P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus

<p>Abstract</p> <p>Background</p> <p>In the present study, we investigated the roles of P2X7 receptor in recruitment and infiltration of neutrophil during epileptogenesis in rat epilepsy models.</p> <p>Methods</p> <p>Status epilepticus (SE) was induced by pilocarpine in rats that were intracerebroventricularly infused with either saline, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), or IL-1Ra (interleukin 1 receptor antagonist) prior to SE induction. Thereafter, we performed immunohistochemical studies for myeloperoxidase (MPO), CD68, interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2).</p> <p>Results</p> <p>In saline-infused animals, neutrophils and monocytes were observed in frontoparietal cortex (FPC) at 1 day and 2 days after SE, respectively. In BzATP-infused animals, infiltrations of neutrophils and monocytes into the FPC were detected at 12 hr and 1 day after SE, respectively. In OxATP-infused animals, neutrophils and monocytes infiltrated into the FPC at 1 day and 2 days after SE, respectively. However, the numbers of both classes of leukocytes were significantly lower than those observed in the saline-infused group. In piriform cortex (PC), massive leukocyte infiltration was detected in layers III/IV of saline-infused animals at 1-4 days after induction of SE. BzATP or OxATP infusion did not affect neutrophil infiltration in the PC. In addition, P2X7 receptor-mediated MCP-1 (released from microglia)/MIP-2 (released from astrocytes) regulation was related to SE-induced leukocyte infiltration in an IL-1β-independent manner.</p> <p>Conclusions</p> <p>Our findings suggest that selective regulation of P2X7 receptor-mediated neutrophil infiltration may provide new therapeutic approaches to SE or epilepsy.</p

Anti-amyloidogenic effect of menaquinone-7 on betaamyloid production and aggregation

Purpose: To investigate the beneficial effects of menaquinone-7 (MK-7), an isoform of vitamin K2, against beta-amyloid (Aβ) production and aggregation in Alzheimer's disease using in vitro assays. Methods: The cytotoxicity of MK-7 was determined by MTT assay. The amount of Aβ produced and secreted into the supernatant by APP-CHO cells treated with MK-7 was evaluated by ELISA. The expression of β-secretases and ADAM10, a representative α-secretase, was determined using western blot analysis. The production of sAPPβ and sAPPα fragments generated by β-secretases and αsecretase, respectively, were also determined by western blot analysis. The effect on Aβ aggregation was assessed using Thioflavin T (Th T) assay. Results: MK-7 (up to 75 nM) significantly decreased Aβ production in APP-CHO cells. This was accompanied by decreased expression of β-secretase and lower production of sAPPβ (p &lt; 0.05). However, expression of ADAM10 and production of sAPPα were not significantly affected. In contrast, MK-7 significantly decreased Aβ aggregation in a dose-dependent manner (p &lt; 0.05). Conclusion: MK-7 exerts anti-amyloidogenic effects via decreased production and lower aggregation of Aβ into oligomers and fibrils. Therefore, dietary supplementation with MK-7 may be beneficial for the prevention of Alzheimer’s disease

Analysis of triterpenoids, carotenoids, and phenylpropanoids in the flowers, leaves, roots, and stems of white bitter melon (Cucurbitaceae, Momordica charantia)

Purpose: To evaluate the contents of carotenoids, triterpenoids, and phenylpropanoids in different parts of white bitter melon.Methods: We evaluated the accumulation of 2 triterpenoids, 10 carotenoids, and 11 phenylpropanoids in different parts of white bitter melon, including fruits at four different developmental stages using HPLC.Results: Charantin, lutein, and rutin were the main triterpenoids, carotenoids, and phenylpropanoids, respectively. The accumulation of triterpenoids (momordicine and charantin), carotenoids (antheraxanthin, lutein, violaxanthin, α-carotene, and β-carotene), and phenylpropanoids (caffeic acid, chlorogenic acid, epicatechin, gallic acid, p-coumaric acid, rutin, and trans-cinnamic acid) was high inthe leaves and/or flowers, which are exposed to direct sunlight, but low in the roots.Conclusion: Most of the analyzed components were accumulated at high levels in the leaves and/or flowers. These results will help exploit the compounds in various parts of white bitter melon that are beneficial for human health. Keywords: Momordica charantia, Bitter melon, Triterpenoid, Carotenoid, Phenylpropanoi

Obsessive-Compulsive Behavior Disappearing after Left Capsular Genu Infarction

This case report describes a 74-year-old woman with obsessive-compulsive behaviors that disappeared following a left capsular genu infarction. The patient's capsular genu infarction likely resulted in thalamocortical disconnection in the cortico-basal ganglia-thalamocortical loop, which may have caused the disappearance of her obsessive-compulsive symptoms. The fact that anterior capsulotomy has been demonstrated to be effective for treating refractory obsessive-compulsive disorder further supports this hypothesis

Does Tumor Size Influence the Diagnostic Accuracy of Ultrasound-Guided Fine-Needle Aspiration Cytology for Thyroid Nodules?

Background. Fine-needle aspiration cytology (FNAC) is diagnostic standard for thyroid nodules. However, the influence of size on FNAC accuracy remains unclear especially in too small or too large thyroid nodules. The objective of this retrospective cohort study was to investigate the effect of nodule size on FNAC accuracy. Methods. All consecutive patients who underwent thyroidectomy for nodules in 2010 were enrolled. FNAC results (according to the Bethesda system) were compared to pathological diagnosis. The nodules were categorized into groups A–E on the basis of maximal diameter on ultrasound (≤0.5, >0.5–1, >1-2, >2–4, and >4 cm, resp.). Results. There were 502 cases with 690 nodules. Overall FNAC sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.4%, 98.2%, 99.4%, 86.4%, and 96.0%, respectively. False-negative rates (FNRs) of groups A–E were 3.2%, 5.1%, 1.3%, 13.3%, and 50%, respectively. Accuracy rates of groups A–E were 96.8%, 94.8%, 99%, 94.7%, and 87.5%, respectively. Conclusion. Although accuracy rates of FNAC in thyroid nodules smaller than 0.5 cm are comparable to the other group, thyroid nodules larger than 4 cm with benign cytology carry a higher risk of malignancy, which suggest that those should be considered for intensive follow-up or repeated biopsy

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p

Issues in Developing and Evaluating a Culturally Tailored Internet Cancer Support Group

The purpose of this paper is to explore practical issues in developing and implementing a culturally tailored Internet Cancer Support Group for a group of ethnic minority cancer patients—Asian American cancer patients. Throughout the research process of the original study testing the Internet cancer support group, research team made written records of practical issues and plausible rationales for the issues. Weekly group discussion among research team members was conducted, and the discussion records were evaluated and analyzed using a content analysis (with individual words as the unit of analysis). The codes from the analysis process were categorized into idea themes, through which the issues were extracted. The issues included those in: (a) difficulties in using multiple languages; (b) collaboration with the IT department and technical challenges (c) difficulties in recruitment; (d) difficulties in retention; (e) optimal timing; and (f) characteristics of the users. Based on the findings, we suggested researchers to plan a workable translation process, check technical needs in advance, use multiple strategies to recruit and retain research participants, plan the right time for data collection, and consider characteristics of the users in the study design

Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts

In addition to its well-known glycolytic activity, GAPDH displays multiple functions, such as nuclear RNA export, DNA replication and repair, and apoptotic cell death. This functional diversity depends on its intracellular localization. In this study, we explored the signal transduction pathways involved in the nuclear translocation of GAPDH using confocal laser scanning microscopy of immunostained human diploid fibroblasts (HDFs). GAPDH was present mainly in the cytoplasm when cultured with 10% FBS. Serum depletion by culturing cells in a serum-free medium (SFM) led to a gradual accumulation of GAPDH in the nucleus, and this nuclear accumulation was reversed by the re-addition of serum or growth factors, such as PDGF and lysophosphatidic acid. The nuclear export induced by the re-addition of serum or growth factors was prevented by LY 294002 and SH-5, inhibitors of phosphoinositide 3-kinase (PI3K) and Akt/protein kinase B, respectively, suggesting an involvement of the PI3K signaling pathway in the nuclear export of GAPDH. In addition, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulated the nuclear translocation of GAPDH and prevented serum- and growth factor-induced GAPDH export. AMPK inhibition by compound C or AMPK depletion by siRNA treatment partially prevented SFM- and AICAR-induced nuclear translocation of GAPDH. Our data suggest that the nuclear translocation of GAPDH might be regulated by the PI3K signaling pathway acting mainly as a nuclear export signal and the AMPK signaling pathway acting as a nuclear import signal.Peairs A, 2009, CLIN EXP IMMUNOL, V156, P542, DOI 10.1111/j.1365-2249.2009.03924.xChen Z, 2009, CIRC RES, V104, P496, DOI 10.1161/CIRCRESAHA.108.187567Cao C, 2008, J BIOL CHEM, V283, P28897, DOI 10.1074/jbc.M804144200Li XX, 2008, ARTERIOSCL THROM VAS, V28, P1789, DOI 10.1161/ATVBAHA.108.172452Lombardi M, 2008, J CELL BIOL, V182, P327Sen N, 2008, NAT CELL BIOL, V10, P866, DOI 10.1038/ncb1747Kim HS, 2008, J BIOL CHEM, V283, P3731, DOI 10.1074/jbc.M704432200Du ZX, 2007, ENDOCRINOLOGY, V148, P4352, DOI 10.1210/en.2006-1511Harada N, 2007, J BIOL CHEM, V282, P22651, DOI 10.1074/jbc.M610724200Goirand F, 2007, J PHYSIOL-LONDON, V581, P1163, DOI 10.1113/jphysiol.2007.132589Barbini L, 2007, MOL CELL BIOCHEM, V300, P19, DOI 10.1007/s11010-006-9341-1Hurley RL, 2006, J BIOL CHEM, V281, P36662, DOI 10.1074/jbc.M606676200Hara MR, 2006, CELL MOL NEUROBIOL, V26, P527, DOI 10.1007/s10571-006-9011-6Tisdale EJ, 2006, J BIOL CHEM, V281, P8436, DOI 10.1074/jbc.M513031200Rattan R, 2005, J BIOL CHEM, V280, P39582, DOI 10.1074/jbc.M507443200Hara MR, 2005, NAT CELL BIOL, V7, P665, DOI 10.1038/ncb1268Sirover MA, 2005, J CELL BIOCHEM, V95, P45, DOI 10.1002/jcb.20399Jones RG, 2005, MOL CELL, V18, P283, DOI 10.1016/j.molcel.2005.03.027Tisdale EJ, 2004, J BIOL CHEM, V279, P54046, DOI 10.1074/jbc.M409472200Hardie DG, 2004, J CELL SCI, V117, P5479, DOI 10.1242/jcs.01540Li J, 2004, AM J PHYSIOL-ENDOC M, V287, pE834, DOI 10.1152/ajpendo.00234.2004Cooray S, 2004, J GEN VIROL, V85, P1065, DOI 10.1099/vir.0.1977-0Brown VM, 2004, J BIOL CHEM, V279, P5984, DOI 10.1074/jbc.M307071200Tisdale EJ, 2003, J BIOL CHEM, V278, P52524, DOI 10.1074/jbc.M309343200HAWLEY SA, 2003, J BIOL, V2, P28Schmitz HD, 2003, CELL BIOL INT, V27, P511, DOI 10.1011/S1065-6995(03)00096-9Tisdale EJ, 2002, J BIOL CHEM, V277, P3334, DOI 10.1074/jbc.M109744200Schmitz HD, 2001, EUR J CELL BIOL, V80, P419Dastoor Z, 2001, J CELL SCI, V114, P1643Yeo EJ, 2000, MOL CELLS, V10, P415Stein SC, 2000, BIOCHEM J, V345, P437Sirover MA, 1999, BBA-PROTEIN STRUCT M, V1432, P159Shashidharan P, 1999, NEUROREPORT, V10, P1149Rameh LE, 1999, J BIOL CHEM, V274, P8347Sawa A, 1997, P NATL ACAD SCI USA, V94, P11669Vincent MF, 1996, BIOCHEM PHARMACOL, V52, P999Reiss N, 1996, BIOCHEM MOL BIOL INT, V38, P711CORTON JM, 1995, EUR J BIOCHEM, V229, P558KAWAMOTO RM, 1986, BIOCHEMISTRY-US, V25, P657BOYCE ST, 1983, J INVEST DERMATOL S, V81, P33