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1.
J Dairy Sci ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908688

RESUMEN

The aim of this study was to evaluate the effect of hoof trimming on overall limb movements by comparing the changes in 8 limb joint angles before and after one week of hoof trimming. Seventeen Holstein-Friesian dairy cows that were able to move freely and had no history of hoof diseases were included in the study. The cows were walked on a rubber mat with a high friction coefficient (HFM) and a low friction coefficient by the spraying of sodium polyacrylate (LFM). A high-speed camera was set to 200 fps on the image analysis software, and the images of the cows that were given 15 reflective markers on their right side were captured while walking on the test mat. The tests were conducted before and after one week of hoof trimming, and the cows were trimmed by the functional hoof trimming method. With image analysis software, video clips of walking cows were confirmed visually and tracked during one gait cycle by each reflective marker attached to the hoof of the forelimb and hindlimb, after which the stance phase and swing phase were identified. The durations of the stance phase and swing phase of the forelimb and hindlimb, respectively, and the maximum, minimum, and range of motion (ROM) values of the 8 joint angles, shoulder joint, elbow joint, carpus joint, forelimb fetlock joint, hip joint, stifle joint, hock joint and hindlimb fetlock joint during one gait cycle were included in the analysis. The maximum and minimum angles of the hip and stifle joints were narrower after hoof trimming than before, although the ROM did not change and was clearer for HFM than for LFM. It was thought that the flexion of the proximal hindlimb would progress smoothly during walking after trimming.

3.
J Dairy Sci ; 106(10): 6710-6722, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37211485

RESUMEN

Yogurt is made by fermenting milk with 2 lactic acid bacteria, Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus. To comprehensively understand the protocooperation mechanism between S. thermophilus and L. bulgaricus in yogurt fermentation, we examined 24 combinations of cocultures comprising 7 fast- or slow-acidifying S. thermophilus strains with 6 fast- or slow-acidifying L. bulgaricus strains. Furthermore, 3 NADH oxidase (Nox)-deficient mutants (Δnox) and one pyruvate formate-lyase deficient mutant (ΔpflB) of S. thermophilus were used to evaluate the factor that determines the acidification rate of S. thermophilus. The results revealed that the acidification rate of S. thermophilus monoculture determined the yogurt fermentation rates, despite the coexistence of L. bulgaricus, whose acidification rate was either fast or slow. Significant correlation was found between the acidification rate of S. thermophilus monoculture and the amount of formate production. Result using ΔpflB showed that the formate was indispensable for the acidification of S. thermophilus. Moreover, results of the Δnox experiments revealed that formate production required Nox activity, which not only regulated dissolved oxygen, but also the redox potential. The Nox provided the large decrease in redox potential required by pyruvate formate-lyase to produce formate. A highly significant correlation was found between formate accumulation and Nox activity in S. thermophilus. In conclusion, the formate production ability provided by the action of Nox activity determines the acidification rate of S. thermophilus, and consequently, regulates yogurt coculture fermentation.


Asunto(s)
Lactobacillus delbrueckii , Yogur , Animales , Yogur/microbiología , Streptococcus thermophilus/fisiología , NAD , Oxidorreductasas , Fermentación , Formiatos , Concentración de Iones de Hidrógeno
4.
J Dent Res ; 102(3): 331-339, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36529984

RESUMEN

Periodontal disease is caused by dysbiosis of the dental biofilm and the host inflammatory response. Various pathogenic factors, such as proteases and lipopolysaccharides (LPSs) produced by bacteria, are involved in disease progression. Endotoxin tolerance is a function of myeloid cells, which sustain inflammation and promote tissue regeneration upon prolonged stimulation by endotoxins such as LPS. The role of endotoxin tolerance is gaining attention in various chronic inflammatory diseases, but its role in periodontal disease remains elusive. Oxidative stress, one of the major risk factors for periodontal disease, promotes disease progression through various mechanisms, of which only some are known. The effect of oxidative stress on endotoxin tolerance has not yet been studied, and we postulated that endotoxin tolerance regulation may be an additional mechanism through which oxidative stress influences periodontal disease. This study aimed to reveal the effect of oxidative stress on endotoxin tolerance and that of endotoxin tolerance on periodontitis progression. The effect of oxidative stress on endotoxin tolerance was analyzed in vitro using peritoneal macrophages of mice and hydrogen peroxide (H2O2). The results showed that oxidative stress inhibits endotoxin tolerance induced by Porphyromonas gingivalis LPS in macrophages, at least partially, by downregulating LPS-elicited negative regulators of Toll-like receptor (TLR) signaling. A novel oxidative stress mouse model was established using SMP30KO mice incapable of ascorbate biosynthesis. Using this model, we revealed that oxidative stress impairs endotoxin tolerance potential in macrophages in vivo. Furthermore, gingival expression of endotoxin tolerance-related genes and TLR signaling negative regulators was decreased, and symptoms of ligature-induced periodontitis were aggravated in the oxidative stress mouse model. Our findings suggest that oxidative stress may contribute to periodontitis progression through endotoxin tolerance inhibition.


Asunto(s)
Lipopolisacáridos , Periodontitis , Humanos , Lipopolisacáridos/farmacología , Tolerancia a Endotoxinas , Peróxido de Hidrógeno , Estrés Oxidativo , Progresión de la Enfermedad , Porphyromonas gingivalis
5.
Transplant Proc ; 55(1): 129-133, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36581508

RESUMEN

BACKGROUND: Nonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center. METHODS: This retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period. RESULTS: Nonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx. CONCLUSIONS: Transient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.


Asunto(s)
Hiperuricemia , Trasplante de Riñón , Humanos , Niño , Trasplante de Riñón/efectos adversos , Hiperuricemia/etiología , Estudios Retrospectivos , Riñón , Factores de Riesgo , Supervivencia de Injerto
6.
Skin Health Dis ; 2(1): e78, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35665216

RESUMEN

Background: The activation of melanocortin 1 receptor (MC1R) on melanocytes stimulates the production of eumelanin. A tridecapeptide α melanocyte-stimulating hormone (αMSH) is known to induce skin pigmentation. Objectives: We characterised the properties of a novel oral MC1R agonist dersimelagon (MT-7117) with respect to its specific binding to MC1R, downstream signalling and eumelanin production in experimental models. Methods: The competitive binding and production of intracellular cyclic adenosine 3', 5'-monophosphate in cells expressing recombinant melanocortin receptors were examined. A mouse melanoma cell line B16F1 was used for the evaluation of in vitro melanin production. The in vitro activity of MT-7117 was determined with αMSH and [Nle4, D-Phe7]-αMSH (NDP-αMSH) as reference comparators. The change of coat colour and skin pigmentation were evaluated after repeat administration of MT-7117 by oral gavage to C57BL/6J-Ay/+ mice and cynomolgus monkeys, respectively. Results: MT-7117 showed the highest affinity for human MC1R compared to the other melanocortin receptors evaluated and agonistic activity for human, cynomolgus monkey and mouse MC1R, with EC50 values in the nanomolar range. In B16F1 cells, MT-7117 increased melanin production in a concentration-dependent manner. In vivo, MT-7117 (≥0.3 mg/kg/day p.o.) significantly induced coat colour darkening in mice. MT-7117 (≥1 mg/kg/day p.o.) induced significant skin pigmentation in monkeys and complete reversibility was observed after cessation of its administration. Conclusions: MT-7117 is a novel oral MC1R agonist that induces melanogenesis in vitro and in vivo, suggesting its potential application for the prevention of phototoxic reactions in patients with photodermatoses, such as erythropoietic protoporphyria and X-linked protoporphyria.

10.
Eur Rev Med Pharmacol Sci ; 24(9): 5140-5147, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32432778

RESUMEN

OBJECTIVE: Sesamin is a functional ingredient in sesame (Sesamum indicum) seeds and has many physiological effects. This study investigated whether sesame lignans, sesamin and episesamin (1:1), can suppress age-related disorders of the kidney. MATERIALS AND METHODS: Twenty-month-old mice were divided into three groups, and each group received a regular diet (O-C), diet containing sesame lignans (O-SE), and diet containing sesame lignans and α-tocopherol (VE; O-SE+VE), respectively, for 5 months. Six-month-old young mice (Y-C) were compared to the older mice. RESULTS: Renal lipofuscin deposition was increased in the O-C group compared to that in the Y-C group and its deposition with aging was significantly decreased in both O-SE and O-SE+VE groups. Plasma blood urea nitrogen levels in the O-C group increased compared to those in the Y-C group; however, those in both O-SE and O-SE+VE groups did not differ from those in the Y-C group. The number of podocytes in the O-C group decreased compared to that in the Y-C group and this effect was attenuated in the O-SE and O-SE+VE groups. The effect was strongest in the O-SE+VE group. Histological examinations showed that glomerular hypertrophy accompanied by mesangial hyperplasia and renal tubular degeneration was less severe in the O-SE and O-SE+VE groups than in the O-C group. Moreover, age-related increases in the mRNA expression of NADPH oxidase- and inflammation-related genes, including p67phox, p40phox, TNFα, and IL-6, in the kidney were suppressed in the O-SE and O-SE+VE groups. CONCLUSIONS: Sesame lignans might be useful to suppress age-related kidney disorders, and these effects could be enhanced with VE.


Asunto(s)
Envejecimiento/efectos de los fármacos , Antioxidantes/farmacología , Dioxoles/farmacología , Enfermedades Renales/tratamiento farmacológico , Lignanos/farmacología , alfa-Tocoferol/farmacología , Animales , Antioxidantes/administración & dosificación , Dieta , Dioxoles/administración & dosificación , Enfermedades Renales/metabolismo , Lignanos/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Sesamum/química , alfa-Tocoferol/administración & dosificación
11.
J Nutr Health Aging ; 23(3): 251-255, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30820513

RESUMEN

AIM: Phase angle (PhA) can be determined through bioelectrical impedance analysis and is a unique variable for skeletal muscle. The objective of this study was to evaluate the relationship between PhA and muscle mass/quality in older adults. In addition, we attempted to determine the cutoff value of PhA for poor muscle function. METHODS: Community-dwelling Japanese older men (n=285, 81.1±7.1 years) and women (n=724, 80.4±6.8 years) participated in this study and were classified into four groups based on the Asian Working Group for Sarcopenia (normal, presarcopenia, dynapenia, and sarcopenia). We measured PhA using bioelectrical impedance analysis, muscle quantity and quality indicators using ultrasonography, muscle strength, and physical performance and compared them in four groups. We also tried to determine the cutoff value of PhA for poor muscle function. RESULTS: We found a significant difference in PhA among the four groups in men (P<0.05), and the dynapenia (3.61±0.75°) and sarcopenia groups (3.40±0.74°) showed significantly lower values than the normal group (4.50±0.86°) (P<0.05), but not the presarcopenia group (4.12±0.85°). In women, a significant difference was also observed among the four groups (P<0.05), and the dynapenia (3.41±0.65°) and sarcopenia groups (3.31±0.66°) showed significantly lower measures than the normal group (4.14±0.71°) (P<0.05), but not the presarcopenia group (4.07±0.51°). The receiver-operating characteristic curve analysis indicated the best cutoff value of PhA (men: 4.05°, women: 3.55°) to discriminate sarcopenia and dynapenia from normal and presarcopenia. CONCLUSION: These findings suggest that PhA is a useful indicator for muscle function.


Asunto(s)
Impedancia Eléctrica/uso terapéutico , Fuerza Muscular/fisiología , Sarcopenia/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino
12.
Br J Surg ; 106(5): 616-625, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30725479

RESUMEN

BACKGROUND: Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula. METHODS: The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor). RESULTS: Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. CONCLUSION: Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevance Clinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated. Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula. Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.


Asunto(s)
Grasa Intraabdominal/fisiopatología , Lipólisis/fisiología , Pancreatectomía/efectos adversos , Fístula Pancreática/etiología , Pancreaticoduodenectomía/efectos adversos , Anciano , Animales , Modelos Animales de Enfermedad , Ácidos Grasos no Esterificados/análisis , Femenino , Humanos , Lipasa/antagonistas & inhibidores , Lipólisis/efectos de los fármacos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Obesidad Abdominal/fisiopatología , Fístula Pancreática/prevención & control , Jugo Pancreático/fisiología , Complicaciones Posoperatorias/fisiopatología , Ratas Sprague-Dawley , Factores de Riesgo
13.
J Nutr Health Aging ; 22(7): 819-823, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30080226

RESUMEN

BACKGROUND: Although several previous studies have found benefits for amino acid supplementation in terms of muscle function, the role of plasma amino acid concentrations on sarcopenia are not well addressed yet. OBJECTIVE: The aim of this study was to compare the amino acid concentrations at each stage of sarcopenia (normal, pre-sarcopenia, dynapenia, and sarcopenia) in community-dwelling older Japanese adults. SETTING AND SUBJECTS: Community-dwelling older Japanese women (n=232, 79.4±7.0 years) participated in this study. MEASUREMENTS: We measured plasma amino acid concentrations, 5-m walking speed, grip strength, and skeletal muscle mass using a bioelectrical impedance data acquisition system and compared them among participants at each stage of sarcopenia. RESULTS: The proportions of normal, pre-sarcopenia, dynapenia, and sarcopenia patients were 40.5% (n=94), 12.1% (n=28), 26.3% (n=61), and 21.1% (n=49), respectively. Significant differences were observed for concentrations of leucine, branched-chain amino acid (BCAAs), and essential amino acid (EAAs) among the four groups (p<0.05), and the dynapenia and sarcopenia groups showed significantly lower concentrations of leucine than the normal group (p<0.05). CONCLUSIONS: This study indicated a positive relationship between plasma leucine, BCAA and EAA concentrations and muscle function. A longitudinal study is needed to determine the causal relationship between leucine/BCAA concentrations and muscle function.


Asunto(s)
Aminoácidos de Cadena Ramificada/sangre , Aminoácidos Esenciales/sangre , Fuerza de la Mano/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiología , Sarcopenia/fisiopatología , Anciano , Impedancia Eléctrica , Femenino , Humanos , Vida Independiente , Japón , Estudios Longitudinales , Caminata/fisiología
14.
Clin Microbiol Infect ; 24(11): 1211.e1-1211.e7, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29454850

RESUMEN

OBJECTIVES: Panton-Valentine leukocidin (PVL) gene (lukS/F-PV)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA), particularly the USA300 clone, is a health concern worldwide. Recently, community-acquired MRSA clones have been found to spread and persist in hospital settings. We aimed to investigate the prevalence and molecular epidemiologic features of lukS/F-PV-positive MRSA in Japanese hospitals. METHODS: A total of 3433 MRSA isolated from nine hospitals in 2011-2015 were assessed. Molecular epidemiologic analysis performed by staphylococcal cassette chromosome mec typing, PVL typing, arginine catabolic mobile element typing, detection of virulence determinants, multilocus sequence typing, pulsed-field gel electrophoresis and antimicrobial susceptibility testing. RESULTS: The detection rate of lukS/F-PV was increased annually from 0.6% (5/817) in 2011 to 3.1% (17/544) in 2015. Molecular epidemiologic analysis for 64 lukS/F-PV-positive MRSA isolates revealed that 42 isolates (65.6%) were the USA300 clone. Resistance rates of levofloxacin and gentamicin among lukS/F-PV-positive isolates increased annually as a result of increased prevalence of the multidrug-resistant USA300 clone. CONCLUSIONS: This is the first report on dissemination of the USA300 clone and PVL-positive MRSA in multiple Japanese hospitals. Our data strongly suggest that the USA300 clone may become epidemic in Japanese hospitals.


Asunto(s)
Antibacterianos/farmacología , Toxinas Bacterianas/genética , Exotoxinas/genética , Leucocidinas/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/microbiología , Microbiología Ambiental , Hospitales , Humanos , Meticilina/farmacología , Resistencia a la Meticilina , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Infecciones Estafilocócicas/epidemiología , Tokio/epidemiología
15.
Plant Biol (Stuttg) ; 20(3): 537-545, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29394530

RESUMEN

Explosive pollen release is a mechanism used by some angiosperms that serves to attach pollen to a pollinator's body. It is usually adopted by species with zygomorphic tubular flowers and pollinated by birds and bees. The tree genus Meliosma (Sabiaceae, Proteales) has unique disc-like flowers that are externally actinomorphic, but internally zygomorphic, and release pollen explosively. To elucidate the adaptive significance of explosive pollen release, we observed flowering behaviour, the breeding system and pollinator visits to flowers of the Japanese species Meliosma tenuis in a temperate forest. Flowers bloomed in June and were nectariferous and protandrous. Explosive pollen release was triggered by slight tactile stimuli to anther filaments or staminodes in male-stage flowers. Because pollen cannot come into contact with the pistils enclosed by staminodes, M. tenuis is functionally protandrous. Artificial pollination treatments revealed that M. tenuis is allogamous. The dominant flower visitors were nectar-seeking drones of the bumblebee species Bombus ardens (Apidae). The drones' behaviour, pollen attachment on their bodies and fruit set of visit-restricted flowers suggest that they are the only agent triggering the explosive pollen release mechanism, and are the main pollinator of M. tenuis. The finding that bumblebee workers rarely visit these flowers suggests that the explosive pollen release has another function, namely to discourage pollen-harvesting bumblebee workers.


Asunto(s)
Abejas/fisiología , Magnoliopsida/fisiología , Polen/fisiología , Polinización/fisiología , Animales , Flores/anatomía & histología , Flores/fisiología , Reproducción/fisiología
16.
Ann Oncol ; 29(3): 624-631, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29293874

RESUMEN

Background: Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients and methods: Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin. Result: Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. Conclusion: S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment. Clinical trials number: UMIN000007834.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Capecitabina/administración & dosificación , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán/administración & dosificación , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Supervivencia sin Progresión , Tegafur/administración & dosificación , Adulto Joven
17.
J Clin Pharm Ther ; 43(2): 170-180, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28850685

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. METHODS: We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. RESULTS AND DISCUSSION: Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. WHAT IS NEW AND CONCLUSION: We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations.


Asunto(s)
Ensayos Clínicos Fase II como Asunto/métodos , Ensayos Clínicos Fase III como Asunto/métodos , Humanos , Proyectos de Investigación , Tamaño de la Muestra , Encuestas y Cuestionarios , Estados Unidos , United States Food and Drug Administration
18.
Int J Tuberc Lung Dis ; 22(12): 1505-1510, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30606324

RESUMEN

SETTING: The number of patients with non-tuberculous mycobacterial lung disease (NTM-LD) worldwide has been increasing. Mycobacterium avium complex lung disease (MAC-LD) accounts for 90% of NTM-LD. MAC-LD necessitates long-term treatment, but adverse reactions with long-term administration of drugs are poorly understood. OBJECTIVE: To evaluate adverse reactions with long-term administration of drugs for MAC-LD. DESIGN: We conducted a retrospective single-centre medical chart review of 364 patients administered two or more drugs between July 2010 and June 2015. RESULTS: The prevalence and median time to onset of adverse reactions were as follows: hepatotoxicity 19.5%, 55 days; leucocytopaenia 20.0%, 41 days; thrombocytopaenia 28.6%, 61.5 days; cutaneous reactions 9.3%, 30 days; ocular toxicity 7.7%, 278 days; and increase in serum creatinine 12.4%, 430.5 days. Multivariate analysis showed that rifampicin use was independently associated with thrombocytopaenia, and ethambutol use was independently associated with increases in serum creatinine. CONCLUSION: The main adverse reactions appeared within 3 months after start of treatment. Most patients were able to continue treatment with liver-supporting therapy, antihistamine agents or desensitisation therapy; however, ocular toxicity must be monitored for up to 1 year after start of treatment.


Asunto(s)
Antibacterianos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedades Pulmonares/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Esquema de Medicación , Etambutol/efectos adversos , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complejo Mycobacterium avium , Estudios Retrospectivos , Rifampin/efectos adversos , Esputo/microbiología , Factores de Tiempo , Adulto Joven
19.
Vet J ; 229: 6-12, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29183575

RESUMEN

There is no evidence-based diagnostic approach for diagnosis of pulmonary thromboembolism (PTE) in dogs. Many dogs with diseases that predispose to thrombosis are hypercoagulable when assessed with thromboelastography (TEG), but no direct link has been established. The aims of this study were: (1) to investigate if diseased dogs with PTE, diagnosed by computed tomography pulmonary angiography (CTPA), had evidence of hypercoagulability by TEG; (2) to characterise haemostatic and inflammatory changes in dogs with PTE; (3) to construct models for prediction of PTE based on combinations of haemostatic and inflammatory variables; and (4) to evaluate the performance of D-dimer measurement for prediction of PTE. Twenty-five dogs were included in this prospective observational study (PTE: n=6; non-PTE: n=19). Clot strength G values did not differ between the PTE and non-PTE groups in tissue factor (TF) or kaolin-activated TEG analyses. Haemostatic and inflammatory variables did not differ between the two groups. Linear discriminant analysis generated a model for prediction of PTE with a sensitivity and specificity of 100% when TF results were used as TEG data, and a model with sensitivity of 83% and specificity of 100% when kaolin results were used as TEG data. Receiver operating characteristic analysis of D-dimer levels showed that a value of >0.3mg/L yielded a sensitivity of 100% and a specificity of 71.4%. In conclusion, the study supports CTPA as method for diagnosing canine PTE, but shows that TEG alone cannot identify dogs with PTE. Models for prediction of PTE were generated, but require further validation.


Asunto(s)
Enfermedades de los Perros/diagnóstico por imagen , Modelos Teóricos , Embolia Pulmonar/veterinaria , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hemostáticos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Embolia Pulmonar/sangre , Embolia Pulmonar/diagnóstico por imagen , Curva ROC , Sensibilidad y Especificidad , Tromboelastografía/veterinaria , Tomografía Computarizada por Rayos X/veterinaria
20.
Sci Rep ; 7(1): 15478, 2017 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-29133830

RESUMEN

Electron- or X-ray-induced characteristic X-ray analysis has been widely used to determine chemical compositions of materials in vast research fields. In recent years, analysis of characteristic X-rays from muonic atoms, in which a muon is captured, has attracted attention because both a muon beam and a muon-induced characteristic X-ray have high transmission abilities. Here we report the first non-destructive elemental analysis of a carbonaceous chondrite using one of the world-leading intense direct current muon beam source (MuSIC; MUon Science Innovative Channel). We successfully detected characteristic muonic X-rays of Mg, Si, Fe, O, S and C from Jbilet Winselwan CM chondrite, of which carbon content is about 2 wt%, and the obtained elemental abundance pattern was consistent with that of CM chondrites. Because of its high sensitivity to carbon, non-destructive elemental analysis with a muon beam can be a novel powerful tool to characterize future retuned samples from carbonaceous asteroids.

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