bluuebunny/crossref_metadata_2025 huggingface dataset:
A poly(ethylene) glycolylated peptide for ocular delivery compacts DNA into nanoparticles for gene delivery to post‐mitotic tissues in vivo
Authors: Read Sarah Parker , Cashman Siobhan M. , Kumar‐Singh Rajendra
Published: November 2009

Background

We have previously shown that a novel synthetic peptide for ocular delivery (POD) can efficiently compact DNA and deliver it to cells in vitro. This observation prompted us to develop use of POD as a nonviral vector in vivo.

Methods

POD peptide was modified using poly(ethylene) glycol (PEG‐POD) and used to compact DNA into nanoparticles that were then analysed using electron microscopy, dynamic light scattering, and fluorescent labeling. Transfection efficiency and localization were determined 48 h post‐injection into the subretinal space of the mouse eye using luciferase and LacZ, respectively. Efficiency of ocular transfection was compared to two other PEGylated peptides: PEG‐TAT and PEG‐CK30.

Results

PEG‐POD can compact DNA and form discrete nanoparticles of approximately 136 nm that can penetrate and transduce the retinal pigment epithelium (RPE) in vivo. PEG‐POD significantly increased expression of plasmid DNA by 215‐fold, PEG‐TAT by 56.52‐fold, and PEG‐CK30 by 24.73‐fold relative to DNA injected alone. In all cases β‐galactosidase was observed primarily in the RPE layer after subretinal injection. Electrophysiological analyses of PEG‐POD transduced retina indicates an absence of PEG‐POD‐mediated toxicity. PEG‐POD can protect plasmid DNA from DNaseI digestion, resulting in significant transfection of the lung after intravenous injection in mice.

Conclusions

PEG‐POD was found to significantly increase gene delivery relative to both DNA alone and other pegylated peptides. These findings highlight the use of pegylated peptides, and specifically PEG‐POD, as novel gene delivery vectors. Copyright © 2009 John Wiley & Sons, Ltd.
Biodistribution of gadolinium‐based contrast agents, including gadolinium deposition
Authors: Aime Silvio , Caravan Peter
Published: November 2009

The biodistribution of approved gadolinium (Gd)‐based contrast agents (GBCAs) is reviewed. After intravenous injection GBCAs distribute in the blood and the extracellular space and transiently through the excretory organs. Preclinical animal studies and the available clinical literature indicate that all these compounds are excreted intact. Elimination tends to be rapid and, for the most part, complete. In renally insufficient patients the plasma elimination half‐life increases substantially from hours to days depending on renal function. In patients with impaired renal function and nephrogenic systemic fibrosis (NSF), the agents gadodiamide, gadoversetamide, and gadopentetate dimeglumine have been shown to result in Gd deposition in the skin and internal organs. In these cases, it is likely that the Gd is no longer present as the GBCA, but this has still not been definitively shown. In preclinical models very small amounts of Gd are retained in the bone and liver, and the amount retained correlates with the kinetic and thermodynamic stability of the GBCA with respect to Gd release in vitro. The pattern of residual Gd deposition in NSF subjects may be different than that observed in preclinical rodent models. GBCAs are designed to be used via intravenous administration. Altering the route of administration and/or the formulation of the GBCA can dramatically alter the biodistribution of the GBCA and can increase the likelihood of Gd deposition. J. Magn. Reson. Imaging 2009;30:1259–1267. © 2009 Wiley‐Liss, Inc.
Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients
Authors: Abujudeh Hani H. , Rolls Hillary , Kaewlai Rathachai , Agarwal Sheela , Gebreananya Zelalem A. , Saini Sanjay , Schaefer Pamela W. , Kay Jonathan
Published: November 2009

From May 2007 to January 2008, patients with Stage 3‐5 chronic kidney disease (CKD) undergoing gadobenate dimeglumine (GBD)‐enhanced magnetic resonance (MR) examinations were included in the retrospective investigation. The electronic medical records were reviewed to assess the prevalence of nephrogenic systemic fibrosis (NSF) in renally impaired patients underwent GBD‐enhanced MR examinations. In all, 250 patients (98 men, mean age 72.6 years) were included: 97% of the patients had Stage 3 CKD (estimated GFR 30–59 mL/min/1.73 m2); 37% had been exclusively exposed to GBD. The remaining were exposed to GBD and other gadolinium‐based contrast agents (GBCAs). The mean dose of GBD was 22 mL (standard deviation [SD], 11.2). Including exposure to other GBCAs, the mean cumulative dose of gadolinium was 61 mL (SD, 62.3). A total of 206 patients (82%) had skin examinations following the last GBD administration (mean duration, 108 days). No evidence of suspected or diagnosed NSF was found. In conclusion, on the basis of a retrospective chart review there was no skin evidence of NSF in predominantly Stage 3 CKD patients who were exposed to GBD at an average follow‐up of 108 days, either solely or in combination with other GBCAs. J. Magn. Reson. Imaging 2009;30:1335–1340. © 2009 Wiley‐Liss, Inc.
Gadolinium‐based contrast agents and nephrogenic systemic fibrosis: Why did it happen and what have we learned?
Authors: Weinreb Jeffrey C. , Abu‐Alfa Ali K.
Published: November 2009

This article addresses two questions about gadolinium‐based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF): “Why did it happen” and “What have we learned”? It reviews the events leading to the discovery of an association between NSF and GBCAs. Various factors are elucidated that contributed to the delay between the time when GBCA came into widespread clinical use and a link was made with NSF, including use in renal‐compromised patients, high‐dose magnetic resonance angiography (MRA), lack of documentation and adequate databases, policy and regulatory changes, and an absence of scientific evidence. The authors conclude that the overriding cause was lack of awareness. J. Magn. Reson. Imaging 2009;30:1236–1239. © 2009 Wiley‐Liss, Inc.
High‐throughput method for on‐target performic acid oxidation of MALDI‐deposited samples
Authors: Williams Brad J. , Russell William K. , Russell David H.
Published: November 2009

An information‐rich on‐target performic acid oxidation method, which is compatible with alkylation for differentiation of free cysteine versus disulfide‐containing peptides, is described. On‐target oxidation is achieved using performic acid vapor to oxidize disulfide‐containing peptides and/or small proteins on the matrix‐assisted laser desorption/ionization (MALDI) sample deposits. The on‐target oxidation method is preferred over solution‐phase oxidation methods because (1) less sample handing is required, (2) oxidation throughput is drastically increased and (3) ion suppression effects are reduced because performic acid is not added directly to the MALDI spot. The utility of this method is demonstrated by simultaneous oxidation of multiple MALDI sample deposits containing model disulfide‐linked peptides, intact bovine insulin and a bovine ribonuclease A proteolytic digest. Copyright © 2009 John Wiley & Sons, Ltd.
Acute hyperosmotic stimulus‐induced Fos expression in neurons depends on activation of astrocytes in the supraoptic nucleus of rats
Authors: Yuan Hua , Gao Bei , Duan Li , Jiang Shan , Cao Rong , Xiong Ying‐Fei , Rao Zhi‐Ren
Published: November 2009

Acute hyperosmolarity induced a time‐dependent expression of Fos protein in both neurons and astrocytes of the rat supraoptic nucleus, with peak Fos expresion occurring at 45 min in astrocytes and at 90 min in neurons after hypertonic stimulation in vivo. To determine whether the two cell types were activated separately or in an integrated manner, animals were pretreated with fluorocitrate, a glial metabolic blocker or carbenoxolone, a gap junction blocker followed by an acute hypertonic stimulation similar to that of the controls. Antibodies against glial fibrillary acidic protein, connexin 43, vasopressin, and oxytocin were used in serial sections to identify the cellular elements of the supraoptic nucleus. It was found that interruption of astrocyte metabolism with fluorocitrate significantly reduced Fos protein expression in both astrocytes and neurons, whereas blockage of gap junctions with carbenoxolone clearly reduced Fos protein expression in neurons, but not in astrocytes. These results indicate that both neurons and astrocytes in the rat supraoptic nucleus are involved in regulating osmolarity. Astrocytes are activated first, whereas connexin 43 functional hemichannels in SON astrocytes are required for the subsequent activation of the neurons. © 2009 Wiley‐Liss, Inc.
Periodicities in Indian monsoon rainfall over spectrally homogeneous regions
Authors: Azad Sarita , Vignesh T. S. , Narasimha R.
Published: November 2009

This work presents results of a sharper search for significant periodicities in Indian monsoon rainfall, based on the recognition of the area's meteorological heterogeneity. Towards this end, a quantitative definition of spectral homogeneity is proposed, and the concept is used to classify India into distinct spectrally homogeneous regions (SHR) by two independent methods. The analysis is then carried out for each of the 10 SHRs, which may cut across or be subsets of homogeneous‐rainfall zones defined earlier by various workers based on different criteria. A particularly interesting region is SHR7, the largest spectrally homogeneous cluster identified by both methods, which includes sub‐divisions from west central and peninsular India. The spectrum here shows a significant dip in the frequency band 0.2–0.31 per year, flanked on either side by a rich structure characterised by nearly coincident spectral peaks in all the seven sub‐divisions constituting the region. The significant peaks (confidence level ≥ 99%) in SHR7 are 3.0, 5.7, 10.9, 13.3, 24.0, 30.3 and 60.6 years. The spectral dip is conjectured to be associated with the ENSO (EI Niño‐Southern Oscillation) phenomenon, which occurs on the period scales of 3–5 years and is known to be anti‐correlated with monsoon rainfall. Copyright © 2009 Royal Meteorological Society
Nitrate modifies the assimilation pattern of ammonium and urea in wheat seedlings
Authors: Garnica Maria , Houdusse Fabrice , Zamarreño Angel M , Garcia‐Mina Jose M
Published: November 2009

BACKGROUND: In certain plant species, ammonium or urea nutrition can cause negative effects on plant development which can result in toxic symptoms. Some authors suggest that the presence of nitrate can alleviate these symptoms by increasing ammonium and urea assimilation, avoiding its accumulation. In order to study this hypothesis, wheat (Triticum aestivum L.) seedlings were grown with various nitrogen supplies containing the main nitrogen forms (ammonium, nitrate and urea). Amino acids content and the activity of the three main enzymes involved in nitrogen assimilation (nitrate reductase, glutamine synthetase and urease) were studied.

RESULTS: The application of nitrate along with urea and/or ammonium was not associated with a time‐sustained increase in the activity of glutamine synthetase and urease. Amino acid analysis revealed that nitrate induced changes in amino acid metabolism enhancing its concentration. Likewise the content of protein was also higher in nitrate‐treated plants.

CONCLUSION: These results suggest that the effect of nitrate is compatible with a rapid and transient increase in the activity of glutamine synthetase and urease during the first hour after the onset of treatments. Nevertheless, a possible effect of nitrate reducing ammonium accumulation through the activation of alternative metabolic pathways different from that involving glutamine synthetase cannot be ruled out. Finally, nitrate effects on amino acid concentration indicate that, whereas ammonium assimilation takes place principally in the root, urea and nitrate assimilation occurred in the shoot, under the conditions of the experiment. Copyright © 2009 Society of Chemical Industry
Aqueous extract of Hibiscus sabdariffa L. decelerates acetaminophen‐induced acute liver damage by reducing cell death and oxidative stress in mouse experimental models
Authors: Liu Liang‐Chih , Wang Chau‐Jong , Lee Ching‐Chih , Su Sheng‐Chi , Chen Huei‐Lin , Hsu Jen‐Dong , Lee Huei‐Jane
Published: November 2009

BACKGROUND: Acetaminophen (AAP)‐induced oxidative stress can cause cell death to induce liver damage. The antioxidant effect of Hibiscus sabdariffa L. (HS) was shown in previous studies. In this study the effect of HS extract (HSE) on AAP‐induced liver injury in BALB/c mice was investigated.

RESULTS: In vivo, BALB/c mice were fed orally with 200, 400 or 600 mg kg−1 HSE for 2 weeks and then injected with 1000 mg kg−1 AAP. Pretreatment with HSE decreased lipid peroxidation and increased catalase activity and glutathione level. It also decreased AAP‐induced liver injury, accompanied by decreased expression of pJNK, Bax and tBid in the liver. Additionally, HSE protected BALB/c normal liver cells from AAP‐induced damage in vitro.

CONCLUSION: It has been demonstrated that HSE can protect the mouse liver from AAP‐induced injury and that the protective mechanism might involve decreasing oxidative stress and reducing cell death. Copyright © 2009 Society of Chemical Industry
Direct purification of tanshinones from Salvia miltiorrhiza Bunge by high‐speed counter‐current chromatography without presaturation of the two‐phase solvent mixture
Authors: Wu Dingfang , Jiang Xinhang , Wu Shihua
Published: November 2009

Tanshen, the rhizome of Salvia miltiorrhiza Bunge, is a famous Traditional Chinese Medicine for multiple therapeutic remedies. This work presents the isolation and purification of tanshinone I and tanshinone IIA from the extract of the rhizome of S. miltiorrhiza by using high‐speed counter‐current chromatography (CCC) without presaturation of the two‐phase solvent mixture. The CCC method combines the results of CCC solvent system selection and components analyses of solvent mixture by GC, and thus it is possible to add accurately each individual solvent to prepare single saturated solvent phase without presaturation. The optimum CCC solvent system is a system of hexane–ethyl acetate–ethanol–water (8:2:7:3, v/v), which has been determined by usual solvent system selection and CCC runs. As a result, over 98% pure tanshinone IIA and over 94% pure tanshinone I have been obtained by using less solvent volume. Their structures have been identified by ESI‐MS, NMR spectra.
Application of MEKC to the monitoring of atrazine sorption behaviour on soils
Authors: Lima Diana L. D. , Erny Guillaume L. , Esteves Valdemar I.
Published: November 2009

Measuring interactions between soils and xenobiotics is critical to assess the threat to water resources posed by potentially harmful chemicals. Such studies are done via batch experiments where the chemical of interest is incubated with the soil for a long period of time. However, the analysis of the remaining concentration in the aqueous phase is often troublesome, due to dissolved organic matter that can interfere with the analysis. Thus, for such application a lengthy sample clean‐up is often needed prior to analysis. The aim of this work was to develop an alternative approach to monitor atrazine using MEKC. A buffer of 10 mM NaH2PO4 and 50 mM SDS was used to separate atrazine and soil organic matter in less than 7 min. Samples were injected without any pre‐treatment leading to a significantly lower total analysis time (sample clean‐up, column conditioning, separation) than HPLC. After full optimisation, good repeatability of retention time (RSD<1%) and peak areas (RSD<3%) was achieved as well as a good linearity (r2=0.9994) and relatively low LOD (0.26 mg/L). The method was applied to study the sorption of atrazine to a soil sample using batch equilibrium technique.
Outcome of Recurrent Hepatitis C Virus After Liver Transplantation in a Randomized Trial of Tacrolimus Monotherapy Versus Triple Therapy
Authors: Manousou Pinelopi , Samonakis Dimitrios , Cholongitas Evangelos , Patch David , O'Beirne James , Dhillon Amar P. , Rolles Keith , McCormick Aiden , Hayes Peter , Burroughs Andrew K.
Published: November 2009

Less potent immunosuppression is considered to reduce the severity of hepatitis C virus (HCV) recurrence after liver transplantation. An optimal regimen is unknown. We evaluated tacrolimus monotherapy versus triple therapy in a randomized trial of 103 first transplants for HCV cirrhosis. One hundred three patients who underwent transplantation for HCV were randomized to tacrolimus monotherapy (n = 54) or triple therapy with tacrolimus, azathioprine, and steroids (n = 49), which were tapered to zero by 3 to 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. The time to reach Ishak stage 4 was the predetermined endpoint. All factors documented in the literature as being associated with HCV recurrence and the allocated treatment were evaluated for reaching stage 4 and HVPG ≥ 10 mm Hg. No significant preoperative, perioperative, or postoperative differences, including the frequency of biopsies between groups, were found. During a mean follow-up of 53.5 months, 9 monotherapy patients and 6 triple therapy patients died, and 5 monotherapy patients and 4 triple therapy patients underwent retransplantation. Stage 4 fibrosis was reached in 17 monotherapy patients and 10 triple therapy patients (P = 0.04), with slower fibrosis progression in the triple therapy patients (P = 0.048). Allocated therapy and histological acute hepatitis were independently associated with stage 4 fibrosis. HVPG increased to ≥10 mm Hg more rapidly in monotherapy patients versus triple therapy patients (P = 0.038). In conclusion, long-term maintenance immunosuppression with azathioprine and shorter term prednisolone with tacrolimus in HCV cirrhosis recipients resulted in a slower onset of histologically proven severe fibrosis and portal hypertension in comparison with tacrolimus alone, and this was independent of known factors affecting fibrosis. Liver Transpl 15:1783-1791, 2009. © 2009 AASLD.
Evaluation of the Microcirculatory Disturbance of Biliary Ischemia After Liver Transplantation with Contrast-Enhanced Ultrasound
Authors: Ren Jie , Lu Ming-De , Zheng Rong-Qin , Lu Min-Qiang , Liao Mei , Mao Yong-Jiang , Zheng Zhi-Juan , Lu Yan
Published: November 2009

The aim of this study was to determine the efficacy of contrast-enhanced ultrasound for depicting the perfusion of hilar bile ducts in ischemic-type biliary lesions after orthotopic liver transplantation. Thirteen transplant recipients with ischemic-type biliary lesions and 12 patients without ischemic-type biliary lesions underwent ultrasound examinations after the injection of 1.5 mL of an intravenous contrast agent. The enhancement of the hilar bile duct wall in the arterial, portal venous, and late phases was qualitatively graded as higher, equal, lower, or none with respect to that of the adjacent liver parenchyma. No or low contrast enhancement was seen in 10 of 13 patients (76.90%) with biliary ischemia, whereas increased contrast enhancement with respect to the normal liver parenchyma was found in all 12 patients without biliary ischemia. The difference in the enhancement patterns between the 2 groups was significant (P = 0.0001). In conclusion, contrast-enhanced ultrasound is a new imaging modality to depict perfusion of the hilar bile duct. No or low contrast enhancement of the bile duct wall in the arterial phase may reflect the microcirculatory disturbance of biliary ischemia and may contribute to its early diagnosis. Liver Transpl 15:1703-1708, 2009. © 2009 AASLD.
Improvement of Renal Function After the Switch from a Calcineurin Inhibitor to Everolimus in Liver Transplant Recipients with Chronic Renal Dysfunction
Authors: Castroagudín Javier F. , Molina Esther , Romero Rafael , Otero Esteban , Tomé Santiago , Varo Evaristo
Published: November 2009

Chronic renal dysfunction is a frequent and severe complication in solid-organ transplant recipients. Calcineurin inhibitors (CNIs) are the main pathogenic factors of renal dysfunction. Switching from CNIs to nonnephrotoxic drugs, such as mammalian target of rapamycin inhibitors (everolimus and sirolimus), can improve renal function in these patients, but available data about the efficacy and safety of everolimus in liver transplant recipients are scarce. Twenty-one liver transplant recipients (19 males, mean age = 60.6 ± 7.8 years) with chronic renal dysfunction (creatinine ≥ 1.5 mg/dL) were prospectively included. The basal creatinine values were 1.79 ± 0.39 mg/dL (range = 1.50-2.90 mg/dL). The basal creatinine clearance, evaluated with the Cockroft-Gault formula, was 54.64 ± 12.47 mL/minute. Everolimus was initiated at a dosage of 0.75 mg twice daily, with target levels of 3 to 8 ng/mL. The withdrawal of CNIs was initiated after the target levels of everolimus were reached. Periodic controls of the weight, arterial pressure, liver function tests, serum creatinine, everolimus levels, proteinuria, creatinine clearance, and glomerular filtration rate at days 30, 90, 180, and 360 were made. After a median follow-up of 19.8 months, the respective creatinine values at 30, 90, 180, and 360 days were 1.68 ± 0.40 (P = 0.012 with respect to basal values), 1.67 ± 0.34 (P = 0.107), 1.70 ± 0.41 (P = 0.521), and 1.57 ± 0.30 mg/dL (P = 0.047). The respective creatinine clearance values at 30, 90, 180, and 360 days were 58.64 ± 16.50 (P = 0.013 with respect to basal values), 59.49 ± 13.27 (P = 0.028), 59.82 ± 16.83 (P = 0.124), and 64.46 ± 16.79 mL/minute (P = 0.025). CNIs were withdrawn in 20 recipients (95.2%). Rejection was not detected in any case. In conclusion, the application in liver transplant recipients with chronic renal dysfunction of an immunosuppressive protocol with everolimus and the withdrawal of CNIs was associated with an initial improvement of renal function tests without an increase in the risk of rejection. Liver Transpl 15:1792-1797, 2009. © 2009 AASLD.
Living Donor Liver Transplantation for Glycogen Storage Disease Type Ib
Authors: Kasahara Mureo , Horikawa Reiko , Sakamoto Seisuke , Shigeta Takanobu , Tanaka Hideaki , Fukuda Akinari , Abe Kiyomi , Yoshii Keisuke , Naiki Yasuhiro , Kosaki Rika , Nakagawa Atsuko
Published: November 2009

Glycogen storage disease type 1b (GSD-1b) is due to an autosomal recessive inborn error of carbohydrate metabolism caused by defects in glucose-6-phosphatase translocase. Patients with GSD-1b have severe hypoglycemia with several clinical manifestations of hepatomegaly, obesity, a doll-like face, and neutropenia. Liver transplantation has been indicated for severe glucose intolerance. This study retrospectively reviewed 4 children with a diagnosis of GSD-1b who underwent living-donor liver transplantation (LDLT). Between November 2005 and June 2008, 96 children underwent LDLT with overall patient and graft survival of 92.3%. Of these, 4 (4.2%) were indicated for GSD-1b. All patients are doing well with an excellent quality of life because of the stabilization of glucose intolerance, decreased hospital admission, and normalized neutrophil count. LDLT appears to be a feasible option and is associated with a better quality of life for patients with GSD-1b. Long-term observation may be necessary to collect sufficient data to confirm the efficacy of this treatment modality. Liver Transpl 15:1867-1871, 2009. © 2009 AASLD.
Ethical Perspectives on Living Donor Organ Transplantation in Asia
Authors: Concejero Allan M. , Chen Chao-Long
Published: November 2009

Live donors are a continuing source of organ grafts for solid organ transplantation in Asia. Ethical issues surrounding the development of living donor organ transplantation in Eastern countries are different from those in Western countries. Donor safety is still the paramount concern in any donor operation. Issues on organ trafficking remain societal concerns in low-income nations. Religion, cultural background, economic prerogatives, and timely legislation contribute to the social acceptance and maturation of organ donation. Liver Transpl 15:1658-1661, 2009. © 2009 AASLD.
Liver Transplantation and Pancreatic Resection
Authors: Stauffer John A. , Steers Jeffery L. , Bonatti Hugo , Dougherty Marjorie K. , Aranda-Michel Jaime , Dickson Rolland C. , Harnois Denise M. , Nguyen Justin H.
Published: November 2009

Liver transplantation may occasionally be indicated in patients with unique clinical scenarios. Little is known regarding the outcomes of patients who have had a pancreatic resection prior to, in combination with, or after liver transplantation. A retrospective review of all patients undergoing liver transplantation from March 1998 to March 2008 identified 17 patients who also underwent pancreatic resection. An additional literature review was performed. Five underwent pancreatic resection prior to liver transplantation (1.7, 3.6, 3.8, 6.8, and 8.1 years), another 9 underwent pancreatic resection together with liver transplantation, and 3 underwent pancreatic resection after liver transplantation (2.2, 2.6, and 3.8 years). Indications for pancreatic resection included cholangiocarcinoma (n = 6), neuroendocrine tumor (n = 5), pancreatic cancer (n = 2), gastrointestinal stromal tumor (n = 1), periampullary adenocarcinoma (n = 1), duodenal adenomas (n = 1), and benign pancreatic mass (n = 1). Indications for liver transplantation were metastatic neuroendocrine tumor disease (n = 5), primary sclerosing cholangitis (n = 5), hepatitis C virus (n = 2), metastatic gastrointestinal stromal tumor (n = 1), Klatskin tumor (n = 1), alcohol cirrhosis (n = 1), alpha-1 antitrypsin deficiency (n = 1), and chemotherapy-induced cirrhosis (n = 1). One patient died intraoperatively, 7 patients died of tumor recurrence, 2 patients died from transplant complications, and 7 patients are still alive. Pancreatic resection-related complications included 4 pancreatic fistulas. A literature review confirmed liver transplantation/pancreatic resection-related complications. In conclusion, liver transplantation and pancreatic resection remain uncommon, and a good outcome can be achieved. Recurrence of malignant disease is the main factor limiting survival, and specific morbidity may be related to pancreatic resection and liver transplantation. Liver Transpl 15:1728-1737, 2009. © 2009 AASLD.
Effect of Ischemic Preconditioning on the Genomic Response to Reperfusion Injury in Deceased Donor Liver Transplantation
Authors: Jassem Wayel , Fuggle Susan , Thompson Richard , Arno Matthew , Taylor Jennifer , Byrne Jane , Heaton Nigel , Rela Mohamed
Published: November 2009

Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained. Total RNA was extracted and hybridized to GeneChip microarrays, and the findings were validated with real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). IP livers showed less of an increase in aspartate aminotransferase after transplantation. A microarray analysis of the IR group showed increased expression of 57 genes mainly involved in cell death, inflammation and immune response, stress, and modulation of the cell cycle. The IP group showed attenuation of the expression of these genes after reperfusion. Additionally, IP led to increased expression of 43 genes involved in growth and maintenance, cell-cycle regulation, proliferation, and development. The expression of the 12 most significant genes was validated in all patients with real-time qRT-PCR, and the fold changes of a number of genes correlated with clinical parameters and graft outcomes. IP protection of liver allografts was associated with a reduction in the expression of immune response genes and promotion of those involved in protection and repair. Liver Transpl 15:1750-1765, 2009. © 2009 AASLD.
Recurrent Disease Following Liver Transplantation for Nonalcoholic Steatohepatitis Cirrhosis
Authors: Malik Shahid M. , deVera Michael E. , Fontes Paulo , Shaikh Obaid , Sasatomi Eizaburo , Ahmad Jawad
Published: November 2009

Recurrence of the original disease following liver transplantation is not uncommon and can lead to graft failure. There are limited data on recurrent fatty liver disease following liver transplantation. The aim of this study was to determine the incidence of recurrent fatty liver disease in patients with biopsy-proven nonalcoholic steatohepatitis, its effect on survival, and whether there are any predictive factors for recurrence. We analyzed patients undergoing liver transplantation for nonalcoholic steatohepatitis cirrhosis from 1997 to 2008 at a single center. Patients undergoing transplantation for cholestatic disease, alcohol, hepatitis C, or cryptogenic cirrhosis were controls. Ninety-eight patients underwent transplantation for nonalcoholic steatohepatitis cirrhosis. Recurrent fatty liver disease was seen in 70%, 25% had recurrent nonalcoholic steatohepatitis, and 18% had stage II/IV or greater fibrosis at a mean of 18 months. No patients with recurrent nonalcoholic steatohepatitis developed graft failure or required retransplantation at a follow-up of 3 years. No recipient or donor factors were associated with disease recurrence, although patients with recurrent nonalcoholic steatohepatitis had a higher incidence of diabetes, weight gain, and dyslipidemia at the time of diagnosis of recurrence. One-third of patients with recurrent nonalcoholic steatohepatitis had normal liver enzymes at the time of diagnosis post-transplantation. In conclusion, recurrent fatty liver disease is common following liver transplantation for nonalcoholic steatohepatitis cirrhosis but does not lead to early allograft failure. Recurrent nonalcoholic steatohepatitis can occur despite normal liver enzymes, and features of metabolic syndrome are associated with disease recurrence. Liver Transpl 15:1843-1851, 2009. © 2009 AASLD.
Increased Risk of Graft Loss from Hepatic Artery Thrombosis After Liver Transplantation with Older Donors
Authors: Stewart Zoe A. , Locke Jayme E. , Segev Dorry L. , Dagher Nabil N. , Singer Andrew L. , Montgomery Robert A. , Cameron Andrew M.
Published: November 2009

Hepatic artery thrombosis (HAT) is the most common vascular complication after liver transplantation; it has been reported to occur in 2% to 5% of liver transplant recipients. Most reports of HAT in the literature describe single-center series with small numbers of patients and lack the power to definitively identify nontechnical risk factors. We used the United Network for Organ Sharing database of adult deceased donor liver transplants from 1987 to 2006 to identify 1246 patients with graft loss from HAT. Univariate and multivariate regression analyses were performed to identify donor and graft risk factors for HAT-induced graft loss. Although most donor predictors of HAT-induced graft loss were surrogates for vessel size, donor age > 50 years was also a significant predictor of graft loss from HAT (relative risk = 1.45, P < 0.001). Furthermore, the risk of graft loss from HAT increased progressively with each decade of donor age > 50 years, such that a 61% increased risk of HAT-related graft loss (relative risk = 1.61, P < 0.001) was associated with donor age > 70 years. A separate analysis of risk factors for early HAT graft loss (≤90 days) and late HAT graft loss (> 90 days) found that older donor age was associated with increased late HAT graft loss. These findings are of interest in an era of ongoing organ shortages requiring maximum utilization of potential allografts and increasing allocation of older allografts. Liver Transpl 15:1688-1695, 2009. © 2009 AASLD.
Predictive Value of Frozen-Section Analysis in the Histological Assessment of Steatosis Before Liver Transplantation
Authors: Fiorentino Michelangelo , Vasuri Francesco , Ravaioli Matteo , Ridolfi Lorenza , Grigioni Walter Franco , Pinna Antonio Daniele , D'Errico-Grigioni Antonia
Published: November 2009

Histological quality assessment of donated livers is a key factor for extending the cadaveric donor pool for liver transplantation. We retrospectively compared frozen-section analysis with routine histological permanent slides and the outcomes of grafts in liver biopsies from 294 candidate donors. The κ concordance coefficient of agreement between frozen-section analysis and routine histological analysis was very good for macrosteatosis (κ = 0.934), microsteatosis (κ = 0.828), and total steatosis (κ = 0.814). The correlation between the mean amounts of macrosteatosis, microsteatosis, and total steatosis in frozen and permanent sections was also significant (P < 0.001, Spearman's test). Macrosteatosis and microsteatosis were overestimated to >30% in 4 of 32 cases (12.5%) and in 23 of 62 cases (37.1%), respectively. The only 2 histological parameters of frozen sections able to predict graft dysfunction within 7 days of transplantation were macrosteatosis and total steatosis (P = 0.018 and P = 0.015, respectively, Mann-Whitney test). None of the other histopathological features evaluated in frozen sections, including portal inflammation, lobular necrosis, myointimal thickening, biliocyte regression, cholestasis, hepatocellular polymorphism, lipofuscin storage, and fibrous septa, were significantly correlated with the graft outcome. The frozen-section histological evaluation of biopsies from cadaveric liver donors is an accurate, time-effective, and predictive method for the assessment of graft suitability. Liver Transpl 15:1821-1825, 2009. © 2010 AASLD.
Plasma Cell Hepatitis in Hepatitis C Virus Patients Post-Liver Transplantation
Authors: Ward Stephen C. , Schiano Thomas D. , Thung Swan N. , Fiel Isabel M.
Published: November 2009

Plasma cell hepatitis (PCH) is characterized by plasma cell infiltration seen in allografts of patients who underwent liver transplantation (LT) for conditions other than autoimmune hepatitis. We identified 40 PCH patients who underwent LT for hepatitis C virus (HCV) by searching our pathology database (1994-2006) for the keywords liver allograft, lymphoplasmacytic, and plasma cell(s). We selected 2 control patients who received LT for HCV for each PCH case. The control patients were matched according to date of LT and availability of biopsy material at the time interval to development of PCH in PCH patients. Explant and post-LT biopsy slides were blindly reviewed by 2 liver pathologists and the severity of the plasma cell infiltrate was scored. A score of 3 (plasma cells composing >30% of the infiltrate) defined PCH in allograft biopsies. Five random areas of dense inflammation were also examined in explant livers and the highest score was used. Poor outcome was defined as death or advanced fibrosis (stage ≥ 4 of 6). We found that PCH patients were more likely to have worse outcomes than control patients (65% versus 40%, P < 0.01), including increased mortality (50% versus 30%, P < 0.05). Kaplan-Meier survival analysis showed significantly worse survival for PCH patients from 4 to 10 years post-LT (P < 0.05). Explants from 40% of PCH patients had a score of 3 compared to 18% of control patients (P < 0.01). We found that the development of PCH is associated with poor outcome in patients undergoing LT for HCV. The association of significant plasma cell infiltrates in native livers of HCV patients developing PCH suggests that some patients may have a predisposition to developing PCH. Liver Transpl 15:1826-1833, 2009. © 2009 AASLD.
Posttransplant Metabolic Syndrome
Authors: Pagadala Mangesh , Dasarathy Srinivasan , Eghtesad Bijan , McCullough Arthur J.
Published: November 2009

With increasing survival after orthotopic liver transplantation (OLT), metabolic syndrome and its individual components, including diabetes mellitus, hypertension, dyslipidemia, and obesity, are increasingly being identified and contributing to cardiovascular complications and late morbidity and mortality. The prevalence of posttransplant metabolic syndrome (PTMS) and its individual components has been found to be higher post-OLT versus a comparable population without OLT. The development of nonalcoholic fatty liver disease (NAFLD) after liver transplantation for non-NAFLD cirrhosis is also being increasingly recognized. A number of predictors have been identified as potential risk factors related to these complications. The pretransplant risk factors include immunosuppression, a higher age at transplant, male gender, a history of smoking, the pretransplant body mass index, pre-OLT diabetes, the etiology of the underlying liver disease that resulted in OLT (hepatitis C, cryptogenic cirrhosis, or alcohol), an increased donor body mass index, and marital status. Although there is an increased risk of cardiovascular events, rejection, and infection among patients with PTMS, the overall impact on long-term survival and mortality remains inconclusive. Strategies to reduce the development of metabolic syndrome after transplantation should include lifestyle modifications involving alterations in diet and increased physical activity. Additional measures that may be potentially beneficial include the use of lipid-lowering agents, the optimal control of blood glucose, and the use of tacrolimus instead of cyclosporine. Liver Transpl 15:1662-1670, 2009. © 2009 AASLD.
Liquid Crystal Alignment Properties of Poly‐(3‐thiopheneacetate)/Dialkyldimethylammonium Complexes
Authors: Yoon Young‐Sik , Kang Hyo , Kim Byoung Gak , Lee Jong‐Chan
Published: November 2009

Liquid crystal alignment properties were investigated in liquid crystal (LC) cells fabricated with poly(3‐thiopheneacetate)/dialkyldimethylammonium (PTA‐Cn) complexes, where n is the number of carbon atoms in the alkyl groups in dialkyldimethylammonium bromide. Homeotropic LC alignment was observed in PTA‐Cn LC cells containing long alkyl groups (n = 14, 16, 18) with high pretilt angles close to 90°. Homeotropic LC alignment was observed from prepared LC cell made from PTA‐C12 film, while the homeotropic LC alignment was gradually changed to random alignment within 10 min. LC cells fabricated from PTA‐C10 always showed random alignment behavior. The surface orientational order parameters of the alkyl groups of PTA‐Cn films were estimated by near edge X‐ray absorption fine structure (NEXAFS) spectroscopy, producing values of 0.040, 0.111, 0.153, 0.151, and 0.170 for PTA‐C10, PTA‐12, PTA‐14, PTA‐16, and PTA‐18, respectively. Therefore, homeotropic LC alignment behavior correlated well with the order of alkyl groups on the complex surface.

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Amphiphilic Hyperbranched Polymers Containing Two Types of β‐Cyclodextrin Segments: Synthesis and Properties
Authors: Tian Wei , Fan Xiao‐Dong , Kong Jie , Liu Yu‐Yang , Zhang Wei‐Hong , Cheng Guang‐Wen , Jiang Min
Published: November 2009

Amphiphilic hyperbranched polymers carrying two types of β‐cyclodextrin groups including ionic and covalent bonding were synthesized via atom transfer radical polymerization and immobilization reaction. Their inclusion capabilities for single or double‐guest molecules were investigated by UV‐visible spectroscopy. Using Chlorambucil and Lonidamine as the double model drugs, their encapsulation efficiencies indicate that these polymers possess the capabilities of high drug‐loading. Furthermore, the release behaviors of these polymers were studied via UV‐visible spectroscopy. The results indicate that they can slow the release rate of double model drugs. Varying the pH values of environment or regulating their shell layer structures can control the release behaviors of double model drugs.

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Construction and Properties of Hydrophobic Association Hydrogels with High Mechanical Strength and Reforming Capability
Authors: Jiang Guoqing , Liu Chang , Liu Xiaoli , Zhang Guohui , Yang Meng , Liu Fengqi
Published: November 2009

Hydrophobic association hydrogels (HA‐gels) with almost ideal properties were successfully prepared by micellar copolymerization, and the associated micelles acted as physical cross‐linking points in the network of HA‐gels. HA‐gels exhibit exceptional mechanical properties and transparency. However, the most striking properties are that HA‐gels possess the capability of self‐healing and remolding, which is mainly due to the dissociation and re‐association process of the associated micelles. Dried‐gels, which were prepared by stretching HA‐gels to a certain elongation for a period of time in the air, can be used as shrinkable or thermal sensitivity materials. HA‐gels have a broad selectivity for components, so we have synthesized HA‐gels with variously available properties by changing a corresponding component: thermoresponsive HA‐gels, nanosphere‐composite HA‐gels, and fluorescent HA‐gels. Therefore, we are sure that HA‐gels will be widely used in various fields, such as biology, medication, sensors, optics, and oil exploitation.

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Droplet Microfluidics for Fabrication of Non‐Spherical Particles
Authors: Shum Ho Cheung , Abate Adam R. , Lee Daeyeon , Studart André R. , Wang Baoguo , Chen Chia‐Hung , Thiele Julian , Shah Rhutesh K. , Krummel Amber , Weitz David A.
Published: November 2009

We describe new developments for controlled fabrication of monodisperse non‐spherical particles using droplet microfluidics. The high degree of control afforded by microfluidic technologies enables generation of single and multiple emulsion droplets. We show that these droplets can be transformed to non‐spherical particles through further simple, spontaneous processing steps, including arrested coalescence, asymmetric polymer solidification, polymerization in microfluidic flow, and evaporation‐driven clustering. These versatile and scalable microfluidic approaches can be used for producing large quantities of non‐spherical particles that are monodisperse in both size and shape; these have great potential for commercial applications.

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Polymer Brushes via Controlled, Surface‐Initiated Atom Transfer Radical Polymerization (ATRP) from Graphene Oxide
Authors: Lee Sun Hwa , Dreyer Daniel R. , An Jinho , Velamakanni Aruna , Piner Richard D. , Park Sungjin , Zhu Yanwu , Kim Sang Ouk , Bielawski Christopher W. , Ruoff Rodney S.
Published: November 2009

A method for growing polymers directly from the surface of graphene oxide is demonstrated. The technique involves the covalent attachment of an initiator followed by the polymerization of styrene, methyl methacrylate, or butyl acrylate using atom transfer radical polymerization (ATRP). The resulting materials were characterized using a range of techniques and were found to significantly improve the solubility properties of graphene oxide. The surface‐grown polymers were saponified from the surface and also characterized. Based on these results, the ATRP reactions were determined to proceed in a controlled manner and were found to leave the structure of the graphene oxide largely intact.

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Mathematical Modeling of PAG‐ and NIPAM‐Based Polymer Gel Dosimeters Contaminated by Oxygen and Inhibitor
Authors: Koeva Valeria I. , Daneshvar Shahab , Senden Robert J. , Imam A. H. M. , Schreiner L. John , McAuley Kimberley B.
Published: November 2009

A mathematical model for crosslinking copolymerization of acrylamide (or NIPAM) and N,N'‐methylenebisacrylamide is extended to account for contamination by oxygen and the inhibitor MEHQ. This model improves basic understanding of interactions among oxygen, MEHQ and polymerization reactions in gel dosimeters that are used to verify radiation doses delivered by cancer treatment equipment. Improved parameter estimates result in a good match between model predictions and data. The model predicts that a larger absorbed dose will be required to overcome the oxygen inhibition with increasing oxygen contamination, in agreement with experimental data. The model also predicts that MEHQ, in the absence of oxygen, has almost no influence on dosimeter response.

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Investigation of Thermal Expansion of Polyimide/SiO2 Nanocomposites by Molecular Dynamics Simulations
Authors: Komarov Pavel V. , Chiu Yu‐Tsung , Chen Shih‐Ming , Reineker Peter
Published: November 2009

In this paper, an atomistic model for PI/SiO2 hybrid nanocomposites was designed for the investigation of physical properties of this material on the base of molecular dynamics simulations. The thermal properties of a reference pure PI matrix in the temperature range of 300–650 K were first investigated. The results for the CTE and the glass transition temperature showed good agreement with the experimental data. Then, the thermal expansion of the model of PI/silica composite material with different SiO2 fractions was investigated at normal conditions. The CTE of the composite model decreases with the increase in the SiO2 content in agreement with experimental studies. The results show a threshold for the SiO2 loading beyond which the material model exhibits ultra‐low thermal expansion.

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A novel tumor suppressor gene RhoBTB2 (DBC2): Frequent loss of expression in sporadic breast cancer
Authors: Mao Haiting , Qu Xun , Yang Yongmei , Zuo Wenshu , Bi Ye , Zhou Chengjun , Yin Haipeng , Deng Biping , Sun Jintang , Zhang Lining
Published: November 2009

RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cancer patients and normal controls and cell samples from cell lines were collected and reverse transcription (RT)‐PCR was used to monitor the presence of RhoBTB2 mRNA. The protein expression of RhoBTB2 was detected by immunohistochemical staining. Cumulative survival time was assessed by the Kaplan–Meier method and Cox regression model. We discovered that RhoBTB2 expression was lacking in a breast ductal epithelial carcinoma cell line T‐47D but was expressed in other types of tumor cell lines and normal tissues we tested. The results from tissue samples showed that RhoBTB2 was absent in 60% of breast cancers on both the mRNA and protein level. The results from RT‐PCR were completely uniform with those from immunohistochemistry. We demonstrated that loss of RhoBTB2 more frequently occurred in postmenopausal patients of age ≥50 yr old and in patients with infiltrating ductal carcinoma of the breast. The prognostic value of RhoBTB2 in breast cancers also be assessed by a long‐term follow‐up investigation and we found that patients with RhoBTB2‐negative breast cancer were linked to poor clinical prognosis. Therefore, the loss of RhoBTB2 expression is a common occurrence in breast cancers and it is an important factor in the development and prognosis of sporadic breast cancer. © 2009 Wiley‐Liss, Inc.