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1.
Am J Kidney Dis ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38522728

RESUMO

We present the case of a 61-year-old man who developed nephrotic syndrome as a result of syphilis-associated secondary membranous nephropathy (MN). The patient showed nephrotic syndrome remission following antibiotic treatment for syphilis alone. Pathologically, the target antigen of immune complexes accumulated on glomerular basement membranes (GBM) in secondary MN caused by syphilis has been reported to be neuron-derived neurotrophic factor (NDNF). His renal histopathology was consistent with secondary MN caused by syphilis, with a full-house pattern on immunofluorescence microscopy, in addition to NDNF deposits that colocalized with IgG deposits granularly on the GBM. However, to date, there is no serological evidence for the involvement of NDNF in the GBM. In the present study, we found that anti-NDNF autoantibodies in the acute-phase serum disappeared in the convalescent-phase serum of a patient who recovered from syphilis and nephrotic syndrome after antibiotic therapy alone. This result supports the hypothesis that treatment of syphilis with antibiotics suppresses NDNF's antigenicity. In summary, we found new serological evidence emphasizing that NDNF is an etiological antigen in secondary MN caused by syphilis.

2.
Heart Vessels ; 38(3): 309-317, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36169707

RESUMO

Chronic vasculitis is considered to be associated with future cardiovascular events. Here, we present major cardiovascular events (MACEs) in patients who underwent coronary computed tomography angiography (CCTA) for screening for coronary artery disease (CAD), and the association between MACEs and the inflammation marker pentraxin (PTX)-3 or highly sensitive C-reactive protein (hsCRP). The patients who underwent CCTA for the purpose of screening for CAD at Fukuoka University Hospital (FU-CCTA registry), 456 patients with suspected CAD or at least one cardiovascular risk factor were followed for up to 5 years. The levels of PTX-3 and hsCRP in blood were measured at the time of CCTA, and the patients were divided into two groups according to the presence (MACEs group) or absence (non-MACEs group) of MACEs. There were no differences in PTX-3 or hsCRP between the MACEs (-) and MACEs ( +) groups in all patients. A multivariate analysis related to the presence or absence of MACEs by logistic regression analysis of inflammation factors (PTX-3 and hsCRP) in addition to conventional risk factors as independent variables was performed. PTX-3 was a predictor of MACEs in males, whereas smoking, but not PTX-3, was a predictor of MACEs in females. PTX-3 could be a predictor of MACEs in males, but not females.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , Masculino , Humanos , Proteína C-Reativa/análise , Angiografia Coronária/métodos , Prognóstico , Doença da Artéria Coronariana/diagnóstico por imagem , Fatores de Risco , Inflamação , Sistema de Registros
3.
BMC Nephrol ; 24(1): 196, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386392

RESUMO

BACKGROUND: Machine Learning has been increasingly used in the medical field, including managing patients undergoing hemodialysis. The random forest classifier is a Machine Learning method that can generate high accuracy and interpretability in the data analysis of various diseases. We attempted to apply Machine Learning to adjust dry weight, the appropriate volume status of patients undergoing hemodialysis, which requires a complex decision-making process considering multiple indicators and the patient's physical conditions. METHODS: All medical data and 69,375 dialysis records of 314 Asian patients undergoing hemodialysis at a single dialysis center in Japan between July 2018 and April 2020 were collected from the electronic medical record system. Using the random forest classifier, we developed models to predict the probabilities of adjusting the dry weight at each dialysis session. RESULTS: The areas under the receiver-operating-characteristic curves of the models for adjusting the dry weight upward and downward were 0.70 and 0.74, respectively. The average probability of upward adjustment of the dry weight had sharp a peak around the actual change over time, while the average probability of downward adjustment of the dry weight formed a gradual peak. Feature importance analysis revealed that median blood pressure decline was a strong predictor for adjusting the dry weight upward. In contrast, elevated serum levels of C-reactive protein and hypoalbuminemia were important indicators for adjusting the dry weight downward. CONCLUSIONS: The random forest classifier should provide a helpful guide to predict the optimal changes to the dry weight with relative accuracy and may be useful in clinical practice.


Assuntos
Asiático , Alterações do Peso Corporal , Aprendizado de Máquina , Diálise Renal , Humanos , Pressão Sanguínea , Peso Corporal , Algoritmo Florestas Aleatórias , Japão
4.
J Clin Biochem Nutr ; 72(2): 171-182, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36936876

RESUMO

This study examined the bioactivities and mechanisms of the non-centrifugal cane sugar polyphenols saponarin, schaftoside, and isoschaftoside in the salivary gland and their effects on salivation. In acute isolated C57BL/6N mouse submandibular gland cells, these polyphenols led to a higher increase in intracellular calcium after stimulation with the muscarinic agonist carbachol. Stimulation of these cells with polyphenols enhanced ATP production, aquaporin-5 translocation to the plasma membrane and eliminated intracellular reactive oxygen species generated by H2O2. In addition, phosphorylation of endothelial nitric oxide synthase and increased nitric oxide production in vascular endothelial cells were observed. In vivo administration of these polyphenols to C57BL/6N male mice resulted in significantly increased blood flow (saponarin, p = 0.040; isoschaftoside, p = 0.010) and salivation (saponarin, p = 0.031). A randomized controlled trial showed that intake of non-centrifugal cane sugar significantly increased saliva secretion compared with placebo (p = 0.003). These data suggest that non-centrifugal cane sugar polyphenols affect several pathways that support salivation and increase saliva secretion by enhancing vasodilation. Hence, non-centrifugal cane sugar polyphenols can be expected to maintain saliva secretion and improve reduced saliva flow.

5.
Histochem Cell Biol ; 157(4): 443-457, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35037129

RESUMO

Stress stimulates both the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal axes. Activation of these axes results in the release of catecholamines, which in turn affects salivary secretion. Thus, repetitive stimulation of the α1-adrenergic receptor could be useful for studying the effects of chronic stress on the salivary gland. Salivary protein concentration and kallikrein activity were significantly lower in mice following chronic phenylephrine (PHE) administration. Chronic PHE administration led to significantly increased expression of the 78-kDa glucose-regulated protein, activating transcription factor 4, and activating transcription factor 6. Histological analyses revealed a decrease in the size of the serous cell and apical cytoplasm. These results suggest that repetitive pharmacological stimulation of the sympathetic nervous system elicits ER stress and translational suppression. In addition, PHE-treated mice exhibited a decrease in intracellular Ca2+ influx elicited by carbachol, a muscarine receptor agonist in the submandibular gland. The present findings suggest that chronic psychological, social, and physical stress could adversely affect Ca2+ regulation.


Assuntos
Estresse do Retículo Endoplasmático , Glândula Submandibular , Agonistas Adrenérgicos/metabolismo , Agonistas Adrenérgicos/farmacologia , Animais , Catecolaminas , Camundongos , Proteínas e Peptídeos Salivares/metabolismo , Proteínas e Peptídeos Salivares/farmacologia , Glândula Submandibular/metabolismo
6.
Transfusion ; 61(3): 738-743, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33166416

RESUMO

BACKGROUND: Alloantibodies against human platelet antigen (HPA)-15 are sometimes detected in patients with platelet transfusion refractoriness (PTR); however, little is known about their impact on PTR. STUDY DESIGN AND METHODS: Two patients who possessed HPA-15 alloantibodies (Patient 1, anti-HPA-15b; Patient 2, anti-HPA-15a) and human leukocyte antigen (HLA) antibodies were enrolled. The efficacy of HPA-15-compatible vs -incompatible platelet transfusion was compared by focusing on ABO- and HLA-matched transfusions on the basis of the 24-hour corrected count increment (CCI-24 hours) for platelets. The titers of HPA-15 antibodies in the patients' sera were also monitored. RESULTS: The patients received 71 and 12 ABO-compatible, HLA-matched platelet transfusions, respectively, during the monitoring periods. Among these transfusions, CCI-24 hours could be calculated in 27 and 10 transfusions, respectively, and the HPA-15 genotype of the donors was determined. There were no significant differences in the CCI-24 hours between the HPA-15 compatible and incompatible transfusions in both patients (P = .30 and .56, respectively, Mann-Whitney U test). There was no significant change in the HPA-15b antibody titer in Patient 1 during the monitoring period, while the HPA-15a antibody level in Patient 2 was undetectable at the end of the monitoring period, although the titer was low at the beginning. CONCLUSION: The efficacy of HPA-15-incompatible platelet transfusions was not necessarily inferior to that of HPA-15 compatible ones. Although the case number was limited, our results suggest that HPA-15 antibodies do not have a significant impact on the effects of platelet transfusion.


Assuntos
Antígenos CD/imunologia , Antígenos de Plaquetas Humanas/imunologia , Isoanticorpos/sangue , Leucemia Mieloide Aguda/imunologia , Síndromes Mielodisplásicas/imunologia , Proteínas de Neoplasias/imunologia , Transfusão de Plaquetas , Idoso , Antígenos CD/sangue , Incompatibilidade de Grupos Sanguíneos , Feminino , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/imunologia , Humanos , Isoanticorpos/imunologia , Japão , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Proteínas de Neoplasias/sangue , Projetos Piloto , Transfusão de Plaquetas/efeitos adversos , Estatísticas não Paramétricas
7.
Pathobiology ; 88(3): 234-241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556940

RESUMO

INTRODUCTION: Type-2 diabetes mellitus (T2DM) is associated with several systemic vascular symptoms and xerostomia. It is considered that hyperglycemia-induced polyuria and dehydration cause decreased body-water volume, leading to decreased saliva secretion and, ultimately, xerostomia. In T2DM, increased production of reactive oxygen species (ROS) causes tissue damage to vascular endothelial cells as well as epithelial tissue, including pancreas and cornea. Hence, a similar phenomenon may occur in other tissues and glands in a hyperglycemic environment. METHODS: Salivary gland tissue injury was examined, using T2DM model mouse (db/db). Transferase-mediated dUTP nick-end labeling (TUNEL) was conducted to evaluate tissue injury. The levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine, Bax/Bcl-2 ratio were measured as indicator of oxidative stress. Moreover, in vitro ROS production and cell injury was evaluated by mouse salivary gland-derived normal cells under high-glucose condition culture. RESULTS: In vivo and in vitro analysis showed a higher percentage of TUNEL-positive cells and higher levels of MDA and 8-hydroxy-2'-deoxyguanosine in salivary gland tissue of db/db mice. This suggests damage of saliva secretion-associated lipids and DNA by hyperglycemic-induced oxidative stress. To analyze the mechanism by which hyperglycemia promotes ROS production, mouse salivary gland-derived cells were isolated. The cell culture with high-glucose medium enhanced ROS production and promotes apoptotic and necrotic cell death. CONCLUSION: These findings suggest a novel mechanism whereby hyperglycemic-induced ROS production promotes salivary gland injury, resulting in hyposalivation.


Assuntos
Apoptose , Hiperglicemia/complicações , Espécies Reativas de Oxigênio/metabolismo , Glândulas Salivares/citologia , Glândulas Salivares/patologia , Animais , Técnicas de Cultura de Células , Meios de Cultura/química , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Modelos Animais de Doenças , Glucose/metabolismo , Camundongos , Estresse Oxidativo
8.
Heart Vessels ; 36(10): 1457-1465, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33744994

RESUMO

It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan-Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana , HDL-Colesterol , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Humanos , Sistema de Registros , Fatores de Risco
9.
Vox Sang ; 115(2): 202-206, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31777077

RESUMO

BACKGROUND AND OBJECTIVES: To detect HPA-15 alloantibodies, we previously developed a human platelet antigen 15 (HPA-15)-expressing cell line-based modified rapid monoclonal antibody immobilization of platelet antigen (CL-MR-MAIPA) assay. In this study, the protocol was modified for easier performance by introducing the mixed-passive haemagglutination (MPHA) principle. MATERIAL AND METHODS: In total, 20 samples that tested negative for HPA alloantibodies and eight that tested positive for HPA-15 alloantibodies (two and six positive for HPA-15a and HPA-15b antibodies, respectively) by CL-MR-MAIPA assay were used in this study. HPA-15 cell lines were incubated with serum/plasma and then solubilized. The lysate was transferred to a round-bottom well, which was coated with anti-human CD109 monoclonal antibodies. After incubation and repeated washings, sheep red blood cells, coated with anti-human IgG, were added to the wells. Haemagglutination was assessed the next day. RESULTS: The proposed cell line-based immune complex capture-dependent mixed-passive haemagglutination (CL-IC-MPHA) assay consisted of four steps, but required only 2 h to perform, except for overnight incubation for haemagglutination. Two HPA-15a alloantibody samples were reactive only for HPA-15a cells, and six HPA-15b alloantibody samples were reactive only for HPA-15b cells with the CL-IC-MPHA assay. The 20 samples that tested negative for HPA alloantibodies did not react with HPA-15a or HPA-15b cells. These data indicated that the CL-IC-MPHA assay was highly specific and sensitive. Unfortunately, the CL-IC-MPHA assay's analytic sensitivity was twofold to eightfold lower than that of the CL-MR-MAIPA assay. CONCLUSION: A novel, easy-to-perform protocol was successfully developed to detect HPA-15 alloantibodies with high specificity and sensitivity.


Assuntos
Antígenos CD/imunologia , Testes de Hemaglutinação/métodos , Técnicas de Imunoadsorção/normas , Proteínas de Neoplasias/imunologia , Antígenos CD/genética , Antígenos CD/metabolismo , Plaquetas/imunologia , Linhagem Celular , Células Cultivadas , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Testes de Hemaglutinação/normas , Humanos , Isoanticorpos/imunologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Sensibilidade e Especificidade
10.
Ann Rheum Dis ; 76(12): 1980-1985, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28330998

RESUMO

OBJECTIVES: To compare the performance of the new 2016 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (SS) with 1999 revised Japanese Ministry of Health criteria for diagnosis of SS (JPN), 2002 American-European Consensus Group classification criteria for SS (AECG) and 2012 ACR classification criteria for SS (ACR) in Japanese patients. METHODS: The study subjects were 499 patients with primary SS (pSS) or suspected pSS who were followed up in June 2012 at 10 hospitals in Japan. All patients had been assessed for all four criteria of JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). The clinical diagnosis by the physician in charge was set as the 'gold standard'. RESULTS: pSS was diagnosed in 302 patients and ruled out in 197 patients by the physician in charge. The sensitivity of the ACR-EULAR criteria in the diagnosis of pSS (95.4%) was higher than those of the JPN, AECG and ACR (82.1%, 89.4% and 79.1%, respectively), while the specificity of the ACR-EULAR (72.1%) was lower than those of the three sets (90.9%, 84.3% and 84.8%, respectively). The differences of sensitivities and specificities between the ACR-EULAR and other three sets of criteria were statistically significant (p<0.001). Eight out of 302 patients with pSS and 11 cases out of 197 non-pSS cases satisfied only the ACR-EULAR criteria, compared with none of the other three sets. CONCLUSIONS: The ACR-EULAR criteria had significantly higher sensitivity and lower specificity in diagnosis of pSS, compared with the currently available three sets of criteria.


Assuntos
Guias de Prática Clínica como Assunto , Reumatologia/normas , Síndrome de Sjogren/diagnóstico , Adulto , Diagnóstico Diferencial , Europa (Continente) , Feminino , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome de Sjogren/classificação , Inquéritos e Questionários , Estados Unidos
11.
Int J Mol Sci ; 18(9)2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28872625

RESUMO

Brain-derived neurotrophic factor (BDNF) is abundant in the hippocampus and plays critical roles in memory and synapse formation, as well as exerting antidepressant-like effects in psychiatric disorders. We previously reported that BDNF is expressed in salivary glands and affects blood BDNF content. However, the function of salivary BDNF remains unclear. The aim of this study was to generate transgenic mice overexpressing BDNF in the salivary glands. Hence, we used the Lama construct (hemagglutinin (HA)-tagged mouse Bdnf cDNA) to specifically express BDNF in mouse salivary glands. Compared with control mice, Bdnf-HA transgenic mice showed increased blood BDNF and expressed salivary BDNF-HA. Molecular analysis revealed enhanced hippocampal BDNF levels and activation of the BDNF receptor, tyrosine kinase B (TrkB), in transgenic mice. In both the open field and elevated-plus maze tests, transgenic mice showed anxiolytic-like behavioral effects compared with control or sialoadenectomized mice. Among downstream components of the BDNF-TrkB signaling pathway, metabolic activation of the γ-aminobutyric acid (GABA) synthetic pathway was found, including higher levels of the GABA synthetic enzyme, glutamate decarboxylase 1 (GAD1). Thus, we have established a transgenic mouse expressing BDNF in the parotid gland that may be useful to examine the hippocampal effects of salivary BDNF.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Glândulas Salivares/metabolismo , Animais , Ansiolíticos/metabolismo , Glutamato Descarboxilase/metabolismo , Hipocampo/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Tirosina Quinases/metabolismo , Ácido gama-Aminobutírico/metabolismo
12.
Pathobiology ; 83(6): 287-94, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27251053

RESUMO

OBJECTIVE: The decrease in female hormone levels at menopause affects whole-body homeostasis. Various therapies including hormone therapy and treatment with herbal supplements are available to improve menopausal symptoms. However, a method for evaluating their effectiveness has not been established. We sought to identify useful biomarkers to assess therapy efficacy. METHODS: We searched for salivary proteins affected by changes in female hormone levels in mouse submandibular glands. RESULTS: The expression of submandibular gland protein C (Smgc) was decreased following ovariectomy, while the expression of the alternative splicing transcript t-Smgc was increased. Notably, Smgc expression increased following ß-estradiol administration, and was barely detectable in the submandibular glands of male mice. CONCLUSION: The results suggest that Smgc expression may be estrogen dependent. Moreover, changes in the SMGC protein amount in the saliva were in accordance with those in mRNA expression in the submandibular gland. Our findings suggest that salivary proteins have potential as markers for evaluating therapies for menopausal symptoms.


Assuntos
Estrogênios/metabolismo , Mucinas/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Glândula Submandibular/metabolismo , Animais , Feminino , Humanos , Masculino , Menopausa/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Caracteres Sexuais
13.
Heart Vessels ; 31(1): 1-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25179298

RESUMO

Atherosclerosis is a disease characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs) and the expression of inflammatory proteins, those may lead to acute coronary syndrome (ACS). We investigated the expression level of TLR-4 in ACS, as compared with TLR-2 and patients with stable angina. Fifty-eight consecutive patients who underwent primary percutaneous coronary intervention (PCI, n = 29) because of ACS and elective PCI (n = 29) because of stable angina using a filter-device distal protection device system were prospectively analyzed. mRNA levels of TLR-2 and TLR-4 in debris containing various inflammatory tissues entrapped in the filter device were altogether analyzed using real-time PCR. There were no significant differences in age, sex distribution, between stable angina and ACS groups. TLR-4 expression levels were higher in patients with ACS than in patients with stable angina. TLR-4 might play a more important role than TLR-2 in atherogenesis, especially in ACS.


Assuntos
Síndrome Coronariana Aguda/genética , Aterosclerose/genética , Placa Aterosclerótica/fisiopatologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Síndrome Coronariana Aguda/cirurgia , Idoso , Angina Estável/genética , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Placa Aterosclerótica/metabolismo , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Regulação para Cima
14.
J Clin Biochem Nutr ; 59(2): 107-112, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27698537

RESUMO

Resveratrol is a natural polyphenol produced by plants in response to environmental stress. This compound has been shown to have pharmacological effects against a wide range of diseases including neurological, hepatic, cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in which loss of lacrimal and salivary gland function occurs, has been studied as an animal model for Sjögren's syndrome. In this study, we confirmed that administration of resveratrol results in increased secretion of saliva in NOD mice. Although resveratrol enhanced Sirt1 activity, inflammatory cell infiltration was not affected. Moreover, expression of the anti-inflammatory cytokine IL-10 in salivary glands was enhanced in the resveratrol-administered group. Thus, we confirmed a novel therapeutic effect for resveratrol on salivary dysfunction in Sjögren's syndrome.

15.
J Cell Biochem ; 116(4): 609-17, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25389129

RESUMO

It has been shown that the treatment of mammalian cells with sucrose leads to vacuole accumulation associated with lysosomes and upregulation of lysosomal enzyme expression and activity. Autophagy is an evolutionarily conserved homeostatic process by which cells deliver cytoplasmic material for degradation into lysosomes, thus it is probable that sucrose affects the autophagic activity. The role of sucrose in autophagy is unknown; however, another disaccharide, trehalose has been shown to induce autophagy. In the current study, we used mouse embryonic fibroblasts to investigate whether sucrose induces autophagy and whether vesicle formation is associated with autophagy. The results showed that sucrose induces autophagy while being accumulated within the endosomes/lysosomes. These vesicles were swollen and packed within the cytoplasm. Furthermore, trehalose and the trisaccharide raffinose, which are not hydrolyzed in mammalian cells, increased the rate of vesicles accumulation and LC3-II level (a protein marker of autophagy). However, fructose and maltose did not show the same effects. The correlation between the two processes, vesicle accumulation and autophagy induction, was confirmed by treatment of cells with sucrose plus invertase, or maltose plus acarbose-the α-glucosidase inhibitor-and by sucrose deprivation. Results also showed that vesicle accumulation was not affected by autophagy inhibition. Therefore, the data suggest that sucrose-induced autophagy through accumulation of sucrose-containing vesicles is caused by the absence of hydrolysis enzymes.


Assuntos
Endossomos/metabolismo , Fibroblastos/efeitos dos fármacos , Lisossomos/metabolismo , Sacarose/farmacologia , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Embrião de Mamíferos/citologia , Endossomos/química , Fibroblastos/citologia , Hidrólise , Lisossomos/química , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Rafinose/farmacologia , Sacarose/farmacocinética , Trealose/farmacologia
16.
J Immunol ; 188(9): 4654-62, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22467650

RESUMO

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a variety of biological effects by binding to environmental pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). Although numerous animal studies have demonstrated the harmful effects of dioxins, it remains controversial whether dioxins pose a risk to human health. Enhanced lytic replication of EBV is a risk factor for the development of autoimmune diseases and cancers. This study evaluated the possibility that ligand-activated AhR reactivates EBV. EBV reactivation and AhR transactivation were evaluated with luciferase assays. Saliva samples were collected from 19 patients with primary Sjögren's syndrome (SS). Control saliva samples were obtained from 10 healthy individuals and nine patients with severe dry mouth. TCDD enhanced BZLF1 transcription, which mediates the switch from the latent to the lytic form of EBV infection in EBV-positive B cell lines and in a salivary gland epithelial cell line. Moreover, TCDD-induced increases in BZLF1 mRNA and EBV genomic DNA levels were confirmed in the B cell lines. Saliva from SS patients activated the transcription of both CYP1A1 and BZLF1. Additionally, there was a positive correlation between CYP1A1 and BZLF1 promoter activities. AhR ligands elicited the reactivation of EBV in activated B cells and salivary epithelial cells, and these ligands are involved in SS. Our findings reveal novel aspects of the biological effects of dioxin and the AhR-dependent pathogenesis of autoimmune diseases.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/fisiologia , Receptores de Hidrocarboneto Arílico/imunologia , Síndrome de Sjogren/imunologia , Ativação Viral/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Linfócitos B/virologia , Callithrix , Linhagem Celular Transformada , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/imunologia , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/farmacologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/imunologia , Células HEK293 , Humanos , Dibenzodioxinas Policloradas/efeitos adversos , Dibenzodioxinas Policloradas/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Risco , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Glândulas Salivares/virologia , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Síndrome de Sjogren/virologia , Transativadores/biossíntese , Transativadores/imunologia , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/imunologia , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/imunologia , Ativação Viral/efeitos dos fármacos
17.
Heart Vessels ; 29(5): 659-66, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23979264

RESUMO

We investigated gender differences in factors influencing the electrocardiographic (ECG) findings of left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). The functional and geometric responses of the left ventricle to chronic pressure overload, such as hypertension and AS, have been reported to be different between men and women. However, gender differences in the factors influencing the ECG findings of LVH in pressure overload remain unknown. We conducted a retrospective observational study in consecutive patients with severe AS (aortic valve area (AVA) assessed by cardiac catheterization <1.0 cm(2)) without concomitant significant aortic regurgitation, mitral stenosis and/or regurgitation, conduction disturbance, or myocardial infarction (n = 35 males, 68 females). The ECG criteria were classified into three categories: (1) high voltage by the Sokolow-Lyon index associated with ST-T wave changes (with no digitalis therapy); (2) high voltage alone; and (3) normal. Groups 1 and 2 were defined as LVH on ECG. We compared the ECG findings in relation to the AS severity between genders. Women were older, but there were no significant differences in the prevalence of hypertension, AVA index (AVAI), mean pressure gradient or peak velocity across the AV, LV mass index (LVMI) derived from echocardiography or the distribution of ECG categories between genders. A multiple logistic regression analysis including age, gender, hypertension, AVAI, mean pressure gradient, and LVMI revealed that the LVMI (P = 0.001) and AVAI (P = 0.0434) were significantly related to the distribution of ECG categories. LVMI significantly predicted LVH on ECG in both genders, but AVAI was a predictive factor in only women. ECG LVH in patients with severe AS may be mainly reflected by LVMI in men and by both LVMI and AVAI in women. Factors other than AVA, such as end-stage disease and/or complicating factors such as hypertension, may underlie the observed differences in ECG findings of LVH between men and women.


Assuntos
Estenose da Valva Aórtica/complicações , Eletrocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico , Potenciais de Ação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Cateterismo Cardíaco , Distribuição de Qui-Quadrado , Comorbidade , Ecocardiografia Doppler em Cores , Ecocardiografia Doppler de Pulso , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Modelos Logísticos , Masculino , Análise Multivariada , Fenótipo , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Processamento de Sinais Assistido por Computador
18.
Lipids Health Dis ; 13: 57, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24673894

RESUMO

BACKGROUND: Metabolic syndrome is now widely appreciated as a cluster of metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing worldwide.In addition, low vegetable consumption has recently become a serious issue in Japan. Furthermore, Japan is facing a shortfall in places offering food that can help prevent metabolic syndrome in the first place. Our study is designed to influence these developments. We conducted a non-randomized controlled trial by offering a Japanese-style healthy lunch menu to middle-aged men in a workplace cafeteria. This menu was designed to prevent and reduce metabolic syndrome. METHODS: This intervention study took the form of a non-randomized controlled trial. Participants chose the control or intervention group. The control group consumed their habitual lunches without restriction and only nutrient contents were assessed. The intervention group received a Japanese-style healthy lunch at a workplace cafeteria for 3 months. The participants worked in offices at a city hall and mostly had low levels of physical activity. Data of 35 males (control group: 7 males, intervention group: 28 males, mean age: 47.2 ± 7.9 years) were collected and analyzed. RESULTS: We obtained an effective outcome by demonstrating that ongoing intake of a Japanese-style healthy lunch decreased blood pressure and serum lipids and increased plasma ghrelin levels. The results grew more pronounced as intake of Japanese-style healthy lunches increased in frequency. CONCLUSIONS: This study presents new empirical data as a result of an original intervention program undertaken in Japan. A Japanese-style healthy lunch menu containing many vegetables consumed can help prevent and/or improve metabolic syndrome.


Assuntos
Pressão Sanguínea/fisiologia , Grelina/sangue , Almoço , Síndrome Metabólica/sangue , Síndrome Metabólica/dietoterapia , Adulto , Feminino , Humanos , Japão , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Verduras
19.
Lipids Health Dis ; 13: 102, 2014 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-24961537

RESUMO

BACKGROUND: Vegetables and fruits are rich in vitamins, minerals and, dietary fiber and contribute to the prevention and improvement of obesity and metabolic syndrome. However, inadequate intake of vegetable and fruit is a concern in Japan.We therefore produced a juice mixture of fresh fruit and komatsuna (Brassica rapa L. var. perviridis: B. rapa) with the aim to investigate the effects of this juice mixture on anthropometric data, blood parameters, and dietary intake differences. METHODS: This study was performed as a single blind and randomized controlled trial. Subjects were 16 men (mean age, 46.4 ± 7.1 years), and they were divided into two groups (control group and intervention group). The intervention group consumed the juice mixture of fresh fruit and B. rapa. The control group consumed commercial vegetable juice. Subjects consumed juice twice a day throughout the weekday, for 4 weeks. We prepared both juices with an equivalent energy balance. RESULTS: Weight and body mass index (BMI) of the control group after 4 weeks were significantly increased compared with baseline values. Serum total cholesterol (T-Chol) and low-density lipoprotein cholesterol (LDL-Chol) of the intervention group after 4 weeks were significantly reduced compared with baseline values. Furthermore, intake of total vegetables and fruits were significantly increased compared with baseline values in both groups. CONCLUSIONS: Both vegetable juices contributed to improved intake of total vegetables and fruit. Compared with the intake of commercial vegetable juice, the intake of fresh fruit and B. rapa juice is highly effective in reducing serum cholesterol. Short-term intake of fresh fruit and B. rapa juice was shown to enhance cholesterol metabolism.


Assuntos
Bebidas , Brassica/química , Colesterol/sangue , Frutas , Verduras , Fibras na Dieta , Humanos , Pessoa de Meia-Idade , Método Simples-Cego
20.
J Clin Biochem Nutr ; 55(3): 168-73, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25411521

RESUMO

Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.

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