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Biomedical subjects

P Coluccia

Publications and source records attributed to P Coluccia.

11 recordsLinked to original sources

Dual role of VEGF in pretreated experimental ePTFE arterial grafts.

BACKGROUND: Lack of endothelialization and abnormal smooth muscle cell (SMC) growth adversely affect the outcome of vascular synthetic grafts. The aims of our study were to investigate how a coating of extracellular matrix (ECM) and vascular endothelial growth factor (VEGF) might affect the endothelialization rate, smooth muscle cells (SMC) proliferation, and myointimal hyperplasia in experimental arterial ePTFE grafts. METHODS: In each of 30 male Lewis rats, a 1-cm-long ePTFE graft was inserted at the level of the abdominal aorta. Animals were randomized in five groups (six animals each): groups A and A1 received ePTFE grafts coated with a synthetic extracellular matrix (growth factor-reduced matrigel) containing VEGF; groups B and B1 received ePTFE grafts coated with synthetic ECM; and group C received ePTFE grafts alone. The grafts were explanted at 30 days from surgery for immunohistochemical analysis. RESULTS: Both endothelialization rate and myointimal hyperplasia were augmented in group A versus groups B and C, and these findings were statistically significant. SMC density resulted significantly higher in group A versus groups B and C, and this was associated with an altered expression of bFGF and TGFbeta. CONCLUSIONS: Pretreating ePTFE grafts with synthetic ECM and VEGF results in better endothelialization, but also in undesired higher SMC density and myointimal hyperplasia.

Animals↗

FLIP is expressed in mouse testis and protects germ cells from apoptosis.

Apoptosis control in adult testis is crucial to achieve normal spermatogenesis. In this study c-FLIP, an apoptosis-modulating protein, was investigated. In Western blot and immunohistochemical analyses, the 55 KDa c-FLIP long isoform (c-FLIP(L)) was found to be expressed strongly in spermatocytes and spermatids, at low levels in spermatogonia and at almost undetectable levels in Sertoli cells. This expression pattern was confirmed by Northern blot analyses. Further experiments carried out on GC-1spg germ cell line revealed that reducing c-FLIP(L) expression increases Fas-dependent apoptosis. Conversely, restoring c-FLIP(L) expression reduces this response to control levels. Caspase-10 expression was found to match c-FLIP(L) expression pattern; further, caspase-10 activation upon anti-Fas treatment inversely correlated with c-FLIP(L) expression. Finally, TUNEL staining of seminiferous tubules incubated with anti-Fas antibody showed that apoptosis occurs mostly in basally located germ cells, indicating that such cells, expressing low levels of c-FLIP(L), are sensitive to Fas-mediated apoptosis. These data indicate for the first time that c-FLIP(L) might control germ cell apoptosis and caspase activity in the adult testis.

Animals↗

Bimodal concentration-dependent effect of thrombin on endothelial cell proliferation and growth factor release in culture.

BACKGROUND: The role of thrombin in the stimulation of endothelial cell (EC) proliferation is controversial. The aim of this study was to investigate if thrombin regulates cell proliferation and production of platelet-derived growth factor (PDGF), bovine fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)) by bovine aortic ECs. METHODS: ECs, obtained from thoracic aortas of calves, were stimulated with thrombin at various concentrations (from 0.05 to 1.0 IU/ml) in serum free culture. Mitogenic activity of thrombin on ECs was determined by tritiated thymidine uptake. The release of PDGF, bFGF, and TGF-beta(1) was assessed by ELISA. PDGF release was confirmed by Western blot and bFGF and TGF-beta(1) mRNA expression was determined by polymerase chain reaction (PCR). RESULTS: Thrombin at high concentrations did not cause any increase in EC proliferation after 72 h of culture and induced inhibition of EC proliferation after 96 h and 8 days of culture. It induced a decrease in PDGF release and an increase in TGF-beta(1) release. Thrombin at low concentrations induced a significant increase in EC proliferation at 72 h, 96 h, and 8 days of culture. It induced an increase in PDGF release and a decrease in TGF-beta(1) release. bFGF release was higher than control at all thrombin concentrations. These data were confirmed by Western blot and PCR studies. CONCLUSIONS: Thrombin regulates EC growth through the inhibition of EC proliferation at high concentrations and through the stimulation of EC proliferation at low physiological concentrations. EC proliferation is partially mediated by autocrine production of PDGF, bFGF, and TGF-beta(1).

Animals↗

Prediction of the extent of coronary artery disease with the evaluation of left ventricular wall motion abnormalities during atrial pacing. A cross-sectional echocardiographic study.

UNLABELLED: In patients with coronary artery disease, left ventricular performance during stress is affected by the degree of coronary stenosis. In order to verify whether there exists a relationship between the extent of wall motion abnormalities detectable during atrial pacing and the degree of coronary obstruction, 76 patients, without previous myocardial infarction, were studied. Each patient underwent cross-sectional echocardiography during transesophageal atrial pacing and exercise electrocardiography before coronary angiography. Of the 76 patients, 46 had significant coronary artery disease (stenosis greater than or equal to 75% of at least one major coronary vessel), while 30 had normal coronaries or a stenosis of less than 75%. Eighteen patients had single-, 14 had two- and 14 had three-vessel disease. For each patient a coronary score was obtained: the score used took into consideration the site, number and severity of the stenosis. This score was then correlated with the wall motion score, obtained from the analysis of 9 segments of the left ventricle. A weak correlation was obtained between wall motion score at rest and coronary score (r = -0.42), while the correlation between coronary score and the difference between wall motion score at rest and during transesophageal atrial pacing was slightly better (r = 0.53); this correlation further improved if wall motion score during pacing was considered (r = -0.63). If the patients with discordant diagnostic tests (echocardiography during transesophageal atrial pacing and exercise electrocardiography) were excluded, the correlation coefficient between coronary score and wall motion score during pacing increased even more (r = -0.77). IN CONCLUSION: (1) analysis of wall motion of the left ventricle during atrial pacing is useful for the non-invasive evaluation of the severity of coronary disease; (2) cross-sectional echocardiography during atrial pacing, apart from being a useful diagnostic tool, is also a help in judging the degree of severity of coronary artery disease.

Adult↗