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1.
Data Brief ; 48: 109105, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37095754

RESUMEN

The data presented in this article are related to the research paper entitled "Observation of night-time emissions of the Earth in the near UV range from the International Space Station with the Mini-EUSO detector" (Remote Sensing of Environment, Volume 284, January 2023, 113336, https://doi.org/10.1016/j.rse.2022.113336). The data have been acquired with the Mini-EUSO detector, an UV telescope operating in the range 290-430 nm and located inside the International Space Station. The detector was launched in August 2019, and it has started operations from the nadir-facing UV-transparent window in the Russian Zvezda module in October 2019. The data presented here refer to 32 sessions acquired between 2019-11-19 and 2021-05-06. The instrument consists of a Fresnel-lens optical system and a focal surface composed of 36 multi-anode photomultiplier tubes, each with 64 channels, for a total of 2304 channels with single photon counting sensitivity. The telescope, with a square field-of-view of 44°, has a spatial resolution on the Earth surface of 6.3 km and saves triggered transient phenomena with a temporal resolution of 2.5 µs and 320 µs. The telescope also operates in continuous acquisition at a 40.96 ms scale. In this article, large-area night-time UV maps obtained processing the 40.96 ms data, taking averages over regions of some specific geographical areas (e.g., Europe, North America) and over the entire globe, are presented. Data are binned into 0.1° × 0.1° or 0.05° × 0.05° cells (depending on the scale of the map) over the Earth's surface. Raw data are made available in the form of tables (latitude, longitude, counts) and .kmz files (containing the .png images). These are - to the best of our knowledge - the highest sensitivity data in this wavelength range and can be of use to various disciplines.

2.
Ann Oncol ; 32(11): 1434-1441, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34391895

RESUMEN

BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.


Asunto(s)
Neoplasias del Colon , Estudio de Asociación del Genoma Completo , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adyuvante , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Fluorouracilo/uso terapéutico , Humanos , Recurrencia Local de Neoplasia , Oxaliplatino/efectos adversos , Estudios Prospectivos
3.
Ann Oncol ; 30(2): 259-265, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30508156

RESUMEN

BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Cetuximab/administración & dosificación , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Piridinas/administración & dosificación , Tasa de Supervivencia
4.
Ann Oncol ; 29(6): 1461-1467, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32151367

RESUMEN

BACKGROUND: The efficacy and safety of naldemedine (a peripherally acting µ-opioid receptor antagonist) for opioid-induced constipation (OIC) in subjects with cancer was demonstrated in the primary report of a phase III, double-blind study (COMPOSE-4) and its open-label extension (COMPOSE-5). The primary end point, the proportion of spontaneous bowel movement (SBM) responders, was met. Here, we report results from secondary end points, including quality of life (QOL) assessments from these studies. PATIENTS AND METHODS: In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 97) or placebo (n = 96) for 2 weeks, and those who continued on to COMPOSE-5 received naldemedine for 12 weeks (n = 131). Secondary assessments in COMPOSE-4 included the proportion of complete SBM (CSBM) responders, SBM or CSBM responders by week, and subjects with ≥1 SBM or CSBM within 24 h postinitial dose. Changes from baseline in the frequency of SBMs or CSBMs per week were assessed at weeks 1 and 2. Time to the first SBM or CSBM postinitial dose was also evaluated. In both studies, QOL impact was evaluated by Patient Assessment of Constipation-Symptoms (PAC-SYM) and PAC-QOL questionnaires. RESULTS: Naldemedine improved bowel function for all secondary efficacy assessments versus placebo (all P ≤ 0.0002). The timely onset of naldemedine activity versus placebo was evidenced by median time to the first SBM (4.7 h versus 26.6 h) and CSBM (24.0 h versus 218.5 h) postinitial dose (all P < 0.0001). In COMPOSE-4, significant differences between groups were observed with the PAC-SYM stool domain (P = 0.045) and PAC-QOL dissatisfaction domain (P = 0.015). In COMPOSE-5, significant improvements from baseline were observed for overall and individual domain scores of PAC-SYM and PAC-QOL. CONCLUSIONS: Naldemedine provided effective and timely symptomatic relief from OIC and improved the QOL of subjects with OIC and cancer. TRIAL REGISTRATION ID: www.ClinicalTrials.jp: JAPIC-CTI-132340 (COMPOSE-4) and JAPIC-CTI-132342 (COMPOSE-5).

5.
Ann Oncol ; 27(8): 1539-46, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27177863

RESUMEN

BACKGROUND: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. PATIENTS AND METHODS: WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396. RESULTS: Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months. CONCLUSION: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. CLINICAL TRIALS NUMBER: UMIN000001396.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Japón , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Modelos de Riesgos Proporcionales , Resultado del Tratamiento
6.
Ann Oncol ; 27(6): 1143-1148, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27069012

RESUMEN

BACKGROUND: Peripheral sensory neuropathy (PSN) is a dose-limiting toxicity of oxaliplatin-based chemotherapy. Several genetic markers have been shown to predict oxaliplatin-induced PSN; however, results remain to be validated in a large-scale and prospective pharmacogenomics study. PATIENTS AND METHODS: Among 882 patients enrolled in the JFMC41-1001-C2 (JOIN trial), which was designed to investigate the tolerability of adjuvant-modified FOLFOX6 (mFOLFOX6) in Japanese Patients with stage II or III colon cancers undergoing curative resection, 465 patients were eligible for this pharmacogenomics analysis. Twelve single-nucleotide polymorphisms (SNPs) were selected based on published data. The effect of each genotype on time to PSN onset was evaluated in all patients (n = 465) using the Cox proportional hazard model. For the association analysis between severity of PSN and 12 SNP markers, 84 patients who failed to complete 12 cycles of mFOLFOX6 from grade 0/1 PSN group were excluded because the termination of the protocol treatment had been caused by reasons other than PSN. RESULTS: Comparison of grade 0/1 PSN with grade 2/3 PSN or grade 3 PSN showed no significant associations with any of the 12 SNP markers after adjustment for total dose of oxaliplatin. Time-to-onset analysis also failed to reveal any significant differences. CONCLUSIONS: Our large-scale and prospective pharmacogenomics study of Japanese patients receiving protocol treatment of adjuvant mFOLFOX6 could not verify a role for any of the 12 SNP markers reported as being significantly associated with PSN. Considering the OR observed in this study (range: 0.76-1.89), further evaluation of these 12 SNP markers in the context of L-OHP-induced PSN is unlikely to be clinically informative.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Colon/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/genética , Farmacogenética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante/efectos adversos , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Femenino , Fluorouracilo/efectos adversos , Humanos , Japón , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , Polimorfismo de Nucleótido Simple/genética
7.
Ann Oncol ; 26(10): 2097-101, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26216386

RESUMEN

BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS: Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Cisplatino/administración & dosificación , Esquema de Medicación , Combinación de Medicamentos , Estudios de Seguimiento , Humanos , Metástasis Linfática , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Tegafur/administración & dosificación
8.
Br J Cancer ; 112(10): 1709-16, 2015 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-25880011

RESUMEN

BACKGROUND: In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle. METHODS: Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350). RESULTS: The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70). CONCLUSIONS: Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan.


Asunto(s)
Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neutropenia/inducido químicamente , Neutropenia/genética , Nomogramas , Anciano , Alelos , Pueblo Asiatico/genética , Bilirrubina/metabolismo , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Glucuronosiltransferasa/genética , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Neutropenia/metabolismo , Neutropenia/patología , Neutrófilos/metabolismo , Neutrófilos/patología , Estudios Prospectivos
9.
Chemistry ; 20(50): 16583-9, 2014 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-25327871

RESUMEN

We investigated the luminescence properties and color tuning of [Pt(dpb)Cl] (dpbH=1,3-di(2-pyridyl)benzene) and its analogues. An almost blue emission was obtained for the complex [Pt(Fmdpb)CN] (FmdpbH=4-fluoro-1,3-di(4-methyl-2-pyridyl)benzene), modified by the introduction of F and CH3 groups to the dpb ligand and the substitution of Cl by CN. As the concentration of the solution was increased, the color of the emission varied from blue to white to orange. The color change resulted from a monomer-excimer equilibrium in the excited state. A broad emission spectrum around 620 nm was clearly detected along with a structured monomer emission around 500 nm. Upon further increases in concentration, another broad peak appeared in the longer wavelength region of the spectrum. We assigned the near-infrared band to the emission from an excited trimer generated by the reaction of the excimer with the ground-state monomer. The emission lifetimes of the monomer, dimer, and trimer were evaluated as τM =12.8 µs, τD =2.13 µs, and τT =0.68 µs, respectively, which were sufficiently long to allow association with another Pt(II) complex and dissociation into a lower order aggregate. Based on equilibrium constants determined from a kinetic study, the formation of the excimer and the excited trimer were concluded to be exothermic processes, with ΔG*D =-24.5 kJ mol(-1) and ΔG*T =-20.4 kJ mol(-1) respectively, at 300 K.

10.
Genet Mol Res ; 13(3): 6272-86, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25158254

RESUMEN

Abscisic acid-responsive element binding protein (AREB1) is a basic domain/leucine zipper transcription factor that binds to the abscisic acid (ABA)-responsive element motif in the promoter region of ABA-inducible genes. Because AREB1 is not sufficient to direct the expression of downstream genes under non-stress conditions, an activated form of AREB1 (AREB1ΔQT) was created. Several reports claim that plants overexpressing AREB1 or AREB1ΔQT show improved drought tolerance. In our studies, soybean plants overexpressing AREB1ΔQT were characterized molecularly, and the phenotype and drought response of three lines were accessed under greenhouse conditions. Under conditions of water deficit, the transformed plants presented a higher survival rate (100%) than those of their isoline, cultivar BR 16 (40%). Moreover, the transformed plants displayed better water use efficiency and had a higher number of leaves than their isoline. Because the transgenic plants had higher stomatal conductance than its isoline under well-watered conditions, it was suggested that the enhanced drought response of AREB1ΔQT soybean plants might not be associated with altered transpiration rates mediated by ABA-dependent stomatal closure. However, it is possible that the smaller leaf area of the transgenic plants reduced their transpiration and water use, causing delayed stress onset. The difference in the degree of wilting and percentage of survival between the 35S-AREB1ΔQT and wildtype plants may also be related to the regulation of genes that protect against dehydration because metabolic impairment of photosynthesis, deduced by an increasing internal CO2 concentration, was not observed in the transgenic plants.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Regulación de la Expresión Génica de las Plantas , Glycine max/genética , Hojas de la Planta/genética , Agua/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Sequías , Hojas de la Planta/metabolismo , Plantas Modificadas Genéticamente , Elementos de Respuesta , Glycine max/metabolismo , Transgenes
11.
J Clin Pharm Ther ; 39(2): 181-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24405193

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Itraconazole, a CYP3A inhibitor, is used for the treatment for onychomycosis with a three-cycle pulse therapy over 3 months, but its effects on in vivo CYP3A activity during the entire course remain unknown. METHODS: Urinary 6ß-hydroxycortisol/cortisol ratios were determined in 19 patients with onychomycosis, before therapy, during three cycles of itraconazole pulse therapy (200 mg twice daily for a week in each monthly cycle) and at 3 month after completion of therapy. RESULTS AND DISCUSSION: The mean 6ß-hydroxycortisol/cortisol ratio was reduced by 68% from baseline (P < 0·05) after the 1st pulse dosing, but the inhibitory effect appeared to be resolved before the next pulse dosing and at 3 months post-treatment. The magnitude of inhibition appeared in proportion to the baseline CYP3A activity. WHAT IS NEW AND CONCLUSION: The inhibitory effect of itraconazole pulse therapy on the in vivo CYP3A activity appears clinically relevant at the end of each cycle, but the inhibition resolves, on average, within 3 weeks.


Asunto(s)
Antifúngicos/uso terapéutico , Inhibidores del Citocromo P-450 CYP3A , Itraconazol/uso terapéutico , Onicomicosis/tratamiento farmacológico , Adulto , Anciano , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Monitoreo de Drogas/métodos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/orina , Itraconazol/administración & dosificación , Itraconazol/farmacología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Quimioterapia por Pulso , Factores de Tiempo , Resultado del Tratamiento
12.
Genet Mol Res ; 10(4): 3641-56, 2011 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-22033903

RESUMEN

We evaluated the molecular, anatomical and physiological properties of a soybean line transformed to improve drought tolerance with an rd29A:AtDREB1A construct. This construct expressed dehydration- responsive element binding protein DREB1A from the stress-inducible rd29A promoter. The greenhouse growth test included four randomized blocks of soybean plants, with each treatment performed in triplicate. Seeds from the non-transformed soybean cultivar BR16 and from the genetically modified soybean P58 line (T(2) generation) were grown at 15% gravimetric humidity for 31 days. To induce water deficit, the humidity was reduced to 5% gravimetric humidity (moderate stress) for 29 days and then to 2.5% gravimetric humidity (severe stress). AtDREB1A gene expression was higher in the genetically modified P58 plants during water deficit, demonstrating transgene stability in T(2) generations and induction of the rd29A promoter. Drought-response genes, including GmPI-PLC, GmSTP, GmGRP, and GmLEA14, were highly expressed in plants submitted to severe stress. Genetically modified plants had higher stomatal conductance and consequently higher photosynthetic and transpiration rates. In addition, they had more chlorophyll. Overexpression of AtDREB1A may contribute to a decrease in leaf thickness; however, a thicker abaxial epidermis was observed. Overexpression of AtDREB1A in soybean appears to enhance drought tolerance.


Asunto(s)
Adaptación Fisiológica/genética , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Sequías , Glycine max/anatomía & histología , Glycine max/genética , Transformación Genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Células del Mesófilo/citología , Células del Mesófilo/ultraestructura , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Glycine max/fisiología , Glycine max/ultraestructura , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
14.
Int J Clin Pharmacol Ther ; 47(11): 701-6, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19840535

RESUMEN

OBJECTIVE: To report a case in which the serum concentration of vancomycin (VCM) reached the supratherapeutic range following oral administration in a patient with severe pseudomembranous colitis and renal insufficiency. CASE SUMMARY: A 65-year-old, 70 kg weighing man with severe acute pancreatitis and acute renal failure was subjected to continuous hemodiafiltration (CHDF). CHDF could only be performed intermittently because of the unstable circulation dynamic of this patient. After admission, intravenous VCM therapy was initiated. Thereafter, oral VCM administration was begun (0.5 g every 6 h). Despite the discontinuation of intravenous VCM after the first 2 days of oral VCM, the serum VCM concentration increased gradually to 49.8 mg/l over a period of 2 weeks from the initiation of oral administration (34.4 mg/l). Based on pharmacokinetic analysis, the bioavailability of VCM was estimated to over 33%. Autopsy findings indicated broadly distributed necrosis on the lamina propria of the mucosa throughout all parts of the intestine below the duodenum. DISCUSSION: This case indicates necessity of the careful monitoring after oral high-dose VCM administration in a patient with a broadly distributed necrosis and renal insufficiency. CONCLUSIONS: TDM should be considered according to renal function, the severity of enteritis and the total dosage of oral VCM administration.


Asunto(s)
Lesión Renal Aguda/complicaciones , Antibacterianos/farmacocinética , Enterocolitis Seudomembranosa/complicaciones , Vancomicina/farmacocinética , Enfermedad Aguda , Lesión Renal Aguda/fisiopatología , Administración Oral , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Disponibilidad Biológica , Monitoreo de Drogas , Enterocolitis Seudomembranosa/fisiopatología , Hemodiafiltración/métodos , Humanos , Masculino , Necrosis/fisiopatología , Pancreatitis Alcohólica/complicaciones , Índice de Severidad de la Enfermedad , Vancomicina/administración & dosificación , Vancomicina/efectos adversos
15.
Artículo en Inglés | MEDLINE | ID: mdl-18519205

RESUMEN

Epitaxial 0.67Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3)-0.33PbTiO(3) (PMN-PT) thin films with electro-optic effects were fabricated on (PMN-PT) thin films with electro-optic effects were fabricated on (La0(0.5)Sr0(0.5))CoO(3) (LSCO)/CeO(2)/YSZ-buffered Si(001) substrates using double-pulse excitation pulsed laser deposition (PLD) method with a mask placed between the target and the substrate. Epitaxial growth of PMN-PT thin films was undertaken using the two-step growth method of PMN-PT film. The PMN-PT seed layer was deposited at 500 degrees C on the LSCO/CeO(2)/YSZ/Si, which temperature was the same as that used for LSCO deposition. The PMN-PT thin films were deposited on the PMN-PT seed layer at 600 degrees C, which enables growth of high-crystallinity PMN-PT films with smooth surfaces. We obtained optimum fabrication conditions of PMNPT film with micrometer-order thickness. Resultant films showed high crystallinity with full width at half maximum (FWHM) = 0.73 deg and 1.6 mum thickness. Electro-optic properties and the refractive index value were measured at 633 nm wavelength using the prism coupling method. The obtained refractive index was 2.59. The electro-optic coefficients r(13) and r(33) were determined by applying the electrical field between a semitransparent, thin top electrode of Pt and a bottom LSCO electrode. The electro-optic coefficient was r(13) = 17 pm/V at transverse electric field (TE) mode and r(33) = 55 pm/V at transverse magnetic field (TM) mode.


Asunto(s)
Cerámica/química , Cristalización/métodos , Membranas Artificiales , Silicio/química , Conductividad Eléctrica , Ensayo de Materiales , Óptica y Fotónica
16.
Arch Virol ; 152(12): 2249-52, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17851731

RESUMEN

Between October and December, 2006, high activity of three genetically distinct norovirus GII-4 subtypes was observed in Chiba prefecture, Japan. One subtype was newly identified in this period and it was detected in 85% of outbreaks.


Asunto(s)
Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Gastroenteritis/epidemiología , Variación Genética , Norovirus/clasificación , Infecciones por Caliciviridae/virología , Gastroenteritis/virología , Genotipo , Humanos , Japón/epidemiología , Datos de Secuencia Molecular , Norovirus/genética , Norovirus/aislamiento & purificación , Filogenia , Análisis de Secuencia de ADN
17.
Plant Cell Rep ; 26(12): 2071-82, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17653723

RESUMEN

Water deficit is the major abiotic constraint affecting crop productivity in peanut (Arachis hypogaea L.). Water use efficiency under drought conditions is thought to be one of the most promising traits to improve and stabilize crop yields under intermittent water deficit. A transcription factor DREB1A from Arabidopsis thaliana, driven by the stress inducible promoter from the rd29A gene, was introduced in a drought-sensitive peanut cultivar JL 24 through Agrobacterium tumefaciens-mediated gene transfer. The stress inducible expression of DREB1A in these transgenic plants did not result in growth retardation or visible phenotypic alterations. T3 progeny of fourteen transgenic events were exposed to progressive soil drying in pot culture. The soil moisture threshold where their transpiration rate begins to decline relative to control well-watered (WW) plants and the number of days needed to deplete the soil water was used to rank the genotypes using the average linkage cluster analysis. Five diverse events were selected from the different clusters and further tested. All the selected transgenic events were able to maintain a transpiration rate equivalent to the WW control in soils dry enough to reduce transpiration rate in wild type JL 24. All transgenic events except one achieved higher transpiration efficiency (TE) under WW conditions and this appeared to be explained by a lower stomatal conductance. Under water limiting conditions, one of the selected transgenic events showed 40% higher TE than the untransformed control.


Asunto(s)
Proteínas de Arabidopsis/genética , Arachis/genética , Transpiración de Plantas/fisiología , Plantas Modificadas Genéticamente/genética , Factores de Transcripción/genética , Proteínas de Arabidopsis/fisiología , Arachis/fisiología , Southern Blotting , Desastres , Regulación de la Expresión Génica de las Plantas , Modelos Genéticos , Fenotipo , Plantas Modificadas Genéticamente/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/fisiología , Agua/metabolismo
18.
Arch Virol ; 152(1): 1-9, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16957827

RESUMEN

The universal primer sets for identification of human adenovirus (HAdV) targeting hexon gene were designed and applied to 121 clinical samples suspected of HAdV infection. The primer sets amplified at least 20 HAdV reference strains of six species. Of these clinical samples, 81 (66.9%) samples were positive for HAdV. They were classified into 11 serotypes belonging to 5 HAdV species (B-F). The primer sets described here are sensitive and reactive to the broad spectrum of HAdV and are useful for rapid diagnosis of various HAdV infections.


Asunto(s)
Adenovirus Humanos/genética , Proteínas de la Cápside/genética , Cartilla de ADN/genética , Genes Virales , Infecciones por Adenovirus Humanos/diagnóstico , Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/clasificación , Adenovirus Humanos/aislamiento & purificación , Secuencia de Bases , ADN Viral/genética , Humanos , Técnicas de Amplificación de Ácido Nucleico , Filogenia , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Serotipificación
19.
Arch Virol ; 151(12): 2503-9, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16847552

RESUMEN

Sapovirus (SV) causes gastroenteritis in humans and comprises genetically divergent viruses. A nested reverse transcription-polymerase chain reaction (RT-PCR) targeting the capsid-protein-coding region was developed using universal and genogroup-specific primer sets. The universal primers were capable of detecting human SV genogroups I, II, IV and V. Genetic analysis of the amplified products enabled us to phylogenetically determine the genotypes of the viruses. In addition, genogroup-specific primers that amplified different lengths of the amplicon depending on the genogroup were developed. These genogroup-specific primers were also used as inner primers for the nested PCR. These two simple RT-PCR methods are powerful tools for both detection and epidemiological studies of human SV.


Asunto(s)
Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sapovirus/genética , Infecciones por Caliciviridae/diagnóstico , Cartilla de ADN , Heces/virología , Gastroenteritis/diagnóstico , Gastroenteritis/virología , Genotipo , Humanos , Filogenia , Sapovirus/clasificación , Sapovirus/aislamiento & purificación
20.
Phys Rev Lett ; 96(15): 157602, 2006 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-16712197

RESUMEN

The in-plane and out-of-plane ferroelectric instabilities in compressed (100)-epitaxial SrTiO3 films were examined by infrared reflection spectroscopy. The strongly stiffened in-plane soft mode frequency softened very slowly on cooling. On the other hand, the silent mode appeared at around 150 K, indicating an out-of-plane ferroelectric transition. This behavior points to a split of in-plane and out-of-plane ferroelectric instability temperatures due to the lowered symmetry of the SrTiO3 lattice caused by mechanical misfit strain. Infrared spectroscopy provides a possibility to detect such an effect in the strained epitaxial ferroelectric films.

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