CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2007
Julio CB Ferreira
SUMMARY 1Maximal lactate steady state (MLSS) corresponds to the highest blood lactate concentration (MLSSc) and workload (MLSSw) that can be maintained over time without continual blood lactate accumulation and is considered an important marker of endurance exercise capacity. The present study was undertaken to determine MLSSw and MLSSc in running mice. In addition, we provide an exercise training protocol for mice based on MLSSw. 2Maximal lactate steady state was determined by blood sampling during multiple sessions of constant-load exercise varying from 9 to 21 m/min in adult male C57BL/6J mice. The constant-load test lasted at least 21 min. The blood lactate concentration was analysed at rest and then at 7 min intervals during exercise. 3The MLSSw was found to be 15.1 ± 0.7 m/min and corresponded to 60 ± 2% of maximal speed achieved during the incremental exercise testing. Intra- and interobserver variability of MLSSc showed reproducible findings. Exercise training was performed at MLSSw over a period of 8 weeks for 1 h/day and 5 days/week. Exercise training led to resting bradycardia (21%) and increased running performance (28%). Of interest, the MLSSw of trained mice was significantly higher than that in sedentary littermates (19.0 ± 0.5 vs 14.2 ± 0.5 m/min; P = 0.05), whereas MLSSc remained unchanged (3.0 mmol/L). 4Altogether, we provide a valid and reliable protocol to improve endurance exercise capacity in mice performed at highest workload with predominant aerobic metabolism based on MLSS assessment. [source]

Gq/11 and Gi/o activation profiles in CHO cells expressing human muscarinic acetylcholine receptors: dependence on agonist as well as receptor-subtype

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001
Elizabeth C Akam
Profiles of G protein activation have been assessed using a [35S]-GTP,S binding/immunoprecipitation strategy in Chinese hamster ovary cells expressing either M1, M2, M3 or M4 muscarinic acetylcholine (mACh) receptor subtypes, where expression levels of M1 and M3, or M2 and M4 receptors were approximately equal. Maximal [35S]-GTP,S binding to Gq/11, stimulated by M1/M3 receptors, or Gi1 , 3, stimulated by M2/M4 receptors occurred within approximately 2 min of agonist addition. The increases in Gq/11,-[35S]-GTP,S binding after M1 and M3 receptor stimulation differed substantially, with M1 receptors causing a 2 , 3 fold greater increase in [35S]-GTP,S binding and requiring 5 fold lower concentrations of methacholine to stimulate a half-maximal response. Comparison of M2 and M4 receptor-mediated Gi1 , 3,-[35S]-GTP,S binding also revealed differences, with M2 receptors causing a greater increase in Gi1 , 3, activation and requiring 10 fold lower concentrations of methacholine to stimulate a half-maximal response. Comparison of methacholine- and pilocarpine-mediated effects revealed that the latter partial agonist is more effective in activating Gi3, compared to Gi1/2, for both M2 and M4 receptors. More marked agonist/partial agonist differences were observed with respect to M1/M3 -mediated stimulations of Gq/11,- and Gi1 , 3,-[35S]-GTP,S binding. Whereas coupling to these G, subclasses decreased proportionately for M1 receptor stimulation by these agonists, pilocarpine possesses a greater intrinsic activity at M3 receptors for Gi, versus Gq/11, activation. These data demonstrate that mACh receptor subtype and the nature of the agonist used govern the repertoire of G proteins activated. They also provide insights into how the diversity of coupling can be pharmacologically exploited, and provide a basis for a better understanding of how multiple receptor subtypes can be differentially regulated. British Journal of Pharmacology (2001) 132, 950,958; doi:10.1038/sj.bjp.0703892 [source]

Normal head-hair length is correlated with its diameter

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2004
J. Nissimov
Summary Shed head-hair fibres of young (16,20-year-old), nonalopecic women (n = 25), exhibiting both exogen clubs and anagen tips (EA) were studied. Such fibres are shown, for the first time, to comprise , 44% of shed hair and to form a uni-modal, positively skewed distribution with a mean length of 16.7 ± 4.9 cm, which is also correlated with the length of the haircut. As individual fibres exit the skin in early anagen VI, their major-axis diameters increase rapidly to maxima at about 25% of their total potential length and subsequently decrease to their exogen clubs, at a rate of 1.31% per cm (n = 28). EA diameters are further correlated with their lengths. Maximal and proximal diameters increase by 1.40% per cm and 1.02% per cm increments in fibre lengths, respectively (P < 0.0001 each; n = 14), these changes being also different from each other (P < 0.001). Besides identifying and characterizing a new class of normal hair (EA) which will probably feature prominently in future hair research, this study reveals several other important aspects of hair growth: (i) the classically described concept of hair miniaturization in androgenetic alopecia (AGA) is excessively broad and should therefore be revised; (ii) female AGA need not necessarily require a mechanism for rapid miniaturization as recently proposed; and (iii) the putative large variability of normal hair diameters is significantly overestimated, which further opens the field of hair diameter evaluation as a biological indicator of disease and physiological function. [source]

Locating a Surveillance Infrastructure in and Near Ports or on Other Planar Surfaces to Monitor Flows

COMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 2 2010
Pitu B. Mirchandani
This article addresses the problem of locating surveillance radars to cover a given target surface that may have barriers through which radar signals cannot penetrate. The area of coverage of a radar is assumed to be a disc, or a partial disc when there are barriers, with a known radius. The article shows that the corresponding location problems relate to two well studied problems: the set-covering model and the maximal covering problem. In the first problem, the minimum number of radars is to be located to completely cover the target area; in the second problem a given number M of radars are to be located to cover the target area as much as possible. Based on a discrete representation of the target area, a Lagrangian heuristic and a two-stage procedure with a conquer-and-divide scaling are developed to solve the above two models. The computational experiences reported demonstrate that the developed method solves well the radar location problems formulated here. [source]

Impaired cardiac functional reserve in type 2 diabetic db/db mice is associated with metabolic, but not structural, remodelling

ACTA PHYSIOLOGICA, Issue 1 2010
A. Daniels
Abstract Aim:, To identify the initial alterations in myocardial tissue associated with the early signs of diabetic cardiac haemodynamic dysfunction, we monitored changes in cardiac function, structural remodelling and gene expression in hearts of type 2 diabetic db/db mice. Methods:, Cardiac dimensions and function were determined echocardiographically at 8, 12, 16 and 18 weeks of age. Left ventricular pressure characteristics were measured at 18 weeks under baseline conditions and upon dobutamine infusion. Results:, The db/db mice were severely diabetic already at 8 weeks after birth, showing elevated fasting blood glucose levels and albuminuria. Nevertheless, echocardiography revealed no significant changes in cardiac function up to 18 weeks of age. At 18 weeks of age, left ventricular pressure characteristics were not significantly different at baseline between diabetic and control mice. However, dobutamine stress test revealed significantly attenuated cardiac inotropic and lusitropic responses in db/db mice. Post-mortem cardiac tissue analyses showed minor structural remodelling and no significant changes in gene expression levels of the sarcoplasmic reticulum calcium ATPase (SERCA2a) or ,1-adrenoceptor (,1-AR). Moreover, the phosphorylation state of known contractile protein targets of protein kinase A (PKA) was not altered, indicating unaffected cardiac ,-adrenergic signalling activity in diabetic animals. By contrast, the substantially increased expression of uncoupling protein-3 (UCP3) and angiopoietin-like-4 (Angptl4), along with decreased phosphorylation of AMP-activated protein kinase (AMPK) in the diabetic heart, is indicative of marked changes in cardiac metabolism. Conclusion:, db/db mice show impaired cardiac functional reserve capacity during maximal ,-adrenergic stimulation which is associated with unfavourable changes in cardiac energy metabolism. [source]

Thyroid hormone receptor , can control action potential duration in mouse ventricular myocytes through the KCNE1 ion channel subunit

ACTA PHYSIOLOGICA, Issue 2 2010
A. Mansén
Abstract Aims:, The reduced heart rate and prolonged QTend duration in mice deficient in thyroid hormone receptor (TR) ,1 may involve aberrant expression of the K+ channel ,-subunit KCNQ1 and its regulatory ,-subunit KCNE1. Here we focus on KCNE1 and study whether increased KCNE1 expression can explain changes in cardiac function observed in TR,1-deficient mice. Methods:, TR-deficient, KCNE1-overexpressing and their respective wildtype (wt) mice were used. mRNA and protein expression were assessed with Northern and Western blot respectively. Telemetry was used to record electrocardiogram and temperature in freely moving mice. Patch-clamp was used to measure action potentials (APs) in isolated cardiomyocytes and ion currents in Chinese hamster ovary (CHO) cells. Results:, KCNE1 was four to 10-fold overexpressed in mice deficient in TR,1. Overexpression of KCNE1 with a heart-specific promoter in transgenic mice resulted in a cardiac phenotype similar to that in TR,1-deficient mice, including a lower heart rate and prolonged QTend time. Cardiomyocytes from KCNE1-overexpressing mice displayed increased AP duration. CHO cells transfected with expression plasmids for KCNQ1 and KCNE1 showed an outward rectifying current that was maximal at equimolar plasmids for KCNQ1-KCNE1 and decreased at higher KCNE1 levels. Conclusion:, The bradycardia and prolonged QTend time in hypothyroid states can be explained by altered K+ channel function due to decreased TR,1-dependent repression of KCNE1 expression. [source]

Study of the MR relaxation of microglia cells labeled with Gd-DTPA-bearing nanoparticles

CONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2009
Emeline Julie Ribot
Abstract Therapies involving cells as vehicles need to visualize in situ the trafficking of the cells concerned. This cellular imaging can be driven by cell contrast agent-based nanoparticle internalization and non-invasive MRI (magnetic resonance imaging) detection. Here, microglial cells, that would transport a suicide gene to a glioma, were incubated for different times, with various concentrations of silica nanoparticles on which numerous Gd-DTPA were grafted. The goal of this study was to investigate the repartition of cell-associated particles. MRI was used to quantitatively follow the particle uptake process. Fluorescence microscopy images showed that, although most of the nanoparticles were internalized, some remained adsorbed on the extracellular membrane surface. The cells were then submitted to various treatments: glycine to release bound nanoparticles and/or ultrasound to destroy the cell membranes. The R1 relaxation rates were measured at 4.7 T. R1 was maximal for 4,h of incubation, decreased after 8,h and remained stable for the 24 following hours. The magnetic resonance signal of ultrasonicated and glycine-treated cells made it possible to quantify the loss of bound nanoparticles after 8,h. Nevertheless, this release did not prevent cell detection since the internalized nanoparticles are enough concentrated to visualize the labeled cells even after 4 days of cell growth. These results highlight the compartmentalization of nanoparticles in microglia and the evolution of the MR signal of the labeled cells. This study could be of importance to interpret in vivo the MR signal changes that could occur after administration of such nanoparticle-labeled cells in therapeutic strategies. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects

ACTA PHYSIOLOGICA, Issue 1 2009
N. Fedirko
Abstract Nuclear calcium signalling has been an important topic of investigation for many years and some aspects have been the subject of debate. Our data from isolated nuclei suggest that the nuclear pore complexes (NPCs) are open even after depletion of the Ca2+ store in the nuclear envelope (NE). The NE contains ryanodine receptors (RyRs) and Ins(1,4,5)P3 receptors [Ins(1,4,5)P3Rs], most likely on both sides of the NE and these can be activated separately and independently: the RyRs by either NAADP or cADPR, and the Ins(1,4,5)P3Rs by Ins(1,4,5)P3. We have also investigated the possible consequences of nuclear calcium signals: the role of Ca2+ in the regulation of immediate early genes (IEG): c-fos, c-myc and c-jun in pancreatic acinar cells. Stimulation with Ca2+ -mobilizing agonists induced significant increases in levels of expression. Cholecystokinin (CCK) (10 nm) evoked a substantial rise in the expression levels, highly dependent on external Ca2+: the IEG expression level was lowest in Ca2+ -free solution, increased at the physiological level of 1 mm [Ca2+]o and was maximal at 10 mm [Ca2+]o, i.e.: 102 ± 22% and 163 ± 15% for c-fos; c-myc ,73 ± 13% and 106 ± 24%; c-jun ,49 ± 8% and 59 ± 9% at 1 and 10 mm of extracellular Ca2+ respectively. A low CCK concentration (10 pm) induced a small increase in expression. We conclude that extracellular Ca2+ together with nuclear Ca2+ signals induced by CCK play important roles in the induction of IEG expression. [source]

The energetic cost of activation in mouse fast-twitch muscle is the same whether measured using reduced filament overlap or N -benzyl- p -toluenesulphonamide

ACTA PHYSIOLOGICA, Issue 4 2008
C. J. Barclay
Abstract Aim:, Force generation and transmembrane ion pumping account for the majority of energy expended by contracting skeletal muscles. Energy turnover for ion pumping, activation energy turnover (EA), can be determined by measuring the energy turnover when force generation has been inhibited. Most measurements show that activation accounts for 25,40% of isometric energy turnover. It was recently reported that when force generation in mouse fast-twitch muscle was inhibited using N -benzyl- p -toluenesulphonamide (BTS), activation accounted for as much as 80% of total energy turnover during submaximal contractions. The purpose of this study was to compare EA measured by inhibiting force generation by: (1) the conventional method of reducing contractile filament overlap; and (2) pharmacological inhibition using BTS. Methods:, Experiments were performed in vitro using bundles of fibres from mouse fast-twitch extensor digitorum longus (EDL) muscle. Energy turnover was quantified by measuring the heat produced during 1-s maximal and submaximal tetanic contractions at 20 and 30 °C. Results:,EA measured using reduced filament overlap was 0.36 ± 0.04 (n = 8) at 20 °C and 0.31 ± 0.05 (n = 6) at 30 °C. The corresponding values measured using BTS in maximal contractions were 0.46 ± 0.06 and 0.38 ± 0.06 (n = 6 in both cases). There were no significant differences among these values. EA was also no different when measured using BTS in submaximal contractions. Conclusion:, Activation energy turnover is the same whether measured using BTS or reduced filament overlap and accounts for slightly more than one-third of isometric energy turnover in mouse EDL muscle. [source]

Transient concentration of a ,-tubulin-related protein with a pericentrin-related protein in the formation of basal bodies and flagella during the differentiation of Naegleria gruberi

CYTOSKELETON, Issue 2 2002
Mi Ra Suh
Abstract The distribution of two proteins in Naegleria gruberi, N-,TRP (Naegleria ,-tubulin-related protein) and N-PRP (Naegleria pericentrin-related protein), was examined during the de novo formation of basal bodies and flagella that occurs during the differentiation of N. gruberi. After the initiation of differentiation, N-,TRP and N-PRP began to concentrate at the same site within cells. The percentage of cells with a concentrated region of N-,TRP and N-PRP was maximal (68%) at 40 min when the synthesis of tubulin had just started but no assembled microtubules were visible. When concentrated tubulin became visible (60 min), the region of concentrated N-,TRP and N-PRP was co-localized with the tubulin spot and then flagella began to elongate from the region of concentrated tubulin. When cells had elongated flagella, the concentrated N-,TRP and N-PRP were translocated to the opposite end of the flagellated cells and disappeared. The transient concentration of N-,TRP coincided with the transient formation of an F-actin spot at which N-,TRP and ,-tubulin mRNA were co-localized. The concentration of N-,TRP and formation of the F-actin spot occurred without the formation of microtubules but were inhibited by cytochalasin D. These observations suggest that the regional concentration of N-,TRP and N-PRP is mediated by actin filaments and might provide a site of microtubule nucleation for the assembly of newly synthesized tubulins into basal bodies and flagella. Cell Motil. Cytoskeleton 52:66,81, 2002. © 2002 Wiley-Liss, Inc. [source]

One of the duplicated matrix metalloproteinase-9 genes is expressed in regressing tail during anuran metamorphosis

DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 4 2006
Kenta Fujimoto
The drastic morphological changes of the tadpole are induced during the climax of anuran metamorphosis, when the concentration of endogenous thyroid hormone is maximal. The tadpole tail, which is twice as long as the body, shortens rapidly and disappears completely in several days. We isolated a cDNA clone, designated as Xl MMP-9TH, similar to the previously reported Xenopus laevis MMP-9 gene, and showed that their Xenopus tropicalis counterparts are located tandemly about 9 kb apart from each other in the genome. The Xenopus MMP-9TH gene was expressed in the regressing tail and gills and the remodeling intestine and central nervous system, and induced in thyroid hormone-treated tail-derived myoblastic cultured cells, while MMP-9 mRNA was detected in embryos. Three thyroid hormone response elements in the distal promoter and the first intron were involved in the upregulation of the Xl MMP-9TH gene by thyroid hormone in transient expression assays, and their relative positions are conserved between X. laevis and X. tropicalis promoters. These data strongly suggest that the MMP-9 gene was duplicated, and differentiated into two genes, one of which was specialized in a common ancestor of X. laevis and X. tropicalis to be expressed in degenerating and remodeling organs as a response to thyroid hormone during metamorphosis. [source]

Transient expression of thyroid hormone nuclear receptor TR,2 sets S opsin patterning during cone photoreceptor genesis

DEVELOPMENTAL DYNAMICS, Issue 5 2007
M.L. Applebury
Abstract Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TR,2, the nuclear thyroid hormone receptor , isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TR,2 acts, we compared the spatiotemporal expression of TR,2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TR,2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TR,2 is expressed uniformly, but transiently, across the retina. mRNA levels are maximal by E17 at completion of cone genesis and again minimal before P5. S opsin is also transcribed by E13, but only in ventral cones. Repression in dorsal cones is established by E17, consistent with the occurrence of patterning during cone cell genesis. The uniform expression of TR,2 suggests that repression of S opsin requires other dorsal-specific factors in addition to TR,2. The mechanism by which TR,2 functions was probed in transgenic animals with TR,2 ablated, TR,2 that is DNA binding defective, and TR,2 that is ligand binding defective. These studies show that TR,2 is necessary for dorsal repression, but not ventral activation of S opsin. TR,2 must bind DNA and the ligand T3 (thyroid hormone) to repress S opsin. Once repression is established, T3 no longer regulates dorsal S opsin repression in adult animals. The transient, embryonic action of TR,2 is consistent with a role (direct and/or indirect) in chromatin remodeling that leads to permanent gene silencing in terminally differentiated, dorsal cone photoreceptors. Developmental Dynamics 236:1203,1212, 2007. © 2007 Wiley-Liss, Inc. [source]

Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus

DIABETIC MEDICINE, Issue 2 2004
A. Russo
Abstract Aims To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus. Methods In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at either 5 mmol/l or 12 mmol/l using a glucose clamp technique. Eight healthy subjects were studied under euglycaemic conditions. Anorectal motor and sensory function was evaluated using a sleeve/sidehole catheter, incorporating a barostat bag. Results In diabetic subjects hyperglycaemia was associated with reductions in maximal (P < 0.05) and plateau (P < 0.05) anal squeeze pressures and the rectal pressure/volume relationship (compliance) during barostat distension (P < 0.01). Hyperglycaemia had no effect on the perception of rectal distension. Apart from a reduction in rectal compliance (P < 0.01) and a trend (P = 0.06) for an increased number of spontaneous anal sphincter relaxations, there were no differences between the patients studied during euglycaemia when compared with healthy subjects. Conclusions In patients with diabetes, acute hyperglycaemia inhibits external anal sphincter function and decreases rectal compliance, potentially increasing the risk of faecal incontinence. Diabet. Med. 21, 176,182 (2004) [source]

Non-random distribution among a guild of parasitoids: implications for community structure and host survival

ECOLOGICAL ENTOMOLOGY, Issue 6 2006
ANTHONY M. ROSSI
Abstract 1.,Immature stages of the gall midge, Asphondylia borrichiae, are attacked by four species of parasitoids, which vary in size and relative abundance within patches of the gall midge's primary host plant, sea oxeye daisy (Borrichia frutescens). 2.,In the current study, a bagging experiment found that the smallest wasp, Galeopsomyia haemon, was most abundant in galls exposed to natural enemies early in the experiment, when gall diameter is smallest, while the wasp with the longest ovipositor, Torymus umbilicatus, dominated the parasitoid community in galls that were not exposed until the 5th and 6th weeks when gall diameter is maximal. 3.,Moreover, the mean number of parasitoids captured using large artificial galls were 70% and 150% higher compared with medium and small galls respectively, while stem height of artificial galls significantly affected parasitoid distribution. Galls that were level with the top of the sea oxeye canopy captured 60% more parasitoids compared with those below the canopy and 50% more than galls higher than the plant canopy. 4.,These non-random patterns were driven primarily by the differential distribution of the largest parasitoid, T. umbilicatus, which was found significantly more often than expected on large galls and the smallest parasitoid of the guild, G. haemon, which tended to be more common on stems level with the top of the plant canopy. 5.,Large Asphondylia galls, especially those located near the top of the Borrichia canopy, were more likely to be discovered by searching parasitoids. Results using artificial galls were consistent with rates of parasitism of Asphondylia galls in native patches of sea oxeye daisy. Gall diameter was 19% greater and the rate of parasitism was reduced by almost 50% on short stems; as a result, gall abundance was 24% higher on short stems compared with ones located near the top of the plant canopy. 6.,These results suggest that parasitoid community composition within galls is regulated by both interspecific differences in ovipositor length and preferences for specific gall size and/or stem length classes. [source]

Autumnal moth , why autumnal?

ECOLOGICAL ENTOMOLOGY, Issue 6 2001
Toomas Tammaru
Summary 1. As for some other spring-feeding moths, adult flight of Epirrita autumnata (Lepidoptera: Geometridae) occurs in late autumn. Late-season flight is a result of a prolonged pupal period. Potential evolutionary explanations for this phenological pattern are evaluated. 2. In a laboratory rearing, there was a weak correlation between pupation date and the time of adult emergence. A substantial genetic difference in pupal period was found between two geographic populations. Adaptive evolution of eclosion time can thus be expected. 3. Metabolic costs of a prolonged pupal period were found to be moderate but still of some ecological significance. Pupal mortality is likely to form the main cost of the prolonged pupal period. 4. Mortality rates of adults, exposed in the field, showed a declining temporal trend from late summer to normal eclosion time in autumn. Lower predation pressure on adults may constitute the decisive selective advantage of late-season flight. It is suggested that ants, not birds, were the main predators responsible for the temporal trend. 5. Egg mortality was estimated to be low; it is thus unlikely that the late adult period is selected for to reduce the time during which eggs are exposed to predators. 6. In a laboratory experiment, oviposition success was maximal at the time of actual flight peak of E. autumnata, however penalties resulting from sub-optimal timing of oviposition remained limited. [source]

Audiogenic kindling in Wistar and WAG/Rij rats: Kindling-prone and kindling-resistant subpopulations

EPILEPSIA, Issue 10 2008
Lyudmila V. Vinogradova
Summary Purpose:, Audiogenic kindling (AK) is a model of naturally occurring epileptogenesis triggered by repeated sound stimulation of rats genetically prone to audiogenic seizures. It is accepted that limbic seizure networks underlie progressive changes in behavioral seizure pattern during AK. The present study investigated AK progression in rats susceptible and unsusceptible to absence seizures. Methods:, Progression of AK as indicated by an appearance and intensification of limbic clonus was examined in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats with genetic absence epilepsy and in Wistar rats. Results:, Subpopulations of kindling-prone and kindling-resistant rats were found in both Wistar and WAG/Rij strains. Despite identical seizure responses to the first sound stimulation, AK progression dramatically differed between the two subpopulations. AK-prone rats exhibited rapid kindling development up to maximal stage-5 severity. In AK-resistant rats, limbic clonus did not appear after 30 stimulations or if it appeared, it did not progress beyond stage 2. The proportions of AK-prone and AK-resistant animals within Wistar and WAG/Rij strains were similar. Comparison of Wistar and WAG/Rij rats within the kindling-prone and kindling-resistant groups did not reveal a significant strain effect on AK progression. However, within the WAG/Rij strain, a significantly higher incidence of absence seizures was found in AK-resistant rats compared to AK-prone rats. Conclusions:, The present study demonstrates that sensitivity to sound-induced epileptogenesis differs dramatically within Wistar and WAG/Rij strains, whereas genetic susceptibility to absence seizures does not change AK progression significantly. It is supposed that an increased incidence of nonconvulsive seizures and resistance to kindling result from a common seizure modulating mechanism. [source]

Postictal But Not Interictal Hemispatial Neglect in Patients with Seizures of Lateralized Onset

EPILEPSIA, Issue 12 2006
Olga Prilipko
Summary:,Purpose: Unilateral spatial neglect, defined as a failure to report, respond, or orient to stimuli that are presented contralaterally, has been widely documented after brain damage to right, and to a lesser degree, left frontotemporoparietal networks. Group studies involving patients with seizures with a lateralized focus have demonstrated transient dysfunctions in memory and language; however, so far, only two case reports have described transient neglect after an epileptic seizure. Methods: To assess the existence and consistency of this phenomenon, we evaluated 33 epilepsy patients on a line-bisection task in interictal and postictal states as compared with an age- and sex-matched control group. Results: Spatial neglect, as determined by this test, was found in the postictal but not interictal examination in patients with right parietal epileptic foci and was maximal for the left-positioned lines, whereas no neglect was found in other groups. Conclusions: Our findings indicate that patients with right parietal foci can present a transient neglect phenomenon on the line-bisection task in the postictal period, even in the absence of overt clinical neglect signs. These findings might be useful in establishing the laterality and even localization of epileptic foci based on the postictal neuropsychological evaluation. [source]

Abnormal radiographic findings in 865 French Standardbred trotters and their relationship to racing performance

EQUINE VETERINARY JOURNAL, Issue S36 2006
A. COUROUCÉ-MALBLANC
Summary Reason for performing study: Developmental orthopaedic lesions are commonly found in French Standardbred horses. One of the main questions asked by trainers, owners and veterinarians is what impact these lesions have on the racing career and racing performances of horses. Objectives: To study the prevalence and distribution of developmental orthopaedic lesions in young French Standardbred trotters and to relate them to racing performance. Methods: Feet, fetlock, tarsus and stifle regions were radiographed in 865 two-year-old French Standardbred trotters. Abnormal radiographic findings (ARF) were evaluated for 12 anatomical sites identified in these areas, and a severity index given. Performance criteria were: success in qualification for racing, maximal and mean index of trot (ITR), an annual index calculated on the basis of the logarithm of earnings per starts, total earnings at 5 years, placed races compared to starts and longevity of the racing career. Analysis of variance were calculated to study the relationships between racing performance and the number of ARF or the severity index. Results: A total of 363 horses (42.0%) showed ARF. Prevalence of ARF was 18.3% in the plantar aspect of the hind fetlock and 10.6% in the proximal tarsus. Among the total population, 833 horses were considered for performance evaluation, 478 of them were qualified for racing. The number of ARF significantly affected racing longevity. However, the number of ARF did not affect performance categories according to maximal ITR. Concerning distribution of ARF, the number of plantar lesions in the fetlock significantly affected mean ITR. The index of severity did not provide more information for prognosis than the number of ARF. Conclusion: Longevity is the only criteria affected by ARF. When evaluating different sites, only the plantar fetlock region showed a significant relationship with mean ITR. Potential relevance: Number of ARF and radiographic score (RS) affect mean ITR and longevity but do not affect maximal ITR. A horse with a good racing ability will be a good performer but might have a racing career shortened because of orthopaedic problems in relation to developmental orthopaedic lesions. [source]

Parents and Practitioners Are Poor Judges of Young Children's Pain Severity

ACADEMIC EMERGENCY MEDICINE, Issue 6 2002
Adam J. Singer MD
Objective: Visual analog pain scales are reliable measures in older children and adults; however, pain studies that include young children often rely on parental or practitioner assessments for measuring pain severity. The authors correlated patient, parental, and practitioner pain assessments for young children with acute pain. Methods: This was a prospective, descriptive study of a convenience sample of 63 emergency department patients aged 4-7 years, with acute pain resulting from acute illness or painful invasive procedures. A trained research assistant administered a structured pain survey containing demographic and historical features to all parents/guardians. Children assessed their pain severity using a validated ordinal scale that uses five different faces with varying degrees of frowning (severe pain) or smiling (no pain). Each face was converted to a numeric value from 0 (no pain) to 4 (severe pain). Parents and practitioners independently assessed their child's pain using a validated 100-mm visual analog scale (VAS) marked "most pain" at the high end. Pairwise correlations between child, parent, and practitioner pain assessments were performed using Spearman's or Pearson's test as appropriate. The association between categorical data was assessed using ,2 tests. Results: Sixty-three children ranging in age from 4 to 7 were included. Mean age (±SD) was 5.7 (±1.1); 42% were female. Fifty-seven successfully completed the face scale. The distribution of the children's scores was 0-17%, 1-9%, 2-30%, 3-14%, and 4-30%. Mean parental and practitioner scores (±SD) on the VAS were 61 (±26) mm and 37 (±26) mm, respectively (maximal = 100 mm). Correlation between child and parent scores was 0.47 (p < 0.001). Correlation between child and practitioner scores was 0.08 (p = 0.54). Correlation between parent and practitioner scores was 0.04 (p = 0.001). Conclusions: There is poor agreement between pain ratings by children, parents, and practitioners. It is unclear which assessment best approximates the true degree of pain the child is experiencing. [source]

Upper limb movement interruptions are correlated to freezing of gait in Parkinson's disease

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009
Alice Nieuwboer
Abstract Freezing of gait (FOG) in patients with Parkinson's disease (PD) is a common problem of unknown origin, which possibly reflects a general motor control deficit. We investigated the relationship between the frequency of freezing episodes during gait and during a bimanual task in control and subjects with PD with and without FOG. Group differences in spatiotemporal characteristics were also examined as well as the effects of visual cueing. Twenty patients with PD in the off-phase of the medication cycle and five age-matched controls performed a repetitive drawing task in an anti-phase pattern on a digitizer tablet. The task was offered at two different speeds (comfortable and maximal) and two different amplitudes (small and large) with and without visual cueing. The results showed that freezing episodes in the upper limbs occurred in only 10.4% of patient trials and that their occurrence was correlated with FOG scores (Spearman's rho = 0.64). Overall, few spatiotemporal differences were found between freezers, non-freezers and controls, except for an overshooting of the target amplitude in controls. Effects of visual cueing were largely similar in all groups, except for the variability of relative phase, which decreased in non-freezers and controls, and was unaffected in freezers. Despite the fact that general motor differences between subgroups were small, freezing episodes were manifest during a bimanual repetitive upper limb task and were correlated to FOG. Further study into upper limb movement breakdown is warranted to understand the parallel deficits that lead up to FOG. [source]

Comparison of spatial integration and surround suppression characteristics in spiking activity and the local field potential in macaque V1

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008
M. A. Gieselmann
Abstract Neurons in primary visual cortex exhibit well documented centre,surround receptive field organization, whereby the centre is dominated by excitatory influences and the surround is generally dominated by inhibitory influences. These effects have largely been established by measuring the output of neurons, i.e. their spiking activity. How excitation and inhibition are reflected in the local field potential (LFP) is little understood. As this can bear on the interpretation of human fMRI BOLD data and on our understanding of the mechanisms of local field potential oscillations, we measured spatial integration and centre,surround properties in single- and multiunit recordings of V1 in the awake fixating macaque monkey, and compared these to spectral power in different frequency bands of simultaneously recorded LFPs. We quantified centre,surround organization by determining the size of the summation and suppression area in spiking activity as well as in different frequency bands of the LFP, with the main focus on the gamma band. Gratings extending beyond the summation area usually inhibited spiking activity while the LFP gamma-band activity increased monotonically for all grating sizes. This increase was maximal for stimuli infringing upon the near classical receptive field surround, where suppression started to dominate spiking activity. Thus, suppressive influences in primary cortex can be inferred from spiking activity, but they also seem to affect specific features of gamma-band LFP activity. [source]

Ventral pallidal neurons code incentive motivation: amplification by mesolimbic sensitization and amphetamine

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2005
Amy J. Tindell
Abstract Neurons in ventral pallidum fire to reward and its predictive cues. We tested mesolimbic activation effects on neural reward coding. Rats learned that a Pavlovian conditioned stimulus (CS+1 tone) predicted a second conditioned stimulus (CS+2 feeder click) followed by an unconditioned stimulus (UCS sucrose reward). Some rats were sensitized to amphetamine after training. Electrophysiological activity of ventral pallidal neurons to stimuli was later recorded under the influence of vehicle or acute amphetamine injection. Both sensitization and acute amphetamine increased ventral pallidum firing at CS+2 (population code and rate code). There were no changes at CS+1 and minimal changes to UCS. With a new ,Profile Analysis', we show that mesolimbic activation by sensitization/amphetamine incrementally shifted neuronal firing profiles away from prediction signal coding (maximal at CS+1) and toward incentive coding (maximal at CS+2), without changing hedonic impact coding (maximal at UCS). This pattern suggests mesolimbic activation specifically amplifies a motivational transform of CS+ predictive information into incentive salience coded by ventral pallidal neurons. Our results support incentive-sensitization predictions and suggest why cues temporally proximal to drug presentation may precipitate cue-triggered relapse in human addicts. [source]

Two-way active avoidance training-specific increases in phosphorylated cAMP response element-binding protein in the dorsal hippocampus, amygdala, and hypothalamus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
Subhash Saha
Abstract Previous studies have demonstrated that the activation of pontine-wave (P-wave) generating cells in the brainstem during post-training rapid eye movement (REM) sleep is critical for the consolidation of memory for two-way active avoidance (TWAA) learning in the rat. Here, using immunocytochemistry, we investigated the spatio-temporal distribution of CREB phosphorylation within different parts of the dorsal hippocampus, amygdala, and hypothalamus following a session of TWAA training in the rat. We show that the TWAA training trials increased phosphorylation of CREB (p-CREB) in the dorsal hippocampus, amygdala, amygdalo-hippocampal junction (AHi), and hypothalamus. However, the time intervals leading to training-induced p-CREB activity were different for different regions of the brain. In the dorsal hippocampus, p-CREB activity was maximal at 90 min and this activity disappeared by 180 min. In the AHi, activity of the p-CREB peaked by 180 min and disappeared by 360 min. In the amygdala, the p-CREB activity peaked at 180 min and still remained higher than the control at the 360 min interval. In the hypothalamus, at 90 min p-CREB activity was present only in the ventromedial hypothalamus; however, by 180 min this p-CREB activity was also present in the dorsal hypothalamus, perifornical area, and lateral hypothalamus. By 360 min, p-CREB activity disappeared from the hypothalamus. This TWAA training trials-induced spatiotemporal characteristic of CREB phosphorylation, for the first time, suggests that REM sleep P-wave generator activation-dependent memory processing involves different parts of the dorsal hippocampus, amygdala, and hypothalamus. [source]

Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005
Joanna Iczkiewicz
Abstract Nigral cell death in Parkinson's disease is characterized by glial cell activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated phosphoprotein that is induced by inflammatory mediators and which we have previously shown to be present in the substantia nigra. However, the role of OPN in the nigral inflammation is not known. We now report on the effects of lipopolysaccharide (LPS)-induced glial cell activation in the substantia nigra of rats on OPN expression. LPS administration induced dopaminergic cell death as shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a corresponding time-dependent increase in both OPN mRNA, which was maximal at 48 h, and protein levels, which peaked at 72 h before returning to control levels by 120 h. This increase was accompanied by marked reactive gliosis as shown by increased OX-42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity. OX-42-positive cells increased in a time-dependent manner, peaking at 72 h before returning to control levels at 120 h. Similarly, ED1-positive cells were present in their greatest numbers at 24 h but then gradually declined. These changes mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In contrast, GFAP-positive cells only started to increase in number at 120 h. Colocalization studies showed that OPN was present in both ED1- and OX-42-positive cells but not in GFAP-positive cells. These data confirm that intranigral injection of LPS induces a rapid and marked gliosis that accompanies the loss of tyrosine hydroxylase-positive neurones and suggest that, after glial cell activation, enhanced expression of OPN occurs linked to increased numbers of microglia and/or macrophages. This suggests that OPN may be functionally important in the control of inflammatory changes. [source]

A role for synGAP in regulating neuronal apoptosis

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005
Irene Knuesel
Abstract The brain-specific Ras/Rap GTPase-activating protein synGAP is a major component of the postsynaptic density at glutamatergic synapses. It is a target for phosphorylation by Ca2+/calmodulin-dependent protein kinase II, which up-regulates its GTPase-activating activity. Thus, SynGAP may play an important role in coupling N -methyl- d -aspartate-type glutamate receptor activation to signaling pathways downstream of Ras or Rap. Homozygous deletion of synGAP is lethal within the first few days after birth. Therefore, to study the functions of synGAP, we used the cre/loxP recombination system to produce conditional mice mutants in which gradual loss of synGAP begins at ,,1 week, and usually becomes maximal by 3 weeks, after birth. The resulting phenotypes fall into two groups. In a small group, the level of synGAP protein is reduced to 20,25% of wild type, and they die at 2,3 weeks of age. In a larger group, the levels remain higher than ,,40% of wild type, and they survive and remain healthy. In all mutants, however, an abnormally high number of neurons in the hippocampus and cortex undergo apoptosis, as detected by caspase-3 activation. The effect is cell autonomous, occurring only in neuronal types in which the synGAP gene is eliminated. The level of caspase-3 activation in neurons correlates inversely with the level of synGAP protein measured at 2 and 8 weeks after birth, indicating that neuronal apoptosis is enhanced by reduction of synGAP. These data show that synGAP plays a role in regulation of the onset of apoptotic neuronal death. [source]

Antisense oligodeoxynucleotide-induced suppression of basal forebrain NMDA-NR1 subunits selectively impairs visual attentional performance in rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001
Janita Turchi
Abstract It is generally agreed that basal forebrain neuronal circuits contribute to the mediation of the ability to detect, select and discriminate signals, to suppress the processing of irrelevant information, and to allocate processing resources to competing tasks. Rats were trained in a task designed to assess sustained attention, or in a cued discrimination task that did not tax attentional processes. Animals were equipped with guide cannula to infuse bilaterally antisense oligodeoxynucleotides (ODNs) against the N -methyl- d -aspartate (NMDA) NR1 subunits, or missense ODNs, into the substantia innominata of the basal forebrain. Infusions of antisense or missense ODNs did not affect cued visual discrimination performance. Infusions of antisense ODNs dose-dependently impaired sustained attention performance by selectively decreasing the animals' ability to detect signals while their ability to reject nonsignal trials remained unchanged. The detrimental attentional effects of antisense infusions were maximal 24 h after the third and final infusion, and performance returned to baseline 24 h later. Missense infusions did not affect attentional performance. Separate experiments demonstrated extensive suppression of NR1 subunit immunoreactivity in the substantia innominata. Furthermore, infusions of antisense did not produce neurotoxic effects in that region as demonstrated by the Fluoro-Jade method. The present data support the hypothesis that NMDA receptor (NMDAR) stimulation in the basal forebrain, largely via glutamatergic inputs originating in the prefrontal cortex, represents a necessary mechanism to activate the basal forebrain corticopetal system for mediation of attentional performance. [source]

Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factor

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001
Elisabetta Vaudano
Abstract This study was designed to determine whether induction and phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of dopaminergic neurons of the substantia nigra pars compacta, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor. In adult rats, delayed dopaminergic neuron cell death induced by intrastriatal 6-hydroxydopamine injection led to a marked increase in the number of both c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra pars compacta. The response was maximal before any significant loss of nigral neurons could be detected (on day 7 post lesion) and was confined to the dopaminergic neurons. Similarly, 6-hydroxydopamine lesion of the striatal dopaminergic terminals or excitotoxic lesion of the striatal target neurons in neonatal rats resulted in an increased number of c-Jun- and phosphorylated c-Jun-immunoreactive nigral nuclei that preceded the loss of nigral dopaminergic neurons. By contrast, after an excitotoxic lesion of the striatal target neurons in the adult rat, resulting in atrophy but not cell death of the nigral dopaminergic neurons, no upregulation of either c-Jun or phosphorylated c-Jun was found. A single injection of 10 µg of glial-cell-line-derived-neurotrophic factor given at day 3 after the intrastriatal 6-hydroxydopamine lesion reduced the number of c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra and protected the dopaminergic neurons from the ensuing cell death. We conclude that c-Jun induction and phosphorylation may be involved in the cellular events leading to death of nigral dopaminergic neurons in vivo and that this response can be modulated by glial-cell-line-derived-neurotrophic factor. [source]

Afferent ingrowth and onset of activity in the rat trigeminal nucleus

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000
P. M. E. Waite
Abstract A novel in vitro preparation, consisting of the rat brainstem with the trigeminal ganglion attached, has been used to study the anatomical and functional development of the trigeminal nucleus from embryonic day (E)13 to postnatal day (P)6. Neurobiotin injections into the trigeminal ganglion showed that primary afferents had reached the trigeminal tract by E13 and had grown simple, mainly unbranched, collaterals into all levels of the nucleus by E15. By E17, these collaterals were extensively branched, with occasional boutons present. Patches of intense neurobiotin-labelled terminals, corresponding to whisker-related patterns, were first seen at E20 and became clearer over the next few days. Terminal arbours at this stage were relatively localized and densely branched, with many boutons. Responses from the trigeminal nucleus were recorded with suction electrodes, following stimulation of the trigeminal ganglion. Recordings from the main sensory nucleus showed a postsynaptic response was first present at E15. At E16, bath application of AP5 and DNQX showed that the response contained both NMDA and AMPA components, with NMDA predominating (75%). The NMDA : AMPA ratio remained high until P1, then gradually declined to 50% by P6. The postsynaptic response was also reduced by bath application of bicuculline, indicating the presence of a GABAA -mediated excitatory component. GABAergic excitation was present at all ages but was maximal from E20 to P1, the age at which whisker-related patterns are developing. It is hypothesized that both GABAergic excitation and NMDA receptor activation play a role in the consolidation of trigeminal connections, and are thus important in the development of whisker-related patterns. [source]

Wavelet analysis of the scale- and location-dependent correlation of modelled and measured nitrous oxide emissions from soil

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 1 2005
A. E. Milne
Summary We used the wavelet transform to quantify the performance of models that predict the rate of emission of nitrous oxide (N2O) from soil. Emissions of N2O and other soil variables that influence emissions were measured on soil cores collected at 256 locations across arable land in Bedfordshire, England. Rate-limiting models of N2O emissions were constructed and fitted to the data by functional analysis. These models were then evaluated by wavelet variance and wavelet correlations, estimated from coefficients of the adapted maximal overlap discrete wavelet transform (AMODWT), of the fitted and measured emission rates. We estimated wavelet variances to assess whether the partition of the variance of modelled rates of N2O emission between scales reflected that of the data. Where the relative distribution of variance in the model is more skewed to coarser scales than is the case for the observation, for example, this indicates that the model predictions are too smooth spatially, and fail adequately to represent some of the variation at finer scales. Scale-dependent wavelet correlations between model and data were used to quantify the model performance at each scale, and in several cases to determine the scale at which the model description of the data broke down. We detected significant changes in correlation between modelled and predicted emissions at each spatial scale, showing that, at some scales, model performance was not uniform in space. This suggested that the influence of a soil variable on N2O emissions, important in one region but not in another, had been omitted from the model or modelled poorly. Change points usually occurred at field boundaries or where soil textural class changed. We show that wavelet analysis can be used to quantify aspects of model performance that other methods cannot. By evaluating model behaviour at several scales and positions wavelet analysis helps us to determine whether a model is suitable for a particular purpose. [source]

Changes in variance and correlation of soil properties with scale and location: analysis using an adapted maximal overlap discrete wavelet transform

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 4 2001
R. M. Lark
Summary The magnitude of variation in soil properties can change from place to place, and this lack of stationarity can preclude conventional geostatistical and spectral analysis. In contrast, wavelets and their scaling functions, which take non-zero values only over short intervals and are therefore local, enable us to handle such variation. Wavelets can be used to analyse scale-dependence and spatial changes in the correlation of two variables where the linear model of coregionalization is inadmissible. We have adapted wavelet methods to analyse soil properties with non-stationary variation and covariation in fairly small sets of data, such as we can expect in soil survey, and we have applied them to measurements of pH and the contents of clay and calcium carbonate on a 3-km transect in Central England. Places on the transect where significant changes in the variance of the soil properties occur were identified. The scale-dependence of the correlations of soil properties was investigated by calculating wavelet correlations for each spatial scale. We identified where the covariance of the properties appeared to change and then computed the wavelet correlations on each side of the change point and compared them. The correlation of topsoil and subsoil clay content was found to be uniform along the transect at one important scale, although there were significant changes in the variance. In contrast, carbonate content and pH of the topsoil were correlated only in parts of the transect. [source]