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Biomedical subjects

C Cortese

Publications and source records attributed to C Cortese.

At least 19 recordsLinked to original sources
PubMed2006

Flow-mediated vasodilatation of the brachial artery and intima-media thickness of carotid artery in never-treated subjects.

AIM: Data on the association between brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (IMT) are contrasting. The present study investigated the relationship between FMD and IMT and carotid atherosclerosis in never treated subjects. METHODS: Seventy-seven subjects were investigated: 46 had no coronary heart disease (CHD) risk factors, 21 had only one, and 10 had more than one risk factor. IMT of the common carotid was measured by ultrasonography and FMD was evaluated according to standardized methods. RESULTS: IMT increased with increasing number of risk factors (0.66+/-0.12, 0.69+/-0.12 and 0.8+/-0.17 mm, respectively, ANOVA P<0.05). FMD decreased with increasing number of risk factors (10.44+/-5.2, 6.52+/-7.11 and 7.35+/-4.42%, respectively, P<0.05). Endothelium-independent vasodilatation was similar in the 3 groups. IMT and FMD did not correlate neither in subjects without risk factors (r=-0.151, P=0.3), nor in those with 1 (r=-0.196, P=0.4) or with 2 or more risk factors (r=-0.387, P=0.2), while in the group as a whole the correlation was borderline significant (r=-0.217, P=0.058). Eleven subjects had carotid atherosclerosis and higher values of IMT, but not reduced FMD. In multiple regression analysis, diabetes and IMT, but not FMD, were associated with carotid atherosclerosis. CONCLUSIONS: The present findings indicate that, in never treated subjects, FMD is not strictly associated with IMT or atherosclerosis of the carotid arteries.

Adult↗
PubMed2002

Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y.

The oxidative stress could have a dual action on glutathione S-transferase (GST) P1-1 metabolism: transcriptional induction and/or polymerization. The former should represent a form of adaptation to oxidative stress and contribute to protect the cell, the latter one should activate apoptosis via c-Jun N-terminal kinase (JNK). We studied the effect of etoposide on human neuroblastoma cell line SH-SY5Y and on an etoposide-resistant clone to investigate whether a pleiotropic effect of etoposide on the redox status of the cell exists which is able to interfere with apoptosis through the GST P1-1 system. Etoposide treatment was able to induce GST P1-1 polymerization and activation of apoptosis. The data obtained from our etoposide-resistant clone and the possibility to reverse the sensitive phenotype to a resistant one by means of hexyl-glutathione preincubation, seem to suggest that cellular levels of glutathione have a key role in protecting GST P1-1 by oxidation and consequently the cell's decision between life and death.

Apoptosis↗
PubMed2002

The pathology of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized form of chronic liver injury. Nonalcoholic steatohepatitis (NASH) is the term applied to the microscopically-defined subset of NAFLD with known progression to cirrhosis and the complications that may be associated, including metabolic imbalances, liver failure and hepatocellular carcinoma. NASH is also being considered as a significant precursor of end-stage liver disease, ''cryptogenic cirrhosis'', in which the histologic features of the initial liver disease can no longer be appreciated. Because of the increasing prevalence and the known significance of this form of liver disease, current investigations are focused on discerning the clinical features of susceptible patients, the histopathologic findings that characterize the entity and serve as markers of progression, pathogenetic mechanisms that result in triglyceride accumulation, liver injury and fibrosis, and ultimately, treatment options.

Journal Article↗
PubMed2001

Identification of an alternative transcript of ABCA1 gene in different human cell types.

We have observed two ABCA1 gene transcripts in human skin fibroblasts. The RT-PCR amplification of the exon 3-exon 8 region generated a normal fragment (740 bp) and an abnormal fragment (600 bp) in a ratio ranging from 3:1 to 8/9:1. These two transcripts were present in other cells such as leukemia T-cells, endothelial and smooth muscle cells as well human hepatoma cells (HepG2). Restriction enzyme analysis and sequencing indicated that in the abnormal fragment exon 3 was followed by exon 5. The complete skipping of exon 4 leads to a premature stop and a predicted translation product of 74 amino acids. The ratio between the normal and alternative transcript is not affected by variation in ABCA1 gene expression induced by incubating cells in serum-free medium and in the presence of cholesterol. It is possible that this alternative splicing represents as mechanism that regulates the ABCA1 content in tissues.

ATP Binding Cassette Transporter 1↗
PubMed2001

Simultaneous determination of inulin and p-aminohippuric acid in plasma and urine by reversed-phase high-performance liquid chromatography.

A simple, accurate and sensitive high-performance liquid chromatographic method with UV detection was carried out to measure simultaneously plasma and urine concentrations of both p-aminohippuric acid and inulin. Following a simplified acid hydrolysis of the sample, the separation was carried out in 4 min using a C18 reversed-phase column with a flow-rate of 1 ml/min, and monitoring the absorbance at 280 nm. Within the investigated concentration ranges of inulin (0.1-3.2 mg/ml) and p-aminohippuric acid (0.0097-0.3 mg/ml), good linearity (r>0.99) was obtained. Within-run RSD ranged from 2.9 to 6.1% and between-run RSD ranged from 6.4 to 10%. Analytical recoveries were 101-112%, with little differences between plasma and urine samples. The detection limit was 1 microg/ml for all the analytes studied. This method might be ideal for renal function studies where a rapid and reproducible assessment of both renal glomerular filtration rate and blood flow-rate is required.

Adult↗
PubMed2001

Association between wall shear stress and flow-mediated vasodilation in healthy men.

Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P</=0.005). To avoid the influence of brachial artery size on FMD, the regression analysis was restricted to subjects with similar diameter (n=12). In these subjects wall shear stress continued to be significantly associated with FMD (r=0.69, P=0.01). Our results demonstrate a strong association between resting wall shear stress and FMD in the brachial artery in healthy men in vivo. This association is independent of age and vessel diameter.

Adult↗
PubMed2001

A multiplex PCR-based DNA assay for the detection of paraoxonase gene cluster polymorphisms.

Paraoxonase (PON) is a high-density lipoprotein (HDL) associated protein which is supposed to protect low-density lipoprotein (LDL) against oxidation and to play a role in the development of atherosclerosis. Interindividual variability in serum PON activity is attributable to common variants in components of the PON gene cluster on chromosome 7. We describe experimental conditions that permit the simultaneous determination of three common PON polymorphisms (PON1-192, PON1-55 and PON2-311) that are tightly associated with an increased risk of atherosclerosis. We used a multiplex PCR-based DNA assay using mismatch primers that introduce a unique recognition site for the endonuclease HinfI in the PCR products in case of presence of the R allele of PON 1-192, of the L allele of PON1-55 and of the S allele of PON2-311. The restriction analysis with HinfI allows to identify an electrophoretic band pattern which is specific for the combination of the three polymorphisms. This technique could be applied in the association studies aimed at assessing the role of PON and their polymorphisms in many clinical settings. In a preliminary study on a small population sample from south Italy about 10% of chromosomes exhibited the presumed risk-related haplotype R(192)/L(55)/S(311).

Alleles↗
PubMed2001

MTHFR gene polymorphism, homocysteine and cardiovascular disease.

Homocysteine is an emerging new risk factor for cardiovascular disease. It is a thiol compound derived from methionine and involved in two main metabolic pathways: the cycle of activated methyl groups, requiring folate and vitamin B12 as cofactors, and the transsulfuration pathway to cystathionine and cysteine requiring vitamin B6 as cofactor. The homocysteine metabolism represents an interesting model of gene-environment interaction. Elevations in homocysteine may be caused by genetic defects in enzymes involved in its metabolism or by deficiencies in cofactor levels. A common polymorphism in the gene coding for the 5,10-methylene tetrahydrofolate reductase (MTHFR) (C677T, Ala --> Val) is associated with a decreased activity of the enzyme due to thermolability. In case of homozygosity for the Val allele, a relative deficiency in the remethylation process of homocysteine into methionine leads to a mild-to-moderate hyperhomocysteinemia, a condition recognized as an independent risk factor for atherosclerosis. The genetic influence of the MTHFR polymorphism on homocysteine levels is attenuated in females in premenopausal age and is not significant in subjects who exhibit serum levels of folate and/or vitamin B12 above the 50th percentile of distribution in the general population. The prevalence of the Val/Val genotype varies among different ethnic groups. It is very low in African populations, whereas in Europe and North America it ranges between 5% and 15%. In Italy an even higher prevalence has been reported in some regions. The question whether the MTHFR polymorphism might be per se an independent contributor to cardiovascular risk is debated. The interaction between this or other genetic factors and environmental/nutritional conditions (i.e. intake of vitamins such as folate) is a key determinant for homocysteine concentrations in healthy conditions as well as in some disease (i.e. in renal disorders). Another example of gene/environment interaction in the field of atherosclerosis is given by the apolipoprotein E polymorphism and its influence in response to diet. The presence of a high prevalence of risk-related allelic variants of such candidate genes within a certain population could serve to locally reinforce the recommendations concerning nutrient intake.

Apolipoproteins E↗
PubMed2000

Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus.

We assessed the contribution of the serum homocysteine (Hcy) level, an independent risk factor for vascular disease, and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism to the variability of intimal-medial thickness (IMT) of the common carotid artery in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) subjects. One hundred thirty NIDDM patients (60 males and 70 females) with a mean age of 53 +/- 10 years and a mean diabetes duration of 11.3 +/- 7.9 years were enrolled for the study. Exclusion criteria included liver, heart, kidney, or other major-organ disease. Fasting total serum Hcy, folate, and vitamin B12 and clinical chemistry analyte levels were measured. MTHFR polymorphism was determined by polymerase chain reaction (PCR). IMT and plaques or stenosis in the common carotid were measured by ultrasonography. Serum Hcy was inversely correlated with vitamin levels and was slightly higher in subjects with the Val/Val genotype versus Ala/Val and Ala/Ala (P = .02); no differences in genotype were found in subjects with folate or vitamin B12 at or above the median level. In univariate analysis, common carotid IMT was significantly associated with age (P = .00001), the body mass index ([BMI] P = .0003), uric acid (P = .004), systolic blood pressure (P = .03), glycemia (P = .03), and total cholesterol (P = .04). No significant association was found between serum Hcy or MTHFR polymorphism and IMT. In multiple regression analysis, age (P = .0001), uric acid (P = .03), glycemia, and the BMI (P = .05) were independently associated with IMT and explained about 42% of IMT variability. In 130 NIDDM patients without nephropathy, basal levels of serum Hcy, as well as MTHFR polymorphism, did not predict significant changes in common carotid IMT.

Arteriosclerosis↗
PubMed2000

Magnetic resonance and positron emission tomography changes during the clinical progression of Rasmussen encephalitis.

The authors describe serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies in a patient with pathologically confirmed Rasmussen Encephalitis (RE). Results of initial PET and MRI studies were normal. Subsequent studies showed involvement of the percentral and postcentral gyri and the putamen on PET, and the precentral and postcentral gyri on MRI. Coregistration of PET and MR images showed good correlation between the precentral and postcentral gyri involvement. However, subcortical involvement occurred earlier on PET than on MRI. The authors demonstrate the evolution of changes on PET and MR images in a patient with RE. Despite early pathologic confirmation of RE, there were no definite structural or functional imaging changes on PET or MRI until 3 years after symptom onset. These findings demonstrate the variability of imaging changes in RE, and the need to carefully correlate electro-physiologic and clinical findings to confirm the diagnosis of RE.

Brain↗
PubMed2000

Genetic variation in human stromelysin gene promoter and common carotid geometry in healthy male subjects.

A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.

Adult↗
PubMed2000

Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype.

Seventy-one mutations of the low density lipoprotein (LDL) receptor gene were identified in 282 unrelated Italian familial hypercholesterolemia (FH) heterozygotes. By extending genotype analysis to families of the index cases, we identified 12 mutation clusters and localized them in specific areas of Italy. To evaluate the impact of these mutations on the clinical expression of FH, the clusters were separated into 2 groups: receptor-defective and receptor-negative, according to the LDL receptor defect caused by each mutation. These 2 groups were comparable in terms of the patients' age, sex distribution, body mass index, arterial hypertension, and smoking status. In receptor-negative subjects, LDL cholesterol was higher (+18%) and high density lipoprotein cholesterol lower (-5%) than the values found in receptor-defective subjects. The prevalence of tendon xanthomas and coronary artery disease (CAD) was 2-fold higher in receptor-negative subjects. In patients >30 years of age in both groups, the presence of CAD was related to age, arterial hypertension, previous smoking, and LDL cholesterol level. Independent contributors to CAD in the receptor-defective subjects were male sex, arterial hypertension, and LDL cholesterol level; in the receptor-negative subjects, the first 2 variables were strong predictors of CAD, whereas the LDL cholesterol level had a lower impact than in receptor-defective subjects. Overall, in receptor-negative subjects, the risk of CAD was 2.6-fold that of receptor-defective subjects. Wide interindividual variability in LDL cholesterol levels was found in each cluster. Apolipoprotein E genotype analysis showed a lowering effect of the epsilon2 allele and a raising effect of the epsilon4 allele on the LDL cholesterol level in both groups; however, the apolipoprotein E genotype accounted for only 4% of the variation in LDL cholesterol. Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors.

Adult↗
PubMed2000

Modulation of GST P1-1 activity by polymerization during apoptosis.

Glutathione S-transferases (GSTs, EC 2.5.1.18) belong to a large family of functionally different enzymes that catalyze the S-conjugation of glutathione with a wide variety of electrophilic compounds including carcinogens and anticancer drugs. Drug resistance may result from reduction in apoptosis of neoplastic cells when exposed to antineoplastic drugs. The c-Jun N-terminal Kinase (JNK) belongs to the family of stress kinases and has been shown to be required for the maximal induction of apoptosis by DNA-damaging agents. Recently, an inhibition of JNK activity by GST P1-1, which was reversed by polymerization induced by oxidative stress, has been reported in 3T3-4A mouse fibroblast cell lines. The finding that GST P1-1 might inhibit JNK activity and that it is frequently highly expressed in tumor tissues suggests its possible implication in "apoptosis resistance" during antineoplastic therapy. We investigated the modulation of GST P1-1 during apoptosis in a neoplastic T-cell line (Jurkat) induced by hydrogen peroxide and etoposide. Apoptosis was paralleled by the appearance of a dimeric form of GST P1-1 on western blotting, associated with an increase in the Km(GSH) and a reduction in GST P1-1 specific activity toward 1-chloro-2,4-dinitrobenzene, which reached statistical significance only in H(2)O(2)-treated cells. Our data seem to suggest that H(2)O(2) and etoposide may partly act through a process of partial inactivation of the GST P1-1, possibly involving the "G" site in the process of dimerization, and thus favoring programmed cell death.

Apoptosis↗
PubMed2000

Characterization and screening of a point mutation in LDL receptor gene found in southern Italy (FHAvellino).

The finding that the missense mutation C331W in the exon 7 of LDL-receptor gene, previously reported to occur in Holland and Belgium, caused the homozygote familial hypercholesterolemia (FH) in an individual from the district of Avellino induced us to search the mutation in a large area of region Campania. This was made with simple screening methods developed by ourselves and based on either the recognition of a primer-induced Fok I restriction site in the mutant allele or the PCR allele-specific amplification (PASA) of mutant allele. They were applied to a total of 144 unrelated cases recruited from where the mutation was more likely to occur. We failed to reveal any new case of C331W mutation that is indeed not common within the area of this screening, at spite of having been found in different countries.

Adult↗
PubMed1999

Modulation of glutathione transferase P1-1 activity by retinoic acid in neuroblastoma cells.

The ability of retinoic acid to modulate glutathione S-transferase P1-1 (GSTP1-1) activity has important implications both for cancer prevention and for anticancer therapy. We investigated GSTP1-1 expression and activity in the human neuroblastoma cell line SK-N-BE(2) (genotype A*/B*) under basal conditions and during 48-h incubation with 0.1 microM all-trans-retinoic acid. The steady-state levels of glutathione transferase P1-1 mRNA and protein during 48-h incubation with all-trans-retinoic acid did not increase substantially, but we detected a significant reduction of GSTP1-1 specific activity. This reduction in enzymatic activity could not be ascribed to a differential action of retinoic acid on the gene variants A* and B*; indeed, the two GSTP1-1 isoforms have different affinities toward 1-chloro-2,4-dinitrobenzene (CDNB), while we found a substantial invariance of the K(m) (CDNB) in the cytosol during retinoid treatment. A modulatory effect of retinoic acid on other enzymes involved in glutathione transferase P1-1 metabolism, such as the retinoic acid-induced tissue trans-glutaminase, might be hypothesized, as well as a direct inactivation of GSTP1-1 by the oxidative stress that characterizes the early phases of apoptosis.

Antineoplastic Agents↗
PubMed1999

Extraction and determination of oxybutynin in human bladder samples by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography method is described for the determination of oxybutynin (OXB) in human bladder samples. Following homogenization, tissue samples underwent double extraction with hexane and eventually were concentrated by freeze-drying before analysis. Chromatographic separation was performed with a mobile phase of acetonitrile-water-1 M ammonium acetate, pH 7.0 (85:13:2, v/v/v) at a flow-rate of 0.5 ml/min and double (electrochemical and UV) detection was applied. The retention time of oxybutynin eluting peak was around 18 min. Using a standard curve range of 10 to 500 ng/ml the quantification limit with electrochemical detection was 5 ng/ml with an injection volume of 100 microl. Within-day and day-to-day relative standard deviation values were 4.9 and 9.81%, respectively, while a 94% accuracy and a 72% recovery was attained. We applied this method to compare the OXB levels into bladder wall tissue samples after passive diffusion and after electromotive drug administration (EMDA), using a two-chambered poly(vinyl chloride) diffusion cell designed and developed in our laboratory. The results obtained show that EMDA enhanced OXB penetration into bladder wall and that this novel way of local drug administration can be potentially used in patients with neurogenic bladder dysfunction or urinary incontinence.

Acetates↗
PubMed1999

Serum homocysteine, MTHFR gene polymorphism, and carotid intimal-medial thickness in NIDDM subjects.

We assessed the contribution of serum homocysteine levels, an independent risk factor for vascular disease, and of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation to the variability of carotid intimal-medial thickness (IMT) in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ninety-five patients (33 males and 62 females, mean age 53 +/- 10 years) without nephropathy or other vascular complications were enrolled. Fasting total serum homocysteine and other biochemical analytes were measured. The MTHFR polymorphism was determined by the polymerase chain reaction. Common carotid IMT and plaques or stenoses in the carotid district were measured by ultrasonography. Serum total homocysteine concentrations were higher in subjects with the mutant (Val/Val) genotype than in those with the Ala/Val plus Ala/Ala genotypes (P = 0.02). On univariate analysis, carotid IMT was significantly associated with age, body mass index (BMI), systolic blood pressure, and total cholesterolemia. No significant association was found between IMT and serum homocysteine or the MTHFR polymorphism, although a slightly greater IMT was observed in the homozygous Val genotypes. On multiple regression analysis, only age and BMI were independently associated with IMT and explained about 40% of IMT variability. The results did not change when the analysis was restricted to the subgroups with or without atherosclerotic plaques in the carotid district. In 95 Italian NIDDM patients without nephropathy, neither basal levels of serum total homocysteine nor the MTHFR C677T polymorphism predicted significant changes in common carotid intimal-medial thickness.

Arteriosclerosis↗