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A Pietrabissa

Publications and source records attributed to A Pietrabissa.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic donor nephrectomy: short learning curve.

INTRODUCTION: The learning curve of laparoscopic donor nephrectomy (LDN) may represent a great technical challenge at centers with low volume of living donors. The number of LDNs required to overcome the learning curve is still unclear. Here we report the modality of approach to LDN at a low-volume living donor transplant center. MATERIALS AND METHODS: We reviewed the records of two groups of donors operated by two different surgeons between January 2002 and October 2005. We compared donor hospital stay, operative time, presence of multiple renal arteries, blood loss, operative details, and complications. RESULTS: The first six operations (group A) were performed by a well-trained laparoscopic surgeon (A.P.) with a consolidated experience in the LDN procedure, attended by our training surgeon (R.D.V.) who conducted the other six cases (group B). No conversion to an open procedure was necessary and there were no major minor complications. Mean operative time was 267.5 (+/-55.9) minutes in group A and 300 (+/-43.4) minutes in group B (P = .28). Mean warm ischemia time was 125 (+/-61.6) seconds in group A and 189.2 (+/-18.6) seconds in group B (P = .035). Mean hospital stay was 5.3 days in group A and 5.6 days in group B. CONCLUSIONS: LDN can be performed safely and efficiently in transplant centers with initial experience. A collaborative approach to this difficult procedure with a surgeon skilled in donor nephrectomy minimizes the risk to the donor and reduces the learning curve.

Female↗
PubMed2005

Pancreas transplants from donors aged 45 years or older.

AIMS: Since donor age of 45 years or more is considered a relative contraindication for pancreas transplantation (PTx), we herein report our experience with these donors. METHODS: Pancreases from donors aged 45 years or older were used in 16 of 147 PTx procedures (11%). The final decision to accept a graft for PTx was based mainly on the quality of visceral perfusion and the gross appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging in age from 45 to 55 years (average, 48.9 years) who were donors, due to cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac arrest (12.5%). Pancreases were transplanted either simultaneously with a cadaveric kidney (n = 6) or as solitary grafts (n = 10). RESULTS: After a mean period of cold preservation of 616 minutes (range, 475 to 844 min), delayed endocrine function occurred in 1 recipient (6%), who subsequently achieved insulin independence. Two recipients died suddenly, with functioning grafts. Two further grafts were lost due to portal vein thrombosis (6%) or late arterial thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively. CONCLUSIONS: Meticulous donor selection and short preservation times allow the safe use of pancreases procured from donors aged 45 years or older, thus expanding the donor pool for PTx procedures.

Age Factors↗
PubMed2005

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation.

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.

Adenosine↗
PubMed2004

Thrombosis in the portal venous system after elective laparoscopic splenectomy.

BACKGROUND: The occurrence of thrombosis in the portal system is an underappreciated complication of splenectomy. Presenting symptoms are usually mild and nonspecific. The short hospital stay associated with the laparoscopic approach could delay the early diagnosis of this condition unless routine imaging controls are planned after discharge. METHODS: The records of 40 patients who underwent laparoscopic splenectomy at our institution were reviewed for clinical signs of thrombosis in the portal system and associated factors. All patients were also enrolled in a color Doppler ultrasound surveillance program. RESULTS: Nine patients (22.5%) developed thrombosis of the splenic vein, progressing to the portal vein in five cases (12.5%). Six patients (15%) were symptomatic. Thrombosis occurred even as late as 4 months after splenectomy. Spleen weight was the only significant factor predictive of postoperative thrombosis. The combination of splenomegaly and an elevated preoperative platelet count was associated with a 75% incidence of this complication. CONCLUSION: The high risk of thrombosis after the laparoscopic resection of large spleens should prompt strict postoperative imaging surveillance, combined with a more aggressive anticoagulation prophylaxis.

Adult↗
PubMed2004

Regional procurement team for abdominal organs.

BACKGROUND: The graft shortages make multiorgan procurements mandatory. We describe the results of a regional procurement team policy that has been employed over a 5-year period. METHODS: Three hundred forty-three multiorgan procurements were performed by a regional team using an en bloc harvesting method. RESULTS: Among 1374 grafts procured, none was discarded because of iatrogenic injuries. In three instances the liver, the pancreas, and the small bowel were procured simultaneously and transplanted to different recipients. In 42 instances the liver was not allocated to our center. Forty liver teams (95%) from 11 institutions agreed to allow the regional procurement team to run the donor procedure. CONCLUSIONS: Our experience confirms that a regional team can successfully manage most multiorgan procurements including complex donor procedures, such as simultaneous procurement of liver, pancreas, and intestine from the same donor for transplantation to different recipients.

Abdomen↗
PubMed2004

Laparoscopic living donor nephrectomy in Italy: a national profile.

BACKGROUND: There are no data concerning the national experience with laparoscopic live donor nephrectomy (LLDN) in Italy. A survey was therefore conducted in May 2003 to establish current practice patterns and to describe the outcome of this procedure. METHODS: A self-administered questionnaire was mailed to the 37 Italian kidney transplant centers. Items covered each center's attitude toward LLDN, number of cases performed, and the outcome of donors and recipients. RESULTS: The return rate was 100%. The surveyed centers performed 4818 kidney transplants between January 2000 and May 2003, including 401 (8.3%) from living donors of whom 113 (28.2%) used grafts retrieved by laparoscopy. Despite an absolute increase in the number of living donors, the occurrence of a similar trend in cadaveric donation did not significantly change the overall living donor rate. Sixty-eight percent of LLDNs were done at only two centers. There was no mortality or graft loss and only a minor morbidity related to LLDN. Italian transplant surgeons showed a positive attitude toward LLDN; only a few of those not performing it had no plans to begin an LLDN program. CONCLUSIONS: Three years after the first national case, LLDN had not yet change the living donor rate, although an increasing number of donor nephrectomies were now performed by laparoscopy. Overall the results with the new technique are encouraging, although the pattern of diffusion of LLDN between different areas is heterogeneous and will demand continuous efforts on training programs in laparoscopic techniques for transplant surgeons.

Cadaver↗
PubMed2004

Perioperative anesthetic management for laparoscopic kidney donation.

OBJECTIVES: To report a single-center experience about the perioperative and anesthetic management of laparoscopic living kidney donation. PATIENTS AND INTERVENTIONS: Subjects undergoing laparoscopic (n = 39) (performed between April 2000 and August 2002) and traditional "open" kidney donation (n = 27) received a standard balanced anesthetic technique. However to counterbalance the reported abdominal insufflation-related kidney dysfunction, laparoscopic donors were administered an extra intravascular volume loading with colloid and crystalloid starting on the night before surgery. RESULTS: Laparoscopic donors underwent longer procedures with lower estimated blood losses (P =.0001), were intraoperatively administered higher amounts of intravenous fluids (P <.01), showed less postoperative analgesic requirement (P <.0001), shorter intensive care unit and overall hospitalization (P <.001), quicker resumption of solid oral intake (P <.01), and full return to work (P <.001) with no difference in the postoperative complication rate. Diuresis resumed intraoperatively in all recipients and early graft function did not differ between the two groups, although the serum creatinine declined earlier, but not significantly, in those receiving kidneys procured by the traditional method. No difference was seen in graft rejection rates. DISCUSSION AND CONCLUSIONS: Laparoscopic kidney donation does not require a particularly complex or expensive anesthetic management or approach; as it has been suggested that intra-abdominal hypertension coming from CO(2) insufflation inside the donor's peritoneal cavity may threaten graft function, during laparoscopic kidney donation it is advisable to adopt a strategy for "renal protection." Thus, when a laparoscopic kidney donation is performed at our center, a multidisciplinary approach is commonly adopted based on three key points: perioperative positive volemic balance in donors; intraoperative urinary output of at least 100 mL/h; inflation with an abdominal pressure not exceeding 12 mm Hg.

Analgesics↗
PubMed2004

Simultaneous cadaver pancreas-living donor kidney transplantation.

BACKGROUND: The expansion of the donor pool achieved with living kidney donation (LKD) is particularly beneficial for diabetic patients, who have a worse prognosis during dialysis when compared to other kidney recipients. Simultaneous cadaver pancreas-living kidney transplantation (SPLKTx) merges the advantages of LKD with those of cadaver donation, and may be an attractive alternative to simultaneous pancreas kidney transplantation (SPKTx). METHODS: The outcomes of 18 SPLKTx were compared with those of 33 SPKTx. RESULTS: LKD expanded the donor pool from 33 to 51 (P =.004). Median wait time was shorter for SPLKTx (14 days) than for SPKTx (95 days) (P =.006). The risk for surgical complications was not increased by SPLKTx, as witnessed by relaparotomy rates (SPLKTx: 2/18, 11.1%; SPKTx: 2/33, 6.1%; P >.05). Hospital stay averaged 26.1 +/- 11.2 days for SPLKTx and 27.1 +/- 16.3 for SPKTx (P >.05) with equivalent 30-day readmission rates (SPLKTx: 5.5%; SPKTx: 6.1%); (P >.05). One acute kidney rejection occurred in SPLKTx (5.5%) as compared with four in SPKTx (12.1%); (P >.05). Equivalent rates for the pancreas were 5.5% (1/18) for SPLKTx and 3.0% (1/33) for SPKTx (P >.05). Two-year recipient survival rates were 100% for SPLKTx as compared with 96.9% for SPKTx. Equivalent figures for kidney and pancreas were 80.0% and 84.0% for SPLKTx and 96.9% and 96.9% for SPKTx. CONCLUSIONS: SPLKTx is a valuable alternative to SPKTx. Further development of SPLKTX relies on increased rates of living kidney donation.

Adult↗
PubMed2004

Pancreas preservation with University of Wisconsin and Celsior solutions.

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.

Adenosine↗
PubMed2004

Simultaneous pancreas-kidney transplantation is improved by living kidney donation program.

BACKGROUND: Shortage of suitable donors and current graft allocation priorities reduce the number of cadaveric kidneys available to diabetic recipients. The concurrent excess of solitary cadaveric pancreata and the excellent results of living kidney transplantation make simultaneous cadaveric pancreas-living kidney transplantation (SPLKTx) an attractive alternative to simultaneous pancreas-kidney transplantation (SPKTx). METHODS: Between June 2001 and June 2003, 80 recipients were enrolled in the SPKTx waiting list. Each recipient's family was counseled about living kidney donation (LKD). Twenty-nine (36.2%) candidates were evaluated for LKD and 8 (27.6%) were disqualified. The remaining 21 candidates were scheduled for LKD and 18 actually donated. RESULTS: Thanks to LKD 18 additional recipients were transplanted, thus expanding the donor pool from 33 to 51 (P =.004). The median waiting time for SPLKTx was 14 days as compared with 95 days for SPKTx (P =.006). Without LKD the median waiting time for SPKTx would have been 198 days (P =.02). Similarly, 1 year after the enrollment on the waiting list 60% of recipients had been transplanted, while without LKD only 42% would had been grafted (P =.01). Two-year recipient survival rate was 100% for SPLKTx compared with 96.9% for SPKTx. Equivalent figures for kidney and pancreas were 80.0% and 84.0% for SPLKTx compared with 96.9% and 96.9% for SPKTx. CONCLUSIONS: LKD expanded the kidney donor pool, reduced the waiting time of recipients listed for a totally cadaveric procedure, and increased their chance to get a timely graft. One-year outcome of SPLKTx equaled that of SPKTx.

Cadaver↗
PubMed2004

Phenotype-genotype relationships of SULT1A1 in human liver and variations in the IC50 of the SULT1A1 inhibitor quercetin.

Human sulfotransferases catalyze sulfate conjugation and 2 polymorphic genes, SULT1A1 and SULT1A2 in this family of transferases have been identified, encoding for 2 isoenzymes with very similar properties and substrate specificities. In order to test the hypothesis that variability in sulfation is due to genetic polymorphism in SULT1A1, the sulfation rate of 4-nitrophenol, a diagnostic substrate, was measured in 50 human liver samples and the genotype at the SULT1A1 locus was analyzed. The rate of 4-nitrophenol sulfation varied from 473 - 1,405 pmol/min/mg between the 5th and 95th percentiles, with a median and a mean +/- SD of 757 and 807 +/- 292 pmol/min/mg, respectively. The activities detected among the SULT1A1*2/*2 homozygotes (5 cases) were significantly lower than those of the other 2 genotypes, SULTA1*11/*1 and SULT1A1*1/*2 (5 and 40 cases, respectively), whereas there was no significant difference found between the SULT1A1*1/*1 and SULT1A1*1/*2 genotypes. To evaluate the possible influence of SULT1A2 polymorphism, genotype assays were also performed for this locus. No SULT1A2*2/*2 carrier, 26 SULT1A2*1/*1 and 24 SULT1A2*1/*2 were detected in the population sample under study. However, no correlation between the rate of 4-nitrophenol sulfation and the SULT1A2 genotype was detected. These results confirm that the variation in the rate of 4-nitrophenol sulfation in human liver is mainly due to SULT1A. Since SULT1A1*1/*2 polymorphism accounts for no more than 10% of the phenotypic variation seen in this cohort, other factors must also contribute to the variability in the rate of 4-nitrophenol sulfation in human liver. However, on the basis of the data obtained, variations in age, gender and liver function as possible causative factors can be excluded. The IC50 of quercetin, a potent inhibitor of 4-nitrophenol sulfation, was measured in the liver samples and ranged from 4.6 to 17.3 nM between the 5th and 95th percentiles. The median and the mean +/- SD were 7.7 nM and 8.3 +/- 2.5 nM, respectively. There was a weak but significant correlation between the IC50 value and age of the liver donors (r = 0.283, p = 0.046). The observed variation did not correlate with the genotypes at the SULT1A1 and SULT1A2 loci.

Adult↗
PubMed2003

Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues.

1. Curcumin has anti-carcinogen effects and is under clinical evaluation as a potential colon cancer chemopreventive agent. The first aim was to see whether curcumin inhibited phenol sulfotransferase (SULT1A1) and, if so, to study the variability of the IC(50) of curcumin for SULT1A1 in 50 human liver samples. For comparative purposes, the inhibition of catechol sulfotransferase (SULT1A3) in five human liver specimens was studied. The second aim was to measure the IC(50) of curcumin against SULT1A1 in five samples of human duodenum, colon, kidney and lung. 2. Curcumin was a potent inhibitor of SULT1A1 in human liver; the mean +/- SD and median of IC(50) were 14.1 +/- 7.3 nM and 12.8 nM, respectively. The IC(50) ranged from 6.2 to 30.6 nM between the 5th and 95th percentiles and the fold of variation was 4.9. The distribution of IC(50) was positively skewed (skewness 1.2) and deviated from normality (p = 0.0004). 3. Curcumin inhibited human SULT1A3, and the inhibition was studied in five liver specimens with an IC(50) of 4324 +/- 1026 nM. This inhibition was greater than the IC(50) of curcumin for SULT1A1 (p < 0.0001). 4. In the extrahepatic tissues, the IC(50) of curcumin for SULT1A1 was 25.9 +/- 4.8 nM (duodenum), 25.4 +/- 6.8 nM (colon), 23.4 +/- 2.2 nM (kidney) and 25.6 +/- 5.6 nM (lung). Inhibition in these tissues is greater than that of curcumin for SULT1A1 in human liver (p < 0.0001). 5. In conclusion, curcumin is a potent inhibitor of SULT1A1 in human liver, duodenum, colon, kidney and lung. The IC(50) of curcumin for SULT1A1 varied 4.9-fold in human liver. The comparison of the present data with those of the literature revealed that the IC(50) of curcumin in the liver and extrahepatic tissues is one order of magnitude lower that the peak serum concentration of curcumin after therapeutic doses of 4 g to humans.

Adult↗
PubMed2003

Perioperative management for laparoscopic kidney donation.

AIM: To report a single centre's experience in the perioperative management of live kidney laparoscopic donations. METHODS. DESIGN: comparative analysis of all laparoscopic kidney donations performed between April 2000 and August 2002 and a corresponding number of "traditional surgery" donors from a historical series. SETTING: kidney transplant centre of a teaching hospital. INTERVENTIONS: 39 and 27 subjects undergoing respectively laparoscopic and traditional "open" kidney donation were studied. A standard balanced anesthesiological technique was used in both groups but, to counterbalance the reported abdominal insufflation-related kidney dysfunction, laparoscopic donors were administered an extra intravascular volume loading with colloids and crystalloids starting from the night before surgery. RESULTS: Laparoscopic donors underwent a longer procedure with a lower estimated blood loss (p=0.0001) and were intraoperatively administered with a higher amount of intravenous fluids (p<0.01); they showed less postoperative analgesic requirement (p<0.0001), a shorter ICU stay and overall hospitalisation (p<0.001), a quicker resumption of solid oral intakes (p<0.01) and full return to work (p<0.001) with no difference in the rate of postoperative complications. Diuresis resumed intraoperatively in all recipients and early graft function did not differ in the 2 groups although serum creatinine declined earlier, but not significantly, in those receiving kidneys by the traditional method. CONCLUSION: Kidney laparoscopic donation does not require a particularly complex or expensive anaesthetic management or approach; it is advisable to adopt strategies to counterbalance laparoscopy-associated abdominal hypertension.

Adult↗
PubMed2002

Grasping and dissecting instrument for hand-assisted laparoscopic surgery: development and early clinical experience.

BACKGROUND: The operative potential of hand-assisted laparoscopic surgery (HALS) could be enhanced by the introduction of a new generation of assisting instruments. These tools will have to meet specific requirements of shape, function, and safety of use. METHODS: Problems related to the working environment of HALS and deriving projectual restrictions of HALS instruments were analyzed in order to develop and manufacture a working prototype with grasping and dissecting properties to assist during HALS procedures. The resulting instrument was mechanically and clinically tested in 22 HALS procedures. RESULTS: The additional benefit of the new device was particularly appreciated during dissection and isolation of vascular pedicles (nephrectomies and splenectomies). It was shown to be safe and effective in providing the additional assistance it was designed for. CONCLUSION: The described grasping and dissecting instrument for HALS is of great value in assisting the surgeon during fine dissection, as required in selected procedures. New generation of HALS instruments should comply with the functional and safety issues analyzed in this report.

Equipment Design↗
PubMed2002

Inhibition of mycophenolic acid glucuronidation by niflumic acid in human liver microsomes.

OBJECTIVES: The first aim of this investigation was to study the variability of mycophenolic acid (MPA) glucuronidation rate in human liver. The second aim was to study the inhibition type of niflumic acid (NA) for MPA glucuronidation in human liver. The third aim was to study the variability of the IC(50) value of NA for MPA glucuronidation in human liver. METHODS: The rate of MPA glucuronidation was measured by employing an assay based on uridine 5'-diphosphate-[U-(14)C]-glucuronic acid (UDPGA), and MPA glucuronide was isolated by means of thin-layer chromatography. The necessary concentration for UDPGA and MPA was 1 mM. The rate of MPA glucuronidation was measured in 50 human liver samples. The inhibition type of NA for MPA glucuronidation was studied in 5 human liver samples. The NA IC(50) value was measured in 27 human liver samples using six concentrations of NA ranging from 1.05 microM to 34 microM. RESULTS: MPA glucuronidation rate was positively skewed, was not gender regulated and did not correlate with the liver donor's age. The rate of MPA glucuronidation varied 4.8-fold within the 5th and 95th percentiles, with a mean+/-SD and a median of 2.8+/-1.0 nmol/min/mg and 2.5 nmol/min/mg, respectively. The inhibition type of NA for MPA glucuronidation was mixed non-competitive. The Ki value of NA (mean+/-SD) was 15+/-10 microM and, in non-inhibited samples, the K(m) value for MPA was 0.41+/-0.06 mM. The distribution of NA IC(50) value varied 3.3-fold within the 5th and 95th percentiles with a mean+/-SD and a median of 5.6+/-2.1 microM and 5.2 microM, respectively. The distribution of NA IC(50) value did not deviate significantly from normality. CONCLUSION: The range of hepatic rate of MPA glucuronidation is narrow relative to those of ethinyloestradiol, testosterone and zidovudine glucuronidation obtained from literature. The Ki value of NA is one order of magnitude lower than the K(m) for MPA in non-inhibited samples. This indicates that the inhibitor affinity for glucuronosyl transferase is greater than that of the substrate. The range of variation of NA IC(50) values is narrow.

Adult↗
PubMed2002

Inhibition of phenol sulfotransferase (SULT1A1) by quercetin in human adult and foetal livers.

1. Quercetin is one of the most abundant flavonoids in edible vegetables, fruit and wine. The aim was to study the type of inhibition of SULT1A1 by quercetin in the human adult and foetal livers. 2. The activity of SULT1A1 was measured with 4 microM 4-nitrophenol and 0.4 microM 3'-phosphoadenosine-5'-phosphosulphate-[(35)S], and its mean (+/-SD) and median were 769 +/- 311 and 740 pmol min(-1) mg(-1), respectively (adult liver, n = 10), and 185 +/- 98 and 201 pmol min(-1) mg(-1), respectively (foetal liver, n = 8, p < 0.0001). 3. In non-inhibited samples, K(m) for SULT1A1 (mean +/- SD) was 0.31 +/- 0.14 microM (adult liver) and 0.49 +/- 0.17 microM (foetal liver, n.s.). V(max) for SULT1A1 (mean +/- SD) was 885 +/- 135 pmol min(-1) mg(-1) (adult liver) and 267 +/- 93 pmol min(-1) mg(-1) (foetal liver, p = 0.007). 4. The IC(50) of quercetin for SULT1A1 was measured in three samples of adult and foetal livers and was 13 +/- 2.1 and 12 +/- 1.4 nM, respectively. 5. The type of inhibition was mixed non-competitive in adult and foetal livers and K(i) was 4.7 +/- 2.5 nM (adult liver) and 4.8 +/- 1.6 nM (foetal liver). 6. In the adult liver, the intrinsic clearance (mean +/- SD) was 3.3 +/- 1.5 ml min(-1) mg(-1) (non-inhibited samples), 0.9 +/- 0.4 ml min(-1) mg(-1) (12.5 nM quercetin) and 0.5 +/- 0.06 ml min(-1) mg(-1) (25 nM quercetin). In the foetal liver, the intrinsic clearance (mean +/- SD) was 0.5 +/- 0.2 ml min(-1) mg(-1) (non-inhibited samples), 0.12 +/- 0.01 ml min(-1) mg(-1) (12.5 nM quercetin) and 0.2 +/- 0.09 ml min(-1) mg(-1) (25 nM quercetin). 7. In conclusion, quercetin is a potent inhibitor of human adult and foetal liver SULT1A1. It reduces the sulphation rate and intrinsic clearance of 4-nitrophenol in both human adult and foetal livers. This suggests that quercetin may inhibit the sulfation rate of those drugs sulphated by SULT1A1. The inhibition of SULT1A1 is complex and not due solely to competition at the catalytic site of SULT1A1.

Adult↗
PubMed2002

7-OH-flavone is sulfated in the human liver and duodenum, whereas 5-OH-flavone and 3-OH-flavone are potent inhibitors of SULT1A1 activity and 7-OH-flavone sulfation rate.

1. The aim of this investigation was to see whether 7-OH-flavone, 5-OH-flavone and 3-OH-flavone, which are present in edible vegetables, fruit and wine, are substrates or inhibitors of human liver and duodenum sulfotransferase. 2. An assay was set up to study the sulfation of 7-OH-flavone, and using this assay, it was observed that 7-OH-flavone was sulfated and the rate of sulfation (mean +/- SD) was 324 +/- 87 pmol min(-1) mg(-1) (liver) and 584 +/- 164 pmol min(-1) mg(-1) (duodenum; p < 0.0001). 3. 7-OH-flavone sulfotransferase followed Michaelis-Menten kinetics and the K(m) (mean +/- SD) was 0.2 +/- 0.04 microM (liver) and 1.1 +/- 0.3 microM (duodenum; p = 0.008). V(max) (mean +/- SD) was 392 +/- 134 pmol min(-1) mg(-1) (liver) and 815 +/- 233 pmol min(-1) mg(-1) (duodenum; p = 0.016). 4. 5-OH-flavone and 3-OH-flavone were not sulfated and were inhibitors of human liver and duodenum SULT1A1 activity and 7-OH-flavone sulfation rate. 5. The IC50 of 5-OH-flavone for SULT1A1 was 0.3 +/- 0.06 microM (liver) and 0.3 +/- 0.1 microM (duodenum; n.s.) and those of 3-OH-flavone were 1.0 +/- 0.1 microM (liver) and 1.6 +/- 0.03 microM (duodenum; p = 0.0006). 6. There was inhibition of 7-OH-flavone sulfation rate by 5-OH-flavone and 3-OH-flavone. The IC(50) of 5-OH-flavone for the sulfation rate of 7-OH-flavone was 3.5 +/- 0.5 microM (liver) and 69 +/- 18 microM (duodenum; p < 0.0001) and for 3-OH-flavone it was 18 +/- 3.4 microM (liver) and 213 +/- 47 microM (duodenum; p < 0.0001). 7. The position of the hydroxy group confers to the molecules of OH-flavones the quality of substrate or inhibitor of sulfotransferase.

Adult↗