Astrocytes play a key role in the protection of neurons from excitotoxicity by taking up excess glutamate and converting it to glutamine via the enzyme glutamine synthetase. In a number of cell types, glucocorticoid hormones induce glutamine synthetase. Glucocorticoids also down-regulate many genes induced by proinflammatory cytokines. As the glucocorticoid receptor has been shown to interact with transcription factors that may also be activated by the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), we hypothesized that IL-1beta or TNF-alpha might oppose the induction of glutamine synthetase by dexamethasone. Primary mouse cortical astrocytes were treated with 10(-7) M dexamethasone and doses of IL-1beta or TNF-alpha ranging from 0.02 to 5 ng/ml or 0.05 to 20 ng/ml, respectively. We found that both cytokines attenuated the dexamethasone induction of glutamine synthetase protein at 24 h and that the effect was dose-dependent. We also found that IL-1beta and TNF-alpha inhibited the induction of glutamine synthetase mRNA by dexamethasone, and that the induction of enzymatic activity was similarly prevented by IL-1beta. As glutamine synthetase can be induced by physiological levels of glucocorticoids, the release of proinflammatory cytokines following acute injury or in neurodegenerative disorders may hinder the ability of astrocytes to protect neurons from excitotoxicity.

Animals↗

PubMed1998

Intraoperative Doppler ultrasound in liver transplantation.

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Adolescent↗

PubMed1997

Metalloprotein analysis by capillary isoelectric focusing.

Capillary isoelectric focusing (cIEF) was used to analyze three metalloproteins: conalbumin, transferrin and metallothionein (MT). Two different ampholyte mixtures were employed that generated linear pH gradients of 3-10 and 5-8. Several different proteins and one peptide with known isoelectric points (pIs) were used to establish linear relationships between peak migration time and pI. These standards were also used as internal markers to estimate peak pI values of the metalloproteins subjected to cIEF. Conalbumin (iron-free) subjected to cIEF with a pH gradient of 3-10 yielded a single major component (pI 7.17). When the protein was saturated with iron (2 Fe3+/mol protein), a shift to lower pI was observed with a major peak (pI 6.24) and a lesser peak (pI 6.09). Mixing iron-free with iron-saturated conalbumin or adding iron to iron-free conalbumin prior to cIEF produced an additional peak (pI 6.68) that was presumed to be conalbumin containing a single iron atom (monoferric form). Human transferrin subjected to cIEF with a pH range of 3-10 gave a similar separation pattern to conalbumin with four major peaks at pI values of 6.25 (apotransferrin), 5.96 (monoferric form), 5.48 and 5.34 (diferric forms). Additional resolution of the molecular forms of both conalbumin and transferrin was achieved using a narrower pH gradient (5-8). Rabbit liver MT subjected to cIEF with a pH gradient of 3-10 gave a complex separation pattern with two prominent peaks (pI values of 3.73 and 3.56) that were presumed to be the fully metal-saturated MT-1 and MT-2 isoforms. When individual MT isoforms (MT-1 and MT-2) were separately subjected to cIEF with a pH gradient of 3-10, heterogeneous peaks with higher pI values (4.12-4.74) were observed. In contrast, horse kidney MT gave a single predominant peak with a pI of 4.09. MT samples could be separated using a pH gradient of 5-8 despite the fact that their apparent pI values were below the limits of the pH gradient established. In general, the heterogeneity observed for conalbumin, transferrin and MT proteins subjected to cIEF reflects the presence or absence of bound metal. Thus, cIEF represents a potentially useful analytical method which can provide information concerning the metal-binding characteristics of these and perhaps other metalloproteins.

Animals↗

PubMed1997

Development of a high-performance capillary isoelectric focusing technique with application to studies of microheterogeneity in chicken conalbumin.

A robust, simple, reproducible isoelectric focusing method using capillary electrophoresis that exhibits high stability, migration time reproducibility and pH linearity over a wide pH gradient was developed. Consecutive runs (over 113 runs) of several proteins and one peptide with isoelectric points (p/s) ranging from 9.45 to 2.75 yielded excellent migration time reproducibility (< 2% R.S.D.). Experimental parameters including buffer aging and capillary-to-capillary variation were thoroughly examined and optimized to improve the migration time reproducibility. The capillary isoelectric focusing (CIEF) method was applied to the analysis of chicken conalbumin (ovotransferrin), an iron-binding protein in egg white. Conalbumin (low iron content) separated into three major components with p/s of 7.2, 6.6 and 6.2. When the protein was saturated with iron (2 Fe/mol), a shift to lower p/s was detected. Chicken serum transferrin subjected to CIEF gave a pattern similar to conalbumin with three p/s of 7.1, 6.6 and 6.1, indicating that it was not fully saturated with iron. Thus, CIEF can be used as a potential analytical method to provide information about the metal-binding properties of specific metalloproteins.

Animals↗

PubMed1997

Variations of the middle and inferior right hepatic vein: application in hepatectomy.

We evaluated the anatomic variations of the middle right hepatic vein (MRHV) and inferior right hepatic vein (IRHV) and their clinical application to the possibility of right subtotal hepatectomy. In 400 of normal livers studied with ultrasound, the IRHV was found to drain segment 6 of the liver and flow into the inferior vena cava (IVC) in 72 (18%) cases. In 22 (5.5%) cases, the MRHV was found to drain segment 5 of the liver and flow into the IVC. The size of the IRHV ranged from 0.1 cm to 0.8 cm with an average of 0.46 cm. For the MRHV, the sizes ranged from 0.1 cm to 0.9 cm with an average of 0.34 cm. In 10/79 (12.6%) cases the IRHV and in 4/ 22 (18.1%) cases the MRHV were bigger than the right hepatic vein (RHV). The distance between the RHV and IRHV ranged from 3 cm to 5 cm with an average of 3.7 cm. The distance between the RHV and MRHV ranged from 3 cm to 3.3 cm with an average of 3.1 cm. A hyperechoic edge, similar to that of the portal vein, was observed at the wall of the hypertrophic IRHV and was 0.3 cm or larger in size. Preoperative delineation of this complex venous anatomy is very important. It provides vital information in the preoperative evaluation needed before performing a right subtotal hepatectomy with preservation of segment 6 or segment 5 of the liver, and with RHV resection. Prior to undertaking a right hepatectomy, clamping the hypertrophic MRHV and IRHV electively may minimize intra-operative blood loss and extrahepatic spread of the malignancy.

Adolescent↗

PubMed1997

Evaluation of liver and brain esterases in the spotted gar fish (Lepisosteus oculatus) as biomarkers of effect in the lower Mississippi River Basin.

Explore the source record for details and available documents.

Acetylcholinesterase↗

PubMed1997

Living related donor liver transplantation.

Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra-operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra-operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n = 10) and glycogen storage disease (n = 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.

Adolescent↗

PubMed1997

Magnetic resonance venography in potential pediatric liver transplant recipients.

Vascular anomalies may be hazardous to liver transplantation, and pre-operative vascular evaluation is important for a safe and successful operation. The purpose of this study was to assess the utility and accuracy of time-of-flight (TOF) magnetic resonance venography (MRV) with three-dimensional (3D) reconstruction as an alternative for conventional catheter angiography in evaluating the portal venous system and inferior vena cava (IVC) in potential pediatric liver transplant recipients. Twenty consecutive cases of small children with biliary atresia were evaluated with TOF MRV with 3D reconstruction by Advantage Window workstation. All 20 cases underwent conventional angiography; two cases received transhepatic portography and three cases received splenoportographic study. The whole MRV examination and filming required less than 30 min. Findings of portal vein and IVC completely agreed with or were superior to the successful catheter angiographic images. The portal vein was occluded in five cases, and patent in fifteen cases which included: twelve hepatopetal flow, two hepatofugal flow and one small caliber portal vein. Varices were found in 18 cases. In the case of the IVC, 18 of them were normal and 2 had congenital abnormalities which included paired vena cava and hypoplasia vena cava with compensatory enlargement of the azygos and hemiazygos systems. Eight of the cases received liver transplantation, and the MRV findings totally correlated with the final anatomy as found intraoperatively. MRV is accurate for evaluating the condition of the portal venous system and IVC, detection, and determining the distribution and extents of the varices. It is a reliable, noninvasive and rapid technique which can be considered as an alternative workup for the invasive angiography and or portography in small children for pre-transplantation evaluation.

Angiography, Digital Subtraction↗