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1.
Sci Rep ; 14(1): 755, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191891

RESUMEN

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1ß protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.


Asunto(s)
Fibras Musculares Esqueléticas , Ácido Oléico , Humanos , Animales , Ratones , Ácido Oléico/farmacología , Músculo Esquelético , Respiración de la Célula , Suplementos Dietéticos , Mamíferos
2.
Gene ; 846: 146852, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36058496

RESUMEN

Sleep in Drosophila was defined in the year 2000 by using Drosophila Activity Monitor (DAM) system. But DAM is very small tube space and one fly per tube is very limited to analyze for fly social behavior. To overcome such demerits of DAM system, we developed a novel automated sleep and rhythm analysis system (AutoCircaS) which monitors and records any behaviors like social mating, sleep, and circadian rhythm in flies (Drosophila) and small fishes medaka (Oryzias latipes) in free space using the time-lapse (one frame per 10 sec) imaging. AutoCircaS can detect the caffeine-induced insomnia in flies in light-dark (LD) and constant dark (DD) conditions. Thus, using the AutoCircaS, we discovered that Japanese traditional herbal medicines, KyushinKannouGan-ki (KKG), NouKassei (NK) as well as, and Sansoninto, significantly improved caffeine-induced insomnia in flies. The data suggest that AutoCircaS is useful for sleep analysis of small animals and screening of new sedative-hypnotics from many origins.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Animales , Cafeína/farmacología , Ritmo Circadiano , Drosophila , Drosophila melanogaster , Hipnóticos y Sedantes/farmacología , Japón , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico
4.
J Clin Monit Comput ; 36(4): 1213-1217, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34468914

RESUMEN

PURPOSE: The aim of the study was to evaluate the plasma rocuronium concentration in autologous blood transfusion obtained from the cell salvage (CS) system following cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This prospective observational study was conducted in a university teaching hospital from July to November 2020. Patients undergoing general anesthesia for cardiac surgery with CPB were enrolled in the study. After separation from CPB, residual blood remaining in the extracorporeal system was collected as the control sample. The second sample (CS blood) was collected from the autologous blood transfusion obtained after completion of the CS system with Cell Saver® Elite®. Hematocrit values of both samples were also examined. RESULTS: Ten subjects (aged 57-86 years) were enrolled in this study. Plasma rocuronium concentrations (ng/ml) were significantly lower in the CS blood (94.0 ± 77.5) compared to the control (2950 ± 812.2) (p = 0.002). Hematocrit values (%) were significantly higher in the CS blood (75.2 ± 11.3) compared to the control (40.2 ± 10.2) (p = 0.002). CONCLUSION: Autologous blood transfusion obtained from CS system following cardiac surgery with CPB, only retained a small amount of plasma rocuronium concentration, therefore, the risk of autologous blood transfusion contributing to clinically relevant residual neuromuscular blockade postoperatively should be considered to be low. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network under registration number UMIN000040877 (registration date; June 24, 2020).


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Pérdida de Sangre Quirúrgica , Transfusión de Sangre Autóloga , Puente Cardiopulmonar , Humanos , Rocuronio
5.
Future Oncol ; 18(1): 93-104, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34652217

RESUMEN

Aim: To describe the treatment landscape and associated economic burden for myelodysplastic syndrome in Japan. Methods: We studied nationwide retrospective claims data from 2008 to 2019. The study cohort was categorized into patients receiving transfusion, erythropoiesis-stimulating agent, erythropoiesis-stimulating agent + transfusion, azacitidine, azacitidine + transfusion and others. Results: Our study found that the azacitidine + transfusion group had the highest medical cost and severity of disease compared with the other groups. In those patients, healthcare resource utilization and the costs of transfusions, including iron chelation therapy, increased medical costs. Conclusion: Our retrospective analysis provides a current snapshot of real-world treatment patterns and associated incremental economic costs of iron chelation therapy with the presence of transfusions that drive an increase in total costs.


Asunto(s)
Síndromes Mielodisplásicos/terapia , Anciano , Anciano de 80 o más Años , Azacitidina , Transfusión Sanguínea , Costo de Enfermedad , Análisis de Datos , Femenino , Costos de la Atención en Salud , Hematínicos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/economía , Síndromes Mielodisplásicos/mortalidad , Estudios Retrospectivos
6.
Hepatol Commun ; 5(9): 1555-1570, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34510840

RESUMEN

How liver tolerance is disrupted in immune-mediated liver injury is currently unclear. There is also insufficient information available regarding susceptibility, precipitation, escalation, and perpetuation of autoimmune hepatitis. To explore how dietary fiber influences hepatic damage, we applied the concanavalin A (ConA)-induced acute immune-mediated liver injury model in mice fed a diet supplemented with 6.8% inulin, a water-soluble fermentable fiber. Twelve hours after ConA administration, inulin-supplemented diet-fed mice demonstrated significantly alleviated hepatic damage histologically and serologically, with down-regulation of hepatic interferon-γ and tumor necrosis factor and reduced myeloperoxidase (MPO)-producing neutrophil infiltration. Preconditioning with an inulin-supplemented diet for 2 weeks significantly reduced hepatic adenosine triphosphate (ATP) content; suramin, a purinergic P2 receptor antagonist, abolished the protective effect. Of note, the portal plasma derived from mice fed the inulin-supplemented diet significantly alleviated ConA-induced immune-mediated liver injury. Mechanistically, increased portal short-chain fatty acid (SCFA) levels, such as those of acetate and butyrate, by inulin supplementation leads to up-regulation of hepatic γ-type peroxisome proliferator-activated receptor (Pparg) and uncoupling protein 2 (Ucp2), which uncouples mitochondrial ATP synthesis downstream of PPARγ. Pparg down-regulating small interfering RNA cancelled the protective effect of inulin supplementation against MPO-producing neutrophil infiltration and the subsequent immune-mediated liver injury, suggesting that the SCFA-PPARγ-UCP2 axis plays a key role in the protective effect by inulin supplementation. Moreover, significant changes in the gut microbiota, including increased operational taxonomic units in genera Akkermansia and Allobaculum, also characterized the protective effect of the inulin-supplemented diet. Conclusion: There is a possible unraveled etiopathophysiological link between the maintenance of liver tolerance and dietary fiber. The SCFA-PPARγ-UCP2 axis may provide therapeutic targets for immune-mediated liver injury in the future.

7.
Gan To Kagaku Ryoho ; 48(13): 1840-1842, 2021 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-35046348

RESUMEN

We present the case of a 31-year-old woman with a chief complaint of a left breast mass. The patient visited our department for an evaluation of this left breast mass. Left breast cancer(cT1cN0M0, cStage Ⅰ, triple negative type)was diagnosed, and left partial mastectomy and sentinel node biopsy were performed. Although the pStage was the same prior to surgery, a BRCA1 mutation was identified on genetic testing. After administration of postoperative adjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel), consorted mastectomy, tissue expander insertion, and breast reconstruction with silicone implant were performed. Spontaneous pregnancy occurred 1 year and 10 months after the first operation. She had an uneventful delivery with a normal course of labor 2 years and 6 months after the surgery. Two years and 11 months after the first operation, she visited our institution with complaints of headache, dizziness, and difficulty eating. Upon assessment, brain, lung, liver, and bone metastases were identified on contrast-enhanced computed tomography. Concentrated glycerin and fructose, steroid administration, and whole-brain irradiation improved the symptoms due to cerebral edema. Thereafter, olaparib was started, and treatment was continued while maintaining partial response(PR).


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteína BRCA1/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Mutación , Embarazo
8.
Phytomedicine ; 80: 153360, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33038867

RESUMEN

BACKGROUND: Curcumin is a naturally occurring polyphenol found in Curcuma longa with multiple therapeutic properties, such as anti-inflammatory, wound healing and anti-cancer effects. Curcuma longa is also used as a galactagogue to improve milk production during lactation. PURPOSE: To assess curcumin could have therapeutic potential for breastfeeding mothers, we investigated whether and how curcumin influences milk production in lactating mammary epithelial cells (MECs) at the cellular and molecular levels. METHODS: We prepared a lactating MEC culture model that produced milk components and formed less-permeable tight junctions (TJs) to investigate the molecular mechanism of curcumin on milk production, TJs, and inflammation in vitro. RESULTS: Curcumin downregulated milk production in lactation MECs concurrently with inactivation of lactogenesis-relating signaling (STAT5 and glucocorticoid receptor). The maintenance of a less-permeable TJ barrier was also confirmed, although the TJ protein claudin-4 increased. Curcumin inactivated NFκB and STAT3 signaling, which are closely involved in inflammatory responses in weaning and mastitis mammary glands. The expression levels of IL-1ß and TNF-α were also decreased by curcumin treatment. Furthermore, curcumin blocked activation of inflammatory signaling by lipopolysaccharide treatment in MECs, similar to those in MECs that were treated with diclofenac sodium. The drastic phosphorylation of ERK was induced by curcumin treatment in the absence of EGF. U0126, an inhibitor of ERK phosphorylation, attenuated the adverse effects of curcumin on lactating MECs. CONCLUSION: The results of the present study suggests that curcumin downregulates milk production via inactivation of STAT5 and GR signaling with concurrent suppression of inflammatory responses via STAT3 and NFκB signaling in MECs. These findings provide new insights into the role of curcumin as a mild suppressor of milk production without inflammatory damages in breastfeeding mothers.


Asunto(s)
Curcumina/farmacología , Células Epiteliales/efectos de los fármacos , Glándulas Mamarias Animales/citología , Leche/metabolismo , Animales , Caseínas/metabolismo , Células Cultivadas , Curcumina/efectos adversos , Células Epiteliales/metabolismo , Femenino , Glucocorticoides/metabolismo , Lactancia/efectos de los fármacos , Lactancia/metabolismo , Lipopolisacáridos/toxicidad , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Mastitis/tratamiento farmacológico , Mastitis/metabolismo , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos
9.
Rinsho Ketsueki ; 61(9): 1205-1211, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33162517

RESUMEN

Frequent packed red blood cell (pRBC) transfusion can cause transfusional iron overload. Excess iron generates reactive oxygen species and provokes organ dysfunction. In lower-risk myelodysplastic syndrome (MDS), hyperferritinemia is known as one of the negative prognostic factors. Thus far, iron chelation therapy (ICT) is the only effective treatment for chronic iron overload induced by transfusion. Transfusional iron overload is diagnosed when serum ferritin (SF) levels are ≥500 ng/ml and cumulative volume of pRBC transfusion is ≥20 JPN units. ICT should be initiated when SF levels are ≥1,000 ng/ml and will be further continued until SF levels decline to <500 ng/ml. ICT serves to ameliorate organ dysfunction. A prospective study demonstrated that in patients with lower-risk MDS, ICT can reduce the risk of combined events, including cardiac events, hepatic events, AML transformation, and death of any cause. In some patients, hematological improvement will be observed. However, clinical features underling this hematological phenomenon are not fully understood. Therefore, ICT should not be performed solely for the purpose of hematological recovery.


Asunto(s)
Terapia por Quelación , Sobrecarga de Hierro , Reacción a la Transfusión , Transfusión Sanguínea , Humanos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/terapia , Estudios Prospectivos , Reacción a la Transfusión/terapia
10.
Rinsho Ketsueki ; 61(5): 475-483, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32507812

RESUMEN

Hepcidin is a key molecule that regulates iron metabolism in the body. Iron refractory iron deficiency anemia (IRIDA) is a genetic disorder caused by a defect in the TMPRSS6 gene encoding matriptase-2, a transmembrane serine protease that physiologically inhibits hepcidin production. In patients with IRIDA, the iron uptake in the intestine is remarkably reduced, and iron deficiency anemia (IDA) develops. However, in contrast to the ordinary IDA, high hepcidin levels in IRIDA keep the serum ferritin levels normal or sometimes high. Due to the malabsorption of iron in the intestine, IRIDA is refractory to oral iron supplementation, but partially responds to parenteral iron administration. A high hepcidin level gives IRIDA a lot of similarities with anemia of chronic disease, and a differential diagnosis between the two disorders needs careful inspection. Diagnosis of IRIDA needs genetic testing that is hardly available in most facilities, and therefore its clinical features are not fully understood.


Asunto(s)
Anemia Ferropénica , Pruebas Genéticas , Hepcidinas , Humanos , Hierro , Mutación
11.
J Agric Food Chem ; 65(50): 11118-11124, 2017 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-29189005

RESUMEN

During lactation, mammary epithelial cells (MECs) form the blood-milk barrier by less-permeable tight junctions (TJs) to prevent the leakage of milk components. Phytoestrogens affect the proliferation, differentiation, and apoptosis of MECs. However, it remains unclear whether phytoestrogens are involved in the blood-milk barrier. Therefore, we investigated the influence of phytoestrogens (coumestrol, genistein, and daidzein) by using an in vitro mouse-MEC-culture model. The results showed that coumestrol and genistein changed the expression of TJ proteins (claudins-3 and -4 and occludin), weakened barrier function, and reduced ß-casein production. Daidzein also weakened barrier function without inhibiting ß-casein production. Additionally, coumestrol and genistein induced apoptosis in MECs. These results indicate that phytoestrogens weaken the blood-milk barrier by directly affecting TJs and the cellular viability of lactating MECs in different ways.


Asunto(s)
Cumestrol/farmacología , Células Epiteliales/metabolismo , Genisteína/farmacología , Isoflavonas/farmacología , Glándulas Mamarias Animales/citología , Leche/metabolismo , Fitoestrógenos/farmacología , Uniones Estrechas/metabolismo , Animales , Caseínas/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/citología , Femenino , Humanos , Lactancia , Glándulas Mamarias Animales/irrigación sanguínea , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Ratones , Ratones Endogámicos ICR , Uniones Estrechas/efectos de los fármacos
12.
Front Psychiatry ; 8: 132, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28824465

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disease, and it is associated with sleep behavior disorders. In Drosophila melanogaster disease model, human α-synuclein A30P overexpressing flies (A30P PD model) have been shown for levy body aggregation and movement disorders. We measured sleep rhythms in the A30P PD model flies using the Drosophila Activity Monitoring system and found that they develop sleep defects at 20 days after eclosion. Furthermore, the total amount of sleep is significantly reduced in middle-aged PD model flies and the reduction has been attributed to nighttime sleep. The number and length of sleep bouts also decreased in middle-aged A30P PD model flies. Feeding of the oriental traditional herbal medicines (Kampo), Kamikihito and Unkei-to significantly ameliorate the level of sleep defects in A30P PD model flies. The Kamikihito and Unkei-to recovered 60-min sleep bouts number in the A30P PD model flies to the level of young (5 days after eclosion) flies. Kamikihito recovered sleep both in wild-type and PD model flies. Unkei-to ameliorates not only sleep but also motor function in PD model flies. The data suggest that Kamikihito and Unkei-to might be useful for the sleep defects in human PD patients as well as healthy human.

13.
Mol Nutr Food Res ; 61(10)2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28605125

RESUMEN

SCOPE: Isoflavones are a class of polyphonic compounds present in legumes and are called phytoestrogens because of their estrogen-like activity. Estrogen influences the behavior of mammary epithelial cells (MECs) during pregnancy and lactation. In this study, we investigated the direct influences of isoflavones and their metabolites in milk production ability of MECs. METHODS AND RESULTS: Mouse MECs were cultured with prolactin and dexamethasone (glucocorticoid analog) to induce milk production ability. Subsequently, lactating MECs were treated with each isoflavone. Coumestrol, biochanin A, genistein, and formononetin decreased the intracellular and secreted ß-casein. On the other hand, p-ethylphenol, daidzein, and equol did not significantly influence ß-casein production at any concentration. Coumestrol, biochanin A and genistein down-regulated the mRNA expression of whey acidic protein (WAP), lactoferrin and α-lactalbumin. In contrast, p-ethylphenol, daidzein and equol up-regulated ß-casein and/or WAP with α-lactalbumin. Furthermore, coumestrol and genistein down-regulated the expression of prolactin receptor and signal transducer and activator of transcription 5 (STAT5) accompanied by a decrease in STAT5 phosphorylation. CONCLUSION: Isoflavones and their metabolites influence the milk production ability of MECs through different interactions with prolactin/STAT5 signaling. Simultaneous intake of multiple isoflavones by consumption of legumes may induce promotive or adverse effects on lactating MECs.


Asunto(s)
Células Epiteliales/efectos de los fármacos , Isoflavonas/farmacología , Leche/química , Prolactina/metabolismo , Factor de Transcripción STAT5/metabolismo , Animales , Caseínas/metabolismo , Células Cultivadas , Cumestrol/farmacología , Células Epiteliales/metabolismo , Femenino , Genisteína/farmacología , Glándulas Mamarias Animales/citología , Glándulas Mamarias Animales/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Fenoles/farmacología , Fosforilación , Fitoestrógenos/farmacología , Prolactina/genética , Factor de Transcripción STAT5/genética
14.
Hematology ; 22(6): 347-353, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28097942

RESUMEN

OBJECTIVES: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated. METHODS: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry. RESULTS: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML. CD25 positivity was significantly correlated with an inferior complete remission (CR), event-free survival (EFS), and overall survival. Multivariate analysis showed CD25 positivity to be a significant prognostic predictor of CR and EFS. A regimen of low-dose cytarabine and aclarubicin combined with granulocyte-colony-stimulating factor (CAG) led to higher CR rates in the CD25-positive AML patients than intensive chemotherapies. CD25 expression was increased at relapse and in the development of leukemic status from myelodysplastic syndrome or myeloproliferative neoplasm. DISCUSSION: An effective treatment strategy for elderly patients with CD25-positive AML has not been established. Further studies are needed to evaluate the effect of a CAG regimen and allogenic stem cell transplantation in patients. CONCLUSION: CD25 is an independent prognostic factor in elderly AML patients. Alternative therapies for CD25-positive elderly AML patients are needed.


Asunto(s)
Biomarcadores de Tumor , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores , Terapia Combinada , Femenino , Humanos , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-2/genética , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
15.
Anim Sci J ; 88(3): 489-499, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27417667

RESUMEN

Our previous studies demonstrated that an 8-week intake of 5% (w/w) apple polyphenol (APP) in the diet improves muscle endurance of young-adult rats. In order to identify a lower limit of the dietary contribution of APP to the effect, the experiments were designed for lower-dose supplementation (8-week feeding of 0.5% APP in AIN-93G diet) to 12-week-old male Sprague-Dawley rats. Results clearly showed that the 0.5% APP diet significantly up-regulates slower myosin-heavy-chain (MyHC) isoform ratios (IIx and IIa relative to total MyHC) and myoglobin expression in lower hind-limb muscles examined (P < 0.05). There was a trend to increased fatigue resistance detected from measurements of relative isometric plantar-flexion force torque generated by a stimulus train delivered to the tibial nerve (F(98, 1372) = 1.246, P = 0.0574). Importantly, there was no significant difference in the animal body-phenotypes or locomotor activity shown as total moving distance in light and dark periods. Therefore, the present study encourages the notion that even low APP-intake may increase the proportions of fatigue-resistant myofibers, and has promise as a strategy for modifying performance in human sports and improving function in age-related muscle atrophy.


Asunto(s)
Suplementos Dietéticos , Malus , Fibras Musculares de Contracción Rápida/metabolismo , Polifenoles/administración & dosificación , Polifenoles/farmacología , Animales , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Fatiga Muscular/efectos de los fármacos , Mioglobina/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Isoformas de Proteínas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos
16.
Int J Hematol ; 105(3): 353-360, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27848180

RESUMEN

Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.


Asunto(s)
Sobrecarga de Hierro/epidemiología , Sobrecarga de Hierro/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Ferritinas/sangre , Hemocromatosis/diagnóstico , Hemocromatosis/epidemiología , Humanos , Hierro/metabolismo , Sobrecarga de Hierro/genética , Japón/epidemiología , Hepatopatías/etiología , Masculino , Redes y Vías Metabólicas/genética , Persona de Mediana Edad , Mutación , Encuestas y Cuestionarios , Reacción a la Transfusión , Adulto Joven
17.
Rinsho Ketsueki ; 56(6): 577-85, 2015 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-26256865

RESUMEN

A significant number of reports have described hematopoietic improvement after iron chelation therapy in iron-overloaded (IO) patients. These observations indicate negative impacts of excess iron on hematopoiesis. To investigate how excess iron affects hematopoiesis, we generated IO mice and examined hematopoietic parameters in these mice. IO mice did not show significant defects in the hematopoietic data of peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution. Quantitative RT-PCR analyses of the bone marrow stromal cells demonstrated remarkably reduced expressions of several important cytokines, e.g. CXCL12, VCAM-1, Kit-ligand and IGF-1, in the IO mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and oxidative stress was significantly increased in the IO bone marrow and liver. Our findings thus indicate that excess iron can damage bone marrow stromal cells and other vital organs that support hematopoiesis, presumably via increased oxidative stress.


Asunto(s)
Hematopoyesis , Sobrecarga de Hierro , Animales , Médula Ósea , Modelos Animales de Enfermedad , Células Madre Hematopoyéticas/citología , Humanos , Ratones , Estrés Oxidativo
18.
Eur J Haematol ; 93(2): 118-28, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24628561

RESUMEN

OBJECTIVES: Increasing numbers of reports have described hematopoietic improvement after iron chelation therapy in iron-overloaded patients. These observations indicate that excess iron could affect hematopoiesis unfavorably. To investigate how excess iron affects hematopoiesis in vivo, we generated iron-overloaded mice and examined hematopoietic parameters in these mice. METHODS: We generated iron-overloaded mice by injecting 200 mg of iron dextran into C57BL/6J mice, and immature hematopoietic cells in the bone marrow were evaluated by flow cytometric analyses, colony-forming assays, and bone marrow transplantation analyses. We also examined changes in molecular profiles of the hematopoietic microenvironment. RESULTS AND CONCLUSIONS: Iron-overloaded (IO) mice did not show significant defects in the hematopoietic data of the peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution, which indicates that excess iron impacts the hematopoietic microenvironment negatively. Microarray and quantitative RT-PCR analyses on the bone marrow stromal cells demonstrated remarkably reduced expression of CXCL12, VCAM-1, Kit-ligand, and IGF-1 in the iron-overloaded mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and increased oxidative stress was observed in the IO bone marrow and liver. Consequently, our findings indicate that excess iron can damage bone marrow stromal cells and other vital organs, disrupting hematopoiesis presumably by increased oxidative stress.


Asunto(s)
Células de la Médula Ósea/metabolismo , Médula Ósea/metabolismo , Microambiente Celular/genética , Sobrecarga de Hierro/genética , Hígado/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Médula Ósea/patología , Células de la Médula Ósea/patología , Trasplante de Médula Ósea , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Eritropoyetina/genética , Eritropoyetina/metabolismo , Expresión Génica , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Sobrecarga de Hierro/inducido químicamente , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/patología , Complejo Hierro-Dextran , Hígado/patología , Células Madre Mesenquimatosas/patología , Ratones , Ratones Endogámicos C57BL , Análisis por Micromatrices , Estrés Oxidativo , Factor de Células Madre/genética , Factor de Células Madre/metabolismo , Trombopoyetina/genética , Trombopoyetina/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo
19.
Int J Biometeorol ; 58(5): 999-1005, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23756607

RESUMEN

To reduce the risks of Japanese-style bathing, half-body bathing (HBLB) has been recommended in Japan, but discomfort due to the cold environment in winter prevents its widespread adoption. The development of the mist sauna, which causes a gradual core temperature rise with sufficient thermal comfort, has reduced the demerits of HBLB. We examined head-out 42 °C mist bathing with 38 °C HBLB up to the navel to see if it could improve thermal comfort without detracting from the merits of HBLB, with and without the effects of facial fanning (FF). The subjects were seven healthy males aged 22-25 years. The following bathing styles were provided: (1) HBLB-head-out half-body low bathing of 38 °C up to the navel (20 min); (2) HOMB-head-out mist bathing of 42 °C and HBLB of 38 °C (20 min); and (3) HOMBFF-HOMB with FF (20 min). HOMB raised the core temperature gradually. HOMBFF suppressed the core temperature rise in a similar fashion to HOMB. Increases in blood pressure and heart rate usually observed in Japanese traditional-style bathing were less marked in HOMBs with no significant difference with and without FF. The greatest body weight loss was observed after Japanese traditional-style bathing, with only one-third of this amount lost after mist bathing, and one-sixth after HBLB. HOMB increased thermal sensation, and FF also enhanced post-bathing invigoration. We conclude that HOMB reduces the risks of Japanese traditional style bathing by mitigating marked changes in the core temperature and hemodynamics, and FF provides thermal comfort and invigoration.


Asunto(s)
Baños/métodos , Temperatura Corporal , Sensación Térmica , Adulto , Presión Sanguínea , Cabeza , Frecuencia Cardíaca , Humanos , Japón , Masculino , Proyectos Piloto , Flujo Sanguíneo Regional , Piel/irrigación sanguínea , Baño de Vapor , Sudoración , Orina , Agua , Adulto Joven
20.
World J Gastroenterol ; 18(21): 2735-8, 2012 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-22690086

RESUMEN

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.


Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Amoxicilina/administración & dosificación , Pruebas Respiratorias/métodos , Quimioterapia Combinada/métodos , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Urea/análisis , Adulto , Anciano , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Rabeprazol , Sensibilidad y Especificidad
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