were performed automatically by a sample processor. Throughput was up to 100 samples in 24 h. The within-run CV ranged from 0.9% to 3.4% and the between-run CV ranged from 1.5% to 6.1%. Analytical recovery was 97-107%, with little difference between plasma and urine samples. The detection limit was approximately 50 nmol/L for all the analytes studied. Thiol concentrations were determined in the plasma of 206 healthy donors and in the urine of 318 healthy donors distributed for age and sex. Mean values of plasma cysteine and homocysteine were significantly lower in infants (ages, <1 y) compared with other age groups (P <0.005). In adults, mean plasma homocysteine values were higher in males than in females (9.2 vs 6.7 micromol/L, P <0.0001) and in the 6- to 10-year-old group (P <0.05). Mean values for glutathione and cysteinylglycine were not sex- and age-dependent. In urine, both cysteine and homocysteine showed a wide range of variation.

Adolescent↗
PubMed1997

Expression of co-factors (SMRT and Trip-1) for retinoic acid receptors in human neuroectodermal cell lines.

Retinoic acid (RA) induces growth inhibition, differentiation or cell death in many human neuroblastoma cell lines. Recently, the transactivation activity of nuclear retinoids receptors has been shown to be modulated through physical association with other proteins that act as co-activators or as co-repressors. We investigated the expression of the co-repressor (SMRT) and co-activator (Trip 1) for retinoid and thyroid-hormone receptors in several neuroectodermal tumour cell lines, and its modulation by all-trans-retinoic acid, as well as by synthetic agonists, for RAR alpha, RAR beta, RAR gamma and RXR. We demonstrate that (i) SMRT and Trip-1 mRNAs are expressed in many human neuroblastoma and melanoma cell lines in basal conditions, (ii) SMRT mRNA expression in human neuroblastoma cell line SK-N-BE(2) increases after 48 hours of incubation with 1 microM RA and RARs specific agonists, (iii) Trip-1 mRNA in the same cell line does not change during incubation with RA or selective synthetic agonists for RARs and RXR.

Chromatography, High Pressure Liquid↗
PubMed1997

5-Lipoxygenase and endotoxin-induced microvascular albumin exchanges and leucocyte recruitment in guinea-pig lungs.

The interference of the 5-lipoxygenase inhibitor, BW B70C ((E)-N-(3-[3-(4-fluorophenoxy)phenyl]-1(R,S)-methyl prop-2-enyl)-N-hydroxyurea), with Escherichia coli lipopolysaccharide (endotoxin)-induced lung leucocyte sequestration and microvascular albumin exchanges was evaluated in the anaesthetised guinea-pig using radioactive tracers, in parallel to the effects on cell counts in the broncho-alveolar lavage fluid, blood tumour necrosis factor (TNF-alpha) content, secretion of phospholipase A2 and synthesis of leukotriene C4 by alveolar macrophages. Intravenous injections of 0.1 or 1 mg/kg endotoxin induced lung leucocyte sequestration but only the higher dose induced an increase in albumin microvascular exchanges and the infiltration of leucocytes towards the airway lumen. Leukotriene B4, a potential mediator of the 5-lipoxygenase-dependent endotoxin effects, induced a rapid and transient lung leucocyte sequestration and leucopenia associated with a more progressive increase in microvascular exchanges. The 5-lipoxygenase inhibitor, BW B70C, injected i.p. (30 mg/kg) prevented leukotriene C4 synthesis by alveolar macrophages and reduced leucocyte migration to the airways lumen as well as albumin microvascular leakage but did not affect the endotoxin-induced increase in the blood level of TNF-alpha and of secreted phospholipase A2. However, BW B70C failed to modify vascular leucocyte margination induced by 1 mg/kg endotoxin, suggesting that, apart from a role of 5-lipoxygenase, alternative pathways operate in response to endotoxin in guinea-pig.

Animals↗
PubMed1997

Alternative splicing of human plasma cholesteryl ester transfer protein mRNA in Caco-2 cells and its modulation by oleic acid.

Cholesteryl ester transfer protein (CETP) is a plasma protein involved in the reverse cholesterol transport and expressed in several human tissues and cell lines. We studied CETP expression in Caco-2 cell line, a model of the human enterocyte epithelium. By reverse-transcriptase polymerase chain reaction, we could demonstrate that in basal condition Caco-2 cells have a low rate of expression of active CETP mRNA. Furthermore, we found that even in this cell line CETP mRNA alternative splicing occurs with deletion of exon 9 sequence. Densitometric analysis of the in vitro amplified fragments showed that under basal conditions about 60% of reverse transcribed CETP cDNA corresponds to exon 9-deleted transcripts. After challenge with 50 microM sodium oleate, there is a approximately 2 fold increase in the transcription rate of the full-length CETP cDNA, as measured by competitive PCR, which is accompanied to an increased activity measured in the cell-conditioned medium. On the contrary, no significant change is seen in the amount of exon 9-deleted cDNA. Consequently, an inversion in the ratio of full-length and exon 9-deleted CETP cDNA is evident, suggesting that sodium oleate selectively enhances the expression of full-length CETP mRNA.

Alternative Splicing↗
PubMed1997

Electromotive administration of oxybutynin into the human bladder wall.

PURPOSE: To compare concentrations of oxybutynin in the human bladder wall after either passive delivery (PD) or electromotive administration (EMDA). MATERIALS AND METHODS: Tissue sections of human bladder were inserted into a diffusion cell with urothelium exposed to the donor compartment containing oxybutynin (4.5 mg. in 100 ml. NaCl 0.45%) and an anode. Twelve paired experiments, "current 5 mA/no current", were conducted over 15 minutes. Oxybutynin tissue contents were measured and tissue viability, morphology and oxybutynin stability were assessed. RESULTS: Mean oxybutynin tissue concentrations were 3.84 micrograms./gm. in samples exposed to EMDA and 0.87 microgram./gm. in samples exposed to PD (p = 0.0006). The mean coefficients of variation were 57.85% in EMDA experiments and 89.78% in PD experiments. Tissues were viable and undamaged histologically and no oxybutynin structural modification was observed. CONCLUSIONS: EMDA enhances oxybutynin administration into viable bladder wall and reduces the variability in drug delivery rate.

Cholinergic Antagonists↗
PubMed1996

Deletion polymorphism in angiotensin converting enzyme gene associated with carotid wall thickening in a healthy male population.

BACKGROUND: Intimal thickening is an adaptive process of the arterial wall, presumably related to atherogenesis. Sex and interethnic differences in intimal thickening, as demonstrated histologically on autoptic material, would indicate a strong genetic control on this process. An insertion/deletion (ID) polymorphism in the angiotensin-converting enzyme (ACE) gene has been shown to be an independent risk factor for cardiovascular disease, especially in subjects otherwise at low risk for coronary heart disease. The aim of the present study was to evaluate the relationship between intimal plus medial thickness (IMT) and ACE-I/D genotype. METHODS: 132 healthy male subjects from Southern Italy were enrolled. IMT has been evaluated from high resolution B-mode echo-Doppler images. Blood lipids and glucose were measured using standard methods. Cigarette consumption was recorded by questionnaire. ACE genotypes were analysed by polymerase chain reaction. RESULTS: Blood lipids, blood pressure and percentage of smokers were similar in the three groups. IMT was greatest in DD subjects, lowest in II subjects and intermediate in heterozygotes. The association between the presence of the D allele and IMT values was statistically significant. Significance was maintained after the elimination of subjects with carotid atherosclerotic plaques. CONCLUSIONS: The present data suggest that the ACE gene seems to be a candidate gene that strongly influences the IMT of the arterial wall and might therefore be involved in the individual's predisposition to the development of atherosclerosis.

Adult↗
PubMed1994

[Correlation of waist-to-hip circumference ratio and cardiovascular risk factors in a population of Southern Italy].

AIM: To evaluate the relationship between body mass index (BMI), body fat distribution and some coronary heart disease risk factors like hyperlipidemia, hypertension and cigarette smoking. STUDY DESIGN: Cross-sectional. PLACE: Tiriolo, a little town close to Catanzaro, of prevalent rural economy. PARTICIPANTS: Volunteers, both males and females, aged more than 30 years and living in Tiriolo. MEASUREMENTS: Body weight and height with subjects in ordinary street clothes and without shoes. Systolic (SBP) and diastolic blood pressure (DBP) by a zero-random sphygmomanometer. Total (TC) and HDL cholesterol (HDL-C) using fingerstick capillary sample technology by a Cholestech analyzer. Waist circumference (W), measured midway between the lower rib margin and the iliac crest, and hip circumference (H) measured at the widest point over the greater trocanthers. Smoking habit by questionnaire. RESULTS: Females had higher values of SBP, DBP, BMI and HDL-C and lower of TC/HDL-C ratio and W/H ratio. Age was similar in both sexes. Females had lower prevalence of hyperlipidemia and cigarette smoking and higher prevalence of hypertension. BMI was strongly associated to blood pressure levels whereas W/H ratio was correlated to TC/HDL-C ratio. CONCLUSION: BMI and W/H ratio give complementary information, useful to assess the cardiovascular risk profile. The simplicity and quickness of these measurements should lead to their large utilization both in epidemiological prevention studies and everyday clinical practice.

Adipose Tissue↗
PubMed1994

SstI RFLP and hypertension as risk factors for extracoronary atherosclerosis in a male population of southern Italy.

The present study was designed to investigate on possible association between SstI polymorphism in the ApoAI-CIII-AIV gene cluster, classical coronary heart disease risk factors and extracoronary atherosclerosis. One hundred and twenty six male subjects were enrolled and underwent echo-Doppler examination of carotid and femoral arteries, coronary heart disease risk factors assessment and SstI genotyping. The frequency of the rare SsI allele was 12.1% and 6.7% in subjects with or without extracoronary lesions respectively and was not associated with differences in the distribution of coronary heart disease risk factors. Forty subjects had hypertension, 34 homozygous for the frequent allele and 6 with presence of the rare allele. Among these, 10 subjects (29%) and 5 subjects (83%), respectively, had extracoronary atherosclerosis. Furthermore, subjects homozygous for the rare allele exhibited lipid abnormalities and a family history positive for hypertension and/or hyperlipidemia. These findings suggest a possible role for the ApoAI-CIII-AIV gene complex in both lipid metabolism and blood pressure regulation and could be of help to identify, within hypertensives, those subjects prone to extracoronary atherosclerosis.

Alleles↗
PubMed1994

Intimal plus media thickness of common carotid arterial wall in subjects with hypertension.

Intimal plus media thickening has been described to be associated with several cardiovascular risk factors. Aim of the present study was to evaluate the intimal plus media thickness in male subjects with hypertension compared to age matched males normotensive controls. Twenty subjects with hypertension, defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg and/or use of antihypertensive drugs, and forty age matched controls have been enrolled. Intimal plus media thickness has been measured from B-mode echography images by a computer. Plasma lipids have been measured by routine methods. A zero random sphygmomanometer has been used to detect blood pressure. Intima plus media thickness resulted enlarged in subjects with hypertension compared to normotensive controls. The thickening of intima-media complex seems related to atherosclerotic lesions, therefore its early detection by noninvasive techniques might improve the identification and the monitoring of high risk hypertensive subjects.

Blood Pressure↗
PubMed1993

Early extracoronary atherosclerosis and coronary heart disease risk factors in a sample of civil servants in southern Italy.

One hundred and thirty-eight male subjects working as civil servants in the Catanzaro city hall, aged over 45, underwent Echo-Doppler examination of carotid and femoral arteries. Forty-one subjects (30%) presented evidence of early atherosclerotic lesions in at least 1 of the 10 examined arteries. Age, systolic blood pressure, serum triglycerides and serum glucose were higher in this group when compared with subjects without evidence of extracoronary atherosclerosis (EA), while HDL cholesterol and apolipoprotein A-I were lower. After adjustment for age, only serum triglycerides and apolipoprotein A-I levels remained significantly different. Only 21 subjects had no major coronary heart disease (CHD) risk factors, 46 had one, 47 two and 24 more than two risk factors. The prevalence of lesions was significantly higher in individuals with total cholesterol/HDL cholesterol ratio greater than 5. The presence of smoking and hypertension was almost equally represented in individuals with or without lesions. Serum triglycerides, total cholesterol/HDL cholesterol > 5 and apolipoprotein A-I seem to play a fundamental role in the development of EA, as detected by Duplex examination of carotid and femoral arteries. Age is also closely related to the presence of lesions, probably reflecting the exposure duration to CHD risk factors.

Arteriosclerosis↗
PubMed1993

[Asymptomatic arteriopathy of the lower limbs. Prevalence and risk factors in a population of southern Italy].

Peripheral vascular diseases, both symptomatic and asymptomatic, are strong predictors of total and cardiovascular mortality. The commonly used Rose questionnaire, although highly specific, has a low sensitivity to detecting peripheral vascular disease and is not adequate for asymptomatic subjects. Doppler ultrasound measurement of the ankle/brachial systolic blood pressure ratio is a non-invasive, reproducible and accurate method of assessment of peripheral vascular disease and has been validated by angiography. METHODS. Five hundred and ten subjects, corresponding to fifty percent of the people working as civil servants in the Catanzaro city hall, were invited to join the study by a letter. Three hundred and eighty four participated. Exclusion criterion was claudicatio intermittens as detected by Rose questionnaire. All the subjects filled a questionnaire to assess coronary heart disease risk factors and underwent a full clinical examination. Brachial blood pressure was measured on both arms with participants in supine position, just before ECG. The systolic ankle blood pressure was measured with ultrasonic technique. The blood pressure cuff was placed just proximal to the medial malleolus. The ankle-brachial systolic pressure index (Winsor Index) was determined by dividing the highest of the posterior tibial or dorsalis pedis pressures by the highest brachial pressure. A limit of 0.95 was chosen to identify subjects with peripheral arterial disease. Venous blood for serum cholesterol and triglycerides, apolipoprotein AI and B and blood glucose, was collected after an overnight fasting, into Vacutainer Tubes (Becton & Dickinson). RESULTS. No subject had claudicatio intermittens. Sixteen subjects were excluded from the statistical analysis because of missing data. Two hundred and sixty-three were males and 105 females. Twenty-one (5.7%) out of 368 participants had a Winsor Index < 0.95 in at least one leg. These subjects had higher values of systolic and diastolic blood pressure compared to normal subjects whereas no differences were observed with regard to age, BMI, lipid profile and blood glucose. Furthermore the prevalence of hypertension was higher in the group of subjects with asymptomatic peripheral arterial disease. The prevalence of other risk factors for atherosclerosis (cigarette smoking, hyperlipidemia, diabetes mellitus, obesity) was similar in subjects with or without peripheral arterial disease. DISCUSSION. In the present study the prevalence of Winsor Index < 0.95 was 5.7%, similar to that reported by other authors. Hypertension was the only risk factor for atherosclerosis associated with peripheral arterial disease. Other authors also reported a higher prevalence of cigarette smoking among subjects with peripheral disease. In our population this association was not found but the participants were younger and consequently the exposure to this risk factor was shorter. CONCLUSION. The measurement of systolic ankle blood pressure by Doppler ultrasounds is a non-invasive, well accepted, highly specific and sensitive method to detect asymptomatic peripheral arterial disease. It might be of value in better defining the cardiovascular risk profile both in epidemiologic studies and clinical practice, especially in subjects with hypertension.

Adult↗
PubMed1993

XbaI polymorphism of the apolipoprotein B gene in patients with hyperlipidemia and echo-Doppler evidence of arterial lesions.

This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups.

Adult↗