This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE₂ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB-α phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.
Cytokines ; Interleukin-1beta ; Interleukin-6 ; Methanol ; Neurodegenerative Diseases ; Nitric Oxide ; Nitric Oxide Synthase ; Phosphorylation ; Prostaglandin-Endoperoxide Synthases ; Reactive Oxygen Species ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Vaccinium*

Human seminal fiuid (HSP) hypersensitivity is rare, but possibly a life-threatening disease. The pathogenesis of seminal plasma hypersensitivity and the exact nature of the HSP allergens remains to be clarified. We report a case of 25-year-old female patient who complained of severe itching sensation, flushing and edema of external genitalia, facial edema and dyspnea after sexual intercourse. The diagnosis was established by skin pr ick test with her husbands diluted semen. Intravaginal desensitization was performed by modified Matloffs method. Dilutions was made with sterile human serum albumin(0.2%) and 0.4% pheno1-0.9% saline solution. Two ml each of progressively greater concentrations of semen dilutions(1: 100,000 v/v, 1: 10,000 v/ v, 1:1,000 v/v, 1:100 v/v, 1:10 v/v) were inserted intravaginally at 45-min intervals, followed by an undiluted specimen. The patient was successfully desensitized and could have unprotected intercourse without anaphylaxis.
Adult ; Allergens ; Anaphylaxis ; Coitus ; Diagnosis ; Dyspnea ; Edema ; Female ; Flushing ; Genitalia ; Humans ; Hypersensitivity* ; Pruritus ; Semen ; Sensation ; Skin ; Sodium Chloride ; Spouses

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*

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase kinase-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and PGE2 production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and GSK-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation.
Cytokines ; Dinoprostone ; DNA ; Eucommiaceae* ; Glycogen Synthase ; Heme Oxygenase-1 ; Mitogen-Activated Protein Kinases ; Phosphorylation ; Reactive Oxygen Species ; Transcription Factors ; Up-Regulation ; Zinc

PURPOSE: We evaluated the usefulness of intracranial stent implantation for treating patients with atherosclerotic stenosis and with recurrent, ischemic, neurological symptoms despite having undergone medical therapy. MATERIALS AND METHODS: Between March 2004 and April 2010, we attempted intracranial, stent-assisted angioplasty in 77 patients with 85 lesions (anterior circulation 73 cases, posterior circulation 12 cases) and who had ischemic neurological symptoms with more than 50% major cerebral artery stenosis. We analyzed the results regarding the technical success rate, complication rate, and restenosis rate during the mean 29.4 month follow-up period. RESULTS: Intracranial stent implantation was successfully performed in 74 cases (87.1%). In nine cases among the 11, failed cases, stent implantation failure was due to the tortuosity of the target vessel. One patient experienced middle cerebral artery rupture during the procedure, and we embolized the vessel using a microcoil. Five patients developed cerebral infarction in three weeks after the procedure, three of whom improved using conservative management, although the other, two patients expired. The mean number of residual stenoses decreased from 72.3% to 14.7%. Three patients demonstrated significant in-stent restenosis, i.e. more than 50%, during the follow-up period. CONCLUSION: As stent-assisted angioplasty in intracranial, atherosclerotic stenosis is effective and relatively safe, it can be considered as an alternative treatment for patients with recurrent, ischemic, neurologic symptoms despite having undergone medical therapy.
Angioplasty ; Cerebral Arteries ; Cerebral Infarction ; Constriction, Pathologic ; Follow-Up Studies ; Glycosaminoglycans ; Humans ; Intracranial Arteriosclerosis ; Middle Cerebral Artery ; Neurologic Manifestations ; Rupture ; Stents

The present study aimed to investigate the clinical characteristics and 1-year outcomes of acute myocardial infarction (AMI) patients without significant stenosis on a coronary angiogram comparison with the clinical characteristics and outcomes of patients with significant coronary artery stenosis. A total of 1,220 patients with AMI were retrospectively classified into Group I (> or =50% diameter stenosis, n=1,120) and Group II (<50%, n=100). Group II was further divided into two subgroups according to the underlying etiology: cryptogenic (Group II-a, n=54) and those with possible causative factors (Group II-b, n=46). Patients in Group II were younger, were more likely to be women, and were less likely to smoke and to have diabetes mellitus than were patients in Group I. The levels of cardiac enzymes, LDL-cholesterol levels, and the apo-B/A1 ratio were lower in Group II. However, 1-month and 12-month rates of major adverse cardiac events (MACE) were not significantly different between the two groups. The Group II-b subgroup comprised 29 patients with vasospasm, 11 with myocardial bridge, and 6 with spontaneous thrombolysis. Left ventricular ejection fraction and creatinine clearance were lower and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) were higher in Group II-a than in Group II-b. However, outcomes including MACE and mortality at 12 months were not significantly different between the two subgroups. The 1-year outcomes of patients in Group II were similar to those of patients in Group I. The clinical outcomes in Group II-a were also similar to those of Group II-b, although the former group showed higher levels of NT-proBNP and hs-CRP.
C-Reactive Protein ; Constriction, Pathologic ; Coronary Angiography ; Coronary Stenosis ; Creatinine ; Diabetes Mellitus ; Female ; Humans ; Myocardial Infarction ; Natriuretic Peptide, Brain ; Peptide Fragments ; Retrospective Studies ; Smoke ; Stroke Volume