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Biomedical subjects

B Grigolo

Publications and source records attributed to B Grigolo.

47 records · Page 3Linked to original sources

23-Methyl-3 alpha,7 beta-dihydroxy-5 beta-cholan-24-oic acid: dose-response study of biliary secretion in rat.

A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 mumoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholic acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Tissue engineering applications: cartilage lesions repair by the use of autologous chondrocytes].

Promising new therapies based on tissue engineering have been recently developed for cartilage repair. The association of biomaterials with autologous chondrocytes expanded in vitro can represent a useful tool to regenerate this tissue. The scaffolds utilised in such therapeutical applications should provide a pre-formed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells and stimulate the phenotype of transplanted cells. Hyaff-11 is a hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell carrier for tissue-engineered repair. From our findings we can state that human chondrocytes seeded on Hyaff-11 are able to maintain in vitro the characteristic of differentiated cells, expressing and producing collagen type II and aggrecan which are the main markers of cartilage phenotype, down-regulating collagen type I. Moreover, it seems to be a useful scaffold for cartilage repair both in animal models and clinical trials in humans, favouring the formation of a hyaline-like tissue. In the light of these data, we can hypothesise, for the future, the use of autologous chondrocyte transplantation together with gene therapy as a treatment for rheumatic diseases such as osteoarthritis.

Animals↗

Expression of different chemokines by human osteosarcoma cells in response to tumor necrosis factor-alpha.

We investigated the expression of different chemokines in the surnatants and inside the cells of four human osteosarcoma cell lines. HOS, U-2 OS, MG63 and Saos-2 cells were cultured for 24, 48, 72 hours both in basal conditions and after stimulus with TNF alpha. Human stromal cells were used as control. IL-8 and MCP-1 are present in higher concentration in the surnatants in contrast to RANTES which is present primarily inside the cells. IL-8 and MCP-1 are not totally expressed by all the human osteosarcoma cell lines in unstimulated conditions, but became detectable after TNF alpha treatment. In general, this cytokine stimulated the production and release of the three chemokines.

Cell Division↗

Tissue engineering for cartilage repair: in vitro properties of a hyaluronan-derivative.

Association of biomaterials with autologous cells can provide a new generation of implantable devices for cartilage and bone repair. Such scaffolds should provide a performed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells, and stimulate the phenotype of transplanted cells. Hyaff-11 is a recently developed hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell scaffolds for tissue-engineered repair. The aim of this study was to evaluate in vitro the potential of Hyaff-11 to support the growth of human chondrocytes and to maintain their original phenotype. Our data indicate that human chondrocytes seeded on Hyaff-11 express and produce collagen type II and aggrecan and downregulate the production of collagen type I. These results provide an in vitro demonstration of therapeutic potential of Hyaff-11 as a delivery vehicle in tissue-engineered repair of articular cartilage defects.

Adolescent↗

Establishment of a new human immortalized chondrocyte cell line.

Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 early function genes: E6 and E7, using the highly efficient cationic liposome-mediated (lipofection) procedure. The transfection was verified by reverse transcriptase-polymerase chain reaction analysis of E7 mRNA and by immunofluorescence localization of the E7 protein in the cell cytoplasm. The established chondrocyte cell line was examined in monolayer and in two culture conditions that were described to re-induce differentiated characteristics: culturing in a serum-free defined medium and seeding on a hyaluronan-based three-dimensional biomaterial. Immortalized cells were able to re-express the main markers of chondrocyte phenotype, both at mRNA and protein levels, under the two defined cultured conditions used. The cell line that we obtained may be a useful tool for increasing our knowledge of the genetic and biochemical events involved in the processes of cartilage growth and differentiation, and of the etiopathogenesis of many rheumatic diseases.

Cell Line↗

Autologous chondrocytes implantation: indications and results in the treatment of articular cartilage lesions of the knee.

Articular cartilage lesions of the knee constitute a frequent event and one that is difficult to treat. In time, different surgical methods have been used with results that are often contradictory. The authors report the indications and results of different methods used in the treatment of cartilage lesions: in particular, the experience initiated in 1997 with autologous chondrocytes implantation is discussed. Between 1997 and 2000, a total of 40 patients were submitted to autologous chondrocytes implantation injected in suspension under a periosteal flap. This method includes wide exposure of the joint lesion by arthrotomy. Between 1999 and 2001, a total of 30 patients were submitted to autologous chondrocytes implantation using a tridimensional matrix. The availability of biomaterial simplified the implant method and made arthroscopy possible. All of the patients were submitted to serial clinical follow-ups. MRI was also conducted for a second arthroscopic look. The results obtained in both series after a mean follow-up of 4 years (range 2 to 6 years) are good, and confirm the effectiveness of the method that allows for complete morphological and structural repair of lesions of the joint cartilage.

Adolescent↗

Copper/zinc superoxide dismutase expression by different human osteosarcoma cell lines.

Oxidative stress has been frequently implicated in the initiation and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process, are lowered in a number of malignancies even though different findings have been reported in the literature. It has been shown that tumors have less copper/zinc superoxide dismutase (Cu/Zn SOD) in comparison with the more metabolically active tissues, but there is a large overlap between normal and tumor tissue. In order to examine the relationship between osteosarcoma at different degrees of proliferation and differentiation and Cu/Zn SOD levels, four different human ostosarcoma cell lines: HOS, U-2 OS, MG63, Saos-2 were studied for their production and release of Cu/Zn SOD. A normal human stromal cell line was used as control. Osteosarcoma cells were stimulated with TNF alpha, a cytokine previously shown to have antiproliferative activity. The release of Cu/Zn SOD into the supernatant was higher for the HOS and U-2 OS lines when compared to the other cell lines evaluated both in basal condition and after incubation with TNF alpha. Elevated intracellular levels of Cu/Zn SOD were shown except for the HOS and U-2 OS which possess high concentrations of the enzyme at 24 hours declining during the other incubation periods. These concentrations were increased after TNF alpha treatment. The different behaviour of the four cell lines evaluated might be explained by their degree of differentiation.

Bone Neoplasms↗