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Biol Pharm Bull ; 44(1): 7-17, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390552


Vitamin K2 is suggested to have a suppressive effect on the peripheral blood mononuclear cells (PBMCs) of pediatric atopic dermatitis patients. We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads array assay. Mitogen-activated protein kinase signaling molecules in concanavalin A-activated PBMCs were examined by enzyme-linked immunosorbent assay (ELISA) assays. At 10-100 µM, vitamin K2 significantly suppressed the proliferation of mitogen-activated PBMCs derived from atopic dermatitis patients and healthy subjects (p < 0.05). The interleukin (IL)-10 concentrations in plasma and the PBMC culture supernatants of atopic dermatitis patients were significantly higher than those of healthy subjects (p < 0.05). The IL-2 concentrations in the culture supernatants of atopic dermatitis PBMCs were significantly lower than those of healthy PBMCs (p < 0.05). Vitamin K2 significantly inhibited the IL-17A, IL-10, and tumor necrosis factor α (TNF-α) production (p < 0.05), and increased the IL-2 production (p < 0.01) in the culture supernatant of atopic dermatitis PBMCs. At 10-100 µM, vitamin K2 markedly decreased the of Mek1, extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and SAPK/c-Jun N-terminal kinase (JNK) expression in atopic dermatitis PBMCs (p < 0.05). Vitamin K2 is suggested to attenuate activated T-cell immunity in atopic dermatitis patients through the inhibition of mitogen-activated protein kinase-Mek1-ERK1/2 and SAPK/JNK signaling pathways.

Pediatr Int ; 61(12): 1188-1195, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31560147


BACKGROUND: Over 20 kinds of steroids, tacrolimus ointments, and cyclosporine capsules are usually recommended for the treatment of atopic dermatitis (AD), depending on the symptoms of patients. However, several side effects sometimes occur with the extensive use of these agents for the treatment of pediatric AD patients. The purpose of this study was to explore whether vitamin K2 could be a new immunosuppressive candidate for pediatric patients with AD. METHODS: The immunosuppressive efficacy of vitamin K2 was evaluated through a cell-culture procedure using mitogen-activated peripheral blood mononuclear cells (PBMCs) obtained from pediatric AD patients. RESULTS: The mean (SD) IC50 value of vitamin K2 for the proliferation of concanavalin A-activated PBMCs was 15.37 (30.05) µmol/L, while the value for tacrolimus was 0.10 (0.28) ng/mL (0.12 (0.35) nmol/L). There was a significant correlation between the IC50 values for vitamin K2 and those for tacrolimus (P = 0.0001, r = 0.8871). However, there was no significant correlation between the IC50 values of vitamin K2 and those of cyclosporine A or methylprednisolone. A significant correlation between the IC50 values of vitamin K2 or tacrolimus and blood eosinophil counts (P = 0.0099, r = 0.7086 and P = 0.0032, r = 0.7722, respectively) was observed. CONCLUSION: Vitamin K2 -inhibited T-cell mitogen stimulated proliferation of PBMCs from pediatric AD patients in a dose-dependent manner. The PBMCs from pediatric AD patients were more sensitive to the immunosuppressive efficacy of vitamin K2 than the PBMCs from healthy subjects. The individual immunosuppressive pharmacological efficacy of vitamin K2 and of tacrolimus could be inferred from the blood eosinophil count of pediatric AD patients.

Dermatitis Atópica/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Vitamina K 2/administración & dosificación , Adulto , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Niño , Preescolar , Ciclosporina/farmacología , Femenino , Voluntarios Sanos , Humanos , Inmunosupresores/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Metilprednisolona/farmacología , Tacrolimus/farmacología , Vitamina K 2/farmacología , Vitamina K 2/uso terapéutico
Allergy Asthma Immunol Res ; 10(5): 478-489, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30088368


PURPOSE: Few studies have compared fractional exhaled nitric oxide (FeNO) measurement by NIOX VERO® (NOV) and other devices in children. Moreover, there is no agreement between differences in FeNO values obtained using different devices in adults. Here, we compared FeNO values obtained using NOV and NObreath® (NOB) systems to derive a correction equation for children. METHODS: Eighty-eight participants (age 7-15 years) who were diagnosed with atopic bronchial asthma and visited Sagamihara National Hospital as outpatients between January and April of 2017 were included. We measured FeNO values obtained using NOB and NOV, and analyzed them using Wilcoxon tests and Altman-Bland plots. RESULTS: The median age of the participants was 11.5 years, and the scored Asthma Control Test (ACT) or Childhood ACT (C-ACT) was 25 (interquartile range, 24-25) or 26 (24-27). NOB and NOV values were significantly different (31 [14-52] versus 36 [20-59] ppb; P = 0.020) and strongly correlated (r = 0.92). An equation to convert NOB values into NOV values was derived using linear regression as follows: log NOV = 0.7329 × log NOB + 0.4704; NOB for 20, 40, 58, 80 and 100 ppb corresponded to NOV for 27, 44, 59, 73 and 86 ppb. Thus, NOB < 58 ppb suggested NOB < NOV, whereas NOB > 58 ppb suggested NOB > NOV. CONCLUSIONS: NOB and NOV values were strongly correlated. Participants whose FeNO values were relatively low represented NOB < NOV, whereas those whose FeNO values were relatively high represented NOB > NOV.

J Infect Chemother ; 24(7): 531-537, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29606414


Reactive arthritis after Group A streptococcal infection (poststreptococcal reactive arthritis: PSRA) that does not meet the Jones criteria for acute rheumatic fever (ARF) has been reported as a new entity for over a decade. In Japan there are few reports of PSRA. We encountered four children with arthritis accompanied with Group A streptococcal infection in our department. We investigated our cases and the recent Japanese literature. Japanese cases of PSRA are frequently accompanied with uveitis and erythema nodosum, and tonsillectomy resolved their symptoms in some cases. There were overlap cases between ARF, juvenile idiopathic arthritis, and PSRA.

Artritis Juvenil/diagnóstico por imagen , Artritis Reactiva/diagnóstico por imagen , Artritis Reactiva/microbiología , Infecciones Estreptocócicas/complicaciones , Adolescente , Antibacterianos/uso terapéutico , Artritis Juvenil/microbiología , Artritis Reactiva/tratamiento farmacológico , Biomarcadores/sangre , Niño , Preescolar , Quimioterapia Combinada , Eritema Nudoso , Femenino , Humanos , Japón , Masculino , Fiebre Reumática/diagnóstico por imagen , Fiebre Reumática/microbiología , Infecciones Estreptocócicas/tratamiento farmacológico , Tonsilectomía , Uveítis
Exp Dermatol ; 27(9): 1058-1060, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29697859


We estimated the pharmacological efficacy of vitamin K1 (VK1 ) and VK2 on the mitogen-activated peripheral blood mononuclear cells (PBMCs) of paediatric atopic dermatitis (AD) patients. VK2 suppressed the in vitro proliferation of T-cell mitogen-activated PBMCs of AD patients. In contrast, VK1 had little effect on the PBMC proliferation. The IL-2 production from the activated PBMCs of AD patients significantly increased (P < .05), while the production significantly decreased by 100 µmol L-1 VK2 (P < .01). In addition, 100 µmol L-1 VK2 reduced the percentage of CD4+ and CD4+CD25+ cells in PBMCs. These results suggest that VK2 can modulate T-cell function in PBMCs of AD patients.

Dermatitis Atópica/sangre , Leucocitos Mononucleares/fisiología , Vitamina K 1/farmacología , Vitamina K 2/farmacología , Vitaminas/farmacología , Recuento de Linfocito CD4 , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Niño , Concanavalina A/farmacología , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Humanos , Interleucina-10/metabolismo , Interleucina-2/metabolismo , Mitógenos/farmacología , Linfocitos T Reguladores/patología
J Infect Chemother ; 21(8): 610-2, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25960155


BACKGROUND: Acute rheumatic fever (ARF) is an illness caused by group A streptococcus (GAS) infection, and remains the leading cause of acquired heart disease in worldwide. Distinguishing between ARF and septic arthritis may be difficult. This report describes a case of suppurative arthritis overlapping with ARF. CASE PRESENTATION: A 4-year-old, previously healthy boy presented with fever and left leg pain. The level of anti-streptolysin O (ASO) was elevated. His throat swab cultures grew GAS, but none were detected in his synovial fluid. Magnetic resonance imaging revealed suspected arthritis and osteomyelitis. The patient was treated for septic arthritis, but was subsequently diagnosed with ARF, after the development of carditis. CONCLUSION: The clinical and laboratory features of ARF and suppurative arthritis demonstrate substantial overlap. Patients with an elevated ASO should undergo a careful cardiac examination for carditis associated with ARF by an echocardiogram.

Artritis Infecciosa/diagnóstico , Artritis Juvenil/diagnóstico , Osteomielitis/diagnóstico , Fiebre Reumática/diagnóstico , Fiebre Reumática/tratamiento farmacológico , Infecciones Estreptocócicas/complicaciones , Streptococcus pyogenes/aislamiento & purificación , Enfermedad Aguda , Artritis Infecciosa/microbiología , Artritis Juvenil/microbiología , Preescolar , Diagnóstico Diferencial , Humanos , Masculino , Miocarditis/microbiología , Osteomielitis/microbiología , Fiebre Reumática/microbiología , Infecciones Estreptocócicas/tratamiento farmacológico