Francesca Carubbi - Academia.edu (original) (raw)
Papers by Francesca Carubbi
Journal of Biological Chemistry
Metabolism of 3 beta-hydroxy-5-cholenoic acid to chenodeoxycholic acid has been found to occur in... more Metabolism of 3 beta-hydroxy-5-cholenoic acid to chenodeoxycholic acid has been found to occur in rabbits and humans, species that cannot 7 alpha-hydroxylate lithocholic acid. This novel pathway for chenodeoxycholic acid synthesis from 3 beta-hydroxy-5-cholenoic acid led to a reinvestigation of the pathway for chenodeoxycholic acid from 3 beta-hydroxy-5-cholenoic acid in the hamster. Simultaneous infusion of equimolar [1,2-3H]lithocholic acid and 3 beta-hydroxy-5-[14C]cholenoic acid indicated that the 14C enrichment of chenodeoxycholic acid was much greater than that of lithocholic acid. Thus, in all these species, a novel 7 alpha-hydroxylation pathway exists that prevents the deleterious biologic effects of 3 beta-hydroxy-5-cholenoic acid.
Advances in therapy, Jan 3, 2015
JIMD Reports, 2013
Glycogen storage disease type I (GSD I) is a chronic metabolic disease that requires a lifelong s... more Glycogen storage disease type I (GSD I) is a chronic metabolic disease that requires a lifelong strict dietetic treatment to avoid hypoglycemia and can lead to severe complications during adult age. Impaired quality of life (QoL) has been reported in affected children, but this aspect has not been previously investigated in adults. To assess QoL in adult patients with GSD I. Italian patients with GSD type Ia and Ib, who were 16 years or older, were asked to complete the SF-36 questionnaire, assessing their QoL. Data on demographic characteristics and clinical history were collected from clinical records and interviews. Thirty-eight patients (22 females, 16 males; 27 with GSD Ia, 11 with GSD Ib, median age 26.5 years) completed the SF-36 questionnaire. Overall, when compared to normal values, patients with GSD I had lower median scores in general health perception and social functioning, but better median scores for bodily pain and mental health. Patients with GSD Ib had a lower Z-score than GSD Ia patients for emotional health problems. Male patients showed better Z-scores in physical functioning, general health perception, and social functioning when compared to females. Emotional health problems Z-score was lower in nephropathic patients. QoL can be impaired in adult patients with GSD I. The results of this study show that patients with GSD type Ib, women, and those with renal complications are more likely to experience a poorer QoL.
Advances in Therapy, 2014
Gaucher disease is a rare autosomal recessive disorder of glycosphingolipid metabolism resulting ... more Gaucher disease is a rare autosomal recessive disorder of glycosphingolipid metabolism resulting from deficient activity of the lysosomal enzyme beta-glucocerebrosidase that causes accumulation of glucosylceramide in tissue macrophage with damage to hematological, visceral, and skeletal organ systems. Severity and progression may vary independently among these domains, necessitating individualized therapy. Skeletal involvement is highly prevalent and often associated with intense pain, impaired mobility, and reduced quality of life. Enzyme replacement therapy improves parameters in all affected domains, but skeletal involvement requires longer treatment and higher dosages to obtain significant results. Despite numerous papers on bone complications in patients with Gaucher disease, there are no specific indications on how to assess properly bone involvement in such condition, the frequency of assessment, the use of markers for osteoblast and osteoclast activity, or the administration of bisphosphonates or other symptomatic drugs in adult and pediatric patients. Starting from a re-evaluation of cases with bone involvement, we have identified some common errors in the diagnostic approach and management. The aim of this paper was to propose a methodological and critical approach to the diagnosis, follow-up and treatment of bone disease in patients with Gaucher disease type 1.
Journal of Inherited Metabolic Disease, 2013
Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably,... more Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or not GSD I is associated with impaired reproductive function is still unclear. Data about female patients with GSD Ia and Ib, who were 16 years or older, were obtained from clinical records and interviews. A total of 32 women with GSD I (25 GSD Ia, 7 GSD Ib), median age 26 years (range 16-55), were included. 9/32 patients had delayed menarche, 17/32 had irregular cycles, 8/22 had documented polycystic ovaries. Five successful spontaneous pregnancies in four patients with GSD Ia and two in a woman with GSD Ib were reported. The latter had development and enlargement of hepatic adenomas during pregnancies. Despite the high prevalence of irregular menstruation cycles and polycystic ovaries, fertility seems not to be impaired in women with GSD I. During pregnancy monitoring for adenoma development is mandatory.
Journal of Hepatology, 1989
Journal of Hepatology, 1991
Journal of Hepatology, 2000
Journal of Hepatology, 1997
Background/Aims: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It i... more Background/Aims: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone. Methods: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6/3-naltrexol, were assayed by reversed-phase HPLC analysis. Results: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6/?-naltrexol (area under the curve: naltrexone, 200&97 ng/mlX 24 h; 6/3-naltrexol, 24672730 ngl N ALTREXONE (N-cyclopropyl-methyl-noroxymorphone) is a potent competitive antagonist of opiates at the receptor level (1,2). When administered orally to human subjects, naltrexone can prevent the pharmacological effects of active doses of heroin for . ml x 24 h, ~~0.01). In severe cirrhosis serum levels of 6/3-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 24 h after drug intake were higher than those of 6P-naltrexol(6b-naltrexobnaltrexone ratio at 2 h: controls, 10.91&4.80; cirrhosis, 0.39+0.18, ~~0.01). The area under the curve for naltrexone (16102629 ng/mlX24 h) was significantly greater than in controls, whereas that for 6B-naltrexol (20212955 ng/mlX24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups. Conclusions: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6/l-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6B_naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
Journal of Hepatology, 1990
Hepatology, 1993
This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxyl... more This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.
Hepatology, 1991
The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid syn... more The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7 alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7 alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7 alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7 alpha-hydroxylation significantly. Simvastatin markedly reduced plasma total and low-density lipoprotein-cholesterol but exerted no change on 7 alpha-hydroxylation rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Alimentary Pharmacology and Therapeutics, 2000
The Italian Journal of Gastroenterology, May 1, 1996
To evaluate the effect of bile acid structure on total protein secretion and composition, 4 diffe... more To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associated with the administration of bile acids that have different physico-chemical structures, may be relevant to the process of cholesterol crystal nucleation and the pathogenesis of gallstone formation.
La radiologia medica
Our study was aimed at describing the diagnostic imaging patterns of carcinoid liver metastases. ... more Our study was aimed at describing the diagnostic imaging patterns of carcinoid liver metastases. Six patients with liver metastases secondary to carcinoid tumor were examined. The metastases were histologically proved in each patient. All patients were examined with ultrasonography (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Digital Subtraction Angiography (DSA). All patients were treated with transcatheter embolization of liver metastases. Diagnostic imaging methods showed ten to many dozen metastases in each patient. Tumor size ranged 0.5 to 14 cm. US showed hypoechoic, hyperechoic and isoechoic carcinoid liver metastases with a hypoechoic halo. Large lesions had anechoic central areas due to colliquative necrosis. Hypoechoic patterns were the most frequent ones. Precontrast CT showed hypodense metastases; very small lesions were isodense relative to surrounding liver. CT during contrast agent injection showed that the metastases were hyperdense in the art...
The Italian journal of gastroenterology, 1996
To evaluate the effect of bile acid structure on total protein secretion and composition, 4 diffe... more To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associa...
Journal des maladies vasculaires, 1995
We report a case of rupture of abdominal aortic aneurysm due to salmonella typhy infection. The p... more We report a case of rupture of abdominal aortic aneurysm due to salmonella typhy infection. The patient had a first operation of prothesis graft which led to infective dehiscence. After a further operation of aortic over renal banding, the patient was in good health. The authors discuss the possibility to make an aortic banding combined with an extra-anatomic revascularization directly, instead of carrying out an in situ reconstruction.
Atherosclerosis Supplements, 2005
Fxr (-I-) mice results from impaired processing and clearance of TG-rich lipoproteins. These data... more Fxr (-I-) mice results from impaired processing and clearance of TG-rich lipoproteins. These data indicate a novel role for bile salts in modulation of postprandial lipoprotein metabolism.
Internal and Emergency Medicine, 2012
Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal en... more Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal enzyme alpha-galactosidase A, causing insufficient breakdown of glycolipids, which are stored in the eyes, kidneys, autonomic nervous system, skin, vessels and cardiovascular system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Females may be severely affected as males and both may die prematurely due to stroke, heart disease and renal failure. Enzyme replacement therapy can stabilize or reduce the progression of the disease. There is a need to improve the knowledge of Fabry disease, as an early therapy may prevent complications of the disease. This brief overview aims to raise awareness of the signs and symptoms of Fabry disease and to summarize the effects of treatments.
Atherosclerosis Supplements, 2006
Journal of Biological Chemistry
Metabolism of 3 beta-hydroxy-5-cholenoic acid to chenodeoxycholic acid has been found to occur in... more Metabolism of 3 beta-hydroxy-5-cholenoic acid to chenodeoxycholic acid has been found to occur in rabbits and humans, species that cannot 7 alpha-hydroxylate lithocholic acid. This novel pathway for chenodeoxycholic acid synthesis from 3 beta-hydroxy-5-cholenoic acid led to a reinvestigation of the pathway for chenodeoxycholic acid from 3 beta-hydroxy-5-cholenoic acid in the hamster. Simultaneous infusion of equimolar [1,2-3H]lithocholic acid and 3 beta-hydroxy-5-[14C]cholenoic acid indicated that the 14C enrichment of chenodeoxycholic acid was much greater than that of lithocholic acid. Thus, in all these species, a novel 7 alpha-hydroxylation pathway exists that prevents the deleterious biologic effects of 3 beta-hydroxy-5-cholenoic acid.
Advances in therapy, Jan 3, 2015
JIMD Reports, 2013
Glycogen storage disease type I (GSD I) is a chronic metabolic disease that requires a lifelong s... more Glycogen storage disease type I (GSD I) is a chronic metabolic disease that requires a lifelong strict dietetic treatment to avoid hypoglycemia and can lead to severe complications during adult age. Impaired quality of life (QoL) has been reported in affected children, but this aspect has not been previously investigated in adults. To assess QoL in adult patients with GSD I. Italian patients with GSD type Ia and Ib, who were 16 years or older, were asked to complete the SF-36 questionnaire, assessing their QoL. Data on demographic characteristics and clinical history were collected from clinical records and interviews. Thirty-eight patients (22 females, 16 males; 27 with GSD Ia, 11 with GSD Ib, median age 26.5 years) completed the SF-36 questionnaire. Overall, when compared to normal values, patients with GSD I had lower median scores in general health perception and social functioning, but better median scores for bodily pain and mental health. Patients with GSD Ib had a lower Z-score than GSD Ia patients for emotional health problems. Male patients showed better Z-scores in physical functioning, general health perception, and social functioning when compared to females. Emotional health problems Z-score was lower in nephropathic patients. QoL can be impaired in adult patients with GSD I. The results of this study show that patients with GSD type Ib, women, and those with renal complications are more likely to experience a poorer QoL.
Advances in Therapy, 2014
Gaucher disease is a rare autosomal recessive disorder of glycosphingolipid metabolism resulting ... more Gaucher disease is a rare autosomal recessive disorder of glycosphingolipid metabolism resulting from deficient activity of the lysosomal enzyme beta-glucocerebrosidase that causes accumulation of glucosylceramide in tissue macrophage with damage to hematological, visceral, and skeletal organ systems. Severity and progression may vary independently among these domains, necessitating individualized therapy. Skeletal involvement is highly prevalent and often associated with intense pain, impaired mobility, and reduced quality of life. Enzyme replacement therapy improves parameters in all affected domains, but skeletal involvement requires longer treatment and higher dosages to obtain significant results. Despite numerous papers on bone complications in patients with Gaucher disease, there are no specific indications on how to assess properly bone involvement in such condition, the frequency of assessment, the use of markers for osteoblast and osteoclast activity, or the administration of bisphosphonates or other symptomatic drugs in adult and pediatric patients. Starting from a re-evaluation of cases with bone involvement, we have identified some common errors in the diagnostic approach and management. The aim of this paper was to propose a methodological and critical approach to the diagnosis, follow-up and treatment of bone disease in patients with Gaucher disease type 1.
Journal of Inherited Metabolic Disease, 2013
Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably,... more Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or not GSD I is associated with impaired reproductive function is still unclear. Data about female patients with GSD Ia and Ib, who were 16 years or older, were obtained from clinical records and interviews. A total of 32 women with GSD I (25 GSD Ia, 7 GSD Ib), median age 26 years (range 16-55), were included. 9/32 patients had delayed menarche, 17/32 had irregular cycles, 8/22 had documented polycystic ovaries. Five successful spontaneous pregnancies in four patients with GSD Ia and two in a woman with GSD Ib were reported. The latter had development and enlargement of hepatic adenomas during pregnancies. Despite the high prevalence of irregular menstruation cycles and polycystic ovaries, fertility seems not to be impaired in women with GSD I. During pregnancy monitoring for adenoma development is mandatory.
Journal of Hepatology, 1989
Journal of Hepatology, 1991
Journal of Hepatology, 2000
Journal of Hepatology, 1997
Background/Aims: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It i... more Background/Aims: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone. Methods: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6/3-naltrexol, were assayed by reversed-phase HPLC analysis. Results: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6/?-naltrexol (area under the curve: naltrexone, 200&97 ng/mlX 24 h; 6/3-naltrexol, 24672730 ngl N ALTREXONE (N-cyclopropyl-methyl-noroxymorphone) is a potent competitive antagonist of opiates at the receptor level (1,2). When administered orally to human subjects, naltrexone can prevent the pharmacological effects of active doses of heroin for . ml x 24 h, ~~0.01). In severe cirrhosis serum levels of 6/3-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 24 h after drug intake were higher than those of 6P-naltrexol(6b-naltrexobnaltrexone ratio at 2 h: controls, 10.91&4.80; cirrhosis, 0.39+0.18, ~~0.01). The area under the curve for naltrexone (16102629 ng/mlX24 h) was significantly greater than in controls, whereas that for 6B-naltrexol (20212955 ng/mlX24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups. Conclusions: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6/l-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6B_naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
Journal of Hepatology, 1990
Hepatology, 1993
This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxyl... more This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.
Hepatology, 1991
The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid syn... more The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7 alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7 alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7 alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7 alpha-hydroxylation significantly. Simvastatin markedly reduced plasma total and low-density lipoprotein-cholesterol but exerted no change on 7 alpha-hydroxylation rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Alimentary Pharmacology and Therapeutics, 2000
The Italian Journal of Gastroenterology, May 1, 1996
To evaluate the effect of bile acid structure on total protein secretion and composition, 4 diffe... more To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associated with the administration of bile acids that have different physico-chemical structures, may be relevant to the process of cholesterol crystal nucleation and the pathogenesis of gallstone formation.
La radiologia medica
Our study was aimed at describing the diagnostic imaging patterns of carcinoid liver metastases. ... more Our study was aimed at describing the diagnostic imaging patterns of carcinoid liver metastases. Six patients with liver metastases secondary to carcinoid tumor were examined. The metastases were histologically proved in each patient. All patients were examined with ultrasonography (US), Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Digital Subtraction Angiography (DSA). All patients were treated with transcatheter embolization of liver metastases. Diagnostic imaging methods showed ten to many dozen metastases in each patient. Tumor size ranged 0.5 to 14 cm. US showed hypoechoic, hyperechoic and isoechoic carcinoid liver metastases with a hypoechoic halo. Large lesions had anechoic central areas due to colliquative necrosis. Hypoechoic patterns were the most frequent ones. Precontrast CT showed hypodense metastases; very small lesions were isodense relative to surrounding liver. CT during contrast agent injection showed that the metastases were hyperdense in the art...
The Italian journal of gastroenterology, 1996
To evaluate the effect of bile acid structure on total protein secretion and composition, 4 diffe... more To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associa...
Journal des maladies vasculaires, 1995
We report a case of rupture of abdominal aortic aneurysm due to salmonella typhy infection. The p... more We report a case of rupture of abdominal aortic aneurysm due to salmonella typhy infection. The patient had a first operation of prothesis graft which led to infective dehiscence. After a further operation of aortic over renal banding, the patient was in good health. The authors discuss the possibility to make an aortic banding combined with an extra-anatomic revascularization directly, instead of carrying out an in situ reconstruction.
Atherosclerosis Supplements, 2005
Fxr (-I-) mice results from impaired processing and clearance of TG-rich lipoproteins. These data... more Fxr (-I-) mice results from impaired processing and clearance of TG-rich lipoproteins. These data indicate a novel role for bile salts in modulation of postprandial lipoprotein metabolism.
Internal and Emergency Medicine, 2012
Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal en... more Fabry disease is an X-linked inherited lysosomal disorder due to dysfunctions of the lysosomal enzyme alpha-galactosidase A, causing insufficient breakdown of glycolipids, which are stored in the eyes, kidneys, autonomic nervous system, skin, vessels and cardiovascular system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms. Clinical onset usually occurs in childhood, but many severe patients are diagnosed in adulthood. Females may be severely affected as males and both may die prematurely due to stroke, heart disease and renal failure. Enzyme replacement therapy can stabilize or reduce the progression of the disease. There is a need to improve the knowledge of Fabry disease, as an early therapy may prevent complications of the disease. This brief overview aims to raise awareness of the signs and symptoms of Fabry disease and to summarize the effects of treatments.
Atherosclerosis Supplements, 2006