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Initial Activation (initial + activation)
Selected AbstractsAcute experimental colitis and human chronic inflammatory diseases share expression of inflammation-related genes with conserved Ets2 binding sitesINFLAMMATORY BOWEL DISEASES, Issue 2 2009Tineke C.T.M. van der Pouw Kraan PhD Abstract Background: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by chronic inflammation of the gastrointestinal tract, with overlapping clinical characteristics and unknown etiology. We reasoned that in intestinal inflammation the initial activation of the innate immune response fails to resolve, finally resulting in uncontrolled chronic inflammatory bowel disease. Methods: To identify the early inflammatory events in colitis that remain active in human chronic colitis, we analyzed the changes of the colonic transcriptome during acute experimental colitis and compared the outcome with previously published profiles of affected tissues from patients with UC and CD, and as a control for intestinal inflammation in general, tissues from celiac disease patients. Rheumatoid arthritis synovial tissues were included as a nonintestinal inflammatory disease. The expression profiles of each disease were analyzed separately, in which diseased tissues were compared to unaffected tissues from the same anatomical location. Results: Gene ontology analysis of significantly regulated genes revealed a marked activation of immunity and defense processes in all diseases, except celiac disease, where immune activation is less prominent. The control region of upregulated genes contained an increase in Ets2 binding sites in experimental colitis, UC, and rheumatoid arthritis, and were associated with upregulated immune activity. In contrast, upregulated genes in celiac disease harbored the transcription factor binding site GLI, which binds to the Gli family of transcription factors involved in hedgehog signaling, affecting development and morphogenesis. Conclusion: Ets2 may be an important transcription factor driving inflammation in acute as well as chronic inflammatory disease. (Inflamm Bowel Dis 2008) [source] Behavioral Interaction Between Nicotine and Ethanol: Possible Modulation by Mouse Cerebellar GlutamateALCOHOLISM, Issue 7 2006Salim Al-Rejaie Background: Epidemiological studies show that people who drink alcoholic beverages also smoke cigarettes and vice versa. Furthermore, animal studies provide circumstantial evidence for ethanol and nicotine interaction. Previously, we demonstrated that intracerebellar nicotine attenuates ethanol ataxia. This study investigated the possible role of glutamate in modulating the interaction of nicotine and ethanol. Methods: Glutamate drugs N -methyl- d -aspartate (NMDA) and (+)- , -amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) as well as their antagonists were directly microinfused into the cerebellum of CD-1 male mice to evaluate their effect on ethanol (2 g/kg i.p.) ataxia. Drug microinfusions were made via stereotaxically implanted stainless-steel guide cannulas. Rotorod was used to evaluate the ataxic response of ethanol. Results: Microinfusion of nicotine (0.3125, 1.25, 5 ng) significantly attenuated ethanol ataxia dose-dependently, confirming the functional interaction between nicotine and ethanol as reported earlier. Intracerebellar pretreatment with hexamethonium, a nicotinic receptor (nAChR) antagonist, significantly blocked nicotine-induced attenuation of ethanol ataxia suggesting participation of nAChRs. When ethanol was injected before nicotine microinfusion, nicotine failed to attenuate ethanol ataxia, indicating the critical importance of initial activation of nAChRs by nicotine. Intracerebellar microinfusion of NMDA (30, 60, 125 ng) and its antagonist, (+)-MK-801 (50, 100, 200 ng), significantly increased and decreased, respectively, the nicotine-induced attenuation of ethanol ataxia in a dose-related manner, suggesting participation of the NMDA receptor. Similarly, intracerebellar microinfusion of AMPA (7.5, 15, 30 ng) and its antagonist, nitro -2, 3-dioxobenzoquinoxaline-sulfonamide (NBQX; 25, 50, 100 ng), significantly increased and decreased, respectively, the nicotine-induced attenuation of ethanol ataxia in a dose-dependent manner. This suggests participation of the AMPA receptor and further supports involvement of the glutamate system in the ethanol,nicotine interaction. Intracerebellar nicotine failed to attenuate sodium-pentobarbital (25 mg/kg i.p.) ataxia, suggesting the relative specificity of the nicotine,ethanol interaction. Conclusions: The results suggested that glutamate modulates the functional interaction between nicotine and ethanol because NMDA and AMPA enhanced the nicotine-induced attenuation of ethanol ataxia, whereas (+)-MK-801 and NBQX reduced the attenuation. [source] Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas,Fas Ligand Signaling Pathway,THE LARYNGOSCOPE, Issue 9 2008Woo Yong Bae MD Abstract Objectives/Hypothesis: Hair cell loss results in the secondary loss of spiral ganglion neurons (SGNs), over a period of several weeks. The death of the SGNs themselves results from apoptosis. Previous studies have shown that several molecules are involved in the apoptosis of SGNs that occurred secondary to hair cell loss. However, the precise mechanism of apoptosis of the SGNs remains unclear. The aim of this study was to ascertain the secondary apoptosis of spiral ganglion cells induced by aminoglycoside and to investigate the role of the Fas,FasL signaling pathway using guinea pigs as an experimental animal model. Study Design: Laboratory study using experimental animals. Methods: Guinea pigs weighing 250 to 300 g (n = 21) from 3 to 4 weeks of age were used. Gentamicin (60 ,L) was injected through a cochleostomy site on their left side. At 1 (n = 7), 2 (n = 7), and 3 (n = 7) weeks after gentamicin treatment, their cochleas were obtained from their temporal bone. Hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were performed to observe apoptosis. To investigate the involvement of the Fas,FasL signaling pathway in the secondary apoptosis of SGNs, we performed reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry. Results: A progressive loss of spiral ganglion cells with increasing time after gentamicin treatment was observed on light microscopic examination. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining demonstrated induction of apoptotic cell death in SGNs after gentamicin treatment. Expression of FasL increased over time after gentamicin treatment as determined by RT-PCR and western blotting. On immunohistochemical staining, we observed the localization of FasL in the SGNs. The proapoptotic molecules Bax and Bad were increased, but levels of the antiapoptotic molecule Bcl-2 were decreased at increasing survival times after gentamicin treatment on RT-PCR. The gentamicin-treated group displayed initial activation of caspase-8 and increased the cleavage of caspase-3, caspase-8, and PARP protein in a time-dependent manner. Conclusions: The secondary apoptosis of SGNs could be a result of the apoptotic Fas,FasL signaling pathway. Blocking the Fas,FasL signaling pathway could be considered as a method for preventing secondary degeneration of SGNs, and further studies are needed to confirm this. [source] Glutamate-induced post-activation inhibition of locus coeruleus neurons is mediated by AMPA/kainate receptors and sodium-dependent potassium currentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2009Teresa Zamalloa Background and purpose:, Locus coeruleus (LC) neurons respond to sensory stimuli with a glutamate-triggered burst of spikes followed by an inhibition. The aim of our work was to characterize the inhibitory effect of glutamate in the LC. Experimental approach:, Single-unit extracellular and patch-clamp recordings were performed to examine glutamate responses in rat brain slices containing the LC. Key results:, Glutamate caused an initial activation followed by a late post-activation inhibition (PAI). Both effects were blocked by an AMPA/kainate receptor antagonist but not by NMDA or metabotropic glutamate receptor antagonists. All glutamate receptor agonists were able to activate neurons, but only AMPA and quisqualate caused inhibition. In neurons clamped at ,60 mV, glutamate and AMPA induced inward, followed by outward, currents, with the latter reversing polarity at ,110 mV. Glutamate-induced PAI was not modified by ,2 -adrenoceptor, µ opioid, A1 adenosine and GABAA/B receptor antagonists or Ca2+ -dependent release blockade, but it was reduced by raising the extracellular K+ concentration. Glutamate-induced PAI was not affected by several potassium channel, Na+/K+ pump, PKC and neuronal NO synthase inhibitors or lowering the extracellular Ca2+ concentration. The Na+ -activated K channel opener bithionol concentration-dependently potentiated glutamate-induced PAI, whereas partial (80%) Na+ replacement reduced glutamate- and AMPA-induced PAI. Finally, reverse transcription polymerase chain reaction assays showed the presence of mRNA for the Ca2+ -impermeable GluR2 subunit in the LC. Conclusions and implications:, Glutamate induces a late PAI in the LC, which may be mediated by a novel postsynaptic Na+ -dependent K+ current triggered by AMPA/kainate receptors. Mandarin translation of abstract [source] The medial and lateral bellies of gastrocnemius: A cadaveric and ultrasound investigationCLINICAL ANATOMY, Issue 1 2008Tony Antonios Abstract It is commonly reported that the medial belly (MG) of the gastrocnemius muscle extends further distally than the lateral belly (LG). This observation is made in several standard anatomy texts with no explanation or quantitative data. In this study, the medial and lateral bellies of gastrocnemius in 45 embalmed cadavers were measured. The observed difference in length of the two bellies was found to be highly significant (mean difference in length = 1.74 cm, P < 0.001). In 8 out of 84 legs examined (9.5%), however, the MG was found to be shorter than the LG (three right legs, five left legs, bilateral in two individuals). Surprisingly, there was no correlation between the difference in muscle belly length in any individual and ipsilateral leg length or total body length, suggesting that the difference in belly length may be unrelated to biomechanical function. An ultrasound investigation into the activity pattern of the two bellies was carried out on five volunteers. Muscle activity was monitored during passive and active movements of the ankle and knee joints at different leg positions. During knee flexion and ankle plantarflexion, the LG contracted first in four of the five subjects, followed by the MG, then a period of either LG predomination or equal contraction. The fifth subject, who showed a reversed pattern of activity, had previously suffered an inversion injury of the ankle. We suggest that the initial activation of the LG may help to stabilize the ankle during plantarflexion. We found no evidence that gastrocnemius acts as a shunt muscle during distraction of the knee. Clin. Anat. 21:66,74, 2008. © 2007 Wiley-Liss, Inc. [source] An electromyographic investigation of the effect of stimulus,response mapping on choice reaction timePSYCHOPHYSIOLOGY, Issue 1 2001Thierry Hasbroucq The activity of the agonist muscles was recorded during the performance of a two-choice visual reaction time (RT) task in which the compatibility of the stimulus,response mapping was manipulated. Correct trials were distinguished according to whether or not the activation of the agonist of the required response was preceded by an activation of the agonist of the nonrequired response. Double activation trials were more numerous for the incompatible than for the compatible mapping. Furthermore, these trials yielded longer RTs than the single muscular activation trials. These results suggest that initial activations of nonrequired responses are more frequently aborted and corrected when the mapping is incompatible than when it is compatible. This finding supports the dimensional overlap model of stimulus,response compatibility (S. Kornblum, T. Hasbroucq, & A. Osman, 1990). [source] | ||||||||||