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Biomedical subjects

C Motti

Publications and source records attributed to C Motti.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Whole blood viscosity and haematocrit are associated with internal carotid atherosclerosis in men.

BACKGROUND: Alterations in blood viscosity and haematocrit have been described in patients with coronary and cerebrovascular diseases. The results have not been conclusive, as modifications of these parameters are often associated with the presence of coronary heart disease (CHD) risk factors. The aim of this study was to verify whether blood viscosity and haematocrit are increased in patients with carotid atherosclerosis, independently of the presence of CHD risk factors. METHODS: Male patients with internal carotid atherosclerosis (ICA+, n = 28) were selected from participants in a cardiovascular disease prevention campaign. Controls (ICA-, n = 28), also participating in the prevention campaign, were matched for age and all the classical CHD risk factors. Plasma lipids, glucose and fibrinogen were determined by routine methods. Cigarette smoking and current drug therapy was established by questionnaire. Whole blood viscosity was measured at shear rates of 450 and 225/s, using a cone-plate viscometer. Echo-Doppler of carotid arteries was performed with an ATL Ultramark 9 HDI using a 5-10 MHz multifrequency probe. RESULTS: Blood pressure, plasma lipids, glucose, body mass index, fibrinogen and plasma viscosity were similar in the two groups. ICA+ patients, compared with the ICA- group, had significantly greater values of blood viscosity (4.52 +/- 0.37 cP compared with 4.18 +/- 0.45 cP, P < 0.005 respectively; shear rate 450/s) and haematocrit (48.57 +/- 3.19% compared with 45.57 +/- 4.81%, P < 0.008 respectively). CONCLUSIONS: Our findings demonstrate that blood viscosity and haematocrit are increased in men with internal carotid atherosclerosis, independently of the presence of risk factors for atherosclerosis.

Adipose Tissue↗
PubMed1998

Carotid atherosclerosis in subjects with different hyperlipidaemia phenotypes.

OBJECTIVE: To evaluate the presence of carotid plaque and/or stenosis in patients with different phenotype of hyperlipidaemia. EXPERIMENTAL DESIGN: Case-control study. SETTING: Outpatients metabolic clinic. PATIENTS: Sixty type IIa, 50 type IIb and 40 type IV hyperlipidaemic subjects were compared with 50 normolipidaemic controls, matched for sex and age. INTERVENTIONS: Blood lipid analysis for phenotype classification was performed after two months of diet. Blood pressure was measured by a zero-random sphygmomanometer. CHD risk factors, smoking habit, previous and ongoing drug therapy were assessed by a self-administered questionnaire. Echo-Doppler examination of the extracranial arteries (common, internal and external carotid artery and bulb) was done by a Multigon Angioview 600 provided with a 7.5 MHz probe for B-mode and 5 MHz for pulsed Doppler. Subjects were classified as having carotid atherosclerosis when a plaque and/or a stenosis was found in at least one of the examined segments and as normal when no atherosclerotic lesions were detected. RESULTS: There were more hypertensives among type IV subjects whereas the prevalence of smokers and diabetics was similar in all four groups. The prevalence of carotid atherosclerosis was higher in type IIb and IIa subjects than in controls (58% and 38% respectively vs 14%, p<0.01) while in type IV subjects it was comparable to that of controls (25%). CONCLUSIONS: The present findings show that hypercholesterolaemia and mixed hyperlipidaemia are frequently associated with carotid atherosclerosis, whereas hypertriglyceridaemia is not. The role of hypertriglyceridaemia in the development of atherosclerosis seems mediated by mechanisms other than plaque formation.

Carotid Stenosis↗
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

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

In vivo association between low wall shear stress and plaque in subjects with asymmetrical carotid atherosclerosis.

BACKGROUND AND PURPOSE: It is known that atherosclerosis does not involve both carotid arteries to the same extent. Pathological investigations have demonstrated that lesions develop in regions of low wall shear stress. The aims of the present study were to verify the degree of carotid atherosclerosis asymmetry in a population-based study and to evaluate whether wall shear stress is lower in carotids with atherosclerotic lesions than in carotids without lesions. METHODS: Participants in a cardiovascular disease prevention campaign (n = 1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of these, 23 subjects who presented plaque in the common carotid or bulb of one side and no plaque in the contralateral carotid tree were enrolled for common carotid wall shear stress measurement. Shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. RESULTS: Of the 1166 subjects screened, 400 (34%) had plaque and/or stenosis in the carotids. Ninety subjects had lesions exclusively in the right carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids but with different degrees of severity, and only 129 had similar lesions in both carotids. In the 23 subjects in whom wall shear stress was measured, peak shear stress was 18.7 +/- 4.1 and 15.3 +/- 4.0 dynes.cm-2 (mean +/- SD) (P < .0001) in the side without and the side with plaque, respectively. Mean shear stress yielded similar results. CONCLUSIONS: The present results demonstrate that the atherosclerotic involvement of carotid arteries is usually asymmetrical and that wall shear stress is lower in the carotid arteries where plaques are present than in plaque-free arteries. These findings provide in vivo evidence for a strong association between shear stress and atherosclerotic lesions.

Arteriosclerosis↗
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

Recognition by human sera and immunogenicity of HBsAg mimotopes selected from an M13 phage display library.

We used two mouse monoclonal antibodies (mAb) specific for the human hepatitis B virus surface antigen (HBsAg) to screen a random peptide library of 15 amino-acid residues displayed as a fusion to protein III of filamentous phage M13. By a combination of affinity selection, immuno-screening and ELISA techniques, we selected peptides that are recognized by the anti-HBsAg mAb and show aa similarity with the natural antigen. The selected phage-displayed epitopes (phagotopes) behave as antigenic mimics of HBsAg. One phagotope is specifically recognized by human sera from HBsAg-immunized individuals, pointing to the possible use of phagotopes as markers to detect the presence of specific Ab in the serum. The same phagotope also elicits Ab directed against HBsAg in mice, indicating that mAb-selected phagotopes can also be immunogenic mimics of the natural antigen. These findings demonstrate that it is possible to identify disease-specific epitopes that can be used as diagnostic reagents and as leads for the development of acellular vaccines.

Animals↗
PubMed1994

A nonsense mutation in the apolipoprotein A-I gene is associated with high-density lipoprotein deficiency and periorbital xanthelasmas.

Conflicting data from epidemiological trials, genetic family studies, transgenic animal models, and in vitro experiments have created controversy regarding the importance of HDL and apolipoprotein (apo) A-I for reverse cholesterol transport and protection from atherosclerosis. In this study we identified a homozygous nonsense mutation in codon 32 (Q32X) of the apoA-I gene as the molecular basis of apoA-I deficiency in a 31-year-old woman who did not present with clinical signs of atherosclerosis. Despite half-normal plasma concentrations of HDL cholesterol and apoA-I in subjects heterozygous for this mutation, the history of the patient's large family did not indicate any increased prevalence of myocardial infarction.

Adult↗
PubMed1993

Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease.

The presence of lecithin:cholesterol acyltransferase (LCAT) deficiency in six probands from five families originating from four different countries was confirmed by the absence or near absence of LCAT activity. Also, other invariate symptoms of LCAT deficiency, a significant increase of unesterified cholesterol in plasma lipoproteins and the reduction of plasma HDL-cholesterol to levels below one-tenth of normal, were present in all probands. In the probands from two families, no mass was detectable, while in others reduced amounts of LCAT mass indicated the presence of a functionally inactive protein. Sequence analysis identified homozygous missense or nonsense mutations in four probands. Two probands from one family both were found to be compound heterozygotes for a missense mutation and for a single base insertion causing a reading frame-shift. Subsequent family analyses were carried out using mutagenic primers for carrier identification. LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members. In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen. The observation that the molecular defects in LCAT deficiency are dispersed in different regions of the enzyme suggests the existence of several functionally important structural domains in this enzyme.

Adolescent↗
PubMed1991

Using mutagenic polymerase chain reaction primers to detect carriers of familial defective apolipoprotein B-100.

Familial defective apolipoprotein (apo) B-100 is a genetic trait characterized by an Arg----Gln substitution in position 3500 of the apo B sequence. This genetic defect is associated with greatly increased concentrations of plasma cholesterol and may thus increase the risk of developing premature atherosclerotic disease. We describe here the use of mutagenic polymerase chain reaction primers, which greatly facilitate identification of carriers of this mutation. Moreover, we demonstrate that this method may also be used for determining the phase between two polymorphic sites. Using apo B-100 as an example we located on different chromosomes the defect in codon 3500 and a mutation in codon 3611, which produces another Arg----Gln change in the encoded apo B-100 amino acid sequence, in two probands heterozygous for both mutations.

Adolescent↗
PubMed1990

Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia.

Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment.

Apolipoproteins↗
PubMed1988

[Plasma prorenin as an index of prognostic evaluation in diabetes].

Plasma renin exists in an active form or as an inactive zymogen (P.P.) which is converted into active enzyme by exposure to trypsin. Inactive renin was first shown to be increased in patients with diabetes mellitus by Bye et al. The relationship between microalbuminuria (M.A.) in diabetic patients and the level of plasma inactive renin activated by trypsin was examined. The patients were divided into two groups: 1st group (Albustix+) and 2nd group (Albustix-). In the 1st group the inactive renin was greatly increased. In the patients with Albustix- albuminuria was measured by the R.I.A. method and two subgroups were identified. In the patients with albumin excretion over 40 mg/24 hr, prorenin was increased and correlated directly (r = 0.60) with M.A. In the group with albumin excretion below 40 mg/24 hr prorenin was normal except in three patients with increased M.A. These findings suggest that increased plasma prorenin levels in uncomplicated diabetes could anticipate the development of overt nephropathies.

Aged↗
PubMedDate not supplied

[Statins: similarities and differences in the pharmacological, clinical and laboratory aspects].

The inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (or statins) are the most powerful drugs affecting lipid and lipoprotein levels in plasma. Results obtained from large controlled trials using simvastatin, pravastatin and lovastatin for the primary or secondary prevention of coronary heart disease have demonstrated that treatment with statins is associated with a significant reduction in coronary morbidity and mortality and in total mortality. This is probably due to a more general anti-atherogenic effect of these drugs beyond their lipid-lowering activity. Meta-analysis of data from these large trials indicates that statins have an impact also on the incidence of cerebrovascular events. Currently, six statins have been approved for therapeutic use in different countries. In spite of the similarities in their chemical structure and mechanisms of action, statins may differ in many aspects such as pharmacological properties (hydrophilic vs lipophilic, elimination half-life, cytochrome P450 metabolism, etc.), effects on lipid and other biochemical variables, or pleiotropic effects on different metabolic processes related to atherosclerosis (endothelial function, platelet aggregation, immune function, etc.). In general, the safety and tolerability profile for all statins currently in use is good with a < 2% incidence of undesirable effects.

Atorvastatin↗
PubMedDate not supplied

[Atherosclerosis in light of the evidence from large statin trials].

The results of the large trials with the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (or statins) in terms of clinical benefits in patients with coronary artery disease indicate that these drugs act in a complex way on several pathways involved in the atherosclerotic process. Beyond their lipid-lowering activity, statins appear to modify many characteristics of the arterial wall, resulting in protection against the progression of plaque growth and/or the precipitation of acute events. The so called "pleiotropic" effects of statins, such as the restoration of endothelial activity, the antioxidant potential or the antiproliferative effect on smooth muscle cells, have been investigated mainly in in vitro experiments. In the near future, it will be necessary to unravel the biological significance and the clinical relevance of these effects, which also involve other pathological conditions such as cancer and osteoporosis. Furthermore, lessons from the trials with statins have allowed a better understanding of the mechanisms leading to atherosclerosis which is now considered as an inflammatory process affecting the vascular wall. This has opened new perspectives in the search for the development of newer and more targeted anti-atherogenic drugs.

Arteriosclerosis↗