INFLUENCE OF TACROLIMUS ON MYCOPHENOLATE MOFETIL METABOLISM IN AN EX VIVO ISOLATED SMALL BOWEL PERFUSION MODEL*

1999 ◽  
Vol 21 (4) ◽  
pp. 445 ◽  
Author(s):  
F Braun ◽  
M Shipkova ◽  
U Christians ◽  
S Laabs ◽  
K Elias ◽  
...  
2000 ◽  
Vol 32 (2) ◽  
pp. 100-106
Author(s):  
M.J. Stangl ◽  
J. Krapp ◽  
D. Theodorou ◽  
M. Eder ◽  
C. Hammer ◽  
...  

1998 ◽  
Vol 30 (6) ◽  
pp. 2613-2615 ◽  
Author(s):  
F Braun ◽  
E Schütz ◽  
S Laabs ◽  
U Hanack ◽  
B Sattler ◽  
...  

1989 ◽  
Vol 62 (03) ◽  
pp. 1034-1039 ◽  
Author(s):  
Jan S Brunkwall ◽  
James C Stanley ◽  
Timothy F Kresowik ◽  
Linda M Graham ◽  
William E Burkel ◽  
...  

SummaryRegulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 ± 40 pg/mm2, declining to 32 ± 10 pg/mm2 after 60 minutes (p <0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p <0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p <0.01). Vessels perfused with thrombin, bradykinin or A A (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of A A to the perfusate. These data indicate that vessel segments subjected to ex vivo perfusion do not maximally utilize enzyme systems responsible for prostanoid production, and after 1 hour perfusion have not depleted their phospholipids, and maintain functioning levels of phospholipase and cyclooxygenase activity. This perfusion model allows for the study of prostacyclin and thromboxane release from arteries and veins and their response to various drugs and other stimuli.


2017 ◽  
Vol 216 (1) ◽  
pp. S280 ◽  
Author(s):  
FRANCESCA M. RUSSO ◽  
SIGRID CONINGS ◽  
PIETER ANNAERT ◽  
TIM VAN MIEGHEM ◽  
JAAN TOELEN ◽  
...  

2021 ◽  
Vol 3 (1) ◽  
pp. e000084
Author(s):  
Amanda Farah Khan ◽  
Matthew Kenneth MacDonald ◽  
Catherine Streutker ◽  
Corwyn Rowsell ◽  
James Drake ◽  
...  

ObjectivesWe aim to determine what threshold of compressive stress small bowel and colon tissues display evidence of significant tissue trauma during laparoscopic surgery.DesignThis study included 10 small bowel and 10 colon samples from patients undergoing routine gastrointestinal surgery. Each sample was compressed with pressures ranging from 100 kPa to 600 kPa. Two pathologists who were blinded to all study conditions, performed a histological analysis of the tissues. Experimentation: November 2018–February 2019. Analysis: March 2019–May 2020.SettingAn inner-city trauma and ambulatory hospital with a 40-bed inpatient general surgery unit with a diverse patient population.ParticipantsPatients were eligible if their surgery procured healthy tissue margins for experimentation (a convenience sample). 26 patient samples were procured; 6 samples were unusable. 10 colon and 10 small bowel samples were tested for a total of 120 experimental cases. No patients withdrew their consent.InterventionsA novel device was created to induce compressive “grasps” to simulate those of a laparoscopic grasper. Experimentation was performed ex-vivo, in-vitro. Grasp conditions of 0–600 kPa for a duration of 10 s were used.ResultsSmall bowel (10), M:F was 7:3, average age was 54.3 years. Colon (10), M:F was 1:1, average age was 65.2 years. All 20 patients experienced a significant difference (p<0.05) in serosal thickness post-compression at both 500 and 600 kPa for both tissue types. A logistic regression analysis with a sensitivity of 100% and a specificity of 84.6% on a test set of data predicts a safety threshold of 329–330 kPa.ConclusionsA threshold was discovered that corresponded to both significant serosal thickness change and a positive histological trauma score rating. This “force limit” could be used in novel sensorized laparoscopic tools to avoid intraoperative tissue injury.


2006 ◽  
Vol 195 (6) ◽  
pp. 1715-1719 ◽  
Author(s):  
Heather J. Holmes ◽  
Brian M. Casey ◽  
Roger E. Bawdon

2019 ◽  
Vol 24 (4) ◽  
pp. 290-295
Author(s):  
Catherine S. Heith ◽  
Lizbeth A. Hansen ◽  
Rhonda M. Bakken ◽  
Sharon L. Ritter ◽  
Breeanna R. Long ◽  
...  

OBJECTIVES With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. METHODS ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO2, and PCO2 were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured. RESULTS Hydromorphone hydrochloride was not as significantly sequestered by the ex vivo pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours. CONCLUSIONS Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.


Planta Medica ◽  
2021 ◽  
Author(s):  
Deborah Spiess ◽  
Vanessa Fabienne Abegg ◽  
Antoine Chauveau ◽  
Andrea Treyer ◽  
Michael Reinehr ◽  
...  

AbstractThe placental passage of humulone and protopine was investigated with a human ex vivo placental perfusion model. The model was first validated with diazepam and citalopram, 2 compounds known to cross the placental barrier, and antipyrine as a positive control. All compounds were quantified by partially validated U(H)PLC-MS/MS bioanalytical methods. Only a small portion of humulone initially present in the maternal circuit reached the fetal circuit. The humulone concentration in the maternal circuit rapidly decreased, likely due to metabolization in the placenta. Protopine was transferred from the maternal to the fetal circuit, with a steady-state reached after 90 min. None of the study compounds affected placental viability or functionality, as glucose consumption, lactate production, beta-human chorionic gonadotropin, and leptin release remained constant. Histopathological evaluation of all placental specimens showed unremarkable, age-appropriate parenchymal maturation with no pathologic findings.


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