Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats

<p>Abstract</p> <p>Background</p> <p>The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats.</p> <p>Results</p> <p>Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation.</p> <p>Conclusion</p> <p>These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.</p

Pure psychiatric presentation of the Lewy body disease is depression: An analysis of 60 cases verified with myocardial meta-iodobenzylguanidine study

Objective Parkinson\u27s disease (PD), Parkinson\u27s disease with dementia (PDD) and dementia with Lewy bodies (DLB) were collectively termed Lewy body disease (LBD). Pure psychiatric presentation (PPP) of the LBD may be the fourth subtype in which psychiatric symptoms without definite parkinsonism and cognitive disturbance lasted for many years. The aim of this study is to localize the presence of the PPP in subjects with low uptake of myocardial meta-iodobenzylguanidine (MIBG). Methods Sixty MIBG-verified patients (28 women and 32 men) were classified into three psychiatric pictures; depression (Group D: 27 patients), isolated visual hallucinations (Group V: 16 patients) and psychosis (Group P: 17 patients). Fifty six cases were examined with single photon emission tomography (SPECT) study of the brains in which hypoperfusion lobes were identified in 37 cases and 19 cases showed no abnormality. After that, we determined final diagnoses; PD, PDD, DLB and PPP with an aid of the DSM-IV, the unified Parkinson\u27s disease rating scale (UPDRS) and Mini-mental state examination (MMSE). Results Of Group D patients 40% remained depressive without parkinsonism and about 50% had or developed typical parkinsonism. Most Group P patients developed clinical pictures of PDD or DLB. Statistics provided four combinations: Group V-DLB-occipital lobe hypoperfusion, Group D-PD without SPECT abnormality, Group P-PDD with temporal lobe hypoperfusion and Group D-PPP without SPECT abnormality. Conclusions PPP featured major depressive disorder and can be preparative of incidental LBD and prodromal depression of PD. Psychosis and dementia were of the same quality that characterizes the PDD. Copyright © 2014 John Wiley & Sons, Ltd

Approach to Utilization of Electronic Whiteboard in Classroom as Japanese Comparative Advantage : Survey on Primary Teacher Training Course Students

本研究の目的は，教室での電子黒板利用に関する日本の学校教育の比較優位性と劣位性を指摘した上で，電子黒板の利用意思向上に有効な要因を明らかにすることである．その為に，先ず現職教員研修の充実と教職学生の学習機会欠如を指摘した上で，次に小学校教員養成課程学生１３０名対象の質問紙調査を通して電子黒板利用意思向上の手掛かりを得た．その上で，同被験者５０名対象の教授実験の結果，電子黒板利用効果の理解が意思向上に有効なことを明らかにした．The purposes of this paper are twofold: （1） to point out the Japanese comparative advantage and disadvantage that resources of using electronic whiteboard in classroom,（2） to investigate the effective factors to improve the pre-service teacher’s intention for using electronic whiteboard. For these purposes, a questionnaire survey was conducted on 130 preservice primary teachers（undergraduate students）. Referring to result of this preliminary survey, we constituted the teaching plan which tries to encourage their intention, and carried out the experimental teaching for the 50 examinee. The results indicated two main points:（a） By diffusion of the electronic whiteboard in classroom, although in-service teachers can gain IT media training on their job, pre-service teachers have little occasion to care for it. （b） Effective factors to improve pre-service teacher’s intention are realization of lesson diversification and understanding of their effects via electronic whiteboard

Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus.</p> <p>Case presentation</p> <p>Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus.</p> <p>Conclusions</p> <p>In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.</p

The Effect of Ocular Surface Regularity on Contrast Sensitivity and Straylight in Dry Eye

Purpose: To investigate the association between visual function and ocular surface regularity in dry eye.Methods: We enrolled 52 eyes of 52 dry eye patients (34 dry eyes with superficial punctate keratopathy [SPK] in the central corneal region [central SPK] and 18 dry eyes without central SPK) and 20 eyes of 20 normal control subjects. All eyes had a best-corrected distance visual acuity better than 20/20. We measured two indices of contrast sensitivity function under photopic conditions: contrast sensitivity and letter contrast sensitivity. The area under the log contrast sensitivity function (AULCSF) was calculated from the obtained contrast sensitivity data. Straylight was quantified using a straylight meter.Results: Dry eyes with central SPK had significantly decreased contrast sensitivity function, including AULCSF and letter contrast sensitivity than those without central SPK and normal eyes (P < 0.05 for each). While the straylight values in both dry eye groups did not differ, straylight values were greater than those in normal eyes (P < 0.05 for both). In dry eye, the AULCSF and letter contrast sensitivity negatively correlated with the central SPK score (R = −0.485, P < 0.001, and R = −0.541, P < 0.001, respectively).Conclusions: In dry eye, reduced contrast sensitivity in part results from central SPK overlying the optical zone and the increased straylight results from tear film instability rather than central SPK

Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery

Topical therapy is the most favored form of treatment for whitening against hyperpigmentation and sunburn because it lends itself to self-administration, patient compliance, and absence of systemic adverse effects. However, transdermal delivery of hydrophilic chemicals is difficult. The main purpose of this study is to develop a delivering system of hydrophilic drugs and proteins across the skin. Hydroquinone (HQ), a well-known tyrosinase inhibitor and antimelanogenesis compound, and enhanced green fluorescent protein (EGFP) were fused with eleven poly-arginine (11R). Both HQ-11R and EGFP-11R were efficiently delivered in B16 cells, a mouse melanoma cell line. HQ-11R was as effective as HQ alone at inhibiting melanin synthesis in B16 cells. EGFP-11R was efficiently delivered into cells of the epidermis with 4-(1-pyrenyl)-butyric acid (PB), a counteranion bearing an aromatic hydrophobic moiety, in vivo, but EGFP alone or EGFP-11R without PB was not. Finally, topical application of HQ-11R with PB significantly inhibited UV irradiation-induced pigmentation in guinea pigs compared with HQ alone. These results suggest that topical therapy using poly-arginine in combination with PB is useful for the delivery of hydrophilic drugs and proteins by the transdermal route

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments:protocol for a multicentre prospective cohort study

Introduction: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs. Methods and analysis: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation. Ethics and dissemination: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals

Adubação nitrogenada e potássica em socas de cana-de-açúcar com e sem queima em solos de cerrado

A adubação representa cerca de 20% dos custos de produção da cana-de-açúcar e entre os nutrientes utilizados, o potássio constitui o elemento mais exigido pela cultura, juntamente com o nitrogênio. O trabalho teve como objetivo estudar os efeitos de doses de nitrogênio e de potássio na produtividade e qualidade das socas de cana-de-açúcar no 3º e 4º ciclos e no 4º ciclo em áreas com palhada (CCP) e sem palhada (CSP) sobre o solo. Os experimentos com os 3º e 4º ciclos foram conduzidos nos anos de 2006 a 2008 com a variedade RB 83-5486 na fazenda Vale da Pecuária, município de Selvíria-MS, e os experimentos com 4º ciclo da cana- de-açúcar em áreas com e sem palhada sobre o solo foram conduzidos nos anos de 2007 a 2008 com variedade RB 86-7515 nas fazendas A Raimundo e Retiro II, respectivamente, no município de Aparecida do Taboado-MS. Todos os experimentos foram desenvolvidos em áreas administradas pela Usina Alcoolvale S/A com quatro doses de nitrogênio (40, 80, 120 e 160 kg ha-1 de N), na forma de uréia, e quatro doses de potássio (40, 80, 120 e 160 kg ha-1 de K2O), na forma de cloreto de potássio, em um esquema fatorial 4x4, totalizando 16 tratamentos dispostos em blocos ao acaso, com quatro repetições. Foram avaliados os teores foliares de macronutrientes nas folhas e nos colmos, açúcares redutores do caldo e da cana, pol do caldo e da cana, pureza do caldo, brix, fibra, produtividade agroindustrial, produção de matéria-seca e produtividade de colmos. Para os experimentos 3º e 4º ciclos da cana-de- açúcar com a variedade RB 83-5486 as doses de N e de K aumentaram os teores de macronutrientes na folha e no colmo. Para os indicadores de qualidade da cana-de-açúcar, houve apenas efeito das doses de N no teor de brix no 3º ciclo, evidenciando que a matéria- prima estava com boa qualidade tecnológica e dentro...The fertilization represents around 20% of the production cost of sugar-cane crop and potassium constitutes its most demanded nutrient, together with nitrogen. The study had the objective of evaluating the effects of nitrogen and potassium rates on 3th and subsequent 4th cycle of sugar-cane crop (ratoon), and on 4th cycle of this crop in areas with or without cane trash burning, on its productivity and quality. The experiments of 3th and 4th cycles were conducted from 2006 to 2008 with the RB 83-5486 variety at Vale da Pecuária farm, Selvíria- MS, and the experiments with 4th cycle of the sugar-cane in areas managed with (+TB) or without (-TB) cane trash burning were conducted from 2007 to 2008 with variety RB 86-7515 at A Raimundo and Retiro II, respectively, in Aparecida do Taboado-MS. All experiments were carried out in areas administered by Usina Alcoolvale S/A, in a randomized block design using a 4x4 factorial scheme, with four rates of nitrogen (40, 80, 120 and 160 kg ha-1), as urea and four of potassium (40, 80, 120 and 160 kg ha-1 of K2O), as potassium chloride, totalizing 16 treatments with four replicates. The macro and micronutrients content in leaf and stem, reducing sugars, pol, purity, Brix, fiber content, tillering number in 10 meters, agro industrial productivity, dry matter and cane productivity were evaluated. For the experiments of 3th and 4th cycles N and K rates increased the leaf and stem macro and micronutrients contents. For the quality indicators, there was effect of N rates only on Brix in the 3th cycle, observing that the raw material had good technological quality and within the adequate patterns. The K rates increased the agro industrial productivity, dry matter and cane productivity only for the 4th cycle. The cane yield increased linearly with K rates. For the experiments of 4th cycle with RB 86-7515, the N and K rates increased... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES