RESUMEN
We compared the effects of an exercise intervention with that of exercise combined with nutrition therapy in patients with possible malnutrition and sarcopenia admitted to a recovery rehabilitation ward, and we examined the differences in the patients' physical function and activities of daily living (ADLs). There were 16 patients in the Exercise group with exercise therapy and ADL exercises, and 14 patients in the Combined intervention group with exercise therapy, ADL exercises, and nutrition therapy. The survey items were body weight, body mass index, grip strength, lower-leg circumference, gait speed, and ADLs, each of which was measured at the baseline and at 2 weeks, 4 weeks, and at discharge. Significant improvements in grip strength were observed in the Combined intervention group as follows: at 4 weeks>at 2 weeks (p<0.05), and at discharge>baseline and 2 weeks (p<0.05). There were no significant changes in the Exercise group, and an interaction was recognized in both groups. Comprehensive rehabilitation including nutrition therapy is necessary for patients with possible malnutrition and/or sarcopenia, as our results indicate that nutrition therapy in addition to exercise therapy has the effect of promoting improvements of physical function in such patients.
Asunto(s)
Desnutrición , Terapia Nutricional , Sarcopenia , Actividades Cotidianas , Terapia por Ejercicio/métodos , Humanos , Desnutrición/terapia , Sarcopenia/terapiaRESUMEN
External application of ethanol enhances tolerance to high salinity, drought, and heat stress in various plant species. However, the effects of ethanol application on increased drought tolerance in woody plants, such as the tropical crop "cassava," remain unknown. In the present study, we analyzed the morphological, physiological, and molecular responses of cassava plants subjected to ethanol pretreatment and subsequent drought stress treatment. Ethanol pretreatment induced a slight accumulation of abscisic acid (ABA) and stomatal closure, resulting in a reduced transpiration rate, higher water content in the leaves during drought stress treatment and the starch accumulation in leaves. Transcriptomic analysis revealed that ethanol pretreatment upregulated the expression of ABA signaling-related genes, such as PP2Cs and AITRs, and stress response and protein-folding-related genes, such as heat shock proteins (HSPs). In addition, the upregulation of drought-inducible genes during drought treatment was delayed in ethanol-pretreated plants compared with that in water-pretreated control plants. These results suggest that ethanol pretreatment induces stomatal closure through activation of the ABA signaling pathway, protein folding-related response by activating the HSP/chaperone network and the changes in sugar and starch metabolism, resulting in increased drought avoidance in plants.
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Manihot , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacología , Sequías , Etanol/farmacología , Regulación de la Expresión Génica de las Plantas , Proteínas de Choque Térmico/genética , Manihot/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Almidón/metabolismo , Estrés Fisiológico/genética , Azúcares/metabolismo , Agua/metabolismoRESUMEN
BACKGROUND: The abnormal conduction zone (ACZ) in the left atrium (LA) has attracted attention as an arrhythmia source in atrial fibrillation (AF). We investigated the hypothesis that the ACZ is related to the low voltage area (LVA) or the LA anatomical contact areas (CoAs) with other organs. METHODS AND RESULTS: We studied 100 patients (49 non-paroxysmal AF, 66 males, and 67.9 ± 9.9 years) who received catheter ablation for AF. High-density LA mapping during high right atrial pacing was constructed. Isochronal activation maps were created at 5-ms interval setting, and the ACZ was identified on the activation map by locating a site with isochronal crowding of ≥3 isochrones, which are calculated as ≤27 cm/s. The LVA was defined as the following; mild ( < 1.3 mV), moderate (<1.0 mV), and severe LVA (<0.5 mV). The CoAs (ascending aorta-anterior LA, descending aorta-posterior LA, and vertebrae-posterior LA) were assessed using computed tomography. The ACZ was linearly distributed, and observed in 95 patients (95%). The ACZ was most frequently observed in the anterior wall region (77%). A longer ACZ was significantly associated with a larger LA size and a prevalence of non-PAF. The 51.2 ± 36.2% of ACZ overlapped with mild LVA, 32.9 ± 32.8% of ACZ with moderate LVA, and 14.6 ± 22.0% of ACZ with severe LVA. In contrast, only 25.6 ± 28.0% of ACZ matched with the CoAs. CONCLUSION: The ACZ reflects LA electrical remodeling and may be a precursor finding of the low voltage zone and not the LA CoAs in patients with atrial fibrillation.
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Fibrilación Atrial , Remodelación Atrial , Ablación por Catéter , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Técnicas Electrofisiológicas Cardíacas , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Humanos , MasculinoAsunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Recuento de Linfocitos , Inhibidores de Proteínas Quinasas/uso terapéutico , Subgrupos de Linfocitos T , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores , Humanos , Inmunofenotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Subgrupos de Linfocitos T/metabolismo , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate a regimen of targeted prophylaxis using rectal swab culture in patients undergoing transrectal ultrasound-guided prostate biopsy, and to investigate the characteristics of isolated fluoroquinolone-resistant Escherichia coli. METHODS: A prospective study was carried out from June 2013 through December 2014. Rectal swabs were cultured on agar plates containing either 2 µg/mL levofloxacin or 1 µg/mL sitafloxacin before transrectal ultrasound-guided prostate biopsy. Patients with susceptible organisms received levofloxacin or sitafloxacin, whereas those with resistant organisms received directed antimicrobial prophylaxis according to the results of the antimicrobial susceptibility test. Patients with infectious complications after prostate biopsy were identified, and characteristics of patients carrying fluoroquinolone-resistant Escherichia coli were analyzed. RESULTS: A total of 397 men underwent transrectal ultrasound-guided prostate biopsy. Of these patients, 74 (18.6%) had fluoroquinolone-resistant Escherichia coli. All fluoroquinolone-resistant Escherichia coli were susceptible to amikacin and meropenem. The risk factor for possible fluoroquinolone-resistant Escherichia coli was age of ≥73 years. Three (0.7%) patients who received appropriate antimicrobial prophylaxis had high-grade fever after the prostate biopsy. However, the pathogens were not fluoroquinolone-resistant Escherichia coli. CONCLUSIONS: Targeted antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided prostate biopsy can be associated with reducing severe infectious complications caused by fluoroquinolone-resistant Escherichia coli.
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Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/prevención & control , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Anciano , Anciano de 80 o más Años , Profilaxis Antibiótica , Farmacorresistencia Bacteriana , Escherichia coli/crecimiento & desarrollo , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Fluoroquinolonas/uso terapéutico , Humanos , Japón/epidemiología , Levofloxacino/uso terapéutico , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Próstata/patología , Quinolonas/uso terapéutico , Recto/microbiología , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Neisseria gonorrhoeae is a principal pathogen for sexually transmitted infections, especially for male urethritis. Currently, the prevalence of multidrug resistance is increasing. Carbapenems are broad-spectrum antimicrobials that are widely used in the clinical setting, especially for multidrug-resistant Gram-negative bacteria. However, susceptibility to carbapenems has not been well evaluated for cephalosporin-resistant N. gonorrhoeae isolates. In this study, we determined the susceptibility to a series of carbapenems (meropenem, imipenem, doripenem, and biapenem) and faropenem against cephalosporin-resistant (resistant to cefixime, but susceptible to ceftriaxone) and cephalosporin-susceptible N. gonorrhoeae clinical isolates. The gene mutations associated with ß-lactam resistance were evaluated. All cephalosporin-resistant N. gonorrhoeae isolates possessed mosaic mutation alleles in penA (NG-STAR penA-10.001, 27.001, or 108.001). They exhibited a low minimum inhibitory concentration (MIC) (≤0.125 mg/L) for meropenem and markedly high MICs (0.5-2 mg/L) for other carbapenems and faropenem. The strongest association was observed between the mosaic alleles in penA and decreased susceptibility to carbapenems and faropenem compared with mutations in mtrR, porB, and ponA. These results suggest that meropenem may serve as an alternative therapeutic agent for cephalosporin-resistant N. gonorrhoeae with a mosaic allele in penA, whereas other carbapenems and faropenem may be ineffective.
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Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Carbapenémicos/uso terapéutico , Resistencia a las Cefalosporinas/efectos de los fármacos , Cefalosporinas/uso terapéutico , Neisseria gonorrhoeae/efectos de los fármacos , beta-Lactamas/uso terapéutico , Alelos , Resistencia a las Cefalosporinas/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Mutación/genética , Neisseria gonorrhoeae/genéticaRESUMEN
OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.
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Extractos Vegetales/administración & dosificación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico , Prostatitis/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/efectos adversos , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/patología , Curva ROC , Secale , Procedimientos InnecesariosAsunto(s)
Fístula Arteriovenosa/patología , Malformaciones Arteriovenosas Intracraneales/patología , Tálamo/patología , Adulto , Cuidados Posteriores , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/cirugía , Angiografía Cerebral , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/cirugía , Imagen por Resonancia Magnética , Masculino , Remisión Espontánea , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Tálamo/cirugía , Derivación Ventriculoperitoneal/métodosRESUMEN
The prophylactic use of antifungal drugs in allogeneic hematopoietic cell transplant recipients has revealed that the rate of non-albicans candidemia has increased. We herein report the case of a patient with adult T-cell leukemia who developed candidemia due to Candida fermentati during micafungin treatment after cord blood transplantation. The isolate was identified on day 47 by sequencing of the internal transcribed spacer region of the ribosomal RNA gene. The sequencing of the hot spot region of fks1p of isolate revealed naturally occurring amino acid substitutions, which conferred reduced echinocandin susceptibility. This case highlights that breakthrough candidemia due to C. fermentati occurred in a patient receiving micafungin treatment.
Asunto(s)
Antifúngicos/farmacología , Candida/fisiología , Candidemia/microbiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Farmacorresistencia Fúngica/genética , Equinocandinas/farmacología , Leucemia-Linfoma de Células T del Adulto/cirugía , Lipopéptidos/farmacología , Anciano , Profilaxis Antibiótica/efectos adversos , Antifúngicos/uso terapéutico , Candida/genética , Candida/aislamiento & purificación , Catéteres Venosos Centrales/efectos adversos , Catéteres Venosos Centrales/microbiología , ADN de Hongos/aislamiento & purificación , Equinocandinas/uso terapéutico , Proteínas Fúngicas/genética , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lipopéptidos/uso terapéutico , Masculino , Micafungina , Pruebas de Sensibilidad Microbiana , Mutación , Análisis de Secuencia de ADN , Receptores de Trasplantes , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodosRESUMEN
Although neuronal studies have shown that audiovisual integration is regulated by temporal factors, there is still little knowledge about the impact of temporal factors on audiovisual integration in older adults. To clarify how stimulus onset asynchrony (SOA) between auditory and visual stimuli modulates age-related audiovisual integration, 20 younger adults (21-24 years) and 20 older adults (61-80 years) were instructed to perform an auditory or visual stimuli discrimination experiment. The results showed that in younger adults, audiovisual integration was altered from an enhancement (AV, A ± 50 V) to a depression (A ± 150 V). In older adults, the alterative pattern was similar to that for younger adults with the expansion of SOA; however, older adults showed significantly delayed onset for the time-window-of-integration and peak latency in all conditions, which further demonstrated that audiovisual integration was delayed more severely with the expansion of SOA, especially in the peak latency for V-preceded-A conditions in older adults. Our study suggested that audiovisual facilitative integration occurs only within a certain SOA range (e.g., -50 to 50 ms) in both younger and older adults. Moreover, our results confirm that the response for older adults was slowed and provided empirical evidence that integration ability is much more sensitive to the temporal alignment of audiovisual stimuli in older adults.
Asunto(s)
Percepción Auditiva/fisiología , Tiempo de Reacción/fisiología , Percepción Visual/fisiología , Estimulación Acústica , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Desempeño Psicomotor/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
AIM: Yokukansan (YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia (BPSD). The present study is the first double-blind, randomized, placebo-controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer's disease (AD). METHODS: A total of 22 sites consisting of clinics, hospitals and nursing homes participated. A total of 145 patients with AD were randomized. Active YKS (7.5 g/day) and placebo were supplied to 75 and 70 participants, respectively. The primary outcome measure was the 4-week change in total score of the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q), an instrument that evaluates BPSD. Secondary outcome measures included 12-week changes in NPI-Q scores, changes in NPI-Q subcategory scores and total scores of the Mini-Mental-State Examination. RESULTS: Four-week changes in NPI-Q total scores did not differ significantly between the treatment and placebo groups. There were also no significant differences between groups in 12-week changes in total NPI-Q scores, NPI-Q subcategory scores or total Mini-Mental-State Examination scores. However, a subgroup with fewer than 20 points on the Mini-Mental-State Examination at baseline showed a greater decrease in "agitation/aggression" score in the YKS group than in the placebo group (P = 0.007). No serious adverse effects were observed during the study. CONCLUSIONS: Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.
Asunto(s)
Enfermedad de Alzheimer/psicología , Síntomas Conductuales/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Trastornos Mentales/tratamiento farmacológico , Fitoterapia , Anciano , Anciano de 80 o más Años , Síntomas Conductuales/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Trastornos Mentales/etiología , Pruebas NeuropsicológicasRESUMEN
Mediastinal aneurysms are rare but potentially life-threatening. Among these, bronchial artery aneurysms are most frequently reported, whereas up to now aneurysms of the proper esophageal artery had never been reported. A 69-year-old woman was referred to our hospital for treatment of a massive mediastinal hematoma. Enhanced computed tomography and selective proper esophageal arteriography revealed a 5-mm aneurysm in the proper esophageal artery that arises from the thoracic aorta at the Th8 level and has an anastomotic branch with the bronchial artery peripherally. Transcatheter arterial embolization was successfully performed using a mixture of N-butyl cyanoacrylate and lipiodol (1:3 ratio, 0.3 ml). Post-embolization angiography showed no filling into the aneurysm. The patient recovered with no complications and was discharged on the 25th post-procedure day.
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Aneurisma Roto/complicaciones , Aneurisma Roto/terapia , Embolización Terapéutica/métodos , Esófago/irrigación sanguínea , Hematoma/complicaciones , Hematoma/terapia , Anciano , Aneurisma Roto/diagnóstico por imagen , Angiografía , Medios de Contraste , Enbucrilato/uso terapéutico , Aceite Etiodizado/uso terapéutico , Femenino , Hematoma/diagnóstico por imagen , Humanos , Mediastino/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy. METHODS: Folic acid and vitamin B12 were given orally for Ë 1 week before pemetrexed administration. The primary end-point was onset of a grade ≥ 3 neutropenia ratio (50% of threshold expression ratios; an expectation expression ratio of 21%; α, 0.05; ß, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180). RESULTS: A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥ 3 neutropenia was 36% (95% CI 22-52 %). Grade ≥ 3 non-hematologic toxicity and hematologic toxicity were seen in 20% (5 cases) and 44% (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle. CONCLUSION: This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/uso terapéutico , Vitamina B 12/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/efectos adversos , Ácido Fólico/uso terapéutico , Homocisteína/sangre , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pemetrexed/efectos adversos , Vitamina B 12/efectos adversos , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/prevención & control , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/efectos adversos , Complejo Vitamínico B/uso terapéuticoRESUMEN
BACKGROUND: Aryl hydrocarbon receptor (AhR) is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells. METHODS: HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS) or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses. RESULTS: All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum. CONCLUSIONS: By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Café/química , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Hidrocarburos Policíclicos Aromáticos/farmacología , Receptores de Hidrocarburo de Aril/genética , Células CACO-2 , Café/clasificación , Medios de Cultivo/química , Células Hep G2 , Humanos , Células MCF-7 , Extractos Vegetales/química , Extractos Vegetales/farmacología , Transcripción Genética/efectos de los fármacosRESUMEN
OBJECTIVES: The increasing prevalence of resistant bacteria such as fluoroquinolone-resistant or extended-spectrum ß-lactamase-producing strains in pathogens causing acute uncomplicated cystitis has been of concern in Japan. Faropenem sodium is a penem antimicrobial that demonstrates a wide antimicrobial spectrum against both aerobic and anaerobic bacteria. It is stable against a number of ß-lactamases. METHODS: We compared 3 and 7 day administration regimens of faropenem in a multicentre, randomized, open-label, controlled study. RESULTS: In total, 200 female patients with cystitis were enrolled and randomized into 3 day (Nâ=â97) or 7 day (Nâ=â103) treatment groups. At the first visit, 161 bacterial strains were isolated from 154 participants, and Escherichia coli accounted for 73.9% (119/161) of bacterial strains. At 5-9 days after the completion of treatment, 73 and 81 patients from the 3 day and 7 day groups, respectively, were evaluated by intention-to-treat analysis; the microbiological efficacies were 58.9% eradication (43/73), 20.5% persistence (15/73) and 8.2% replaced (6/73), and 66.7% eradication (54/81), 6.2% persistence (5/81) and 7.4% replaced (6/81), respectively (Pâ=â0.048). The clinical efficacies were 76.7% (56/73) and 80.2% (65/81), respectively (Pâ=â0.695). Adverse events due to faropenem were reported in 9.5% of participants (19/200), and the most common adverse event was diarrhoea. CONCLUSIONS: The 7 day regimen showed a superior rate of microbiological response. E. coli strains were in general susceptible to faropenem, including fluoroquinolone- and cephalosporin-resistant strains.
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Antibacterianos/uso terapéutico , Cistitis/tratamiento farmacológico , beta-Lactamas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Cistitis/microbiología , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven , beta-Lactamas/farmacologíaRESUMEN
We report a case of metastatic renal cell carcinoma (RCC) treated with cytoreductive nephrectomy, cytokine therapy, and molecular targeted therapy followed by metastasectomy. A 47-year-old man was diagnosed as having bilateral RCC with metastases to the lung, liver, left adrenal gland, and lymph nodes in the mediastinum. He initially received right radical nephrectomy, left partial nephrectomy, and left adrenalectomy. The pathological diagnosis was clear cell RCC, which was found in all excised specimens. After the initial surgery, cytokine therapy was started but it did not generate a response in the evaluation at 3 months. He then received sorafenib for 2.5 years and the treatment produced a 75% response rate with only one metastasis remaining. The following sequential therapy with everolimus and sunitinib did not reduce the size of the lung metastasis. For a long time, the metastasis was limited only to the lung and its size did not become larger and there were no new lesions in any organs. Then, lung metastasectomy was performed. From the time of surgery in January 2010 until November 2012, he has had no recurrence of the disease. In some selected cases, sequential therapy with targeted agents followed by metastatectomy may result in a favorable clinical outcome for patients with metastatic RCC.
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Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Neoplasias Renales/patología , Neoplasias Renales/terapia , Terapia Molecular Dirigida , Adrenalectomía , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Nefrectomía , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , SorafenibRESUMEN
We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.
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Bebidas , Proantocianidinas/uso terapéutico , Prevención Secundaria , Infecciones Urinarias/prevención & control , Vaccinium macrocarpon , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Fitoterapia , Adulto JovenRESUMEN
Previous clinical trials suggest that the traditional Japanese medicine yokukansan has beneficial effects on the behavioral and psychological symptoms of dementia (BPSD). The present study was conducted to elucidate the efficacy of yokukansan on BPSD in patients with vascular dementia. Thirteen Japanese patients (9 men and 4 women) who were diagnosed as having vascular dementia (VaD) according to the diagnostic criteria of NINDS-AIREN were subjected to the open-label clinical trial in which yokukansan (7.5g/day) has been given for 4 weeks. Their mean age was 71.2±6.5 years. The BPSD was evaluated using the Neuropsychiatric Inventory (NPI), cognitive function was evaluated by the Mini-Mental State Examination (MMSE), the activities of daily living was evaluated by Barthel index (BI) and Disability Assessment for Dementia (DAD), and the extrapyramidal signs were evaluated by United Parkinson's Disease Rating Scale (UPDRS). The mean NPI was 33.0±17.3 and 23.6±13.9 for the baseline and after treatment, respectively. It was significantly improved after treatment (p<0.05). In the NPI-subcategories, there was a significant improvement in agitation and disinhibition after the treatment. There was no significant change in MMSE, BI, DAD or UPDRS before and after the treatment. There was no adverse effect during the treatment period. The present results suggest that yokukansan is beneficial for the treatment of BPSD in VaD patients.
Asunto(s)
Síntomas Conductuales/tratamiento farmacológico , Demencia Vascular/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Anciano , Evaluación de Medicamentos , Femenino , Humanos , Japón , Masculino , Medicina Tradicional de Asia OrientalRESUMEN
The human glyoxalase I (hGLO I), which is a rate-limiting enzyme in the pathway for detoxification of apoptosis-inducible methylglyoxal (MG), has been expected as an attractive target for the development of new anti-cancer drugs. We have previously identified a natural compound myricetin as a substrate transition-state (Zn(2+)-bound MG-glutathione (GSH) hemithioacetal) mimetic inhibitor of hGLO I. Here, we constructed a hGLO I/inhibitor 4-point pharmacophore based on the binding mode of myricetin to hGLO I. Using this pharmacophore, in silico screening of chemical library was performed by docking study. Consequently, a new type of compound, which has a unique benzothiazole ring with a carboxyl group, named TLSC702, was found to inhibit hGLO I more effectively than S-p-bromobenzylglutathione (BBG), a well-known GSH analog inhibitor. The computational simulation of the binding mode indicates the contribution of Zn(2+)-chelating carboxyl group of TLSC702 to the hGLO I inhibitory activity. This implies an important scaffold-hopping of myricetin to TLSC702. Thus, TLSC702 may be a valuable seed compound for the generation of a new lead of anti-cancer pharmaceuticals targeting hGLO I.
Asunto(s)
Inhibidores Enzimáticos/química , Flavonoides/química , Lactoilglutatión Liasa/antagonistas & inhibidores , Sitios de Unión , Dominio Catalítico , Simulación por Computador , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Humanos , Lactoilglutatión Liasa/genética , Lactoilglutatión Liasa/metabolismo , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relación Estructura-ActividadRESUMEN
To identify molecular therapeutic targets for glioma, we performed gene expression profiling by using a complementary DNA (cDNA) microarray method and identified the urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) as a gene expressed highly in glioma tissue compared with the normal brain tissue. The uPARAP is an endocytic receptor for collagen. In certain cell types, uPARAP occurs in a complex with the urokinase plasminogen activator receptor (uPAR) where it fulfills other functions in addition to collagenolysis. Quantitative PCR analysis using a cDNA panel revealed higher expression levels of uPARAP in glioma tissue compared with normal brain tissue. Western blot analysis revealed that the uPARAP protein was expressed in glioma samples and two glioma cell lines, KNS42 and KNS81, but not expressed in control tissue from the normal brain. Introduction of small interfering RNA-targeted uPARAP into the two different glioma cell lines, KNS42 and KNS81, resulted in downregulation of uPARAP expression, and it significantly suppressed glioma cell migration and invasion in vitro. Control glioma cells showed small cell bodies, whereas uPARAP siRNA-treated glioma cells exhibited large and flat morphology. Most of the polymeric actin in the control glioma cells was concentrated in the lamellipodia that are observed in mobile cells. In contrast, in the uPARAP siRNA-treated glioma cells, polymeric actin became organized in stress fibers and the lamellipodia disappeared, characteristic of immobile cells. Our present study suggests that uPARAP may be involved in glioma cell invasiveness through actin cytoskeletal rearrangement. downregulation of uPARAP may be a novel anti-invasion therapeutic strategy for malignant gliomas.