bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoflurane modulates glutamatergic and GABAergic neurotransmission in the amygdala
Authors: Ranft Andreas , Kurz Jörg , Deuringer Martin , Haseneder Rainer , Dodt Hans‐Ulrich , Zieglgänsberger Walter , Kochs Eberhard , Eder Matthias , Hapfelmeier Gerhard
Published: September 2004

Attempts have been made to attribute the particular features of general anaesthesia such as hypnosis, analgesia, amnesia and autonomic stability to certain brain regions. In the present study, we examined the effects of the commonplace volatile anaesthetic isoflurane on synaptic transmission in an in vitro slice preparation of the murine amygdala. Despite the established role of this limbic structure in the formation of aversive memories, conditioned fear and anxiety, as well as pain processing and regulation of sympathetic tone, the influence of volatile anaesthetics on synaptic signalling has not yet been investigated in this region of the brain. Evoked postsynaptic currents were monitored from principal neurons in the basolateral nucleus of the amygdala by means of patch‐clamp recording. The mixed postsynaptic currents were mediated by non‐NMDA, NMDA, GABAA and GABAB receptors. Isoflurane added to the perfusion medium reduced the strength of synaptic signalling following the activation of non‐NMDA, NMDA, and GABAB receptors, whereas the GABAA receptor‐mediated responses were enhanced. The overall reduction of neuronal excitability was also reflected in a reduction of field potential amplitudes. Isoflurane neither changed the membrane resting potential nor the input resistance of principal neurons in the amygdala. The present results may contribute to the understanding of how stress reactions and long‐lasting neuroplastic processes are suppressed under general anaesthesia.
RFa‐related peptides are algogenic: evidence in vitro and in vivo
Authors: Yudin Yevgen K. , Tamarova Zinayida A. , Ostrovskaya Olga I. , Moroz Leonid L. , Krishtal Oleg A.
Published: September 2004

RFamide (RFa)‐related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as ‘anti‐opioid’. They also decrease the rate of desensitization of acid‐sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133–141]. We have tested the role of mollusc‐derived peptide, FMRFa (Phe‐Met‐Arg‐Phe‐amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa‐related peptides powerfully excite the majority of C‐fibres in the skin–nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long‐lasting discharges to the application of peptides (20 µm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185–1190]: the activation of C‐fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C‐fibres to RFa peptides, protons and amiloride: 74% of tested RFa‐sensitive C‐fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa‐related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.
PRIVATISATION O F ENERGY: WAS IT NECESSARY?
Authors: Essex Nigel
Published: September 2004

The economic circumstances of the time produced a favourable climate for energy privatisation. Significant economic benefits flowed from this. Nevertheless, determining the most appropriate approach to privatisation and the structure of regulation after privatisation are not straightforward and depend on technological and economic factors.
WATER PRIVATISATION : TOO MUCH REGULATION?
Authors: Robinson Colin
Published: September 2004

Water privatisation has had some success in allowing capital to be raised without going to government, in improving efficiency and in depoliticising industry decisions. But there is little sign of the liberalisation that, in other privatised utilities (notably gas and electricity), has been so beneficial to customers. It is time to reconsider the view that ‘water is different’ and to examine how to liberalise the water market. Two necessary steps appear to be to separate the pipeline networks from other activities and to adopt a more light‐handed approach to environmental and quality regulation.
THE UK RAILWAY PRIVATISATION : FAILING TO SUCCEED?
Authors: Tyrrall David
Published: September 2004

Railway privatisation has been a mixture of success and failure. Increasing passenger numbers and improvements in rolling stock have been offset by failures in infrastructure maintenance, service quality and most notably cost management. These outcomes can be attributed to the suboptimal structure of the privatised industry.
IT'S NOT TOO LATE TO PRIVATISE ROYAL MAIL
Authors: Senior Ian
Published: September 2004

In classical myth Cerberus was the three‐headed dog that guarded the entrance to hell. The Royal Mail Group (‘RMG’), as the holding company is currently called, is a three‐headed dog that should be put down. This paper examines the problems underlying RMG's three businesses ‐ letters, parcels and counters ‐ and suggests that if Cerberus were privatised as three ordinary dogs and the holding company abolished, they would have much better prospects of profitable survival.
THE MORECAMBE BAY COCKLE PICKERS: MARKET FAILURE OR GOVERNMENT DISASTER?
Authors: Meadowcroft John , Blundell John
Published: September 2004

The tragic deaths of twenty‐three young Chinese cockle pickers in Morecambe Bay on the Lancashire coast have been attributed to the machinations of global capitalism. In fact, these migrant workers came to the UK to escape the poverty created by socialism in China and were working under a regime of state‐regulated access to the cockle beds. An alternative market‐orientated regime of private property rights in the cockle beds might have prevented the tragedy.
Genomics of cellulose biosynthesis in poplars
Authors: Joshi Chandrashekhar P. , Bhandari Suchita , Ranjan Priya , Kalluri Udaya C. , Liang Xiaoe , Fujino Takeshi , Samuga Anita
Published: September 2004

Genetic improvement of cellulose production in commercially important trees is one of the formidable goals of current forest biotechnology research. To achieve this goal, we must first decipher the enigmatic and complex process of cellulose biosynthesis in trees. The recent availability of rich genomic resources in poplars make Populus the first tree genus for which genetic augmentation of cellulose may soon become possible. Fortunately, because of the structural conservation of key cellulose biosynthesis genes between Arabidopsis and poplar genomes, the lessons learned from exploring the functions of Arabidopsis genes may be applied directly to poplars. However, regulation of these genes will most likely be distinct in these two‐model systems because of their inherent biological differences. This research review covers the current state of knowledge about the three major cellulose biosynthesis‐related gene families from poplar genomes: cellulose synthases, sucrose synthases and korrigan cellulases. Furthermore, we also suggest some future research directions that may have significant economical impacts on global forest product industries.
Mitochondrial mechanisms of neural cell apoptosis
Authors: Polster Brian M. , Fiskum Gary
Published: September 2004

The importance of calcium overload, mitochondrial dysfunction, and free radical generation to neuropathological processes has been recognized for many years. Only more recently has evidence accumulated that the programmed cell death process of apoptosis plays an integral role not only in the development of the nervous system, but in the loss of cells following acute neurological insults and chronic disease. In 1996 came the landmark discovery that cytochrome c, an evolutionary old and essential component of the respiratory chain, has a second and deadly function when it escapes the mitochondrion: triggering the cell death cascade. A flurry of activity has since ensued in an effort to understand the mechanistic events associated with mitochondrial permeabilization during apoptosis and regulation by an enigmatic family of proteins characterized by homology to the proto‐oncogene Bcl‐2. This review discusses the evidence for various release mechanisms of apoptotic proteins (e.g. cytochrome c) from neural cell mitochondria, focusing particularly on roles for calcium, Bax, p53, and oxidative stress. The need for new drugs that act at the level of the mitochondrion to prevent apoptosis is also highlighted.
Functional dissociation of apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure
Authors: Messari Said El , Iturrioz Xavier , Fassot Celine , De Mota Nadia , Roesch Darren , Llorens‐Cortes Catherine
Published: September 2004

Apelin is a novel neuropeptide involved in the regulation of body fluid homeostasis and cardiovascular functions. It acts through a G protein‐coupled receptor, the APJ receptor. We studied the structure–activity relationships of apelin at the rat apelin receptor, tagged at its C‐terminal end with enhanced green fluorescent protein and stably expressed in CHO cells. We evaluated the potency of N‐ and C‐terminal deleted fragments of K17F to bind with high affinity to the apelin receptor, and to inhibit cAMP production and to induce apelin receptor internalization. We first characterized the internalization and trafficking of the rat apelin receptor. This receptor was internalized via a clathrin‐dependent mechanism and our results suggest that receptor trafficking may follow a recycling pathway. We then tried to identify the amino acids of K17F required for apelin activity. The first five N‐terminal and the last two C‐terminal amino acids of K17F were not essential for apelin binding or the inhibition of cAMP production. However, the full‐length sequence of K17F was the most potent inducer of apelin receptor internalization because successive N‐terminal amino‐acid deletions progressively reduced internalization and the removal of a single amino acid at the C‐terminus abolished this process. Finally, the most novel observation of this work is that hypotensive actions of apelin peptides correlate best with the ability of those ligands to internalize. Thus, apelin receptor signaling and endocytosis are functionally dissociated, possibly reflecting the existence of several conformational states of this receptor, stabilized by the binding of different apelin fragments to the apelin receptor.
Erk1/2 but not PI3K pathway is required for neurotrophin 3‐induced oligodendrocyte differentiation of post‐natal neural stem cells
Authors: Hu Xinhua , Jin Lu , Feng Linyin
Published: September 2004

Neurotrophin 3 (NT3) induces mouse cortical stem cells to an asymmetric division from a symmetric division, suggesting that NT3 may work as an early differentiative signal for neural stem cells (NSCs). Here, using cultured post‐natal hippocampal stem cells as a model, we demonstrated that NT3‐stimulation causes NSCs to differentiate into oligodendrocyte precursors (OLPs) through an extracellular signal‐related kinase1/2 (Erk1/2)‐dependent pathway. Following the treatment of NT3 for 24 h, NSCs differentiated into more OLPs and fewer neurons, whereas the proliferation and survival of OLPs were not affected. NT3 induced a series of intracellular responses including enhancement of phosphorylation of Erk1/2 or Akt and increase of expression of oligodendrocyte lineage gene (Olig)‐1, a transcriptional factor known to participate in oligodendrocyte development. Application of U0126, a specific inhibitor of MEK1/2 which are upstream to Erk1/2, blocked the phosphorylation of Erk1/2, suppressed the expression of Olig‐1 and prevented NSC differentiation into OLPs in response to NT3 stimulation. Blockade of TrkC also inhibited the differentiation of NSCs to OLPs induced by NT3. However, administration of LY294002, an inhibitor of phosphatidylinositol 3 kinase (PI3K), blocked the phosphorylation of Akt but did not affect the effect of NT3 on the expression of Olig‐1 and on NSC differentiation into OLPs. Taken together, these results suggest that NT3 induce NSCs to differentiate into OLPs by enhancing the expression of Olig‐1 through an Erk1/2‐dependent pathway.
PEN‐2 enhances γ‐cleavage after presenilin heterodimer formation
Authors: Shiraishi Hirohisa , Sai Xiaorei , Wang Hua‐Qin , Maeda Yasuhiro , Kurono Yukihisa , Nishimura Masaki , Yanagisawa Katsuhiko , Komano Hiroto
Published: September 2004

The presenilin (PS) complex, including PS, nicastrin, APH‐1 and PEN‐2, is essential for γ‐secretase activity, which is required for amyloid β‐protein (Aβ) generation. However, the precise individual roles of the three cofactors in the PS complex in Aβ generation remain to be clarified. Here, to distinguish the roles of PS cofactors in γ‐secretase activity from those in PS endoproteolysis, we investigated their roles in the γ‐secretase activity reconstituted by the coexpression of PS N‐ and C‐terminal fragments (NTF and CTF) in PS‐null cells. We demonstrate that the coexpression of PS1 NTF and CTF forms the heterodimer and restores Aβ generation in PS‐null cells. The generation of Aβ was saturable at a certain expression level of PS1 NTF/CTF, while the overexpression of PEN‐2 alone resulted in a further increase in Aβ generation. Although PEN‐2 did not enhance PS1 NTF/CTF heterodimer formation, PEN‐2 expression reduced the IC50 of a specific γ‐secretase inhibitor, a transition state analogue, for Aβ generation, suggesting that PEN‐2 expression enhances the affinity or the accessibility of the substrate to the catalytic site. Thus, our results strongly suggest that PEN‐2 is not only an essential component of the γ‐secretase complex but also an enhancer of γ‐cleavage after PS heterodimer formation.
Counteraction of axonal growth inhibitory properties of Semaphorin 3A and myelin‐associated proteins by a synthetic neurotrophic compound
Authors: Hanbali Mazen , Bernard Frédéric , Berton Caroline , Gatineau Gilles , Perraut Martine , Aunis Dominique , Luu Bang , Bagnard Dominique
Published: September 2004

One of the reasons for the lack of nerve regeneration in the CNS is the formation of a glial scar over‐expressing multiple inhibitory factors including myelin‐associated proteins and members of the Semaphorin family. Innovative therapeutic strategies must stimulate axon extension across the lesion site despite this inhibitory molecular barrier. We recently developed a synthetic neurotrophic compound combining an ω‐alkanol with a retinol‐like cycle (3‐(15‐hydroxy‐pentadecyl)‐2,4,4,‐trimethyl‐cyclohexen‐2‐one (tCFA15)). Here, we demonstrate that tCFA15 is able to promote cortical axon outgrowth in vitro even in the presence of the inhibitory Semaphorin 3A and myelin extracts. This growth‐promoting effect is selectively observed in axons and requires multiple growth‐associated intracellular pathways. Our results illustrate the potential use of synthetic neurotrophic compounds to promote nerve regeneration by counteracting the axonal growth inhibition triggered by glial scar‐associated inhibitory factors.
Modulation of extracellular signal‐regulated kinase (ERK) activity by acute and chronic opioid treatment in neuronal and glial cell lines
Authors: Moulédous Lionel , Diaz Miguel F. , Gutstein Howard B.
Published: September 2004

Acute mu opioid application has been shown to activate extracellular signal‐related kinases (ERKs) in various non‐neural cell lines. However, ERK activation in neuronal cells following acute morphine treatment is more questionable. Moreover, the ERK activation phenomenon observed in vivo after withdrawal of chronic opioids has never been demonstrated in vitro. The goal of this study was to determine if mu agonist treatment induced ERK activation acutely or after withdrawal of chronic opioids in one glial and three neuronal cell lines. We found that acute application of opioids was not able to activate ERK in neuronal cell lines but was able to activate ERK in a glial cell line. In another set of experiments, cells were chronically treated with escalating doses of a mu opioid agonist. After 8 days, the agonist was removed from the media and naloxone applied. Acute ERK activation was not seen in any tested cell line after agonist removal. These findings suggest that opioids may acutely activate ERK in non‐neuronal cells, and that the acute ERK activation observed in some brain regions during opioid withdrawal in vivo might be mediated by indirect effects on neuronal cells.
5‐HT stimulates eEF2 dephosphorylation in a rapamycin‐sensitive manner in Aplysia neurites
Authors: Carroll Matthew , Warren Otis , Fan Xiaotang , Sossin Wayne S.
Published: September 2004

In Aplysia, serotonin mediates behavioral sensitization by increasing the strength of the synapse between sensory and motor neurons, a process known as facilitation. The retention of long‐term facilitation is blocked by rapamycin, an inhibitor of a specific translational pathway. One possible rapamycin‐sensitive target is the increased translation of 5′‐terminal oligopyrimidine mRNAs. These transcripts encode components of the translational machinery and have been proposed to be important for retention of long‐term facilitation. We have cloned the 5′‐terminal oligopyrimidine mRNA encoding eukaryotic elongation factor 2 and shown that serotonin increased its translation in synaptosomes. Another possible rapamycin‐sensitive target is the inactivation of eukaryotic elongation factor 2 kinase. Eukaryotic elongation factor 2 kinase phosphorylates and inactivates eukaryotic elongation factor 2, blocking translational elongation. Serotonin application decreased eukaryotic elongation factor 2 phosphorylation in synaptosomes and in isolated neurites, and this was blocked by rapamycin. We propose a role for the rapamycin‐sensitive pathway in neurons. Stimulation blocks translation by inducing calcium entry and phosphorylation of eukaryotic elongation factor 2. This block is reversed through activation of the rapamycin‐sensitive system and dephosphorylation of eukaryotic elongation factor 2.
Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines
Authors: Zimmermann Martina , Gardoni Fabrizio , Marcello Elena , Colciaghi Francesca , Borroni Barbara , Padovani Alessandro , Cattabeni Flaminio , Di Luca Monica
Published: September 2004

Acetylcholinesterase inhibitors (AChEIs) are the only currently available drugs for treating Alzheimer's Disease (AD). Some authors have suggested a function of AChEIs not only in the induction of AChE overproduction and alternative splicing shifts but also a possible role of these drugs in amyloid metabolism beyond their well‐known symptomatic effect. Here, we investigate the mechanisms of action of the AChEI donepezil on APP (amyloid precursor protein) metabolism and on the activity/trafficking of the alpha‐secretase candidate ADAM 10, in differentiated human neuroblastoma cells (SH‐SY5Y). In these cells, the activity of AChE is significantly decreased after 2 h of donepezil treatment. Further, SH‐SY5Y cells released significantly more sAPPα into the medium, whereas total APP levels in cell lysates were unchanged. Interestingly, treated cells showed increased ADAM 10 levels in membrane compartments. This effect was prevented by pretreatment with tunicamycin or brefeldin, suggesting that donepezil affects trafficking and/or maturation of ADAM 10; additionally, this pretreatment significantly decreased sAPPα levels. Pre‐incubation with atropine decreased release of sAPPα significantly but did not revert ADAM 10 activity to control levels further suggesting that donepezil acts not solely through a purely receptor mediated pathway. These findings indicate that donepezil exerts multiple mechanisms involving processing and trafficking of key proteins involved in AD pathogenesis.
Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor‐kappa B in interleukin‐1β‐induced matrix metalloproteinase‐9 expression in rat brain astrocytes
Authors: Wu Cheng‐Ying , Hsieh Hsi‐Lung , Jou Mei‐Jie , Yang Chuen‐Mao
Published: September 2004

Matrix metalloproteinase (MMP)‐9 expression induced by interleukin‐1β (IL‐1β) was investigated in rat brain astrocyte‐1 (RBA‐1). Here we report that the mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB) pathways participate in the induction of MMP‐9 expression by IL‐1β. Zymographic, western blotting, and RT‐PCR analyses showed that IL‐1β increased expression of MMP‐9 mRNA and protein, which were inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). In accordance with these findings, IL‐1β stimulated phosphorylation of p42/p44 MAPK, p38, and c‐Jun N‐terminal kinase (JNK), which was attenuated by U0126, SB202190, or SP600125, respectively. Furthermore, this up‐regulation of MMP‐9 mRNA and protein was blocked by a specific NF‐κB inhibitor helenalin. Consistently, IL‐1β‐stimulated translocation of NF‐κB into the nucleus and degradation of inhibitory kappa B‐α (IκB‐α) was revealed by western blotting and immunofluorescence staining, which was blocked by helenalin, but not by U0126, SB202190, or SP600125. Taken together, these results suggest that in RBA‐1 cells, activation of p42/p44 MAPK, p38, JNK and NF‐κB pathways is essential for IL‐1β‐induced MMP‐9 gene expression via transcription and translation processes. An increased understanding of the signal transduction pathways involved in IL‐1β‐induced MMP‐9 expression on RBA‐1 may be of potential therapeutic value in the treatment of inflammatory disease.
Application of proteasomal inhibitors to mouse sympathetic neurons activates the intrinsic apoptotic pathway
Authors: Lang‐Rollin Isabelle , Vekrellis Konstantinos , Wang Qiaohong , Rideout Hardy J. , Stefanis Leonidas
Published: September 2004

Proteasomal dysfunction may play a role in a number of neurodegenerative conditions, and in particular Parkinson's disease (PD) and related Lewy body (LB) diseases. Application of proteasomal inhibitors to neuronal cell culture systems is associated with survival‐promoting effects or with cell death depending on the model system. We have applied pharmacological proteasomal inhibitors to cultured neonatal mouse sympathetic neurons in order to investigate whether these catecholaminergic neurons, which are affected in PD, are sensitive to proteasomal inhibition and, if so, which cell death pathway is activated. We report here that proteasomal inhibition leads to apoptotic death of mouse sympathetic neurons. This death is accompanied by caspase 3 activation and cytochrome c release from the mitochondria and is abrogated by caspase inhibition. Bax deletion prevented both cytochrome c release and caspase 3 activation, and also provided complete protection against proteasomal inhibition‐induced death. Bcl‐2 overexpression achieved a similar survival‐promoting effect. There was no change in Bax levels following proteasomal inhibition, suggesting that Bax itself is not regulated by the proteasome in this cell culture system, and that a primary increase in Bax is unlikely to account for death. In contrast, levels of the BH3‐only protein, Bim, increased with proteasomal inhibition. We conclude that proteasomal inhibition of mouse sympathetic neurons activates the intrinsic apoptotic pathway involving bcl‐2 family members and the mitochondria.
Neuregulin induces GABAA receptor β2 subunit expression in cultured rat cerebellar granule neurons by activating multiple signaling pathways
Authors: Xie Fang , Raetzman Lori T. , Siegel Ruth E.
Published: September 2004

The GABAA receptor β subunit is required to confer sensitivity to γ‐aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. In previous studies we demonstrated that the growth and differentiation factor neuregulin 1 (NRG1) selectively induced expression of the β2 subunit mRNA and encoded protein in rat cerebellar granule neurons in culture. In the present report we examine the signaling pathways that mediate this effect. These studies demonstrate that the effects of NRG1 on β2 subunit polypeptide expression require activation of the ErbB4 receptor tyrosine kinase; its effects are inhibited by pharmacological blockade of ErbB4 phosphorylation or reduction of receptor level with an antisense oligodeoxynucleotide. The NRG1‐induced activation of ErbB4 stimulates the mitogen‐activated protein kinase (MAPK), phosphatidylinositol 3‐kinase (PI3K) and cyclin‐dependent kinase‐5 (cdk5) pathways. Pharmacological blockade of any of these pathways inhibits increased β2 subunit expression, demonstrating that all three pathways are required to mediate the effects of NRG1 on GABAA receptor subunit expression in cerebellar granule neurons. These studies provide novel information concerning the actions of NRG1 on GABAA receptor expression in the CNS.
System dynamics modelling for supply‐chain management: A case study on a supermarket chain in the UK
Authors: Ge Y. , Yang J.‐B. , Proudlove N. , Spring M.
Published: September 2004

This paper presents a system dynamics (SD) approach for the analysis of the demand amplification problem, also known as the bullwhip effect, which has been studied fairly extensively in the literature. The construction of an SD model is reported using a part of a supermarket chain system in the UK as an example. Based on the model, the causes of the dynamic behaviour of the system and the sources of amplification from the downstream to the upstream of the chain are investigated. The impact of information delays, demand forecasting and information sharing on the performance of the multi‐echelon supply chain is analysed. Some implementation issues are also addressed based on the simulation analysis.
A parallel hybrid local search algorithm for the container loading problem
Authors: Mack D. , Bortfeldt A. , Gehring H.
Published: September 2004

In this contribution, a parallel hybrid local search algorithm for the three‐dimensional container loading problem (CLP) is proposed. First a simulated annealing method for the CLP is developed, which is then combined with an existing tabu search algorithm to form a hybrid metaheuristic. Finally, parallel versions are introduced for these algorithms. The emphasis is on CLP instances with a weakly heterogeneous load. Numerical tests based on the well‐known 700 test instances from Bischoff and Ratcliff are performed, and the outcome is compared with methods from other authors. The results show a high solution quality obtained with reasonable computing time.
Applying the shortest‐path‐counting problem to evaluate the importance of city road segments and the connectedness of the network‐structured system
Authors: Oyama Tatsuo , Morohosi Hozumi
Published: September 2004

We consider the shortest‐path‐counting problem (SPCP), which asks how many shortest paths is each edge of a network contained in? There are n(n−1) shortest paths in a network with n nodes, so among all these shortest paths the SPCP requires us to count the number of shortest paths passing through each edge. We obtain theoretical results in the form of explicit expressions for special types of networks such as trees, grid type, circular type, etc. We apply the SPCP to measure the importance of city road segments, which will certainly contribute to estimate the traffic congestion of the city road segments. Then we propose a quantitative method for evaluating the stable connectedness of the network‐structured system using shortest‐path‐counting methods. We define the stable‐connection function and the expected stable‐connection function for the network‐structured system. Then we derive some theoretical results for some special types of network such as single path, cycle graph, and complete graph. Several properties and characteristics of the stable‐connection function are also shown with some theoretical results. We show the application of the Monte Carlo method to estimate the expected stable‐connection function. This method can be applied to measure the strength of connectedness of the Japanese road network system.
The optimal allocation of a circular principal road based on the average traveling distance of an urban traffic model
Authors: Li Mingzhe
Published: September 2004

In this paper, considering the average distance traveled by car commuters in principal roads, we theoretically give the optimal allocation of a circular principal road based on an urban traffic model. The results obtained and related properties are considered to be meaningful at the very beginning stage of designing some urban cities.
Resident forum abstracts EVALUATION OF THROMBOELASTOGRAPHY (TEG) IN NORMAL CATS
Authors: Alwood AJ , Downend AB , Slensky KA , Fox JA , Simpson SA , Donahue SM , Waddell LS , Otto CM
Published: September 2004

Objective: To establish normal parameters of thromboelastography (TEG) in healthy adult cats.

Background: Thromboelastography (TEG) is an in vitro test of coagulation that has been shown to be useful in humans, dogs and select species to identify and quantify alterations of hemostasis (e.g., hypercoagulable and hypocoagulable states). It has also been demonstrated to be useful in monitoring effects of anticoagulant therapies. This test has not been evaluated in cats.

Methods: Blood was collected from 25 clinically normal cats by venipuncture using a 21 gauge×3 1/2 inch butterfly catheter and syringe for medial saphenous or jugular venipuncture. A single 1.8 mL sample in 3.8% Sodium Citrate (9:1) was collected from each cat. Recalcified whole blood was analyzed 30 minutes following collection with the TEG® 5000 analyzer (Haemoscope, Niles, IL). Analysis temperature was 37.6°C. TEG parameters recorded included: R‐value (represents initial fibrin formation), K (time from R to standard fixed measure of clot firmness which represents contributions of platelets and fibrinogen), maximum amplitude (MA; represents absolute clot strength), and alpha angle (α; the slope of TEG tracing which represents rate of clot formation). The coagulation index (CI) was derived from the formula generated for humans to provide an overall assessment of whether the sample was hyper‐ or hypocoagulable.

Results: Values for the 25 normal cat samples are reported as mean ±2 standard deviations. R=2.97; 1.23–4.72; K=1.54, 0.38–2.71; α=70.70, 57.76–83.65; MA=58.50, 45.26–71.74 and CI=2.27, 0.07–4.46. Compared to historical information obtained on normal dogs, cats have significantly shorter R and K and larger α, MA and CI.

Conclusions: TEG does have reproducible performance when used to evaluate coagulation status in normal cats. Compared to dogs, normal cats favor a hypercoagulable state. Species‐specific normal values are necessary for interpretation of TEG results. This test bears potential value for use in future experimental and clinical work to investigate hemostasis in cats receiving anticoagulant therapies or in cats suffering from diseases such as cardiomyopathy which are thought to be associated with altered coagulation status.
ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME IN CATS: 65 CASES (1993–2003)
Authors: Sauvé V , Parent C , Seiler G , French A , VanWinkle TJ , King LG
Published: September 2004

Objectives: 1) Describe the clinical course and diagnostic findings of cats with histopathologic evidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 2) Identify risk factors for ALI/ARDS in cats.

Animals: Sixty‐five client‐owned cats with moderate to severe interstitial pneumonia, pneumonitis or alveolitis consistent with ALI/ARDS on post‐mortem examination and clinical evidence of respiratory compromise.

Procedure: Retrospective evaluation of medical records, postmortem examination and radiographs.

Results: Cats in this study tended to be middle aged (mean 6.5±4.9 years). They had a short duration of illness (median 4 days; range 0–120 days) and of dyspnea (median 1 day; range 1–7 days). On presentation, the cats were tachypneic (mean respiratory rate 53±23 bpm) and relatively bradycardic (mean heart rate 166±43 bpm). The majority of cats were dyspneic (n=39) at presentation; all others developed respiratory difficulties during hospitalization. The mean white blood cell count was within normal limits (14.6±14.0 k/μL); 8 cats had a leukocytosis and 7 were leucopenic. Clinical findings consistent with SIRS (n=39) and sepsis (n=10) were common. Thoracic radiographs were reviewed in 31 cats and alveolar disease was the most frequent pattern (105 lung lobes) followed by interstitial disease (86 lung lobes). No cat had normal thoracic radiographs throughout hospitalization. Underlying disease was not identified on post‐mortem examination in 15 cats (23%), but in the remaining cats underlying diseases included infectious systemic disease (n=11), neoplasia (n=8), respiratory (n=8) and urinary (n=7) system disorders, acute pancreatitis (n=7), hepatic diseases (n=5), major trauma (n=4), sepsis (n=3), CNS (n=2) and other systems (n=5). Nine cats had more then one underlying process.

Conclusions: This study describes a naturally‐occurring syndrome of ALI/ARDS in cats analogous to that which occurs in dogs and humans. In cats, ALI/ARDS occurs as a sequela of a variety of underlying systemic diseases, but in approximately one‐quarter of patients an underlying cause is not identified at necropsy. It is important to consider ALI/ARDS in systemically ill cats who become dyspneic; in cats with pulmonary disease with acute worsening of respiratory status and in cats with pulmonary infiltrates for which no other cause can be identified.
ANALYZER‐CALCULATED OXYHEMOGLOBIN SATURATION AND OXYGEN CONTENT VALUES ARE COMPARABLE TO HAND‐CALCULATED VALUES USING A NORMAL CANINE OXYHEMOGLOBIN DISSOCIATION RELATIONSHIP IN UNSEDATED HEALTHY DOGS
Authors: Scott NE , Haskins SC , Aldrich J
Published: September 2004

Introduction: The amount of oxygen in blood is an important measure of lung function. There are three ways to quantify the amount of oxygen in blood: 1) the oxygen tension (PO2); 2) the percent of hemoglobin saturated with oxygen (HbO2); and 3) the absolute content of oxygen in the blood (ContO2). PO2 is commonly measured. HbO2 and ContO2 are usually calculated from the normal human oxyhemoglobin relationship, but can be measured directly. The canine curve is similar to, but not the same as, that of humans. The purpose of this study was to compare, in dogs, direct measurements of HbO2 and ContO2 with analyzer‐calculated values derived using the human oxyhemoglobin curve, and with hand‐calculated values derived using a canine oxyhemoglobin curve.

Materials And Methods: Arterial and jugular venous samples from 17 healthy dogs were analyzed by an ABL 705 blood gas and electrolyte analyzer, an OSM3 co‐oximeter, and a LexO2con oxygen content analyzer. HbO2 was calculated from the measured PO2 using a published formula based on normal canine data (Reeves, 1982), and compared to measured and analyzer‐calculated values. ContO2 values were calculated, and compared to measured and analyzer‐calculated values. Means and standard deviations were compared by analysis of variance for repeated measures. Differences were considered significant at p<0.05.

Results: Arterial HbO2 determined by the ABL 705 factory‐programmed algorithm, reported by the OSM3 co‐oximeter, and calculated from Reeves' canine formula were significantly different (97.1±0.57, 98.2±0.58, and 96.6±0.74, respectively). The calculated canine HbO2 was significantly lower than that measured by the OSM3 or calculated by the ABL for both arterial and jugular venous samples. Calculated and measured arterial and venous ContO2 were similar, as were arterial‐venous ContO2 differences. However, values derived from the calculated canine HbO2 (canine‐calculated) resulted in the greatest arterial‐venous ContO2 difference.

Conclusion: ABL‐calculated and canine‐calculated HbO2 were similar to measured values. Likewise, ABL‐calculated, canine‐calculated, and OSM3‐calculated ContO2 were very similar to measured values. Although some of the values generated by the different methods are statistically significantly different, these differences are unlikely to be clinically important in the healthy dog.
RETROPERITONEAL EFFUSION IN DOGS AND CATS
Authors: Stoneham AE , O'Toole TE , De Laforcade AM , King R , Sato AF
Published: September 2004

Although cases of retroperitoneal effusion associated with adrenal gland neoplasia have been reported in the veterinary literature, these clinical reports have been largely anecdotal. To our knowledge, no comprehensive evaluation of the causes or clinical indications of effusion (RPE) in the retroperitoneal space exists. In this retrospective study, we evaluated the causes, presenting signs, clinical findings and outcomes associated with RPE. The records of 23 cats and 44 dogs presenting to the Tufts University School of Veterinary Medicine between 1996 and 2003 and having been identified with RPE were reviewed. The presence of RPE was identified using abdominal ultrasonography. All of the cats and 84% (n=38) of dogs in this study presented through the Emergency Service. Diagnoses for RPE were categorized as follows: (Group 1) 14 dogs and 3 cats with acute renal failure associated with infection; (Group 2) 5 dogs and 6 cats with acute renal failure of unknown etiology; (Group 3) 3 cats with acute renal failure due to urinary tract obstruction; (Group 4) 8 dogs with adrenal gland neoplasia; (Group 5) 7 dogs and 1 cat with non‐adrenal gland neoplasia; (Group 6) 5 dogs and 4 cats with other renal disease, and (Group 7) 5 dogs and 6 cats with RPF due to other causes. The most frequent presenting complaints in all categories except for those in Group 4 included anorexia, lethargy and vomiting. Physical examination findings were very similar for all categories except for those in Group 4 and included abdominal pain, dehydration, mental depression, lethargy and weakness. For those in Group 4, the most common complaints were collapse or marked weakness, anorexia, lethargy, and discomfort. The physical examination findings for dogs in Group 4 also included collapse or marked weakness, and abdominal distension. Percent mortality for dogs was 39% and, for cats, 43%. In each category, the percent mortalities are as follows (euthanized=e, died=d): Group 1: dogs: 14% (e n=1, d n=1), and cats: 33% (e n=1); Group 2: dogs: 100% (e n=4, d n=1) and cats 67% (e n=4).; Group 3: cats: 100% (e n=2, d n=1); Group 4: dogs: 32% (e n=3); Group 5: dogs: 71% (e n=5) and cats: 0%;. Group 6: dogs: 0% and cats: 25% (e n=1), and Group 7: dogs: 40% (e n=2) and cats: 17% (e n=1). Retroperitoneal effusion, regardless of cause, is associated with significant disease. In people, another category of disease associated with RPE is trauma. Although this category is not included in this study, abdominal ultrasonography of trauma victims may identify a veterinary population with RPE.
ONE KNOT CONTINUOUS SHOE‐LACE TECHNIQUE FOR THORACIC WALL CLOSURE
Authors: Crowe DT
Published: September 2004

A new closure technique developed for lateral thoracotomy approaches in emergency surgeries was used to close 20 thoracotomies in 5 cats and 15 dogs, and the results were compared retrospectively to a previously recommended and published technique. The continuous shoe‐lace technique involved the use of monofilament 2–0 (cats) to 2 sized (large dogs) polypropylene on a swaged on taper needle. The closure pattern began at the dorsal aspect of the intercostal opening just caudal to the caudal rib and then moved to just cranial to the cranial rib. The pattern continued in a continuous fashion, placing a suture bite every 1–2 cm (cats) to every 3–4 cm (large dogs). At the ventral aspect of the incision, the closure continued back dorsally with a continuous lacing‐like pattern. At the conclusion of the pattern dorsally the sutures on each side of the incision were pulled tight. The opening between the ribs was brought together with this tightening. The single knot was then tied. Results revealed a more rapid closure than the conventional closure (averaging 10 minutes versus 20 minutes, respectively). No dehiscence was observed with either technique. The single knot was able to be tied without any difficulty. No other complications were observed. This study proved that the new closure technique was very effective. It is recommended over the routine previously accepted and published method because of increased speed and less suture material buried. This is especially helpful in emergency surgery where surgery time needs to be as short as possible.
CRANIAL TIBIAL ARTERY CATHETER FOR MONITORING PRESSURES AND SAMPLING
Authors: Crowe DT
Published: September 2004

A technique for placement of a long‐term arterial catheter that the author developed was used in 20 canine patients. The catheter was used for pressure monitoring and arterial blood sampling. The technique involved the following steps post‐sedation and placement of a local anesthetic:

Clipping and prepping of the medial aspect of the distal tibia and proximal metatarsal region;

Incision over the medial tibial malleolus just caudal to the cranial tibial muscle‐tendon;

Blunt dissection of the space just caudal to the cranial tibialis tendon;

Isolation of the cranial tibial artery and loop placement proximally and distally;

Placement of a 3 Fr. polyurethane 4–8 cm catheter using a Seldinger wire technique;

Placement of a suture in the periosteium of the distal tibia and anchoring of the catheter with this suture;

Closure of the skin incision with sutures or staples;

Bandage application to hold the catheter in place.

The entire surgical procedure was done using sterile technique. The catheter was able to be kept in place and working for up to 9 days (averaged 4 days). This compared favorably retrospectively over dorsalis pedis catheters that lasted only a maximum of 4 days. (average 1.5 days). Because of the size of the catheter (3 Fr.) it provided improved waveforms over that observed with the dorsalis pedis catheter (22 g) and its occlusion rate was very low (2 in 20). The cranial tibial artery catheter was found to be particularly effective because the catheter was able to be inserted several cm up the artery and the catheter was able to be anchored well. No major complications were observed with this technique. Because of its effectiveness it is recommended to be used routinely over femoral artery and dorsal pedis artery catheters.
CLOSTRIDIUM TETANUS INFECTION IN 13 DOGS AND ONE CAT
Authors: Bandt C , Steinberg T , Shaw SP
Published: September 2004

Clostridium tetani infection is uncommon in dogs and cats. Up to this point in time just single case reports have been published in veterinary medicine. The goal of this retrospective study was to describe the clinical features and outcome of 13 dogs and one cat affected with Clostridium tetani. The medical records of the last ten year were reviewed. Dogs and cats that were identified as being infected with Clostridium tetani on the basis of characteristic clinical signs and/or bacterial culture from infected wounds were eligible for study inclusion. Thirteen dogs and one cat met the criteria for study inclusion. Six different breeds and mix‐breed dogs were affected, German Shepherd dogs (n=4, 29%) and Labrador retriever (n=3, 21%) were the most frequently affected breeds. Observed clinical complications were ventricular aspiration pneumonia (n=7), laryngeal spasm (n=6), hypersalivation (n=4), ventricular tachycardia (n=3), and third degree AV block (n=1). Median days from onset of clinical signs until first signs of improvement were 10 days (range: 9–12 days). Median hospitalisation time was 18 days (range: 14–22 days). Six animals showed full recovery and 8 animals died or were euthanized. Death was associated with acute onset of ventricular tachycardia in 2 dogs, 1 dog died with non‐responsive third degree AV‐block, 3 dogs died after developing aspiration pneumonia, and 1 dog died of unknown causes.
SIMPLE AUTOTRANSUSION IN SEVERE HEMORRHAGE: SUCCESS IN 8 OF 12 DOGS
Authors: Crowe DT
Published: September 2004

A simple technique for autotransfusion has been developed and used in the successful resuscitation of dogs suffering severe trauma and /or hemorrhage. The purpose of this abstract is three‐fold: 1) Describe the criteria used in case selection; 2) Describe the method used; and 3) Describe the results of its use in a limited number of cases.

Case Selection: The criteria used were the following: 1. Ongoing significant hemorrhage or severe hemorrhage noted in a body cavity where the blood could be collected; 2. Acute hemorrhage amounts deemed to be life‐threatening (>40% calculated blood volume [88 ml/kg]); 3. Where other choices (fresh or stored homologus blood, Oxyglobin) in amounts needed were not possible.

Method: Blood was aspirated into a suction canister using a Pool or Yankauer suction tip, with the tip placed under the pool (s) of blood to eliminate as many bubbles in the collection process as possible. If the canister was not sterilized it was scrubbed with a surgical prep solution and then rinsed with tap water prior to blood collection. The blood in the canister was poured into a wide opening in a hanging empty plastic intravenous fluid bag with a blood administration set inserted. The blood was intravenously administered by gravity drip as needed. No attempt was made to use any anticoagulant. Amounts of blood given, clinical responses, and complications were recorded.

Results: The procedure was used in 12 dogs: 5 abdominal hemorrhage, 3 thoracic hemorrhage, 2 hemorrhage from both abdomen and chest, 2 vertebral vein hemorrhage. All blood administered was given during the operation or within 2 hours. Amounts transfused ranged from 30 to 120 ml/kg (body weight [mean 48 ml/kg]). No animals died acutely from signs thought to be associated with the transfusion of this blood. Those cases surviving to discharge were 4 abdominal, 2 thoracic, 1 combined, and 1 vertebral vein. There were no infections attributed to the autotransfusion. It is concluded that this technique can be recommended and may be considered life‐saving in selected cases.