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Biomedical subjects

F Uggeri

Publications and source records attributed to F Uggeri.

At least 19 recordsLinked to original sources

Radical surgery does not recover immunodeficiency associated with gastric cancer.

Cell-mediated immunodeficiency is known to occur in advanced cancer patients, but it is less characterized in earlier stages. Pre-existing immunodeficiency may impair the recovery of postoperative lymphocytopenia, occurring generally within 8-14 days after surgical stress. This study was aimed to verify whether immunodeficiency exists in patients with operable gastric adenocarcinoma and whether radical surgery may restore a count of peripheral blood T helper cells (CD4) and CD4/CD8 ratio within physiological normal values in the late postoperative period. Thirty-five consecutive patients (M/F 18/17; mean age 67 years, range 42-82) with histologically proven gastric adenocarcinoma, undergoing surgery with radical intent, were studied. Assessment of total lymphocyte count and lymphocyte subsets was performed by FAC scan at baseline, then postoperatively 14 and 50 days after surgery. Normal reference values were according to CDC criteria for HIV immunodeficiency (total lymphocyte > 1500/mmc; CD4 cells > 500/mmc; CD4/CD8 > 1.2). Surgical interventions, including D2 locoregional lymphadenectomy, were as follows: 19 Roux Y total gastrectomies; 3 Roux Y subtotal gastrectomies and 13 Billroth II subtotal gastrectomies. Pathological nodal staging was pN0 in 18 and pN+ in 17 cases. Hystotype was intestinal in 14 patients, diffuse in 14 and unclassifiable in 7. Grading was G1 n = 7; G2 n = 7; G3 n = 21. Lymphocyte immunodeficiency was found at baseline in 41% of patients and at 14 days after surgery in 67% of patients. Recovery of postoperative surgery-induced lymphocytopenia occurred on the 50th day only in those patients with normal values at baseline (59%). CD4 deficiency was significantly more frequent in pN+ vs. pN0 patients, either at baseline (p < 0.001 ), on the 14th day (p < 0.02) and on the 50th day (p < 0.007) postoperatively. Cancer-related CD4 deficiency was a frequent finding in our consecutive series of gastric cancer patients; this systemic immune impairment was not restored after complete tumor removal, even in late postoperative period (50th day ). Further studies on a larger number of cases may confirm the prognostic value of lymphocyte count in early gastric cancer stages, and to verify whether early and late postoperative immunodeficiency may be prevented by IL-2 administration.

Adenocarcinoma↗

Laparoscopic splenectomy using Ligasure. Preliminary experience.

BACKGROUND: Intraoperative bleeding is the main complication and main cause of conversion during laparoscopic splenectomy (LS). We present the advantages of the use of the Ligasure Vessel Sealing System added to lateral approach for achieving a safe vascular control. METHODS: Ligasure is an energy-based device which works applying a precise amount of bipolar energy and pressure to the tissue, achieving a permanent seal. We have performed a total of 35 LS in a 5-year period using different approaches and methods of dissection, including the anterior approach, monopolar coagulation, clips, endostaplers, and ultrasonic shears. In the last 10 patients (4 males and 6 females, mean age 24 yr) we employed a technique with 4 trocars, right semilateral position associated with the entire dissection of the spleen and vessels sealing (lower pole vessels, main vascular pedicles, short gastric vessels) performed with Ligasure. Six had thrombocytopenic idiopatic purpura (ITP), 2 hereditary spherocytosis and one each b-thalassemia and hemolytic anemia. RESULTS: Nine LS were completed with one (10%) conversion because of hilar bleeding due to accidental injury with Ligasure. The average splenic weight was 485 g (range 265-1800), with an average diameter of 16 cm (range 12-25). In all but one patients (the converted one) the intraoperative blood loss was less than 100 mL (range 50-100 mL, average 80 mL). No blood transfusion were needed. The average operative time was 120 min (range 90-165), including 2 patients undergoing combined laparoscopic cholecystectomy. There was no mortality, with one (10%) postoperative complication (thrombosis of the spleno-portal axis), treated with a conservative approach. The average postoperative hospital stay was 3.5 days (range 3-6). CONCLUSIONS: The use of Ligasure, associated with the lateral position, results in a gain of time and safety. Furthermore, the average intraoperative bleeding of this series is very low.

Adult↗

Mesenteric cyst neoformation. A case report.

Mesenteric cysts are rare lesions, with 1 case per 100,000 hospital admission reported. They have to be differentiated from ovarian cysts, gastrointestinal duplications and desmoid cysts. The symptoms are variable, ranging from asymptomatic cases with incidental discovery to chronic abdominal discomfort and acute abdomen. They are usually correlated to the location and the size of the lesion. Abdominal ultrasonography and computed tomography may lead to a correct diagnosis, which is regularly made at the time of abdominal exploration. Surgery is the treatment of choice, consisting with the removal of the cyst, eventually associated with bowel resection. It has to be radical in order to prevent the recurrence of the disease. A case of mesenteric cyst in a sixty-nine-years-old woman hospitalized for chronic abdominal pain is reported. In this case the cyst has been enucleated from the mesentery with open surgery without the need for bowel resection.

Aged↗

Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles.

The mechanism of excretion into bile of hepatospecific magnetic resonance imaging (MRI) contrast media employed labeled Gd-reagents EOB.DTPA, BOPTA, B 20790 (iopanoate-linked), and B 21690 (glycocholate-linked) for measurement in rat liver canalicular plasma membrane vesicles and yeast vacuoles. The presence of ATP gave threefold greater transport of B 20790 and B 21690 than of EOB.DTPA and BOPTA. In yeast vacuoles the ATP stimulatory effect was eightfold with B 20790 and fivefold greater for B 21690, whereas in YCF1- or YLLO115w-deleted yeast cells the transport was significantly reduced and absent from double mutants, YCF1 and YLLO15w. The transport was similar in wild-type and deletant cells for B 21690; taurocholate gave 85% inhibition. These data suggest that bilary secretion of structurally related MRI agents depend on molecular structure. The findings are suggestive as of possible value for clinical diagnosis of inherited hyperbilirubinemias and other liver disorders.

ATP-Binding Cassette Transporters↗

Phase IB study on prevention of surgery-induced immunodeficiency with preoperative administration of low-dose subcutaneous interleukin-2 in gastric cancer patients.

BACKGROUND AND OBJECTIVES: Low count of total and T helper lymphocytes predicts a poor prognosis in cancer patients and surgical trauma can worsen cancer-related immunodeficiency. Aim of this phase IB study is to verify toxicity and biological effects of interleukin-2 (IL-2) at 9 million IU/day subcutaneously (sc.) administered one, two or three preoperative days in patients with gastric cancer undergoing radical surgery. METHODS: Absolute value of total and T-helper (CD4) lymphocytes were measured at baseline and at 7th, 14th, and 50th postoperative days in 12 gastric cancer patients, who preoperatively received IL-2 at 9 million IU/day sc. as follows: group A (4 pts) 1-day; group B (4 pts) 2-days; group C (4 pts) 3-days administration. T and total lymphocytes count were recorded and retrospectively analyzed in a historical control-group of 22 consecutive patients, age and stage-matched. RESULTS: Toxicity consisted of fever grade I. In group A (1 day) T helper lymphocytes count decreased at 7th and at 14th postoperative day; in group B (2 days) and group C (3 days) no decrease of neither total nor T helper lymphocyte count occurred postoperatively, whereas in the historical group these parameters decreased significantly postoperatively and recovered only at 50th day. CONCLUSIONS: Two- and three-day schedules of sc. IL-2 preoperative administration at 9 million IU/daily prevented postoperative lymphocytopenia, whereas one-day administration did not. Since the IL-2 dose was so tolerable, that it could be given safely as outpatient, based on the previous results on survival observed in colorectal cancer patients with 3-days schedule we suggest that a 3-day schedule of Interleukin-2 as outpatient preoperative treatment seems advisable for further studies in gastric cancer patients.

Adenocarcinoma↗

Mixed micelles containing lipophilic gadolinium complexes as MRA contrast agents.

Mixed micelles for MRA are multicomponent systems containing a phospholipid, a biocompatible non-ionic surfactant (e.g. Synperonic(R) F-108) and a lipophilic gadolinium complex. A variety of lipophilic gadolinium complexes were designed taking into account features such as: (i) nature of ligand (cyclic versus acyclic); (ii) lipophilic moiety; (iii) global charge of the complex; and (iv) nature of bond connecting the complex to the lipophilic moiety. All the lipophilic gadolinium complexes after formulation as mixed micelles show high relaxivities in water and in blood (rat). Mixed micelles containing gadolinium complexes bearing only one aliphatic chain cannot be used as MRA contrast agents because they have a high haemolytic effect. Furthermore, in rats they are quickly eliminated from the blood stream. These drawbacks are completely circumvented using gadolinium complexes bearing two aliphatic chains. Mixed micelles containing such complexes show high relaxivities, no haemolytic effect and long blood permanence. This makes them promising candidates as MRA contrast agents. However, elimination, which occurs exclusively through the liver, is not complete, even after 7 days. Complexes containing labile (e.g. ester) bonds between the lipophilic moieties and the chelate subunit are eliminated through both the liver and the kidneys. However, elimination is still not complete after 7 days.

Animals↗

Laparoscopic cholecystectomy and unsuspected gallbladder cancer.

Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope.

Cholecystectomy, Laparoscopic↗

[Stomach lymphoma].

BACKGROUND: Primitive gastric lymphoma (PGL) is a rare tumour, and although its incidence is rising it is difficult to state the role of the various therapeutic methods in treating this disease. Aim of this study is to point out what sequence of treatment is more effective trying to find out some guidelines which can be useful in clinical practice. METHODS: Retrospective analysis of clinical data of 54 patients with PGL admitted at a University surgical department during 10 years. All the patients underwent neoadjuvant or adjuvant chemotherapy and D2 gastrectomy. Follow-up ranged from 6 to 120 months. Survival was related to: Mushoff's stage of disease, the grade according to the Working Formulation and the sequence of treatment. Statistical analysis was performed by Kaplan-Maier method and the difference between survival curves was compared by log-rank test. RESULTS: Mean postoperative hospital stay was 12 days and morbidity was 18%. Five and 10 years overall survival rates were 70 and 85%. There was a significant difference in survival between patients with high grade PGL and those with intermediate grade (p=0.0188) as well as in those with low grade (p=0.0435). Patients in stages IE-II1E had a significantly longer survival than those in stages IIIE-IVE (p=0.0123). Patients in stages IE-II1E underwent neadjuvant chemotherapy and surgery and survived longer than those in whom surgery preceded chemotherapy (p=0.0293) instead for patients in stages IIIE-IVE neoadjuvant chemotherapy shortened survival (p=0.0403). CONCLUSIONS: In personal opinion, in patients in stages IE-II1E chemotherapy should be carried out before surgery, while in those in stages IIIE-IVE the reverse scheme is more effective in achieving longer survival rates.

Adult↗

[Serious complications of vertical banded gastroplasty. Case report].

Vertical banded gastroplasty, reported by Mason in 1982, is an effective method to control pathologic obesity (BMI>40 kg/m2). With the widespread of this procedure and the introduction of laparoscopic approach several complications are described in literature: gastroesophageal reflux, esophagitis, gastritis, gastric bleeding and perforations, prolonged vomit, dislocation of gastric ring, cholelithiasis, gastric fistulas, gastric stomal stenosis, dehiscence of vertical stomach staple line. From 2 to 10% of patients are reoperated because of inefficacy of treatment or short and long-term complications. Morbidity and mortality associated to reoperations are still high and it is difficult to identify criteria for an appropriate revision procedure. This can occur through endoscopy, laparotomy or laparoscopy, depending on clinical and radiologic feature. Dehiscence of vertical stomach staple line, observed in 10-20% of cases, even if asymptomatic, can lead to bad complications such as fistulas, peritonitis and sepsis. The case of a young woman, who underwent a vertical banded gastroplasty for pathologic obesity (117 kg, h 167 cm, BMI 42/m2) and subsequent laparotomies in the attempt to correct vertical staple line dehiscence, is reported. The patient came to our observation in a septic shock caused by peritonitis and ARDS and a total gastrectomy with Roux-en-Y esophago-jejunostomy was performed.

Adult↗

[The use of the biofragmentable ring (BAR-Valtrac) in colon surgery].

BACKGROUND: Clinical results of colic anastomosis using biofragmentable anastomosis ring (BAR-Valtrac) are presented. Such a method showed to be a real alternative technique to the usual ones. METHODS: Eighty-six colic anastomosis using BAR are collected, 76 of which performed as elective surgery and 10 in emergency. The patients were 47 males and 39 females, with a mean age of 64 years. In 63 cases the patients were affected by colic neoplastic disease, in 16 by complicated diverticular disease (stenosis or perforation) and 7 patients had neoplastic disease of other organs involving the colon BAR device was used in 48 colic reconstructions after segmentary resection and in 38 colic reconstructions after left hemicolectomy. In each case 31-34 mm BAR were used. RESULTS: No perioperative death occurred in our series. Only one case (2%) of anastomotic leak was observed, while in 3 cases (4%) intestinal canalization disorders occurred. No problems for ring expulsion occurred in any patient. Three late complications were observed, as three cases of asymptomatic substenosis discovered during instrumental follow-up and spontaneously cleared up. CONCLUSIONS: On the basis of clinical results, and according to those reported in literature BAR anastomosis is considered a safe, feasible and easy technique to perform colic anastomosis, even in emergency, limited to the intraperitoneal tract of the colon.

Adult↗

[Videolaparoscopic cholecystectomy. Experience and results in 1019 cases].

BACKGROUND: Laparoscopic cholecystectomy is now worldwide considered the elective therapy for biliary lithiasis. Morbidity, mortality and conversion rates reported in the literature are assessed between 1 and 6%, 0 and 0.9%, 3.6 and 7.2% respectively. Data on personal experience with 1019 attempted laparoscopic cholecystectomy are reported. METHODS: In the period between 1991 and 1997 1019 laparoscopic cholecystectomy were performed. Patients were 361 males and 658 females (ratio M:F 1:2), with an average age of 51 years (range 5-85). Indications were: 647 symptomatic cholelithiasis, 28 hydrops, 121 empyemas, 76 cholecystocholedocolithiasis and 13 alithiasic cholecystopathy. RESULTS: Conversion was necessary in 61 cases, with a conversion rate of 6%. Mean duration of surgery was 65 minutes (range 30-240) with a mean hospital stay of 2.1 days (range 1-10). No deaths occurred in our series, with a morbidity rate of 1.8% (18 cases, 7 major and 11 minor). Only 1 case of bile duct injury (0.1%) is reported. CONCLUSIONS: In consideration of low conversion rate, low early and late morbidity, absence of bile duct injury, advantages for the patient and the opportunity of evolution of this surgery, laparoscopic cholecystectomy can be considered the standard treatment for biliary lithiasis.

Adolescent↗

Laparoscopic versus open splenectomy: a comparative study.

Laparoscopic splenectomy (LS) is gaining wide acceptance as a safe, effective alternative to open splenectomy (OS) in the treatment of hematologic disorders in adult and pediatric patients, with low conversion rates and complications. The aim of this retrospective case-control study was to compare two cohorts of patients, with similar characteristics, who underwent OS or LS in a single institution. The medical records of the initial 20 consecutive patients who underwent LS were reviewed and compared with a control group of 28 patients undergoing OS, matched for age, gender, diagnosis, splenic size and weight, and American Society of Anesthesiologists score. Data were collected regarding operative time, blood loss, blood transfusions, pathologic findings, accessory spleen detection, complications, ileus duration, and postoperative hospital stay. Nineteen patients underwent attempted LS. One procedure (5%) was converted to OS for uncontrolled hilar bleeding. Accessory spleens were detected in two cases in the LS group compared with four cases in the OS group (14%). Mean operative time was 165 minutes (range: 100-240 minutes) for LS and 114 minutes (75-180 minutes) for OS (P < 0.001). In the LS group a regular diet was tolerated 36 hours (range: 24-48 hours) after surgery compared with 72 hours (range: 48-96 hours) for the OS group (P < 0.001), and mean postoperative hospital stay was 4.1 days (range: 3-8 days) for LS, compared with 8.1 days (range: 5-12 days) for OS (P < 0.001). No differences were observed in blood loss, complication rates, or transfusion requirements. Compared with OS, LS requires more operative time (showing a learning curve), is comparable in blood loss, transfusion requirements, complication rates, and detection of accessory spleens and appears to be superior in terms of return of bowel function and hospital stay.

Adolescent↗

[Hernia repair with prolene mesh according to the Lichtenstein technique. Results of 692 cases].

BACKGROUND: Inguinal hernia repair with prolene mesh according to Lichtenstein "tension free" technique has gained great acceptance worldwide, showing efficacy to consolidate the posterior wall of the inguinal canal and to reduce recurrence risk because of tension on suture lines and postoperative pain. Personal experience of 692 hernias treated with this technique is reported. METHODS: From January 1989 to December 1997, 692 patients were treated according to Lichtenstein at the General Surgery Department of the San Gerardo Hospital. Mean age was 60 years (range 18-88) with a male: female ratio of 13:1. Surgery was performed under local anesthesia in 185 cases, under epidural anesthesia in 317 and under general anesthesia in 190. Hernia was primitive in 647 cases (411 obliquo-external and 236 direct), while in 45 patients it was a recurrent hernia. In this series, 619 patients had monolateral inguinal hernia, while 73 had a bilateral one. In 40 cases hernia was incarcerated and in 8 strangulated. RESULTS: Mean hospital stay was 2.3 days (range 1-8). Eleven (1.6%) early complications, were observed, with one periprosthetic infection which resolved after patch removal, 3 hematomas, 2 seromas and 2 wound infections. Furthermore, there were 32 (4.6%) late complications with only one recurrence (0.14%) in this series and 25 cases of persistent nerve irritation. CONCLUSIONS: The results obtained with Lichtenstein "tension free" repairs of inguinal hernias confirmed this technique as easy to perform, also under local anesthesia, and associated with low rates of complications and without recurrences.

Adolescent↗

[Sequential endo-laparoscopic treatment in patients with common bile calculi].

BACKGROUND: Laparoscopic treatment of common bile duct (CBD) stones is gaining great acceptance worldwide, but actually it requires skills and technologies too expensive for a great part of general surgeons. So endoscopic removal of CBD stones before cholecystectomy is usually performed. Since 1991 in our department we started a policy of selective preoperative cholangiopancreatography (ERCP) in patients suspected for choledocholithiasis and waiting for laparoscopic cholecystectomy. METHODS: A retrospective study has been made on a population of 1100 patients who underwent elective laparoscopic cholecystectomy in the period between January 1991 and December 1997. They were 391 male and 719 female with a mean age of 52 years, 126 of whom (11.5%) were selected to have ERCP preoperatively because they had clinical, biochemical and ultrasound signs of the presence of common bile duct stones (CBDS). RESULTS: Successful cannulation of the CBD was achieved in 124 cases (98.4%), with failures due to ampullary diverticula. In 7 cases (5.5%) a precut was necessary to obtain cannulation. Sphincterotomy was performed in 113 patients (89.7%). In 93 patients (73.8%) stones were found (87 macrolithiasis and 6 microlithiasis); in 91 (97.8%) stones were removed in one (87) or two (4) endoscopic session. There were 2 major complications (one bleeding and one severe pancreatitis) due to ERCP or a sphincterotomy. Two patients developed symptoms from unsuspected common bile duct stones after LC and were removed endoscopically. No complications during LC were due to ERCP or ES. CONCLUSIONS: Selective preoperative ERCP is an effective way of clearing the CBD stones before laparoscopic cholecystectomy, with low rate of complications related to endoscopic and laparoscopic procedures, and short mean hospital stay (5.5 days), according to the concept of minimally invasive treatment.

Adolescent↗

[Gallbladder carcinoma and laparoscopic cholecystectomy. An emergent problem].

BACKGROUND: Gallbladder cancer (GC) is reported in 1.5-3% of cholecystectomies. Since the introduction of laparoscopic surgery, cholecystectomies have increased and occult GC may therefore be more frequent. METHODS: Here we conduct a retrospective study on a series of 1200 LC performed between January 1991 and December 1998 at our Institution, to determine whether there was an increase in GC. We also evaluated the risk factors for this outcome and the possibilities of treatment, in case of unsuspected GC discovered after LC at histological examination. Seven cases of GC undiagnosed before surgery (0.6% of the study population) were submitted to LC (against 0.3% GC discovered after open surgery). The clinical course depended on the histopathologic stage of the cancer. RESULTS: After a median follow-up of 18 months (range 12-48), 2 pT1 patients were alive and well, 2 pT2 patients were alive and disease free (in 1 case after a surgical removal of a trocar site metastasis appeared 6 months after LC). The other 3 patients died, 2 (1 pT2 and 1 pT3) after an additional resection of the liver bed with lymph node dissection, due to peritoneal dissemination of the disease. In 2 cases we found a gallbladder polyp pre and intraoperatively, which proved to be a carcinoma. CONCLUSIONS: Undiagnosed GC is on the increase with the introduction of LC. Polypoid lesions of the gallbladder, age > 70 years: a long history of stones and a thickened gallbladder wall all represent significant risk factors. If one or more is present, examination of the gallbladder and a frozen section are recommended.

Adenocarcinoma↗

Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents.

The mechanisms were investigated for the hepatic transport of 4 different gadolinium complexes used as contrast agents for magnetic resonance imaging (MRI). In basolateral rat hepatocyte plasma membrane vesicles, Gd-DTPA uptake was indistinguishable from non-specific binding to vesicles; Gd-BOPTA and Gd-EOB-DTPA entered plasma membrane vesicles following a linear, concentration-dependent mechanism up to 1.5 mM of substrate. By contrast, Gd-B 20790 uptake followed a saturative kinetic with an apparent Km of 92 +/- 15 microM and a Vmax of 143 +/- 42 pmol/mg prot/15 sec, and it occurred into an osmotic-sensitive space. Sulfobromophthalein ant taurocholate, but not unconjugated bilirubin inhibited the uptake rate of Gd-B 20790 but not that of the other three compounds. Injection into Xenopus laevis oocytes of 5 ng of human OATP cRNA resulted, after 3 days, in a >/=2-fold stimulation (p < 0.001) of transport of Gd-B 20790 but not of Gd-BOPTA or Gd-EOB-DTPA. Collectively, these data indicate that the hepatic uptake of the MRI contrast agent Gd-B 20790 is a carrier-mediated mechanism operated by OATP while MRI compounds with other chemical structures enter the hepatocyte by other mechanisms.

Animals↗

Combined laparoscopic splenectomy and cholecystectomy for the treatment of hereditary spherocytosis: is it safe and effective?

Hereditary spherocytosis is the most common red blood cell membrane disorder and often is associated with hemolytic crisis and premature cholelithiasis. Splenectomy is the only effective therapy for this disorder and often it is performed in combination with cholecystectomy. Conventional surgery requires a wide upper abdominal incision for correct exposure of the gallbladder and spleen. Laparoscopic cholecystectomy and splenectomy have been performed safely worldwide. We report our experience with seven patients (one male and six female, average age 12 years) who underwent combined laparoscopic splenectomy and cholecystectomy for hereditary spherocytosis. The patient was placed in supine position and the procedure performed with a five-trocar technique. Cholecystectomy was performed first, then splenectomy was achieved and the spleen removed by morcellation into a retrieval bag (five cases) or via a 4- to 5-cm left subcostal incision (two cases). No patient required conversion to open technique or blood transfusion. The mean blood loss was 162 mL, mean operative time 207 minutes, mean spleen size 14.5 cm, and median postoperative hospital stay 4 days. No perioperative mortality or major complications occurred in our series. After a median follow-up of 18 months all patients showed sharp hematologic improvement. Despite the small number of cases, we consider the combined laparoscopic approach safe and effective for the treatment of hereditary spherocytosis.

Child↗

Hepatocyte-directed MR contrast agents. Can we take advantage of bile acids?

A series of gadolinium complexes conjugated to bile acids was prepared and investigated as possible hepatospecific MR imaging contrast agents. In the design of such compounds, features such as the nature of the bile acid, the site of conjugation on the bile acid skeleton, and the global charge of the conjugate were taken into account. Relaxivity measurements carried out in human serum indicate interaction of the conjugates with human serum proteins; even small structural variations significantly affect relaxivity in human serum. Pharmacokinetic data (biliary elimination in the range of 18.4-45.6%) show that bile acids can be used as address moieties to transport gadolinium complexes through hepatocytes. For a homogeneous series of compounds, differing only in the bile acid residue conjugated, it was unexpectedly found that cholic acid is twice as efficient an address moiety as cholylglycine or cholyltaurine. Preliminary results show that none of the conjugates is transported through the basolateral membrane of hepatocytes by the Na+/taurocholate carrier.

Animals↗