Evaluation of Medetomidine-Ketamine and atipamezole for reversible anesthesia of free-ranging gray wolves (Canis lupus)

This article is published in Journal of Wildlife Diseases, 49(2), 2013, pp. 403–407Twenty-eight anesthetic events were carried out on 24 free-ranging Scandinavian gray wolves (Canis lupus) by darting from a helicopter with 5 mg medetomidine and 250 mg ketamine during winter in 2002 and 2003. Mean6SD doses were 0.16260.008 mg medetomidine/ kg and 8.160.4 mg ketamine/kg in juveniles (7–10 mo old) and 0.11060.014 mg medetomidine/kg and 5.760.5 mg ketamine/kg in adults (.19 mo old). Mean6SD induction time was shorter (P,0.01) in juveniles (2.360.8 min) than in adults (4.160.6 min). In 26 cases, the animals were completely immobilized after one dart. Muscle relaxation was good, palpebral reflexes were present, and there were no reactions to handling orminor painful stimuli. Mild to severe hyperthermia was detected in 14/ 28 anesthetic events. Atipamezole (5 mg per mg medetomidine) was injected intramuscularly for reversal 98628 and 94640 min after darting in juveniles and adults, respectively. Mean6SD time from administration of atipamezole to coordinated walking was 38620 min in juveniles and 41621 min in adults. Recovery was uneventful in 25 anesthetic events, although vomiting was observed in five animals. One adult that did not respond to atipamezole was given intravenous fluids and was fully recovered 8 hr after darting. Two animals died 7–9 hr after capture, despite intensive care. Both mortalities were attributed to shock and circulatory collapse following stress-induced hyperthermia. Although effective, this combination cannot be recommended for darting free-ranging wolves from helicopter at the doses presented here because of the severe hyperthermia seen in several wolves, two deaths, and prolonged recovery in one individual

Long-Term Safety of Intraperitoneal Radio Transmitter Implants in Brown Bears (Ursus arctos)

Intraperitoneal radio transmitters have been widely used in free-ranging wild mammals, but there are no long-term studies on their biocompatibility or technical stability within the abdominal cavity of animals. Possible negative health effects may bias results from ecological studies on instrumented animals and raise concerns over animal welfare issues. The aim of this study was to evaluate the long-term technical stability and pathological effects of Telonics intraperitoneal very high frequency (VHF) radio transmitters in brown bears (Ursus arctos). We instrumented 305 individual bears with intraperitoneal VHF radio transmitters during a 19-year period. We surgically removed devices that had been in bears for 1–9 years and collected transmitters from animals that died 1–13 years after implantation. We took biopsies for histopathology from tissue encapsulating implants in live bears. Retrieved transmitters underwent a technical inspection. Of the 125 transmitters removed from live bears, 66 were free-floating in the peritoneal cavity [a mean (SD) of 3.8 (1.5) years after implantation], whereas 59 were encapsulated in the greater omentum [4.0 (1.8) years after implantation]. Histopathology of biopsies of the 1–15 mm thick capsules in 33 individuals showed that it consisted of organized layers of connective tissue. In one third of the bears, the inner part of the capsule was characterized by a foreign body reaction. We inspected 68 implants that had been in bears for 3.9 (2.4) years. The batteries had short-circuited four (5.9%) of these devices. This resulted in the death of two animals 10 and 13 years after implantation. In two other bears that underwent surgery, we found the short-circuited devices to be fully encapsulated within the peritoneal cavity 5 and 6 years after implantation. A significant proportion of the other 64 inspected implants showed serious technical problems, such as corrosion of metal parts or the batteries (50%), detachment of the end cap (11.8%), and erosion (7.4%) or melting (5.9%) of the wax coating. We conclude that the wax coating of the transmitters was not biocompatible, that the technical quality of the devices was poor, and that these implants should not be used in brown bears

E-Glass Fiber Reinforced Composites in Dental Applications

Fiber reinforced composites (FRCs) are more and more widely applied in dentistry to substitute for metallic restorations: periodontal splints, fixed partial dentures, endodontic posts, orthodontic appliances, and some other indirect restorations. In general in FRCs, the fiber reinforcement provides the composite structure with better biomechanical performance due to their superior properties in tension and flexure. Nowadays, the E-glass fiber is most frequently used because of its chemical resistance and relatively low cost. Growing interest is being paid to enhance its clinical performance. Moreover, various techniques are utilized to reinforce the adhesion between the fiber and the matrix. Oral conditions set special requirements and challenges for the clinical applications of FRCs. The biomechanical properties of dental materials are of high importance in dentistry, and given this, there is on-going scientific interest to develop E-glass fiber reinforced composite systems. FRCs are generally biocompatible and their toxicity is not a concern. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase

Cellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways. To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies. The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21Waf1/Cip1 and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed. Conclusion: These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies

Testing the Effect of Relative Pollen Productivity on the REVEALS Model : A Validated Reconstruction of Europe-Wide Holocene Vegetation

Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1° × 1°) over the Holocene (last 11.7 ka BP) using the 'Regional Estimates of VEgetation Abundance from Large Sites' (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity

Evaluation of Medetomidine-Ketamine and atipamezole for reversible anesthesia of free-ranging gray wolves (Canis lupus)

Twenty-eight anesthetic events were carried out on 24 free-ranging Scandinavian gray wolves (Canis lupus) by darting from a helicopter with 5 mg medetomidine and 250 mg ketamine during winter in 2002 and 2003. Mean6SD doses were 0.16260.008 mg medetomidine/ kg and 8.160.4 mg ketamine/kg in juveniles (7–10 mo old) and 0.11060.014 mg medetomidine/kg and 5.760.5 mg ketamine/kg in adults (.19 mo old). Mean6SD induction time was shorter (P,0.01) in juveniles (2.360.8 min) than in adults (4.160.6 min). In 26 cases, the animals were completely immobilized after one dart. Muscle relaxation was good, palpebral reflexes were present, and there were no reactions to handling orminor painful stimuli. Mild to severe hyperthermia was detected in 14/ 28 anesthetic events. Atipamezole (5 mg per mg medetomidine) was injected intramuscularly for reversal 98628 and 94640 min after darting in juveniles and adults, respectively. Mean6SD time from administration of atipamezole to coordinated walking was 38620 min in juveniles and 41621 min in adults. Recovery was uneventful in 25 anesthetic events, although vomiting was observed in five animals. One adult that did not respond to atipamezole was given intravenous fluids and was fully recovered 8 hr after darting. Two animals died 7–9 hr after capture, despite intensive care. Both mortalities were attributed to shock and circulatory collapse following stress-induced hyperthermia. Although effective, this combination cannot be recommended for darting free-ranging wolves from helicopter at the doses presented here because of the severe hyperthermia seen in several wolves, two deaths, and prolonged recovery in one individual

Selection, characterization and in vivo evaluation of novel CD44v6-targeting antibodies for targeted molecular radiotherapy

Abstract Molecular radiotherapy combines the advantages of systemic administration of highly specific antibodies or peptides and the localized potency of ionizing radiation. A potential target for molecular radiotherapy is the cell surface antigen CD44v6, which is overexpressed in numerous cancers, with limited expression in normal tissues. The aim of the present study was to generate and characterize a panel of human anti-CD44v6 antibodies and identify a suitable candidate for future use in molecular radiotherapy of CD44v6-expressing cancers. Binders were first isolated from large synthetic phage display libraries containing human scFv and Fab antibody fragments. The antibodies were extensively analyzed through in vitro investigations of binding kinetics, affinity, off-target binding, and cell binding. Lead candidates were further subjected to in vivo biodistribution studies in mice bearing anaplastic thyroid cancer xenografts that express high levels of CD44v6. Additionally, antigen-dependent tumor uptake of the lead candidate was verified in additional xenograft models with varying levels of target expression. Interestingly, although only small differences were observed among the top antibody candidates in vitro, significant differences in tumor uptake and retention were uncovered in in vivo experiments. A high-affinity anti-CD44v6 lead drug candidate was identified, mAb UU-40, which exhibited favorable target binding properties and in vivo distribution. In conclusion, a panel of human anti-CD44v6 antibodies was successfully generated and characterized in this study. Through comprehensive evaluation, mAb UU-40 was identified as a promising lead candidate for future molecular radiotherapy of CD44v6-expressing cancers due to its high affinity, excellent target binding properties, and desirable in vivo distribution characteristics