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Biomedical subjects

L Barberi

Publications and source records attributed to L Barberi.

17 recordsLinked to original sources

DNA dose and sequence dependence in sperm-mediated gene transfer.

We have tested three parameters in sperm-mediated gene transfer assays with mice and pigs: (i) the epididymal versus ejaculated origin of sperm cells, (ii) the primary structure, and (iii) the amount of the challenging foreign DNA. We have found that the pVLCNhGH construct, of retrotransposon origin, causes a massive embryo lethality and yet increases the yield of genetic transformation among born animals of both species compared to viral constructs. Arrest of embryonic development is a DNA dose-dependent effect, which is observed with high DNA doses, while lower doses are compatible with development. Finally, the overall efficiency of sperm-mediated gene transfer is higher when ejaculated, versus epididymal, spermatozoa are used. We suggest that this difference is related to the highly efficient apoptotic response in epididymal compared to ejaculated spermatozoa, triggered by the interaction of exogenous DNA molecules with the sperm membrane.

Animals↗

E2F transcription factors are differentially expressed in murine gametes and early embryos.

We have examined the murine genes encoding transcription factors E2F1, -3, -5 and -6 in gametes and early embryos. All genes are expressed as maternal transcripts and all are efficiently transcribed after the blastocyst stage. Between those two stages, each E2F mRNA is transcribed with a distinctive and unique pattern. E2F proteins are also differentially expressed and compartmentalized in pre-implantation embryos.

3T3 Cells↗

Oxidized lipoproteins and endothelium.

Endothelium is an early target of pro-atherosclerotic events, which may result in functional and morphological perturbations. Oxidized low density lipoproteins, an atherogenic factor with strong cytotoxicity, may potentially contribute to altered endothelial function through the activation of a stress response, which would rescue cells to full vitality, or, conversely, by leading to cell death. Evidence is presented here for the ability of chemically oxidized low density lipoproteins to induce the synthesis of the inducible form of heat shock protein 70 in cultured human endothelial cells, and for the association of epitopes of these modified lipoproteins with apoptotic endothelial cells in aortic sections from hypercholesterolemic rabbits.

Animals↗

Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits.

The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases.

Angiotensin-Converting Enzyme Inhibitors↗

Dual effects of the antioxidant agents probucol and carvedilol on proliferative and fatty lesions in hypercholesterolemic rabbits.

The in vivo direct antiatherogenic activity of the antioxidant probucol (200 mg/kg per day) or the beta-blocker with antioxidant properties carvedilol (10 and 20 mg/kg per day) was tested in the same animal in two different types of atherosclerotic lesion (proliferative and fatty lesions) induced in cholesterol-fed rabbits (1%). Drugs were given daily mixed with standard diet for 8 weeks; body weight and plasma lipid profile were not different among groups throughout the study. Aortic fatty lesions were induced by cholesterol feeding (n = 25 in each group) and their extent expressed as % of aorta inner surface covered by plaques was significantly reduced by both drugs (28.2+/-9.6%, P <0.05, 19.9+/-6.2%, P <0.01 for low- and high-dose carvedilol, respectively; 22.3+/-7.6%, P <0.01 for probucol, versus 41.6+/-10.7% in control rabbits). Proliferative lesions were obtained by positioning a hollow silastic collar around one carotid artery 6 weeks after dietary and drug treatments started (n = 5 in each group). The neointimal formation, mostly composed by myocytes, was determined by measuring cross-sectional thickness ratio of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals, collared arteries resulted in a significant neointimal cell accumulation compared to the sham (1.10+/-0.14 versus 0.02+/-0.01) without change in medial thickness. I/M ratio was reduced by about 50% in animals treated with probucol (0.51+/-0.1) and carvedilol (0.66+/-0.21 and 0.52+/-0.1 in the low- and high-dose group, respectively). Total plasma TBARS were more than 50% lower in both probucol- and high-dose carvedilol-treated rabbits. Results show that pharmacological pretreatment with antioxidants directly inhibits early atherogenic processes, representing a potentially useful approach in the prevention of atherosclerosis.

Adrenergic beta-Antagonists↗

Effect of lercanidipine and its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits.

The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+/-0.02, whereas in carotids with a collar the ratio was 2+/-0.42. In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed. I/M ratios were 0.73+/-0.4, 0.42+/-0.1, 0.32+/-0.1 for 0.3, 1, and 3 mg kg(-1) week(-1), respectively (P<0.05). The lercanidipine enantiomer (3 mg kg(-1) week(-1)) was as effective as the racemate (0.41+/-0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively. The area of fatty-streaks in the aorta (n = 11-15) was significantly reduced by lercanidipine (3 mg kg(-1) week(-1), 16% vs 27%, P<0.05), a trend was observed also with lower doses. When different segments of the aorta were considered (arch, thoracic, abdominal) a significant and dose-dependent effect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as effective as lercanidipine. These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity.

Animals↗

Effect of lacidipine on fatty and proliferative lesions induced in hypercholesterolaemic rabbits.

1. The in vivo antiatherogenic activity of the calcium antagonist, lacidipine, was investigated in two different types of atherosclerotic lesions (proliferative and fatty lesions) induced in rabbits. 2. The proliferative lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty lesions were induced by cholesterol feeding. Cholesterol (1%) and lacidipine (1, 3, and 10 mg kg-1) were given daily mixed with standard diet for 8 weeks to White New Zealand rabbits. The intimal hyperplasia (proliferative lesion) was induced 6 weeks after dietary and drug treatment started. 3. The neointimal formation was determined by measuring cross sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals (n = 5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries with no collar (sham) showed an I/M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.62 +/- 0.12. In lacidipine-treated animals a significant and dose-dependent effect on proliferative lesions at all three doses tested, was observed. I/M ratios were 0.47 +/- 0.02, 0.40 +/- 0.09, 0.32 +/- 0.02 for doses 1, 3, and 10 mg kg-1 day-1, respectively (P < 0.05). 4. The fatty lesion extent was significantly reduced by lacidipine at the 10 mg kg-1 day-1 dose, although a trend was also observed with lower dosage. 5. These results suggest a direct antiatherosclerotic effect of lacidipine, independent of modulation of risk factors such as hypercholesterolaemia and/or hypertension. Furthermore, the proliferative lesions are apparently more sensitive to lacidipine than are lipid-rich lesions.

Animals↗

Effect of lacidipine on the carotid intimal hyperplasia induced by cuff injury.

The in vivo antiatherogenic activity of the calcium antagonist lacidipine was investigated in arterial hyperplasia induced by perivascular manipulation of hypercholesterolemic carotid rabbits. This was accomplished by positioning a hollow silastic collar around one carotid, which within a few days induces an atherosclerotic lesion (proliferative lesion) showing biochemical and morphologic changes similar to those of early human atherosclerosis: the contralateral carotid, with no collar, served as control in the same animal. The effect of lacidipine was also investigated in aortic atherosclerotic lesions (fatty lesions) induced by hypercholesterolemia mixed with either cholesterol (1%) and lacidipine (3 mg/kg/day) or cholesterol (1%) alone for 8 weeks. Hypercholesterolemic New Zealand White rabbits were fed daily a standard diet. Intimal hyperplasia was mechanically induced in one carotid artery of each rabbit 6 weeks after dietary and drug treatment started. Neointimal formation was followed by measuring by light microscopy the cross-sectional thickness of intimal (I) and medial (M) tissue of fixed arteries. In positive control animals receiving dietary cholesterol only (n = 10), by 14 d after collar positioning the process of intimal hyperplasia was significantly pronounced. The control arteries showed an I:M tissue ratio of 0.03 +/- 0.02, whereas in the carotid with collar the ratio was 0.56 +/- 0.11. In the animals receiving lacidipine, neointimal formation was significantly lower [I:M tissue ratio 0.32 +/- 0.1 (n = 10), about 60% of positive controls]. Measurement of the percent area of the aortic intima covered by plaques did not show significant differences between control and lacidipine-treated animals. These results suggest a direct antiatherosclerotic effect of lacidipine on proliferative lesions.

Animals↗

Leber's optic neuritis.

The authors give a résumé of the main clinical characteristics of Leber's disease with presentation of pedigrees of three affected families.

Adolescent↗

Aicardi's syndrome.

Some cases of complete Aicardi's syndrome (agenesis of the corpus callosum, infantile spasmus, mental retardation, costovertebral anomalies and a characteristic lacunar chorioretinopathy) are reported together with other unusual cases (isolated lacunar chorioretinopathy).

Abnormalities, Multiple↗

Ocular manifestations in Kniest syndrome, Smith-Lemli-Opitz syndrome, Hallermann-Streiff-François syndrome, Rubinstein-Taybi syndrome and median cleft face syndrome.

In the pathology of malformations it is only in very few cases possible to identify a complete syndromal picture; the authors present some multimalformative syndromes, observed in the past few years at the Department of Pediatric Ophthalmology of the University of Siena. The ocular findings are reported and discussed in relation with the general features in order to make a correct diagnosis.

Abnormalities, Multiple↗

SIM 6080, a new calcium antagonist, reduces aortic atherosclerosis in cholesterol-fed rabbits.

SIM 6080 is a new calcium antagonist, structurally related to diphenylalkylamines, which combines transmembrane and intracellular calcium antagonist activities. In the present study we investigated the effect of SIM 6080 on atherogenesis in cholesterol-fed rabbits. Subcutaneous administration of the compound at 0.33, 1, and 3 mg kg-1/bid for 60 days neither affected plasma lipids nor blood pressure. However at 1 and 3 mg kg-1/bid SIM 6080 reduced in a dose-dependent manner both the area of the aorta covered by plaques and aortic cholesterol content. Determination of SIM 6080 plasma and aortic content indicated that the compound could concentrate up to 10 times in the arterial tissue. In vitro studies demonstrated that at concentrations similar to those observed in the aorta this compound may stimulate rabbit beta VLDL catabolism by smooth muscle cells in an homologous system suggesting that the up-regulation of LDL-receptors in the aorta may contribute to the antiatherosclerotic properties of SIM 6080.

Animals↗

Anterior optic pathways gliomas. The dilemma of treatment.

Anterior optic pathways gliomas are classifiable histologically and clinically with other pilocytic gliomas of the midline (of hypothalamus and brainstem), especially of childhood. The very slow course, sometimes imperceptible over the years, that characterizes the majority of them should not be taken to mean lack of growth. Tumultuous courses and acute episodic deteriorations are both possible. Hence the need for therapy. Indefinite abstention cannot be upheld, at least in the great majority of cases. In gliomas of a nerve only the object of surgery is usually removal, using the intraorbital, intracanalicular and intracranial approaches, but in gliomas of the chiasm or chiasm-hypothalamus the object is more exploratory and decompressive. Radiotherapy is generally accepted as affective only in the latter cases. No single standard protocol is possible: treatment had to be individualized case by case.

Adult↗

Medical therapy of orbit rhabdomyosarcoma in children.

Rhabdomyosarcoma is the most frequent malignant tumour of the orbit in the pediatric age. The chances of survival of patients affected by such a highly malignant neoplasia have significantly improved in recent years. The results obtained up until now with various therapeutic approaches are reviewed briefly and the results obtained in four children affected by rhabdomyosarcoma of the orbit are reported who were treated at the Ophthalmology and Pediatric Clinics of Siena University. The possibility is advanced that the less aggressive and a cautiously conservative treatment can produce the equivalent excellent results which are presently obtained by very destructive therapeutic approaches.

Antineoplastic Agents↗

Medical therapy of retinoblastoma in children.

Retinoblastoma is the most common ocular tumour which occurs in infancy. Unfortunately, it is diagnosed only when the disease is in an advanced phase and the prognosis is decidedly unfavorable. Patients treated early, in the first stage of the disease can be cured with surgical and radiation treatment. For patients who are already in an advanced stage, the risk of metastatic dissemination is very high and therefore the introduction of chemotherapy, particularly vincristine and cyclophosphamide is believed to be useful. The authors report on their results obtained in patients with retinoblastoma who have been treated with combined surgical, radio- and chemotherapic treatment.

Antineoplastic Agents↗