Biomedical subjects

S Frigerio

Publications and source records attributed to S Frigerio.

28 records · Page 2Linked to original sources

PubMed1998

Cerebrospinal fluid thrombomodulin and sVCAM-1 in different clinical stages of multiple sclerosis patients.

In order to investigate whether brain endothelial cells activation and/or damage could be selectively monitorized, soluble vascular cell adhesion molecule 1 (sVCAM-1) and thrombomodulin (TM) levels were studied in serum and cerebrospinal fluid (CSF) of 39 multiple sclerosis (MS) patients in various phases of the disease, 19 patients with other non-inflammatory neurological diseases (OND) and 15 patients with inflammatory neurological diseases (IND). No differences in sVCAM-1 CSF levels were detected, except for lower levels in IND compared to OND. Serum TM levels were lower in IND compared to progressive MS patients. Moreover, a significant decrease both in VCAM index and in TM index was detected in IND compared to all other groups. TM index was higher in MS patients in progression as compared to OND. The combined analysis of sVCAM-1 and TM might be a useful tool in monitoring brain endothelium activation or damage in different phases of MS.

Adult↗

PubMed1998

Immunocompetence of human microvascular brain endothelial cells: cytokine regulation of IL-1beta, MCP-1, IL-10, sICAM-1 and sVCAM-1.

Endothelia from the brains of four patients undergoing neurosurgery, including one multiple sclerosis (MS) patient, were studied in vitro to determine cytokine and chemokine production; the release of soluble adhesion molecules was also investigated. The same procedure was repeated on human umbilical vein endothelial cells (HUVECs) in order to detect possible district-specific differences. After isolation, the endothelium was cultured and stimulated with gamma-interferon (IFN), tumour necrosis factor alpha (TNF-alpha) and LPS. The results showed that brain endothelium, in our experimental conditions, does not produce interleukin (IL)-10 and produces lower amounts of IL-1beta and soluble intercellular adhesion molecule-(sICAM-1) than HUVECs do; no differences were detected in soluble vascular cell adhesion molecule-(sVCAM-1) production. MCP-1 mRNA was detected both without and after stimulation with TNF-alpha and gamma-IFN in HUVECs and MS human brain endothelial cells (HBECs), while in non-MS-HBECs it was found only after gamma-IFN stimulation.

Adult↗

PubMed1997

Reduced adhesion of PBMNCs to endothelium in methylprednisolone-treated MS patients: preliminary results.

Methylprednisolone (MP) is a synthetic steroid commonly used in the treatment of multiple sclerosis (MS) relapses. It has a wide spectrum of activities on immune cells: it might also act by preventing mononuclear cell/endothelium adhesion. We studied adhesion phenomena between cultured human umbilical vein endothelial cells (HUVECs) and PBMNCs (CD45+, CD14+) from 6 MS patients treated in vivo with MP. We also studied fluctuations in CD11a and CD18 levels on lymphocytes and monocytes, as well as changes in serum sICAM-1 and sVCAM-1 concentrations. After MP treatment, PBMNCs adhesion to endothelium decreased at 3 h, while it went back to baseline levels at 24 h. A tendency to increase in both CD11a and CD18 on the surface of lymphocytes was detected, while an increase in serum sVCAM-1 was seen at 3 h.

Adult↗

PubMed1996

Structure-antigastrin activity relationships of new spiroglumide amido acid derivatives.

A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbit gastric parietal cells. Appropriate chemical manipulations of the structure of spiroglumide (CR 2194), i.e., (R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro[4.5]decan- 8-yl)-5-oxopentanoic acid, led to potent and selective antagonists of CCKB/gastrin receptors. Structure-activity relationships are discussed. Some of these new derivatives, as, for example, compound 54 (CR 2622), i.e., (S)-4-[[(R)-4'-[(3,5-dichlorobenzoyl)-amino]-5'-(8- azaspiro[4.5]decan-8-yl)-5'-oxo-pentanoyl]amino]-5- (1-naphthylamino)-5-oxopentanoic acid, exhibit activity 70-170 times greater than that of spiroglumide, depending upon the model used (IC50 = 2 x 10(-8) vs 140 x 10(-8) mol in binding inhibition of [3H]-N-Me-N-Leu-CCK-8 in guinea pig brain cortex and IC50 = 0.7 x 10(-8) vs 122.3 x 10(-8) mol in inhibition of gastrin-induced Ca2+ mobilization in parietal cells of rabbit, respectively). Computer-assisted conformational analysis studies were carried out in order to compare the chemical structure of both the agonist (pentagastrin) and the antagonist (54).

Animals↗

PubMed1996

Human brain endothelial cells and astrocytes produce IL-1 beta but not IL-10.

The ability of human brain endothelial cells to produce mRNA for interleukin-10, and release IL-10 in culture supernatants after in vitro stimulation with LPS, TNF-alpha and gamma-IFN was assessed and compared to that of astrocytes, peripheral blood mononuclear cells and human umbilical vein endothelial cells. IL-1 beta and beta 2-microglobulin release were also analysed. IL-10 and TNF-alpha mRNA presence was investigated in normal brain as well as in three plaques from two multiple sclerosis patients. While increased IL-1 beta and beta 2-microglobulin release in the supernatants of stimulated cells could be detected in all the studied cell lineages, IL-10 mRNA and protein release was only seen in LPS-stimulated PBMNCs. Similarly, mRNA for IL-10 was not detected in CNS tissues, while TNF-alpha was present in all plaques. The lack of production of significant amounts of IL-10 by astrocytes and human brain endothelial cells suggests that these cells may not be the primary source of in vivo IL-10-mediated down-regulation of immune reactions within the central nervous system.

Adult↗

PubMed1992

[The possible effects of galactosaminoglucuronoglycan sulfate on blood coagulation processes].

Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance.

Adult↗

PubMedDate not supplied

Phagocytosis of hemozoin (native and synthetic malaria pigment), and Plasmodium falciparum intraerythrocyte-stage parasites by human and mouse phagocytes.

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary, whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.

Animals↗

PubMedDate not supplied

Immunocytochemical and immunoelectron microscopical analysis of BCL2 expression in thyroid oxyphilic tumors.

In both human lymphoma and carcinoma, BCL2 expression contributes to the neoplastic development by preventing normal turnover due to programmed cell death. In thyroid carcinoma it was shown that BCL2 expression is related to cell differentiation and appears to be associated with a less aggressive behavior. Using immunogold electron microscopy labeling techniques on ultrathin frozen sections, the authors undertook an analysis of bcl-2 protein localization in 7 cases of thyroid tumor with (4 cases) or without (3 cases) oncocytic differentiation, which displayed histopathological features, corresponding to different degree of aggressiveness. All thyroid tumors and a lymphoblastoid cell line overexpressing BCL2 showed a preferential labeling of mitochondrial circumference, while the 4 cases with oncocytic differentiation displayed a bcl-2 protein location, not only on the circumference but also on the cristae of a consistent number of mitochondria. These results may indicate a bcl-2 protein interaction with intramitochondrial constituents related to the neoplastic transformation in oncocytic tumor.

Adenoma, Oxyphilic↗

PubMedDate not supplied

Lycopersicon esculentum lectin: an effective and versatile endothelial marker of normal and tumoral blood vessels in the central nervous system.

The binding of Lycopersicon esculentum lectin (LEA) to the vascular endothelium was studied in the central nervous system of rat, mouse and guinea pig at different developmental ages, and in a gliosarcoma model. Our observations showed that LEA consistently stained the entire vascular tree in the spinal cord and in the brain of all animal species at all developmental ages investigated. In the tumor model, the staining of the vascular network was very reproducible, enabled an easy identification of vascular profiles and displayed a higher efficiency when compared to two other commonly used vascular marker (EHS laminin and PECAM-1). Moreover, our results showed that LEA staining was comparable in both vibratome and paraffin sections and could be easily combined with other markers in double labeling experiments. These observations indicate that LEA staining may represent an effective and versatile endothelial marker for the study of the vasculature of the central nervous system in different animal species and experimental conditions.

Animals↗

PubMedDate not supplied

[Open repair of pararenal aortic aneurysms].

Surgical treatment of pararenal aortic aneurysms, if compared to open repair of infrarenal aneurysms, is characterized by more technical difficulties and haemodynamic problems. Since endovascular repair has become feasible in most cases of infrarenal aneurysms, surgical treatment of pararenal aneurysms is a matter of great interest for vascular surgery. Detection of pararenal aneurysms needs a careful preoperative diagnosis, assessment of cardiac, renal and pulmonary status of the patient and planning of the surgical intervention. The surgeon needs to face an extended proximal aorta exposure, to manage the left renal vein and to choose an appropriate clamping site. Then a skilled and quick reconstruction of the visceral arteries is fundamental to minimize organ disfunction. Coupled intraoperative selective perfusion of visceral arteries and systemic administration of nephroprotective drugs optimizes organ protection during ischemia. To better define challenges, risks and results, we reviewed our experience with the treatment of pararenal aortic aneurysms. In the period between January 1993 and May 2003, 98 consecutive patients underwent surgery for pararenal aneurysms at our Institution. We treated 98 pararenal aneurysms, divided in 68 juxtarenal and 30 pararenal ones. In the juxtarenal aneurysms group, the 30 days mortality rate was 5.8% (4/68); 3 of these patients underwent urgent operation for ruptured aneurysm. In the suprarenal aneurysms group, the 30 days mortality rate was 3.3% (1/30). In conclusion pararenal aneurysm repair is a safe procedure, especially if performed electively, and represents an interesting field of research to improve surgical and anesthesiologic techniques.

Aged↗