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1.
Neuroimage ; 224: 117434, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039616

RESUMO

To minimize motion-related distortion of reconstructed images, conventional positron emission tomography (PET) measurements of the brain inevitably require a firm and tight head restraint. While such a restraint is now a routine procedure in brain imaging, the physiological and psychological consequences resulting from the restraint have not been elucidated. To address this problem, we developed a restraint-free brain PET system and conducted PET scans under both restrained and non-restrained conditions. We examined whether head restraint during PET scans could alter brain activities such as regional cerebral blood flow (rCBF) and dopamine release along with psychological stress related to head restraint. Under both conditions, 20 healthy male participants underwent [15O]H2O and [11C]Raclopride PET scans during working memory tasks with the same PET system. Before, during, and after each PET scan, we measured physiological and psychological stress responses, including the State-Trait Anxiety Inventory (STAI) scores. Analysis of the [15O]H2O-PET data revealed higher rCBF in regions such as the parahippocampus in the restrained condition. We found the binding potential (BPND) of [11C]Raclopride in the putamen was significantly reduced in the restrained condition, which reflects an increase in dopamine release. Moreover, the restraint-induced change in BPND was correlated with a shift in the state anxiety score of the STAI, indicating that less anxiety accompanied smaller dopamine release. These results suggest that the stress from head restraint could cause unsolicited responses in brain physiology and emotional states. The restraint-free imaging system may thus be a key enabling technology for the natural depiction of the mind.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Dopamina/metabolismo , Cabeça , Memória de Curto Prazo , Tomografia por Emissão de Pósitrons/métodos , Restrição Física/psicologia , Estresse Psicológico/diagnóstico por imagem , Adulto , Ansiedade/diagnóstico por imagem , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Radioisótopos de Carbono , Neuroimagem Funcional , Voluntários Saudáveis , Humanos , Masculino , Radioisótopos de Oxigênio , Putamen/diagnóstico por imagem , Putamen/metabolismo , Putamen/fisiopatologia , Racloprida , Estresse Fisiológico , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Adulto Jovem
2.
Rapid Commun Mass Spectrom ; 32(23): 1991-1998, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30153343

RESUMO

RATIONALE: Sulfur is widely distributed in nature, and sulfur isotopic measurements have been applied to elucidate the origin and transport of sulfuric compounds in the lithosphere, biosphere, and atmosphere. Analyses of samples containing small amounts of sulfur, such as the Antarctic ice core samples analyzed herein, require a high-sensitivity analytical method. METHODS: We developed a high-sensitivity sulfur isotopic ratio (δ34 S value) analytical system equipped with an elemental analyzer, a cryo-flow device, and an isotope ratio mass spectrometer, and established a measurement and calibration procedure. RESULTS: Using this system, we precisely measured the δ34 S values of samples containing 5-40 nmol sulfate. Test runs were performed on samples from the Antarctic shallow ice core DF01, and the data obtained were consistent with those obtained by previous studies that reported δ34 S values for Antarctic snow and ice samples of more than 200 g (containing more than 150 nmol sulfate). Among the analyzed samples, one showed a peak sulfate concentration in its depth profile that is considered to have resulted from a large volcanic eruption. The δ34 S value obtained at that depth in the sample was distinct from values at other depths and consistent with reported values for volcanic sulfates. CONCLUSIONS: The analytical system developed herein is a powerful tool for trace sulfur isotopic analyses. The results obtained from the DF01 ice core samples are the first step towards elucidating high-time-resolution (less than 1 year) paleo-environmental changes by sulfur isotopic analyses.

3.
Exp Cell Res ; 336(2): 171-81, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26116467

RESUMO

The development of the efficient screening system of detecting compounds that promote myogenesis and prevent muscle atrophy is important. Mouse C2C12 cells are widely used to evaluate myogenesis but the procedures of the assay are not simple and the quantification is not easy. We established C2C12 cells expressing the N-terminal green fluorescence protein (GFP) and the C-terminal GFP (GFP1-10 and GFP11 cells). GFP1-10 and GFP11 cells do not exhibit GFP signals until they are fused. The signal intensity correlates with the expression of myogenic markers and myofusion. Myogenesis-promoting reagents, such as insulin-like growth factor-1 (IGF1) and ß-guanidinopropionic acid (GPA), enhance the signals, whereas the poly-caspase inhibitor, z-VAD-FMK, suppresses it. GFP signals are observed when myotubes formed by GFP1-10 cells are fused with single nuclear GFP11 cells, and enhanced by IGF1, GPA, and IBS008738, a recently-reported myogenesis-promoting reagent. Fusion between myotubes formed by GFP1-10 and GFP11 cells is associated with the appearance of GFP signals. IGF1 and GPA augment these signals, whereas NSC23766, Rac inhibitor, decreases them. The conditioned medium of cancer cells suppresses GFP signals during myogenesis and reduces the width of GFP-positive myotubes after differentiation. Thus the novel split GFP-based assay will provide the useful method for the study of myogenesis, myofusion, and atrophy.


Assuntos
Proteínas de Fluorescência Verde/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/citologia , Atrofia Muscular/prevenção & controle , Mioblastos/citologia , Clorometilcetonas de Aminoácidos/farmacologia , Aminoquinolinas/farmacologia , Animais , Inibidores de Caspase/farmacologia , Diferenciação Celular , Fusão Celular , Linhagem Celular , Proteínas de Fluorescência Verde/genética , Guanidinas/farmacologia , Células HEK293 , Humanos , Imidazóis/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos , Propionatos/farmacologia , Pirimidinas/farmacologia , Proteínas rac de Ligação ao GTP/antagonistas & inibidores
4.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 70(6): 542-8, 2014 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-24953319

RESUMO

While point spread function (PSF)-based positron emission tomography (PET) reconstruction effectively improves the spatial resolution and image quality of PET, it may damage its quantitative properties by producing edge artifacts, or Gibbs artifacts, which appear to cause overestimation of regional radioactivity concentration. In this report, we investigated how edge artifacts produce negative effects on the quantitative properties of PET. Experiments with a National Electrical Manufacturers Association (NEMA) phantom, containing radioactive spheres of a variety of sizes and background filled with cold air or water, or radioactive solutions, showed that profiles modified by edge artifacts were reproducible regardless of background µ values, and the effects of edge artifacts increased with increasing sphere-to-background radioactivity concentration ratio (S/B ratio). Profiles were also affected by edge artifacts in complex fashion in response to variable combinations of sphere sizes and S/B ratios; and central single-peak overestimation up to 50% was occasionally noted in relatively small spheres with high S/B ratios. Effects of edge artifacts were obscured in spheres with low S/B ratios. In patient images with a variety of focal lesions, areas of higher radioactivity accumulation were generally more enhanced by edge artifacts, but the effects were variable depending on the size of and accumulation in the lesion. PET images generated using PSF-based reconstruction are therefore not appropriate for the evaluation of SUV.


Assuntos
Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Humanos , Tomografia Computadorizada por Raios X/métodos
5.
J Atheroscler Thromb ; 31(7): 1048-1057, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38311417

RESUMO

AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. METHODS: From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. RESULTS: Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. CONCLUSION: The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.


Assuntos
Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Criança , Feminino , Masculino , Japão/epidemiologia , Testes Genéticos/métodos , Testes Genéticos/normas , Adolescente , LDL-Colesterol/sangue , Guias de Prática Clínica como Assunto , Pré-Escolar , Aterosclerose/diagnóstico , Aterosclerose/sangue , Sensibilidade e Especificidade , Sociedades Médicas
6.
Langmuir ; 29(37): 11667-80, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23957575

RESUMO

We designed novel peptide gemini surfactants (PG-surfactants), DKDKC12K and DKDKC12D, which can solubilize Photosystem I (PSI) of Thermosynecoccus elongatus and Photosystem II (PSII) of Thermosynecoccus vulcanus in an aqueous buffer solution. To assess the detailed effects of PG-surfactants on the original supramolecular membrane protein complexes and functions of PSI and PSII, we applied the surfactant exchange method to the isolated PSI and PSII. Spectroscopic properties, light-induced electron transfer activity, and dynamic light scattering measurements showed that PSI and PSII could be solubilized not only with retention of the original supramolecular protein complexes and functions but also without forming aggregates. Furthermore, measurement of the lifetime of light-induced charge-separation state in PSI revealed that both surfactants, especially DKDKC12D, displayed slight improvement against thermal denaturation below 60 °C compared with that using ß-DDM. This degree of improvement in thermal resistance still seems low, implying that the peptide moieties did not interact directly with membrane protein surfaces. By conjugating an electron mediator such as methyl viologen (MV(2+)) to DKDKC12K (denoted MV-DKDKC12K), we obtained derivatives that can trap the generated reductive electrons from the light-irradiated PSI. After immobilization onto an indium tin oxide electrode, a cathodic photocurrent from the electrode to the PSI/MV-DKDKC12K conjugate was observed in response to the interval of light irradiation. These findings indicate that the PG-surfactants DKDKC12K and DKDKC12D provide not only a new class of solubilization surfactants but also insights into designing other derivatives that confer new functions on PSI and PSII.


Assuntos
Cianobactérias/química , Peptídeos/química , Complexo de Proteína do Fotossistema I/química , Complexo de Proteína do Fotossistema II/química , Tensoativos/química , Tensoativos/síntese química , Cianobactérias/metabolismo , Estrutura Molecular , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Solubilidade
7.
Bioorg Med Chem Lett ; 22(4): 1756-60, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22285943

RESUMO

Vitamin D receptor (VDR) is a nuclear receptor for 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)), and is an attractive target for multiple clinical applications. We recently developed novel non-secosteroidal VDR ligands bearing a hydrophobic p-carborane cage, thereby establishing the utility of this spherical hydrophobic core structure for development of VDR ligands. Here, we synthesized two series of novel non-secosteroidal VDR ligands with different spherical hydrophobic cores, that is, bicyclo[2.2.2]octane derivatives and p-carborane derivatives, and compared their biological activities in order to examine the difference between the interactions of the C-H hydrocarbon surface and the B-H carborane surface with the receptor. Carborane derivatives exhibited more potent differentiation-inducing activity toward HL-60 cells than did the corresponding bicyclo[2.2.2]octane derivatives. These results suggest that the hydrophobic carborane cage may interact more efficiently than the hydrocarbons with the hydrophobic surface of VDR. This finding further supports the view that carborane structure is a promising option for drug development.


Assuntos
Boranos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Ligantes , Receptores de Calcitriol/agonistas , Boranos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células HL-60 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Receptores de Calcitriol/química
8.
J Atheroscler Thromb ; 29(6): 839-849, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34176852

RESUMO

AIM: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. METHOD: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. RESULTS: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. CONCLUSION: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.


Assuntos
Hiperlipoproteinemia Tipo II , Apolipoproteínas B/genética , Criança , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Japão/epidemiologia , Mutação , Pró-Proteína Convertase 9/genética
9.
Biosci Biotechnol Biochem ; 75(1): 20-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21228483

RESUMO

To understand better the host defense mechanisms of mollusks against pathogens, we examined the anti-microbial activity of mucus from the giant African snail Achatina fulica. Hemagglutination activity of the mucus secreted by the integument of snails inoculated with Escherichia coli was observed to increase and to cause hemagglutination of rabbit red blood cells. Purification of the snail mucus lectin by sequential column chromatography revealed that the relative molecular mass of the lectin was 350 kDa. The hemagglutination activity of the lectin was Ca(2+)-dependent and was inhibited by galactose. Growth arrest tests showed that the lectin did not inhibit bacterial growth, but did induce agglutination of gram-positive and gram-negative bacteria. Tissue distribution analyses using a polyclonal antibody revealed that the lectin was expressed in the tissues of the mantle collar. The lectin isolated from the mucus of the snail appeared to contribute to its innate immunity.


Assuntos
Lectinas/química , Lectinas/isolamento & purificação , Muco/química , Caramujos/química , Animais , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Hemaglutinação/efeitos dos fármacos , Hemolinfa/química , Hemolinfa/microbiologia , Lectinas/sangue , Lectinas/farmacologia , Peso Molecular , Muco/microbiologia , Transporte Proteico , Coelhos , Caramujos/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
10.
Sci Technol Adv Mater ; 12(5): 054203, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27877430

RESUMO

A powder library of layered Li(Ni,Co,Ti)O2 (Ni ≤ 0.8, Ti ≤ 0.2) compounds was prepared by electrostatic spray deposition. From powder x-ray diffraction patterns, most of the powder library sintered at 700 ○C was indexed as a single phase belonging to the space group R[Formula: see text]m. These results were almost identical to those obtained from a study by combinatorial exploration. We investigated the charge-discharge characteristics of the Li(Ni,Co,Ti)O2 powder library in a voltage range from 4.2 to 2.8 V at 1 C and found favorable cycling properties in the LiNi x Co0.9-x Ti0.1O2 (0 ≤x ≤ 0.6) compounds.

11.
Brain Stimul ; 14(1): 154-160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33359603

RESUMO

BACKGROUND: Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown. OBJECTIVE: To investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS. METHOD: This study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [11C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters. RESULTS: MRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [11C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release. CONCLUSION: The present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Encéfalo/diagnóstico por imagem , Dopamina , Método Duplo-Cego , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/diagnóstico por imagem , Ácido gama-Aminobutírico
12.
Chem Pharm Bull (Tokyo) ; 58(6): 825-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20522993

RESUMO

Monophenyl-substituted dihydropyrazines (Ph-DHP-1 to 4) of 2,3-dihydro-5,6-dimethylpyrazine (Me-DHP-1), which have the inductive effects of apoptosis and mutagenesis, were synthesized and their biological effect was investigated in terms of DNA strand-breakage. Differences between the phenyl- and methyl-substituted dihydropyrazines were examined.


Assuntos
Quebras de DNA/efeitos dos fármacos , DNA/metabolismo , Pirazinas/química , Pirazinas/farmacologia
13.
Chem Pharm Bull (Tokyo) ; 58(7): 922-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20606338

RESUMO

Tautomerization of methyl-substituted dihydropyrazine (DHP) derivatives to their latent enamine form was investigated theoretically and empirically. Among two types of hydrogen transfer model simulated by means of density functional theory calculation, a simple intramolecular hydrogen shift mechanism for 5,6-dimethyl-2,3-dihydropyrazine (1) and 5-methyl-6-phenyl-2,3-dihydropyrazine (3) required high activation energies for tautomerism, while a water-assisted intermolecular hydrogen transfer mechanism gave smaller activation energies (about 160 kJ/mol). Examination of the deuterium exchange reaction of 3 in 50% (v/v) D(2)O/dimethyl sulfoxide-d(6) solution revealed temperature-dependent and stepwise deuterium exchange of the 5-methyl group. Reaction of compound 3 with phenyl isocyanate in acetonitrile afforded a mono adduct (7) at the 5-methyl group, and a cyclic adduct (8). These results represent evidence of tautomerism of 5-methyl-2,3-dihydropyrazines (imine forms) to the latent enamine tautomers, and suggest that DHPs may behave as enamines to a significant degree under physiological conditions.


Assuntos
Pirazinas/química , Deutério/química , Medição da Troca de Deutério , Isomerismo , Espectroscopia de Ressonância Magnética , Temperatura , Termodinâmica , Água/química
14.
PLoS One ; 15(4): e0231265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267872

RESUMO

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in the regulation of cell proliferation and differentiation. TAZ activity changes in response to the cellular environment such as mechanic and nutritional stimuli, osmolarity, and hypoxia. To understand the physiological roles of TAZ, chemical compounds that activate TAZ in cells are useful as experimental reagents. Kaempferol, TM-25659, and ethacridine are reported as TAZ activators. However, as each TAZ activator has a distinct property in cellular functions, additional TAZ activators are awaiting. We screened for TAZ activators and previously reported IB008738 as a TAZ activator that promotes myogenesis in C2C12 cells. In this study, we have characterized IBS004735 that was obtained in the same screening. IBS004735 also promotes myogenesis in C2C12 cells, but is not similar to IBS008738 in the structure. IBS004735 activates TAZ via Akt and has no effect on TAZ phosphorylation, which is the well-described key modification to regulate TAZ activity. Thus, we introduce IBS004735 as a novel TAZ activator that regulates TAZ in a yet unidentified mechanism.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Imidazóis/farmacologia , Desenvolvimento Muscular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tetrazóis/farmacologia , Transativadores/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Animais , Diferenciação Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Camundongos , Mioblastos Esqueléticos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Transativadores/genética , Transfecção
15.
Anticancer Res ; 29(6): 2403-10, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19528508

RESUMO

The anthropogenic substance 4,4'-biphenol and its analogues are estrogenic and cytotoxic. It has been previously found that synthesized ortho-dimers of phenolic compounds possess potent antioxidative and anti-inflammatory activity. To clarify the relationships between radical-scavenging and anti-inflammatory activities, the radical-scavenging activities of 4,4'-biphenol, 2,2'-biphenol and phenol were investigated by using differential scanning calorimetry to measure the induction period for polymerization of methyl methacrylate initiated by thermal decomposition of 2,2'-azobisisobutyronitrile. We also investigated tThe inhibitory effects of these compounds on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) mRNA and protein expression and on binding of activator-protein-1 (AP-1) and nuclear factor kappa-B (NF-kappaB) to their respective consensus sequences were also investigated in RAW 264.7 cells. Furthermore, theoretical parameters such as phenolic-OH bond dissociation enthalpy (BDE) and ionization potential (IP(koopman)) were calculated at the density functional theory (DFT)/B3LYP levels. Cytotoxicity declined in the order 4,4'-biphenol > 2,2'-biphenol >> phenol. 2,2'-Biphenol, but not 4,4'-biphenol, showed inhibitory effects on LPS-stimulated COX-2 expression and on AP-1 and NF-kappaB binding to their consensus sequences at 1-10 muM. Expression of COX-2 in RAW cells was enhanced by 4,4'-biphenol plus LPS, possibly because of radical-mediated transformation of 4,4'-biphenol to the cytotoxic diphenylquinone, as judged by the stoichiometric factor (n value) of 3.429 and low IP(koopman) value of this biphenol. In contrast, the anti-inflammatory activity of 2,2'-biphenol may be the result of the formation of a dimer derived from oxidation of this compound, as suggested by its n value close to 1. Phenol showed anti-inflammatory activity but did not completely inhibit COX-2 expression, even at higher concentrations.


Assuntos
Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Fenol/farmacologia , Fenóis/farmacologia , Animais , Northern Blotting , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 1/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Macrófagos/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos
16.
Radiol Phys Technol ; 12(2): 210-215, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30937726

RESUMO

The psoas-major muscle has been reported as a predictive factor of sarcopenia. The cross-sectional area (CSA) of the psoas-major muscle in axial images has been indicated to correlate well with the whole-body skeletal muscle mass. In this study, we evaluated the segmentation accuracy of low-dose X-ray computed tomography (CT) images of the psoas-major muscle using the U-Net convolutional neural network, which is a deep-learning technique. Deep learning has been recently known to outperform conventional image-segmentation techniques. We used fivefold cross validation to validate the segmentation performance (n = 100) of the psoas-major muscle. For the intersection over union and CSA ratio, segmentation accuracies of 86.0 and 103.1%, respectively, were achieved. These results suggest that the U-Net network is competitive compared with the previous methods. Therefore, the proposed technique is useful for segmenting the psoas-major muscle even in low-dose CT images.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Músculos/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X , Automação , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade
17.
Transl Psychiatry ; 9(1): 115, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30877269

RESUMO

Transcranial direct-current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) has been established as an effective and noninvasive method to modulate cognitive function. Nevertheless, the mechanisms causing those cognitive changes under the tDCS remain largely unknown. We strove to elucidate the cognito-biological relation under the tDCS condition by examining whether the dopamine system activated by tDCS is involved in cognitive changes in human participants, or not. To evaluate the dopamine system, we used [11C]-raclopride positron emission tomography (PET) scanning: 20 healthy men underwent two [11C]-raclopride PET scans and subsequent neuropsychological tests. One scan was conducted after tDCS to the DLPFC. One was conducted after sham stimulation (control). Results of [11C]-raclopride PET measurements demonstrate that tDCS to the DLPFC caused dopamine release in the right ventral striatum. Neuropsychological tests for attentiveness revealed that tDCS to the DLPFC-enhanced participants' accuracy. Moreover, this effect was correlated significantly with dopamine release. This finding provides clinico-biological evidence, demonstrating that enhancement of dopamine signaling by tDCS in the ventral striatum is associated with attention enhancement.


Assuntos
Atenção , Dopamina/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua , Estriado Ventral/fisiologia , Adulto , Estudos Cross-Over , Antagonistas de Dopamina/farmacocinética , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Racloprida/farmacocinética , Estriado Ventral/diagnóstico por imagem , Adulto Jovem
18.
Anticancer Res ; 28(2A): 699-707, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18507010

RESUMO

Curcumin and its reduced derivative tetrahydrocurcumin have been shown to exhibit chemopreventive activity. Cyclooxygenase-2 (COX-2) inhibition in lipopolysaccharide (LPS)- or Porphyromonas gingivalis fimbria-stimulated RAW 264.7 cells was investigated using Northern blot analysis. The fimbria-stimulated expression of the COX-2 gene was inhibited by curcumin but not by tetrahydrocurcumin. LPS-stimulated COX-2 gene expression was completely inhibited by curcumin, but an increase in the concentration of tetrahydrocurcumin did not cause complete inhibition of COX-2 expression. The inhibitory effect of curcumin on nuclear factor kappa B (NF-kappaB) activation in the cells was clearly observed, but that of tetrahydrocurcumin was incomplete even at a concentration of 20 microM. To explain the difference in effect between the two compounds, analysis of the frontier orbital was performed using ab initio 6-31G* wave function. The calculated chemical hardness (eta) for curcumin was clearly smaller, whereas its electronegativity (chi) and electrophilicity (omega) were clearly greater than the corresponding values for the curcumin-related compounds tetrahydrocurcumin, isoeugenol and eugenol. This suggested that the anti-inflammatory activities of curcumin may be related to eta-, chi- and/or omega-controlled enzymes. In addition, the bond dissociation enthalpy (BDE) of the phenolic OH was calculated using the density function theory (DFT)/B3LY. The total BDE values of curcumin and tetrahydrocurcumin were almost identical, but the BDE of one-electron oxidation and ionization potential (IP) for curcumin were lower than those for tetrahydrocurcumin, suggesting the highly pro-oxidative activity of curcumin. Curcumin has both oxidant and antioxidant properties. A causal link between the anti-inflammatory activities and molecular properties of phenolic antioxidants is suggested.


Assuntos
Anti-Inflamatórios/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Animais , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2 , Ligação de Hidrogênio , Hidróxidos/química , Lipopolissacarídeos/farmacologia , Camundongos , Fenol/química , Porphyromonas gingivalis/citologia , Proteínas Serina-Treonina Quinases/metabolismo , Quinase Induzida por NF-kappaB
19.
In Vivo ; 22(3): 289-96, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18610738

RESUMO

BACKGROUND: 2-t-Butyl-4-methoxyphenol (BHA) has considerable toxicity and undesirable potential tumor-promoting activities. To clarify the free radical mechanism of BHA-induced toxicity, the comparative radical-scavenging activity of BHA and its dimer (bis-BHA, 3,3'-ditert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) with or without 2-mercapto-1-methylimidazole (MMI) was studied using the induction period method. MATERIALS AND METHODS: The induction period and propagation rate (Rp) were determined by differential scanning calorimetry (DSC) monitoring of polymerization of methyl methacrylate, initiated by the thermal decomposition of benzoyl peroxide (a source of the peroxy radical, PhCOO*) or 2,2'-azobisisobutyronitrile (a source of the alkyl radical, R*) under nearly anaerobic conditions. The anti-1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical- and O2(-)-scavenging activities were also investigated. Furthermore, theoretical parameters were calculated from the DEFT/B3LYP and HF/6-31G*//B3LYP levels. RESULTS: For both PhCOO* and R* the inhibition rate constant (k(inh)) for BHA and bis-BHA was almost identical, but a marked decrease in the Rp(inh)/Rp(con) was found for the former. The BHA/MMI mixture (1:1 molar ratio) oxidized by R* reduced the total radical-scavenging activity by approximately 20% . BHA showed lower anti-DPPH radical- and higher O2(-)-scavenging activity. CONCLUSION: Upon PhCOO* or R* scavenging, BHA with a lower BDE, IP(koopman's), electronegativity, and electrophilicity value, but not bis-BHA with higher corresponding values, highly suppressed propagation. This may be due to the formation of highly reactive free-radical intermediates, which are potentially toxic.


Assuntos
Hidroxianisol Butilado/química , Sequestradores de Radicais Livres/química , Oxigênio/química , Alquilação , Compostos de Bifenilo/química , Dimerização , Hidrazinas/química , Imidazóis/química , Estrutura Molecular , Oxirredução , Picratos
20.
J Arthroplasty ; 23(5): 689-93, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18534378

RESUMO

Thirty cases whose femoral side was operated with interface bioactive bone cement technique in revision total hip arthroplasty for aseptic loosening and followed for more than 6 years were evaluated. The present study includes 2 men and 28 women with an average age at operation of 60 years. Mean postoperative follow-up period was 9 years. Rerevision of femoral component was not found. Possible loosening was observed in 1 case, using the criteria of Harris. Among 21 cases whose cementing grade was assessed as B or C in postoperative x-ray, radiolucent line at bone-cement interface has disappeared before last follow-up in 11 cases. The present study revealed that the good result was obtained using the interface bioactive bone cement technique for reconstruction of aseptic femoral loosening.


Assuntos
Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Cimentos Ósseos , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Fixadores Internos , Adulto , Idoso , Idoso de 80 Anos ou mais , Materiais Biocompatíveis , Durapatita , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Reoperação , Resultado do Tratamento
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