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Cateterismo Cardíaco , Implantación de Prótesis de Válvulas Cardíacas , Válvula Pulmonar , Trombosis , Humanos , Trombosis/etiología , Trombosis/diagnóstico por imagen , Trombosis/diagnóstico , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Válvula Pulmonar/cirugía , Válvula Pulmonar/diagnóstico por imagen , Cateterismo Cardíaco/efectos adversos , Masculino , Femenino , Insuficiencia de la Válvula Pulmonar/etiología , Insuficiencia de la Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/fisiopatología , Ecocardiografía Transesofágica , Prótesis Valvulares Cardíacas/efectos adversos , Resultado del TratamientoRESUMEN
Background: In this study, we report the case of a 14-month-old female patient transferred from another hospital to our hospital with a 9-day history of fever and worsening dyspnea. Case Report. The patient tested positive for influenza type B virus 7 days before being transferred to our hospital but was never treated. The physical examination performed at presentation revealed redness and swelling of the skin at the site of the peripheral venous catheter insertion performed at the previous hospital. Her electrocardiogram revealed ST segment elevations in leads II, III, aVF, and V2-V6. An emergent transthoracic echocardiogram revealed pericardial effusion. As ventricular dysfunction due to pericardial effusion was not present, pericardiocentesis was not performed. Furthermore, blood culture revealed methicillin-resistant Staphylococcus aureus (MRSA). Thus, a diagnosis of acute pericarditis complicated with sepsis and peripheral venous catheter-related bloodstream infection (PVC-BSI) due to MRSA was made. Frequent bedside ultrasound examinations were performed to evaluate the outcomes of the treatment. After administering vancomycin, aspirin, and colchicine, the patient's general condition stabilized. Conclusions: In children, it is crucial to identify the causative organism and provide appropriate targeted therapy to prevent worsening of the condition and mortality due to acute pericarditis. Moreover, it is important to carefully monitor the clinical course for the progression of acute pericarditis to cardiac tamponade and evaluate the treatment outcomes.
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BACKGROUND: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old. METHODS: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed. RESULTS: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase. CONCLUSIONS: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.
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Desfibriladores Implantables , Adulto , Humanos , Niño , Adolescente , Estudios Retrospectivos , Resultado del Tratamiento , Desfibriladores Implantables/efectos adversos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Arritmias CardíacasRESUMEN
Stevens-Johnson syndrome (SJS) with respiratory distress can lead to fatal outcomes. However, there are a few reports of drug-induced lung injury with diffuse alveolar damage caused by acetaminophen, the most severe type. Here, we describe a fatal case of acetaminophen-induced SJS in a child with irreversible lung lesions.
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BACKGROUND: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.MethodsâandâResults:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. CONCLUSIONS: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.
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Cardiomiopatía Hipertrófica , Adolescente , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/epidemiología , Niño , Electrocardiografía/métodos , Humanos , Japón , Estudios ProspectivosAsunto(s)
Anomalías de los Vasos Coronarios/cirugía , Vasos Coronarios/cirugía , Remodelación Vascular , Adolescente , Anomalías de los Vasos Coronarios/complicaciones , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Anomalías de los Vasos Coronarios/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Humanos , Masculino , Paro Cardíaco Extrahospitalario/etiología , Fútbol , Resultado del TratamientoRESUMEN
Brain abscesses, infections within the brain parenchyma, can arise as complications of various conditions including infections, trauma, and surgery. However, brain abscesses due to polymicrobial organisms have rarely been reported in children. We herein report a case of a 9-year-old girl with unresolved congenital cyanotic heart disease (CCHD) presenting with right hemiplegia who was diagnosed with brain abscess caused by Streptococcus intermedius, Parvimonas micra, and Fusobacterium nucleatum after oropharyngeal injury. She was treated with intravenous antimicrobial therapy, drainage under craniotomy, and antiedema therapy with glycerol and goreisan, which led to the improvement of right hemiplegia to baseline; she was discharged following eight weeks of intravenous antimicrobial therapy. The clinical diagnosis of the brain abscess was difficult due to the nonspecific presentation, highlighting the importance of cranial imaging without haste in patients at increased risk for brain abscesses such as those with CCHD, presenting with fever in the absence of localizing symptoms or fever, accompanied with abnormal neurological findings.
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BACKGROUND: Recently, a student died of idiopathic ventricular fibrillation in a school where an automated external defibrillator (AED) had been installed. The tragedy could not be prevented because the only AED in the school was installed in the teachers' office, far from the school ground where the accident took place. This prompted establishment of a multiple AED system in schools. The aim of this study was to analyze the efficacy of the multiple AED system to prevent sudden death in school-aged children. METHODS: Assumed accident sites consisted of the school ground, gymnasium, Judo and Kendo hall, swimming pool, and classrooms on the first and the fourth floor. Multiple AED were installed in the teachers' office, gymnasium, some classrooms, and also provided as a portable AED in a rucksack. The time from the accident site to the teachers' office for single AED, and from the accident site to the nearest AED for multiple AED, was calculated. RESULTS: The AED retrieval time was significantly shorter in 55 elementary schools and in 29 junior high schools when multiple AED were installed compared with single AED. Except for the classroom on the fourth floor, the number of people who took >120 s to bring the AED to the accident site was lower when multiple AED were installed compared with the single AED. CONCLUSION: Multiple AED provided in appropriate sites can reduce the time to reach the casualty and hence prevent sudden death in school-aged children.
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Muerte Súbita/prevención & control , Desfibriladores , Instituciones Académicas , Fibrilación Ventricular/terapia , Adolescente , Niño , Femenino , Humanos , Masculino , EstudiantesRESUMEN
BACKGROUND: Sarcopenic obesity, age-related muscle loss, which is compensated by an increase in fat mass, impairs quality of life in elderly people. Although the increase in intramuscular fat is associated with decreased insulin sensitivity and increased metabolic risk factors, the origin of diabetes-associated intramuscular fat has not been elucidated. Here, we investigated intramuscular fat deposition using a muscle injury model in type 2 diabetic mice. METHODS: Male 8-week-old C57BL/6 and 8-week-old and 26-week-old KKAy underwent intramuscular injection of cardiotoxin (Ctx) (100 µL/10 µM) into the tibialis anterior (TA) muscles. After 2 weeks, the muscles were removed and evaluated. RESULTS: KKAy exhibited impaired muscle regeneration and ectopic fat deposition. Such impairment was more marked in older KKAy. These changes were also observed in another diabetic mouse model, db/db and diet-induced obese mice but not in streptozocin-induced diabetic mice. Deposited fat was platelet-derived growth factor (PDGF) receptor alpha positive and its cytoskeleton was stained with Masson's trichrome, indicating it to be of fibro-adipocyte progenitor cell origin. Expression of a myogenic marker, myoD, was lower and that of PDGF receptor alpha and CCAAT/enhancer binding protein (CEBP) alpha was higher in Ctx-injured TA of KKAy compared with that of C57BL/6. Peroxisome proliferator-activated receptor γ (PPARγ) was highly expressed in fat-forming lesions in older KKAy. Treatment with all-trans retinoic acid prevented the formation of intramuscular fat; however, treatment with GW9662, a PPARγ antagonist, increased the fibrotic change in muscle. CONCLUSIONS: Diabetic mice showed impaired muscle regeneration with fat deposition, suggesting that diabetes may enhance sarcopenic obesity through a mechanism involving anomalous fibro-adipocyte progenitor cell differentiation.
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BACKGROUND: We investigated the effects of fetal growth restriction (FGR) induced by maternal protein restriction on inflammatory vascular remodeling using a cuff-induced vascular injury mouse model. METHODS: Dams (C57BL/6J strain mice) were fed an isocaloric diet containing 20% protein (normal protein; NP) or 8% protein (low protein; LP) from 10 weeks of age until delivery. On the day of delivery, all dams were returned to the NP diet. After weaning, offspring were fed the NP diet. When offspring were 10 weeks of age, vascular injury was induced by polyethylene cuff placement around the femoral artery. RESULTS: Birth weight in offspring from dams fed LP until delivery (LPO) was significantly lower, but body weight was the same at 2 weeks after birth compared with that in NP offspring (NPO). Arterial blood pressure at 12 weeks of age did not differ between LPO and NPO. Neointima formation was exaggerated in LPO compared with NPO and associated with an increase in cell proliferation assessed by proliferating cell nuclear antigen (PCNA) staining index. Moreover, LPO showed enhanced expression of monocyte chemotactic protein-1, interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, and production of superoxide anion in the injured artery. Moreover, mRNA expression of isoforms of NAD(P)H oxidase subunits such as p22phox, p40phox, p47phox, p67phox, gp91phpx, and Rac1 in the injured arteries were enhanced in LPO. Furthermore, HIF-1α expression was increased in LPO compared with that in NPO. CONCLUSIONS: These results suggest that maternal low-protein diet-induced FGR increases susceptibility of the vasculature to postnatal injury.
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Dieta con Restricción de Proteínas/efectos adversos , Retardo del Crecimiento Fetal/patología , Neointima/embriología , Preñez , Efectos Tardíos de la Exposición Prenatal/patología , Remodelación Vascular/fisiología , Lesiones del Sistema Vascular/etiología , Animales , Animales Recién Nacidos , Peso Corporal , Proliferación Celular , Femenino , Desarrollo Fetal , Masculino , Ratones , Ratones Endogámicos C57BL , Embarazo , Lesiones del Sistema Vascular/embriología , Lesiones del Sistema Vascular/patologíaRESUMEN
BACKGROUND: Angiotensin II type 2 (AT2) receptor stimulation could exert beneficial effects on vascular remodeling. Previously, we reported that AT2 receptor stimulation ameliorated insulin resistance in diabetic mice accompanied by PPARγ activation which also plays a variety of crucial roles in the vasculature. Therefore, this study aimed to investigate the vascular protective effect of the AT2 receptor with activation of PPARγ involving AT2 receptor-interacting protein (ATIP). METHODS AND RESULTS: Vascular injury was induced by polyethylene-cuff placement around the femoral artery in C57BL/6J mice. Treatment with compound 21 (C21), an AT2 receptor agonist, decreased neointimal formation, cell proliferation, and the mRNA levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin-1ß, and phosphorylation of nuclear factor-kappa B, and increased PPARγ DNA-binding activity in the injured artery, whereas these inhibitory effects of C21 were attenuated by co-treatment with a PPARγ antagonist, GW9662. Treatment of vascular smooth muscle cells (VSMC) with C21 prepared from smAT2 transgenic mice, which highly express the AT2 receptor in VSMC, increased both PPARγ activity and its DNA-binding activity determined by dual-luciferase assay and electrophoresis mobility shift assay (EMSA), respectively. We observed that ATIP was involved in PPARγ complex formation, and that transfection of siRNA of ATIP1 attenuated the AT2 receptor-mediated increase in PPARγ activity in VSMC. In response to AT2 receptor stimulation, ATIP was translocated from the plasma membrane to the nucleus. CONCLUSIONS: Our results suggest a new mechanism by which AT2 receptor stimulation activates PPARγ, thereby resulting in amelioration of vascular intimal proliferation, and that ATIP plays an important role in AT2 receptor-mediated PPARγ activation.
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Proteínas Portadoras/metabolismo , Neointima , PPAR gamma/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Remodelación Vascular , Animales , Masculino , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/metabolismo , Sulfonamidas , TiofenosRESUMEN
The classical renin-angiotensin system (RAS), known as the angiotensin (Ang)-converting enzyme (ACE)/Ang II/Ang II type 1 (AT1) receptor axis, induces various organ damages including cognitive decline. On the other hand, the ACE2/Ang-(1-7)/Mas receptor axis has been highlighted as exerting antagonistic actions against the classical RAS axis in the cardiovascular system. However, the roles of the ACE2/Ang-(1-7)/Mas axis in cognitive function largely remain to be elucidated, and we therefore examined possible roles of ACE2 in cognitive function. Male, 10-week-old C57BL6 (wild type, WT) mice and ACE2 knockout (KO) mice were subjected to the Morris water maze task and Y maze test to evaluate cognitive function. ACE2KO mice exhibited significant impairment of cognitive function, compared with that in WT mice. Superoxide anion production increased in ACE2KO mice, with increased mRNA levels of NADPH oxidase subunit, p22phox, p40phox, p67phox, and gp91phox in the hippocampus of ACE2KO mice compared with WT mice. The protein level of SOD3 decreased in ACE2KO mice compared with WT mice. The AT1 receptor mRNA level in the hippocampus was higher in ACE2KO mice compared with WT mice. In contrast, the AT2 receptor mRNA level in the hippocampus did not differ between the two strains. Mas receptor mRNA was highly expressed in the hippocampus compared with the cortex. Brain-derived neurotrophic factor (BDNF) mRNA and protein levels were lower in the hippocampus in ACE2KO mice compared with WT mice. Taken together, ACE2 deficiency resulted in impaired cognitive function, probably at least in part because of enhanced oxidative stress and a decrease in BDNF.
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Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after stroke. Natriuretic peptides, which are increased by a neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of valsartan (VAL) compared with LCZ696 (VAL+ neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium chloride staining, and oxidative stress was determined by dihydroethidium staining. Blood pressure and heart rate were not significantly different before and after treatment. Pre-treatment with LCZ696 or VAL reduced the ischemic area, and this effect of LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or LCZ696 pre-treatment significantly decreased the increase of superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and superoxide anion production was observed between VAL and LCZ696 pre-treatment. The preventive effect of LCZ696 on ischemic brain damage after stroke was more marked than that of VAL. LCZ696 could be used as a new approach to prevent brain damage after stroke. (246 words).
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Aminobutiratos/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Infarto de la Arteria Cerebral Media/prevención & control , Neprilisina/antagonistas & inhibidores , Inhibidores de Proteasas/farmacología , Tetrazoles/farmacología , Administración Oral , Aminobutiratos/administración & dosificación , Angiotensina II/sangre , Antagonistas de Receptores de Angiotensina/administración & dosificación , Animales , Factor Natriurético Atrial/sangre , Compuestos de Bifenilo , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Combinación de Medicamentos , Infarto de la Arteria Cerebral Media/sangre , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Inhibidores de Proteasas/administración & dosificación , Renina/sangre , Sodio/sangre , Tetrazoles/administración & dosificación , Valsartán , Agua/metabolismoRESUMEN
Infantile hemangioma (IH) is the most common tumor of infancy, and it sometimes associated with Kasabach-Meritt syndrome (KMS) characterized by anemia, intraperitoneal hemorrhage secondary to rupture, coagulopathy, jaundice, and vascular malformations involving the brain, skin, gut, and other organs. Here, we report two newborn patients having IH with KMS at birth. The first patient had a giant hemangioma in the liver, which was successfully treated with i.v. corticosteroid and coil embolization. The second patient had a large hemangioma of the right axillary region, which was also successfully treated with i.v. corticosteroid, beta-blocker, coil embolization and local irradiation. All symptoms were controlled without any side-effects in both patients. According to these findings, combination therapy including coil embolization and corticosteroid is effective for IH patients with KMS. The indications for and timing of coil embolization should be determined further cases have been accumulated.
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Embolización Terapéutica/métodos , Hemangioma/terapia , Síndrome de Kasabach-Merritt/terapia , Neoplasias Hepáticas/terapia , Neoplasias de los Tejidos Blandos/terapia , Angiografía , Axila , Terapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Hemangioma/diagnóstico por imagen , Hemangioma/patología , Humanos , Recién Nacido , Síndrome de Kasabach-Merritt/diagnóstico por imagen , Síndrome de Kasabach-Merritt/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/patología , Tomografía Computarizada por Rayos X , Ultrasonografía PrenatalRESUMEN
INTRODUCTION: Binge eating disorder (BED) is associated with dopaminergic activation as food reward, resulting in metabolism-related disorders. Stimulation of angiotensin type 2 (AT2) receptor is reported to inhibit dopamine synthesis. We investigated the possible roles of AT2 receptor-mediated dopamine regulation in the pathogenesis of BED. MATERIALS AND METHODS: Male C57BL/6 mice, type 2 diabetic (KKAy) mice and AT2 receptor-null (AT2KO) mice at eight weeks old were treated with AT2 receptor agonist, compound 21 (C21) or saline for two weeks. Mice were subjected to fasting for two days followed by re-feeding for seven days. RESULTS: Treatment with C21 attenuated the rebound proportion of body weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT2KO mice. Dopamine concentration in the striatum was further increased by fasting in KKAy and AT2KO mice. Administration of C21 significantly attenuated this fasting-induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2 expression in the substantia nigra were markedly lower in KKAy mice compared with C57BL/6 mice, while administration of C21 increased their expression in KKAy mice. CONCLUSIONS: Our study suggests that AT2 receptor stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance.
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Trastorno por Atracón/metabolismo , Encéfalo/metabolismo , Dopamina/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal , Animales , Conducta Animal , Presión Sanguínea , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ayuno , Eliminación de Gen , Inmunohistoquímica , Masculino , Ratones Endogámicos C57BL , Neostriado/metabolismo , Receptores Dopaminérgicos/metabolismo , Sístole , Aumento de PesoRESUMEN
Angiotensin II type 2 (AT(2)) receptor activation has been reported to play a role in cognitive function, although its detailed mechanisms and pathologic significance are not fully understood. We examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) could prevent cognitive decline associated with hypoperfusion in the brain.We employed a bilateral common carotid artery stenosis (BCAS) model in mice as a model of vascular dementia. The Morris water maze task was performed 6 weeks after BCAS operation. Azilsartan (0.1 mg/kg/day) or C21 (10 µg/kg/day) was administered from 1 week before BCAS. Cerebral blood flow (CBF) and inflammatory cytokine levels were also determined. Wild-type (WT) mice showed significant prolongation of escape latency after BCAS, and this cognitive impairment was attenuated by pretreatment with azilsartan. Cognitive impairment was more marked in AT(2) receptor knockout (AT(2)KO) mice, and the preventive effect of azilsartan on cognitive decline was weaker in AT(2)KO mice than in WT mice, suggesting that the improvement of cognitive decline by azilsartan may involve stimulation of the AT(2) receptor. The significant impairment of spatial learning after BCAS in WT mice was attenuated by C21 treatment. The decrease in CBF in the BCAS-treated group was blunted by C21 treatment, and the increase in TNF-α and MCP-1 mRNA expression after BCAS was attenuated by C21 treatment. These findings indicate that direct AT(2) receptor stimulation attenuates ischemic vascular dementia induced by hypoperfusion at least in part through an increase in CBF, and a reduction of inflammation.
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Demencia Vascular/prevención & control , Receptor de Angiotensina Tipo 2/agonistas , Sulfonamidas/farmacología , Tiofenos/farmacología , Animales , Bencimidazoles/farmacología , Encéfalo/irrigación sanguínea , Estenosis Carotídea , Corteza Cerebral/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Aprendizaje por Laberinto , Ratones Endogámicos C57BL , Oxadiazoles/farmacología , ARN Mensajero/metabolismo , Flujo Sanguíneo Regional/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI.
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Bebidas , Citrus/química , Ingestión de Líquidos , Frutas/química , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/fisiopatología , Animales , Proliferación Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neointima/prevención & control , Superóxidos/metabolismo , Remodelación Vascular , Lesiones del Sistema Vascular/inmunología , Lesiones del Sistema Vascular/metabolismoRESUMEN
BACKGROUND: Serum procalcitonin (PCT) increases in various respiratory disorders such as acute respiratory distress syndrome. Elevated PCT is also observed in healthy neonates. In this study, we investigated whether PCT is a good marker of respiratory disorder in neonates. METHODS: A total of 155 neonates with or without respiratory disorder, were eligible for the study. PCT was measured on electrochemiluminescence immunoassay. Each neonate was allocated to the non-respiratory disorder (control) group (n = 95), or a respiratory disorder group (n = 60). PCT was compared between the groups, and association with other markers, including C-reactive protein (CRP) and white blood cell (WBC) count, was analyzed. RESULTS: Of the 60 neonates in the respiratory disorder group, 39, 10, five, one, two, two, and one neonates had transient tachypnea of the newborn, respiratory distress syndrome, air leak syndrome, meconium aspiration syndrome, 18-trisomy, neonatal asphyxia, and congenital diaphragmatic hernia, respectively. Mean PCT, CRP and WBC count in the respiratory disorder group were 9.01 ng/mL, 0.26 mg/dL, and 16,100 cells/µL, respectively. The area under the curve obtained for PCT in distinguishing between the respiratory disorder and control groups was 0.85 (sensitivity, 66.7%; specificity, 93.0%; optimum cut-off, 3.73 ng/mL), that for CRP was 0.72 (sensitivity, 75.0%; specificity, 64.6%; optimum cut-off, 0.14 mg/dL), and for WBC it was 0.44 (sensitivity, 60.0%; specificity, 29.6%; optimum cut-off, 15,000 cells/µL). CONCLUSIONS: PCT is more susceptible, as a diagnostic parameter of infection, to the effect of respiratory disturbance than CRP and WBC.
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Biomarcadores/sangre , Calcitonina/sangre , Trastornos Respiratorios/diagnóstico , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Recién Nacido , Recuento de Leucocitos , Mediciones Luminiscentes , Masculino , Curva ROC , Sensibilidad y EspecificidadRESUMEN
The possible counteracting effect of angiotensin (Ang)-converting enzyme (ACE)2/Ang-(1-7)/Mas axis against the ACE/Ang II/Ang II type 1 (AT1) receptor axis in blood pressure control has been previously described. We examined the possibility that this pathway might be involved in the anti-hypertensive effect of a newly developed AT1 receptor blocker (ARB), azilsartan, and compared azilsartan's effects with those of another ARB, olmesartan. Transgenic mice carrying the human renin and angiotensinogen genes (hRN/hANG-Tg) were given azilsartan or olmesartan. Systolic and diastolic blood pressure, as determined by radiotelemetry, were significantly higher in hRN/hANG-Tg mice than in wild-type (WT) mice. Treatment with azilsartan or olmesartan (1 or 5 mg kg(-1) per day) significantly decreased systolic and diastolic blood pressure, and the blood pressure-lowering effect of azilsartan was more marked than that of olmesartan. The urinary Na concentration decreased in an age-dependent manner in hRN/hANG-Tg mice. Administration of azilsartan or olmesartan increased urinary Na concentration, and this effect was weaker with olmesartan than with azilsartan. Azilsartan decreased ENaC-α mRNA expression in the kidney and decreased the ratio of heart to body weight. Olmesartan had a similar but less-marked effect. ACE2 mRNA expression was lower in the kidneys and hearts of hRN/hANG-Tg mice than in WT mice. This decrease in ACE2 mRNA expression was attenuated by azilsartan, but not by olmesartan. These results suggest that the hypotensive and anti-hypertrophic effects of azilsartan may involve activation of the ACE2/Ang-(1-7)/Mas axis with AT1 receptor blockade.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Angiotensina I/farmacología , Antihipertensivos/farmacología , Bencimidazoles/farmacología , Oxadiazoles/farmacología , Fragmentos de Péptidos/farmacología , Peptidil-Dipeptidasa A/fisiología , Proteínas Proto-Oncogénicas/fisiología , Receptores Acoplados a Proteínas G/fisiología , Enzima Convertidora de Angiotensina 2 , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/prevención & control , Canales Epiteliales de Sodio/genética , Imidazoles/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Peptidil-Dipeptidasa A/genética , Proto-Oncogenes Mas , Sodio/orina , Tetrazoles/farmacologíaRESUMEN
BACKGROUND: Stroke is a leading cause of death and disability; however, meta-analysis of randomized controlled trials of blood pressure-lowering drugs in acute stroke has shown no definite evidence of a beneficial effect on functional outcome. Accumulating evidence suggests that angiotensin II type 1 receptor blockade with angiotensin II type 2 (AT2) receptor stimulation could contribute to protection against ischemic brain damage. We examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) initiated even after stroke can prevent ischemic brain damage. METHODS: Stroke was induced by middle cerebral artery (MCA) occlusion, and the area of cerebral infarction was measured by magnetic resonant imaging. C21 (10 µg/kg/day) treatment was initiated immediately after MCA occlusion by intraperitoneal injection followed by treatment with C21 once daily. RESULTS: We observed that ischemic area was enlarged in a time dependent fashion and decreased on day 5 after MCA occlusion. Treatment with C21 initiated after MCA occlusion significantly reduced the ischemic area, with improvement of neurological deficit in a time-dependent manner without affecting blood pressure. The decrease of cerebral blood flow after MCA occlusion was also ameliorated by C21 treatment. Moreover, treatment with C21 significantly attenuated superoxide anion production and expression of proinflammatory cytokines, monocyte chemoattractant protein 1, and tumor necrosis factor α. Interestingly, C21 administration significantly decreased blood-brain barrier permeability and cerebral edema on the ischemic side. CONCLUSIONS: These results provide new evidence that direct AT2 receptor stimulation with C21 is a novel therapeutic approach to prevent ischemic brain damage after acute stroke.