JOURNAL OF PHYCOLOGY, Issue 2000
A. Place
Recently, very-long-chain (C28) highly unsaturated fatty acids (VLC-HUFA) were identified in seven marine dinoflagellate species (Manour et al., Phytochemistry, 1999, 50: 541,548). In general, the proportion of these fatty acids accounted for less than 2.3% of the total fatty acids in these species. As part of a study investigating the modulation of the hemolytic fatty acid 18:5n3, cultures of Prorocentrum mininum were grown in artificial seawater with varying molarities of sodium selenite (0, 1, 10, and 100 nM). Optimal growth was observed at 1 nM with this media. As expected, the level of 18:5n3 was modulated by the selenium in the culture medium (7.0 ± 0.2, 14.5 ± 0.6, 7.4 ± 0.8, and 3.9 ± 0.8% of total fatty acid, respectively), with the highest percentage found at 1 nM. Unexpectedly the level of VLC-HUFA (28:8n3) increased to 7.3 ± 2.8% at 0 nM sodium selenite, while at all other selenite concentrations the VLC-HUFA was less than 1%. A possible biochemical basis for this finding will be discussed. [source]

MODULATION OF ATTENTION IN SEXUAL CUE PROCESSING

PSYCHOPHYSIOLOGY, Issue 2008
Article first published online: 12 AUG 200
No abstract is available for this article. [source]

EPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009
Dan-Dan Chen
SUMMARY 1It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and ,-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52%vs TAC, respectively), accompanied by significant inhibition of nuclear factor-,B and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. 4In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals. [source]

PODOCYTE INJURY IS SUPPRESSED BY 1,25-DIHYDROXYVITAMIN D3 VIA MODULATION OF TRANSFORMING GROWTH FACTOR-,1/BONE MORPHOGENETIC PROTEIN-7 SIGNALLING IN PUROMYCIN AMINONUCLEOSIDE NEPHROPATHY RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009
Hou-Qin Xiao
SUMMARY 1Accumulating evidence suggests that vitamin D and its analogues are renoprotective. However, the precise mechanisms and the molecular targets by which active vitamin D exerts its beneficial effects remain obscure. The objective of the present study was to evaluate the effect of active vitamin D on rats with puromycin aminonucleoside (PAN) nephropathy, a model that is characterized by predominant podocyte injury. 2The PAN nephropathy rats were created by a single intravenous injection of 100 mg/kg PAN. Changes in renal pathology and podocyte numbers were observed. Real-time polymerase chain reaction (PCR) was performed to examine mRNA expression of nephrin, transforming growth factor (TGF)-,1 and bone morphogenetic protein (BMP)-7. Protein expression of nephrin, TGF-,1, BMP-7 and p-Smad2/3 and p-Smad1/5/8 was examined by immunofluorescence, immunohistochemistry and western blotting, respectively. Rats were treated with 1,25(OH)2D3 by gastric gavage at a dose of 2.5 µg/kg per day, starting 2 days before PAN injection and continuing throughout the experiment. 3A single injection of PAN induced massive proteinuria and elevated serum creatinine on Day 7, both of which were significantly suppressed by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Immunofluorescence and real-time PCR of the podocyte-associated protein nephrin revealed reduced and discontinuous staining and this change was reversed by 1,25(OH)2D3. In PAN nephropathy rats, TGF-,1 and p-Smad2/3 expression was upregulated, whereas that of BMP-7 and p-Smad1/5/8 was downregulated. Treatment with 1,25(OH)2D3 significantly restored BMP-7/Smad signalling while suppressing TGF-,1/Smad signalling. 4In conclusion, 1,25(OH)2D3 can ameliorate podocyte damage and proteinuria induced by PAN. The beneficial effects of 1,25(OH)2D3 on podocytes may be attributable, in part, to direct modulation of TGF-,1/BMP-7 signalling. [source]

MODULATION OF SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION (STAT) FACTOR PATHWAYS DURING FOCAL CEREBRAL ISCHAEMIA: A GENE EXPRESSION ARRAY STUDY IN RAT HIPPOCAMPUS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2007
Sheng-Li Sun
SUMMARY 1Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis. 2The present study used middle cerebral artery occlusion (MCAO) to induce ischaemia and reperfusion in Sprague-Dawley rats. Using superarray Q series Janus tyrosine kinases (Jak)/STAT signalling pathway gene array, a total of 96 genes was screened in adult male rat hippocampus after transient focal cerebral ischaemia. 3The results showed that 23 genes were upregulated at least twofold by ischaemia treatment and that 12 genes were downregulated at least threefold by ischaemia treatment compared with controls. 4After confirmation by quantitative real-time polymerase chain reaction, the data suggest that the gene expression of STAT2, 5a, 5b, 6 and suppressor of cytokine signalling (SOCS) 4 was increased by ischaemia, probably due to a compensatory response of the brain, which may play a protective role in damaged brain tissue. 5The results of the present study provide evidence on global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion, in which STAT2, 5a, 5b, 6 and SOCS4 were confirmed to be significantly modulated during focal cerebral ischaemia. [source]

EFFICACY OF SARGASSUM POLYCYSTUM (PHAEOPHYCEAE) SULPHATED POLYSACCHARIDE AGAINST PARACETAMOL-INDUCED DNA FRAGMENTATION AND MODULATION OF MEMBRANE-BOUND PHOSPHATASES DURING TOXIC HEPATITIS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2007
HB Raghavendran
SUMMARY 1The aim of the present study was to assess the protective effect of Sargassum polycystum (sulphated polysaccharide) extract against paracetamol-induced DNA strand breaks and modulation of membrane-bound phosphatases, protein thiols and inorganic cations during toxic hepatitis. 2Seaweed extract (200 mg/kg per day for 21 days) was administered to male Wistar rats against paracetamol challenge. Serum and liver tissues were used to assess levels of ATPase, protein thiols and inorganic cations using atomic absorption spectroscopy. The fragmentation of DNA was assessed by agarose gel electrophoresis. 3Paracetamol induced intracellular stress, accompanied by changes in the structural and functional characteristics of liver cell membranes, which affected DNA integrity, membrane-bound ATPase and inorganic cations homeostasis. Rats intoxicated with paracetamol (800 mg/kg, i.p.) showed significant impairment in activities of total ATPase, Mg2+ -ATPase, Ca+ -ATPase and Na+/K+ -ATPase, with concomitant changes in the levels of tissue protein thiols and inorganic cations, such as Na+, K+ and Ca2+. These changes were prevented in animals pretreated with S. polycystum extract, which indicates that S. polycystum supplementation could exert some protective effect against paracetamol-induced toxic hepatitis in rats. 4The protective effect of the seaweed extract may be due to the presence of sulphated compounds that have free radical-scavenging activity. [source]

Modulation and metamodulation of synapses by adenosine

ACTA PHYSIOLOGICA, Issue 2 2010
J. A. Ribeiro
Abstract The presence of adenosine in all nervous system cells (neurones and glia) together with its intensive release following insults makes adenosine as a sort of ,regulator' of synaptic communication, leading to the homeostatic coordination of brain function. Besides the direct actions of adenosine on the neurosecretory mechanisms, to tune neurotransmitter release, adenosine receptors interact with other receptors as well as with transporters as part of its attempt to fine-tune synaptic transmission. This review will focus on examples of the different ways adenosine can use to modulate or metamodulate synapses, in other words, to trigger or brake the action of some neurotransmitters and neuromodulators, to cross-talk with other G protein-coupled receptors, with ionotropic receptors and with receptor kinases as well as with transporters. Most of these interactions occur through A2A receptors, which in spite of their low density in some brain areas, such as the hippocampus, may function as amplifiers of the signalling of other mediators at synapses. [source]

Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping technique

ACTA PHYSIOLOGICA, Issue 4 2009
D. V. Abramochkin
Abstract Aims:, Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. Methods:, A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. Results:, Acetylcholine (10 ,m) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 ± 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 ,m) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 ± 1.3% of the control rate of the rhythm, always accompanied the shift. Conclusions:, Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift. [source]

Modulation of calcium signalling by intracellular organelles seen with targeted aequorins

ACTA PHYSIOLOGICA, Issue 1 2009
M. T. Alonso
Abstract The cytosolic Ca2+ signals that trigger cell responses occur either as localized domains of high Ca2+ concentration or as propagating Ca2+ waves. Cytoplasmic organelles, taking up or releasing Ca2+ to the cytosol, shape the cytosolic signals. On the other hand, Ca2+ concentration inside organelles is also important in physiology and pathophysiology. Comprehensive study of these matters requires to measure [Ca2+] inside organelles and at the relevant cytosolic domains. Aequorins, the best-known chemiluminescent Ca2+ probes, are excellent for this end as they do not require stressing illumination, have a large dynamic range and a sharp Ca2+ -dependence, can be targeted to the appropriate location and engineered to have the proper Ca2+ affinity. Using this methodology, we have evidenced the existence in chromaffin cells of functional units composed by three closely interrelated elements: (1) plasma membrane Ca2+ channels, (2) subplasmalemmal endoplasmic reticulum and (3) mitochondria. These Ca2+ -signalling triads optimize Ca2+ microdomains for secretion and prevent propagation of the Ca2+ wave towards the cell core. Oscillatory cytosolic Ca2+ signals originate also oscillations of mitochondrial Ca2+ in several cell types. The nuclear envelope slows down the propagation of the Ca2+ wave to the nucleus and filters high frequencies. On the other hand, inositol-trisphosphate may produce direct release of Ca2+ to the nucleoplasm in GH3 pituitary cells, thus providing mechanisms for selective nuclear signalling. Aequorins emitting at different wavelengths, prepared by fusion either with green or red fluorescent protein, permit simultaneous and independent monitorization of the Ca2+ signals in different subcellular domains within the same cell. [source]

Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug-induced regulatory phenomenon.

CYTOMETRY, Issue 3 2010
Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group
Abstract Background: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon. Methods: We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout. Results: The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on. Conclusions: Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection. © 2010 Clinical Cytometry Society [source]

Cell distribution of stress fibres in response to the geometry of the adhesive environment

CYTOSKELETON, Issue 6 2006
Manuel Théry
Abstract Cells display a large variety of shapes when plated in classical culture conditions despite their belonging to a common cell type. These shapes are transitory, since cells permanently disassemble and reassemble their cytoskeleton while moving. Adhesive micropatterns are commonly used to confine cell shape within a given geometry. In addition the micropattern can be designed so as to impose cells to spread upon adhesive and nonadhesive areas. Modulation of the pattern geometry allows the analysis of the mechanisms governing the determination of cell shape in response to external adhesive conditions. In this study, we show that the acquisition of cell shape follows two stages where initially the cell forms contact with the micropattern. Here, the most distal contacts made by the cell with the micropattern define the apices of the cell shape. Then secondly, the cell borders that link two apices move so as to minimise the distance between the two apices. In these cell borders, the absence of an underlying adhesive substrate is overcome by stress fibres forming between the apices, which in turn are marked by an accumulation of focal adhesions. By inhibiting myosin function, cell borders on nonadhesive zones become more concave, suggesting that the stress fibres work against the membrane tension in the cell border. Moreover, this suggested that traction forces are unevenly distributed in stationary, nonmigrating, cells. By comparing the stress fibres in cells with one, two, or three nonadherent cell borders it was reasoned that stress fibre strength is inversely proportional to number. We conclude that cells of a given area can generate the same total sum of tractional forces but that these tractional forces are differently spaced depending on the spatial distribution of its adherence contacts. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source]

Modulation of spatial attention in a child with developmental unilateral neglect

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2003
Veronika B Dobler MD
Attentional neglect of left space is one of the most striking acquired neurological disorders of adulthood. Recent evidence indicates a link between left spatial neglect and general right-hemisphere impairments in sustained attention and alertness. Poor sustained attention and alertness is also a central feature of other disorders, particularly childhood attention-deficit-hyperactivity disorder (ADHD). Here we present the case of a 7-year-old male showing that frank neglect can be present in children with sustained attention problems without a clear aetiological event, or obvious structural brain abnormalities as indicated by a normal MRI. Experimental amelioration of the neglect through left-hand movement and externally alerting stimulation by uninformative sounds further suggest close similarities to the adult disorder. We suggest that such distortions of spatial attention may be more common in childhood than previously thought. [source]

GABAergic modulation of primary gustatory afferent synaptic efficacy

DEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002
Andrew A. Sharp
Abstract Modulation of synaptic transmission at the primary sensory afferent synapse is well documented for the somatosensory and olfactory systems. The present study was undertaken to test whether GABA impacts on transmission of gustatory information at the primary afferent synapse. In goldfish, the vagal gustatory input terminates in a laminated structure, the vagal lobes, whose sensory layers are homologous to the mammalian nucleus of the solitary tract. We relied on immunoreactivity for the GABA-transporter, GAT-1, to determine the distribution of GABAergic synapses in the vagal lobe. Immunocytochemistry showed dense, punctate GAT-1 immunoreactivity coincident with the layers of termination of primary afferent fibers. The laminar nature and polarized dendritic structure of the vagal lobe make it amenable to an in vitro slice preparation to study early synaptic events in the transmission of gustatory input. Electrical stimulation of the gustatory nerves in vitro produces synaptic field potentials (fEPSPs) predominantly mediated by ionotropic glutamate receptors. Bath application of either the GABAA receptor agonist muscimol or the GABAB receptor agonist baclofen caused a nearly complete suppression of the primary fEPSP. Coapplication of the appropriate GABAA or GABAB receptor antagonist bicuculline or CGP-55845 significantly reversed the effects of the agonists. These data indicate that GABAergic terminals situated in proximity to primary gustatory afferent terminals can modulate primary afferent input via both GABAA and GABAB receptors. The mechanism of action of GABAB receptors suggests a presynaptic locus of action for that receptor. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 133,143, 2002 [source]

Influence of parental deprivation on the behavioral development in Octodon degus: Modulation by maternal vocalizations

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2003
Katharina Braun
Abstract Repeated separation from the family during very early stages of life is a stressful emotional experience which induces a variety of neuronal and synaptic changes in limbic cortical areas that may be related to behavioral alterations. First, we investigated whether repeated parental separation and handling, without separation from the family, leads to altered spontaneous exploratory behavior in a novel environment (open field test) in 8-day-old Octodon degus. Second, we tested whether the parentally deprived and handled animals display different stimulus-evoked exploratory behaviors in a modified open field version, in which a positive emotional stimulus, the maternal call, was presented. In the open field test a significant influence of previous emotional experience was found for the parameters of running, rearing, and vocalization. Parentally deprived degus displayed increased horizontal (running) and vertical (rearing) motoric activities, but decreased vocalization, compared to normal and handled controls. The presentation of maternal vocalizations significantly modified running, vocalization, and grooming activities, which in the case of running activity was dependent on previous emotional experience. Both deprivation-induced locomotor hyperactivity together with the reduced behavioral response towards a familiar acoustic emotional signal are similar to behavioral disturbances observed in human attachment disorders. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 237,245, 2003. [source]

Eye remember you two: gaze direction modulates face recognition in a developmental study

DEVELOPMENTAL SCIENCE, Issue 5 2006
Alastair D. Smith
The effects of gaze direction on memory for faces were studied in children from three different age groups (6,7, 8,9, and 10,11 years old) using a computerized version of a task devised by Hood, Macrae, Cole-Davies and Dias (2003). Participants were presented with a sequence of faces in an encoding phase, and were then required to judge which faces they had previously encountered in a surprise two-alternative forced-choice recognition test. In one condition, stimulus eye gaze was either direct or deviated at the viewing phase, and eyes were closed at the test phase. In another condition, stimulus eyes were closed at the viewing phase, with either direct or deviated gaze at the test phase. Modulation of gaze direction affected hit rates, with participants demonstrating greater accuracy for direct gaze targets compared to deviated gaze targets in both conditions. Reaction times (RT) to correctly recognized stimuli were faster for direct gaze stimuli at the viewing phase, but not at the test phase. The age group of participants differentially affected these measures: there was a greater hit rate advantage for direct gaze stimuli in older children, although RTs were less affected by age. These findings suggest that while the facilitation of face recognition by gaze direction is robust across encoding and recognition stages, the efficiency of the process is affected by the stage at which gaze is modulated. [source]

Electrochemically Induced Modulation of the Catalytic Activity of a Reversible Redoxsensitive Riboswitch

ELECTROANALYSIS, Issue 9 2008
Denise Strohbach
Abstract Over the past decade, RNA conformation has been shown to respond to external stimuli. Thus, dependent on the presence of a high affinity ligand, specifically designed ribozymes can be regulated in a classical allosteric way. In this scenario, a binding event in one part of the RNA structure induces conformational changes in a separated part, which constitutes the catalytic centre. As a result activity is switched on (positive regulation) or off (negative regulation). We have developed a hairpin aptazyme responding to flavine mononucleotide (FMN). Ribozyme activity is dependent on binding of FMN and thus is switched on in the presence of FMN in its oxidized form. Under reducing conditions, however, FMN changes its molecular geometry, which is associated with loss of binding and consequently down-regulation of ribozyme activity. While in previous experiments sodium dithionite was used for reduction of FMN, we now present an assay for electrochemically induced activity switching. We have developed an electrochemical microcell that allows for iterative cycles of reduction/oxidation of FMN in an oxygen free atmosphere and thus for reversible switching of ribozyme activity. The reaction proceeds in droplets of 3 to 10,,L at micro- to nanomolar concentrations of the reaction components. [source]

Modulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse models

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2003
Daniëlle M.J. Curfs
Abstract The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were highest in aorta (10.8 ± 1.4 adducts/108 nucleotides), followed by brain (7.8 ± 1.3), lung (3.3 ± 0.7), heart (3.1 ± 0.6), liver (1.5 ± 0.2) and stomach (1.2 ± 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 ± 0.7, 5.0 ± 0.5 and 4.6 ± 0.4, respectively), followed by stomach (2.7 ± 0.4), brain (2.3 ± 0.2), and liver (1.7 ± 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 ± 0.2), heart (1.9 ± 0.2), and brain (2.9 ± 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 ± 1.5). A similar but nonsignificant trend was observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases. Environ. Mol. Mutagen. 42:243,249, 2003. © 2003 Wiley-Liss, Inc. [source]

Intracellular Calcium Increase in Epileptiform Activity: Modulation by Levetiracetam and Lamotrigine

EPILEPSIA, Issue 7 2004
Antonio Pisani
Summary:,Purpose: Alterations in neuronal calcium (Ca2+) homeostasis are believed to play an essential role in the generation and propagation of epileptiform events. Levetiracetam (LEV) and lamotrigine (LTG), novel antiepileptic drugs (AEDs), were tested on epileptiform events and the corresponding elevations in intracellular Ca2+ concentration ([Ca2+]i) recorded from rat neocortical slices. Methods: Electrophysiological recordings were performed from single pyramidal neurons from a slice preparation. Spontaneous epileptiform events consisting of long-lasting, repetitive paroxysmal depolarization shifts (PDSs) and interictal spike activity were induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4-aminopyridine. Simultaneously, microfluorimetric measurements of [Ca2+]i were performed. Optical imaging with Ca2+ indicators revealed a close correlation between Ca2+ transients and epileptiform events. Results: Both LEV and LTG were able to reduce both amplitude and duration of PDSs, as well as the concomitant elevation in [Ca2+]i, in a dose-dependent fashion. Whole-cell patch-clamp recordings from isolated neocortical neurons revealed that LEV significantly reduced N-, and partially P/Q-type high-voltage-activated (HVA) Ca2+ currents, whereas sodium currents were unaffected. Interestingly, the inhibitory effects of LEV were mimicked and occluded by LTG or by a combination of ,-conotoxin GVIA and ,-agatoxin IVA, selective blockers of N- and P/Q-type HVA channels, respectively, suggesting a common site of action for these AEDs. Conclusions: These results demonstrate that large, transient elevations in neuronal [Ca2+]i correlate to epileptiform discharges. The antagonistic effects of LEV and LTG on [Ca2+]i overload might represent the basis for their anticonvulsant efficacy and could preserve neuronal viability. [source]

Corticothalamic Modulation during Absence Seizures in Rats: A Functional MRI Assessment

EPILEPSIA, Issue 9 2003
Jeffrey R. Tenney
Summary:,Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level,dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using ,-butyrolactone (GBL; 200 mg/kg, intraperitoneal). Results: The corticothalamic circuitry, critical for spike,wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. [source]

In Vivo Modulation of Hippocampal Epileptiform Activity with Radial Electric Fields

EPILEPSIA, Issue 6 2003
Kristen A. Richardson
Summary: Purpose: Electric field stimulation can interact with brain activity in a subthreshold manner. Electric fields have been previously adaptively applied to control seizures in vitro. We report the first results from establishing suitable electrode geometries and trajectories, as well as stimulation and recording electronics, to apply this technology in vivo. Methods: Electric field stimulation was performed in a rat kainic acid injection seizure model. Radial electric fields were generated unilaterally in hippocampus from an axial depth electrode. Both sinusoidal and multiphasic stimuli were applied. Hippocampal activity was recorded bilaterally from tungsten microelectrode pairs. Histologic examination was performed to establish electrode trajectory and characterize lesioning. Results: Electric field modulation of epileptiform neural activity in phase with the stimulus was observed in five of six sinusoidal and six of six multiphasic waveform experiments. Both excitatory and suppressive modulation were observed in the two experiments with stimulation electrodes most centrally placed within the hippocampus. Distinctive modulation was observed in the period preceding seizure-onset detection in two of six experiments. Short-term histologic tissue damage was observed in one of six experiments associated with high unbalanced charge delivery. Conclusions: We demonstrated in vivo electric field modulation of epileptiform hippocampal activity, suggesting that electric field control of in vivo seizures may be technically feasible. The response to stimulation before seizure could be useful for triggering control systems, and may be a novel approach to define a preseizure state. [source]

Enemy Recognition of Reed Warblers (Acrocephalus scirpaceus): Threats and Reproductive Value Act Independently in Nest Defence Modulation

ETHOLOGY, Issue 6 2010
Daniela Campobello
Organisms should respond more aggressively towards species perceived as a danger to their offspring, but intensity of defence may be gauged by the value of current offspring weighed against the value of future reproductive opportunities. We tested whether defensive responses of nesting reed warblers (Acrocephalus scirpaceus) are the result of an interaction effect between the type of stimulus confronted and the value of the warbler's nesting attempt. We quantified the ability of reed warblers to discriminate among brood parasites, nestling predators and non-threatening species at different stages of the breeding cycle. We also determined whether variables that influence the value of offspring, such as time of season, size and age of clutch or brood, and time of day and number of visits to the nest, explain variation in the intensity of defence recorded during the egg and nestling stages. Responses to the three stimuli differed significantly, as reed warblers consistently directed their mobbing calls and attacks towards parasites, whereas they were less conspicuous when confronted with models of predators. Reed warblers modulated their responses towards each stimulus in accordance with the threat each posed at a specific nesting stage, whereas they were not affected by other variables relative to their reproductive potential. The churr call, however, was uttered independently of the stimulus, as it was triggered by the mere presence of nestlings in the nest. [source]

After the Health Check What is the Future for the Common Agricultural Policy?

EUROCHOICES, Issue 1 2009
Nach dem Gesundheitscheck: Wie geht es weiter mit der Gemeinsamen Agrarpolitik?
Summary After the Health Check What is the Future for the Common Agricultural Policy? The CAP has now completed another stage in its development. The Health Check negotiating marathon has ended. The Czech Republic has been against unequal conditions for member states as these deform fair competition and the common market. Progressive modulation in the originally proposed form would have created barriers to a unified Europe, thus going against the motto of the Czech presidency ,Europe without Barriers'. The Czech Republic can certainly be satisfied with the essence of the compromise. The cancellation of the milk quota in 2015 is a liberalising measure, and as such we support it. The Health Check opens the door to the Czech presidency for a discussion on the elimination of unfair differences in direct payments between member states and we will definitely take up the opportunity. After 2013 the CAP will have to take much greater account of the situation following the unprecedented expansion of the EU in 2004 and 2006. For the Czech Republic, a further reinforcing of freedom in decision making for farmers and their focus on the specific needs of the local, community and global market is fundamental. Further simplification of the CAP and ,better regulation', focussing on a reduction in the administrative burden on farmers, is one of the priority challenges. La PAC a maintenant atteint un autre stade de son développement. Le marathon de négociation du bilan de santé a abouti. La République tchèque s'est opposée aux conditions inégales proposées aux pays membres car elles faussent la concurrence équitable et le marché commun. La modulation progressive sous sa forme initiale aurait créé des barrières dans une Europe unifiée, ce qui va à l'encontre de la devise de la présidence tchèque "Une Europe sans barrières". La République tchèque peut certainement être satisfaite de l'essence du compromis. La suppression du système des quotas laitiers en 2015 est une mesure de libéralisation et nous la soutenons en tant que telle. Le bilan de santé ouvre la porte à la présidence tchèque pour une discussion sur l'élimination des différences injustes entre paiements directs selon le pays membre et nous profiterons bien entendu de l'occasion. Après 2013, la PAC devra prendre davantage en compte la situation créée par l'élargissement sans précédent de l'UE entre 2004 et 2006. Pour la République tchèque, il est fondamental de renforcer encore la liberté qu'ont les agriculteurs pour prendre leurs décisions et de s'orienter vers les besoins spécifiques du marché local, communautaire et mondial. Un des défis prioritaires est de continuer à simplifier la PAC et d'améliorer la réglementation en s'orientant vers une réduction de la charge administrative qui pèse sur les agriculteurs. Eine weitere Phase in der Entwicklung der Gemeinsamen Agrarpolitik ist nun abgeschlossen. Der Verhandlungsmarathon hinsichtlich des Gesundheitschecks ist vorbei. Die Tschechische Republik war dagegen, dass für die Mitgliedsstaaten unterschiedliche Bedingungen gelten sollen, da diese den fairen Wettbewerb und den gemeinsamen Markt verzerren. Eine progressive Modulation in der ursprünglich vorgeschlagenen Form hätte einem einheitlichen Europa Steine in den Weg gelegt und somit dem Motto "Europa ohne Grenzen" der tschechischen Präsidentschaft widersprochen. Die Tschechische Republik hat zweifellos mit dem Kompromiss ein im Wesentlichen zufriedenstellendes Ergebnis erzielt. Die Abschaffung der Milchquote bis 2015 ist eine Maßnahme zur Liberalisierung, und als solche findet sie unsere Unterstützung. Der Gesundheitscheck eröffnet der tschechischen Präsidentschaft die Diskussion über die Beseitigung unterschiedlich hoher , und somit ungerechter , Direktzahlungen an die Mitgliedsstaaten. Diese Gelegenheit werden wir uns nicht entgehen lassen. Nach 2013 wird sich die GAP sehr viel mehr mit der Situation beschäftigen müssen, die sich aus der beispiellosen EU-Erweiterung aus den Jahren 2004 und 2006 ergibt. Für die Tschechische Republik ist es von grundlegender Bedeutung, die Entscheidungsfreiheit für Landwirte und deren Orientierung an den lokalen, regionalen und globalen Märkten fortwährend zu stärken. Die weitere Vereinfachung der GAP und eine "bessere Regulierung", die den Verwaltungsaufwand für Landwirte verringern soll, gehören zu den vorrangigen Zielen. [source]

Modulation of 2B4 (CD244) activity and regulated SAP expression in human NK cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007
Johanna Endt
Abstract The adapter protein SAP is important for the signal transduction of the family of SLAM-related receptors (SRR), which have important immune-modulating functions. The importance of SAP and SRR for a functional immune reaction becomes obvious in patients suffering from X-linked lymphoproliferative disease, which is characterized by non-functional SAP. Here we investigate the regulation of SAP expression in human NK cells. We demonstrate that SAP mRNA expression and protein levels are low in freshly isolated resting NK cells. IL-2 stimulation leads to an up-regulation of SAP expression, which can be enhanced by IL-12, the stimulation of TLR3 by polyinosinic-polycytidylic acid (poly(I:C))and to a lesser extent by IFN-,. EAT-2, a SAP-related adapter protein, is already detectable in resting NK cells and does not change its expression after IL-2 stimulation. The regulation of SAP has functional consequences for the stimulation of NK cell cytotoxicity by 2B4. In resting NK cells, 2B4 stimulation can only enhance NK cell lysis when co-triggered with other activating NK cell receptors. In IL-2-activated NK cells with high SAP expression the triggering of 2B4 alone is sufficient to induce NK cell cytotoxicity, demonstrating a correlation between the regulated SAP expression and the function of 2B4. [source]

Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epithelium

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006
Matt Butler
Abstract A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGF,) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24,h. Co-culture resulted in DC with reduced expression of MHC class,II, CD86, and CD80, and poor T,cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGF, production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGF, antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a ,tolerogenic' environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces. [source]

PRECLINICAL STUDY: Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in mice

ADDICTION BIOLOGY, Issue 3 2009
Emilie Belkaï
ABSTRACT The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. [source]

Modulation of the Communication between Redox Centers in a Tris(ferrocene)-tren Ligand by Complexation of Lanthanide Ions

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 23 2003
Marie Heitzmann
The tripodal ligand L built on the tren platform and bearing three chemically equivalent ferrocene units was prepared and characterized. Electrochemical investigations indicate that electrostatic communication occurs between the three ferrocene groups in L, which leads to the observation of two distinct voltammetric waves. The electrochemical communication between the three ferrocene moieties is disrupted in 1:1 (L:M3+) type complexes formed between L and Y3+ or Eu3+ metal cations and their electrochemical response tends towards that of a single three-independent-electrons oxidation wave. Modulation of the electrochemical properties of L in the presence of lanthanide ions might be exploited with a view to their electrochemical sensing in organic and aqueous media. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Modulation of spinal inhibitory reflex responses to cutaneous nociceptive stimuli during upper limb movement

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008
Romildo Don
Abstract In the present study we investigated the probability, latency and duration of the inhibitory component of the withdrawal reflex elicited by painful electrical stimulation of the index finger in humans. The stimulus consisted of a train of high-intensity pulses. The investigation was carried out in several upper limb muscles during isometric contractions of different strengths and during a motor sequence consisting of reaching, picking up and transporting an object. We used a new algorithm to detect and characterize the inhibitory reflex. The reflex was found in all muscles except the brachioradialis at all the isometric contraction strengths, and showed a distal-to-proximal gradient of latency and duration. Conversely, during movement the reflex probability was high (> 80%) in the anterior deltoid and triceps muscles during reaching, in the extensor carpi radialis muscle during transporting of the object, and in the first interosseous muscle during both picking up and transporting of the object. This modulation of inhibitory reflex transmission in the upper limb muscles suggests that the motor response is organized in such a way as to inhibit the overall ongoing motor task by interrupting motion during reaching and by releasing the object during transporting. This pattern of modulation appears to differ markedly from that previously reported for the excitatory component of the withdrawal reflex. Study of the nociceptive inhibitory reflexes during movement offers new and more profound insights into the functional anatomical organization of the spinal interneuronal network mediating sensory,motor integration. [source]

Modulation of spontaneous and evoked EPSCs and IPSCs in optic lobe neurons of cuttlefish Sepia officinalis by the neuropeptide FMRF-amide

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Abdesslam Chrachri
Abstract The effects of the neuropeptide FMRFa on spontaneous excitatory postsynaptic currents (sEPSCs) and inhibitory postsynaptic currents (sIPSCs), as well as on evoked EPSCs and IPSCs, in two types of neurons within the central optic lobe of cuttlefish were examined using the whole-cell voltage-clamp technique. FMRFa (1,10 µm) did not affect cell membrane resting potentials, but reversibly reduced both the frequency and amplitude of sEPSCs in neurons within the medulla region of the optic lobe while increasing the frequency and amplitude of their sIPSCs. For centrifugal neurons in the inner granule cell layer of the optic lobe, FMRFa (1,10 µm) decreased both the frequency and amplitude of sEPSCs. In the presence of tetrodotoxin (0.5 µm), neither the interevent interval, nor amplitude distributions of the miniature EPSCs or the miniature IPSCs, were affected by FMRFa, implying a presynaptic action of FMRFa on the optic lobe neurons. Bath application of the neuropeptide also abolished or reduced in amplitude the evoked EPSCs and increased the amplitude of evoked IPSCs in optic lobe neurons, showing that FMRFa induced similar effects on evoked as on spontaneous postsynaptic currents. These results demonstrate the complex range of modulatory effects FMRFa can have within central nervous system circuits. [source]

Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003
Manel M. Santafé
Abstract We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30,40 days) and newborn (3,6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ,-conotoxin-GVIA and ,-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 µm) reduced evoked neurotransmission (, 47%). The M2 receptor-selective antagonist methoctramine (1 µm) increased the evoked release (, 67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3,6-day newborn rats, pirenzepine reduced the evoked release (, 30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 µm) unexpectedly decreased the evoked release (, 40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. [source]

Modulation by adenosine of both muscarinic M1 -facilitation and M2 -inhibition of [3H]-acetylcholine release from the rat motor nerve terminals

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002
Laura Oliveira
Abstract The crosstalk between adenosine and muscarinic autoreceptors regulating evoked [3H]-acetylcholine ([3H]-ACh) release was investigated on rat phrenic nerve-hemidiaphragm preparations. Motor nerve terminals possess facilitatory M1 and inhibitory M2 autoreceptors that can be activated by McN-A-343 (1,30 µm) and oxotremorine (0.3,100 µm), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm,10 µm), caused a biphasic (inhibitory/facilitatory) effect, indicating that M1 -facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF,DX 116-sensitive M2 receptors was partially attenuated, as pretreatment with M1 antagonists, muscarinic toxin 7 (MT-7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A2A -adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN-A-343-induced facilitation into a small inhibitory effect. Conversely, the A1 -receptor agonist, R- N6 -phenylisopropyl adenosine (R-PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN-A-343. Synergism between A2A and M2 receptors is regulated by a reciprocal interaction with facilitatory M1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz-bursts, facilitation (M1) of [3H]-ACh release by McN-A-343 disappeared, while the inhibitory (M2) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A2A receptors, as it was precluded by the selective A2A receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A1 receptors. During high frequency bursts, tonic activation of A2A receptors promotes M2 autoinhibition by braking the M1 receptor operated counteraction. [source]