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1.
J Oral Biosci ; 66(1): 98-104, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37979655

RESUMEN

OBJECTIVES: Immunoglobulin (Ig)A nephropathy has been associated with oral infections such as periodontitis, but its pathogenesis is not fully understood; no treatments exist. This study analyzes the influence of IgA nephropathy, an autoimmune disease, on the pathogenesis of pulpitis and apical periodontitis. METHODS: Two groups of mice were used in pulp infection experiments: high serum IgA nephropathy model mice (HIGA) and control mice (BALB/c). Histologic analyses of the pulp and apical periodontal tissues were performed on days 3, 5, 7, 14, and 28 following oral bacterial infection. The dynamics of odontoblasts, apoptotic cells, and IgA expression were analyzed using anti-Nestin, TUNEL, and anti-IgA staining, respectively. RESULTS: Inflammatory cells infiltrated the exposed pulp at day three in both groups and by 14 days, these cells had infiltrated from the pulp to the apical periodontal tissue. The area of necrotic pulp tissue increased significantly in the control group at seven days. Odontoblasts decreased from day three onwards and disappeared by 28 days in both groups. The number of apoptotic cells in the pulp and apical periodontal tissues was significantly higher in the experimental group at day 28. The experimental group exhibited a significant increase in IgA production in the pulp after 14 days. Bone resorption in the apical periodontal tissue was significantly decreased in the experimental group at day 28. CONCLUSIONS: The results of this study suggest that IgA nephropathy may modulate the inflammatory response and sustain long-term biological defense responses in pulpitis and apical periodontitis in HIGA mice.


Asunto(s)
Glomerulonefritis por IGA , Periodontitis Periapical , Pulpitis , Ratones , Animales , Pulpitis/complicaciones , Pulpitis/patología , Glomerulonefritis por IGA/etiología , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/patología , Periodontitis Periapical/complicaciones , Periodontitis Periapical/patología , Pulpa Dental/metabolismo , Pulpa Dental/patología , Inmunoglobulina A
2.
Cureus ; 15(7): e42668, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37525863

RESUMEN

Introduction Intravesical onabotulinumA injection is actively used for the treatment of overactive bladder (OAB). However, it occasionally results in significant post-void residual urine (PVR) volume, which can lead to complications and can further impair the activities of daily living in older people. Therefore, this study aimed to identify the predictors of a high post-onabotulinumA injection PVR volume in older women with severe OAB. Methods An observational study was conducted on older women who had previously received intravesical onabotulinumA injections to treat OAB between 2020 and 2022. Urodynamic studies and symptom assessments were conducted, and machine learning models, including random forest and support vector machine (SVM) models, were developed using the R code generated by Chat Generative Pre-trained Transformer 4 (ChatGPT, OpenAI, San Francisco, USA). Results Among 128 patients with OAB, 23 (18.0%) had a PVR volume of > 200 mL after receiving onabotulinumA injections. The factors associated with a PVR volume of > 200 mL were investigated using univariate and multivariate analyses. Age, frailty, OAB-wet, daytime frequency, and nocturia were significant predictors. Random forest analysis highlighted daytime frequency, frailty, and voiding efficiency as important factors. An SVM model incorporating daytime frequency, frailty, and voiding efficiency improved PVR volume prediction. Logit(p) estimation yielded an area under the receiver operating characteristic curve of 0.926294.  Conclusion The study found daytime frequency, frailty, and voiding inefficiency to be significant factors associated with a PVR volume of > 200 mL, in older women with severe OAB. Utilizing advanced machine learning techniques and following the guidance of ChatGPT, this research emphasizes the relevance of considering multiple intersecting factors for predicting PVR volume. The findings contribute to our understanding of onabotulinumA injection treatment for OAB and support evidence-based decision-making using readily available information.

3.
Blood Purif ; 52(1): 54-59, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35468597

RESUMEN

INTRODUCTION: Air bubbles in the dialysis circuit are rarely visible after automatic priming; however, they are often visible after the needles are manually connected to the circuit. To prevent this issue, we thought to prime needles with a circuit at automatic priming by the hemodialysis machine. In order to achieve this idea, we designed and manufactured a novel capped needle to connect the needles to the extracorporeal circuit before the automatic priming of the hemodialysis machine. This study investigated the effectiveness of this novel capped needle and compared it with the conventional method for preventing air bubble contamination. METHODS: We tested novel capped needles ten times to evaluate whether the dialysis machine works appropriately and removes air bubbles even with the attached capped needle. Next, we performed 25 trials using the conventional method, in which skilled nurses manually connect the needle. In both methods, we thoroughly counted the air bubbles with our naked eyes. We predicted that the capped needle would leave few bubbles in the circuit. In order to evaluate fewer bubbles, we conducted an additional experiment using a microparticle counter to measure the size and number of the bubbles. RESULTS: We thoroughly searched for air bubbles during each of the ten tests but could not find any bubbles visible to the naked eye. In the conventional method, bubbles were visible in 29 out of 50 cases. The bubble count was significantly lower in the capped-needle method than in the conventional method (p < 0.0001, Pearson's χ2 test). In the additional experiments using the microparticle counter, the average remaining air volume in the extracorporeal circuit was 0.0999 ± 0.2438 nL when the priming was performed using the novel capped needles. CONCLUSION: The novel capped needle eliminated all visible bubbles efficiently and effectively; therefore, it could be a valuable device for hemodialysis treatment. The reduction of air from the dialysis circuit may improve patient prognosis.


Asunto(s)
Microburbujas , Diálisis Renal , Humanos , Diálisis Renal/métodos
4.
J Pharmacol Sci ; 148(2): 214-220, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35063136

RESUMEN

Pulmonary hypertension (PH) is a severe and progressive disease that causes elevated right ventricular systolic pressure, right ventricular hypertrophy and ultimately right heart failure. However, the underlying pathophysiologic mechanisms are poorly understood. We previously showed that 3,4-l-dihydroxylphenyalanine (DOPA) sensitizes vasomotor response to sympathetic tone via coupling between the adrenergic receptor alpha1 (ADRA1) and a G protein-coupled receptor 143 (GPR143), a DOPA receptor. We investigated whether DOPA similarly enhances ADRA1-mediated contraction in pulmonary arteries isolated from rats, and whether GPR143 is involved in the PH pathogenesis. Pretreating the isolated pulmonary arteries with DOPA 1 µM enhanced vasoconstriction in response to phenylephrine, an ADRA1 agonist, but not to U-46619, a thromboxane A2 agonist or endothelin-1. We generated Gpr143 gene-deficient (Gpr143-/y) rats, and confirmed that DOPA did not augment phenylephrine-induced contractile response in Gpr143-/y rat pulmonary arteries. We utilized a rat model of monocrotaline (MCT)-induced PH. In the MCT model, the right ventricular systolic pressure was attenuated in the Gpr143-/y rats than in WT rats. Phenylephrine-induced cell migration and proliferation were also suppressed in Gpr143-/y pulmonary artery smooth muscle cells than in WT cells. Our result suggests that GPR143 is involved in the PH pathogenesis in the rat models of PH.


Asunto(s)
Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/genética , Monocrotalina/efectos adversos , Receptores Acoplados a Proteínas G/fisiología , Receptores de Neurotransmisores/genética , Sístole , Función Ventricular Derecha/genética , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Animales , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/etiología , Hipertrofia Ventricular Derecha/etiología , Técnicas In Vitro , Masculino , Arteria Pulmonar/fisiología , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 1/fisiología , Vasoconstricción/efectos de los fármacos , Vasoconstricción/genética , Disfunción Ventricular Derecha/etiología
5.
Sci Rep ; 11(1): 16843, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34413390

RESUMEN

Elevated angiotensin-converting enzyme 2 (ACE2) expression in organs that are potential targets of severe acute respiratory syndrome coronavirus 2 may increase the risk of coronavirus disease 2019 (COVID-19) infection. Previous reports show that ACE2 alter its tissue-specific expression patterns under various pathological conditions, including renal diseases. Here, we examined changes in pulmonary ACE2 expression in two mouse chronic kidney disease (CKD) models: adenine-induced (adenine mice) and aristolochic acid-induced (AA mice). We also investigated changes in pulmonary ACE2 expression due to renin-angiotensin system (RAS) blocker (olmesartan) treatment in these mice. Adenine mice showed significant renal functional decline and elevated blood pressure, compared with controls. AA mice also showed significant renal functional decline, compared with vehicles; blood pressure did not differ between groups. Renal ACE2 expression was significantly reduced in adenine mice and AA mice; pulmonary expression was unaffected. Olmesartan attenuated urinary albumin excretion in adenine mice, but did not affect renal or pulmonary ACE2 expression levels. The results suggest that the risk of COVID-19 infection may not be elevated in patients with CKD because of their stable pulmonary ACE2 expression. Moreover, RAS blockers can be used safely in treatment of COVID-19 patients with CKD.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , Riñón/metabolismo , Insuficiencia Renal Crónica/metabolismo , SARS-CoV-2/fisiología , Adenina , Enzima Convertidora de Angiotensina 2/genética , Animales , Ácidos Aristolóquicos , Modelos Animales de Enfermedad , Regulación hacia Abajo , Humanos , Imidazoles/administración & dosificación , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Especificidad de Órganos , Tetrazoles/administración & dosificación
6.
Neurosci Res ; 170: 370-375, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32896531

RESUMEN

Nicotine exerts its reinforcing actions by activating nicotinic acetylcholine receptors (nAChRs), but the detailed mechanisms remain unclear. Nicotine releases 3, 4-dihydroxyphenylalanine (DOPA), a neurotransmitter candidate in the central nervous system. Here, we investigated the distribution of GPR143, a receptor of DOPA, and nAChR subunits in the nigrostriatal and mesolimbic regions. We found GPR143 mRNA-positive cells in the striatum and nucleus accumbens. Some of them were surrounded by tyrosine hydroxylase (TH)-immunoreactive fibers. There were some GPR143 mRNA-positive cells coexpressing TH, and nAChR subunit α4 or α7 in the substantia nigra and ventral tegmental area. These findings suggest that DOPA-GPR143 signaling may be involved in the nicotine action in the nigrostriatal and mesolimbic dopaminergic systems.


Asunto(s)
Receptores Nicotínicos , Dihidroxifenilalanina , Nicotina/farmacología , ARN Mensajero , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Sustancia Negra/metabolismo , Área Tegmental Ventral/metabolismo
7.
J Pharmacol Sci ; 144(2): 89-93, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32763057

RESUMEN

l-3,4-dihydroxyphenylalanine (l-DOPA) is a candidate neurotransmitter. l-DOPA is released by nicotine through nicotinic receptors. Recently, G-protein coupled receptor GPR143, was identified as a receptor for l-DOPA. In this study, genetic association studies between GPR143 genetic polymorphisms and smoking behaviors revealed that the single-nucleotide polymorphism rs6640499, in the GPR143 gene, was associated with traits of smoking behaviors in Japanese individuals. In Gpr143 gene-deficient mice, nicotine-induced hypolocomotion and rewarding effect were attenuated compared to those in wild-type mice. Our findings suggest the involvement of GPR143 in the smoking behaviors.


Asunto(s)
Proteínas del Ojo/genética , Eliminación de Gen , Estudios de Asociación Genética , Glicoproteínas de Membrana/genética , Nicotina/efectos adversos , Polimorfismo de Nucleótido Simple , Receptores Acoplados a Proteínas G/genética , Receptores de Neurotransmisores/genética , Refuerzo en Psicología , Trastornos Relacionados con Sustancias/genética , Animales , Pueblo Asiatico , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Índice de Severidad de la Enfermedad
8.
Front Pharmacol ; 10: 1119, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31632270

RESUMEN

l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective therapeutic agent for Parkinson's disease (PD). l-DOPA is traditionally believed to be an inert amino acid that exerts actions and effectiveness in PD through its conversion to dopamine. In contrast to this generally accepted idea, l-DOPA is proposed to be a neurotransmitter. Recently, GPR143 (OA1), the gene product of ocular albinism 1 was identified as a receptor candidate for l-DOPA. GPR143 is widely expressed in the central and peripheral nervous system. GPR143 immunoreactivity was colocalized with phosphorylated α-synuclein in Lewy bodies in PD brains. GPR143 may contribute to the therapeutic effectiveness of l-DOPA and might be related to pathogenesis of PD.

9.
J Biochem ; 166(5): 383-392, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31504625

RESUMEN

The apelin receptor (APJ), a receptor for apelin and elabela/apela, induces vasodilation and vasoconstriction in blood vessels. However, the prolonged effects of increased APJ-mediated signalling, involving vasoconstriction, in smooth muscle cells have not been fully characterized. Here, we investigated the vasoactive effects of APJ gain of function under the control of the smooth muscle actin (SMA) gene promoter in mice. Transgenic overexpression of APJ (SMA-APJ) conferred sensitivity to blood pressure and vascular contraction induced by apelin administration in vivo. Interestingly, ex vivo experiments showed that apelin markedly increased the vasoconstriction of isolated aorta induced by noradrenaline (NA), an agonist for α- and ß-adrenergic receptors, or phenylephrine, a specific agonist for α1-adrenergic receptor (α1-AR). In addition, intracellular calcium influx was augmented by apelin with NA in HEK293T cells expressing APJ and α1A-AR. To examine the cooperative action of APJ and α1A-AR in the regulation of vasoconstriction, we developed α1A-AR deficient mice using a genome-editing technique, and then established SMA-APJ/α1A-AR-KO mice. In the latter mouse line, aortic vasoconstriction induced by a specific agonist for α1A-AR, A-61603, were significantly less than in SMA-APJ mice. These results suggest that the APJ-enhanced response requires α1A-AR to contract vessels coordinately.


Asunto(s)
Receptores de Apelina/metabolismo , Músculo Liso Vascular/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Vasoconstricción , Animales , Humanos , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Músculo Liso Vascular/química
10.
Ther Apher Dial ; 22(5): 476-484, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29968399

RESUMEN

Oxidative stress accelerates the development of cardiovascular disease. Plasma cystine, a thiol oxidative stress marker, is related to several established factors for cardiovascular disease risk and prognosis. Although a comprehensive oxidative stress index is clinically required for hemodialysis patients with high oxidative stress, there are few reports concerning thiol oxidative stress markers predicting their prognosis. We investigated the relationship between plasma amino acids including cystine levels and cardiovascular disease-related and all-cause mortality in 132 maintenance hemodialysis patients. Higher cystine levels were associated with old age, longer hemodialysis duration, hemodialysis-associated hypotension, higher cardiothoracic ratio, higher blood urea nitrogen, and lower ankle-brachial index. Multivariate Cox regression analysis revealed that high plasma cystine was independently related with both cardiovascular disease mortality and all-cause mortality. Thus, high plasma cystine levels predict the prognosis of hemodialysis patients. High cystine levels necessitate a careful investigation for the cause of oxidative stress and comorbidities like vascular injury.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Cistina/sangre , Estrés Oxidativo , Diálisis Renal/métodos , Factores de Edad , Anciano , Índice Tobillo Braquial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
11.
Clin Exp Nephrol ; 22(4): 773-781, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29230587

RESUMEN

BACKGROUND: Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg -/-) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-ß1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-ß1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required. METHODS: We performed renal denervation and administered the α2-adrenergic receptor (AR) antagonist, atipamezole, to Atg -/- mice. A renin inhibitor, aliskiren, which was preliminarily confirmed to reduce TGF-ß1 gene expression in kidneys of the mice, was additionally administered to assess the effect on the arterial hypertrophy and interstitial fibrosis. RESULTS: Norepinephrine content in kidneys of Atg -/- mice was three times higher than in kidneys of wild-type mice. Interventions by renal denervation and atipamezole resulted in amelioration of the histological findings. Overexpression of TGF-ß1 gene in kidneys of Atg -/- mice was altered in a manner linked to the histological findings. Surprisingly, aliskiren reduced α2-AR gene expression, interstitial fibrosis, and arterial hypertrophy in kidneys of Atg -/- mice, which lack renin substrate. CONCLUSIONS: Alpha2-AR signaling is one of the causes of persistent renal arterial hypertrophy in Atg -/- mice. Aliskiren also angiotensinogen-independently reduces the extent of renal arterial hypertrophy, partly thorough downregulation of α2-ARs. Although renal arterial hypertrophy in Atg -/- mice appears to be of multifactorial origin, TGF-ß1 may play a key role in the persistence of such hypertrophy.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Amidas/farmacología , Fumaratos/farmacología , Arteria Renal/patología , Angiotensinógeno/genética , Animales , Fibrosis , Hipertrofia , Japón , Riñón , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Renina , Tokio , Factor de Crecimiento Transformador beta1
12.
JCI Insight ; 2(18)2017 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-28931752

RESUMEN

Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure. This response was attenuated in Gpr143 gene-deficient (Gpr143-/y) mice. Specific knockout of Gpr143 in vascular smooth muscle cells (VSMCs) also showed a similar phenotype, indicating that L-DOPA directly modulates ADRA1 signaling in the VSMCs. L-DOPA at nanomolar concentrations alone produced no effect on the VSMCs, but it enhanced phenylephrine-induced vasoconstriction and intracellular Ca2+ responses. Phenylephrine also augmented the phosphorylation of extracellular signal-regulated kinases in cultured VSMCs from WT but not Gpr143-/y mice. In WT mice, blood pressure increased during the transition from light-rest to dark-active phases. This elevation was not observed in Gpr143-/y mice. Taken together, our findings provide evidence for L-DOPA/GPR143 signaling that exerts precursor control of sympathetic neurotransmission through sensitizing vascular ADRA1.


Asunto(s)
Levodopa/farmacología , Tono Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Animales , Calcio/metabolismo , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiología , Fenilefrina/farmacología , Fosforilación , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Vasoconstrictores/farmacología
13.
J Atheroscler Thromb ; 24(2): 147-156, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-27453255

RESUMEN

AIM: Patients with orthostatic hypotension (OH) have high arterial stiffness. Patients with diabetes mellitus (DM) often have cardiac autonomic neuropathy that leads to OH; however, whether OH is an indicator of arterial stiffness progression is unclear. We aimed to investigate whether the cardio-ankle vascular index (CAVI) varies between DM patients with and without OH using the sit-to-stand test (STST). METHODS: One hundred and fifty-nine patients with DM underwent CAVI assessment and blood pressure (BP) and heart rate change evaluation during the STST. OH was defined as a decline in systolic BP (SBP) and/or diastolic BP of at least 20 mmHg or 10 mmHg, respectively, in the initial and late upright positions compared with that in the sitting position. RESULTS: OH was diagnosed in 42 patients (26.4%). DM patients with OH had significantly higher CAVI (9.36±1.15 versus 8.89±1.18, p=0.026) than those without OH. CAVI was significantly inversely correlated with systolic and diastolic BP changes (R=-0.347, p<0.001 and R=-0.314, p<0.001, respectively) in the initial upright position. Multivariate regression analysis revealed that age, SBP changes, and low frequency component in the initial upright position were independent determinants of CAVI. CONCLUSION: Patients with DM having large BP drops occurring when moving from sitting to standing have high arterial stiffness. A significant BP drop during the STST necessitates careful evaluation of advanced arterial stiffness in patient with DM.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Biomarcadores/análisis , Presión Sanguínea/fisiología , Diabetes Mellitus/diagnóstico , Prueba de Esfuerzo/métodos , Hipotensión Ortostática/fisiopatología , Rigidez Vascular/fisiología , Adulto , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus/metabolismo , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Equilibrio Postural/fisiología , Pronóstico , Análisis de la Onda del Pulso
14.
Atherosclerosis ; 240(1): 297-304, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25818388

RESUMEN

OBJECTIVE: There is no clinical evidence that supports the benefit of integrative medicine, defined as combination therapy of oriental and western medicine, on obesity-related hypertension. This study evaluates the efficacy of Bofu-tsusho-san (BOF), an oriental herbal medicine, on the ambulatory blood pressure (BP) profile in hypertensive patients with obesity. METHODS: The study design was a multicenter, randomized, open-label, parallel-group controlled trial in 107 hypertensive patients with obesity. Participants were randomly assigned to receive either the conventional control therapy or BOF add-on therapy. In both groups antihypertensive therapy was aimed at achieving the target clinic BP. The primary outcome was change in the ambulatory BP profile from baseline to 24 weeks after randomization. RESULTS: Daytime systolic BP variability, an important parameter of ambulatory BP profile, was decreased in the BOF group, and the difference in the changes in daytime systolic BP variability was significant between the BOF and control group (Control vs BOF; the change from baseline in daytime systolic BP variability, 1.0±3.3 vs -1.0±3.3%; p=0.006). CONCLUSION: The BOF add-on therapy effectively improved the ambulatory BP variability. This is the first report suggesting that an integrative medicine approach may exert favorable effects on obesity-related hypertension compared with conventional pharmaceutical treatment. CLINICAL TRIAL REGISTRATION: UMIN000003878.


Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Hipertensión/tratamiento farmacológico , Obesidad/complicaciones , Anciano , Antihipertensivos/efectos adversos , Monitoreo Ambulatorio de la Presión Arterial , Quimioterapia Combinada , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Hipertensión/fisiopatología , Japón , Masculino , Persona de Mediana Edad , Fitoterapia , Plantas Medicinales , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
15.
Intern Med ; 52(10): 1079-83, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23676594

RESUMEN

The case of a 68-year-old woman with purpura nephritis associated with nephrotic syndrome is herein described. The patient's clinical course and the findings of a renal biopsy study revealed purpura nephritis. Following treatment with corticosteroids and intravenous cyclophosphamide accompanied by an angiotensin II type I receptor-blocker, an anti-platelet drug and an hydroxymethylglutaryl (HMG)-CoA, the proteinuria mildly decreased. Additional rituximab therapy led to a complete remission. This report describes our successful experience using rituximab to treat refractory nephrotic syndrome of purpura nephritis. Further studies are required to confirm the efficacy of rituximab as an alternative therapy for nephrotic syndrome.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Vasculitis por IgA/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Nefritis/etiología , Síndrome Nefrótico/etiología , Administración Oral , Anciano , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/etiología , Vasculitis por IgA/complicaciones , Infusiones Intravenosas , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Nefritis/patología , Síndrome Nefrótico/patología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prednisolona/administración & dosificación , Prednisolona/uso terapéutico , Proteinuria/etiología , Inducción de Remisión , Rituximab
16.
Liver Int ; 33(1): 118-26, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23121371

RESUMEN

BACKGROUND: Apelin-APJ signalling is known to play important roles in heart physiology and pathology; however, its functions in liver physiology and pathology remain unclear. On the other hand, Fas is an important molecule in hepatitis and other liver disease that belongs to the death receptor family. The aim of this study was to assess the relationship between apelin-APJ signaling and Fas-mediated liver injury in mice. METHODS: APJ(-/-) mice and wild type (WT) mice were administered an intraperitoneal injection of an agonistic anti-Fas antibody (clone; Jo2), and sacrificed after 3 or 6 h to assess the liver histology. The expression levels of apelin and APJ, plasma levels of transaminases, activities of hepatic caspases and activations of stress-activated protein kinases were also analysed. RESULTS: Before the Jo2 injection, APJ was weakly expressed in the hepatocytes in spots; on the other hand, after the Jo2 injection, it had spread into whole hepatocytes. Moreover, the mRNA expression level of apelin and APJ in the liver increased after Jo2 injection. In the APJ(-/-) mice, the liver injuries and apoptotic changes were significantly inhibited as compared with those in the WT mice. Dramatic increase in JNK activation was observed in the WT mice after Jo2 injection, whereas such activation was completely absent in the APJ(-/-) mice. JNK inhibitor partially, but significantly suppressed Jo2-mediated liver injury in WT mice. CONCLUSION: Apelin-APJ signalling may promote Fas-induced liver injury at least partially via JNK activation, and may thus serve as a potential therapeutic target in cases of acute liver injury.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/metabolismo , Hepatopatías/metabolismo , Hígado/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptor fas/metabolismo , Adipoquinas , Animales , Anticuerpos Monoclonales , Anticuerpos Monoclonales de Origen Murino , Apelina , Receptores de Apelina , Apoptosis , Caspasas/metabolismo , Modelos Animales de Enfermedad , Activación Enzimática , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hepatopatías/etiología , Hepatopatías/genética , Hepatopatías/patología , Hepatopatías/prevención & control , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Factores de Tiempo
17.
Nature ; 487(7408): 477-81, 2012 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-22837003

RESUMEN

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.


Asunto(s)
Colitis/etiología , Colitis/microbiología , Intestinos/microbiología , Desnutrición/complicaciones , Metagenoma , Peptidil-Dipeptidasa A/metabolismo , Triptófano/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , Biocatálisis , Colitis/tratamiento farmacológico , Colitis/patología , Sulfato de Dextran , Diarrea/complicaciones , Proteínas en la Dieta/metabolismo , Proteínas en la Dieta/farmacología , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Vida Libre de Gérmenes , Homeostasis , Inmunidad Innata , Intestinos/patología , Masculino , Desnutrición/metabolismo , Ratones , Modelos Biológicos , Niacinamida/metabolismo , Niacinamida/farmacología , Niacinamida/uso terapéutico , Peptidil-Dipeptidasa A/deficiencia , Peptidil-Dipeptidasa A/genética , Sistema Renina-Angiotensina/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Ácido Trinitrobencenosulfónico , Triptófano/farmacología , Triptófano/uso terapéutico
18.
Clin Exp Hypertens ; 31(3): 259-70, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19387902

RESUMEN

We examined risk factors for coronary heart disease (CHD) by ambulatory blood pressure (BP) monitoring in 72 diabetic hypertensives who were hospitalized for the educational program. The patients were divided into two groups (CHD group, 19 subjects; and non-CHD group, 53 subjects) along with or without co-existing CHD. On ambulatory BP monitoring, no significant differences were found between the groups regarding BP values through the day. However, the CHD group had a significantly greater BP variability than non-CHD group. The result of logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor for CHD.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Enfermedad Coronaria/epidemiología , Complicaciones de la Diabetes/complicaciones , Hipertensión/complicaciones , Anciano , Enfermedad Coronaria/fisiopatología , Estudios Transversales , Complicaciones de la Diabetes/fisiopatología , Femenino , Humanos , Hipertensión/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo
19.
Nephron Exp Nephrol ; 111(1): e20-30, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19052474

RESUMEN

BACKGROUNDS/AIMS: It has been reported that urinary oxidative stress markers are higher in diabetic patients with proteinuria. We performed the present study to elucidate the relationship between urinary excretion of oxidative stress markers, albumin excretion, and histological changes, and to confirm the potential utility of oxidative stress markers for clinical treatment. METHODS: Diabetic db/db mice or nondiabetic db/m mice were administered candesartan (10 mg/kg/day) or hydralazine (50 mg/kg/day) for 18 weeks. RESULTS: Thirty-week-old male db/db mice treated with control vehicle revealed elevated urinary excretion and immunohistological levels of 8-hydroxydeoxyguanosine in glomeruli when compared to db/m mice. Treatment with candesartan, but not hydralazine, reduced these values to levels in db/m mice. Increased mesangial expansion, urinary excretion of albumin and 8-isoprostane, and glomerular immunohistological levels of nitrotyrosine in db/db mice were also decreased markedly by candesartan but not hydralazine. Interestingly, correlations between levels of albumin and oxidative stress markers in urine were very high, even when groups undergoing long-term (44 weeks) treatment were included (correlation coefficient 0.767 with respect to 8-hydroxydeoxyguanosine, 0.888 with respect to 8-isoprostane). CONCLUSION: It is anticipated that urinary concentrations of oxidative stress markers will be direct barometers of glomerulus-derived oxidative stress and glomerular injury in diabetic nephropathy.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bencimidazoles/uso terapéutico , Desoxiguanosina/análogos & derivados , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/orina , Dinoprost/análogos & derivados , Tetrazoles/uso terapéutico , Tirosina/análogos & derivados , 8-Hidroxi-2'-Desoxicoguanosina , Albuminuria/orina , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Animales , Antihipertensivos/uso terapéutico , Bencimidazoles/farmacocinética , Biomarcadores/orina , Compuestos de Bifenilo , Desoxiguanosina/orina , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/orina , Nefropatías Diabéticas/fisiopatología , Dinoprost/orina , Modelos Animales de Enfermedad , Hidralazina/uso terapéutico , Glomérulos Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/fisiología , Tetrazoles/farmacocinética , Resultado del Tratamiento , Tirosina/orina
20.
Clin Exp Nephrol ; 12(3): 224-7, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18224274

RESUMEN

A 65-year-old woman with a 48-year history of Behçet's disease associated with nephrotic syndrome is described. Immunofluorescence study revealed IgA nephropathy. Following treatment with an angiotensin II type-I receptor-blocker, an anti-platelet drug, and an HMG-CoA reductase inhibitor, accompanied by dietary restrictions of protein and sodium, proteinuria was markedly decreased. This report describes our experience with a rare entity of Behçet's disease complicated by nephrotic syndrome due to IgA nephropathy. Routine urine examination and renal biopsy are needed for the detection and diagnosis of renal problems with Behçet's disease.


Asunto(s)
Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Glomerulonefritis por IGA/complicaciones , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/diagnóstico , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Atorvastatina , Síndrome de Behçet/tratamiento farmacológico , Bencimidazoles/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Dilazep/uso terapéutico , Quimioterapia Combinada , Femenino , Ácidos Heptanoicos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Síndrome Nefrótico/etiología , Pirroles/uso terapéutico , Tetrazoles/uso terapéutico , Vasodilatadores/uso terapéutico
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