A Cooperative Industry - Government Woodland Caribou Research Program in Northeastern Alberta

Rapid development of large scale logging and increasingly intensive petroleum exploration and development in northeastern Alberta prompted the establishment of a cooperative research program to investigate various aspects of woodland caribou (Rangifer tarandus caribou) biology. The ultimate goal of the program is to develop an effective plan that will ensure the long term survival of caribou while allowing for renewable and non-renewable resource development. There are three parts to the program. Part I began early in 1991 and makes use of conventional radio telemetry as a means of recording various parameters of general caribou biology. The study area encompasses approximately 4000 km2 of low relief, boreal mixedwood forest. Preliminary results from 2500 radio locations (involving 50 individuals) indicate that woodland caribou inhabiting the study area are non-migratory and are strongly associated with some of the more scarce peatland forest types present in the area. Investigations to document the basic biology and ecology will continue for another two years. Part II began in early 1993 as a part of a two-year investigation into the disturbance effects of petroleum exploration and development on caribou movements and behaviour. One objective of this study is to develop a predictive model useful in determining the cumulative effects of varying intensities of disturbance on caribou. Part III began in early 1994 with a proposed three-year investigation to determine the mechanism of spatial and temporal separation of caribou and moose in the study area. These relationships may indicate the means by which caribou minimize the impact of wolf predation on their populations in northeastern Alberta. Results will be applied to industrial land use and specifically to large scale forest harvesting planned for the area. The research program is supported through cooperative funding contributed by 24 petroleum companies, 1 forest company, 2 peat companies and the Alberta Departments of Environmental Protection and Energy. The research aspect of the program has been developed and implemented by staff of the University of Alberta, Alberta-Pacific Forest Industries, the Alberta Fish and Wildlife and Forest Services and the Alberta Environmental Centre. The program also incorporates a public information and liaison function. Newsletters, information videos, brochures and public consultation are the means used to accomplish this task

Helical Peptides Derived from Lactoferrin Bind Hepatitis C Virus Envelope Protein E2

Hepatitis C virus is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma infecting more than 170 million people. Hepatitis C virus envelope 2 glycoprotein (E2) binds several cell‐surface molecules that act as receptor candidates mediating hepatitis C virus entry into hepatocytes. Peptides derived from human lactoferrin have been shown to bind hepatitis C virus‐E2 protein thereby preventing hepatitis C virus entry in cultured hepatocytes. In this study, starting from a 33‐residue human lactoferrin‐derived peptide, a number of biotin‐linked α‐peptides were synthesized and investigated for their E2 protein binding activity. E2 protein from hepatitis C virus genotype 1b was expressed in 293 human embrionic kidney cells and purified using affinity chromatography. A biotin‐streptavidin based binding assay was developed to determine the binding affinity of the synthetic peptides for E2 protein. Two of the peptides bound E2 specifically with submicromolar to low micromolar affinity [equilibrium dissociation constant (Kd) of 0.569 and 28.8 μm]. Further, these two peptides had the highest helical content in solution as observed by circular dichroism spectroscopy, suggesting that binding affinity increases with increase in helicity. These results have provided new lead peptides for future investigations of hepatitis C virus entry inhibitors that may provide an interesting approach to prevent hepatitis C virus infectivity

Winter Habitat Use by Wolves, Canis lupus, in Relation to Forest Harvesting in West-central Alberta

Forested landscapes in west-central Alberta are facing increased pressures from forest harvesting and other land-use activities, which may alter the movements and distribution of Wolves and ungulates. Information on habitat use by Wolves in logged forests is scarce, potentially limiting effective land-use planning in the boreal forest. Nine Wolves, from four Wolf packs, were fitted with GPS radiocollars in the Rocky Mountain foothills, near Grande Cache, Alberta (2000-2001). We found Wolves did not use the landscape randomly, but rather exhibited a significant preference for non-forested natural habitats (shrubs, water), relative to their availability. Within forest habitats, Wolves used cutblocks proportionately more than unharvested forest and non-forested anthropogenic habitats (pipelines, clearings); however, selection of forest cutblocks was not statistically significant. We found no evidence that Wolves preferred or avoided forest cutblock edges. Wolf pack territories contained various levels of timber harvesting, but most areas were still in the early stages of harvest. Nevertheless, these areas have been allocated for large-scale harvesting. Understanding the potential responses of Wolves to rapidly changing landscape mosaics poses a significant challenge to researchers and managers, but such information is important to informing future land-management and conservation strategies for boreal forest Wolf-prey systems

The place of downstaging for hepatocellular carcinoma

In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation.While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word “downstaging” designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed.The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature

Pack Size of Wolves, Canis lupus, on Caribou, Rangifer tarandus, Winter Ranges in Westcentral Alberta

We studied pack size of Wolves (Canis lupus) on Woodland Caribou (Rangifer tarandus caribou) winter ranges in westcentral Alberta. These Caribou winter ranges are experiencing increasing pressure from resource extraction industries (forestry, energy sector) and concerns have been raised regarding increased Wolf predation pressure on Caribou in conjunction with landscape change. Thirty-one Wolves, from eight Wolf packs, were fitted with radiocollars on two Caribou winter ranges in the Rocky Mountain foothills, near Grande Cache, Alberta (2000-2001). There was a mean of 8.2 Wolves/pack and between 30 and 39 Wolves on each of the RedRock/Prairie Creek and Little Smoky Caribou ranges. The average pack size of Wolves in this region does not appear to have increased over that recorded historically, but the range (5-18) in the number of Wolves per pack varied considerably over our study area. Wolves preyed predominately on Moose (Alces alces), averaging one Moose kill every three to five days. There was some indication that pack size was related to prey size, with the smallest pack preying on Deer (Odocoileus spp.). It was clear that Caribou could not be the primary prey for Wolves, due to their low numbers, and relative to the pack size and Wolf kills we observed

Review: Research Toward Safer Resection of the Cirrhotic Liver

Despite recent advances in hepatic surgery, resection of the cirrhotic liver continues to be fraught with high morbidity and mortality rates. As a result, for many patients requiring resection of HCC the postoperative course is complicated and the probability of cure is diminished by coexisting cirrhosis. In this review, we discuss the characteristics of the cirrhotic liver which make it poorly tolerant of resection and the most common complications that follow such surgery. The main purpose of this paper is to review recent attempts to identify interventions that might be beneficial to cirrhotic patients undergoing resection. These interventions include assessment of liver reserve, advances in surgical technique, and improvement in liver function and regeneration

Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.S-S Liau is in receipt of the MRC Clinician Scientist Fellowship. He is also funded by University of Cambridge Parke-Davis Fellowship, Royal Society of Medicine Ellison-Cliffe Fellowship, Dowager Countess Eleanor Peel Fellowship, HCA International Foundation Fellowship, European Society of Surgical Oncology Minor Fellowship, and MRC Centenary Early Career Award.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S074879831401097X#

Identifying Risk Factors for Central Pontine and Extrapontine Myelinolysis After Liver Transplantation: A Case-Control Study

Background: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome. Methods: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4%) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score. Results: The 19 patients with CPEPM (7F, mean age 52.1±2years) had a mean MELD score of 26±2.2. Before OLT, patients who develop CPEPM presented more frequently low (2 of these conditions were strongly associated with CPEPM (p=0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13%, p<0.0001). Conclusions: High MELD score patients undergoing OLT, receiving massive perfusions of Na-rich products, experiencing surgery-related hemorrhagic complication and important fluctuations of Na are at risk of developing CPEPM. Therefore careful monitoring of natremia in the perioperative period and use of water-free perfusion in case of massive blood-products transfusion are critical points of this patient management

Islet isolation assessment in man and large animals

Recent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity and in vitro and in vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 μ diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason, in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers. © 1990 Casa Editrice il Ponte

Therapeutic Efficacy of Human Hepatocyte Transplantation in a SCID/uPA Mouse Model with Inducible Liver Disease

Severe Combined Immune Deficient (SCID)/Urokinase-type Plasminogen Activator (uPA) mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH) which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk)/ganciclovir (GCV) system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK)/GCV system of hepatic failure in SCID/uPA mice.In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32-87%). Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH.Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes. Functional support by engrafted HH may be secured by strategies aimed at limiting this bystander effect