Nociception is one of the most complex senses that is affected not only by external stimulation but also internal conditions. Previous studies have suggested that circadian rhythm is important in modulating nociception. REV-ERBα knock-out (KO) mice have disrupted circadian rhythm and altered mood-related phenotypes. In this study, we examined the role of REV-ERBα in inflammatory nociception. We found that the nociceptive sensitivity of KO mice was partially enhanced in mechanical nociception. However, this partial alteration was independent of the circadian rhythm. Taken together, deletion of REV-ERBα induced a mild change in mechanical nociceptive sensitivity but this alteration was not dependent on the circadian rhythm.
Animals ; Circadian Rhythm ; Mice ; Mice, Knockout* ; Nociception ; Phenotype

No abstract available.
Adenoma* ; Common Bile Duct*

Currently, compared to jaw-closing (JC) α-motoneurons, the information on the distribution and morphology of glutamatergic synapses on the jaw-closing (JC) γ-motoneurons, which may help elucidate the mechanism of isometric contraction of the JC muscle, is very limited. This study investigated the distribution and ultrastructural features of vesicular glutamate transporter 1 (VGLUT1)- and VGLUT2-immunopositive (+) axon terminals (boutons) on JC γ-motoneurons by retrograde tracing with horseradish peroxidase, electron microscopic immunocytochemistry, and quantitative analysis. About 35% of the boutons on identified JC γ-motoneurons were VGLUT+, and of those, 99% were VGLUT2+. The fraction of VGLUT1+ boutons of all boutons and the percentage of membrane of JC γ-motoneurons covered by these boutons were significantly lower than those for the JC α-motoneurons, revealed in our previous work. The bouton volume, mitochondrial volume, and active zone area of the VGLUT2+ boutons on the JC γ-motoneurons were uniformly small. These findings suggest that the JC γ-motoneurons, in contrast to the JC α-motoneurons, receive generally weak glutamatergic synaptic input almost exclusively from VGLUT2+ premotoneurons that form direct synapse with motoneurons.
Animals ; Horseradish Peroxidase ; Immunohistochemistry ; Isometric Contraction ; Membranes ; Microscopy, Electron ; Mitochondrial Size ; Motor Neurons ; Presynaptic Terminals ; Rats ; Synapses ; Vesicular Glutamate Transport Protein 1

Prefrontal cortex is called psycological cortex, since it deals with making up of individual personality, regulation of personal depth of feeling, working memory, planning, maintaining attention, etc. Whereas, nucleus accumbens (septi) is called the center of reward and motivation or the center of pleasure, since it deals with feeding, drinking, sex, exploration, appetitive learning, drug addiction, etc. Present study was aimed at the proving the prefronto-accumbens input ultrastructurally. Sprague Dawley rats anesthetized with sodium pentobarbital and were removed their prefrontal cortex with suction instrument. Two days following the operation, heads of rats were fixed by perfusion of with 1% glutaraldehyde-1% paraformaldehyde solution via left ventricle. Peristaltic pump was used during perfusion. Two hours later, brains were removed and refixed for 24 hours in the refrigerator, and small tissues of the nucleus accumbens were punched out with punching needle. Tissue blocks were fixed in 2% osmic acid for 2 hours and were embedded in araldite mixture. Ultrathin sections stained with uranyl acetate-lead citrate solution were observed with JEOL 100 CX II electron microscope. In the nucleus accumbens, some axodendritic terminals and axospinous terminals were found degenerated, and volume of activated glial cytoplasm was increased. The degenerated terminals were seen isolated from intact structures by activated glial processes and removed by glial cytoplasm. The result confirms that axon terminals coming from prefrontal cortex input to the spiny neurons of nucleus accumbens septi, on their dendrites and/or dendritic spines.
Animals ; Brain ; Citric Acid ; Cytoplasm ; Dendrites ; Dendritic Spines ; Drinking ; Head ; Heart Ventricles ; Humans ; Learning ; Memory, Short-Term ; Motivation ; Needles ; Neurons ; Nucleus Accumbens ; Osmium Tetroxide ; Pentobarbital ; Perfusion ; Pleasure ; Prefrontal Cortex ; Presynaptic Terminals ; Rats* ; Rats, Sprague-Dawley ; Reward ; Sodium ; Substance-Related Disorders ; Suction ; Synapses*

To study the tumor-suppression effect of a newly developed anti-tumor agent AG60 [ acriflavine (1) : guanosine (1) composition, Taerim Pharm. Co., Seoul, Korea], each Ehrlich carcinoma (107 cells)-inoculated mouse received the subcutaneous injection of 0.2 ml of saline, 5mg/kg of AG60, and 30 mg/kg of AG60, every other day for two weeks. Animals were sacrificed, and stomach, duodenum, appendix vermiformis and rectal tissues were resected and fixed in 10% neutral formalin. Tissue blocks were washed, dehydrated, embedded and cut in 6 microgram-thick sections. For immunocytochemistry, the streptavidine-biotin-peroxidse method was used with a InnoGenex (San Ramon, Calif., USA) staining kit. The tissues were incubated with rabbit antisera against somatostatin (Biogenesis, Poole, England, UK) diluted 1 : 300, secretin (Biogenesis, Poole, England, UK) diluted 1 : 2,400, neurotensin (Biogenesis, Poole, England, UK) diluted 1 : 2,600, or motilin (Biogenesis, Poole, England, UK) diluted 1 : 1,000 for 24 hour at 4dreeges C, followed by incubation in biotinylated antirabbit IgG and horseradish peroxidase-streptavidin conjugate for 1 hour at room temperature. The antigen-antibody reaction sites were visualized by incubating the sections with diaminobezidine tetrahydrochloride (DAB) for 5~15 minutes at room temperature. After mounting in canada balsam, they were examined in a Leica DM RB microscope. The number of the immunoreactive cells in the area of gastrointestinal mucosae (mean number of immunoreactive cells per 0.25mm2) were observed and calculated. The results are as follows : 1. In the fundic gland of normal mouse, somatostatin immunoreactive cells were detected (18.5+/-0.71), but neurotensin, secretin, or motilin immunoreactive cells were not found. In the duodenal mucosa of normal mouse, somatostatin immunoreactive cells were detected (7.0+/-0.10), but neurotensin, secretin or motilin immunoreactive cells were rarely found. 2. Immunoreactivity of somatostatin, secretin, neurotensin or motilin cells was not found in appendix vermiformis and rectum of normal mouse. 3. On immunocytochemical study, somatostatin immunoreactive cells in the fundic glands of normal, experimental control, AG60 (5mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were 18.5+/-0.71, 10.0+/-4.20, 11.5+/-0.71, 13.5+/-2.10, 11.5+/-2.71, respectively. 4. On immunocytochemical study, somatostatin immunoreactive cells in the duodenal mucosae of normal, experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were 7.0+/-2.10, 0.5+/-2.71, 3.0+/-1.41, 0.5+/-0.71, 2.50+/-0.71, respectively. 5. On immunocytochemical study, secretin immunoreactive cells in the duodenal mucosae of normal, experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were rarely found. 6. On immunocytochemical study, neurotensin and motilin immunoreactive cells in the duodenal mucosae of normal groups were detected, but immunoreactivies were not detected in experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated or 5-fluorouracil (60 mg/kg)-treated groups.
Acriflavine ; Animals ; Antigen-Antibody Reactions ; Appendix ; Armoracia ; Canada ; Duodenum ; England ; Enteroendocrine Cells* ; Fluorouracil ; Formaldehyde ; Guanosine ; Immune Sera ; Immunoglobulin G ; Immunohistochemistry ; Injections, Subcutaneous ; Mice* ; Motilin ; Mucous Membrane ; Neurotensin ; Rectum ; Secretin ; Seoul ; Somatostatin ; Stomach

PURPOSE: To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. MATERIALS AND METHODS: Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT.In 21 patients, urokinase(5-15 X 105IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with thoseof intravenous heparin(N=19) and urokinase infusion(n=19). RESULTS: Complete or partial angiographic recanalization of occluded segment was found in 18 patients(67%), and neurologic improvement was followed in 14patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higherin those two groups than in the intravenous heparin infusion group. CONCLUSION: IAUK infusion may be effectivefor the treatment of acute cerebral stroke.
Brain ; Heparin* ; Humans ; Stroke* ; Thrombosis ; Urokinase-Type Plasminogen Activator*

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.
Animals ; Cerebral Cortex ; Cyclic AMP-Dependent Protein Kinases ; Dopamine ; gamma-Aminobutyric Acid ; Humans ; Hypnotics and Sedatives ; Melatonin ; Mice* ; Mitogen-Activated Protein Kinases ; Motor Activity ; Neurotransmitter Agents ; p38 Mitogen-Activated Protein Kinases* ; Pentobarbital* ; Phosphotransferases ; Protein Kinase C ; Protein Kinases ; Quinpirole*

Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immune-deficiency syndrome, and bone marrow transplantation (BMT) has become a curative modality. However, the transplant with the alternative donor needed more intensive conditioning with increased treatment-related toxicities. Recently, fludarabine-based reduced toxicity myeloablative conditioning regimens have been developed for adult myeloid malignancies with promising results of good engraftment and low treatment-related toxicities. To increase the engraftment potential without serious complications, a boy with WAS received successful unrelated BMT with a reduced toxicity myeloablative conditioning regimen composed of fludarabine (40 mg/m(2) on days -8, -7, -6, -5, -4, -3), busulfan (0.8 mg/kg i. v. q 6 hr on days -6, -5, -4, -3), and thymoglobulin (2.5 mg/kg on days -4, -3, -2). This novel conditioning regimen could improve the outcome of allogeneic transplantation for other non-malignant diseases such as congenital immune-deficiency syndromes or metabolic storage diseases.
*Bone Marrow Transplantation/adverse effects ; Child, Preschool ; Graft vs Host Disease/etiology ; Humans ; Male ; *Transplantation Conditioning ; Wiskott-Aldrich Syndrome/*surgery

Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.
Animals ; Behavior Rating Scale ; Blotting, Western ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Cognition ; Glycyrrhiza ; Hippocampus ; In Vitro Techniques ; Learning ; Medicine, East Asian Traditional ; Memory ; Mice* ; N-Methylaspartate* ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Receptors, N-Methyl-D-Aspartate* ; Response Elements

PURPOSE: To evaluate the different angio-architectures of brain arteriovenour malformatigns (AVMs) accordingto the presence of non-hemorrhagic symptoms or intracerebral (ICH) and/or intraventricular hemorrhage(IVH). MATERIALS AND METHODS: The results of complete cerebral angiography obtained in 215 patients with AVM between1989 and 1994 were retrospectively reviewed. The M:F ratio was 136:78 and their mean age was 29 (ranged 4 - 66)years. On the based of clincal presentation, CT and/or MR images, they were divided into hemorrhagic andnon-hemorrhagic groups. Angiograms were analyzed by two radiologists for the size and location of nidus; thenumber of feeding arteries and the extent of aneurysm, stenosis, dural supply, and angiomatous change; the numberof draining veins and the extent of deep or superficial drainage, stenosis, ectasia, kinking, and stasis. Thestandard chi-square test was used for statistical analysis. RESULTS: Hemorrhage was noted in 140 patients(65%),and no hemorrhage in 75(35%). Hemorrhage was more common in AVM with deep-seated and callosal locations, a nidusof less than 2cm, single feeder and single venous drainage, and deep venous drainage only (p < 0.05 - 0.001).Non-hemorrhagic presentations were more common in AVM with cortical and subcortical location, a nidus of more than5cm, angiomatous change, dural supply, both superficial and deep venous drainage, kinking, and stasis (p <0.05-0.001). CONCLUSION: The angio-architechture of AVM with hemorrhage correlated with clinical symptomaticpresentation. Analysis of the patterns of angioarchitectureis useful for prognosis and in deeiding the direetionof freatment.
Aneurysm ; Arteries ; Arteriovenous Malformations* ; Brain* ; Cerebral Angiography ; Constriction, Pathologic ; Dilatation, Pathologic ; Drainage ; Hemorrhage ; Humans ; Intracranial Arteriovenous Malformations ; Prognosis ; Retrospective Studies ; Veins