bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron chelation and regulation of the cell cycle: 2 mechanisms of posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion
Authors: Fu Dong , Richardson Des R.
Published: April 2007

Iron (Fe) plays a critical role in proliferation, and Fe deficiency results in G1/S arrest and apoptosis. However, the precise role of Fe in cell-cycle control remains unclear. We observed that Fe depletion increased the mRNA of the universal cyclin-dependent kinase inhibitor, p21CIP1/WAF1, while its protein level was not elevated. This observation is unique to the G1/S arrest seen after Fe deprivation, as increased p21CIP1/WAF1 mRNA and protein are usually found when arrest is induced by other stimuli. In this study, we examined the posttranscriptional regulation of p21CIP1/WAF1 after Fe depletion and demonstrated that its down-regulation was due to 2 mechanisms: (1) inhibited translocation of p21CIP1/WAF1 mRNA from the nucleus to cytosolic translational machinery; and (2) induction of ubiquitin-independent proteasomal degradation. Iron chelation significantly (P < .01) decreased p21CIP1/WAF1 protein half-life from 61 (± 4 minutes; n = 3) to 28 (± 9 minutes, n = 3). Proteasomal inhibitors rescued the chelator-mediated decrease in p21CIP1/WAF1 protein, while lysosomotropic agents were not effective. In Fe-replete cells, p21CIP1/WAF1 was degraded in an ubiquitin-dependent manner, while after Fe depletion, ubiquitin-independent proteasomal degradation occurred. These results are important for considering the mechanism of Fe depletion–mediated cell-cycle arrest and apoptosis and the efficacy of chelators as antitumor agents.
β2-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking
Authors: Zhang G. , Hayden C. M. , Khoo S-K. , Candelaria P. , Laing I. A. , Turner S. , Franklin P. , Stick S. , Landau L. , Goldblatt J. , Le Souëf P. N.
Published: April 2007

The aim of the present study was to assess the effects of possible interactions between β2-adrenoceptor gene polymorphisms and passive smoking on forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and exhaled nitric oxide (eNO) in children aged 11 yrs.

A cross-sectional analysis of the longitudinal cohort was conducted for associations between β2-adrenoceptor gene polymorphisms and lung function and eNO with regard to passive smoking.

Among children exposed to tobacco smoke, those with Arg16 (at least one Arg allele) exhibited lower adjusted mean FEV1(2.19versus2.38 L) and FVC (2.43versus2.64 L) than Gly16 homozygotes. Those with Gln27 (at least one Gln allele) also exhibited a lower adjusted mean FEV1relative to Glu27 homozygotes (2.24versus2.39 L). Among children with no exposure to smoking, those with Arg16 or Gln27 showed lower adjusted geometric mean eNO levels compared with Gly16 homozygotes (15.4versus30.9 ppb) and Glu27 homozygotes (18.0versus49.7 ppb).

In conclusion, passive smoking had a significant effect on associations between β2-adrenoceptor gene polymorphisms and asthma-related phenotypes, enhancing the relationship between Arg16 and lung function and removing the relationship between Arg16 or Gln27 and exhaled nitric oxide levels.
Nab controls the activity of the zinc-finger transcription factors Squeeze and Rotund inDrosophiladevelopment
Authors: Félix Javier Terriente , Magariños Marta , Díaz-Benjumea Fernando J.
Published: April 2007

Nab proteins form an evolutionarily conserved family of transcriptional co-regulators implicated in multiple developmental events in various organisms. They lack DNA-binding domains and act by associating with other transcription factors, but their precise roles in development are not known. Here we analyze the role of nab in Drosophila development. By employing genetic approaches we found that nab is required for proximodistal patterning of the wing imaginal disc and also for determining specific neuronal fates in the embryonic CNS. We identified two partners of Nab: the zinc-finger transcription factors Rotund and Squeeze. Nab is co-expressed with squeeze in a subset of neurons in the embryonic ventral nerve cord and with rotund in a circular domain of the distal-most area of the wing disc. Our results indicate that Nab is a co-activator of Squeeze and is required to limit the number of neurons that express the LIM-homeodomain gene apterous and to specify Tv neuronal fate. Conversely, Nab is a co-repressor of Rotund in wing development and is required to limit the expression of wingless (wg) in the wing hinge, where wg plays a mitogenic role. We also showed by pull-down assays that Nab binds directly to Rotund and Squeeze via its conserved C-terminal domain. We propose two mechanisms by which the activation of wg expression by Rotund in the wing hinge is repressed in the distal wing.
Stratified exhaust gas recirculation under lean operation of a liquefied petroleum gas spark-ignition engine with liquid phase injection
Authors: Woo Youngmin , Bae Choongsik
Published: April 2007

Stratified exhaust gas recirculation (EGR) not only achieves reductions in NOx emissions and fuel consumption but also improves combustion stability for highly dilute mixtures. In this study, EGR stratification within a cylinder was completed by installing a fast-response solenoid valve in an EGR line and controlling its timing and duration. Lean burn of liquefied petroleum gas (LPG) with stratified EGR was examined to attain lower emissions and better fuel economy.

The obvious stratification of EGR along the vertical distance from the spark plug was observed through a concentration measurement by a planar laser-induced fluorescence (PLIF) technique. Properly stratified EGR showed faster combustion and improved combustion stability for both stoichiometric and lean mixtures compared to those from homogeneous EGR. With a 30 per cent EGR rate, the peak heat release was 10 per cent higher, accompanied by a shorter combustion duration in the stratified EGR (SEGR) case than in the homogeneous EGR (HEGR) case. Addition of EGR into a lean mixture of λ=1.2 led to a further 3 per cent further reduction in fuel consumption, which was attainable only with stratified EGR but not with homogeneous EGR. More EGR could be admitted and NOx emission further reduced with less increase in hydrocarbon emission with stratified EGR than with homogeneous EGR. Those results are due to the dominance of stratified EGR over homogeneous EGR in combustion speed and stability.
Fuel chemistry and cetane effects on diesel homogeneous charge compression ignition performance, combustion, and emissions
Authors: Bunting B G , Wildman C B , Szybist J P , Lewis S , Storey J
Published: April 2007

The effects of cetane number (CN) on homogeneous charge compression ignition (HCCI) performance and emissions were investigated in a single-cylinder engine with port fuel injection, using intake air temperature for control. Commercial fuels and blends of the diesel secondary reference fuels were evaluated, covering a CN range from 19 to 76. Sweeps of intake air temperature showed that low-CN fuels needed higher intake temperatures than high-CN fuels to achieve ignition. As a function of intake air temperature, each fuel passed through a point of maximum indicated mean effective pressure (i.m.e.p.). High-CN fuels required a combustion phasing approximately 10 crank angle degrees (CAD) earlier than the lowest CN fuels in order to prevent misfire. The high-CN fuels exhibited a strong low-temperature heat release (LTHR) event, while no LTHR was detected for fuels with CN ≤ 34. All of the fuels yielded comparable NOx emissions (< 6 ppm at 3.5 bar i.m.e.p.) at their respective maximum i.m.e.p. timeing. Low-CN fuels were prone to excessive pressure rise rates and NOx emissions at advanced phasing, while high-CN fuels were prone to excessive CO emissions at retarded phasing. These results suggest that the products of LTHR, which are high in CO, are more sensitive to the quenching effects of cylinder expansion. Engine speed was found to suppress LTHR since higher engine speed reduces the time allowed for the LTHR reactions. In addition to measurements of standard gaseous emissions, additional sampling and analysis techniques were used to identify and measure the individual exhaust HC species including an array of oxygenated compounds. In addition to high concentrations of formaldehyde and other low molecular weight carbonyls, results showed an abundance of organic acids, ranging from formic to nonanoic acid. Concentrations of high molecular weight partially oxidized species were highest for the high-CN fuels at retarded phasing, and are believed to be a direct product of LTHR.
Combustion phasing of residual-effected homogeneous charge compression ignition
Authors: Caton P A
Published: April 2007

Residual-effected homogeneous charge compression ignition (HCCI) is defined as an approach which relies on the reintroduction of combustion products to achieve both the required dilution and sensible energy rise to enable compression ignition. While convenient, this strategy introduces a coupling between the initial charge temperature and composition which is unique to this approach. Increasing the residual fraction tends to increase the initial charge temperature while simultaneously lowering reactant (fuel-air) concentrations. While intuition into chemical kinetics suggests that the initial thermal state should have the most significant impact on combustion phasing, experimental data for residual-effected HCCI show that increasing residual fraction delays phasing, despite higher apparent initial charge temperature. A kinetics-based model of residual-effected HCCI shows that two regimes of operation exist: A thermally-limited regime, in which phasing is most sensitive to the initial charge temperature, and a concentration-limited regime, in which phasing is most sensitive to the residual fraction. Because HCCI operation is practically limited by the rate of pressure rise as dilution decreases, the model suggests that residual-effected HCCI can occur solely in the concentration-limited regime. Therefore, control strategies for residual-effected HCCI should consider the dilution level as an input of primary importance.
Validation of engine combustion models against detailed in-cylinder optical diagnostics data for a heavy-duty compression-ignition engine
Authors: Singh S , Reitz R D , Musculus M P B , Lachaux T
Published: April 2007

Three different approaches for modelling in-cylinder compression-ignition engine processes for partially premixed combustion modes are compared with experimentally observed cylinder pressure and in-cylinder images of liquid- and vapour-fuel penetration, ignition, combustion, and soot formation in an optically accessible heavy-duty direct injection engine. A multi-dimensional computational fluid dynamics model for engine combustion, KIVA-3V, served as a common platform into which three different combustion submodels were integrated: (1) characteristic time combustion (KIVA-CTC); (2) representative interactive flamelet (KIVA-RIF); and (3) direct integration using detailed chemistry (KIVA-CHEMKIN). Three different engine operating strategies with significant premixing of fuel and air prior to ignition were investigated: Low-temperature combustion achieved by charge dilution, with fuel injection either (1) early, or (2) late in the engine cycle, and (3) long ignition delay, high-temperature combustion (i.e. no charge dilution) with fuel injection near top dead centre of the piston stroke.

Comparison of simulated cylinder pressure and heat-release rates with the experimental results shows that all the combustion submodels predict the cylinder pressures and heat-release rates reasonably well, but predictions of in-cylinder phenomena were significantly different among the submodels. The KIVA-CHEMKIN submodel predictions agree best with experimental observations of the location of ignition sites and the spatial distribution of soot and OH. The KIVA-RIF model, which uses global quantities to account for turbulence-chemistry interactions, under-predicts the flame lift-off, while ignition sites and species distributions are broader than observed experimentally. The KIVA-CTC submodel greatly over-predicts the spatial extent and total amount of in-cylinder soot.
Diesel-fuelled homogeneous charge compression ignition engine with optimized premixing strategies
Authors: Kook Sanghoon , Bae Choongsik , Kim Jangheon
Published: April 2007

The operation of a diesel-fuelled homogeneous charge compression ignition (HCCI) engine was studied in a single-cylinder, direct-injection diesel engine with regard to three key parameters: Spray penetration, time for premixing, and dilution of the premixed charge. The relationships between these parameters were clarified through spray measurements, flame imaging, and combustion analysis. The spray penetration was optimized by a small included angle to avoid wall impingement at low pressure and temperature in the cylinder. However, the hole diameter did not affect spray penetration. Sufficient time for premixing was realized by advanced injections earlier than 100 crank angle degrees (CAD) before top dead centre (BTDC) at 800 r/min. Dilution of the premixed charge to control ignition timing was investigated by adopting exhaust gas recirculation (EGR). The optimized premixing strategies of two-stage injection, with a small amount of the ignition-promoting fuel (1.5 mm3) - which was injected near TDC to assist the combustion of a premixed charge (10 mm3) - resulted in an indicated mean effective pressure of up to 250 kPa within 3 per cent fluctuation, along with a significant reduction in particle matter and nitrogen oxides emissions, while 46 per cent EGR rate was applied to the premixed charge with preheated intake air at 433 K.
Quantitative relationship between plasma potassium levels and QT interval in beagle dogs
Authors: Hanton G , Yvon A , Provost J-P , Racaud A , Doubovetzky M
Published: April 2007

The aim of the current study was to establish the quantitative relationship between plasma potassium concentrations and the QT interval of the electrocardiogram in dogs. Furosemide, a potent diuretic, was given at increasing doses (5–60 mg/kg) to five male and five female beagle dogs. Electrocardiogram (ECG) was recorded three times each day, simultaneous to blood sampling for measurement of plasma potassium. Furosemide treatment produced a clear hypokalaemia, which was associated with an increase in QT and corrected QT intervals (QTc) duration. On average, the slopes of the negative linear correlation between potassium plasma levels and QT or QTc were steeper in females than in males. These results show that a decrease in potassium plasma level may explain a concomitant increase in QT duration in a toxicity study in dogs, in particular if potassium values are decreased below 3.3 mmol/L. Correction of QT interval for K+ plasma level has, therefore, been established separately for males and females. A global formula correcting QT for K+ and heart rate simultaneously was established. Hypokalaemia was also associated with changes in the morphology of the T wave recorded in CV5RL, in particular, with a flattening and/or a notching of the wave (appearance of a second peak), biphasic aspect or inversion of polarity. These changes are probably related to an increased heterogeneity of repolarization between different populations of cardiomyocytes. In conclusion, hypokalaemia is quantitatively associated with an increase in QT and QTc duration in dogs. The relationship is apparently stronger for females than for males. A formula may be used to correct QT for potassium plasma level.
Morphological and functional evaluation of angiogenesis of a xenografted human sarcoma in nude mice
Authors: Pöttgen Christoph , Hilken Gero , Vanhoefer Udo , Stuschke Martin , Stüben Georg
Published: April 2007

The implantation of tumour cells in normal tissues and the subsequent induction of angiogenesis by the growing xenograft were studied by means of immunohistochemistry and digital image analysis. Tumour growth was induced by injection of a human spindle cell sarcoma (ES3) into the subcutis of HsdCpb:NMRI- nu/nu mice. In vivo injection of Hoechst 33342 was used as a marker of perfusion. The vasculature was stained with specific antibodies and subsequently analysed by digital image analysis. Starting at day 3 up to day 6, angiogenesis could be detected and the relative amount of perfusion within the investigated area reached a peak at day 6. This method, which allows investigation of both functional and morphometric characteristics of human xenograft vasculature, serves as an excellent assay for evaluation of antiangiogenic therapies in translational research of experimental tumours.
Isolation of the mite Myocoptes musculinus Koch from the Spinifex Hopping mouse (Notomys alexis)
Authors: Old J M , Hill N J , Deane E M
Published: April 2007

This paper reports on the isolation and identification of the fur-clasping mite, Myocoptes musculinus, from the faeces of the Spinifex Hopping mouse ( Notomys alexis). This investigation adds to the sparse records of ectoparasites collected from native Australian murids.
Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments
Authors: Smith J A , van den Broek F A R , Martorell J Cantó , Hackbarth H , Ruksenas O , Zeller W
Published: April 2007

This paper summarizes a more detailed report produced by the Federation of European Laboratory Animal Science Associations (FELASA 2005), which describes and explores a set of principles for the conduct of ethical review of laboratory animal use. It presents a synopsis of results from a questionnaire that elicited information on how each of 20 countries represented in FELASA currently approaches such ethical review. This information suggests that, although local practices differ, there is an emerging consensus on the key elements that any ethical review process should involve. Drawing on the questionnaire findings, this summary also includes a brief discussion to support and amplify a series of recommendations, covering the objectives of ethical review; legal requirements; the scope of work reviewed and the 'level' at which review is approached; general principles for the organization of ethical review processes; the factors considered in the review; needs for ongoing review after initial authorization; participants in the review process; wider impacts of the review process; and strategies that can help to ensure quality and consistency of review outcomes. For further information and examples of current practice, as well as more detailed discussion to support the recommendations, readers are urged to refer to the complete report, available at http://www.lal.org.uk/pdffiles/FELASA_ethics_FULL_Report. pdf or via: http://www.felasa.eu/recommendations.htm.
The Effect of Cultural Orientation on Consumer Responses to Personalization
Authors: Kramer Thomas , Spolter-Weisfeld Suri , Thakkar Maneesh
Published: April 2007

While marketing activities increasingly involve personalizing product offers to individually elicited preferences, these unique specifications may not be universally important for product choice. Providing evidence of the limits of treating each customer differently, three experiments show that individuals who exhibit interdependent or collectivistic tendencies tend to be more receptive to recommendations that are not personalized to their own preferences, but instead to the collective preferences of relevant in-groups. However, we find that cultural orientation affects responses to personalized recommendations for only those products whose consumption or choice decision is subject to public scrutiny. We further demonstrate that the favorability of thoughts elicited by ads offering targeted versus personalized offers mediates the effect of cultural orientation on responses to personalization. Finally, both individualistic and collectivistic consumers respond more favorably to offers of targeted recommendations when they believe relevant others share their preferences and when their level of expertise is relatively low.
The Impact of a Product-Harm Crisis on Marketing Effectiveness
Authors: Van Heerde Harald , Helsen Kristiaan , Dekimpe Marnik G.
Published: April 2007

Product-harm crises are among a firm’s worst nightmares. A firm may experience (i) a loss in baseline sales, (ii) a reduced own effectiveness for its marketing instruments, (iii) an increased cross sensitivity to rival firms’ marketing-mix activities, and (iv) a decreased cross impact of its marketing-mix instruments on the sales of competing, unaffected brands. We find that this quadruple jeopardy materialized in a case study of an Australian product-harm crisis faced by Kraft peanut butter. We arrive at this conclusion by using a time-varying error-correction model that quantifies the consequences of this crisis on base sales, and on own- and cross-brand short- and long-term effectiveness. The proposed modeling approach allows managers to make more informed decisions on how to regain the brands’ pre-crisis performance levels.
New Product Development Under Channel Acceptance
Authors: Luo Lan , Kannan P. K. , Ratchford Brian T.
Published: April 2007

In channel structures characterized by a powerful retailer (e.g., Wal-Mart, Home Depot), the dominant retailer’s acceptance of a manufacturer’s new product often determines the success of the new offering. Focusing on a manufacturer in such a market, we develop an approach to positioning and pricing a new product that directly incorporates the retailer’s acceptance criteria into the development process. Our method also accounts for the retailer’s product assortment and the competing manufacturers’ potential reactions in wholesale prices. Our method merges individual-level conjoint models of preference with game-theoretic models of retailer and manufacturer behavior that are specific to the institutional setting of the focal manufacturer. The application of our approach in the context of a new power tool development project undertaken by this manufacturer also highlights the potential of our approach to other analogous institutional settings.
Editorial—The Anna Karenina Bias: Which Variables to Observe?
Authors: Shugan Steven M.
Published: April 2007

The opening of Count Lev Nikolayevich (Leo) Tolstoy’s novel inspired linguist, molecular physiologist and biogeographer Jared M. Diamond’s eponym for the Anna Karenina principle (Diamond 1997). The principle suggests that no one property guarantees success but many guarantee failure. The Anna Karenina (TAK) bias is a logical consequence. TAK bias is more insidious than the kindred Survivor bias, which cautions that measured variables for passively observed survivors often differ from easily overlooked nonsurvivors. TAK bias, in contrast, cautions that the observed variables themselves might differ for survivors. The most revealing variables might exhibit negligible variation among survivors because survivors are necessarily alike. Perhaps variability is inversely related to the variable’s importance for survival. TAK bias is more problematic for descriptive research, in contrast to normative (i.e., prescriptive) research, which seeks the true causal variables. Normative research only offers conditional aid to the decision maker on specific variables. To avoid TAK bias, we must not passively let accountants decide which variables we observe. We must actively collect data guided by predictions from deductive theory.
Steam Alternating Solvent Process
Authors: Zhao L.
Published: April 2007

A new heavy-oil-recovery process, the steam alternating solvent (SAS) process, is proposed and studied using numerical simulation. The process is intended to combine the advantages of the steam-assisted gravity drainage (SAGD) and vapor-extraction (va-pex) processes to minimize the energy input per unit oil recovered. The SAS process involves injecting steam and solvent alternately, and the basic well configurations are the same as those in the SAGD process.

Field-scale simulations were conducted to assess the SAS process performance under typical Cold Lake, Alberta, reservoir conditions. These results suggested that the oil-production rate of an SAS process could be higher than that of a SAGD process, while the energy input was 18% less than that of a SAGD process. By varying the length of the steam- and solvent-injection periods in a cycle, a different set of steam/oil and solvent/oil ratios may be obtained because the temperature profiles and solvent-concentration distributions in the vapor chamber can be affected by the injection pattern. The process therefore can be optimized for a specific reservoir under certain economic conditions.
Grid-System Requirements in Numerical Modeling of Pressure-Transient Tests in Horizontal Wells
Authors: Al-Mohannadi N. , Ozkan E. , Kazemi H.
Published: April 2007

The common approach of using refined grids and small timesteps usually does not provide accurate and efficient numerical models to simulate horizontal-well pressure-transient tests. In most cases, this approach requires impracticably long computational times or creates artifacts on pressure and derivative responses that may be confused with the characteristics of certain flow regimes. This paper presents an investigation of the grid and timestep requirements for the conventional well index (WI) to provide accurate simulations of horizontal-well pressure-transient responses. The results of this study indicate that the conventional WI should be used with log-distributed grid and timesteps to obtain a closer match to the analytical solution at early times. There is a limit to grid refinement beyond which the results do not improve. For these cases, the transient well index (TWI) introduced in this paper allows larger grids while improving the accuracy of simulations, especially at early times.
Estimating Productivity-Controlling Parameters in Gas/Condensate Wells From Transient Pressure Data
Authors: Bozorgzadeh Manijeh , Gringarten Alain C.
Published: April 2007

The ability to predict well deliverability is a key issue for the development of gas/condensate reservoirs. We show in this paper that well deliverability depends mainly on the gas relative permeabilities at both the endpoint and the near-wellbore saturations, as well as on the reservoir permeability. We then demonstrate how these parameters and the base capillary number can be obtained from pressure-buildup data by using single-phase and two-phase pseudopressures simultaneously. These parameters can in turn be used to estimate gas relative permeability curves. Finally, we illustrate this approach with both simulated pressure-buildup data and an actual field case.
A New-Generation LWD Tool With Colocated Sensors Opens New Opportunities for Formation Evaluation
Authors: Neville Thomas J. , Weller Geoff , Faivre Ollivier , Sun Haitao
Published: April 2007

A new logging-while-drilling (LWD) tool that combines traditional measurements of gamma ray, propagation resistivity, gamma-gamma density, and thermal-neutron porosity with measurements unique to the LWD arena, including neutron capture spectroscopy and capture cross section, opens up new opportunities for formation evaluation on LWD.

The compact design of the new-generation LWD tool greatly increases the likelihood that measurements will be made before the onset of significant invasion. The colocation of resistivity- and neutron-based sensors also means that key measurements are being made at the same depth at the same time and on a similar volume of the formation. These features ensure that all measurements are essentially seeing the same amount of invasion, thus removing a major complication in conventional LWD interpretation.
Cyclical endometrial steroid hormone receptor expression and proliferation intensity in the mare
Authors: Aupperle H. , Özgen S. , Schoon H.‐A. , Schoon D. , Hoppen H.‐O. , Sieme H. , Tannapfel A.
Published: April 2007

The aims of this study were to investigate the steroid hormone receptor expression and the proliferation intensity during the equine endometrial cycle by immunohistological methods, established for routine examination of formalin‐ fixed, paraplast‐embedded specimens. Endometrial biopsy specimens were obtained during one cycle from 7 mares. In comparison with the blood steroid hormone levels the quantity and distribution of oestrogen (ER) and progesterone receptors (PR) and the proliferation marker Ki‐67 antigen expression were investigated. Rising 17β‐oestradiol concentrations in preoestrus induce a synchronous expression of ER, PR and Ki‐67 antigen in stromal cells. In the early dioestrus 17β‐oestradiol levels decrease and progesterone levels reach their maxima. This correlates with an intense proliferation activity and the highest hormone receptor expression in epithelial cells. In accordance to the morphological features of asynchronous glandular differentiation in fibrotic areas (endometrosis) their epithelial hormone receptor expression is out of phase.
Effect of age and training on murmurs of atrioventricular valvular regurgitation in young Thoroughbreds
Authors: Young L. E. , Wood J. L. N.
Published: April 2007

Cardiac auscultation was carried out on 111 Thoroughbred horses age 2–5 years to test the hypothesis that athletic training might influence the development of atrioventricular (AV) valve regurgitation in young Thoroughbreds. Murmurs of valvular regurgitation were identified and graded on a 1–6 scale. There were 2 sources of auscultation data: 1) 55 2‐year‐old horses that were examined by auscultation before training commenced and 9 months later when at race fitness; 2) 56 horses age 2–5 years that were examined on one occasion only (25 2‐year‐olds, 23 3‐year‐olds, five 4‐year‐olds and five 5‐year olds). All horses in the second data set were in full training and racing regularly at the time of the examination. To conclude the study, 35 horses were selected randomly from both groups of horses and examined with colour‐flow Doppler echocardiography. The aim of the final part of the study was to check specificity and sensitivity of auscultation for detection of AV valve murmurs and therefore validate the auscultation findings.

Priorto training, the prevalence in 2‐year‐old racehorses of murmurs of mitral regurgitation and tricuspid regurgitation was 7.3% (4/55) and 12.7% (7/55), respectively. After training, the prevalence proportions increased to 21.8% (12/55) and 25.5% (14/55). After training, one horse developed a murmur characteristic of aortic regurgitation. The differences in murmur prevalence were statistically significant for mitral and tricuspid regurgitation (pairedttest results: mitral regurgitation, P = 0.019; tricuspid regurgitation, P = 0.007), as were the differences in mean murmurgrade (P= 0.018 and P= 0.0006, respectively). There were no significant effects of age on the prevalence of valvular regurgitation in 56 horses examined at race fitness. Auscultation was a specific (specificity 100%) and reasonably sensitive method for detection of murmurs of mitral and tricuspid regurgitation (mitral regurgitation: positive predictive value 100%, negative predictive value 84%, tricuspid regurgitation: positive predictive value 100%, negative predictive value 65%).

These data suggest that the prevalence and grade of murmurs of mitral and tricuspid valvular regurgitation increase in 2‐year‐old Thoroughbreds after 9 months of athletic training. Whereas the effects of age and growth on the prevalence of murmurs cannot be ruled out from these data, this study suggests that there is an influence of athletic training on the development of atrioventicular valvular regurgitation in flat‐racing Thoroughbreds.
Equine dental disease Part 4: a long‐term study of 400 cases: apical infections of cheek teeth
Authors: Dixon P. M. , Tremaine W. H. , Pickles K. , Kuhns L. , Hawe C. , Mccann J. , Mcgorum B. C. , Railton D. I. , Brammer S.
Published: April 2007

Of 400 horses referred because of equine dental disease, 162 suffered from primary apical infections of their cheek teeth (CT), including 92 with maxillary CT infections and 70 with mandibular CT infections. Maxillary swellings and sinus tracts were more common (82 and 26% incidence, respectively) with infections of the rostral 3 maxillary CT, than with infections of the caudal 3 maxillary CT(39 and 5% incidence, respectively). Nasal discharge was more commonly present with caudal (95%) than rostral (23%) maxillary CT infections. Mandibular CT apical infections commonly had mandibular swellings (91%) and mandibular sinus tracts (59%) and these infections were closely related to eruption of the affected CT. A variety of treatments, including medical treatment, apical curettage, repulsion and oral extraction of affected teeth were utilised in these cases, with oral extraction appearing to be most satisfactory. Infections of caudal maxillary CT with a secondary paranasal sinusitis were most refractory to treatment, with a complete response to the initial treatment achieved in just 33% of these cases. Most other cases responded fully to their initial treatment. The long‐term response to treatment was good in most cases.
Headshaking in horses: possible aetiopathogenesis suggested by the results of diagnostic tests and several treatment regimes used in 20 cases
Authors: Newton S. A. , Knottenbelt D. C. , Eldridge P. R.
Published: April 2007

Twenty mature horses with typical headshaking of 2 week‐7 year duration were studied. Clinical examinations included radiography of the head and nasopharyngeal endoscopy. All were assessed at rest and at exercise, both before and after fitting an occlusive nasal mask, application of tinted contact lenses and the perineural anaesthesia of the infraorbital and posterior ethmoidal branches of the trigeminal nerve. Infraorbital anaesthesia had no effect in 6/7 cases but 11/17 (65%) cases showed a 90–100% improvement following posterior ethmoidal nerve anaesthesia. Tinted contact lenses had no apparent long‐term benefit, although 2 cases showed a transient improvement. We found no other evidence to suggest a photic aetiology in the current series of cases. Treatment regimens based on the results of the diagnostic investigative methods included sclerosis of the posterior ethmoidal branch of the trigeminal nerve. This was effective in some cases but the benefits were temporary. Cyproheptadine alone was ineffective but the addition of carbamazepine resulted in 80–100% improvement in 80% of cases. Carbemazepine alone was effective in 88% of cases but results were unpredictable at predefined dose rates. The positive response to carbamazepine, combined with the clinical features is consistent with involvement of the trigeminal nerve, particularly the more proximal branches such as the posterior ethmoidal nerve.

Headshaking has some clinical features in common with trigeminal neuralgia in humans. As a result of the findings detailed in this paper, we conclude that a trigeminal neuritis or neuralgia may be the basis of the underlying aetiopathology of equine headshaking. Initial observations of the positive response of headshakers to carbamazepine therapy is encouraging. However, future studies will include a more detailed investigation of dosages, duration of effectiveness (in some cases it appears short‐lived) and other effects. In practice there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other future investigations will include details of the functional anatomy of the trigeminal nerve and the role of the P2 myelin protein in headshaking and other neurological disease.
Functional adaptation of equine articular cartilage: the formation of regional biochemical characteristics up to age one year
Authors: Brama P. A. J. , Tekoppele J. M. , Bank R. A. , Barneveld A. , Van Weeren P. R.
Published: April 2007

Biochemical heterogeneity of cartilage within a joint is well known in mature individuals. It has recently been reported that heterogeneity forproteoglycan content and chondrocyte metabolism in sheep develops postnatally underthe influence of loading. No data exist on the collagen network in general or on the specific situation in the horse.

The objective of this study was to investigate the alterations in equine articular cartilage biochemistry that occur from birth up to age one year, testing the hypothesis that the molecular composition of equine cartilage matrix is uniform at birth and biochemical heterogeneity is formed postnatally.

Water content, DNA content, glycosaminoglycan content (GAG) and biochemical characteristics of the collagen network (collagen content, hydroxylysine content and hydroxylysylpyridinoline [HP] crosslinks) were measured in immature articularcartilage of neonatal (n = 16), 5‐month‐old foals (n = 16) and yearlings (n = 16) at 2 predefined differently loaded sites within the metacarpophalangeal joint. Statistical differences between sites were analysed by ANOVA (P<0.01), and age correlation was tested by Pearson's product moment correlation analysis (P<0.01). In neonatal cartilage no significant site differences were found for any of the measured biochemical parameters. This revealed that the horse has a biochemically uniform joint (i.e. the cartilage) at birth. In the 5‐month‐old foals and yearlings, significant site differences, comparable to those in the mature horse, were found for DNA, GAG, collagen content and hydroxylysine content. This indicates that functional adaptation of articular cartilage to weight bearing for these biochemical parameters takes place during the first monthspostpartum.Water content and HP crosslinks showed no difference between the 2 sites from neonatal horses, 5‐month‐ old animals and yearlings. At both sites water, DNA and GAG decreased during maturation while collagen content, hydroxylysine content and HPcrosslinks increased.

We propose that a foal is born with a uniform biochemical composition of cartilage in which the functional adaptation to weight bearing takes place early in life. This adaptation results in biochemical and therefore biomechanical heterogeneity and is thought to be essential to resist the different loading conditions to which articular cartilage is subjected during later life. As collagen turnover is extremely low at mature age, an undisturbed functional adaptation of the collagen network of articularcartilage at a young age may be of significant importance for future strength and resistance to injury.
Respiratory responses of mature horses to intravenous lobeline bolus
Authors: Marlin D. J. , Roberts C. A. , Schroter R. C. , Lekeux P.
Published: April 2007

The respiratory stimulant lobeline has been used in equine clinical practice to increase inspiratory and expiratory airflow rates at rest in orderto facilitate investigation of both lower and upper airway function. Some of the responses to lobeline in the pony have been reported, but the detailed time course, effect of dose, possible side effects and reproducibility associated with lobeline administration have not been described in the horse. Respiratory airflow rates and oesophageal pressure were measured with a Fleisch No. 5 pneumotachometer and lightweight facemask and a microtip pressure transducer catheter, respectively. The output of the Fleisch pneumotachometer was calibrated for flow rates up to ± 70 l/s. Seven mature horses with no clinical signs of respiratory disease were studied. Investigations were conducted to determine: (1) the responses to different doses of lobeline (0.15, 0.20, 0.25 and 0.30 mg/kg bwt) as a rapid i.v. bolus (6 horses); (2) arterial blood gases during and after lobeline administration (0.20 mg/kg bwt; 3 horses); and (3) the reproducibility of lobeline‐stimulated hyperpnoea (5 horses; 2 doses of 0.20 mg/kg bwt lobeline, 15 min apart). All horses tolerated the lobeline‐stimulated hyperpnoea well, although one always coughed or snorted at the onset. Mild tremor was noted following the highest dose in several horses. Apnoea of approximately 40 s was common after the hyperpnoea. Both tidal volume (VT) and frequency (fR) increased with lobeline dose. During peak hyperpnoea at a dose of 0.30 mg/kg bwt, peak inspired flow rate (PIF), peak expired flow rate (PEF) and minute ventilation (VE) were mean ± s.e. 41 ± 5 l/s, 61 ± 10 l/s and 920 ± 99 l/min, respectively. The hyperpnoea also caused marked changes in arterial PaO2, PaCO2 and pHa at 90 s after lobeline (0.20 mg/kg bwt) administration (mean ± s.e. 146.0 ± 6.9 mmHg, 20.6 ± 0.8 mmHg and 7.707 ± 0.020, respectively) compared to at rest (mean ± s.e. 104.0 ± 4.0 mmHg, 50.6 ± 2.8 mmHg and 7.432 ± 0.012). Dynamic lung compliance (Cdyn) was unaltered by lobeline administration. The lobeline‐induced hyperpnoea was highly reproducible, with no significant difference in any of the parameters during 2 stimulations 15 min apart. Lobeline induced highly reproducible responses without any apparent adverse effects and may be useful in the investigation of pulmonary function in healthy horses and those with airway disease.
Repeatability of Doppler ultrasound measurements of hindlimb blood flow in halothane anaesthetised horses
Authors: Raisis A. L. , Young L. E. , Meire H. , Walsh K. , Taylor P. M. , Lekeux P.
Published: April 2007

The purpose of this study was to determine the repeatability of femoral blood flow recorded using Doppler ultrasound in anaesthetised horses. Doppler ultrasound of the femoral artery and vein was performed in 6 horses anaesthetised with halothane and positioned in left lateral recumbency. Velocity spectra, recorded using low pulse repetition frequency, were used to calculate time‐averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb), volumetric flow, early diastolic deceleration slope (EDDS) and pulsatility index (PI). Within‐patient variability was determined for sequential Doppler measurements recorded during a single standardised anaesthetic episode. Within‐patient variability was also determined for Doppler and cardiovascular measurements recorded during 4 separate standardised anaesthetic episodes performed at intervals of at least one month.

Within‐patient variation during a single anaesthetic episode was small. Coefficients of variation (cv) were <12.5% for arterial measurements and <17% for venous measurements. Intraclass correlation coefficient was >0.75 for all measurements. No significant change was observed in measurements of cardiovascular function suggesting that within‐patient variation observed during a single anaesthetic episode was due to measurement error. In contrast, within‐patient variation during 4 separate anaesthetic episodes was marked (cv>17%) for most Doppler measurements obtained from arteries and veins. Variation in measurements of cardiovascular function were marked (cv>20%), suggesting that there is marked biological variation in central and peripheral haemodynamics during different anaesthetic episodes.

Therefore the results of this study show that Doppler ultrasound is a noninvasive, repeatable method for measuring blood velocity, volumetric flow and indices of peripheral resistance in femoral vessels of anaesthetised horses. However, marked biological variation in haemodynamic measurements between different anaesthetic episodes could limit the ability of Doppler ultrasound to detect differences between anaesthetic agents. Ultimately, detection of differences in central and peripheral haemodynamics associated with different anaesthetic agents depends on the magnitude of the change observed. Further studies are warranted to determine the ability of this technique to detect differences in blood flow during administration of different anaesthetic agents.
Clinical studies on daily low dose oxytocin in mares at term
Authors: Camillo F. , Marmorini P. , Romagnoli S. , Cela M. , Duchamp G. , Palmer E.
Published: April 2007

The aim of this study was to test whether low dose oxytocin i.v. injection once a day to mares diagnosed as being ready for birth by mammary secretion calcium strip test measurements could be used as a reliable method to induce parturition and/or predict the mare would not foal during the following night if parturition did not occur within 2 h of treatment.

Fifty‐one near‐term Haflinger mares were used and a single injection of 2.5 iu oxytocin was given between 1700 and 1900 h, including 10 mares used as controls which were administered a placebo. Administration of oxytocin resulted in the delivery of a normal foal within 120 min in 95% of mares. Twenty‐fourout of 38 (63%) treated animals foaled in response to the first oxytocin injection, 9 out of 38 (24%) in response to the second injection and 3 out of 38 (8%) in response to the third treatment. Two out of 38 (5%) treated mares foaled during the night irrespective of treatment whereas 7 out of 10 (70%) control mares foaled during the night. It was concluded that the majoradvantage of injecting a daily low dose of oxytocin appears to be that such a low dose induces delivery only in mares carrying a mature fetus and which are ready to foal.
Transmission ofEhrlichia risticii, the agent of Potomac horse fever, using naturally infected aquatic insects and helminth vectors: preliminary report
Authors: Madigan J. E. , Pusterla N. , Johnson E. , Chae J.‐S. , Pusterla J. Berger , Derock E. , Lawler S. P.
Published: April 2007

Ehrlichia risticii, the agent of Potomac horse fever (PHF), has been recently detected in trematode stages found in snail secretions and in aquatic insects. Based on these findings, horses could conceivably be exposed toE. risticiiby skin penetration with infected cercariae, by ingestion of infected cercariae in water or via metacercariae in a second intermediate host, such as an aquatic insect. In order to test this hypothesis, horses were challenged with infectious snail secretions and aquatic insects collected from a PHFendemic region in northern California. Two horses stood with their front feet in waterharbouringE. risticii‐infected cercariae, 2 horses drank water harbouringE. risticii‐infected cercariae, and 6 horses were fed pools of different aquatic insects harbouringE. risticii‐infected metacercariae.

In this preliminary study, only the one horse infected orally with mature caddisflies (Dicosmoecus gilvipes) developed the clinical and haematological disease syndrome of PHF. The agent was isolated from the blood of the infected horse in a continuous cell line and identified asE. risticiiby characterisation of the 16S rRNA gene. Therefore,E. risticiiis maintained in nature in a complex aquatic ecosystem and transmission to horses can occur through accidental ingestion of insects such as caddisflies containing infected metacercariae. At present, the small number of horses used in this study does not exclude other insects and free trematode stages as potential sources of infection.