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Biomedical subjects

B Grigolo

Publications and source records attributed to B Grigolo.

At least 19 recordsLinked to original sources
PubMed2005

Analysis of mesenchymal stem cells grown on a three-dimensional HYAFF 11-based prototype ligament scaffold.

Ligaments are complex structures that maintain the mechanical stability of the joint. Healing of injured ligaments involves the interactions of different cell types, local cellular environment, and the use of devices. To gain new information on the complex interactions between mesenchymal stem cells (MSCs) and a specific hyaluronan-based prototype scaffold (HYAFF, useful for ligament tissue engineering, short time-course experiments were performed to analyze the proliferation, vitality, and phenotype of MSCs grown on the scaffold. MSC proliferation was analyzed using the MTT test, during the early time points (2, 4, 6, days). Viability was assessed using calcein/acetyloxymethylester immunofluorescence dye and confocal microscopy analysis. Hyaluronic acid receptor (CD44), typical matrix ligament proteins (collagen type I, type III, laminin, fibronectin, actin), and chondrogenic/osteogenic markers (collagen type II and bone sialoprotein) were evaluated by immunohistochemistry. Our data demonstrated that MSC growth and viability were cell density-dependent. MSCs completely wrapped the fibers of the scaffold, expressed CD44, collagen type I, type III, laminin, fibronectin, and actin, and were negative to collagen type II and bone sialoprotein. These data demonstrate that MSCs survive well in the hyaluronan-based prototype ligament scaffold, as assessed after 2 days from seeding, and express CD44, a receptor important for scaffold interaction, and proteins responsible for the functional characteristics of the ligaments.

Animals↗
PubMed2005

The detached osteochondral fragment as a source of cells for autologous chondrocyte implantation (ACI) in the ankle joint.

OBJECTIVE: Autologous chondrocyte implantation (ACI) has been successfully used for the treatment of osteochondral lesions of the talus. One of the main problems of this surgical strategy is related to the harvesting of the cartilage slice from a healthy knee. The aim of this study was to examine the capacity of chondrocytes harvested from a detached osteochondral fragment to proliferate and to serve as a source of viable cells for ACI in the repair of ankle cartilage defects. METHODS: Detached osteochondral fragments harvested from the ankle joint of 20 patients with osteochondral lesions of the talus served as the source of human articular cartilage specimens. All of the osteochondral lesions were chronic and of traumatic origin. In all cases, the fragments were utilized to evaluate the viability and proliferation of the cells, the histological appearance of the cartilage tissue and the expression of specific cartilage markers by real-time polymerase chain reaction (PCR). In the 16 patients scheduled for ACI, the expanded chondrocytes were used for chondrocyte implantation. In the other 4 patients, with lesion size <1.5cm(2), microfractures were created during the initial arthroscopic step. As a control group, 7 patients with comparable osteochondral lesions underwent the same surgery, but received chondrocytes harvested from the ipsilateral knee. RESULTS: According to the American Orthopaedic Foot and Ankle Scoring (AOFAS) system, patients in the experimental group had a preoperative score of 54.2+/-16 points and a postoperative one of 89+/-9.6 points after a minimum follow-up time of 12 months (P<0.0005). The control group of patients had a preoperative score of 54.6+/-11.7 points and a postoperative one of 90.2+/-9.7 points at a minimum follow-up time of 12 months (P<0.0005). The clinical results of the two groups did not differ significantly from each other. Chondrocytes isolated from the detached fragments were highly viable, phenotypically stable, proliferated in culture and redifferentiated when grown within the three-dimensional scaffold used for ACI. The morphological and molecular characteristics of the cartilage samples obtained from the detached osteochondral fragments were similar to those of healthy hyaline articular cartilage. CONCLUSIONS: The good results achieved with this strategy indicate that cells derived from the lesioned area may be useful in the treatment of osteochondral defects of the talus.

Adult↗
PubMed2002

Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes: Maintenance of differentiated phenotype under defined culture conditions.

OBJECTIVE: To establish an immortalized normal human articular chondrocyte line which could be useful for a better understanding of cell molecular mechanisms relevant for the development of new therapeutic approaches in rheumatic diseases. DESIGN: Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 (HPV-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 immunofluorence 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 supplemented with an insulin-containing serum substitute and seeding on a hyaluronan-based non-woven structured biomaterial. The expression of markers characteristic of cartilage was shown in the mRNA by reverse transcriptase-polymerase chain reaction. Immunohistological staining and Western blotting analysis were performed to evaluate type II collagen synthesis. Proteoglycans deposition was detected by Alcian Blue staining. A Field Emission In Lens Scanning Microscopy was used to look at the morphology of the immortalized cells at very high magnification. RESULTS: Normal human articular chondrocytes were efficiently transfected leading to the establishment of an immortalized cell line as confirmed by HPV-16 E7 mRNA and protein detection. These cells were able to re-express type II collagen both at mRNA and protein levels under the two defined cultured conditions we used, still maintaining type I collagen expression. Collagen IX mRNA was present only in early primary culture while collagen type X and aggrecan transcripts were always detected. Alcian Blue staining showed a proteoglycan-rich matrix production. The ultrastructural analysis of the immortalized cells revealed that their morphology strictly resembled that of normal chondrocytes. CONCLUSIONS: 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. Moreover, it appears to be a suitable model for pharmacological and toxicological studies related to rheumatic diseases relevant to humans.

Blotting, Western↗
PubMed2001

Transplantation of chondrocytes seeded on a hyaluronan derivative (hyaff-11) into cartilage defects in rabbits.

Different methods have been used to improve chondrocyte transplantation for the repair of articular cartilage defects. Several groups of biomaterials have been proposed as support for in vitro cell growth and for in vivo implantation. Here. we describe a new approach investigating the healing of rabbit cartilage by means of autologous chondrocytes seeded on a hyaluronan derivative referred to as Hyaff-11. Full thickness defects were created bilaterally in the weight-bearing surface of the medial femoral condyle of both femora of New Zealand male rabbits. The wounds were then repaired using both chondrocytes seeded on the biomaterial and biomaterial alone. Controls were similarly treated but received either no treatment or implants of the delivery substance. Histologic samples from in and around the defect sites were examined 1, 3 and 6 months after surgery and were scored from 0 to 16. Statistically significant differences in the quality of the regenerated tissue were found between the grafts carried out with biomaterial carrying chondrocyte cells compared to the biomaterial alone or controls. This study demonstrates the efficacy of this hyaluronan-based scaffold for autologous chondrocytes transplantation.

Animals↗
PubMed2001

Autologous chondrocyte transplantation in osteochondral lesions of the ankle joint.

The aim of this study was to assess the repair of osteochondral defects of the ankle joint with hyaline cartilage. For this purpose we have been using a technique of autologous chondrocyte transplantation for osteochondral defects of the talus for the last two years. Until the method described in the paper, treatment methods proposed for the repair of cartilaginous defects have not been histologically effective in restoring the hyaline cartilage sheath, and in all cases the neoformation of cartilage was of a fibrocartilaginous nature with varying cellular characteristics. Clinical and histological results obtained using this surgical technique have confirmed its validity. Furthermore, neither subjective nor objective complications have been reported. Less pain and better articular function have also been observed. According to the AOFAS score, an improvement from an average score of 32/100 points pre-op. to 91/100 points at 24 months of follow up was obtained. Laboratory data have confirmed the presence of reconstructed cartilage with chondrocytes and expression of collagen II, characteristic of hyaline cartilage.

Adolescent↗
PubMed2001

Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis.

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.

Adult↗
PubMed2000

Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLA-B35.

We have previously detected autoantibodies against topoisomerase II alpha (anti-topo II alpha) in sera from patients with idiopathic pulmonary fibrosis. To determine whether anti-topo II alpha is also present in systemic sclerosis (SSc) patients with pulmonary involvement, we screened sera from 92 patients and 34 healthy controls. Presence of anti-topo II alpha was investigated with respect to clinical and serological features, including the frequencies of HLA class I and II alleles. Anti-topo II alpha was detected in 20/92 (21.7%) patients. No association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or anti-centromere antibodies. However, anti-topo II alpha was associated with the presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and with a decrease of carbon monoxide diffusing capacity. Anti-topo II alpha was strongly associated with the presence of the class I antigen HLA-B35. No significant association was found with HLA class II antigens. HLA-B35 also turned out to be associated with the presence of PHT. These results indicate that in SSc patients, the presence of anti-topo II alpha is associated with PHT, and that the simultaneous presence of HLA-B35 seems to add to the risk of developing PHT.

Adult↗
PubMed1998

Mapping of topoisomerase II alpha epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis.

Autoantibodies against DNA topoisomerase II alpha have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti-topoisomerase II-positive sera against a series of recombinant proteins which covered the full length of topoisomerase II alpha. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854-1147 and 1370-1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide-sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure-dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti-topoisomerase II autoreactivity evolves following an antigen-driven process.

Adult↗
PubMed1997

Generation of free radicals during anoxia and reoxygenation in perfused osteoblastlike cells.

Sensitivity to ischemia and reperfusion injury is a main problem afflicting tissues exposed to a prolonged period of oxygen deprivation. The generation of oxygen free radicals, in particular, is considered a major cause of postischemic reperfusion injury. However, studies on the mechanisms of production of free radicals are limited by the difficulty to measure in real time their formation and to discriminate between the different oxyradical species. The aim of this study was to determine whether the formation of oxygen free radicals occurs in murine osteoblastlike cells (MC3T3-E1) exposed to anoxia and reoxygenation and to explore its relation to the reoxygenation injury. Cells were cast in agarose and perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Anoxia was obtained by shifting the gas phase of the media to 95% N2-5% CO2. Oxygen free radicals were detected by enhanced chemiluminescence: anion superoxide or hydrogen peroxide was measured by adding lucigenin or luminol plus horseradish peroxidase to the media, respectively. Cell injury was assessed by the rate of lactate dehydrogenase release. During the control period, lucigenin and luminol plus horseradish chemiluminescences were 15 +/- 1 nA per chamber and 20 +/- 2 nA per chamber, respectively. and lactate dehydrogenase release was 10 +/- 1 mU per minute. During anoxia, both chemiluminescences dropped to background levels, although lactate dehydrogenase release increased progressively to 38 +/- 7 mU per minute. During reoxygenation, O2 formation increased sharply to 45 +/- 6 nA and decreased to control levels; H2O2 production increased slowly, reaching 42 +/- 7 nA at the end of the reoxygenation period; lactate dehydrogenase declined progressively to control values. These results show that osteoblastlike cells produce measurable amounts of superoxide and hydrogen peroxide radicals during reoxygenation. Because lactate dehydrogenase release did not appear to relate to chemiluminescence, oxyradical flux may serve as a signal for other events that eventually lead to cell injury.

Animals↗
PubMed1996

Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis.

Rheumatoid arthritis is characterized by a chronic hypertrophic synovitis leading to destruction of connective tissue and functional damage of cartilage and bone structures. Reactive oxygen species play an important role in tissue injury in this disease. To clarify the role of the cellular antioxidant system in the protection against oxygen free radicals, we examined the levels of copper/zinc superoxide dismutase in the sera of patients with rheumatoid arthritis. We used an enzyme-linked immunosorbent assay which determines the concentration of copper/zinc superoxide dismutase independently from its enzymatic activity. We found that patients with rheumatoid arthritis have higher serum copper/zinc superoxide dismutase levels than control subjects. Copper/zinc superoxide dismutase also correlated positively with serum levels of both neopterin and rheumatoid factor, sensitive markers for disease activity in rheumatoid arthritis. These results support the hypothesis that the increased amount of copper/zinc superoxide dismutase is probably inadequate to exert an effective antioxidant protection but can result in a pro-inflammatory, pathogenic effect enhancing tissue damage. Furthermore, copper/zinc superoxide dismutase might be used as a marker of inflammatory activity in rheumatoid arthritis.

Adult↗
PubMed1995

Comparison of different methods for the detection of autoantibodies in autoimmune diseases.

Different immunological techniques were compared for their sensitivity in detecting some important autoantibodies in the sera of patients with rheumatic diseases. Sera of patients with systemic lupus erythematosus were screened for anti-dsDNA, Sm, and RNP autoantibodies by Crithidia luciliae assay, Farr assay, enzyme immunoassay, and immunoblotting. Sera of patients with Sjögren's syndrome were screened for anti-SSA and anti-SSB antibodies by enzyme immunoassay, counter immunoelectrophoresis, and immunoblotting and sera of patients with scleroderma for SCL-70 autoantibodies by enzyme immunoassay counter immunoelectrophoresis, and immunofluorescence on Hep-2 cells. Enzyme immunoassay and counter immunoelectrophoresis gave the most positive results and the best agreement compared with the other techniques. Immunofluorescence gave few positive results for each antibody evaluated. Immunoblotting gave intermediate results for all autoantibodies except anti-SSA, where the prevalence was low. There was no relationship between levels of dsDNA, Sm, and RNP antibodies and disease activity score in systemic lupus erythematosus patients.

Adult↗
PubMed1995

Endothelin-1 in idiopathic pulmonary fibrosis.

AIMS--To evaluate whether endothelin-1 is involved in the pathology of idiopathic pulmonary fibrosis (IPF). METHODS--Plasma endothelin-1 concentrations were evaluated in 37 patients with IPF and 27 normal controls by radioimmunoassay. In addition, expression of endothelin-1 in lung tissue was evaluated in biopsy specimens obtained from four patients with IPF. Three biopsy specimens of normal lung were used as controls. Endothelin-1 immunoreactivity was detected using immunohistochemistry. RESULTS--Elevated endothelin-1 plasma concentrations were found in patients with IPF compared with controls and a positive correlation was found with duration of disease. No significant difference was observed between treated and untreated patients with IPF. Increased endothelin-1 immunoreactivity was found in lungs of three of four patients with IPF. Endothelin-1 positive consisted mainly of small vessel endothelial cells. Some scattered macrophages were also positive. CONCLUSIONS--Elevated plasma concentrations and expression of endothelin-1 in lung tissue are suggestive of increased production of endothelin-1 in at least a proportion of patients with IPF. Consequently, endothelin-1 activity could play a role in the fibrogenic process of the disease.

Adult↗
PubMed1994

Intracellular Cu/Zn superoxide dismutase levels in T and non-T cells from normal aged subjects.

The decreased immune response associated with aging may, in part, reflect intrinsic age-related biochemical alteration in lymphocytes from older subjects. The 'reactive oxygen species hypothesis' of aging postulates that these molecules are involved in the modifications leading to cellular senescence. Superoxide dismutase (SOD), and in particular the Cu/Zn-dependent intracellular form, plays a critical role in the defense against these species, but it is controversial whether this function declines in lymphocytes in old age. We utilized two different methods to evaluate Cu/Zn SOD levels in T and non-T cells (CD3+, CD3-, CD4+, CD8+, CD16+) from young and old individuals: a specific and sensitive enzyme immunoassay performed on extracts of sorted cells, and a flow cytometry double fluorescence technique with monoclonal antibodies against Cu/Zn SOD and the different lymphocyte subsets. The Cu/Zn SOD cell content was assayed both in basal conditions and after peripheral blood lymphocyte stimulation with Concanavalin A, anti-CD3 monoclonal antibody and phorbol myristate acetate. In basal conditions, and considering the various subsets, no differences were found between young and old individuals, although data analysis revealed high and low responders in both groups. Taking all the subjects together, higher levels of this enzyme were found in CD3+ T lymphocytes, in particular in the CD4+ cells. After peripheral blood lymphocyte stimulation, Cu/Zn SOD concentration was higher than levels in unstimulated cells, both in young and old individuals, and particularly using Concanavalin A with respect to anti-CD3 and phorbol myristate acetate. In conclusion, the synthesis of Cu/Zn SOD does not seem to be affected by aging in proliferating cells. The highest levels of Cu/Zn SOD present in CD4+ cells, both from young and old individuals, may prevent the oxidant stress of these elements which play a major role in the inflammation sites.

Adult↗
PubMed1993

Elevated serum superoxide dismutase levels correlate with disease severity and neutrophil degranulation in idiopathic pulmonary fibrosis.

1. Tissue damage in idiopathic pulmonary fibrosis is due in part to oxidant-antioxidant imbalance. 2. We evaluated the serum levels of the antioxidant enzyme Cu/Zn superoxide dismutase (EC 1.15.1.1) in 25 patients with idiopathic pulmonary fibrosis, 34 patients with sarcoidosis and 40 healthy control subjects by an enzyme immunometric assay. 3. We found that patients with idiopathic pulmonary fibrosis have higher serum Cu/Zn superoxide dismutase levels than control subjects and patients with sarcoidosis. In addition, serum Cu/Zn superoxide dismutase levels correlate with disease severity indexes in patients with idiopathic pulmonary fibrosis. 4. The increase in serum Cu/Zn superoxide dismutase level in idiopathic pulmonary fibrosis could depend on degranulation of activated neutrophils or release from damaged cells. To elucidate the contribution of neutrophil degranulation we determined the polymorphonuclear cell elastase level in the same specimens. We found a strong correlation between serum Cu/Zn superoxide dismutase and polymorphonuclear cell elastase activities, and, in patients with idiopathic pulmonary fibrosis, we observed higher levels of polymorphonuclear cell elastase than in control subjects and patients with sarcoidosis, which correlated positively with disease severity indexes. 5. Cu/Zn superoxide dismutase can catalyse the dismutation of O2 into H2O2 and generate OH.. These oxygen radicals are probably the major factors responsible for tissue damage (in particular, alveolar and endothelial cells) and fibrosis in experimental lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Comparative evaluation of chenodeoxycholic and ursodeoxycholic acids in obese patients. Effects on biliary lipid metabolism during weight maintenance and weight reduction.

Obesity is a condition associated with an increased frequency of gallstone disease. This study attempted to evaluate the comparative effects of two gallstone-dissolving agents, chenodeoxycholic acid and ursodeoxycholic acid, on bile acid metabolism and biliary lipid secretion in obese subjects in order to identify the bile acid of choice in preventing and treating gallstone disease in obesity. Twenty obese subjects (greater than 120% ideal body wt) were randomly treated with ursodeoxycholic acid (10 mg.kg-1.day-1.1 mo-1) and then with chenodeoxycholic acid (15 mg.kg-1.day-1.1 mo-1) or with chenodeoxycholic acid first and then with ursodeoxycholic acid. Patients 1-10 were studied while eating an unrestricted weight-maintenance diet, whereas patients 11-20 were eating a 1080-kcal/d hypocaloric diet. Biliary lipid composition, cholesterol saturation index, and biliary bile acid pattern were evaluated in all subjects before and after each treatment period; in subjects 6-10 and 16-20, biliary lipid secretion rates and bile acid pool size were also evaluated. Both ursodeoxycholic acid and chenodeoxycholic acid decreased cholesterol outputs and cholesterol saturation index. However, during the weight-maintenance period the decrease induced by chenodeoxycholic acid was not significant. Biliary cholesterol outputs and cholesterol saturation index were always lower during ursodeoxycholic acid administration than during chenodeoxycholic acid therapy. Ursodeoxycholic acid levels during ursodeoxycholic acid administration and chenodeoxycholic acid levels during chenodeoxycholic acid administration increased in bile to 50% and 77%, respectively, of total bile acid levels. Bile acid pool size remained unchanged during chenodeoxycholic acid administration and was significantly reduced by ursodeoxycholic acid administration during the weight-reduction period. In conclusion, ursodeoxycholic acid in obese subjects seems more effective than chenodeoxycholic acid, at least during weight maintenance, in reducing cholesterol saturation of bile. This effect is related to a significant decrease of biliary cholesterol output.

Adolescent↗
PubMed1991

Microdialysis and luminescent probe: analytical and clinical aspects.

Immobilized enzymes are widely used in the clinical laboratory to assay several analytes and enzymes. The use of immobilized enzymes makes these reagents recoverable, disposable and in most cases increases their stability and catalytic activity. In conjunction with bioluminescent enzymes (firefly and bacterial luciferases) and chemiluminescent catalyst (peroxidase) we set up high-sensitive flow sensors based on the use of nylon tube coil or epoxy methacrylate column as solid support. For in-vivo determination a suitable microdialysis probe inserted directly into brain or blood allows continuous measurement of extracellular lactate levels by means of a bioluminescent flow detector system. This procedure performs more measurements in the same time interval than other systems (HPLC), e.g. to give a detailed description of the effects of ischemia, or other pathological events, on lactate concentration in the brain.

Animals↗
PubMed1991

Pharmacokinetics of ursodeoxycholic acid in rat.

The pharmacokinetic behaviour and metabolism of ursodeoxycholic acid (UDCA) have been studied in the rat. After oral administration of both 3H-labelled (4 muCi/kg body wt) and unlabelled (20 mg) UDCA, UDCA appeared in serum almost entirely in conjugated form (taurine conjugated); UDCA was present in bile mostly as taurine conjugated; the more relevant metabolite is 3 alpha,6 alpha, 7 beta-trihydroxycholanoic acid which represents 10% of the total bile acid pool. UDCA increased bile flow and selectively decreased biliary cholesterol secretion, while phospholipid secretion was unaffected. Faecal UDCA excretion was 15-20% while the urinary extraction was 1.5% during 24 h. The data show that UDCA, when administered in high dose, is promptly secreted into bile almost entirely metabolized to tauroursodeoxycholic acid, where it (1) desaturates the cholesterol in bile, (2) exerts choleretic properties.

Administration, Oral↗