Ajuste autonômico e endotelial frente a eletroestimulação ganglionar em homens com insuficiência cardíaca chagásica : ensaio controlado e randomizado

Tese (doutorado)—Universidade de Brasília, Faculdade de Ceilândia, Programa de Pós-Graduação Stricto Sensu em Ciências e Tecnologias e Saúde, 2018.Tese (doutorado)—Universidade de Brasília, Faculdade de Ceilândia, Programa de Pós-Graduação Stricto Sensu em Ciências e Tecnologias e Saúde, 2018.Introdução: A estimulação elétrica nervosa transcutânea (TENS) aplicada na região cérvico-torácica tem demonstrado capacidade de aumentar o fluxo sanguíneo periférico por meio da modulação autonômica em indivíduos saudáveis e isquemia vascular. Pacientes com insuficiência cardíaca de etiologia chagásica manifestam fibrose das fibras miocárdicas que induz uma sobrecarga autonômica compensatória. Nossa hipótese é que a EEG possa modular a hiperatividade simpática e melhorar a função vascular nessa população. Objetivos - Avaliar o efeito da estimulação elétrica nervosa transcutânea ganglionar na variabilidade da frequência cardíaca (VFC) e na dilatação mediada por fluxo (FMD) em homens com insuficiência cardíaca chagásica. Métodos: Foi realizado um ensaio clínico randomizado. Vinte homens (10 saudáveis e 10 chagásicos) foram submetidos a uma intervenção (TENS ou placebo) aplicada sobre a região ganglionar (vértebras C7 e T4) durante 30 minutos. A VFC e as imagens de fluxo sanguíneo e resistência vascular foram continuamente monitoradas durante as sete etapas do protocolo de coleta enquanto que as imagens da FMD foram registradas antes e após a intervenção durante os 5 minutos de liberação do manguito da oclusão da artéria braquial. Os efeitos da intervenção foram comparados utilizando-se o Teste ANOVA Two-way com Teste post-hoc de Tukey para ambos os grupos, considerando um p <0,05. Resultados: A FMD aumentou 69,93% nos indivíduos saudáveis (6,32 ± 2,39% para 10,74 ± 2,52%) e 28,45% em pacientes chagásicos (8,33 ± 2,44% para 10,7 ± 1,98%) após aplicação da TENS ganglionar. A VFC apresentou um padrão de redução da atividade simpática durante a modulação autonômica. Conclusão: Apesar de não alterar os índices da VFC, a aplicação da TENS sobre a região cérvico-torácica melhorou o ajuste da função endotelial da artéria braquial. Este resultado ratifica o efeito vascular da TENS aplicada sobre o gânglio estrelado e demonstra a capacidade preservada de dilatação dos vasos na insuficiência cardíaca chagásica.Introdução: A estimulação elétrica nervosa transcutânea (TENS) aplicada na região cérvico-torácica tem demonstrado capacidade de aumentar o fluxo sanguíneo periférico por meio da modulação autonômica em indivíduos saudáveis e isquemia vascular. Pacientes com insuficiência cardíaca de etiologia chagásica manifestam fibrose das fibras miocárdicas que induz uma sobrecarga autonômica compensatória. Nossa hipótese é que a EEG possa modular a hiperatividade simpática e melhorar a função vascular nessa população. Objetivos - Avaliar o efeito da estimulação elétrica nervosa transcutânea ganglionar na variabilidade da frequência cardíaca (VFC) e na dilatação mediada por fluxo (FMD) em homens com insuficiência cardíaca chagásica. Métodos: Foi realizado um ensaio clínico randomizado. Vinte homens (10 saudáveis e 10 chagásicos) foram submetidos a uma intervenção (TENS ou placebo) aplicada sobre a região ganglionar (vértebras C7 e T4) durante 30 minutos. A VFC e as imagens de fluxo sanguíneo e resistência vascular foram continuamente monitoradas durante as sete etapas do protocolo de coleta enquanto que as imagens da FMD foram registradas antes e após a intervenção durante os 5 minutos de liberação do manguito da oclusão da artéria braquial. Os efeitos da intervenção foram comparados utilizando-se o Teste ANOVA Two-way com Teste post-hoc de Tukey para ambos os grupos, considerando um p <0,05. Resultados: A FMD aumentou 69,93% nos indivíduos saudáveis (6,32 ± 2,39% para 10,74 ± 2,52%) e 28,45% em pacientes chagásicos (8,33 ± 2,44% para 10,7 ± 1,98%) após aplicação da TENS ganglionar. A VFC apresentou um padrão de redução da atividade simpática durante a modulação autonômica. Conclusão: Apesar de não alterar os índices da VFC, a aplicação da TENS sobre a região cérvico-torácica melhorou o ajuste da função endotelial da artéria braquial. Este resultado ratifica o efeito vascular da TENS aplicada sobre o gânglio estrelado e demonstra a capacidade preservada de dilatação dos vasos na insuficiência cardíaca chagásica.Background: Transcutaneous electrical nerve stimulation (TENS) over cervicothoracic region has been shown to increase peripheral blood flow through autonomic modulation in healthy individuals and vascular ischemia. Patients with heart failure with chagasic etiology show fibrosis of the myocardial fibers without severe vascular impairment, but with greater compensatory autonomic overload. Our hypothesis is that GEE may modulate sympathetic hyperactivity and vascular function in this population. Objectives - To evaluate the effect of ganglionic transcutaneous electrical nerve stimulation on heart rate variability (HRV) and flow - mediated dilatation (FMD) in patients with chagasic heart failure. Methods: It was a randomized controlled trial. Twenty men (10 healthy and 10 chagasic) underwent interventional stimulation (TENS or placebo) applied over the ganglionic region (C7 and T4 vertebrae) for 30 minutes. HRV and images of blood flow and vascular resistance were continuously monitored during the seven steps of the collection protocol while images of FMD were recorded before and after the intervention during the 5 minutes of cuff-occlusion release of brachial artery. The effects of the intervention were compared using the Two-Way ANOVA test with Tukey Post-hoc test for bothe groups considering a p <0.05. Results: Flow-mediated dilation (FMD) increased 69.93% in healthy subjects (6.32 ± 2.39% to 10.74 ± 2.52%) and 28.45% in chagasic patients (8.33 ± 2.44% to 10.7 ± 1.98%) after GEE application. Heart rate variability (HRV) showed a pattern of reduction of sympathetic activity during autonomic modulation. Conclusion: Despite we didn't find any change in HRV indexes, the application of TENS over cervico-thoracic region improved the endothelial function of the brachial artery. This result ratifies the vascular effect of TENS applied on the star ganglion and demonstrates the preserved capacity of vessel dilatation in chagasic heart failure.Background: Transcutaneous electrical nerve stimulation (TENS) over cervicothoracic region has been shown to increase peripheral blood flow through autonomic modulation in healthy individuals and vascular ischemia. Patients with heart failure with chagasic etiology show fibrosis of the myocardial fibers without severe vascular impairment, but with greater compensatory autonomic overload. Our hypothesis is that GEE may modulate sympathetic hyperactivity and vascular function in this population. Objectives - To evaluate the effect of ganglionic transcutaneous electrical nerve stimulation on heart rate variability (HRV) and flow - mediated dilatation (FMD) in patients with chagasic heart failure. Methods: It was a randomized controlled trial. Twenty men (10 healthy and 10 chagasic) underwent interventional stimulation (TENS or placebo) applied over the ganglionic region (C7 and T4 vertebrae) for 30 minutes. HRV and images of blood flow and vascular resistance were continuously monitored during the seven steps of the collection protocol while images of FMD were recorded before and after the intervention during the 5 minutes of cuff-occlusion release of brachial artery. The effects of the intervention were compared using the Two-Way ANOVA test with Tukey Post-hoc test for bothe groups considering a p <0.05. Results: Flow-mediated dilation (FMD) increased 69.93% in healthy subjects (6.32 ± 2.39% to 10.74 ± 2.52%) and 28.45% in chagasic patients (8.33 ± 2.44% to 10.7 ± 1.98%) after GEE application. Heart rate variability (HRV) showed a pattern of reduction of sympathetic activity during autonomic modulation. Conclusion: Despite we didn't find any change in HRV indexes, the application of TENS over cervico-thoracic region improved the endothelial function of the brachial artery. This result ratifies the vascular effect of TENS applied on the star ganglion and demonstrates the preserved capacity of vessel dilatation in chagasic heart failure

変形性膝関節炎患者膝関節液中の細胞外マトリックス成分と可溶性VCAM-1

It is generally accepted that the number of patients with osteoarthritis (OA) of the knee must increase in the future because of the increase of the aged. The pathogenic mechanisms of OA haven't been elucidated yet, but it is supposed that mediate pannus may cause the factors for irreversible cartilage damage in the inflammatory process. Therefore it is very important to find and predict OA at the early stage. Now there were many indices to determine joint damage with OA, for example, cytokines including IL, TNF, TGF, matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMPs), proteoglycan (PG), hyaluronate (HA), super oxide, adhesion molecules including, ICAM-1, VCAM-1 and PECAM. In this study, we measured that the soluble VCAM-1 (sVCAM-1), soluble collagen (sCOLL), heparansulfate proteoglycan (HSPG), uronic acis and CRP in synovial fluids (SF) with OA. A positive correlation between the level of sVCAM-1 and sCOLL (ρ = 0.652) was noted. However there was no factor showing a correlation with CRP. It was suggested that the levels of sVCAM-1 and sCOLL in the synovia fluid were active inflammation indices of knee damage, as the different aspects from CRP. The level of HSPG also showed a unique trend because HSPG on the cell surface was quickly digested endocytosis, so that it was not suitable for the inflammatory index in synovial fluid with OA.変形性膝関節炎(OA)患者は,高齢化社会の到来とともに今後ますます増加するものと考えられる｡OAの発症メカニズムについては,関節軟骨の破壊･修復やパンヌス形成に関わる多くの関連因子(サイトカイン,マトリックス分解酵素,分解酵素抑制因子,プロテオグリカン,活性酸素,細胞接着因子など)について,多面的に研究が進んでいる｡しかし,膝関節の炎症初期の病態のメカニズムについては,なお詳細に解明されておらず,関節炎初期の炎症指標の検索が今後さらに必要と考えられる｡本研究で私たちは, OA患者膝関節液中の細胞外マトリックス構成成分であるコラーゲン,へパラン硫酸プロテオグリカン,ウロン酸および炎症の最も初期に血管内皮細胞に出現するVCAM-1等の可溶化成分濃度を測定した｡患者膝関節液(SF)中の可溶性コラーゲン量と可溶性VCAM-1(sVCAM-1)量とは有意な正の相関関係が(ρ=0.652)観察された｡しかし,ヘパラン硫酸プロテオグリカン(HSPG)と可溶性コラーゲン(sCOLL)値間には有意な相関関係は確認されなかった｡また,一般に炎症の指標として用いられるCRP値とも比戟検討したが,CRP値と他の測定項目値とは一定の相関関係は存在しなかった。以上の結果より,OA患者のSF中の炎症マーカ-として,急性炎症時には従来の炎症指標蛋白質であるCRP値が有力であるというSipe JDの報告から推測するとsCOLLとsVCAM-1はCRP値と一定の相関を示さないことより,CRPの動態とは異なった炎症指標としての有用性が考えられる｡しかし,HSPGはエンドサイトシスにより速やかに代謝されるためSF中への解離が少なく,炎症指標としての可能性は低いと考えられる

Division Charts as Granules and Their Merging Algorithm for Rule Generation in Nondeterministic Data

We have been proposing a framework rough Nondeterministic information analysis, which considers granular computing concepts in tables with incomplete and nondeterministic information, as well as rule generation. We have recently defined an expression named division chart with respect to an implication and a subset of objects. Each division chart takes the role of the minimum granule for rule generation, and it takes the role of contingency table in statistics. In this paper, we at first define a division chart in deterministic information systems (DISs) and clarify the relation between a division chart and a corresponding implication. We also consider a merging algorithm for two division charts and extend the relation in DISs to nondeterministic information systems. The relation gives us the foundations of rule generation in tables with nondeterministic information

Development of Tumor-Specific Caffeine-Potentiated Chemotherapy Using Span 80 Nano-Vesicles DDS

Osteosarcoma cases with metastasis have poor prognosis in general. Recently, caffeinepotentiated chemotherapy, which is chemotherapy with caffeine dosage against malignancies, has manifested potently high efficacy as well as diverse effects. Recently, we demonstrated that nonionic vesicles prepared from Span 80 have promising physicochemical properties, which let them an attractive option besides the common liposomes. Here, we manifested the tumor-specific caffeine-potentiated chemotherapy against osteosarcoma in murine model employing a novel drug delivery system (DDS) with Span 80 nano-vesicles. C3H/HeJ mice underwent transplantation of LM8 osteosarcoma cell line and then were doped with therapeutic agents. Caffeine was employed as an enhancer in addition to ifosfamide (IFO) as the antitumor agent. in vitro, the united administration of IV + CV revealed significant induction of tumor apoptosis in the early phase. In vivo study manifested that IV + CV-administration markedly decreased the tumor volume as well as the viable tumor area than in the other groups. No marked organ damage was observed in the IV or IV + CV groups as well as fertility injury and/or malformations in their progeny. This novel DDS might have the importance for clinical application in primary tumors as well as the metastatic osteosarcoma

チュウソクヨウシ アルファリュウシナラビニチッソイオンノアルミニウム ニッケル セレニウム ギン マタワキンニオケルエネルギーソンシツノケンキュウ

京都大学0048新制・課程博士工学博士甲第1122号工博第263号新制||工||196(附属図書館)2921UT51-46-E422京都大学大学院工学研究科原子核工学専攻(主査)教授 向坂 正勝, 教授 兵藤 知典, 教授 大石 純学位規則第5条第1項該当Kyoto UniversityDA

Dynamics and stabilization mechanism of mitochondrial cristae morphofunction associated with turgor-driven cardiolipin biosynthesis under salt stress conditions

Maintaining energy production efficiency is of vital importance to plants growing under changing environments. Cardiolipin localized in the inner mitochondrial membrane plays various important roles in mitochondrial function and its activity, although the regulation of mitochondrial morphology to various stress conditions remains obscure, particularly in the context of changes in cellular water relations and metabolisms. By combining single-cell metabolomics with transmission electron microscopy, we have investigated the adaptation mechanism in tomato trichome stalk cells at moderate salt stress to determine the kinetics of cellular parameters and metabolisms. We have found that turgor loss occurred just after the stress conditions, followed by the contrasting volumetric changes in mitochondria and cells, the accumulation of TCA cycle-related metabolites at osmotic adjustment, and a temporal increase in cardiolipin concentration, resulting in a reversible topological modification in the tubulo-vesicular cristae. Because all of these cellular events were dynamically observed in the same single-cells without causing any disturbance for redox states and cytoplasmic streaming, we conclude that turgor pressure might play a regulatory role in the mitochondrial morphological switch throughout the temporal activation of cardiolipin biosynthesis, which sustains mitochondrial respiration and energy conversion even under the salt stress conditions.Fil: Nakata, Keisuke. Ehime University; JapónFil: Hatakeyama, Yuto. Ehime University; JapónFil: Erra Balsells, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Nonami, Hiroshi. Ehime University; JapónFil: Wada, Hiroshi. Ehime University; Japó

Granules for Association Rules and Decision Support in the getRNIA System

This paper proposes granules for association rules in Deterministic Information Systems (DISs) and Non-deterministic Information Systems (NISs). Granules for an association rule are defined for every implication, and give us a new methodology for knowledge discovery and decision support. We see that decision support based on a table under the condition P is to fix the decision Q by using the most proper association rule P〵Rightarrow Q. We recently implemented a system getRNIA powered by granules for association rules. This paper describes how the getRNIA system deals with decision support under uncertainty, and shows some results of the experiment

Rules and Apriori Algorithm in Non-deterministic Information Systems

This paper presents a framework of rule generation in Non-deterministic Information Systems (NISs), which follows rough sets based rule generation in Deterministic Information Systems (DISs). Our previous work about NISs coped with certain rules, minimal certain rules and possible rules. These rules are characterized by the concept of consistency. This paper relates possible rules to rules by the criteria support and accuracy in NISs. On the basis of the information incompleteness in NISs, it is possible to define new criteria, i.e., minimum support, maximum support, minimum accuracy and maximum accuracy. Then, two strategies of rule generation are proposed based on these criteria. The first strategy is Lower Approximation strategy, which defines rule generation under the worst condition. The second strategy is Upper Approximation strategy, which defines rule generation under the best condition. To implement these strategies, we extend Apriori algorithm in DISs to Apriori algorithm in NISs. A prototype system is implemented, and this system is applied to some data sets with incomplete information

Alteration of thermostable phosphatase activity after hydrophobic chromatography

耐熱性ホスファターゼを含んだBacillus stearothermophilus 粗酵素試料を、リソースIsoによる疎水性クロマトグラフィにかけ分離を行った。1.5M→0M 硫酸アンモニウムの直線逆濃度勾配によって溶出を行ったところ、ホスファターゼは不活性な形で溶出され、これは硫酸アンモニウムによる濃度依存的阻害に起因することが判明した。ホスタファーゼの反応混合液に種々の濃度の硫酸アンモニウムを添加したところ、0.15Mの硫酸アンモニウム存在下で約80％の阻害が認められた。加えて、この阻害作用は単に硫酸アンモニウムの添加によってpHが酸性側に傾くことによるものではないことも明らかとなった。Thermostable phosphatase partially purified from thermophilic bacteria, Bacillus stearothermophilus, was chromatographed on Resource Iso hydrophobic resin. When linear reverse gradient elution with 1.5 M → 0 M ( NH(4))(2)SO(4) was performed, phosphatase was found to be eluted as latent form, which revealed dose-dependent inhibitory effect of (NH(4))(2)SO(4) on phosphatase. When various concentrations of (NH(4))(2)SO(4) were added into phosphatase reaction mixture, about 80% inhibition was observed in the presence of 0.15 M (NH(4))(2)SO(4). Acidification by adding (NH(4))(2)SO(4) was not responsible for this inhibition, because addition of (NH(4))(2)SO(4) solution which pH was previously adjusted to 9.0 showed same inhibitory effect

On NIS-Apriori Based Data Mining in SQL

We have proposed a framework of Rough Non-deterministic Information Analysis (RNIA) for tables with non-deterministic information, and applied RNIA to analyzing tables with uncertainty. We have also developed the RNIA software tool in Prolog and getRNIA in Python, in addition to these two tools we newly consider the RNIA software tool in SQL for handling large size data sets. This paper reports the current state of the prototype named NIS-Apriori in SQL, which will afford us more convenient environment for data analysis.International Joint Conference on Rough Sets　(IJCRS 2016), October 7-11, 2016, Santiago, Chil