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R Paoletti

Publications and source records attributed to R Paoletti.

227 records · Page 13Linked to original sources

Lipid-modified proteins as biomarkers for cardiovascular disease: a review.

Lipid-modified proteins are classified based on the identity of the attached lipid, a post- or co-translational modification required for their biological function. At least five different lipid modifications of cysteines, glycines and other residues on the COOH- and NH(2)-terminal domains have been described. Cysteine residues may be modified by the addition of a 16-carbon saturated fatty acyl group by a labile thioester bond (palmitoylation) or by prenylation processes that catalyze the formation of thioether bond with mevalonate derived isoprenoids, farnesol and geranylgeraniol. The NH(2)-terminal glycine residues may undergo a quite distinct process involving the formation of an amide bond with a 14-carbon saturated acyl group (myristoylation), while glycine residues in the COOH-terminal may be covalently attached with a cholesterol moiety by an ester bond. Finally, cell surface proteins can be anchored to the membrane through the addition of glycosylphosphatidylinositol moiety. Several lines of evidence suggest that lipid-modified proteins are directly involved in different steps of the development of lesions of atherosclerosis, from leukocyte recruitment to plaque rupture, and their expression or lipid modification are likely altered during atherogenesis. This review will briefly summarize the different enzymatic pathways of lipid modification and propose a series of lipid-modified proteins that can be used as biomarkers for cardiovascular disease.

Acyltransferases↗

Sirenomelia. Pathological features, antenatal ultrasonographic clues, and a review of current embryogenic theories.

We aimed to discuss the prenatal diagnosis and pathological features of sirenomelia, and to review current embryogenic theories. We observed two sirenomelic fetuses that were at the 19th and 16th gestational week respectively. In the former, transvaginal ultrasound revealed severe oligohydramnios and internal abortion, whereas bilateral renal agenesis, absence of a normally tapered lumbosacral spine, and a single, dysmorphic lower limb were detected in the latter. In both cases, X-rays and autoptic examination allowed categorization on the basis of the skeletal deformity. Subtotal sacrococcygeal agenesis was present in both cases. Agenesis of the urinary apparatus and external genitalia and anorectal atresia were also found. Classification of sirenomelia separately from caudal regression syndrome is still debated. Recent advances in the understanding of axial mesoderm patterning during early embryonic development suggest that sirenomelia represents the most severe end of the caudal regression spectrum. Third-trimester ultrasonographic diagnosis is usually impaired by severe oligohydramnios related to bilateral renal agenesis, whereas during the early second trimester the amount of amniotic fluid may be sufficient to allow diagnosis. Early antenatal sonographic diagnosis is important in view of the dismal prognosis, and allows for earlier, less traumatic termination of pregnancy.

Ectromelia↗

Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

With the increasing knowledge of the pathogenesis of atherosclerosis, it appears that in the future the prevention of cardiovascular disease will involve not only risk factor correction, but also direct pharmacological control of processes occurring in the arterial wall. Among these, a pivotal role is played by smooth muscle cell (SMC) migration and proliferation, which, together with lipid deposition, are prominent features of atherogenesis and restenosis after angioplasty. Mevalonate and other intermediates of cholesterol synthesis (isoprenoids) are essential for cell growth, hence drugs affecting this metabolic pathway are potential antiatherosclerotic agents. Recently, we provided in vitro and in vivo evidence that fluvastatin, simvastatin and lovastatin, but not pravastatin, decrease SMC migration and proliferation dose dependently, independently of their hypocholesterolemic properties. The in vitro inhibition of cell migration and proliferation induced by simvastatin and fluvastatin (70-90% decrease) was prevented completely by the addition of mevalonate, and partially prevented by farnesol and geranylgeraniol (80%), confirming the specific role of isoprenoid metabolites in regulating these cellular events, probably through prenylated protein(s). The in vivo antiproliferative activity of fluvastatin on neointimal hyperplasia in normocholesterolemic rabbits was also prevented fully by the local delivery of mevalonate, by means of an Alzet pump. Fluvastatin and simvastatin also inhibited cholesterol esterification and deposition induced by acetylated LDL in cultured macrophages. This effect was fully prevented by the addition of mevalonate or geranylgeraniol. Taken together, these results suggest that, beyond their effects on plasma lipids, HMG-CoA reductase inhibitors exert a direct antiatherosclerotic effect on the arterial wall, probably through local inhibition of isoprenoid biosynthesis.

Animals↗

[Opinions and attitudes of youngsters about sexually transmitted diseases].

A group of 1.085 students (582 M, 503 F) attending high school (742) and nursing school (343) filled in an anonymous questionnaire on their sexual habits and their knowledge of contraception and sexually transmitted diseases. Overall, 57% of the study population had already a complete sexual intercourse at a mean age of 16,4 (SD +/- 1,8). 74% had 1-3 sexual partners, whereas 28% had more than 3. All students affirmed that it was possible to prevent sexually transmitted diseases and 92,6% indicated correct methods. However 10% of students did not know that AIDS is transmitted sexually as 47% hepatitis B. The responses made by nursing students were more correct that those of high school students.

Adolescent↗

Regression of the atherosclerotic lesion in man: the impact of noninvasive techniques.

Experimental studies demonstrate that atherosclerotic plaques induced in animals can regress following appropriate treatment, but evidence in favour of the regression of atherosclerotic lesions in man is still scanty. New imaging techniques, such as high resolution B-mode echotomography, allow the visualization and measurement of anatomical parameters of the arterial wall in sample arteries of human patients "in vivo", introducing the possibility of a much more precise monitoring of early atherosclerotic lesions. New information on the natural history of atherosclerotic disease in man, including the possibility of differentiating between lesions of different clinical significance, can be expected from the wide application of these techniques to atherosclerosis research. A more precise testing of diets, drugs and physical procedures intended to obtain the regression of atherosclerosis in human beings will also be possible.

Animals↗

[Variations in the pulsatile index of the uterine arteries in postmenopausal women receiving hormone replacement therapy].

The authors studied variations in the pulsatility index of the uterine arteries in postmenopausal women who had received hormone replacement treatment (HRT) for at least one year and compared them to those in a control group not receiving HRT. The results showed a significant variation in this index with the tendency to assume lower values compared to the control group, thus resulting in increased uterine vascularization, almost resembling that observed during the child-bearing period. This drop in the pulsatility index should probably be considered the anatomo-functional in patients not receiving HRT.

Adult↗