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1.
Cureus ; 14(9): e28699, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36204036

RESUMEN

Breast cancers frequently metastasize to bone. Several guidelines recommend denosumab to control metastasis. In the current case, denosumab allowed the calcification of cervicothoracic spinal metastases following bone decalcification by breast cancer. Six years after administration, denosumab was discontinued and the metastatic lesions became decalcified, but recalcification occurred after re-administration of denosumab. There were no reports of serious decalcification after discontinuation of denosumab. The patient was a 71-year-old woman who was unable to walk independently because of a fracture of the seventh cervical vertebra and severe spinal cord compression. After immobilization with a halo vest, posterior fixation was performed. Examination of the pathology of the breast and cervical spine revealed ductal carcinoma of the breast. After docetaxel for four months, tegafur-gimeracil-oteracil potassium (TS-1) was administered and monthly denosumab was initiated. CT showed postoperative recalcification of the cervicothoracic spine, and MRI revealed spinal cord decompression. The first occurrence of medication-related osteonecrosis of the jaw (MRONJ) occurred five years after cervicothoracic spinal surgery and the second occurrence of MRONJ occurred after six years. Denosumab was discontinued and TS-1 was resumed four months after discontinuation. Fourteen months after discontinuation of denosumab, the patient felt muscle weakness in the right upper extremity and numbness in both hands. CT showed cervicothoracic spine decalcification and MRI showed spinal cord compression. As there were no signs of recurrence in the primary lesion around the left breast, TS-1 was continued and denosumab was resumed. Three months after the re-administration of denosumab, CT showed recalcification and recovery of upper extremity muscle strength, and MRI revealed improvement in spinal cord compression.

2.
N Engl J Med ; 386(21): 1973-1985, 2022 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-35403841

RESUMEN

BACKGROUND: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings. METHODS: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients. RESULTS: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. CONCLUSIONS: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Nivolumab , Compuestos de Platino , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Ipilimumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Compuestos de Platino/efectos adversos , Compuestos de Platino/uso terapéutico
3.
J Cardiovasc Electrophysiol ; 30(10): 1914-1922, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31392788

RESUMEN

INTRODUCTION: Left bundle branch block (LBBB) with superior axis is common in patients with idiopathic-ventricular arrhythmia (VA) originating from the tricuspid annulus (TA) and rarely from the cardiac basal crux and mitral annulus (MA). We described the electrocardiography and electrophysiological findings of idiopathic-VA presenting with LBBB and superior axis. METHODS AND RESULTS: We described 42 idiopathic-VA patients who had an LBBB and superior axis; 15 basal crux-VA, 17 TA-VA, and 10 MA-VA. No patient had a structural heart disease. Among patients with idiopathic-VA referred for ablation, we investigated the electrocardiogram and clinical characteristics of basal crux-VA as compared with other LBBB and superior axis-VA. The left ventricular ejection fraction with MA-VA was significantly lower in comparison with basal crux-VA (P = .01). All patients had a positive R wave in lead I and aVL. The maximum deflection index with basal crux-VA was significantly higher in comparison with TA-VA or MA-VA (P = .01). Patients with basal crux-VA presented with QS wave in lead II more frequently as compared with TA-VA or MA-VA (P = .001). All MA-VA patients had Rs wave in V6, and basal crux-VA, and TA-VA patients had a monophasic R wave or Rs wave in V6. Basal crux-VA patients underwent ablation in the middle cardiac vein (MCV) or coronary sinus (success rate: 94%, recurrence rate: 6%). CONCLUSIONS: We could distinguish basal crux-VA, TA-VA, and MA-VA, using a combination of clinical and electrocardiographic findings. These findings might be useful for counseling patients about an ablation strategy. Ablation via the MCV is effective for eliminating basal crux-VA.


Asunto(s)
Potenciales de Acción , Bloqueo de Rama/diagnóstico , Seno Coronario/fisiopatología , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Frecuencia Cardíaca , Taquicardia Ventricular/diagnóstico , Adulto , Anciano , Bloqueo de Rama/fisiopatología , Ablación por Catéter , Seno Coronario/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Volumen Sistólico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/cirugía , Resultado del Tratamiento , Función Ventricular Izquierda
4.
JACC Clin Electrophysiol ; 4(7): 872-880, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30025686

RESUMEN

OBJECTIVES: This study hypothesized that early coupled ventricular extrastimuli (V2) stimulation might yield a more robust differentiation between atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT). BACKGROUND: Programmed V2 during supraventricular tachycardia are useful to differentiate AVNRT from AVRT by subtracting the ventriculoatrial (VA) interval from the stimulus to atrial depolarization (stimulus atrial [SA]) interval, but all such maneuvers have limitations. METHODS: Patients with either AVNRT or AVRT were investigated. The entire tachycardia cycle length (TCL) was scanned with V2 delivered from the right ventricular apex. The SA-VA difference was calculated with V2 clearly resetting the tachycardia. The prematurity of V2 was calculated by dividing the coupling interval (CI) by the TCL. RESULTS: A total of 210 patients (102 with AVNRT) were included. The SA-VA difference was >70 ms in all AVNRT patients and was <70 ms in all AVRT patients with right and septal accessory pathways (APs), except for those with decremental APs, in whom there was an overlap between AVNRT and AVRT with left APs. However, a SA-VA difference >110 ms with a CI/TCL of <65% distinguished AVNRT from AVRT using the left AP, with sensitivity and specificity of 87% and 100%, respectively. Ventricular overdrive pacing resulted in tachycardia termination or AV dissociation in 28% of patients compared with 15% of patients using the V2 technique (p = 0.008). CONCLUSIONS: A SA-VA of >70 ms using the V2 technique differentiated AVNRT from AVRT using septal and right APs. Use of the V2 technique with a short CI differentiated AVNRT from AVRT using left APs. The V2 technique less frequently resulted in tachycardia termination compared with ventricular entrainment.


Asunto(s)
Técnicas Electrofisiológicas Cardíacas/métodos , Sistema de Conducción Cardíaco/fisiopatología , Taquicardia por Reentrada en el Nodo Atrioventricular , Taquicardia Supraventricular , Adolescente , Adulto , Anciano , Niño , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Taquicardia por Reentrada en el Nodo Atrioventricular/clasificación , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia Supraventricular/clasificación , Taquicardia Supraventricular/diagnóstico , Adulto Joven
5.
Opt Lett ; 41(2): 289-92, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26766696

RESUMEN

We demonstrate a Si sub-bandgap photodiode in a photonic crystal slow-light waveguide that operates at telecom wavelengths and can be fabricated using a Ge-free, standard Si-photonics CMOS process. In photodiodes based on absorption via mid-bandgap states, the slow-light enhancement enables performance that is well balanced among high responsivity, low dark current, high speed, wide working spectrum, and CMOS-process compatibility, all of which are otherwise difficult to achieve simultaneously. Owing to the slow-light effect and supplemental gain at a high reverse bias, the photodiode shows a responsivity of 0.15 A/W with a low dark current of 40 nA, which is attributed to no particular processes such as ion implantation and excess exposure of the Si surface. The maximum responsivity was 0.36 A/W. The modest gain allows for sufficient frequency bandwidth to observe an eye opening at up to 30 Gb/s.

6.
Pacing Clin Electrophysiol ; 38(10): 1173-80, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26137999

RESUMEN

INTRODUCTION: There are several methods to induce ventricular fibrillation (VF) during defibrillation threshold (DFT) testing. Delivering a shock at a critical time during the T wave (T-shock) is the conventional approach, while delivering a constant direct current voltage (DC stim) from the implantable cardioverter defibrillator is an alternative method. Only a few reports compare VF induction methods. The purpose of this study was to evaluate the effects and safety of DC stim versus T-shock. METHODS: We retrospectively investigated 414 consecutive patients undergoing DFT testing. We compared the two groups (DC stim and T-shock) with respect to clinical characteristics, electrocardiogram (ECG) changes, and complications. RESULTS: Ventricular arrhythmia, including ventricular tachycardia (VT) and VF, was induced by DC stim in 93 patients or T-shock in 321 patients. No more than three attempts were performed during one procedure. There was no significant difference in the baseline ECG, induced tachycardia cycle length (TCL), or complications between the two groups. However, the induced TCL was significantly shorter than the clinical TCL regardless of induction method (P = 0.001). Five patients suffered major complications (i.e., electromechanical dissociation or incessant VT). A history of atrial fibrillation was significantly greater in patients with major complications than the others (80% vs 24%, P = 0.004), and was an independent predictor on multivariate analysis. CONCLUSIONS: There is no significant difference in induced TCL or complications between the DC stim and T-shock. The induced TCL is significantly shorter than clinical TCL regardless of induction method.


Asunto(s)
Desfibriladores Implantables/estadística & datos numéricos , Estimulación Eléctrica/métodos , Técnicas Electrofisiológicas Cardíacas/estadística & datos numéricos , Disfunción Ventricular Izquierda/epidemiología , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/prevención & control , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Umbral Diferencial , Estimulación Eléctrica/efectos adversos , Técnicas Electrofisiológicas Cardíacas/efectos adversos , Técnicas Electrofisiológicas Cardíacas/métodos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , San Francisco/epidemiología , Distribución por Sexo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/etiología , Fibrilación Ventricular/epidemiología
7.
Neurosci Lett ; 583: 194-8, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25281790

RESUMEN

The role of the serotonergic system in regulating the expression of estrogen receptor (ER) α in the hypothalamus was investigated in ovariectomized rats by injecting a serotonin synthesis inhibitor, parachlorophenylalanine (PCPA), or by destroying the dorsal raphe nucleus (DR). The number of ERα-immunoreactive (ir) cells was counted in the anteroventral periventricular nucleus in the preoptic area (AVPV), ventrolateral ventromedial hypothalamic nucleus (vlVMN), and arcuate nucleus (ARCN). Seven days after ovariectomy, 100mg/kg PCPA or saline was injected daily for 4 days. Alternatively, radiofrequency lesioning of the DR (DRL) or sham lesions were made on the same time of ovariectomy. One-day after the last injection of PCPA or 7 days after brain surgery, the brain was fixed for immunostaining of ERα and the number of ERα-ir cell were counted in the nuclei of interest. The mean number of ERα-ir cells/mm(3) (density) in the AVPV of the PCPA or DRL groups was statistically higher than that in the saline or sham group. In the vlVMN and ARCN of the PCPA or DRL groups, the mean density of ERα-ir cells was comparable to the saline or sham groups. These results suggest that the serotonergic system of the DR plays an inhibitory role on the expression of ERα in the AVPV, but not in the vlVMN and ARCN.


Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Fenclonina/farmacología , Hipotálamo/metabolismo , Antagonistas de la Serotonina/farmacología , Animales , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Núcleo Dorsal del Rafe/fisiología , Femenino , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Hipotálamo Anterior/citología , Hipotálamo Anterior/efectos de los fármacos , Hipotálamo Anterior/metabolismo , Ovariectomía , Área Preóptica/citología , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Ratas Wistar , Núcleo Hipotalámico Ventromedial/citología , Núcleo Hipotalámico Ventromedial/efectos de los fármacos , Núcleo Hipotalámico Ventromedial/metabolismo
8.
Biosci Biotechnol Biochem ; 77(9): 1854-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24018661

RESUMEN

The higher plant ADP-glucose (ADPG) pyrophosphorylase (AGPase), composed of two small subunits and two large subunits (LSs), produces ADPG, the sole substrate for starch biosynthesis from α-D-glucose 1-phosphate and ATP. This enzyme controls a key step in starch synthesis as its catalytic activity is activated by 3-phosphoglycerate (3-PGA) and inhibited by orthophosphate (Pi). Previously, two mutations in the LS of potato AGPase (PLS), PLS-E38K and PLS-G101N, were found to increase sensitivity to 3-PGA activation and tolerance to Pi inhibition. In the present study, the double mutated enzyme (PLS-E38K/G101N) was evaluated. In a complementation assay of ADPG synthesis in an Escherichia coli mutant defective in the synthesis of ADPG, expression of PLS-E38K/G101N mediated higher glycogen production than wild-type potato AGPase (PLS-WT) and the single mutant enzymes, PLS-E38K and PLS-G101N, individually. Purified PLS-E38K/G101N showed higher sensitivity to 3-PGA activation and tolerance to Pi inhibition than PLS-E38K or PLS-G101N. Moreover, the enzyme activities of PLS-E38K, PLS-G101N, and PLS-E38K/G101N were more readily stimulated by other major phosphate-ester metabolites, such as fructose 6-phosphate, fructose 2,6-bisphosphate, and ribose 5-phosphate, than was that of PLS-WT. Hence, although the specific enzyme activities of the LS mutants toward 3-PGA were impaired to some extent by the mutations, our results suggest that their enhanced allosteric regulatory properties and the broadened effector selectivity gained by the same mutations not only offset the lowered enzyme catalytic turnover rates but also increase the net performance of potato AGPase in vivo in view of increased glycogen production in bacterial cells.


Asunto(s)
Glucosa-1-Fosfato Adenililtransferasa/química , Glucosa-1-Fosfato Adenililtransferasa/metabolismo , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutación , Tubérculos de la Planta/enzimología , Solanum tuberosum/enzimología , Regulación Alostérica/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucosa-1-Fosfato Adenililtransferasa/genética , Ácidos Glicéricos/farmacología , Cinética , Modelos Moleculares , Proteínas Mutantes/genética , Multimerización de Proteína , Estructura Cuaternaria de Proteína
10.
Jpn J Radiol ; 29(8): 570-5, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21927999

RESUMEN

PURPOSE: Cisplatin has shown a high tumor response rate among head and neck carcinomas, and the tumor response is related to the cisplatin dosage. The purpose of this study was to evaluate the efficacy and toxicity of selective intraarterial chemoradiation therapy for oropharyngeal carcinomas with high-dose cisplatin. MATERIALS AND METHODS: This retrospective study consisted of 21 patients with oropharyngeal carcinoma, stages II-IVB, in whom intraarterial chemoradiation therapy was performed between 2000 and 2008. All patients were given two courses of selective intraarterial infusions of cisplatin (300 mg/m(2)), systemic chemotherapy with 5-fluorouracil, and simultaneous radiation therapy (58-61 Gy/30 fractions), with a 1-week rest period. RESULTS: The 2-year overall survival rate of the 15 patients who completed the therapeutic regimen was 71.3%. The 2-year locoregional control rate and disease-free survival rate were 95.0% and 67.7%, respectively. CONCLUSION: Selective intraarterial high-dose cisplatin chemotherapy with concomitant radiation therapy shows results similar to those of original methods in terms of survival and locoregional control with a reduction in the number of procedure times.


Asunto(s)
Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/radioterapia , Adulto , Anciano , Angiografía , Terapia Combinada , Medios de Contraste , Fraccionamiento de la Dosis de Radiación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intraarteriales , Yohexol , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/diagnóstico por imagen , Neoplasias Orofaríngeas/patología , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X
11.
Biosci Biotechnol Biochem ; 75(9): 1740-5, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21897044

RESUMEN

Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the transfer of the γ-phosphoryl group from a nucleoside triphosphate to a nucleoside diphosphate. In this study, we examined the subcellular localization, tissue-specific gene expression, and enzymatic characteristics of three rice NDPK isozymes (OsNDPK1-OsNDPK3). Sequence comparison of the three OsNDPKs suggested differential subcellular localization. Transient expression of green fluorescence protein-fused proteins in onion cells indicated that OsNDPK2 and OsNDPK3 are localized to plastid and mitochondria respectively, while OsNDPK1 is localized to the cytosol. Expression analysis indicated that all the OsNDPKs are expressed in the leaf, leaf sheath, and immature seeds, except for OsNDPK1, in the leaf sheath. Recombinant OsNDPK2 and OsNDPK3 showed lower optimum pH and higher stability under acidic pH than OsNDPK1. In ATP formation, all the OsNDPKs displayed lower K(m) values for the second substrate, ADP, than for the first substrate, NTP, and showed lowest and highest K(m) values for GTP and CTP respectively.


Asunto(s)
Proteínas Fluorescentes Verdes/metabolismo , Isoenzimas/metabolismo , Nucleósido-Difosfato Quinasa/metabolismo , Cebollas/enzimología , Oryza/enzimología , Proteínas Recombinantes de Fusión/metabolismo , Adenosina Difosfato/metabolismo , Clonación Molecular , Citosol/enzimología , Estabilidad de Enzimas , Escherichia coli , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/genética , Concentración de Iones de Hidrógeno , Isoenzimas/química , Isoenzimas/genética , Cinética , Microscopía Fluorescente , Mitocondrias/enzimología , Nucleósido-Difosfato Quinasa/química , Nucleósido-Difosfato Quinasa/genética , Cebollas/citología , Cebollas/genética , Oryza/genética , Hojas de la Planta/enzimología , Plásmidos , Plastidios/enzimología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Semillas/enzimología , Especificidad por Sustrato , Transformación Bacteriana
12.
J Nutr ; 140(12): 2121-7, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20943955

RESUMEN

We investigated whether feeding a purified compared with nonpurified diet supplemented with or without fructo-oligosaccharide (FOS; 50 g/kg diet) altered the response of C57BL/6 mice to DSS-induced diarrhea. In Expt. 1, we examined disease severity in mice receiving DSS (2% in drinking water) for 5 d. In Expt. 2, we measured cecal organic acid concentrations and fecal water-holding capacity (WHC). In Expts. 3 and 4, we tested whether polycarbophil calcium (PC), a water-absorbing polymer, altered fecal WHC and disease severity. FOS exacerbated diarrhea and weight loss in mice fed the purified diet and reduced fecal bleeding in mice fed the nonpurified diet (P < 0.05). Without DSS administration, cecal acetate and butyrate concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). Fecal WHC was higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). One day after starting DSS administration, cecal succinate concentrations were higher in mice fed the FOS-supplemented purified diet than in mice fed the other 3 diets, whereas SCFA concentrations were higher in mice fed the nonpurified diet than in mice fed the purified diet (P < 0.05). PC supplementation increased fecal WHC and prevented FOS exacerbation of diarrhea in mice fed the purified diet (P < 0.05). We conclude that the effects of FOS on DSS-induced diarrhea differ in mice fed the purified and nonpurified diets. The protective effect of nonpurified diet was associated with increased production of organic acids and WHC in the intestinal contents.


Asunto(s)
Colitis/inducido químicamente , Dieta , Carbohidratos de la Dieta/administración & dosificación , Oligosacáridos/administración & dosificación , Animales , Femenino , Ratones , Ratones Endogámicos C57BL
13.
J Nutr ; 140(11): 1963-9, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20826633

RESUMEN

We tested whether a high-fat diet (HFD) impairs the survival of probiotics in mice. In Expt. 1, after feeding either a HFD (62.7% energy) or a normal-fat diet (NFD; 11.1% energy) for 2 d, C57BL/6 mice were i.g. administered Lactobacillus plantarum No. 14. Fecal recovery of viable L. plantarum was significantly decreased 99% by the HFD compared with the NFD. Total bile acid concentrations in the small intestine and cecum were significantly higher (1.5- and 2.2-fold of NFD, respectively) in mice fed HFD than in those fed NFD. Cholic acid and deoxycholic acid significantly reduced the viability of L. plantarum No. 14 in culture experiments. In Expt. 2, after feeding HFD for 2 d, simultaneous administration of inulin (10 mg) with L. plantarum No. 14 significantly increased (100-fold of that without inulin) the fecal recovery of viable L. plantarum. Inulin administration did not alter intestinal bile acid concentrations. In Expt. 3, after feeding HFD for 2 d, mice were i.g. administered either inulin (10 mg) or vehicle and, after 6 h, cecal contents were subjected to culture experiments. Growth of L. plantarum No. 14 was significantly higher in the cecal contents of inulin-administered mice than vehicle-administered mice. Inulin supplementation to cecal contents of vehicle-administered mice significantly enhanced the growth of L. plantarum No. 14. We propose that HFD impairs the survival of probiotics in the gut due to increased bile acid stress and that simultaneous administration of inulin prolongs the survival of probiotics in mice fed HFD.


Asunto(s)
Grasas de la Dieta/efectos adversos , Inulina/administración & dosificación , Lactobacillus plantarum/crecimiento & desarrollo , Viabilidad Microbiana , Probióticos/administración & dosificación , Animales , Antibacterianos/análisis , Antibacterianos/farmacología , Ácidos y Sales Biliares/análisis , Ciego/microbiología , Ácido Cólico/análisis , Ácido Cólico/farmacología , Recuento de Colonia Microbiana , Ácido Desoxicólico/análisis , Ácido Desoxicólico/farmacología , Heces/microbiología , Femenino , Contenido Digestivo/química , Contenido Digestivo/microbiología , Intestino Delgado/microbiología , Inulina/metabolismo , Lactobacillus/genética , Lactobacillus/crecimiento & desarrollo , Lactobacillus/aislamiento & purificación , Lactobacillus plantarum/efectos de los fármacos , Lactobacillus plantarum/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL , Concentración Osmolar , Probióticos/metabolismo , Factores de Tiempo
14.
Phytochemistry ; 71(11-12): 1280-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20570296

RESUMEN

Tuberonic acid (TA) and its glucoside (TAG) have been isolated from potato (Solanum tuberosum L.) leaflets and shown to exhibit tuber-inducing properties. These compounds were reported to be biosynthesized from jasmonic acid (JA) by hydroxylation and subsequent glycosylation, and to be contained in various plant species. Here we describe the in vivo hydrolytic activity of TAG in rice. In this study, the TA resulting from TAG was not converted into JA. Tuberonic acid glucoside (TAG)-hydrolyzing beta-glucosidase, designated OsTAGG1, was purified from rice by six purification steps with an approximately 4300-fold purification. The purified enzyme migrated as a single band on native PAGE, but as two bands with molecular masses of 42 and 26 kDa on SDS-PAGE. Results from N-terminal sequencing and peptide mass fingerprinting of both polypeptides suggested that both bands were derived from a single polypeptide, which is a member of the glycosyl hydrolase family 1. In the native enzyme, the K(m) and V(max) values of TAG were 31.7 microM and 0.25 microkatal/mg protein, OsTAGG1 preferentially hydrolyzed TAG and methyl TAG. Here we report that OsTAGG1 is a specific beta-glucosidase hydrolyzing TAG, which releases the physiologically active TA.


Asunto(s)
Acetatos/aislamiento & purificación , Ciclopentanos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Oryza/enzimología , Solanum tuberosum/química , beta-Glucosidasa/metabolismo , Acetatos/química , Acetatos/metabolismo , Ciclopentanos/química , Ciclopentanos/metabolismo , Electroforesis en Gel de Poliacrilamida , Glucósidos/genética , Glicosilación , Hidrólisis , Estructura Molecular , Oryza/metabolismo , Oxilipinas , Mapeo Peptídico , Hojas de la Planta/química , Tubérculos de la Planta/efectos de los fármacos , Plantas/química , beta-Glucosidasa/química , beta-Glucosidasa/aislamiento & purificación
15.
Neurosci Res ; 67(1): 33-9, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20144667

RESUMEN

To determine sex and regional differences in the properties of serotonin (5-HT) neurons of the raphe nuclei, the responsiveness to parachlorophenylalanine (PCPA) of 5-HT neurons in the dorsal and median raphe nuclei (DR and MR) and the nucleus raphe magnus (RMg) was analyzed by counting 5-HT-immunoreactive (5-HT-ir) cells. Gonadectomized male (OCX) and female (OVX) rats were treated with 100mg/kg b.wt PCPA or saline daily for 4 days. The brains were removed and fixed one day after the last injection. Frozen sections were stained with serotonin antibody and the numbers of 5-HT-ir cells in the raphe nuclei were counted. As a result, in female rats, the densities of 5-HT-ir cells in these 3 raphe nuclei were almost the same when compared the PCPA-treated and saline-treated groups. On the other hand, in male rats, the densities of 5-HT-ir cells in the DR and MR of PCPA-treated rats were lower than in saline-treated rats. In the male RMg, no difference was seen. These results suggest that responsiveness of 5-HT neurons to PCPA in the DR and MR, but not in the RMg, were sexually dimorphic.


Asunto(s)
Fenclonina/farmacología , Núcleos del Rafe/efectos de los fármacos , Serotonina/metabolismo , Animales , Femenino , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/ultraestructura , Inmunohistoquímica , Masculino , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/metabolismo , Orquiectomía , Especificidad de Órganos , Ovariectomía , Núcleos del Rafe/citología , Núcleos del Rafe/metabolismo , Ratas , Ratas Wistar , Factores Sexuales
16.
Pharmacology ; 84(4): 227-33, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19752586

RESUMEN

Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 microg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.


Asunto(s)
Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Tránsito Gastrointestinal/efectos de los fármacos , Aceites de Plantas/uso terapéutico , Animales , Atropina/farmacología , Clonidina , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Indoles/farmacología , Loperamida , Masculino , Ratones , Ratones Endogámicos , Planta de la Mostaza , Naloxona/farmacología , Canal Catiónico TRPA1 , Canales de Potencial de Receptor Transitorio/agonistas , Yohimbina/farmacología
17.
Neurosci Lett ; 463(2): 135-9, 2009 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-19646508

RESUMEN

Sensitivity of neurons to estrogen in down-regulation of estrogen receptor alpha (ERalpha) can be thought to make a sex difference in regulatory system of reproductive activities. In this study, to investigate the sex difference of expression of ERalpha in the hypothalamus and midbrain, the number of ERalpha immunoreactive (-ir) cells was counted in orchidectomized (OCX) and ovariectomized (OVX) rats with or without treatment with estrogen. A week after the gonadectomy, 5 rats in each female and male were injected with 1mg estradiol benzoate (EB). The remaining 5 rats in both sexes did not receive EB. The brain was fixed 24h after EB-injection and 50 microm-serial frozen sections were made. After immunohistochemical staining for ERalpha, the number of ERalpha-ir cells was counted in a 0.2-mm2 frame in the anteroventral periventricular nucleus (AVPvN), the ventrolateral part of the ventromedial hypothalamic nucleus (vlVMN), the arcuate nucleus (ARCN), and the lateral mesencephalic central gray (lMCG) in 2 or 3 sections. The total number of ERalpha-ir cells was changed to a density value (number per 1mm3). As the results, in EB-treated rats, the density of ERalpha-ir cells in all regions, except the male AVPvN and male lMCG, were lower than those in untreated rats of both sexes. In the vlVMN, the density of ERalpha-ir cells in OVX rats was higher than in OCX rats. These results suggest that there are sex and regional differences in the mechanisms of down-regulation of ERalpha by estrogen in the rat brain.


Asunto(s)
Estradiol/análogos & derivados , Receptor alfa de Estrógeno/biosíntesis , Estrógenos/farmacología , Hipotálamo/efectos de los fármacos , Mesencéfalo/efectos de los fármacos , Animales , Estradiol/farmacología , Femenino , Hipotálamo/anatomía & histología , Hipotálamo/metabolismo , Inmunohistoquímica , Masculino , Mesencéfalo/anatomía & histología , Mesencéfalo/metabolismo , Orquiectomía , Ovariectomía , Ratas , Ratas Wistar , Factores Sexuales
18.
J Nutr ; 139(9): 1640-7, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19605529

RESUMEN

We examined the role of soluble fiber viscosity in small intestinal mucin secretion. Viscosities were defined as the area under the viscosity curve (VAUC). Rats were fed a control diet or diets containing konjac mannan (KM) [low, medium, or high molecular weight (LKM, MKM, HKM), respectively] at 50 g/kg diet for 10 d. Luminal mucin content and goblet cell number increased in proportion to the molecular weight of KM. Such effects with the HKM diet were nullified by the concurrent ingestion of 2 g cellulase/kg diet. Diet containing LKM, MKM, HKM, guar gums (high or low molecular weight; HGG, LGG), psyllium (PS), or pectin (PC) at 50 g/kg was fed to rats. Fibers with higher VAUC (MKM, HKM, HGG, and PS) increased goblet cell numbers, but not those with lower VAUC (LKM, LGG, and PC). Luminal mucins were greater in rats fed HKM, PC, and PS diets. Goblet cell numbers and VAUC were correlated (r = 0.98; P < 0.01). In rats fed the HKM diet, ileal Muc2 gene expression was not affected, but that of Muc3 was lower than in those fed the control diet, indicating that the increase in luminal mucins after ingestion of HKM diet occurred independently of enhanced Muc gene expression. An incorporation study of 5'-bromo-deoxyuridine (BrdU) showed the position of the uppermost-BrdU labeled cell along the villi was higher in rats fed the HKM diet than in those fed the control diet. The results suggest that soluble fibers, except PC, upregulate baseline secretion of luminal mucins by increasing goblet cell numbers in proportion to fiber VAUC.


Asunto(s)
Carbohidratos de la Dieta/farmacología , Fibras de la Dieta/farmacología , Expresión Génica/efectos de los fármacos , Células Caliciformes/efectos de los fármacos , Íleon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucinas/metabolismo , Amorphophallus , Animales , Bromodesoxiuridina/metabolismo , Celulasa/farmacología , Dieta , Células Epiteliales/efectos de los fármacos , Galactanos/farmacología , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Mananos/farmacología , Mucina 3/genética , Mucina 3/metabolismo , Mucinas/genética , Pectinas/farmacología , Gomas de Plantas/farmacología , Poliestirenos/farmacología , Psyllium/farmacología , Ratas , Ratas Wistar , Solubilidad , Viscosidad
19.
Phytochemistry ; 70(3): 370-9, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19233441

RESUMEN

Tuberonic acid (12-hydroxy epi-jasmonic acid, TA) and its glucoside (TAG) were isolated from potato leaflets (Solanumtuberosum L.) and shown to have tuber-inducing properties. The metabolism of jasmonic acid (JA) to TAG in plant leaflets, and translocation of the resulting TAG to the distal parts, was demonstrated in a previous study. It is thought that TAG generated from JA transmits a signal from the damaged parts to the undamaged parts by this mechanism. In this report, the metabolism of TA in higher plants was demonstrated using [12-(3)H]TA, and a glucosyltransferase active toward TA was purified from the rice cell cultures. The purified protein was shown to be a putative salicylic acid (SA) glucosyltransferase (OsSGT) by MALDI-TOF-MS analysis. Recombinant OsSGT obtained by overexpression in Escherichia coli was active not only toward TA but also toward SA. The OsSGT characterized in this research was not specific, but this is the first report of a glucosyltransferase active toward TA. mRNA expressional analysis of OsSGT and quantification of TA, TAG, SA and SAG after mechanical wounding indicated that OsSGT is involved in the wounding response. These results demonstrated a crucial role for TAG not only in potato tuber formation, but also in the stress response in plants and that the SA glucosyltransferase can work for TA glucosylation.


Asunto(s)
Acetatos/metabolismo , Ciclopentanos/metabolismo , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismo , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Acetatos/química , Línea Celular , Clonación Molecular , Ciclopentanos/química , ADN Complementario , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Glucósidos/química , Glucósidos/metabolismo , Estructura Molecular , Oryza/enzimología , Oryza/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Salicilatos/metabolismo , Solanum tuberosum/enzimología , Solanum tuberosum/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
20.
J Interv Card Electrophysiol ; 8(3): 203-8, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12815306

RESUMEN

A 52-years old man with a previous pericardiotomy for idiopathic constrictive pericarditis underwent catheter ablation for drug-resistant atrial tachycardia (AT). The mechanism of the AT was considered as reentry because of resetting response and the entrainment phenomenon during AT. We introduced a 64-electrode basket catheter into the superior vena cava (SVC) during AT to obtain precise mapping. A fractionated potential preceding local atrial electrogram was recorded in the SVC. The earliest activation site of the potential was located at the anterior aspect of the SVC, 2 cm above the SVC-right atrium junction determined fluoroscopically. The fractionated potential at this site preceded the onset of the P wave by 115 msec. Radiofrequency catheter ablation at this site eliminated the tachycardia. At 6 months follow-up, the patient is free of AT. Reentrant AT involving the SVC is a candidate of RF ablation. Multielectrode basket catheter is useful for a detailed mapping of the SVC.


Asunto(s)
Taquicardia Atrial Ectópica/diagnóstico , Vena Cava Superior , Ablación por Catéter , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas/métodos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Taquicardia Atrial Ectópica/etiología , Taquicardia Atrial Ectópica/cirugía , Resultado del Tratamiento , Vena Cava Superior/fisiopatología
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