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1.
Immun Inflamm Dis ; 8(2): 228-235, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32180373

RESUMO

INTRODUCTION: We previously reported that fibroblast growth factor 23 (FGF23)-klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23-klotho signaling pathway in immune cells may occur in these patients. METHODS: We analyzed the number of klotho-positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme-linked immunosorbent assay. RESULTS: The number of klotho-positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients. CONCLUSIONS: We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti-inflammatory and immunosuppressive factor.


Assuntos
Proteína ADAM17/sangue , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/sangue , Leucócitos Mononucleares/metabolismo , Insuficiência Renal Crônica/genética , Proteína ADAM17/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Linhagem Celular , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/genética , Humanos , Hospedeiro Imunocomprometido , Proteínas Klotho , Masculino , Camundongos , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Uremia/sangue , Uremia/genética
2.
J Pharm Biomed Anal ; 182: 113139, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32045827

RESUMO

Osteocytes play an important role in the regulation of serum phosphorus by producing fibroblast growth factor 23 (FGF23). FGF23 production is stimulated by 1α,25-dihydroxyvitamin D in osteocytes. However, it is unclear whether vitamin D induces FGF23 production in osteocytes directly. Therefore, we investigated vitamin D-induced FGF23 production in osteocyte-like cells derived from MC3T3-E1 osteocyte progenitor cells. We also investigated differences in the induction of FGF23 by 1α,25-dihydroxyvitamin D and various vitamin D analogs. MC3T3-E1 cells were differentiated into osteocyte-like cells (MCT3-E1-OLCs) by treatment with various agents including ß-glycerophosphate and ascorbic acid. MCT3-E1-OLCs were stimulated with 1α,25-dihydroxyvitamin D3 and subsequent FGF23 gene expression was 2631 ± 605 times higher compared with untreated cells. The expression of FGF23 in MCT3-E1-OLCs transfected with a knockdown sequence against vitamin D receptor (VDR) was significantly decreased compared with that in cells transfected with the control vector. Therefore, the induction of FGF23 in osteocytes by vitamin D may be primarily mediated via VDR. The potential of 25(OH)vitamin D3, paricalcitol, and maxacalcitol to induce FGF23 production was almost the same as that of 1α,25-dihydroxyvitamin D3. However, falecalcitriol and eldecalcitol demonstrated a reduced potential to induce FGF23 compared with 1α,25-dihydroxyvitamin D3. Our results demonstrate that FGF23 induction is different among the analogs of 1α,25-dihydroxyvitamin D3. Therefore, an appropriate vitamin D analog should be chosen for each patient with mineral and bone disorder, considering its effect on FGF23 production.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Osteócitos/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Vitamina D/análogos & derivados , Animais , Diferenciação Celular , Linhagem Celular , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Camundongos , Osteócitos/metabolismo , Receptores de Calcitriol/genética , Vitamina D/farmacologia
3.
Semin Dial ; 31(5): 519-527, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29738093

RESUMO

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short- and long-term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end-stage renal disease requiring dialysis or transplantation is attracting increased attention.


Assuntos
Injúria Renal Aguda/epidemiologia , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Doenças Cardiovasculares/etiologia , Estado Terminal/mortalidade , Estado Terminal/terapia , Humanos , Incidência , Insuficiência Renal Crônica/etiologia , Fatores de Risco
4.
Growth Factors ; 34(5-6): 196-202, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28095739

RESUMO

The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220+ CD21/CD35+ CD1d+ CD43- marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c+ CD45R/B220+ CD11b- CD8α- were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23-Klotho signaling could play a biological or immunological role in the spleen.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glucuronidase/metabolismo , Baço/metabolismo , Animais , Linfócitos B/metabolismo , Células Dendríticas/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/genética , Glucuronidase/genética , Proteínas Klotho , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Baço/citologia
5.
Intern Med ; 54(17): 2207-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26328648

RESUMO

A 29-year-old woman was diagnosed with Henoch-Schönlein purpura nephritis (HSPN) based on the presence of purpura and histopathological findings showing crescent formation, mesangial proliferation and IgA deposition in the glomerular mesangium. She was treated with high-dose steroids; however, the nephritic syndrome persisted. Therefore, we diagnosed her with steroid-resistant HSPN and decided to add treatment with cyclosphamide pulse therapy. After one year of treatment, the histopathological findings, including crescent formation and IgA deposition, improved, as confirmed on a renal biopsy, and the patient fulfilled the criteria for complete remission. Cyclophosphamide pulse therapy may be considered an effective treatment for intractable HSPN.


Assuntos
Ciclofosfamida/administração & dosagem , Vasculite por IgA/tratamento farmacológico , Imunossupressores/administração & dosagem , Nefrite/patologia , Pulsoterapia , Esteroides/administração & dosagem , Adulto , Ciclofosfamida/efeitos adversos , Feminino , Frequência Cardíaca , Humanos , Vasculite por IgA/patologia , Imunossupressores/efeitos adversos , Monitorização Fisiológica , Nefrite/imunologia , Indução de Remissão , Resultado do Tratamento
7.
Intern Med ; 51(14): 1827-33, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22821095

RESUMO

OBJECTIVE: We investigated the present state of, and trends in, hemodialysis therapy in Wakayama, with the aim of identifying present and future problems. METHODS: We compared the number of patients on maintenance hemodialysis, patients newly commencing hemodialysis each year, and proportion of diseases prompting the initiation of hemodialysis, between Wakayama and all Japan from 2002 to 2009, using the CD-ROM, "An overview of dialysis treatment in Japan," published by the Japanese Society for Dialysis Therapy. RESULTS: The number of patients on maintenance hemodialysis per head of population was higher in Wakayama than in all Japan throughout the study period. The number of patients newly commencing hemodialysis per head of population was higher in Wakayama than in all Japan from 2002 to 2004, but no significant difference was seen after 2005. The proportion of patients with chronic glomerulonephritis as the causative disease for hemodialysis initiation was higher in Wakayama than in all Japan. However, nephrosclerosis was less common as the causative condition in Wakayama than in all Japan. The proportions of the different causative diseases were similar in all patients on maintenance hemodialysis in Wakayama as in the newly initiated patients. Accordingly, some patients diagnosed with chronic glomerulonephritis might actually have nephrosclerosis, or treatment may be inadequate. CONCLUSION: In order to reduce the number of patients requiring maintenance hemodailysis, it is important to accurately differentiate between chronic glomerulonephritis and nephrosclerosis, and also to treat patients with either disease appropriately.


Assuntos
Glomerulonefrite/diagnóstico , Glomerulonefrite/terapia , Nefroesclerose/diagnóstico , Nefroesclerose/terapia , Diálise Renal , Doença Crônica , Diagnóstico Diferencial , Educação Médica , Glomerulonefrite/epidemiologia , Humanos , Japão/epidemiologia , Nefroesclerose/epidemiologia , Diálise Renal/estatística & dados numéricos
8.
Artigo em Inglês | MEDLINE | ID: mdl-22723728

RESUMO

Hyperphosphatemia has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. In addition, it influences the clinical course of patients with chronic kidney disease. Phosphate (Pi) binder is required in the management of hyperparaphosphatemia, because dietary Pi restriction and Pi removal by hemodialysis alone are insufficient. Lanthanum carbonate, a powerful Pi binder, has a similar effect to aluminum hydroxide in reducing serum Pi levels. As it is excreted via the liver, lanthanum carbonate has an advantage in patients with renal failure. The effect of lanthanum carbonate on serum Pi levels is almost two times higher than that of calcium (Ca) carbonate, which is commonly used. Lanthanum carbonate and Ca carbonate have an additive effect. Worldwide, there is 6 years worth of clinical treatment data on lanthanum carbonate; however, we have 3 years of clinical use in Japanese patients with hyperphosphatemia. No serious side effects have been reported. However, the most important concern is bone toxicity, which has been observed with use of aluminum hydroxide. For this study, clinical research involved analysis of bone biopsies. Although osteomalacia is the most noticeable side effect, this was not observed. Both the high- and the low-turnover bone disease concentrated into a normal bone turnover state. However, as the authors have less than 10 years' clinical experience with lanthanum carbonate, patients should be monitored carefully. In addition, it is necessary to demonstrate whether potent treatment effects on hyperphosphatemia improve the long-term outcome.

9.
Clin Calcium ; 19(2): 219-23, 2009 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-19182362

RESUMO

The lanthanum carbonate which is the new phosphate binder decreased serum phosphorus value significantly in comparison with the placebo group, showed equal serum phosphorus decrease action to those at the capacity which in addition is less than calcium carbonate and sevelamer hydrochloride.


Assuntos
Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Nefropatias/complicações , Lantânio/uso terapêutico , Doença Crônica , Humanos , Lantânio/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
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