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Selected AbstractsUnilateral Intracarotid Amobarbital Procedure for Language LateralizationEPILEPSIA, Issue 11 2005Jörg Wellmer Summary:,Purpose: The determination of language dominance as part of the presurgical workup of patients with pharmacoresistant epilepsies has experienced fundamental changes. With the introduction of noninvasive functional magnetic resonance imaging (fMRI), the number of patients receiving intracarotid amobarbital procedures (IAPs) for assessment of language dominance has decreased considerably. However, recent studies show that because of methodologic limitations of fMRI, IAP remains an important tool for language lateralization. The current study examines whether unilateral instead of bilateral IAP is an adequate way to apply IAP with reduced invasiveness. Methods: We retrospectively examine the predictive value of unilateral IAP for the results of bilateral IAP based on a sample of 75 patients with various types of language dominance. Target parameters are the prediction of the language-dominant hemisphere and the identification of patients with atypical language dominance. For language assessment based on unilateral IAP, we introduce the measure hemispheric language capacity (HLC). Results: Unilateral IAP performed on the side of intended surgery quantifies language capacity contralateral to the intended surgery. It detects atypical (bilateral or right) language dominance in the majority of patients. Experience with a separate series of 107 patients requiring presurgical language lateralization shows that in >80%, bilateral IAPs are redundant. Conclusions: Unilateral IAP is principally sufficient for language lateralization in the presurgical evaluation of patients with pharmacoresistant epilepsies. Necessity of bilateral IAP is restricted to few indications (e.g., callosotomy). In times of noninvasive language lateralization, we propose unilateral IAP as the method of choice for the verification of doubtful (bilateral) fMRI activation patterns. [source] Taurine selectively modulates the secretory activity of vasopressin neurons in conscious ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001Mario Engelmann Abstract Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic,neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 °C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABAA receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states. [source] Profile of P-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption processJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Belén Valenzuela Abstract The intrinsic absorption of salbutamol in different intestinal segments of the rat was measured and related with the corresponding intestinal P-glycoprotein (P-gp) expression levels. The apparent absorption rate constants (ka, h,1) observed in each fraction by means of the "in situ" rat gut absorption method after perfusion of a 0.29-mM isotonic solution of salbutamol were used as absorption indexes. In a separate series of studies, a semiquantitative analysis of the mRNA expression of P-gp by means of polymerase chain reaction and Western blot with an antibody raised against the P-gp were also performed. The "in situ" ka values determined in the different segments (h,1) showed that the absorption is not homogeneous along the intestinal tract, that is, 0.499,±,0.054 for colon, 0.474,±,0.052 for the proximal segment, 0.345,±,0.014 for the mean, and 0.330,±,0.023 for the distal fraction. Addition of verapamil to the perfusion fluid did provide a better absorption of salbutamol in the distal segment. The analysis of the mRNA expression and levels of P-gp showed that the enzyme content in each section of the intestine was inversely related to salbutamol absorption. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1641,1648, 2004 [source] Sex Differences in Ethanol-Induced Hypothermia in Ethanol-Naïve and Ethanol-Dependent/Withdrawn RatsALCOHOLISM, Issue 1 2009Anna N. Taylor Background:, Human and animal findings indicate that males and females display major differences in risk for and consequences of alcohol abuse and alcoholism. These differences are in large part mediated by sex-specific hormonal environments. Gonadal and adrenal secretory products are known to modulate the neurobehavioral responses of ethanol (EtOH) dependence and withdrawal. However, the effects of these steroids on physiological adaptations, such as thermoregulation, are less well established. To study the role of sex-related hormones in mediating sex differences in the hypothermic response to acute challenge with EtOH, we compared the EtOH-induced hypothermic responses of EtOH-naïve male and female rats and EtOH-dependent (on the third day of withdrawal) male and female rats before (intact) and after depletion of all gonadal and adrenal steroids by gonadectomy (GDX) with or without adrenalectomy (ADX). Methods:, Intact and GDX male and female rats, with or without ADX, were fed an EtOH-containing liquid diet for 15 days while control (EtOH-naïve) rats were pairfed the isocaloric liquid diet without EtOH or fed normal rat chow and water. On the third day of withdrawal from the EtOH diet we tested the hypothermic response to EtOH challenge (1.5 g/kg BWt, ip). Blood alcohol content (BAC) and corticosterone (CORT) content were analyzed in a separate series of intact and GDX males and females with and without ADX in response to the EtOH challenge. Results:, Ethanol-induced hypothermia was significantly greater and its duration significantly longer in intact males than females when subjects were EtOH-naïve. EtOH-induced hypothermia was significantly greater in intact females than males by the third day of withdrawal from EtOH dependence. GDX in males significantly shortened the duration of the hypothermic response and tended to blunt EtOH-induced hypothermia while response duration was significantly extended by GDX in females that tended to enhance EtOH-hypothermia. EtOH-induced hypothermia was significantly enhanced and its duration significantly lengthened by combined GDX and ADX in EtOH-naïve and -withdrawn males and by combined GDX and ADX in EtOH-naïve but not EtOH-withdrawn females. These differential EtOH-induced hypothermic responses did not appear to be caused by differences in EtOH handling among the groups. The absence of adrenal activation by EtOH in the GDX,ADX males and females contributes to their enhanced EtOH-induced hypothermic responses. Conclusions:, These results implicate the direct and indirect effects of removal of gonadal and adrenal secretory products as mediators of the thermoregulatory actions of EtOH. [source] Likelihood of Illegal Alcohol Sales at Professional Sport StadiumsALCOHOLISM, Issue 11 2008Traci L. Toomey Background:, Several studies have assessed the propensity for illegal alcohol sales at licensed alcohol establishments and community festivals, but no previous studies examined the propensity for these sales at professional sport stadiums. In this study, we assessed the likelihood of alcohol sales to both underage youth and obviously intoxicated patrons at professional sports stadiums across the United States, and assessed the factors related to likelihood of both types of alcohol sales. Methods:, We conducted pseudo-underage (i.e., persons age 21 or older who appear under 21) and pseudo-intoxicated (i.e., persons feigning intoxication) alcohol purchase attempts at stadiums that house professional hockey, basketball, baseball, and football teams. We conducted the purchase attempts at 16 sport stadiums located in 5 states. We measured 2 outcome variables: pseudo-underage sale (yes, no) and pseudo-intoxicated sale (yes, no), and 3 types of independent variables: (1) seller characteristics, (2) purchase attempt characteristics, and (3) event characteristics. Following univariate and bivariate analyses, we a separate series of logistic generalized mixed regression models for each outcome variable. Results:, The overall sales rates to the pseudo-underage and pseudo-intoxicated buyers were 18% and 74%, respectively. In the multivariate logistic analyses, we found that the odds of a sale to a pseudo-underage buyer in the stands was 2.9 as large as the odds of a sale at the concession booths (30% vs. 13%; p = 0.01). The odds of a sale to an obviously intoxicated buyer in the stands was 2.9 as large as the odds of a sale at the concession booths (89% vs. 73%; p = 0.02). Conclusions:, Similar to studies assessing illegal alcohol sales at licensed alcohol establishments and community festivals, findings from this study shows the need for interventions specifically focused on illegal alcohol sales at professional sporting events. [source] Feedback inhibition of action potential discharge by endogenous adenosine enhancement of the medium afterhyperpolarizationTHE JOURNAL OF PHYSIOLOGY, Issue 5 2009Ming Ruan Phasic activity in supraoptic nucleus vasopressin neurones is characterized by alternating periods of activity (bursts) and silence. During bursts, activation of a medium afterhyperpolarization induces spike frequency adaptation. Antagonism of A1 adenosine receptors within the supraoptic nucleus decreases spike frequency adaptation and prolongs phasic bursts in vivo, indicating that endogenous adenosine contributes to spike frequency adaptation. Here we used sharp electrode intracellular recordings from supraoptic nucleus neurones in hypothalamic explants to show that endogenous adenosine increases medium afterhyperpolarization amplitude to enhance spike frequency adaptation during phasic bursts. Superfusion of the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT, 10 ,m) increased intraburst firing rate of phasic neurones (by 2.0 ± 0.7 spikes s,1, P= 0.03) and burst duration (by 141 ± 113 s, P= 0.03). The CPT-induced increase in intraburst firing rate developed over the first few seconds of firing and persisted thereafter. In a separate series of experiments, CPT reduced the amplitude of the medium afterhyperpolarization evoked by a 1 s 20 Hz spike train (by 0.8 ± 0.3 mV, P < 0.001) in supraoptic nucleus neurones; this inhibition was not prevented by 3 mm CsCl (0.8 ± 0.1 mV decrease, P < 0.01) to block the afterdepolarization (which overlaps temporally with the medium afterhyperpolarization). In the presence of apamin to block the medium afterhyperpolarization, CPT did not alter afterdepolarization amplitude. Taken together, these data show that endogenous adenosine enhances medium afterhyperpolarization amplitude to contribute to spike frequency adaptation in phasic supraoptic nucleus neurones. [source] Disruption of axoplasmic transport induces mechanical sensitivity in intact rat C-fibre nociceptor axonsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2008Andrew Dilley Peripheral nerve inflammation can cause axons conducting through the inflamed site to become mechanically sensitive. Axonal mechanical sensitivity (AMS) of intact axons may explain symptoms in a diverse number of conditions characterized by radiating pain evoked by movements of the affected nerve. Because nerve inflammation also disrupts axoplasmic transport, we hypothesized that the disruption of axoplasmic transport by nerve inflammation could cause the cellular components responsible for mechanical transduction to accumulate and become inserted at the inflamed site, causing AMS. This was tested by examining AMS in C-fibre nociceptors following the application of axoplasmic transport blockers (colchicine and vinblastine) to the sciatic nerve. Both 10 mm colchicine and 0.1 mm vinblastine caused AMS to develop in 30.6% and 33.3% of intact axons, respectively (P < 0.05 compared to sham treatment). Since high doses of colchicine (> 50 mm) can damage axons, and inflammation is involved in the removal of axonal debris, experiments were performed to assess conduction across the treatment site as well as signs of inflammation. Results indicated minimal axonal loss (95% of A- and C-fibres conducting), consistent with the normal microscopic appearance of the colchicine treatment site and absence of ED1-positive (recruited) macrophages. In a separate series of experiments, the block of axoplasmic transport proximal to a localized neuritis significantly reduced inflammation-induced AMS (15.6% compared to 55.6%; P < 0.05), further supporting that the components necessary for AMS are moved by anterograde transport. In summary, nerve inflammation that causes the disruption of axoplasmic transport in patients with painful conditions may result in the accumulation and insertion of mechanosensitive elements at the inflamed site. [source] True and Apparent Temperature Dependence of Protein Adsorption Equilibrium in Reversed-Phase HPLCBIOTECHNOLOGY PROGRESS, Issue 6 2002Szabelski The adsorption behavior of bovine insulin on a C8 -bonded silica stationary phase was investigated at different column pressures and temperatures in isocratic reversed-phase HPLC. Changes in the molar volume of insulin (, Vm) upon adsorption were derived from the pressure dependence of the isothermal retention factor ( k,). The values of , Vm were found to be practically independent of the temperature between 25 and 50 °C at ,96 mL/mol and to increase with increasing temperature, up to ,108 mL/mol reached at 50 °C. This trend was confirmed by two separate series of measurements of the thermal dependence of ln( k,). In the first series the average column pressure was kept constant. The second series involved measurements of ln( k,) under constant mobile-phase flow rate, the average column pressure varying with the temperature. In both cases, a parabolic shape relationship was observed between ln( k,) and the temperature, but the values obtained for ln k, were higher in the first than in the second case. The relative difference in ln( k,), caused by the change in pressure drop induced by the temperature, is equivalent to a systematic error in the estimate of the Gibbs free energy of 12%. Thus, a substantial error is made in the estimates of the enthalpy and entropy of adsorption when neglecting the pressure effects associated with the change in the molar volume of insulin. This work proves that the average column pressure must be kept constant during thermodynamic measurements of protein adsorption constants, especially in RPLC and HIC. Our results show also that there is a critical temperature, Tc , 53 °C, at which ln( k,) is maximum and the insulin adsorption process changes from an exothermic to an endothermic one. This temperature determines also the transition point in the molecular mechanism of insulin adsorption that involves successive unfolding of the protein chain. [source] In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen5,DTrp7,Dab8]urotensin II(4,11) (UFP-803)BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006Valeria Camarda The novel urotensin-II (U-II) receptor (UT) ligand, [Pen5,DTrp7,Dab8]U-II(4,11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to the right, revealing a competitive type of antagonism and a pA2 value of 7.46. In the FLIPR [Ca2+]i assay, performed at room temperature in HEK293hUT and HEK293rUT cells, U-II increased [Ca2+]i with pEC50 values of 8.11 and 8.48. Urantide and UFP-803 were inactive as agonists, but antagonized the actions of U-II by reducing, in a concentration-dependent manner, the agonist maximal effects with apparent pKB values in the range of 8.45,9.05. In a separate series of experiments performed at 37°C using a cuvette-based [Ca2+]i assay and CHOhUT cells, urantide mimicked the [Ca2+]i stimulatory effect of U-II with an intrinsic activity (,) of 0.80, while UFP-803 displayed a small (,=0.21) but consistent residual agonist activity. When the same experiments were repeated at 22°C (a temperature similar to that in FLIPR experiments), urantide displayed a very small intrinsic activity (,=0.11) and UFP-803 was completely inactive as an agonist. In vivo in mice, UFP-803 (10 nmol kg,1) antagonized U-II (1 nmol kg,1)-induced increase in plasma extravasation in various vascular beds, while being inactive alone. In conclusion, UFP-803 is a potent UT receptor ligand which displays competitive/noncompetitive antagonist behavior depending on the assay. While UFP-803 is less potent than urantide, it displayed reduced residual agonist activity and as such may be a useful pharmacological tool. British Journal of Pharmacology (2006) 147, 92,100. doi:10.1038/sj.bjp.0706438 [source] Glutamine attenuates hyperoxia-induced acute lung injury in miceCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1 2010Wann-Cherng Perng Summary 1.,Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo. 2.,Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored. 3.,Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-, and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice. 4.,In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia. 5.,The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival. [source] | |||||||||||||