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pregnane X receptor and constitutive androstane receptor modulate differently CYp3A-mediated metabolism in earlyand late-stage cholestasis

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World Journal of Gastroenterology 2017年第42期23卷 7519-7530页

作者： Daniela Gabbia Arianna Dalla Pozza Laura Albertoni Roberta Lazzari Giorgia Zigiotto Maria Carrara Vincenzo Baldo Tatjana Baldovin annarosa floreani Sara De Martin Department of Pharmaceutical and Pharmacological Sciences University of Padova Department of Medicine General Pathology and Cytopathology UnitUniversity of Padova Department of Cardiac Thoracicand Vascular SciencesHygiene and Public Health UnitUniversity of Padova Department of Surgery Oncology and GastroenterologyUniversity of Padova

AIM To ascertain whether cholestasis affects the expression of two CYP3 A isoforms(CYP3 A1 and CYP3 A2) and of pregnane X receptor(PXR) and constitutive androstane receptor(CAR).METHODS Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3 A1 and CYP3 A2 were assessed by means of q RT-PCR and Western blot, respectively. Alterations in CYP3 A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3 A *** The m RNA and protein expression of CYP3 A1 increased significantly in mild cholestasis(P < 0.01). At variance, m RNA and protein expression of CYP3 A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3 A1 and CYP3 A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently, probably as consequence of the different activation of PXR and *** Early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3 Amediated liver detoxification.

关键词： Cholestasis CYP3A Drug metabolism Pregnane X receptor Constitutive androstane receptor

Is osteoporosis a peculiar association with primary biliary cirrhosis?

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World Journal of Gastroenterology 2005年第34期11卷 5347-5350页

作者： annarosa floreani Andrea Mega Valentina Camozzi Vincenzo Baldo Mario Plebani Patrizia Burra Giovanni Luisetto Department of Surgical and Gastroenterological Sciences University of Padova Italy Department of Medical and Surgical Sciences University of Padova Italy Department of Public Health University of Padova Italy Department of Clinical Chemistry University of Padova Italy

AIM：（1） To compare the prevalence of osteoporosis （t-score ≤-2.5 SD） between stage IV PBC patients, and two groups of age- and sex-matched controls： one with hepatitis C virus （HCV）-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population, （2） to identify the main risk factors for the development of bone loss. METHODS： Thirty-five stage IV PBC patients （mean age 52.5±10 years）, 49 females with HCV-related cirrhosis （mean age 52.9±5.8 years） and 33 healthy females （mean age 51.8±2.22 years） were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin （Ca corr.）, 25-hydroxy vitamin D （25-OH vit D）, parathyroid hormone, osteocaldn. Bone mineral density （BMD） was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS： Osteoporosis was present in 5/35 PBC patients （14.2%） and in 7/49 HCV-related drrhotic patients （14.3%）, without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI〈23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION： PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.

关键词： Osteoporosis Primary biliary cirrhosis HCV infection

Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: In vivo and in vitro studies

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World Journal of Gastroenterology 2007年第27期13卷 3677-3683页

作者： A Federico A Filippelli M Falciani C Tuccillo A Tiso A floreani R Naccarato F Rossi C Del Vecchio Blanco C Loguercio Inter-University Research Centre on Foods Nutrition and Gastrointestinal Tract Gastroenterology School 2nd University of Naples Italy Department of Experimental Medicine 2nd University of Naples Italy Department of Surgical and Gastroenterological Sciences University of Padua Italy

AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO), nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA), 4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO). RESULTS: In vivo , S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts 150 000/μL. In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen. CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.

关键词： Liver disease Function of platelets Hepatitis C Oxidative stress Anti-aggregant

把互联网送上太空轨道探索IP网络技术在空间科学中的应用潜力

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中国新通信 2006年第12期8卷 81-83页

作者： Daniel floreani Lloyd Wood 思科全球防卫空间和安全部空间项目组思科全球防卫空间和安全部

2004年10月4日，伯特·鲁坦设计的“太空飞船一号”飞行器以超过100公里的飞行高度，成为世界上第一个到达太空边缘的私人开发的载人飞船，这一纪录被载入史册。

关键词：太空轨道 IP网络技术空间科学互联网飞行高度太空飞船载人飞船飞行器

酒精是意大利北部丙型肝炎患者发生肝细胞脂肪变性和肝纤维化的重要协同因素

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世界核心医学期刊文摘（胃肠病学分册） 2005年第2期1卷 59-59页

作者： Fabris P. floreani A. Carlotto A. 黎一兵

Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosi s in patientswith CHC. A consecutive series of 349 patients were evaluated for s teatosis. At liver biopsy, patients were tested for virological, and laboratory analysis and questioned for alcohol consumption. Logistic regression analysis de monstrated that steatosis was independently associated with genotype 3a (odds ra tio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (O R 2.7). In multivariate analysis the presence of fibrosis was associated with pa st alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P =0.05), which disappeared excluding patients without past or current alcohol int ake. A direct correlation emerged between grade of steatosis and both ‘grading ’and ‘staging’only in patients with genotypes other than 3a. Genotype 3a is t hemain risk factor for steatosis in patientswith CHC. The grade of steatosis cor related with both grading and staging only in patients with genotypes other than 3a and this relationship is strictly linked to alcohol consumption.

关键词：丙型肝炎患者肝细胞脂肪变性肝纤维化意大利北部慢性丙型肝炎肝脂肪变性宿主因素病毒学检查饮酒量实验室分析