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Subsequent Administration (subsequent + administration)
Selected AbstractsEffect of halothane on type 2 immobility-related hippocampal theta field activity and theta-on/theta-off cell dischargesHIPPOCAMPUS, Issue 1 2003Brian H. Bland Abstract Rats were studied in acute and chronic (freely moving) recording conditions during exposure to different levels of the volatile anesthetic halothane, in order to assess effects on hippocampal theta field activity in the chronic condition and on theta-related cellular discharges in the acute condition. Previous work has shown that the generation of hippocampal type 2 theta depends on the coactivation of cholinergic and GABAergic inputs from the medial septum. Based on these data and recent findings that halothane acts on interneuron GABAA receptors, we predicted that exposure of rats to subanesthetic levels would result in the induction of type 2 theta field activity. In the chronic condition, exposure to subanesthetic levels of halothane (0.5,1.0 vol %) was found to induce theta field activity during periods of immobility (type 2 theta) with a mean increase of 39% in amplitude (mV) compared to control levels during movement. The total percentage of signal power (V2) associated with peak theta frequencies (80% compared to control levels of 47%) was also increased by halothane. Over the whole range of administered halothane concentrations, theta field frequency progressively declined from a mean peak frequency of 6.5 ± 0.8 Hz at 0.5 vol % halothane to a mean peak frequency of 4.0 ± 1.8 Hz at 2.0 vol % halothane. Subsequent administration of a muscarinic cholinergic antagonist, atropine sulfate, selectively abolished all type 2 immobility-related theta field activity, while type 1 movement-related theta was still intact. At anesthetic levels (1.5,2.0 vol %) in acute experiments, hippocampal field activity spontaneously cycled between theta and large-amplitude irregular activity. Analysis of depth profiles in four experiments revealed they were identical to those previously described for rats under urethane anesthesia conditions. In addition, the discharge properties of 31 theta-related cells, classified as tonic and phasic theta-on and tonic and phasic theta-off cells, did not differ significantly from those described previously in rats anesthetized with urethane. These data provide further support for an involvement of GABAA receptors in the generation of hippocampal theta. Hippocampus 2003;13:38,47. © 2003 Wiley-Liss, Inc. [source] Glutamate-induced calcium increase mediates magnesium release from mitochondria in rat hippocampal neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2010Yutaka Shindo Abstract Excess administration of glutamate is known to induce Ca2+ overload in neurons, which is the first step in excitotoxicity. Although some reports have suggested a role for Mg2+ in the excitotoxicity, little is known about its actual contribution. To investigate the role of Mg2+ in the excitotoxicity, we simultaneously measured intracellular Ca2+ and Mg2+, using fluorescent dyes, Fura red, a fluorescent Ca2+ probe, and KMG-104, a highly selective fluorescent Mg2+ probe developed by our group, respectively. Administration of 100 ,M glutamate supplemented with 10 ,M glycine to rat hippocampal neurons induced an increase in intracellular Mg2+ concentration ([Mg2+]i). Extracellular Mg2+ was not required for this glutamate-induced increase in [Mg2+]i, and no increase in intracellular Ca2+ concentration ([Ca2+]i) or [Mg2+]i was observed in neurons in nominally Ca2+ -free medium. Application of 5 ,M carbonyl cyanide p -(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of mitochondrial inner membrane potential, also elicited increases in [Ca2+]i and [Mg2+]i. Subsequent administration of glutamate and glycine following FCCP treatment did not induce a further increase in [Mg2+]i but did induce an additive increase in [Ca2+]i. Moreover, the glutamate-induced increase in [Mg2+]i was observed only in mitochondria localized areas. These results support the idea that glutamate is able to induced Mg2+ efflux from mitochondria to the cytosol. Furthermore, pretreatment with Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, prevented this [Mg2+]i increase. These results indicate that glutamate-induced increases in [Mg2+]i result from the Mg2+ release from mitochondria and that Ca2+ accumulation in the mitochondria is required for this Mg2+ release. © 2010 Wiley-Liss, Inc. [source] Retinal and optic nerve oxygenation and carbonic anhydrase inhibitionACTA OPHTHALMOLOGICA, Issue 2009M LA COUR Purpose To study the effects of carbonic anhydrase inhibition on porcine retinal and optic nerve oxygenation under physiological conditions and in experimental models of ischemia. Methods Polarographic oxygen electrodes were used to measure the oxygen tension in the vitreous 500 microns in front of the optic nerve and retina. Retinal ischemia was produced by diathermia of the superior arcade vein, producing a branch retinal vein occlusion, BRVO. Optic nerve ischemia was produced by intravenous administration of 100 mg Indomethacin intravenously. Results One week after induction of BRVO, the oxygen tension over BRVO affected retina was significantly decreased by 29%. Administration of the carbonic anhydrase inhibitor dorzolamide (500 mg) caused a significant increase in the oxygen tension over BRVO affected retina, and in effect restored this tension to normal values (n=5). Intravenous administration of 300 mg Indomethacin caused a decrease of optic nerve oxygen tension by 41%. Subsequent administration of 500 mg dorzolamide increased the optic nerve oxygen tension, albeit not to normal levels (n=6). Conclusion Carbonic anhydrase inhibition increases the oxygen tension in the retina and optic nerve. In BRVO affected retina, carbonic anhydrase inhibition restores oxygen tension to normal levels. [source] A Gene Therapy Technology-Based Biomaterial for the Trigger-Inducible Release of Biopharmaceuticals in MiceADVANCED FUNCTIONAL MATERIALS, Issue 15 2010Michael M. Kämpf Abstract Gene therapy scientists have developed expression systems for therapeutic transgenes within patients, which must be seamlessly integrated into the patient's physiology by developing sophisticated control mechanisms to titrate expression levels of the transgenes into the therapeutic window. However, despite these efforts, gene-based medicine still faces security concerns related to the administration of the therapeutic transgene vector. Here, molecular tools developed for therapeutic transgene expression can readily be transferred to materials science to design a humanized drug depot that can be implanted into mice and enables the trigger-inducible release of a therapeutic protein in response to a small-molecule inducer. The drug depot is constructed by embedding the vascular endothelial growth factor (VEGF121) as model therapeutic protein into a hydrogel consisting of linear polyacrylamide crosslinked with a homodimeric variant of the human FK-binding protein 12 (FM), originally developed for gene therapeutic applications, as well as with dimethylsuberimidate. Administrating increasing concentrations of the inducer molecule FK506 triggers the dissociation of FM thereby loosening the hydrogel structure and releasing the VEGF121 payload in a dose-adjustable manner. Subcutaneous implantation of the drug depot into mice and subsequent administration of the inducer by injection or by oral intake triggers the release of VEGF121 as monitored in the mouse serum. This study is the first demonstration of a stimuli-responsive hydrogel that can be used in mammals to release a therapeutic protein on demand by the application of a small-molecule stimulus. This trigger-inducible release is a starting point for the further development of externally controlled drug depots for patient-compliant administration of biopharmaceuticals. [source] Neuroprotective effects of prior limb use in 6-hydroxydopamine-treated rats: possible role of GDNFJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Ann D. Cohen Abstract Unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) causes a loss of dopamine (DA) in the ipsilateral striatum and contralateral motor deficits. However, if a cast is placed on the ipsilateral limb during the first 7 days following 6-OHDA infusion, forcing the animal to use its contralateral limb, both the behavioral and neurochemical deficits are reduced. Here, we examine the effect of forced reliance on a forelimb during the 7 days prior to ipsilateral infusion of 6-OHDA on the deficits characteristic of this lesion model. Casted animals displayed no behavioral asymmetries as measured 14,28 days postlesion and a marked attenuation in the loss of striatal DA and its metabolites at 30 days. In addition, animals receiving a unilateral cast alone had an increase in glial cell-line derived neurotrophic factor (GDNF) protein in the striatum corresponding to the overused limb. GDNF increased within 1 day after the onset of casting, peaked at 3 days, and returned to baseline within 7 days. These results suggest that preinjury forced limb-use can prevent the behavioral and neurochemical deficits to the subsequent administration of 6-OHDA and that this may be due in part to neuroprotective effects of GDNF. [source] Anaphylaxis during anaesthesia: diagnostic approachALLERGY, Issue 5 2007D. G. Ebo Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds. However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done. This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the diagnostic approach of this rare but potentially life-threatening complication. Apart from general principles about the diagnostic approach, history taking and importance of tryptase quantification, more specific confirmatory diagnostic procedures are organized on the basis of the major causes of perioperative anaphylactic reactions. [source] Elapid snake envenomation in dogs in New South Wales: a reviewAUSTRALIAN VETERINARY JOURNAL, Issue 11 2007J Heller Elapid snake envenomation in dogs is a commonly occurring yet poorly described clinical entity. Twelve species of dangerously venomous elapid snakes are found in New South Wales that are capable of causing disease in dogs. Geographical distribution of these species varies, as does their venom composition and systemic envenomation syndromes produced in target species. Elapid venom may be divided into the components of prothrombin activating enzymes, lipases and peptidic neurotoxins. Each species of elapid snake may possess venom components that fit any or all of these classifications. The action of these venom components may result in neurotoxic (pre-synaptic and post-synaptic), haemotoxic (red-cell destruction and coagulation disturbance), cardiovascular, myotoxic and secondary nephrotoxic effects. Marked variability may occur in venom composition between and within snake species, resulting in varying toxicity between species and also potentially unreliable clinical syndromes following envenomation. The existence of certain components consistently within the venom of each snake species allows the broad definition of basic pathological processes and clinicopathological changes resulting from snake species-specific envenomation and these are discussed. Diagnosis of snake envenomation is unreliable if based on clinical signs alone and the use of these signs in conjunction with history, physical examination and laboratory investigation, including snake venom detection kits, is recommended. Treatment of systemic envenomation should be undertaken with initial effective first aid and subsequent administration of snake species-specific antivenom. [source] Existence Of ,1A - and ,1B -Adrenoceptor Subtypes In Canine Mandibular Alveolar ArteriesCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2001Yuichi Taguchi SUMMARY 1. The present study attempted to pharmacologically characterize the , -adrenoceptor subtypes mediating vasoconstriction in canine isolated and perfused mandibular alveolar artery (MAA). 2. Noradrenaline (NA) and phenylephrine (PE) induced a strong vasoconstriction in a dose-dependent manner. The PE-induced vascular constriction was significantly inhibited by treatment with prazosin. Xylazine evoked a moderate vascular constriction and the xylazine-induced response was suppressed by rauwolscine. The NA-induced response was partially inhibited by rauwolscine and the remaining response to NA was abolished by subsequent administration of prazosin. 3. Treatment of MAA with WB4101 produced a dose- dependent inhibition of NA-induced vasoconstriction. Pretreatment of tissues with 10 ,mol/L chloroethylclonidine produced a slight and statistically significant inhibition of NA-induced responses. BMY 7378, a selective ,1D -adrenoceptor antagonist, failed to significantly affect vasoconstrictor responses to NA. 4. The present results suggests that: (i) both ,1 - and ,2 -adrenoceptors are involved in vasoconstrictor responses in the canine MAA; and (ii) the ,1 -adrenoceptors involved in the vasoconstrictor responses in the MAA are characterized as mainly of the ,1A - and partially of the ,1B -adrenoceptor subtype. [source] | |||||||||||||