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Situ Perfusion (situ + perfusion)

Distribution by Scientific Domains
Medical Sciences75%

Selected Abstracts

Effects of endothelin-1 on portal-systemic collaterals of common bile duct-ligated cirrhotic rats

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2004
C.-C. Chan
Abstract Background/Aims, Endothelin-1 (ET-1) may induce intrahepatic vasoconstriction and consequently increase portal pressure. Endothelin-1 has been shown to exert a direct vasoconstrictive effect on the collateral vessels in partially portal vein-ligated rats with a high degree of portal-systemic shunting. This study investigated the collateral vascular responses to ET-1, the receptors in mediation and the regulation of ET-1 action by nitric oxide and prostaglandin in cirrhotic rats with a relatively low degree of portal-systemic shunting. Methods, The portal-systemic collaterals of common bile duct-ligated (BDL) cirrhotic rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10,10,10,7 m) with or without BQ-123 (ETA receptor antagonist, 2 × 10,6 m), BQ-788 (ETB receptor antagonist, 10,7 m) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of N, -nitro-L-arginine (NNA, 10,4 M), indomethacin (INDO, 10,5 M) or in combination were assessed. Results, Endothelin-1 significantly increased the perfusion pressures of portal-systemic collaterals. The ET-1-induced constrictive effects were inhibited by BQ-123 or BQ-123 plus BQ-788 but not by BQ-788 alone. The inhibitory effect was greater in the combination group. Pretreatment of NNA or NNA plus INDO equivalently enhanced the response of ET-1 while pretreatment of INDO alone exerted no effect. Conclusion, Endothelin-1 has a direct vasoconstrictive effect on the collaterals of BDL cirrhotic rats, mainly mediated by ETA receptor. Endogenous nitric oxide may play an important role in modulating the effects of ET-1 in the portal-systemic collaterals of BDL cirrhotic rats. [source]

Expression of intercellular adhesion molecule-1 in hepatic stellate cells

JOURNAL OF DIGESTIVE DISEASES, Issue 1 2000
Lu Lungen
OBJECTIVE: To explore the expression of intercellular adhesion molecule-1 (ICAM-1) in hepatic stellate cells (HSC). METHODS: Via in situ perfusion with proteinase and collagenase and density-gradient centrifugation with Nycodenz, HSC were isolated and cultured from the livers of both normal Wistar rats and the livers of rats treated with carbon tetrachloride. Expression of ICAM-1 in HSC was detected by an immunohistochemistry assay and reverse transcription,polymerase chain reaction (RT-PCR). RESULTS: No ICAM-1 was expressed in the freshly isolated HSC of normal rats, but ICAM-1 was found in primary cultures of HSC at day 10 and in secondary cultures of HSC at day 7. Additionally, the intensity of the expression increased over time. Expression of ICAM-1 was observed in freshly isolated HSC from the livers of rats treated with carbon tetrachloride. CONCLUSIONS: Expression of ICAM-1 is related to the activation of HSC, hepatic inflammation and hepatic fibrogenesis. [source]

Ionization-specific prediction of blood,brain permeability

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2009
Kiril Lanevskij
Abstract This study presents a mechanistic QSAR analysis of passive blood,brain barrier permeability of drugs and drug-like compounds in rats and mice. The experimental data represented in vivo log,PS (permeability-surface area product) from in situ perfusion, brain uptake index, and intravenous administration studies. A data set of 280 log,PS values was compiled. A subset of 178 compounds was assumed to be driven by passive transport that is free of plasma protein binding and carrier-mediated effects. This subset was described in terms of nonlinear lipophilicity and ionization dependences, that account for multiple kinetic and thermodynamic effects: (i) drug's kinetic diffusion, (ii) ion-specific partitioning between plasma and brain capillary endothelial cell membranes, and (iii) hydrophobic entrapment in phospholipid bilayer. The obtained QSAR model provides both good statistical significance (RMSE,<,0.5) and simple physicochemical interpretations (log,P and pKa), thus providing a clear route towards property-based design of new CNS drugs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:122,134, 2009 [source]

Peritoneal Cooling May Provide Improved Protection for Uncontrolled Donors After Cardiac Death: An Exploratory Porcine Study

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
A. P. Navarro
Uncontrolled donation after cardiac death (DCD) renal transplantation relies on rapid establishment of organ preservation interventions. We have developed a model of the uncontrolled DCD, comparing current in situ perfusion (ISP) techniques with additional peritoneal cooling (PC). Ten pigs were killed and subjected to a 2 h ischemia period. The ISP group modeled current DCD protocols. The PC group (PC) modeled current protocols plus PC. Two animals were used as controls and subjected to 2 h of warm ischemia. Core renal temperature and microdialysis markers of ischemia were measured. Preservation interventions began at 30 min, with rapid laparotomy and kidney recovery performed at 2 h, prior to machine perfusion viability testing. The final mean renal temperature achieved in the ISP group was 26.3°C versus 16.9°C in the PC group (p = 0.0001). A significant cryopreservation benefit was suggested by lower peak microdialysate lactate and glycerol levels (ISP vs. PC, p = 0.0003 and 0.0008), and the superiority of the PC group viability criteria (p = 0.0147). This pilot study has demonstrated significant temperature, ischemia protection and viability assessment benefits with the use of supplementary PC. The data suggests a need for further research to determine the potential for reductions in the rates of ischemia-related clinical phenomena for uncontrolled DCDs. [source]