bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPA and kainate receptors mediate mutually exclusive effects on GABAA receptor expression in cultured mouse cerebellar granule neurones
Authors: Payne Helen L. , Ives Jane H. , Sieghart Werner , Thompson Christopher L.
Published: September 2007

Studies on animal models of epilepsy and cerebellar ataxia, e.g., stargazer mice (stg) have identified changes in the GABAergic properties of neurones associated with the affected brain loci. Whether these changes contribute to or constitute homeostatic adaptations to a state of altered neuronal excitability is as yet unknown. Using cultured cerebellar granule neurones from control [+/+; α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazolepropionate receptor (AMPAR)‐competent, Kainate receptor (KAR)‐competent] and stg (AMPAR‐incompetent, KAR‐competent), we investigated whether non‐NMDA receptor (NMDAR) activity regulates GABAA receptor (GABAR) expression. Neurones were maintained in 5 mmol/L KCl‐containing basal media or depolarizing media containing either 25 mmol/L KCl or the non‐NMDAR agonist kainic acid (KA) (100 μmol/L). KCl‐ and KA‐mediated depolarization down‐regulated GABAR α1, α6 and β2, but up‐regulated α4, β3 and δ subunits in +/+ neurones. The KCl‐evoked but not KA‐evoked effects were reciprocated in stg neurones compatible with AMPAR‐regulation of GABAR expression. Conversely, GABAR γ2 expression was insensitive to KCl‐mediated depolarization, but was down‐regulated by KA‐treatment in a 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX)‐reversible manner in +/+ and stg neurones compatible with a KAR–mediated response. KA‐mediated up‐regulation of GABAR α4, β3 and δ was inhibited by L‐type voltage‐gated calcium channel (L‐VGCC) blockers and the Ca2+/calmodulin‐dependent protein kinase inhibitor, 4‐[(2S)‐2‐[(5‐isoquinolinylsulfonyl)methylamino]‐3‐oxo‐3‐(4‐phenyl‐1‐piperazinyl)propyl] phenyl isoquinoline sulfonic acid ester (KN‐62). Up‐regulation of GABAR α4 and β3 was also prevented by calcineurin (CaN) inhibitors, FK506 and cyclosporin A. Down‐regulation of GABAR α1, α6 and β2 was independent of L‐VGCC activity, but was prevented by inhibitors of CaN. Thus, we provide evidence that a KAR‐mediated and at least three mutually exclusive AMPAR‐mediated signalling mechanisms regulate neuronal GABAR expression.
Regulation of A2Aadenosine receptor expression and functioning following permanent focal ischemia in rat brain
Authors: Trincavelli Maria L. , Melani Alessia , Guidi Sara , Cuboni Serena , Cipriani Sara , Pedata Felicita , Martini Claudia
Published: September 2007

Ischemia, through modulation of adenosine receptors (ARs), may influence adenosine‐mediated‐cellular responses. In the present study, we investigated the modulation of rat A2Areceptor expression and functioning, in rat cerebral cortex and striatum, followingin vivofocal ischemia (24 h). In cortex, middle cerebral artery occlusion did not induce any alterations in A2Areceptor binding and functioning. On the contrary, in striatum, a significant decrease in A2Aligand affinity, associated with an increase in receptor density, were detected. In striatum, ischemia also induced a significant reduction both in G protein pool and in A2Areceptor‐G protein coupling. On the contrary, A2Areceptor functional responsiveness, measured as stimulation of adenylyl cyclise, was not affected by ischemia, suggesting receptor up‐regulation may represent a compensatory mechanism to maintain receptor functioning during cerebral damage. Immunohistochemical study showed that following 24 h middle cerebral artery occlusion, A2AARs were definitely expressed both on neurons and activated microglia in ischemic striatum and cortex, but were not detected on astrocytes. In the non‐ischemic hemisphere and in sham‐operated rats A2AARs were barely detected. Modifications of ARs may play a significant role in determining adenosine effects during ischemia and therefore should be taken into account when evaluating time‐dependent protective effects of specific A2Aactive compounds.
SPAR2, a novel SPAR‐related protein with GAP activity for Rap1 and Rap2
Authors: Spilker Christina , Acuña Sanhueza Gustavo A. , Böckers Tobias M. , Kreutz Michael R. , Gundelfinger Eckart D.
Published: September 2007

Spine‐associated RapGAP 2 (SPAR2) is a novel GTPase activating protein (GAP) for the small GTPase Rap that shows significant sequence homology to SPAR, a synaptic RapGAP that was reported to regulate spine morphology in hippocampal neurons. SPAR2, like SPAR, interacts with the recently described synaptic scaffolding protein ProSAP‐interacting protein (ProSAPiP), which in turn binds to the PDZ domain of ProSAP/Shank post‐synaptic density proteins. In subcellular fractionation experiments, SPAR2 is enriched in synaptosomes and post‐synaptic density fractions indicating that it is a synaptic protein. Furthermore, we could show using in vitro GAP assays that SPAR2 has GAP activity for Rap1 and Rap2. Expression in COS‐7 cells, however, revealed different actin‐binding properties of SPAR2 and SPAR. Additionally, over‐expression of SPAR2 in cultured hippocampal neurons did not affect spine morphology as it was reported for SPAR. In situ hybridization studies also revealed a differential tissue distribution of SPAR and SPAR2 with SPAR2 transcripts being mainly expressed in cerebellar and hippocampal granule cells. Moreover, in the cerebellum SPAR2 is developmentally regulated with a peak of expression around the period of synapse formation. Our results imply that SPAR2 is a new RapGAP with specific functions in cerebellar and hippocampal granule cells.
Glial cell‐derived glutamate mediates autocrine cell volume regulation in the retina: activation by VEGF
Authors: Wurm Antje , Pannicke Thomas , Wiedemann Peter , Reichenbach Andreas , Bringmann Andreas
Published: September 2007

Astroglial cells are a source for gliotransmitters such as glutamate and ATP. We demonstrate here that gliotransmitters have autocrine functions in the regulation of cellular volume. Hypoosmotic stress in the presence of inflammatory mediators or oxidative stress, and during blockade or down‐regulation of potassium channels, induces swelling of retinal glial cells. Vascular endothelial growth factor inhibits the osmotic swelling of glial cells in retinal slices or isolated cells. This effect was mediated by a kinase domain region/flk‐1 receptor‐evoked calcium dependent release of glutamate from glial cells, and subsequent stimulation of glial group I/II metabotropic glutamate receptors. Activation of kinase domain region/flk‐1 or glutamate receptors evoked an autocrine swelling‐inhibitory purinergic signaling cascade that was calcium‐independent. This cascade involved the release of ATP and adenosine, and the activation of purinergic P2Y1 and adenosine A1 receptors, resulting in the opening of potassium and chloride channels and inhibition of cellular swelling. The glutamatergic‐purinergic regulation of the glial cell volume may be functionally important in the homeostasis of the extracellular space volume during intense neuronal activation which is associated with a swelling of neuronal cell structures in the retina. However, glial cell‐derived glutamate may also contribute to the swelling of activated neurons since metabolic poisoning of glial cells by iodoacetate inhibits the neuronal cell swelling mediated by activation of ionotropic glutamate receptors.
Astroglial nuclear factor‐κB regulates learning and memory and synaptic plasticity in female mice
Authors: Bracchi‐Ricard Valerie , Brambilla Roberta , Levenson Jonathan , Hu Wen‐Hui , Bramwell Annmarie , Sweatt J. David , Green Edward J. , Bethea John R.
Published: September 2007

Astrocytes play a pivotal role in regulating synaptic plasticity and synapse formation. The nuclear factor‐kappa B (NF‐κB) family of transcription factors has recently been demonstrated to be an important modulator of synaptic plasticity and learning/memory. In this study, we investigated the role of astroglial NF‐κB in synaptic plasticity and learning/memory using transgenic mice over‐expressing an N‐terminal truncated form of inhibitor of NF‐κB alpha (IκBα) in astrocytes (GFAP‐IκΒα‐dn). We demonstrated that female transgenic mice, but not males, have robust deficits in hippocampal and extra‐hippocampal‐dependent learning and memory. We also determined that there are significant deficits in LTP and expression of metabotropic glutamate receptor 5 and post‐synaptic density protein 95 (PSD95) in female transgenic mice. These findings indicate that astroglial NF‐κB is an important regulator of learning/memory and synaptic plasticity.
RGMa inhibits neurite outgrowth of neuronal progenitors from murine enteric nervous system via the neogenin receptor in vitro
Authors: Metzger Marco , Conrad Sabine , Skutella Thomas , Just Lothar
Published: September 2007

The enteric nervous system (ENS) in vertebrate embryos is formed by neural crest‐derived cells. During development, these cells undergo extensive migration from the vagal and sacral regions to colonize the entire gut, where they differentiate into neurons and glial cells. Guidance molecules like netrins, semaphorins, slits, and ephrins are known to be involved in neuronal migration and axon guidance. In the CNS, the repulsive guidance molecule (RGMa) has been implicated in neuronal differentiation, migration, and apoptosis. Recently, we described the expression of the subtypes RGMa and RGMb and their receptor neogenin during murine gut development. In the present study, we investigated the influence of RGMa on neurosphere cultures derived from fetal ENS. In functional in vitro assays, RGMa strongly inhibited neurite outgrowth of differentiating progenitors via the receptor neogenin. The repulsive effect of RGMa on processes of differentiated enteric neural progenitors could be demonstrated by collapse assay. The influence of the RGM receptor on ENS was also analyzed in neogenin knockout mice. In the adult large intestine of mutants we observed disturbed ganglia formation in the myenteric plexus. Our data indicate that RGMa may be involved in differentiation processes of enteric neurons in the murine gut.
Neurotoxicity of microglial cathepsin D revealed by secretome analysis
Authors: Kim Sangseop , Ock Jiyeon , Kim Ae Kyung , Lee Ho Won , Cho Je‐Yoel , Kim Deok Ryong , Park Jae‐Yong , Suk Kyoungho
Published: September 2007

Microglia‐driven inflammatory responses have both neuroprotective and neurotoxic effects in the CNS. The excessive and chronic activation of microglia, however, may shift the balance towards neurotoxic effects. In this regard, proteins secreted from activated microglia likely play a key role in the neurotoxic effects. To characterize secreted proteins of activated microglia, conditioned media obtained from BV‐2 mouse microglia cells were analyzed by two‐dimensional gel electrophoresis or liquid chromatography coupled with tandem mass spectrometry. Among many proteins identified in the secretome of activated microglia, an aspartic endoprotease cathepsin D has been found to mediate microglial neurotoxicity based on the following results: (i) the expression of cathepsin D protein was markedly increased in lipopolysaccharide/interferon‐γ‐stimulated microglia compared with resting microglia as determined by western blot analysis of conditioned media; (ii) knockdown of cathepsin D expression in microglia using short hairpin RNA diminished the neurotoxicity in the coculture of microglia and neuroblastoma cells and (iii) recombinant procathepsin D protein exerted cytotoxic effects toward cultured neurons. In conclusion, cathepsin D appears to play a central role in the microglial neurotoxicity, and could be a potential biomarker or drug target for the diagnosis and treatment of neurodegenerative diseases that are associated with excessive microglial activation and subsequent neurotoxic inflammation.
Mitochondrial dysfunction, oxidative stress, regulation of exocytosis and their relevance to neurodegenerative diseases
Authors: Keating Damien J.
Published: September 2007

A common feature in the early stages of many neurodegenerative diseases lies in mitochondrial dysfunction, oxidative stress, and reduced levels of synaptic transmission. Many genes associated with neurodegenerative diseases are now known to regulate either mitochondrial function, redox state, or the exocytosis of neurotransmitters. Mitochondria are the primary source of reactive oxygen species and ATP and control apoptosis. Mitochondria are concentrated in synapses and significant alterations to synaptic mitochondrial localization, number, morphology, or function can be detrimental to synaptic transmission. Mitochondrial by‐products are capable of regulating various steps of neurotransmission and mitochondrial dysfunction and oxidative stress occur in the early stages of many neurodegenerative diseases. This mini‐review will highlight the prospect that mitochondria regulates synaptic exocytosis by controlling synaptic ATP and reactive oxygen species levels and that dysfunctional exocytosis caused by mitochondrial abnormalities may be a common underlying phenomenon in the initial stages of some human neurodegenerative diseases.
Myelinated axons contain β‐actin mRNA and ZBP‐1 in periaxoplasmic ribosomal plaques and depend on cyclic AMP and F‐actin integrity for in vitro translation
Authors: Sotelo‐Silveira José , Crispino Marianna , Puppo Agostina , Sotelo José R. , Koenig Edward
Published: September 2007

Periaxoplasmic ribosomal plaques (PARPs) are periodic structural formations containing ribosomes, which are likely cortical sites of translation along myelinated fibers. β‐actin mRNA, and its trans‐acting binding factor, zipcode‐binding protein‐1, were co‐distributed within PARP domains of axoplasmic whole‐mounts isolated from goldfish Mauthner, rabbit and rat nerve fibers. The distribution of co‐localization signals of fluorophore pixels, however, was asymmetric in PARP domains, possibly indicative of endpoint trafficking of RNPs. β‐actin mRNA in RNA extracted from axoplasm of single Mauthner fibers was confirmed by RT‐PCR. A metabolically active isolated Mauthner fiber system, which required cAMP to activate translation, was developed in order to probe cycloheximide‐sensitivity, and the importance of the actin cytoskeleton. cAMP greatly stimulated protein synthesis in axoplasm after a period of pre‐incubation, while being inhibited strongly by cycloheximide, or by cytochalasin D. Cytochalasin D reduced incorporation only modestly in the associated myelin sheath. We conclude that mechanisms for targeting and localizing β‐actin mRNA to discrete PARP domains are probably similar to those described for dendritic synaptic domains. Moreover, optimal translation in axoplasm depends on the integrity of the actin cytoskeleton, and can be modulated by cAMP as well.
Functional blockage of the cannabinoid receptor type 1 evokes a kappa‐opiate‐dependent analgesia
Authors: Sáez‐Cassanelli José L. , Fontanella German H. , Delgado‐García José M. , Carrión Ángel M.
Published: September 2007

Progress in the control and treatment of pain may be facilitated by a better understanding of mechanisms underlying nociceptive processing. Cannabinoids and opioids are endogenous modulator of pain sensation, but therapies based in these compounds are not completely exploited because of their side effects. To test the role of cannabinoid receptor type 1 (CB1‐R) inhibition in nociception, we performed a subchronic administration of the CB1‐R antagonistN‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM281) in mice. This treatment provoked analgesia in peripheral thermal and visceral models of pain. Analysis of genes encoded for the opioid system in the spinal cord showed an increase in the expression of genes encoded for the κ‐opioid system in AM281‐injected mice compared with vehicle‐injected ones. Furthermore, systemic administration of nor‐binaltorphimine, a κ‐opioid receptor antagonist, blocked AM281‐induced analgesia. Finally, c‐fos expression in the dorsal spinal cord and higher centers of pain processing after noxious stimulation were significantly lower in AM281‐injected mice than in vehicle‐injected animals, indicating that dynorphin could block nociceptive information transmission at the spinal cord level. These results indicate the existence of a cross‐talk between opioid and cannabinoid systems in nociception. Furthermore, the results suggest that CB1‐R antagonists could be useful as a new therapeutic approach for pain relief.
PERMANENT GENETIC RESOURCES: Isolation and characterization of microsatellite loci from the Arctic cisco (Coregonus autumnalis)
Authors: RAMEY A. , GRAZIANO S. L. , NIELSEN J. L.
Published: September 2007

Eight polymorphic microsatellite loci were isolated and characterized for the Arctic cisco, Coregonus autumnalis. Loci were evaluated in 21 samples from the Colville River subsistence fishery. The number of alleles per locus ranged from two to 18. Observed heterozygosity of loci varied from 0.10 to 1.00, and expected heterozygosity ranged from 0.09 to 0.92. All eight microsatellite markers were in Hardy–Weinberg equilibrium. The loci presented here will be useful in describing population structure and exploring populations of origin for Arctic cisco.
Isolation and characterization of microsatellite loci in the western long‐fingered bat, Miniopterus magnater
Authors: HAN B. Y. , HUA P. Y. , GU X. M. , MILLER‐BUTTERWORTH C. M. , ZHANG S. Y.
Published: September 2007

We isolated and characterized 10 microsatellite loci in the western long‐fingered bat, Miniopterus magnater. These loci were tested on 48 individuals from Anhui Province of China, and all loci were highly polymorphic. The mean number of observed alleles per locus was 13.6 (range from six to 27). Observed and expected heterozygosity values ranged from 0.364 to 0.957, and from 0.676 to 0.951, respectively. After Bonferroni correction, four loci deviated significantly from Hardy–Weinberg equilibrium. No pairs of loci were in linkage disequilibrium. These polymorphic markers will be used to examine population structure and genetic diversity in this species.
Eleven polymorphic microsatellite markers in Cory's shearwater, Calonectris diomedea, and cross‐species amplification on threatened Procellariiformes
Authors: BRIED JOËL , DUBOIS MARIE‐PIERRE , JOUVENTIN PIERRE , SANTOS RICARDO S.
Published: September 2007

For the first time, we describe 11 variable dinucleotide microsatellites and the conditions for multiplexing and simultaneous genotyping sets of loci in Cory's shearwater, Calonectris diomedea. Microsatellite variability was assessed in a colony from the Azores archipelago (Atlantic Ocean). Two to eight alleles were detected per locus, the mean gene diversity being 4.5. Cross‐species amplification in three other seabirds (Diomedea exulans, Procellaria aequinoctialis and Bulweria bulwerii) revealed some variability at one, two and eight loci, respectively.
bels: backward elimination locus selection for studies of mixture composition or individual assignment
Authors: BROMAGHIN JEFFREY F.
Published: September 2007

Methods of evaluating loci in studies of mixture composition or individual assignment are largely based on performance characteristics of individual loci. Synergisms between loci are not exploited. Loci are often evaluated based on their ability to resolve individual populations, even though multipopulation aggregations are more commonly of interest. In addition, measures of locus performance may indirectly relate to investigative objectives. A new computer program, bels, offers an alternative that addresses these limitations and may be preferable to existing methods in some applications. The algorithm is illustrated using Yukon River chum salmon (Oncorhynchus keta) data.
ORIGIN, EVOLUTION AND CLASSIFICATION OF THE NEW SUPERORDER NEPIOMORPHIA (MOLLUSCA, BIVALVIA, LOWER PALAEOZOIC)
Authors: KŘÍŽ JIŘÍ
Published: September 2007

Abstract: Anumber of bivalve taxa defined in the past as ‘Cryptodonten’ by Neumayr, 1884 were grouped together in the high‐level taxon Palaeoconchae Neumayr, 1884. Cox (1969) noted that Palaeoconchae and Cryptodonta were synonymous and Newell (1969) used Cryptodonta as a subclass of bivalves. However, for the past 120 years, the Cryptodonta has been poorly conceptualized and the name was used for poorly understood genera or those lacking dentition. As used by Newell, Cryptodonta included taxa now placed in the subclasses Protobranchia Pelseneer and Autolamellibranchiata Grobben, and to the class Rostroconchia Pojeta, Runnegar, Morris and Newell. The bulk of Newell's use of Cryptodonta was made up of Silurian and Devonian taxa first described by Barrande (1881) from Bohemia; Newell placed these in the order Praecardioida Newell. In effect, Cryptodonta became a ‘wastebasket’ grouping for what, at the time, were poorly understood taxa. Many of the formerly poorly understood praecardioids are now better known and are herein placed in the new superorder Nepiomorphia. The Nepiomorphia contains two orders: (1) order Praecardioida that includes the families Slavidae Kříž, Cardiolidae Hoernes, Praecardiidae Hoernes and Buchiolidae Grimm; and (2) new order Antipleuroida that includes the families Stolidotidae fam. nov., Spanilidae fam. nov. and Antipleuridae Neumayr. The Nepiomorphia originated probably in the early Silurian as result of r‐selection progenesis. When the marine current system became re‐established after the late Ordovician glaciation and in the early Silurian, an at least temporary ventilation of the shallow waters by surface currents was renewed in higher latitudes of peri‐Gondwana and Siberia, producing acceptable sea‐bottom environments. Larvae were distributed by surface currents from the warm tropical regions of Laurentia and Baltica and were among the first benthic organisms to colonize the new environments. Temporary ventilation created frequent density‐independent catastrophic mortalities of early ontogenetic stages, with no competitors and with super‐abundant resources. During the Silurian and early Devonian, the Nepiomorphia underwent several diversifications in the recurring cephalopod limestone biofacies characteristic of peri‐Gondwana, and evolved infaunal, semi‐infaunal and epifaunal modes of life in several lineages. The Nepiomorphia most probably became extinct during the early Carboniferous and had no role in the future evolution of the Bivalvia.
Electronic Paint: Understanding Children's Representation through their Interactions with Digital Paint
Authors: Matthews John , Seow Peter
Published: September 2007

This article investigates very young children's use of a stylus‐driven, electronic painting and drawing on the tablet PC. The authors compare their development in the use of this device with their use of other mark‐making media, including those which derive from pencil and paper technologies and also with mouse‐driven electronic paintbox programs. After experience of using of electronic paint, two of the children were introduced to simple programming software. The authors wanted to find out how the introduction of electronic, digital, interactive devices impact upon children's development in semiotic understanding.
Towards a Theory that Links Experience in the Arts with the Acquisition of Knowledge
Authors: Dahlman Ylva
Published: September 2007

The origin of this article is an investigation of an academic course, Graphic Arts and Design for students of natural and social sciences. The article describes the benefits of attending the class for the science students, which were an increased ability to solve problems, new and different ways to observe the environment, greater self confidence, and a higher understanding and valuing of the working process. The participants considered that the artistic activities affected their academic courses since the exercises were seen as creative and meaningful, which led to a changed attitude towards their studies. The exercises developed a comprehensive view and an ability to concentrate, which were conducive to problem solving. The article compares the process of drawing with the cognitive approach of philosophical pragmatism described by Charles Peirce and John Dewey. Michael Polanyi's concept of tacit knowing and some theories on the function of metaphors are also discussed in relation to some concrete pedagogical examples.
Aesthetics, Popular Visual Culture, and Designer Capitalism
Authors: Duncum Paul
Published: September 2007

While rejecting modernist philosophical aesthetics, the author argues for the use in art education of a current, ordinary‐language definition of aesthetics as visual appearance and effect, and its widespread use in many diverse cultural sites is demonstrated. Employing such a site‐specific use of aesthetics enables art education to more clearly address the realities of everyday life under designer capitalism, a socio‐economy based on the drive to create evermore desire. Aesthetic manipulation is viewed as a primary means to facilitate the smooth operation of this system. The recent craze for Bratz dolls is used to illustrate the centrality of aesthetics to designer capitalism. Finally, the author offers suggestions as to how art education can view consumer products like Bratz as pedagogic opportunities.
Creating New Identities in Design Education
Authors: Mendoza Hannah Rose , Bernasconi Claudia , MacDonald Nora M.
Published: September 2007

An international education opportunity has been created for design students at West Virginia University. This experience is unique because it takes an interdisciplinary approach to design that exposes students to the idea of a larger design methodology common to design professions. Students take core courses with students from a variety of design fields, including interior design, fashion design, fashion merchandising, landscape architecture, art, and graphic design. Through this interaction, students gain an understanding of the interrelationships among design fields, learn to appreciate new perspectives, and begin to appreciate the place of their field as part of the design community as a whole.
The Evaluation of Community Arts Projects and the Problems with Social Impact Methodology
Authors: Clements Paul
Published: September 2007

This article focuses on the evaluation of participatory community arts programmes and analyses the shift in educational emphasis from aesthetic to social outcomes. It considers a range of theoretical models and practices in the field which includes my own experience.

The history of evaluative methodology highlights procedural concerns which are applied to current strategies of evaluating social impact. This is critiqued with regards to consent and participant intention, lack of discrimination between ‘natural’ and ‘synthetic’ instrumentality, and issues surrounding measurement and the validation of impact through social auditing.

This foregrounds broader debates concerning the politics of evaluation. An ideal democratic method is suggested that encourages participant involvement, empowerment and self‐management. This is compared to normative bureaucratic and autocratic approaches steeped in top‐down agendas which may exacerbate social problems.
Comparison of Analgesic Efficacy of Preoperative or Postoperative Carprofen with or Without Preincisional Mepivacaine Epidural Anesthesia in Canine Pelvic or Femoral Fracture Repair
Authors: BERGMANN HANNES M. , NOLTE INGO , KRAMER SABINE
Published: September 2007

Objective—To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen.

Study Design—Blind, randomized clinical study.

Animals—Dogs with femoral (n=18) or pelvic (27) fractures.

Methods—Dogs were grouped by restricted randomization into 4 groups: group 1=carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2=carprofen immediately after extubation, no epidural anesthesia; group 3=carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4=mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia.

Results—Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables.

Conclusions—Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen.

Clinical Relevance—Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.
Risk Factors for Ventral Luxation in Canine Total Hip Replacement
Authors: NELSON LAURA L. , DYCE JONATHAN , SHOTT SUSAN
Published: September 2007

Objective— To identify risk factors associated with ventral luxation (VL) of canine total hip replacement (THR), and outcome.

Study Design— Retrospective study.

Animals— Dogs (n=602) that had THR (563 cemented, 35 cementless, 4 hybrid).

Methods— Dogs (1999–2004) with VL after THR were compared with dogs with uncomplicated THR. Data included signalment, body weight, diagnosis, implant size, acetabular cup orientation, and femoral displacement ratio (FDR).

Results— VL was diagnosed in 11 (1.8%) dogs after primary THR. Including 2 other dogs that had VL after the study period, 10 (77%) of 13 dogs had VL within 7 days of surgery. Risk factors for VL included Saint Bernard‐type dogs (P=.0001), short neck extension (P=.0005), and high angle of lateral opening in other breeds (P=.018). There were trends toward higher risk of VL with lower FDR in Saint Bernardtypes (P=.060), and with cementless implants (P=.061). Twelve dogs had revision arthroplasty that was successful in all cementless and 2 cemented VL cases. Five dogs had recurrent VL and a poor outcome.

Conclusion— VL is generally an early complication of THR, with no single common risk factor identified.

Clinical Relevance— Saint Bernard types and short neck extensions are associated with increased risk of VL. Poor cup orientation is a determining factor for VL in some dogs, but a protective orientation of the acetabular cup was not found. Revision is successful in most dogs, but recurrent VL merits a guarded prognosis.
Relationship of Physical Examination Test of Shoulder Instability to Arthroscopic Findings in Dogs
Authors: DEVITT CHAD M. , NEELY MARLON R. , VANVECHTEN BRIAN J.
Published: September 2007

Objective— To determine the diagnostic validity of commonly used physical examination maneuvers for shoulder instability.

Study Design— Retrospective study.

Animals— Dogs (n=24) referred for shoulder arthroscopy.

Methods— Results of physical maneuvers and arthroscopic findings were recorded and sensitivity, specificity, positive likelihood ratios (LR+), and negative likelihood ratios (LR−) were calculated for each of 4 physical examination test findings for arthroscopic changes in the medial, lateral, cranial, or caudal compartments of the shoulder joint viewed in dorsal recumbency by lateral and craniomedial portals.

Results— Distribution of compartment changes was: medial (17 dogs), caudal (15), cranial (12), and lateral (5). The biceps test had a moderate effect (LR+=9) on post‐test probability of cranial compartment changes and a small effect on post‐test probability of lateral and caudal compartment changes (LR+=3 and 2.4, respectively). Hyperabduction had a minimal effect and mediolateral instability test had a small effect (LR+=1.64 and 2.68, respectively) on post‐test probability of medial compartment changes. Craniocaudal instability test had little to no effect on post‐test probability of changes in any compartment.

Conclusions— Physical examination tests evaluated were limited in their ability to predict the type of arthroscopic pathology in this study population.

Clinical Relevance — Clinicians should understand that a diagnostic test performs inconsistently based on prevalence of a condition in a given patient population. The use of likelihood ratios can assist clinicians in determining the probability of intraarticular changes from a group with a differing prevalence than the patient population presented.
Minimally Invasive Cholecystostomy in the Dog: Evaluation of Placement Techniques and Use in Extrahepatic Biliary Obstruction
Authors: MURPHY SEAN M. , RODRÍGUEZ JULIAN D. , McANULTY JONATHAN F.
Published: September 2007

Objective— To evaluate 4 methods of cholecystostomy catheter placement and to report on laparoscopic (Lap) cholecystostomy for the management of extrahepatic biliary obstruction (EHBO) in 3 dogs.

Study Design— Experimental study and clinical report.

Animals— Cadaveric dogs (n=20); 2 canine and 1 feline patient.

Methods— Pigtail cholecystostomy catheters were inserted in 20 canine cadavers using ultrasound (US) or Lap guidance. Insertion routes were either transperitoneal or transhepatic. Methods studied included Lap‐transperitoneal, US‐transperitoneal, US‐transhepatic, and US‐Seldinger (n=5 dogs/group). Insertion success, pleural penetration, and insertion site leakage (Lap‐transperitoneal group) were evaluated. Three clinical EHBO cases were treated by Lap‐transperitoneal technique.

Results— Insertion success was 100% by Lap‐transperitoneal but 0% with US‐transperitoneal and US‐Seldinger methods. US‐transhepatic yielded 3 of 5 successful placements. The pleura was penetrated in all US‐transhepatic and US‐Seldinger insertions. Leakage pressure for Lap‐transperitoneal catheters averaged 75 cm H2O (±20 cm H2O). Lap‐transperitoneal cholecystostomy resulted in marked improvement in 2 dogs, but the catheter became obstructed in the cat. One dog spontaneously regained common bile duct patency and the remaining 2 animals had successful cholecystoenterostomy.

Conclusions— In cadaver testing, the Lap‐transperitoneal cholecystostomy method was superior based on high insertion success with no pleural penetration. In 2 clinical cases, Lap‐transperitoneal placement successfully provided biliary drainage for patient stabilization.

Clinical Relevance— The role for temporary cholecystostomy has yet to be established, but may aid patient stabilization and mortality reduction in EHBO.
The Use of Vacuum‐Assisted Closure Therapy for the Treatment of Distal Extremity Wounds in 15 Dogs
Authors: BEN‐AMOTZ RON , LANZ OTTO I. , MILLER JONATHAN M. , FILIPOWICZ DEAN E. , KING MICHAEL D.
Published: September 2007

Objective— To evaluate clinical outcome after vacuum‐assisted closure (VAC) therapy in dogs with traumatic wounds located in the distal extremities and report our early experience with VAC.

Study Design— Retrospective study.

Animals— Dogs (n=15) with traumatic distal extremity wounds.

Methods— Medical records (1999–2003) of dogs with traumatic injuries to the distal extremities managed by VAC were evaluated. Data included signalment, location of wound, time until surgical intervention, wound reconstruction methods, orthopedic procedures, outcome, complications associated with VAC, and length of hospitalization.

Results— The mean number of days until reconstruction was 4.6 days (range, 2–7 days). Reconstructive surgery was successful in all cases. Mean hospitalization was 9.7 days (range, 6–16 days). Complications included dermatitis at the wound margin and loss of vacuum causing wound desiccation.

Conclusion— VAC therapy can be used to achieve adequate management of traumatic distal extremity wounds. VAC provides an effective method of securing skin grafts over the wound bed.

Clinical Relevance— VAC therapy can be used as an ancillary treatment for distal extremity wounds in dogs before surgical repair as well as a method for securing skin grafts to the wound bed.
Radiographic, Computed Tomographic, and Arthroscopic Evaluation of Experimental Radio‐Ulnar Incongruence in the Dog
Authors: WAGNER KAHRMA , GRIFFON DOMINIQUE J. , THOMAS MICHEAL W. , SCHAEFFER DAVID J. , SCHULZ KURT , SAMII VALERIE F. , NECAS ALOIS
Published: September 2007

Objective—To compare the diagnostic value of arthroscopy, computed tomography (CT), and radiography for evaluation of radio‐ulnar incongruence (RUI).

Study Design—Experimental evaluation of induced progressive RUI.

Sample Population—Cadaveric Labrador forelimbs (n=11).

Methods—The radius was shortened by 1, 2, and 3 mm with a surgical model of RUI. RUI was scored on radiographs, CT (2 radiologists), and arthroscopy (2 surgeons) before and after each modification. The sensitivity and specificity of each modality were compared. The effects of arthroscope and elbow position on arthroscopy observations were evaluated. Agreement between surgeons, radiologists, and each imaging technique and the known status of the elbow was calculated.

Results—Complete arthroscopic sessions had an averaged sensitivity of 94% and specificity of 81.9%. The ability to detect mild incongruity (1 mm step) was greater at the incisure than other locations (P<.001). The average sensitivity and specificity of radiography were 99.3% and 42.4%, and for CT were 85.05% and 45.8%, respectively. The average agreement between imaging techniques and the known status of the elbows was greater with complete arthroscopic sessions (89.75%) than radiography (70.1%) and CT (76.85%). Inter‐investigator agreement was greater between surgeons scoring arthroscopic examinations (88.6%) than radiologists scoring CT studies (43.9%).

Conclusions—Evaluation of arthroscopic images allows sensitive and reproducible detection of experimental RUI, especially at the incisure. Arthroscopic evaluation of experimental RUI reached a higher diagnostic value than radiographs and CT images, because of its specificity and reproducibility.

Clinical Relevance—The diagnostic value and reproducibility of arthroscopy may compare favorably with those of CT when evaluating RUI in dogs with elbow disease.
Surgical Treatment of Lumbosacral Foraminal Stenosis Using a Lateral Approach in Twenty Dogs with Degenerative Lumbosacral Stenosis
Authors: GÖDDE THOMAS , STEFFEN FRANK
Published: September 2007

Objectives— To describe clinical signs, magnetic resonance imaging (MRI) and surgical findings using a lateral approach to the lumbosacral intervertebral foramen and to evaluate clinical outcomes in dogs with or without concurrent dorsal decompression and annulectomy.

Study Design— Retrospective study.

Animals— Dogs (n=20) with degenerative lumbosacral stenosis (DLSS).

Methods— Medical records (2002–2006) of dogs that had lumbosacral lateral foraminotomy alone or in combination with dorsal decompression were reviewed. Degree of dysfunction was assessed separately for each pelvic limb; dogs with unilateral signs were included in group A, those with bilateral signs in group B. Retrieved data were: signalment, history, neurologic status on admission, 3 days, 6 weeks, and 6 months postoperatively, duration of clinical signs, results of MRI, surgical site(s), intraoperative findings, and outcome.

Results— Based on the clinical and MRI findings unilateral foraminotomy was performed in 8 dogs, bilateral foraminotomy in 1 dog, unilateral foraminotomy with concurrent dorsal decompression in 7 dogs, and bilateral foraminotomy with concomitant dorsal decompression in 4 dogs. Surgery confirmed the presence of foraminal stenosis in all dogs, with osteophyte formation and soft tissue proliferations being the most common lesions. Outcome was good to excellent in 19 dogs and poor in 1 dog. Mean follow‐up was 15.2 months (range, 6–42 months).

Conclusion— Lateral foraminotomy addresses compressive lesions within exit and middle zones of the lumbosacral foramen.

Clinical Relevance— Successful surgical management of DLSS is dependent on recognition and correction of each of the compressive lesions within the lumbosacral junction.
Humic Acids as a Complexible Fuel for Combustion Synthesis of Ceramic Nanoparticles
Authors: Zhu Wei , Zhao Fei , Yao Jianfeng , Zhang Xinyi , Wang Huanting , Xia Changrong , Li Chun‐Zhu
Published: September 2007

A novel combustion synthesis of ceramic powder has been developed using humic acids (HA) as the complexible fuel. Synthesis of mixed oxide (Sm0.5Sr0.5CoO3 (SSC)) ceramic nanoparticles was chosen to illustrate synthetic procedures. SSC nanoparticles obtained by combustion of HA–metal complexes exhibited particle sizes of 50–100 nm, and good electrochemical performance as the cathode material for solid oxide fuel cells. The process of using renewable HA as the complexible fuel is of low cost, and thus suitable for sustainable production of various oxide ceramic materials.
Utilization of Multiple‐Stage Sintering to Control Ni Electrode Continuity in Ultrathin Ni–BaTiO3 Multilayer Capacitors
Authors: Polotai Anton V. , Yang Gai‐Ying , Dickey Elizabeth C. , Randall Clive A.
Published: September 2007

Microstructural control in thin‐layer multilayer ceramic capacitors (MLCCs) is one of the present‐day challenges for maintaining an increase in capacitive volumetric efficiency. The present paper continues a series of investigations aimed at understanding and controlling the microstructural stability of ultrathin Ni electrodes in MLCCs. Here, a kinetic approach based on the control of sintering profiles is used. Ni–BaTiO3 MLCC chips (0805‐type with 300 active layers) are nonisothermally sintered up to 900°–1300°C with different heating rates in the range from 200° to 3000°C/h. In general, the continuity of the Ni electrodes increases with heating rate. However, a strong nonlinear dependence of Ni electrode continuity on sintering temperature is observed. It is concluded that a low‐melting interfacial liquid (Ni,Ba,Ti) alloy layer initiates at temperatures between 1000° and 1100°C when the Ni electrodes are under tension. This interfacial liquid phase accelerates a stress‐induced diffusion and is the key cause of the severe electrode discontinuities during heating. At higher temperatures (above 1100°C), where compressive stresses are active, the interfacial liquid alloy layer facilitates some recovery of the Ni electrode microstructure. The formation of the interfacial liquid alloy layer can be kinetically controlled using fast‐heating rates, which improves the Ni electrode continuity.
Insulin‐Like Growth Factor‐Binding Protein‐5 Enters Vesicular Structures but Not the Nucleus
Authors: Jurgeit Andreas , Berlato Chiara , Obrist Peter , Ploner Christian , Massoner Petra , Schmölzer Judith , Haffner Michael C. , Klocker Helmut , Huber Lukas A. , Geley Stephan , Doppler Wolfgang
Published: September 2007

In addition to its extracellular function as a secreted protein, IGF‐binding protein (IGFBP)‐5 has been postulated to act as a signaling molecule in the nucleus. This study aims to assess the significance of this postulated nuclear localization. By confocal immunofluorescence microscopy, we detected IGFBP‐5 in the vesicular compartment of mammary epithelial cells in culture, while no nuclear staining was observed. Immunohistochemistry performed on paraffin sections of the involuting mammary gland revealed IGFBP‐5 positive staining of epithelial cells only outside the nucleus. To evaluate the contribution of reuptake of extracellular IGFBP‐5, T47D cells were incubated with Alexa Fluor 647‐labeled IGFBP‐5. The protein was taken up into intracellular vesicles and again was neither detectable in the cytoplasm outside of vesicular structures nor in the nucleus. Quantification of the time and concentration dependence of uptake by immunoblotting revealed that the process was saturable at IGFBP‐5 concentrations between 1 and 2 μm and partially reversible with 30% remaining in the cell after a 1‐h chase. The observation of nuclear uptake of IGFBP‐5 was restricted to artificial conditions such as expression of non‐secreted forms of IGFBP‐5 or selective permeabilization of the plasma membrane by digitonin.
Microtubule‐Tethering Junctions are Fine Structural Distinct Entities that Deserve Attention
Authors: Reipert Siegfried
Published: September 2007

Microtubule tethering at cell junctions, as studied by light microscopy (Ligon and Holzbaur, Traffic 2007;8:808–819), exist as easily recognizable ultrastructural entities that are distinct from adherence junctions. Here, we encourage systematic analysis of cortical microtubule capture by electron microscopy.
Disparate osteogenic response of mandible and iliac crest bone marrow stromal cells to pamidronate
Authors: Stefanik D , Sarin J , Lam T , Levin L , Leboy PS , Akintoye SO
Published: September 2007

Objective:  Long‐term administration of intravenous bisphosphonates like pamidronate is associated with jaw osteonecrosis but axial and appendicular bones remain unaffected. Pathogenesis of bisphosphonate‐associated jaw osteonecrosis may relate to skeletal site‐specific effects of bisphosphonates on osteogenic differentiation of bone marrow stromal cells (BMSCs) of orofacial and axial / appendicular bones. This study evaluated and compared skeletal site‐specific osteogenic response of mandible (orofacial bone) and iliac crest (axial bone) human BMSCs to pamidronate.

Materials and methods:  Mandible and iliac crest BMSCs from six normal healthy volunteers were established in culture and tested with pamidronate to evaluate and compare cell survival, osteogenic marker alkaline phosphatase, osteoclast differentiation in co‐cultures with CD34+ hematopoietic stem cells, gene expression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin, and in vivo bone regeneration.

Results:  Mandible BMSCs were more susceptible to pamidronate than iliac crest BMSCs based on decreased cell survival, lower alkaline phosphatase production, and structurally less organized in vivo bone regeneration. Pamidronate promoted higher RANKL gene expression and osteoclast recruitment by mandible BMSCs.

Conclusion:  Mandible and iliac crest BMSC survival and osteogenic differentiation are disparately affected by pamidronate to favor dysregulated mandible bone homeostasis.