RESUMO
BACKGROUND: Astaxanthin has a strong antioxidant effect. We recently demonstrated that following 3-month astaxanthin supplementation, cardiac contractility and exercise tolerance improved, possibly through the suppression of oxidative stress in a small pilot study involving patients with heart failure with left ventricular systolic dysfunction. This is a sub-study of our pilot study to investigate whether improvements of selfreported physical activity and health-related quality of life were observed following 3-month astaxanthin supplementation. METHODS: We investigated the changes in physical activity by the Specific Activity Scale score and healthrelated quality of life by physical and mental component summary scores in Short Form-8 at baseline and after 3-month astaxanthin supplementation. RESULTS: Data from 17 patients with heart failure were assessed. Following 3-month astaxanthin supplementation, the Specific Activity Scale score increased from the median of 4.5 (interquartile range, 2.0) to 6.5 (interquartile range, 1.1) metabolic equivalent (P=0.001), and the physical and mental component summary scores increased from 46.1±9.2 to 50.8±6.8 (P=0.015) and from 48.9±9.1 to 53.8±4.8 (P=0.022), respectively. There was a linear relationship of the baseline heart rate, or mental component summary score with the percent change in the Specific Activity Scale score (r=0.523, P=0.031 and r=-0.505, P=0.039, respectively). In addition, there was a direct relationship of ischemic etiology with the percent change in the physical component summary score (r=0.483, P=0.049, respectively). Finally, there was a linear relationship between the percent change in the Specific Activity Scale score and that in the mental component summary score (r=0.595, P=0.012). CONCLUSIONS: Following 3-month astaxanthin supplementation, improvements of the self-reported physical activity level and health-related quality of life in both mental and physical components were observed. In patients with heart failure, those with higher baseline heart rate, ischemic etiology, and poorer baseline health-related quality of life have potentials to have greater improvement of physical activity and/or health-related quality of life.
Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Suplementos Nutricionais , Exercício Físico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Projetos Piloto , Autorrelato , XantofilasRESUMO
Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers-serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 ± 82.6 U.CARR to 346.5 ± 56.9 U.CARR (p = 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1 ± 8.6% to 38.0 ± 10.0% (p = 0.031) and 6MWD increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Projetos Piloto , Estudos Prospectivos , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Xantofilas/administração & dosagemRESUMO
Grape extract (GE), which contains various polyphenolic compounds, exerts protective effects against lifestyle-related diseases, such as diabetes and hypertension. We pharmacologically investigated whether dietary supplements with an extract from Chardonnay exerted antihypertensive effects in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. GE increased nitric oxide (NO) production by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in cultured endothelial cells and induced vasorelaxation in the aorta and mesenteric artery via the same pathway. The development and progression of hypertension by the DOCA-salt treatment was significantly inhibited in GE-fed rats. Reduced vasoreactive responses to acetylcholine in the aorta of DOCA-salt rats were significantly ameliorated by the GE diet. Dietary GE supplements slightly diminished vascular superoxide anion production induced by the DOCA-salt treatment. On the other hand, dietary GE supplements had no effect on the progression of hypertension in rats in which NO synthase was pharmacologically and chronically suppressed. In addition, the oral administration of GE for 5 d in healthy rats enhanced endothelial NO synthase (eNOS) gene expression and vascular reactivity to acetylcholine in the aorta. Thus, GE has endothelium-dependent vasorelaxant properties that are mediated by the activation of endothelial NO synthase via the PI3K/Akt pathway, and this mechanism is conducive to the antihypertensive effects of GE observed in DOCA-salt-treated rats.
Assuntos
Hipertensão/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vasodilatadores/uso terapêutico , Vitis , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Linhagem Celular , Acetato de Desoxicorticosterona , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Sementes , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Arctium , Carcinoma Adenoescamoso/sangue , Carcinoma Ductal Pancreático/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Furanos/uso terapêutico , Ácido Láctico/sangue , Lignanas/uso terapêutico , Neoplasias Pancreáticas/sangue , Extratos Vegetais/uso terapêutico , Antineoplásicos Fitogênicos/farmacocinética , Arctium/química , Área Sob a Curva , Biomarcadores/sangue , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/farmacocinética , Furanos/farmacocinética , Gluconeogênese/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Lignanas/farmacocinética , Fígado/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , GencitabinaRESUMO
In December 2012, a 32-year-old woman with no previous medical history and no previous antibiotic treatment had a fever and diarrhea 2 days after a cesarean section in which cefazolin was used as a prophylactic antimicrobial agent. She was transferred to our hospital 5 days after the cesarean for severe colitis. A rapid test of stool for Clostridium difficile toxin A and B was positive. Although oral vancomycin (0.5-2.0 g/day) and intravenous immunoglobulin (5 g/day) were administered after her transfer, 7 days after admission emergency exploratory surgery was performed because of poor response to therapy. Bowel perforation was noted and a temporary colostomy was created without colectomy. Vancomycin (2.0 g/day) was administered via the colostomy, in addition to a vancomycin enema (2.0 g/day), oral metronidazole (1500 mg/day), and oral vancomycin (2.0 g/day). Three days after the operation, linezolid (1200 mg/day IV) was added. She was treated with antibiotics against C. difficile for a total of 18 days after the operation. The same strain was not isolated from other patients in the same ward. Microbiological analysis of the isolate revealed housekeeping gene (tpi), toxin A gene (tcdA), toxin B gene (tcdB), and binary toxin gene (cdtA and cdtB). DNA sequencing of tcdC revealed a base 117 deletion and contained an 18-bp tcdC deletion. PCR ribotyping showed ribotype 027 patterns. The MIC of moxifloxacin was >32 µg/ml, indicating resistance to fluoroquinolones. This isolate was considered as the epidemic strain. Our case of fulminant colitis is apparently the first case involving the epidemic strain ribotype 027 in Japan.
Assuntos
Clostridioides difficile/isolamento & purificação , Enterocolite Pseudomembranosa/microbiologia , Adulto , Antibacterianos/uso terapêutico , Clostridioides difficile/classificação , Clostridioides difficile/genética , Colostomia , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/cirurgia , Epidemias , Feminino , Humanos , Japão , RibotipagemRESUMO
Multidrug-resistant Pseudomonas aeruginosa (MDRP) strains are defined as having resistance to the following 3 groups of antibiotics: carbapenems, aminoglycosides, and fluoroquinolones. Antibiotic combinations have demonstrated increased activity in vitro compared with a single agent. As an in vitro method of determining the combination activity of antibiotics, the Break-point Checkerboard Plate (BC-plate) can be used routinely in clinical microbiology laboratories. We evaluated the effectiveness of the BC-plate for MDRP infections in clinical settings. We retrospectively selected cases of MDRP infection treated with combination therapy of antibiotics in Tokyo Medical University Hospital (1015 beds), Tokyo, Japan, from November 2010 to October 2012. A total of 28 MDRP strains were clinically isolated from 28 patients during the study period. This study design is a case series of MDRP infection. Six infections among the 28 patients were treated based on the results of the BC-plate assay, and the 6 strains tested positive for MBL. One patient had pneumonia, 3 had urinary tract infections, 1 had vertebral osteomyelitis, and 1 had nasal abscess. The combination of aztreonam with amikacin demonstrated the most frequently recognized in vitro effect (5 patients). Next, aztreonam with ciprofloxacin and piperacillin with amikacin revealed equivalent in vitro effects (3 patients, respectively). The clinical cure rate was 83.3% (5/6 patients). Antibiotic combination therapy based on the results of the BC-plate assay might indicate the effective therapy against MDRP infection in clinical settings.
Assuntos
Antibacterianos/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Amicacina/administração & dosagem , Aztreonam/administração & dosagem , Ciprofloxacina/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana/métodos , Piperacilina/administração & dosagem , Estudos RetrospectivosRESUMO
Anodic aluminum oxide (AAO) containing arrays of aligned cylindrical nanopores infiltrated with polymers is a well-defined model system for the study of hypersound propagation in polymer nanocomposites. Hypersonic phononic properties of AAO/polymer nanocomposites such as phonon localization and anisotropic sound propagation can be tailored by adjusting elastic contrast and density contrast between the components. Changes in density and elastic properties of the component located in the nanopores induced by phase transitions allow reversible modification of the phononic band structure and mode switching. As example in case, the crystallization and melting of poly(vinylidene difluoride) inside AAO was investigated.
Assuntos
Óxido de Alumínio/química , Cristalização/métodos , Eletrodos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação , Acústica , Módulo de Elasticidade , Impedância Elétrica , Desenho de Equipamento , Análise de Falha de Equipamento , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
A randomized controlled trial is being conducted in Japan to compare hepatectomy alone with hepatectomy followed by adjuvant chemotherapy as treatment in patients with curatively resected liver metastases from colorectal cancer to improve survival with intensive chemotherapy. Between 42 and 70 days after liver resection, patients are randomly assigned to either hepatectomy alone or hepatectomy followed by 12 cycles of modified FOLFOX6 (mFOLFOX6) regimen. A total of 300 patients (including 78 patients in Phase II) will be accrued from 38 institutions within 3 years. The primary endpoint is treatment compliance at nine courses of mFOLFOX6 regimen in Phase II and disease-free survival in Phase III. The secondary endpoints are overall survival, incidence of adverse events and patterns of recurrence.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Neoplasias Hepáticas/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/cirurgia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Invasividade Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Resultado do TratamentoRESUMO
The wood of Taxus yunnanensis (Taxaceae) showed growth inhibitory activities against human cancer cell lines, such as cervical HeLa adenocarcinoma. The morphological changes indicated that the cellular growth inhibitions were caused by apoptosis. To determine the active components, T. yunnanensis wood was analyzed by using a liquid chromatography-Fourier-transform MS (LC/FT-MS) technique. As a result, taxane-type diterpenes, such as 10-deacetylcephalomannine and 10-deacetyltaxol, were found to be present in amounts consistent with the growth inhibitory activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Taxus/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida , Diterpenos/química , Diterpenos/isolamento & purificação , Análise de Fourier , Células HeLa , Humanos , Espectrometria de Massas , Casca de Planta/química , Madeira/químicaRESUMO
A randomized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer. Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively randomized to either open or laparoscopic colorectal resection. Surgeons in 24 specialized institutions will recruit 818 patients. The primary end-point is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the proportion of conversion from laparoscopic surgery to open surgery, and the proportion of completion of laparoscopic surgery.