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Biomedical subjects

M E Ferrero

Publications and source records attributed to M E Ferrero.

At least 19 recordsLinked to original sources
PubMed2002

Regulation of endothelial cell shape and barrier function by chromogranin A.

We have found that chromogranin A (CgA), a protein released in circulation by neuroendocrine cells and neurons, prevents the vascular leakage induced by tumor necrosis factor (TNF) in a mouse model. Studies of the mechanism of action showed that CgA and its NH(2)-terminal fragments inhibit TNF-induced vascular permeability by preventing endothelial cytoskeleton rearrangements. We propose that neuronal/endocrine secretion of CgA could contribute to the regulation of endothelial barrier function and the protection of vessels against plasma leakage in inflammatory diseases.

Animals↗
PubMed2001

Roles of tumor necrosis factor p55 and p75 receptors in TNF-alpha-induced vascular permeability.

We have investigated the role of p55 and p75 tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2, respectively) in TNF-induced alteration of endothelial permeability in vitro and in vivo. Stimulation of TNFR1 with an agonist antibody or a receptor-selective TNF mutein increased the flux of (125)I-albumin through endothelial cell monolayers. An antagonist anti-TNFR1 antibody, but not antagonist anti-TNFR2 antibodies, blocked the activity of TNF in vitro. Stimulation of TNFR1, but not TNFR2, induced cytoskeletal reorganization associated with increased permeability. SB-203580, a p38 mitogen-activated protein kinase inhibitor, blocked TNFR1-induced cytoskeletal reorganization and permeability. A selective mouse TNFR1 agonist and human TNF, which binds to murine TNFR1, increased the leakage of trypan blue-albumin from liver vessels in mice. These results indicate that stimulation of TNFR1 is necessary and sufficient to increase endothelial permeability in vitro and in vivo. However, an antagonist anti-murine TNFR2 antibody partially inhibited the effect of murine TNF on liver vessels, suggesting that TNFR2 also plays a role in the regulation of TNF-induced vascular permeability in vivo.

Animals↗
PubMed1999

RANTES and MCP-1 chemokine plasma levels in chronic renal transplant dysfunction and chronic renal failure.

OBJECTIVES: Procedures to diagnose renal allograft rejection depend on detection of graft dysfunction due to the presence of mononuclear leukocytic infiltrates. DESIGN AND METHODS: In our study, we pursued an immunodiagnostic approach utilizing an ELISA method on plasma samples to monitor patients waiting to undergo transplantation in order to evidence prognostic developments in renal transplantation and, at least, to diagnose renal chronic transplant dysfunction. We analyzed blood levels of two chemokines, RANTES and MCP-1, which are normally overexpressed locally in renal chronic rejection. RESULTS: Our results showed that patients affected by chronic renal failure (and waiting for kidney transplant), as well as kidney-grafted patients affected by chronic transplant dysfunction, had plasma levels of RANTES significantly higher than those of controls (patients without acute or chronic pathologies). CONCLUSIONS: Our data suggest a simple method to evaluate the plasmatic presence of RANTES, which could be involved in longterm kidney graft failure.

Adolescent↗
PubMed1999

Effect of somatostatin on beta-endorphin release in rat experimental chronic inflammation.

The aim of the present study was to investigate the effect of somatostatin administration in arthritic rats. Inflammation was induced by daily interplantar injection of 100 microl of Freund's complete adjuvant into the left hind paw of the rat. Arthritis developed 20 days following the first injection and was stable in the inoculate paw. Arthritic rats were treated interplantarly with somatostatin (5 or 10 microg) or with indomethacin (100 microg) daily for 14 days. Inflammatory response was studied at 12 h, 7 and 14 days following drug administration. The effect of somatostatin was determined by local (into popliteal lymph nodes) and systemic production of beta-endorphin. Our results showed that somatostatin treatment significantly increased beta-endorphin levels in the blood and lymphocytes from popliteal lymph nodes. Greater efficiency was seen when 5 microg instead of 10 microg of somatostatin was used. A significant decrease of absolute leukocytosis was observed at the 14th day following somatostatin administration. Moreover, a significant reduction of plasmatic beta-globulins at 12 h and the 7th day and of plasmatic alpha2-globulins at the 14th day was observed after the beginning of somatostatin treatment.

Alpha-Globulins↗
PubMed1999

Resveratrol, a natural stilbene in grapes and wine, enhances intraphagocytosis in human promonocytes: a co-factor in antiinflammatory and anticancer chemopreventive activity.

Trans-resveratrol, a natural stilbene present in wine and grapes, has been studied mainly for its antiinflammatory and anticancer activities. In this study the activity of resveratrol on proliferative immunological parameters (differentiation, apoptosis, phagocytosis and intracellular killing) was studied using a U937 human promonocytic cell line in comparison with another polyphenol, quercetin. After incubation of the pathogen, Candida albicans, intracellular killing by macrophage-like cells was decreased by quercetin and resveratrol 10 microM but was enhanced by resveratrol 1 microM after 20 h of treatment. Phagocytosis rate, expressed as phagocytosis frequency, (i.e., percentage number of phagocytosing cells/total cells) at 20 h was highest with resveratrol 10 microM and was higher with quercetin 10 microM than with resveratrol 1 microM. The phagocytosis index exhibited the same trend. While both polyphenols demonstrated cytostatic activity on U937 growth, a prointraphagocytic effect for resveratrol 10 microM-treated cells at 10 min, resveratrol 1 microM-treated cells at 20 h and resveratrol 10 microM-treated cells at 48 h was observed. Morphological examination with optic microscopy demonstrated both apoptotic and differentiating cells, even after 10 min treatment. Resveratrol-induced apoptosis (following 4 h treatment) was confirmed by flow cytometry at concentrations as low as 1 microM and 100 nM in the assay for detection of membrane phosphatidylserine. Resveratrol- or quercetin-treated, but unstimulated cells, did not produce tumor necrosis factor-alpha protein. As phosphatidylserine externalization triggers specific recognition by monocytes and macrophages, removal of intact apoptotic cells is important a) in cell population selection and differentiation for antiblastic therapy, and b) in preventing the release of toxic inflammatory substances such as reactive oxygen substances and proteolytic enzymes by dying cells. This observation suggests that wine polyphenols, at the same concentrations as those found in plasma after moderate wine consumption, are important cofactors in antiinfective, antiinflammatory and anticancer nonspecific immune reactions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced CD3zeta and CD16zeta chain down-regulation in human peripheral blood lymphocytes and lymphokine-activated killer cells.

We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form of Procysteine, kindly donated by Transcend Therapeutics] could protect peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells from CD3zeta and CD16zeta chain down-regulation induced by H2O2 produced by lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance glutathione production in cells in which glutathione was depleted by reactive oxygen species. Our data showed that OTC induced a significant increase in CD3zeta and CD16zeta chain expression in peripheral blood lymphocytes and LAK cells, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC significantly protected peripheral blood lymphocytes and LAK against decreased zeta chain expression induced by lipopolysaccharide-activated monocytes or the addition of H2O2 to the culture medium. Our experiments thus suggested that alterations in signal-transducing molecules, such as decreased CD3zeta and CD16zeta expression observed in cytotoxic T lymphocytes and LAK cells in response to oxidative stress, could be prevented by the use of OTC.

CD3 Complex↗
PubMed1998

CD4+ and CD8+ T cell subset distribution in the blood of small-bowel-grafted rats: modification during graft-versus-host disease.

We studied the modifications of blood T cell distribution following small-bowel allografting in rats under different experimental conditions. Group 1: ACI (RT1a) rats were used as small-bowel donors for ACI x Wistar (RT1y) F1 hybrid rats (WAF1) in which graft-versus-host disease (GVHD) developed. Group 2: WAF1 rats were used as small-bowel donors to ACI rats which developed rejection. Group 3: WAF1 rats received small bowel from ACI rats hyperimmunized for 10 days (by grafting them with WAF1 skin) and GVHD developed. Group 4: Wistar rats received small bowel from ACI rats hyperimmunized for 10 days (by Wistar skin) and bidirectional GVHD and rejection were assured. A second set of the same groups which were continuously administered with cyclosporine (15 mg/kg per day s.c. for 15 consecutive days) was also studied. Recipient peripheral blood lymphocytes, obtained at 7 and 15 days following small-bowel transplantation, were stained with monoclonal antibodies anti-rat CD4 and CD8 and then analyzed in an automated flow cytometer. A significant major reduction of CD4+/CD8+ T cell ratios was shown in rats that developed simultaneous GVHD and rejection with respect to ungrafted rats.

Animals↗
PubMed1998

Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium.

BACKGROUND: Resveratrol is a phytoalexin present in red wine. It has been shown to protect LDL from peroxidative degradation. OBJECTIVE: In consideration of the low plasma concentration of orally adsorbed resveratrol (which is insufficient for antioxidant protection of LDL), we studied another effect of the compound. DESIGN: Because resveratrol is a tyrosine kinase inhibitor like other members of the tyrphostin family, we hypothesized that it has the ability to modify intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression by stimulated endothelial cells. We studied the ability of resveratrol to inhibit such adhesion molecule expression and to block the adhesion of monocytes and granulocytes to endothelial cells. RESULTS: We showed that resveratrol, at concentrations as low as 1 micromol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively. In addition, we showed that resveratrol induced a significant inhibition in the adhesion of U937 monocytoid cells to lipopolysaccharide-stimulated HSVEC. Such inhibition was comparable with that obtained when anti-VCAM-1 monoclonal antibody was used instead of resveratrol. Resveratrol also significantly inhibited the adhesion of neutrophils to TNF-alpha-stimulated NIH/3T3 ICAM-1-transfected cells, whereas neutrophils activated by formyl-methionyl-leucyl-phenylalanine did not significantly modify adhesion to NIH/3T3 ICAM-1-transfected cells. CONCLUSIONS: Our results indicate activity of resveratrol on endothelial cells and a new interpretation of an effect independent of its antioxidant function.

Antioxidants↗
PubMed1998

Intracerebroventricular injection of capsaicin or substance P provokes the micturition reflex in the rat.

Acute intracerebroventricular injection of 25 micrograms capsaicin or 40 micrograms substance P in isotonic saline elicited approximately similar effects on the micturition reflex, but capsaicin had twice as much effect as substance P. This effect is specific, since acute intracerebroventricular injection of isotonic saline did not produce the micturition reflex. It can be hypothesized that capsaicin and substance P may act on the brain micturition centers directly or by mediation of neuropeptides such as tachykinins, but other hypotheses are also made.

Animals↗
PubMed1998

The therapeutic potential of Aloe Vera in tumor-bearing rats.

Aloe Vera has been claimed to contain several important therapeutic properties, including anticancer effects. The effect of Aloe Vera administration was studied on a pleural tumor in rat. Growth of Yoshida AH-130 ascite hepatoma cells injected (2 x 10(5) in 0.1 ml) into pleura of male inbred Fisher rats was evaluated at different times (7th and 14th days). Data show that the use of Aloe Vera proved a therapeutic method, and that the present experimental model could be useful in the study of other therapeutics treatments in vivo.

Aloe↗
PubMed1997

The effect of somatostatin on experimental inflammation in rats.

UNLABELLED: The aim of the present study was to investigate the effect of somatostatin administration on experimentally induced inflammation in rats. Inflammation was induced by the intraplantar injection of carrageenan (50 microL) into the hind paw of the rat. Animals were treated intraplantarly with somatostatin in a volume of 50 microL at different doses (2.5, 25, and 250 ng, 10 microg). The inflammatory response was studied 120, 180, and 240 min after drug administration. The antinociceptive effect of somatostatin was determined by using the Randall and Selitto test and by local production of beta-endorphin from lymphocytes obtained from popliteal lymph nodes. Data show that small doses of somatostatin were the most effective in reducing hyperalgesia. Moreover, our results show that somatostatin treatment significantly increased beta-endorphin in lymphocytes from popliteal lymph nodes. The secretion of opioid peptides, which enhance analgesia, could be stimulated by locally administered somatostatin. IMPLICATIONS: Acute pain because of intraplantar inflammation induced in rats by carrageenan injection was significantly reduced by small-dose, local administration of somatostatin, which possibly favors beta-endorphin release as a mechanism. These results may have implications regarding treatment of pain conditions associated with an inflammatory response.

Animals↗
PubMed1997

Effect of acute and chronic inflammation on plasma growth hormone levels in rats.

We investigated the effect of acute and chronic stress on growth hormone (GH) plasma levels in rats. Acute stress was provoked by intravenous administrations of IL-1 beta and TNF-alpha. Determinations were made at 10, 30, 60, 120 and 180 min following i.v. injection of these cytokines into the caudal vein. We also investigated the chronic stress induced by hind paw injections of Freund's adjuvant. Arthritis was developed by 21 days following such injection. GH levels were studied at 7, 14 and 21 days after induction of arthritis on several blood samples which were withdrawn from tail veins, and long-term hormonal profiles (3 hours' sampling) were determined at 12.00 am, 1.30 pm and 3.00 pm. Local administration of dexamethasone and the monoclonal antibody anti-ICAM-1 were also used in arthritic rats. Following acute stress, a significant reduction of plasma GH levels has been evidenced, possibly related to the stimulation of corticotropin-releasing hormone. Following chronic stress, we demonstrated a significant increase of GH levels, which were significantly reduced by dexamethasone treatment and to a lesser extent by anti-ICAM-1 administration.

Acute Disease↗
PubMed1996

Tumor necrosis factor alpha-induced vascular leakage involves PECAM1 phosphorylation.

Herein we show that exposure of human umbilical vein endothelial cells to tumor necrosis factor alpha (TNFalpha) led to platelet endothelial cell adhesion molecule-1 (PECAM1) surface redistribution, disruption of cytoskeleton connections, and increased PECAM1 phosphorylation, accompanied by increased permeability to macromolecules. The in vitro use of inhibitors of tyrosine or serine-threonine kinases could prevent both PECAM1 surface redistribution and the increase in permeability induced by the cytokine. In vivo administration of lavendustin A, a natural tyrosine kinase inhibitor, protected endothelial cells from TNFalpha-dependent vascular leakage in mouse liver. We propose that the involvement of PECAM1 in TNFalpha-mediated effects on vascular permeability may depend on a dynamically regulated cytoskeletal association, related to the degree of PECAM1 phosphorylation.

Alkaloids↗
PubMed1996

End-to-side anastomosis in heterotopic rat organ transplantation.

A partial modification of the standard end-to-side anastomosis usually performed in heterotopic vascularized organ transplantation in the rat is described. Use of the method completely abolished the approximately 20% severe post-declamping bleeding due to gaps in those blind areas, the stitching of which are at risk using previously described methods. The authors thus recommend the method for performing heart, kidney, pancreas and small bowel transplantations in the rat.

Anastomosis, Surgical↗
PubMed1996

The anti-ischemic drugs defibrotide and oligotide analogously inhibit leukocyte-endothelial cell adhesion in vitro.

Defibrotide (a polydeoxyribonucleotide) and oligotide (an oligodeoxyribonucleotide) obtained from mammalian single-stranded DNA, have been demonstrated to have anti-ischemic activity in some experimental models of ischemia/reperfusion of kidney in rats. We hypothesized that their anti-ischemic activity could be related to an inhibition of leukocyte-endothelial cell adhesion and also the consequent generation of oxygen free radicals by leukocytes. We studied the in vitro adhesion of neutrophils to human umbilical vein endothelial cells under basal conditions and following neutrophil or endothelial cell activation (using 10(-7) fMLP and 500 U/ml TNF-alpha, respectively). Defibrotide and oligotide significantly inhibited neutrophil adhesion to endothelial cells (after only 1 min of drug treatment). When the anti-LFA-1 70H12 F(ab)2 monoclonal antibody was used, the drugs exerted only slight additional inhibition of the adhesion of fMLP-activated neutrophils to endothelium. These results, confirmed in NIH/3T3-ICAM-1-transfected cells, demonstrate that defibrotide and oligotide interfere with leukocyte adhesion to endothelial cells by an LFA-1-dependent mechanism.

3T3 Cells↗
PubMed1996

Drug-induced in vitro inhibition of neutrophil-endothelial cell adhesion.

1. Leukocyte-endothelial cell interactions play an important role during ischaemia-reperfusion events. Adhesion molecules are specifically implicated in this interaction process. 2. Since defibrotide has been shown to be an efficient drug in reducing damage due to ischaemia-reperfusion in many experimental models, we analysed the effect of defibrotide in vitro on leukocyte adhesion to endothelial cells in basal conditions and after their stimulation. 3. In basal conditions, defibrotide (1000 micrograms ml-1) partially inhibited leukocyte adhesion to endothelial cells by 17.3% +/- 3.6 (P < 0.05), and after endothelial cell stimulation (TNF-alpha, 500 u ml-1) or after leukocyte stimulation (fMLP, 10(-7) M), it inhibited leukocyte adhesion by 26.5% +/- 3.4 and 32.4% +/- 1.8, respectively (P < 0.05). 4. In adhesion blockage experiments, the use of the monoclonal antibody anti-CD31 (5 micrograms ml-1) did not demonstrate a significant inhibitory effect whereas use of the monoclonal antibody anti-LFA-1 (5 micrograms ml-1) significantly interfered with the effect of defibrotide. 5. This result was confirmed in NIH/3T3-ICAM-1 transfected cells. 6. We conclude that defibrotide is able to interfere with leukocyte adhesion to endothelial cells mainly in activated conditions and that the ICAM-1/LFA-1 adhesion system is involved in the defibrotide mechanism of action.

Cell Adhesion↗