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Biomedical subjects

A Orlandi

Publications and source records attributed to A Orlandi.

At least 19 recordsLinked to original sources

Effect of long-term treatment with propionyl-L-carnitine on smooth muscle cell polyploidy in spontaneously hypertensive rats.

Experimental studies suggest that DNA content is increased in the smooth muscle cells of the arteries of hypertensive animals. It is unclear whether an increase in DNA content occurring in the smooth muscle cells of hypertensive rats represents a pressure-dependent effect. To evaluate the antihypertensive effect of long-term treatment with propionyl-L-carnitine and the possible morphological changes in thoracic smooth muscle cells correlated with this effect, we studied 4-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) randomly divided into five groups. One group of SHR was treated with propionyl-L-carnitine for 12 months; the other four groups of SHR and WKY received no treatment and were controls. We used static and flow cytometry to evaluate the polyploid cell content in thoracic aorta smooth muscle cells. Systolic pressure in untreated SHR progressively increased during the experiment. Treatment did not significantly influence pressure values in SHR. In WKY, blood pressure was significantly lower than that in treated and untreated age-matched SHR (2P < .02). The number of polyploid smooth muscle cells was significantly lower in the propionyl-L-carnitine-treated SHR than in the untreated rats (2P < .04) and similar to values for WKY. The reduction of polyploid cells in treated SHR was paralleled by a significant decrease of the aortic total DNA content, whereas no modifications occurred in smooth muscle cell mass. Long-term treatment with propionyl-L-carnitine may interfere with cellular mechanisms regulating the secondary responses involved in DNA synthesis.

Animals

Age-related changes affecting atherosclerotic risk. Potential for pharmacological intervention.

The incidence of cardiovascular diseases that are related to the atherosclerotic process increases exponentially with age. Organ lesions, the clinical manifestation of atherosclerotic disease, are late events due to complications in the plaque (ulceration, thrombosis, calcification) which are the result of an increased vulnerability to disruption of a previously stable plaque. The higher incidence of age-related clinical events could be explained by a rising sensitivity of plaques to destabilising factors, both parietal and humoral. The increased probability that a plaque in an elderly patient will became vulnerable could be related to those destabilising factors that significantly increase with aging, such as advanced glycation end-products. For these reasons, it seems most important that the analysis of these age-related destabilising factors, rather than those factors that promote the development of early atherosclerotic plaques, should be undertaken. Taking the point of view of a pharmacological intervention, this should eventually lead to a more complete understanding of this process.

Age Factors

Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits.

We have characterized the extent and the phenotype of total and proliferating cell population of aortic plaques in aged rabbits receiving a long-term low-dose cholesterol hyperlipemic diet, which represents an experimental model of atherosclerosis. For nine months, rabbits received the hypercholesterolemic diet alone or in addition to a treatment with propionyl-L-carnitine (PLC), a derivative of carnitine, an intramitochondrial carrier of fatty acids present in most cell types. We observed that, in both PLC-treated and control hyperlipemic rabbits, the ratio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides, while plasma cholesterol was slightly and transiently reduced. Moreover, PLC-treated hyperlipemic rabbits exhibited a reduction of plaque thickness and extent, a slight but significant reduction of the percentage of macrophage-derived cells as compared to control hyperlipemic animals and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells. Finally, both proliferating and non-proliferating plaque cells expressed large amounts of macrophage colony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pattern obtained by a long-term oral administration of PLC was associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.

Aging

Intramuscular myxoma of the face: an unusual localization. A clinicopathological study.

BACKGROUND: Intramuscular myxoma is a rare benign mesenchymal lesion. Only very rare cases of cutaneous localization of this tumor have been described, in particular related to the somatic soft tissues of the face. This unusual localization may clinically mimic nodular or cystic facial lesions having different origins. OBJECTIVE: The aim of our work was to well characterize the phenotype of the spindle cells characteristic of intramuscular mixoma. METHODS: Tissue samples were processed for morphological and ultrastructural studies. Moreover, immunohistochemical stainings were performed to characterize the expression of different nonmuscular and muscular cytoskeletal proteins. RESULTS: The tumor was composed of sparse spindle cells embedded in a prominent mucoid matrix. Besides the predominance of a fibroblast-like appearance, some neoplastic cells displayed immunohistochemical and ultrastructural features resembling either myofibroblasts or primitive mesenchymal cells, with a modulation of cell actin expression. CONCLUSION: The presence of multiple phenotypes of nonmuscular, mesenchymal pathway of differentiation can be considered a peculiar feature of intramuscular myxoma.

Facial Neoplasms

Solid alveolar rhabdomyosarcoma of the hand in adolescence: a clinical, histologic, immunologic, and ultrastructural study.

Rhabdomyosarcoma (RMS), a high-grade, malignant, skeletal muscle tumor, represents approximately 5% of neoplasms in children. The poorly differentiated forms of RMS are often not easily diagnosed and classified. Among the four histologic variants, alveolar RMS is the least frequently reported subtype. A poorly differentiated solid variant of alveolar RMS occurred on the right hand of a 16-year-old girl. Because of the tumor size, local invasiveness, and occurrence of cutaneous and breast metastases at presentation, the clinical staging was group IV (T2/NO/M1). Surgical excisions of the primary and metastatic locations were performed and chemotherapy with vincristine, dactinomycin, cyclophosphamide, and doxorubicin was administered. Light and electron microscopy studies revealed a solid proliferation with a focal alveolar pattern of monomorphous, small, round neoplastic cells without easily detectable muscular morphologic features. The skeletal muscle origin was revealed by the positive immunostaining for desmin, alpha-sarcomeric actin, muscle-specific actins, and enolase, and confirmed by immunoblotting for desmin. Despite the age of our patient, which is considered by some authors an independent predictor of outcome, all prognostic variables were unfavorable. However, a disease-free interval during three years of follow-up underlines the importance of multidisciplinary regimens for the treatment of this rare solid tumor of childhood and adolescence.

Adolescent

Proliferative activity and alpha-smooth muscle actin expression in cultured rat aortic smooth muscle cells are differently modulated by transforming growth factor-beta 1 and heparin.

Locally liberated cytokines and extracellular matrix components influence the proliferation and differentiation of arterial smooth muscle cells (SMC), thus playing a role in the development of the atheromatous plaque. It has been proposed that the response of SMC to these factors is influenced by their own phenotype. We have tested the effects of transforming growth factor-beta 1 (TGF-beta 1) and heparin on proliferation and expression of alpha-smooth muscle (SM) actin, a well-established SMC differentiation marker, by cultured rat SMC obtained from the normal aorta of young or old rats and from the intimal thickening developed 15 days after endothelial denudation in young rats; these SMC are known to express different phenotypic features. Heparin and TGF-beta 1 reduced serum-induced proliferation in SMC from young and old rats. Heparin increased the expression of alpha-SM actin protein and mRNA in SMC from young and old rats, while TGF-beta 1 exerted the opposite action. Moreover, TGF-beta 1 induced the appearance of an elongated shape in SMC from both young and old rats. In SMC cultured from intimal thickening, heparin induced a reduction of cell proliferation without modifying their characteristic epithelioid shape; TGF-beta 1 increased the proliferative activity and induced an elongated cell shape as well as a "hills and valleys" growth pattern similar to that observed in control medial SMC; both heparin and TGF-beta 1 induced an increase of alpha-SM actin expression. Our results show that TGF-beta 1 and heparin exert different effects on the same SMC, suggesting that these substances act at least in part independently. They are also compatible with the view that the action of cytokines and of extracellular matrix components depends on the phenotype of target SMC.

Actins

Punctate porokeratotic keratoderma--its occurrence with internal neoplasia.

Punctate porokeratotic keratoderma (PPK) represents a diffuse involvement of palms and soles by multiple, accuminate keratotic papules and plugs, histologically identified by parakeratotic cornoid lamellae. A possible association between PPK and internal malignancy has been previously noted by Herman in 1973. A patient with a 3-month history of PPK is described in which a bronchial carcinoma was recently diagnosed. This association led us to speculate that PPK could be a sign of internal neoplasia, as already established for other forms of palmoplantar keratoderma. We suggest that the presence of an underlying malignancy must be screened for when a diagnosis of PPK is proposed.

Bronchial Neoplasms

Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro.

Endothelial denudation by balloon injury of the rat aorta induces the development of a neointima as a consequence of the migration and proliferation of smooth muscle cells (SMCs). Initially, intimal SMCs show a dedifferentiated phenotype, which reverts to a normal differentiated phenotype after endothelial cells have resurfaced the vessel lumen. We investigated in vitro the proliferative and phenotypic features of SMCs from different layers of rat aorta isolated 15 and 60 days after endothelial denudation. Freshly isolated intimal cells 15 days after balloon injury (IT-15) appeared rounded and showed a decreased content of alpha-smooth muscle actin, smooth muscle myosin, and desmin compared with intimal cells isolated 60 days after balloon injury (IT-60). No morphological and cytoskeletal differences were observed among freshly isolated IT-60 cells and other medial populations, which included medial SMCs that underlie the intimal thickening. In culture, IT-15 cells showed increased proliferative activity both in monolayers and in free-floating collagen lattices. Decreased expression of alpha-smooth muscle actin and smooth muscle myosin was documented in IT-15 cells compared with IT-60 cells and other medial SMC populations in monolayer. Moreover, IT-15 cells suspended in collagen lattices were poor at contracting these collagen lattices compared with IT-60 and control SMCs. IT-60 cells were equivalent to control SMCs at lattice contraction except for a temporary delay at day 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Erythema Multiforme

Age-related modification of average volume and anisotropy of vascular smooth muscle cells.

The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall.

Aging

Age-dependent increase of rabbit aortic atherosclerosis. A morphometric approach.

Aging has been indicated as one of the major risk factors for development of atherosclerotic lesions, although the role aging plays, lacks accurate evaluation. Our study was aimed at quantitatively defining such a role by using morphometric analysis. Aged (median age 3 years and 8 months) and young (4 months) white New Zealand rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 16 months. At regular intervals, levels of serum lipemic parameters were checked. A Quantimet 920 image analyzer was used on paraffin-embedded sections of the entire aortas to measure the volume density of the tunica intima, the volume density of atheroma, the ratio intima/media and the surface area of the tunica intima. Our results indicated for aged hyperlipemic rabbits a statistically significant increase in all morphometric parameters examined as compared to young hyperlipemic animals, and no statistically significant differences in serum cholesterol, triglycerides and phospholipids.

Aging

Aging and atherosclerosis in the rabbit. 1. Distribution, prevalence and morphology of atherosclerotic lesions.

Aging is considered a risk factor in the pathogenesis of atherosclerosis. It is not clear, however, whether the relationship between aging and atherosclerosis is the result of increased susceptibility of the arterial wall related to intrinsic alterations or the expression of the increase in intensity or duration of exposure to risk factors. In this study, we used aged (median age 46 months) and young (4 months old) New Zealand white rabbits. Nine aged and 11 young rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 18 months. Eleven aged and 8 young rabbits, fed standard chow for the same period, were used as controls. Using morphologic and morphometric methods, we detected in aged hyperlipemic rabbits (a) a marked prevalence of fibroatheromatous plaques (as opposed to fatty streaks in young hyperlipemic rabbits); (b) aortic lesions more extensive and of greater dimensions than in young hyperlipemic rabbits; (c) fibroatheromatous plaques in carotids and raised fatty streaks in the large subepicardial coronary branches. Our results show an increased susceptibility of the aged arterial wall to hypercholesterolemia.

Aging

Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype.

Proliferative activity of smooth muscle cells and foam cells characterizes experimental atherosclerotic plaques as they first appear. Immunohistochemical and ultrastructural methods were applied to cells arrested in metaphase by colchicine and the phenotype of cells in mitosis was detected. Most of the metaphase arrested FC found in aortic plaques of cholesterol fed New Zealand rabbits were positive to the anti-macrophage monoclonal antibody and negative to the anti-smooth muscle actin monoclonal antibody. Moreover, most of the metaphase blocked FC had the ultrastructural features of macrophages. These preliminary results further strengthen previous observations on rabbit plaques that the FC pool is mainly constituted by macrophages and show, for the first time, that the dimension of this pool depends not only on migration of circulating monocytes but also on the in situ proliferation of macrophages.

Animals

High-dose synthetic progestogens inhibit foam and smooth muscle cell proliferation and atherosclerotic plaque formation in aortas of rabbits fed a hypercholesterolemic diet.

Female rabbits on a hypercholesterolemic atherogenic diet were treated with high doses of the synthetic progestogens norethisterone and medroxyprogesterone acetate in order to clarify the effect and possibly some of the mechanism of action of these hormones on diet-induced atherogenesis. We employed morphometric studies to determine the surface area of the rabbit aorta occupied by and the maximum thickness of lipid plaques. Autoradiography with tritiated thymidine was performed to demonstrate the effect of the progestogens on cell proliferation, which plays a key role in atherogenesis. Medroxyprogesterone acetate-treated and, above all, norethisterone-treated animals exhibit a more marked reduction of atherosclerosis than control rabbits fed the same diet. Our results suggest that both progestogens we used inhibit the development of atherosclerosis mainly by blocking the proliferation of smooth muscle cells in the tunica media and the cell population of the plaque.

Animals

[Prevention of tuberculosis today].

After a summary of main defences to prevent tubercular disease, Author refers that only 0,5% of 159,204 BCG-vaccinated subjects at his Institute contracted tuberculosis. Other data confirm that the rôle of an healthy environment is important to prevent the disease, also without BCG intervention and that BCG alone can defend from tuberculosis also without the influence of an healthy environment. A risk environment reduces the BCG effectiveness, but not so significantly. Then the BCG vaccination showed itself an useful means of preventing tuberculosis that today is still indispensable as first antitubercular protection.

BCG Vaccine