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1.
J Phys Chem A ; 128(16): 3051-3061, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38626323

RESUMEN

In order to elucidate the origins of the stable structures of dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate] and the four derivatives with halogenated aromatic rings, the conformational stability and intramolecular interactions were investigated by DFT calculations. In all of these complexes, the conformation in which all ligands face in the same direction is the most stable. When adjacent ligands are in the same orientation, destabilization due to exchange repulsion is larger than that when they are in opposite orientations. However, this destabilizing effect is reversed by the sum of the stabilizing effects of the electronic and charge transfer interactions. The imide carbonyl group plays an important role in these stabilizing interactions. The negatively charged site and bond orbitals in the imide carbonyl group interact with the positively charged sites and bond orbitals in the aromatic ring, the carboxylate group, and the α-position of the carboxylate group in the adjacent ligands. In addition, the lone-pair orbitals of the halogen atoms contribute to conformational stabilization by interacting with the vacant orbitals in the adjacent ligands. However, the combinations of these charged sites or bond orbitals, which effectively contribute to the stabilization, are different for each complex.

2.
Biosci Biotechnol Biochem ; 87(8): 890-897, 2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37156505

RESUMEN

Taste is an essential factor for evaluating the quality of agricultural products. However, it is usually difficult to compare data acquired at different times or by different people because there is no invariant reference and because the evaluation methods are largely subjective. Here, we addressed these problems by developing a method for standardizing strawberry sourness and sweetness intensities using a taste sensor approach with a taste standard solution composed of sour and sweet compounds. This standard solution allows highly efficient sensor measurements because it contains the standard compounds citric acid and sucrose. In addition, we found that polyphenol destabilized the sensor response for strawberry sweetness, and its removal from the sample by appropriate treatment with polyvinylpolypyrrolidone allowed stable evaluation of the sweetness intensity. The taste sensor data obtained using this method were in good agreement with the chemical analysis values related to human sensory evaluation.


Asunto(s)
Fragaria , Frutas , Fragaria/química , Gusto , Frutas/química , Polifenoles/análisis , Azúcares/análisis , Estándares de Referencia
3.
Analyst ; 147(20): 4480-4488, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36065797

RESUMEN

To evaluate sensory intensities of tastes, astringency, or pungency with ease and high reproducibility, the present study proposes a method using a fluorescent substance as a sensor. Unlike conventional taste sensors that each require a specialized system, this approach has the advantage in that it can be conducted using common analytical equipment such as a fluorescence spectrometer. In this report, a method to detect catechins and its application toward astringent evaluation is described. The binding of a sensor molecule with eight catechins revealed that the sensor molecule has higher affinity for catechins with stronger astringency. The complexation with the more astringent catechins showed larger fluorescence quenching. The change in the fluorescence intensity of a sample solution with the sensor molecule based on a reference solution was defined as the astringent intensity. Evaluation tests of green tea astringency demonstrated that the outputs of the sensor molecule correlate highly with the results by the human sense.


Asunto(s)
Catequina , Astringentes , Catequina/química , Humanos , Reproducibilidad de los Resultados , Gusto , Té/química
4.
Biosci Biotechnol Biochem ; 84(12): 2569-2575, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32772904

RESUMEN

To enable the taste evaluation of many food samples at a time as well as the comparison of taste evaluation data acquired at different times, a standardization method for taste intensities was developed by a combination of a taste sensor system and a standard solution prepared with taste substances. In the case of tomato juices, citric acid, sucrose, and monosodium glutamate were used as standard taste substances for sourness, sweetness, and umami taste, respectively. Each standard point of the taste intensities was determined using only one standard solution including these standard substances. The taste intensity was described as a value on a scale based on discrimination thresholds of human gustation, where intensities of sourness, sweetness, and umami taste of the tomato juices were classified into multiple levels. Organoleptic evaluation supported these results. Validation for the present standardization method revealed that this approach has enough precision for practical tomato taste evaluation.


Asunto(s)
Jugos de Frutas y Vegetales/análisis , Solanum lycopersicum/química , Gusto , Estándares de Referencia
5.
J Agric Food Chem ; 68(1): 323-331, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31880932

RESUMEN

4G-α-Glucopyranosylrutin (monoglucosylrutin, MGR) is a flavonol glycoside with quercetin as an aglycone, is pale yellow in color, and engages in both copigmentation and anticopigmentation. In this study, we elucidated the mechanism underlying the copigmentation of MGR upon complexation with caffeine. Three approaches were used: binding analyses based on changes in the absorbance spectrum, NOESY experiments, and DFT and TDDFT calculations using an explicit solvation model. Our findings show that copigmentation mainly results from a bathochromic shift in the absorbance spectrum and not a from hyperchromic effect. MGR and caffeine form a complex in both 1:1 and 1:2 stoichiometric ratios. The calculated optimized 1:1 and 1:2 complex structures were supported by the NOESY spectrum and form a cluster with 13 and 11 water molecules, respectively, through hydrogen bonds. Although HOMO and LUMO contribute most to the excitation of both the MGR monomer and the complexes, these frontier molecular orbitals in the complexes are distributed more widely than those in the MGR monomer. In particular, LUMO in the complexes spreads into the copigment caffeine and the solvent water molecules. This increase in electron delocalization reduces the energy gap between the frontier molecular orbitals, resulting in copigmentation with a bathochromic shift.


Asunto(s)
Cafeína/química , Flavonoles/química , Glucósidos/química , Color , Enlace de Hidrógeno
6.
Biochem Biophys Res Commun ; 511(2): 318-322, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30803755

RESUMEN

The Kururu no ß-glu® (KBG) is a commercial hydrothermal-treated Aureobasidium pullulans ß-glucan produced by a unique hydrothermal process that results in high solubility of the ß-glucan. In this study, we examined the biological activities of this reagent. RAW264.7 cells do not express Dictin-1 on the cell surface, but cells still respond to various pathogen molecular patterns. Lipopolysaccharide (LPS) induced nitrogen oxide (NO) synthesis and TNF-α production in RAW264.7 cells, and those were suppressed by KBG in a dose-dependent manner. The major signaling cell surface receptor respond to LPS is the TLR4/MD-2 complex. The UT12 antibody against to the TLR4/MD-2 complex mimics LPS function and induces cell responses. NO generation and TNF-α production were similarly induced in cells by stimulation with the antibody, but those were not suppressed by KBG. Cell responses induced by other TLR ligands, such as CPG (TLR9 ligand) and Pam3CSK4 (TLR1/TLR2 ligand), were also suppressed by KBG. Therefore, the target molecule for KBG is different from TLR receptors and Dictin-1. Although we also examined the suppressive activities of several other ß-glucan products, comparable activities were not detected with other reagents. A unique hydrothermal process may produce the active reagent. Reprocessing KBG increased low molecular weight fractions, and suppressive activities were markedly enhanced. Therefore, low molecular weight fractions obtained by hydrothermal processing of KBG may result in potential reagents that control inflammation induced by various pathogens.


Asunto(s)
Antiinflamatorios/farmacología , Ascomicetos , Macrófagos/efectos de los fármacos , Receptores Toll-Like/inmunología , beta-Glucanos/farmacología , Animales , Antiinflamatorios/química , Ascomicetos/química , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Ratones , Células RAW 264.7 , beta-Glucanos/química
7.
J Nat Prod ; 82(1): 2-8, 2019 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-30589259

RESUMEN

The addition of ent-gallocatechin-3- O-gallate ( ent-GCg) or epigallocatechin-3- O-gallate (EGCg) to an aqueous solution of 4G-α-glucopyranosylrutin (monoglucosylrutin, MGR) causes the color of the solution to weaken due to complexation between MGR and these flavan-3-ols. Copigmentation is a well-known color change phenomenon resulting from the complexation of flavonoids that deepens and strengthens the color of the solution, whereas MGR/catechin complexation results in the opposite change in color (i.e., weakening). In order to gain insight into the mechanism underlying the rare changes in the color of solutions of complexes between flavonoids, the structures of the MGR monomer and the complexes in aqueous solutions and their photochemical properties were investigated by computational methods. Molecular dynamics simulations and subsequent density functional theory (DFT) calculations revealed that the complex structures are stabilized through aromatic/aromatic, CH/π, and OH/O interactions as direct intermolecular forces and that many solvent water networks would contribute to the complexations. Time-dependent DFT calculations showed that the change in the color of an MGR/ ent-GCg solution is due only to a decrease in absorbance, whereas that of an MGR/EGCg solution is due to both a decrease in absorbance and a hypsochromic shift.


Asunto(s)
Catequina/análogos & derivados , Rutina/análogos & derivados , Catequina/química , Color , Simulación de Dinámica Molecular , Rutina/química , Soluciones
8.
Int J Clin Oncol ; 23(6): 1015-1022, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29971621

RESUMEN

BACKGROUND: To determine the current practice of stereotactic irradiation (STI) for brain metastases in Japan by a questionnaire survey. METHODS: A questionnaire was distributed to 313 institutions performing STI with one of the following machines: Gamma Knife (GK), CyberKnife (CK), Novalis (Nov), or other linear accelerator (LINAC)-based systems (OLS). The participation was voluntary. RESULTS: There were 163 responding institutions. The total number of STI treatments between April 2013 and March 2014 was 10,684. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) were performed in 8624 (80.7%) and 2060 (19.3%) cases, respectively. Whole-brain radiation therapy (WBRT) was performed for a total of 3515 cases. For a case model of a 1.5-cm solitary brain metastasis in a non-eloquent area, the most common GTV-PTV margin was 2 mm (22 of 114 institutions), and an institutional standard fraction was 1 (75 of 114 institutions). The doses for the model case also varied from 13.0 to 26.0 Gy (Median 20 Gy) when converted to SRS (α/ß = 10). A prescription point was at the PTV margin the most. The median dose constraints which were converted to SRS (α/ß = 3) to organs at risk were 12.2, 12.7, and 13.7 Gy for optic nerves, cavernous sinus, and brainstem, respectively. CONCLUSIONS: STI for brain metastases in current practice varied significantly among institutions. These different strategies relied mostly on the type of treatment machine used. It is thus necessary to establish a common guideline to express dose prescriptions and plan qualities for different STI machines.


Asunto(s)
Neoplasias Encefálicas/cirugía , Pautas de la Práctica en Medicina/tendencias , Oncología por Radiación/normas , Radiocirugia/métodos , Neoplasias Encefálicas/secundario , Humanos , Japón , Encuestas y Cuestionarios
9.
J Phys Chem A ; 121(44): 8484-8494, 2017 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-29028337

RESUMEN

The geometries of the two hydroxy groups in 1,2-ethanediol or 2,3-butanediols are more stable in a gauche orientation than those in an anti orientation. This has been generally explained in terms of the gauche effect, which is stabilization due to antiperiplanar electron delocalization between an antibonding orbital of the C-O bond (σCO*) and a bonding orbital of the C-H or C-C bond (σCH or σCC). However, a C-C single bond rotation simultaneously determines the geometries of the six vicinal bonds. Therefore, it is important to understand the effects on conformational stability of other interactions of the bond orbitals adjacent to the rotating C1-C2 bond. Bond model analysis revealed that antiperiplanar bond orbital interactions as a whole contribute to the higher stabilities of hydroxy/hydroxy gauche conformers, where the C-O/C-H or C-O/C-C combination including the σCO*/σCH or σCO*/σCC delocalization is not the dominant interaction stabilizing hydroxy/hydroxy gauche conformers. Rather, our results show that a large destabilization due to the antiperiplanar C-O/C-O combination in hydroxy/hydroxy anti conformers relatively increases the stabilities of hydroxy/hydroxy gauche conformers. This destabilization results mainly from the repulsion between the antiperiplanar bonding orbitals (σCO/σCO), which have a larger overlap compared to the synclinal σCO/σCO combination. The sum of the interbond energies between the vicinal bond orbitals of these 1,2-alkanediols is more advantageous for stability in gauche conformers. In addition, interactions between the gauche-oriented hydroxy groups provide large stabilization energies and the corresponding interactions in anti conformers are negligible. The relative conformational stabilities of 1,2-ethanediol and erythro-2,3-butanediol can be explained by the interactions between the antiperiplanar bond orbitals, between the vicinal bond orbitals, or between the hydroxy groups in addition to the combination of interactions between the vicinal bond orbitals and between the hydroxy groups. In contrast, in threo-2,3-butanediol, differences in the relative stabilities of the three conformers can be understood by the combination of the interactions between the vicinal bond orbitals and between the hydroxy groups.

10.
Thorac Cancer ; 8(6): 577-581, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28771961

RESUMEN

BACKGROUND: Chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non-squamous NSCLC. METHODS: The eligibility criteria were as follows: aged ≥75 with inoperable stage IIIA or IIIB non-squamous NSCLC, no history of chemotherapy or radiotherapy, a performance status of 0 or 1, and adequate organ function. The patients were scheduled to receive pemetrexed on days 1, 22, 43, and 64 with concurrent once daily thoracic radiotherapy (60 Gy). The initial pemetrexed dose was 400 (level 1), and it was planned to increase the dose to 500 mg/m2 (level 2). RESULTS: Two patients were enrolled in this trial. In the first case, the patient suffered prolonged leukocytopenia, and treatment was discontinued on day 35. In the second case, febrile neutropenia occurred on day 32, and the patient developed drug-induced pneumonitis and acute respiratory distress syndrome. Both patients experienced dose-limiting toxicities; therefore, the level 1 dose was considered to be the MTD. CONCLUSIONS: During combined treatment with pemetrexed and concurrent radiotherapy, a pemetrexed dose of 400 mg/m2 was the MTD; we did not set up a phase II study. Concurrent chemoradiotherapy might be too toxic for elderly patients aged ≥75 with locally advanced NSCLC.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Pemetrexed/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioradioterapia , Esquema de Medicación , Humanos , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Estadificación de Neoplasias , Pemetrexed/efectos adversos , Resultado del Tratamiento
11.
J Nat Prod ; 80(2): 319-327, 2017 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-28124903

RESUMEN

To elucidate the conformations and their relative stabilities of flavan-3-ols in water, the optimized structures and energies were calculated by density functional theory, in which M06-2X, ωB97X-D, B3LYP, and CAM-B3LYP were examined as exchange-correlation functionals. The results were evaluated by comparing calculated spin-spin coupling constants of vicinal protons with the corresponding values observed in experimental 1H NMR spectra in D2O. The M06-2X and ωB97X-D results showed good agreement with the experimental NMR data and revealed that the B-ring (pseudoequatorial)/3-O (pseudoaxial) conformers were more stable [5.4-8.7 kJ/mol (1.3-2.1 kcal/mol)] than the B-ring (pseudoaxial)/3-O (pseudoequatorial) conformers in the 2,3-cis-flavan-3-ols, while the B-ring (pseudoequatorial)/3-O (pseudoequatorial) conformers and the B-ring (pseudoaxial)/3-O (pseudoaxial) conformers had similar stabilities in the 2,3-trans-flavan-3-ols.


Asunto(s)
Flavonoides/química , Modelos Moleculares , Agua/química , Enlace de Hidrógeno , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Protones
12.
Crit Rev Biotechnol ; 37(2): 177-189, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26953525

RESUMEN

Although there have been approximately 60 chemical compounds identified as potent fermentation inhibitors in lignocellulose hydrolysate, our research group recently discovered glycolaldehyde as a key fermentation inhibitor during second generation biofuel production. Accordingly, we have developed a yeast S. cerevisiae strain exhibiting tolerance to glycolaldehyde. During this glycolaldehyde study, we established novel approaches for rational engineering of inhibitor-tolerant S. cerevisiae strains, including engineering redox cofactors and engineering the SUMOylation pathway. These new technical dimensions provide a novel platform for engineering S. cerevisiae strains to overcome one of the key barriers for industrialization of lignocellulosic ethanol production. As such, this review discusses novel biochemical insight of glycolaldehyde in the context of the biofuel industry.


Asunto(s)
Acetaldehído/análogos & derivados , Saccharomyces cerevisiae/efectos de los fármacos , Acetaldehído/farmacología , Acetaldehído/toxicidad , Biocombustibles , Etanol/metabolismo , Glicol de Etileno/metabolismo , Fermentación/efectos de los fármacos , Glutatión/metabolismo , Lignina/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Saccharomyces cerevisiae/metabolismo , Sumoilación
13.
Biocontrol Sci ; 21(1): 21-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27009506

RESUMEN

Povidone-iodine solutions prepared to various concentrations (0.01, 0.1, 1 and 10%) with 0.2M phosphate buffer (pH 7.0) (PVP-I PB) were analyzed to determine their free iodine concentrations using membrane permeation cells, and their inactivation effects on three viruses (influenza A virus, poliovirus type 1 and adenovirus type 3) were examined. The free iodine concentrations in the 0.01-10% PVP-I PB were determined to be 1.84, 4.88, 1.58 and 0.17 ppm (approximate values), respectively, with the maximum obtained for the 0.1% solution. The virucidal efficacy of these PVP-I PB against poliovirus type 1 and adenovirus type 3 was found to be generally dependent on free iodine concentration, with the 0.1% solution being the most effective. Influenza A virus was inactivated with an action time of 15 s at all four concentrations examined. The results of this study suggested an association between free iodine concentration and virucidal efficacy for the 0.01-10% PVP-I PB.


Asunto(s)
Antivirales/farmacología , Yodo/farmacología , Povidona Yodada/farmacología , Tampones (Química) , Yodo/química , Viabilidad Microbiana/efectos de los fármacos , Povidona Yodada/química , Virus/efectos de los fármacos
14.
J Nat Prod ; 79(1): 66-73, 2016 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-26720794

RESUMEN

Associations between catechin molecules were investigated by (1)H NMR titration experiments. Eight green tea catechins formed self-assembled dimers in water, and gallate-type catechins had a greater tendency to self-associate than non-gallate-type catechins. All eight catechins also associated as 1:1 heterodimer complexes. Investigation of complex formation of epigallocatechin-3-O-gallate (EGCg) and epigallocatechin (EGC) with the other catechins showed that the affinity between EGCg and 2,3-trans-gallate-type catechins was remarkably high, and the binding affinity of EGCg for ECg was also rather strong. In contrast, the non-gallate-type catechin EGC exhibited generally low binding affinity for other catechins. Structural analyses of the complexes by ROESY experiments and density functional theory calculations demonstrated that the higher binding abilities of gallate-type catechins are due to providing multiple intermolecular interactions that remain effective in an aqueous environment, such as aromatic/aromatic or CH/π interactions.


Asunto(s)
Catequina/análogos & derivados , Té/química , Catequina/química , Catequina/aislamiento & purificación , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Estereoisomerismo , Agua/química
15.
J Clin Neurosci ; 22(2): 320-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25443082

RESUMEN

We examined the characteristic changes in vestibular schwannoma (VS) volume after treatment with linear accelerator-based radiosurgery (LBRS) and the long-term therapeutic effects, by performing three-dimensional (3D) MRI evaluations of tumor volumes. We included 44 patients in whom tumor volume changes could be observed using 3D-spoiled gradient-echo MRI for at least 5 years. Examinations were performed every 3-4 months for the first 2 years after treatment and every 6-12 months thereafter. Enlargement or shrinkage was determined as a change of at least 20% from the volume at the time of treatment. The median observation period was 13.8 years (range, 5.5-19.5 years). The tumor control rates at 5 and 10 years after treatment and at the final MRI were 90.9%, 90.0%, and 88.6%, respectively. Tumor volume changes were categorized into the following four patterns: enlargement, five patients (11.4%); stable, three patients (6.8%); transient enlargement, 24 patients (54.5%); and direct shrinkage, 12 patients (27.3%). Bimodal peaks were observed in three of the 24 patients with transient enlargement. Tumor volume changes from 5 and 10 years post-LBRS to the final observation point were observed in 27 (64.2%) and 10 patients (33.3%), respectively. The long-term tumor volume changes observed after LBRS suggest that radiation exerts long-term effects on tumors. Furthermore, while transient enlargements in tumor volume were characteristic, true tumor enlargements should be characterized by increased volumes of more than two-fold and continued growth for at least 2 years.


Asunto(s)
Neuroma Acústico/patología , Neuroma Acústico/cirugía , Radiocirugia/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Aceleradores de Partículas , Carga Tumoral
16.
Appl Microbiol Biotechnol ; 99(1): 501-15, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25359478

RESUMEN

The complex inhibitory effects of inhibitors present in lignocellulose hydrolysate suppress the ethanol fermentation of Saccharomyces cerevisiae. Although the interactive inhibitory effects play important roles in the actual hydrolysate, few studies have investigated glycolaldehyde, the key inhibitor of hot-compressed water-treated lignocellulose hydrolysate. Given this challenge, we investigated the interactive effects of mixed fermentation inhibitors, including glycolaldehyde. First, we confirmed that glycolaldehyde was the most potent inhibitor in the hydrolysate and exerted interactive inhibitory effects in combination with major inhibitors. Next, through genome-wide analysis and megavariate data modeling, we identified SUMOylation as a novel potential mechanism to overcome the combinational inhibitory effects of fermentation inhibitors. Indeed, overall SUMOylation was increased and Pgk1, which produces an ATP molecule in glycolysis by substrate-level phosphorylation, was SUMOylated and degraded in response to glycolaldehyde. Augmenting the SUMO-dependent ubiquitin system in the ADH1-expressing strain significantly shortened the lag phase of growth, released cells from G2/M arrest, and improved energy status and glucose uptake in the inhibitor-containing medium. In summary, our study was the first to establish SUMOylation as a novel platform for regulating the lag phase caused by complex fermentation inhibitors.


Asunto(s)
Antifúngicos/metabolismo , Antifúngicos/toxicidad , Lignina/metabolismo , Lignina/toxicidad , Proteína SUMO-1/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo , Acetaldehído/análogos & derivados , Acetaldehído/metabolismo , Acetaldehído/toxicidad , Biotecnología/métodos , Ciclo Celular , Metabolismo Energético , Fermentación , Proteína SUMO-1/genética , Saccharomyces cerevisiae/genética
17.
Int J Radiat Oncol Biol Phys ; 89(3): 576-83, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24803036

RESUMEN

PURPOSE: Although radiosurgery is an accepted treatment method for intracranial arteriovenous malformations (AVMs), its long-term therapeutic effects have not been sufficiently evaluated, and many reports of long-term observations are from gamma-knife facilities. Furthermore, there are few reported results of treatment using only linear accelerator (LINAC)-based radiosurgery (LBRS). METHODS AND MATERIALS: Over a period of more than 12 years, we followed the long-term results of LBRS treatment performed in 51 AVM patients. RESULTS: The actuarial obliteration rates, after a single radiosurgery session, at 3, 5, 10, and 15 years were 46.9%, 54.0%, 64.4%, and 68.0%, respectively; when subsequent radiosurgeries were included, the rates were 46.9%, 61.3%, 74.2%, and 90.3%, respectively. Obliteration rates were significantly related to target volumes ≥4 cm(3), marginal doses ≥12 Gy, Spetzler-Martin grades (1 vs other), and AVM scores ≥1.5; multivariate analyses revealed a significant difference for target volumes ≥4 cm(3). The postprocedural actuarial symptomatic radiation injury rates, after a single radiation surgery session, at 5, 10, and 15 years were 12.3%, 16.8%, and 19.1%, respectively. Volumes ≥4 cm(3), location (lobular or other), AVM scores ≥1.5, and the number of radiosurgery were related to radiation injury incidence; multivariate analyses revealed significant differences associated with volumes ≥4 cm(3) and location (lobular or other). CONCLUSIONS: Positive results can be obtained with LBRS when performed with a target volume ≤4 cm(3), an AVM score ≤1.5, and ≥12 Gy radiation. Bleeding and radiation injuries may appear even 10 years after treatment, necessitating long-term observation.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales/cirugía , Aceleradores de Partículas , Traumatismos por Radiación/epidemiología , Radiocirugia/efectos adversos , Adolescente , Adulto , Anciano , Análisis de Varianza , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Dosis de Radiación , Radiocirugia/instrumentación , Radiocirugia/métodos , Radiocirugia/estadística & datos numéricos , Factores de Tiempo , Adulto Joven
18.
Clin Neurol Neurosurg ; 121: 10-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24793466

RESUMEN

OBJECTIVE: Cyst formation is a well-known complication following radiosurgery for arteriovenous malformations (AVMs). In this retrospective study, the authors studied predictors for AVMs using magnetic resonance imaging (MRI) to assess the mechanism of cyst formation after linac-based radiosurgery (LBRS). METHODS: From April 1993 to April 2008, LBRS was performed on 109 patients with cerebral AVMs at our institution. Six patients (5.5%) were diagnosed with cyst formation after LBRS, and 5 of them underwent regular MRI follow-up every 3-4 months for 2 years post-LBRS, and every 6-12 months thereafter. RESULTS: Time from initial LBRS until cyst formation ranged from 8 months to 10.5 years. MRI showed contrast changes at the irradiated site and its periphery within a period of 4 months to 7 years after the initial LBRS. Moreover, the emergence of a high-intensity area (HIA) was observed on T2-weighted MRI (T2W-MRI) during the same period when changes were found on contrast-enhanced imaging. The emergence of a low-intensity area on T2W-MRI was observed prior to cyst formation or expansion, which was believed to be due to a subclinical hemorrhage near the irradiated region in all patients. Histological examination of the cyst nodule revealed hemosiderin deposits and microbleeding. CONCLUSIONS: Future cyst formation was suggested by the emergence of subclinical hemorrhage (microbleeding) in an irradiated field after gadolinium-enhanced MRI showed contrast changes and T2W-MRI showed a HIA around the irradiated field. MRI follow-up should be conducted on a regular basis in such patients, even after a complete occlusion has been diagnosed.


Asunto(s)
Malformaciones Arteriovenosas/cirugía , Encéfalo/patología , Quistes/cirugía , Imagen por Resonancia Magnética , Radiocirugia , Femenino , Humanos , Masculino , Radiocirugia/métodos , Estudios Retrospectivos
19.
Appl Microbiol Biotechnol ; 97(14): 6589-600, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23744286

RESUMEN

Hot-compressed water treatment of lignocellulose liberates numerous inhibitors that prevent ethanol fermentation of yeast Saccharomyces cerevisiae. Glycolaldehyde is one of the strongest fermentation inhibitors and we developed a tolerant strain by overexpressing ADH1 encoding an NADH-dependent reductase; however, its recovery was partial. In this study, to overcome this technical barrier, redox cofactor preference of glycolaldehyde detoxification was investigated. Glycolaldehyde-reducing activity of the ADH1-overexpressing strain was NADH-dependent but not NADPH-dependent. Moreover, genes encoding components of the pentose phosphate pathway, which generates intracellular NADPH, was upregulated in response to high concentrations of glycolaldehyde. Mutants defective in pentose phosphate pathways were sensitive to glycolaldehyde. Genome-wide survey identified GRE2 encoding a NADPH-dependent reductase as the gene that confers tolerance to glycolaldehyde. Overexpression of GRE2 in addition to ADH1 further improved the tolerance to glycolaldehyde. NADPH-dependent glycolaldehyde conversion to ethylene glycol and NADP+ content of the strain overexpressing both ADH1 and GRE2 were increased at 5 mM glycolaldehyde. Expression of GRE2 was increased in response to glycolaldehyde. Carbon metabolism of the strain was rerouted from glycerol to ethanol. Thus, it was concluded that the overexpression of GRE2 together with ADH1 restores glycolaldehyde tolerance by augmenting the NADPH-dependent reduction pathway in addition to NADH-dependent reduction pathway. The redox cofactor control for detoxification of glycolaldehyde proposed in this study could influence strategies for improving the tolerance of other fermentation inhibitors.


Asunto(s)
Acetaldehído/análogos & derivados , Etanol/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Acetaldehído/metabolismo , Alcohol Deshidrogenasa/genética , Alcohol Deshidrogenasa/metabolismo , Fermentación , Microbiología Industrial , Ingeniería Metabólica , NAD/metabolismo , NADP/metabolismo , Oxidación-Reducción , Vía de Pentosa Fosfato , Saccharomyces cerevisiae/enzimología , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
20.
Neurol Med Chir (Tokyo) ; 52(12): 933-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23269054

RESUMEN

A 63-year-old woman presented with right hearing disturbance and vertigo. Magnetic resonance (MR) imaging revealed the presence of right vestibular schwannoma (VS). Stereotactic radiosurgery (SRS) was performed with a tumor marginal dose of 14 Gy using two isocenters. She was followed up clinically and neuroradiologically using three-dimensional spoiled gradient-echo MR imaging. She experienced temporal neurological deterioration due to peritumoral edema in her right cerebellar peduncle and pons for a few months beginning 1.5 years after SRS, when she experienced transient right facial dysesthesia and hearing deterioration. Ten years after SRS, the patient presented with sudden onset of vertigo, gait disturbance, diplopia, dysarthria, and nausea. MR imaging demonstrated a new lesion in the right cerebellar peduncle, which was diagnosed as radiation-induced stroke. The patient was followed up conservatively and her symptoms disappeared within a few months. Multiple delayed onset radiation injuries are possible sequelae of SRS for VS.


Asunto(s)
Cerebelo/efectos de la radiación , Neuroma Acústico/cirugía , Complicaciones Posoperatorias/diagnóstico , Traumatismos por Radiación/diagnóstico , Radiocirugia/efectos adversos , Accidente Cerebrovascular/diagnóstico , Edema Encefálico/diagnóstico , Cerebelo/irrigación sanguínea , Femenino , Estudios de Seguimiento , Humanos , Interpretación de Imagen Asistida por Computador , Imagenología Tridimensional , Imagen por Resonancia Magnética , Persona de Mediana Edad , Examen Neurológico
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