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1.
Sci Rep ; 10(1): 9061, 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32472009

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Artículo en Inglés | MEDLINE | ID: mdl-32469254

RESUMEN

Background - Genome-wide association studies (GWAS) provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. GWAS in diverse populations have the potential to advance our understanding of CAD. Methods - We conducted two GWAS for CAD in the Japanese population, which included 12,494 cases and 28,879 controls, and 2,808 cases and 7,261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the CARDIoGRAMplusC4D 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. Results - We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies, and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. Conclusions - We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

3.
Nitric Oxide ; 100-101: 45-49, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32407788

RESUMEN

BACKGROUND: Fractional exhaled nitric oxide levels are related to various clinical diseases. This study investigated the associations between the clinical characteristics and the level of fractional exhaled nitric oxide in patients with adult congenital heart disease. METHODS AND RESULTS: Fractional exhaled nitric oxide values were measured in 30 adult patients with stable congenital heart disease who had undergone right heart catheterization and 17 healthy individuals (controls). There was no significant difference in fractional exhaled nitric oxide values between patients with congenital heart disease and healthy controls. Depending on whether their fractional exhaled nitric oxide values were above or below the median value, patients with congenital heart disease were divided into two groups (low vs. high fractional exhaled nitric oxide groups). The relationship between fractional exhaled nitric oxide values and clinical characteristics was investigated. There was a higher percentage of patients with cyanosis in the low fractional exhaled nitric oxide group (50%) than in the high fractional exhaled nitric oxide group (7.1%). There was no significant difference in right heart catheterization data between the low and high fractional exhaled nitric oxide groups. The fractional exhaled nitric oxide value was correlated to the number of neutrophils in patients with cyanosis (r = 0.84 (N = 8), p = 0.005). CONCLUSIONS: In this cohort of patients with adult congenital heart disease, lower levels of fractional exhaled nitric oxide corresponded to the presence of cyanosis.

4.
J Hypertens ; 38(6): 1140-1148, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32371804

RESUMEN

OBJECTIVES: Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort. METHODS: We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS). RESULTS: CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P < 0.001), whereas weakly, but positively correlated with LA volume index and pump strain (r = 0.12 and 0.09, both P < 0.01). In multivariable analysis, CAVI was significantly associated with reservoir and conduit strain independent of traditional cardiovascular risk factors and LV morphology and function including LVGLS (standardized ß = -0.22 and -0.27, respectively, both P < 0.001), whereas there was no independent association with LA volume index and pump strain. In the categorical analysis, the abnormal CAVI (≥9.0) carried the significant risk of impaired reservoir and conduit strain (adjusted odds ratio = 2.61 and 3.73 vs. normal CAVI, both P < 0.01) in a fully adjusted model including laboratory and echocardiographic parameters. CONCLUSION: Arterial stiffness was independently associated with LA phasic function, even in the absence of overt cardiovascular disease, which may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.

5.
Int Heart J ; 61(2): 413-418, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32224603

RESUMEN

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.


Asunto(s)
Anticuerpos Antinucleares/inmunología , Centriolos/inmunología , Antagonistas de los Receptores de Endotelina/uso terapéutico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Esclerodermia Sistémica/inmunología , Vasodilatadores/uso terapéutico , Anciano , Anciano de 80 o más Años , Autoanticuerpos/inmunología , Bosentán/uso terapéutico , Cateterismo Cardíaco , Quimioterapia Combinada , Epoprostenol/análogos & derivados , Epoprostenol/uso terapéutico , Femenino , Volumen Espiratorio Forzado , Humanos , Mesilato de Imatinib/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/fisiopatología , Capacidad de Difusión Pulmonar , Pirimidinas/uso terapéutico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Citrato de Sildenafil/uso terapéutico , Sulfonamidas/uso terapéutico , Tadalafilo/uso terapéutico , Tomografía Computarizada por Rayos X
6.
J Nat Med ; 74(3): 571-578, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32328863

RESUMEN

Three new quassinoids, javanicinols A and B (1 and 2) and 4-keto-(16S)-methoxyjavanicin B (3), together with three known quassinoids (4-6) were isolated from the chloroform-soluble fraction of the methanol extract of the Picrasma javanica wood. The structures of 1-3 were determined by spectroscopic analyses, including 1D and 2D NMR, HRESIMS, and CD. The anti-HIV-1 viral protein R (Vpr) assay revealed that 1 and 2 exhibited potent anti-Vpr activities at 1.25 µM. Furthermore, the assay also revealed the potent anti-Vpr activities of (16R)-methoxyjavanicin B (7) and (16S)-methoxyjavanicin B (8), which were previously isolated from the Picrasma javanica wood.

8.
ESC Heart Fail ; 2020 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-32253826

RESUMEN

AIMS: Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease. METHODS AND RESULTS: We examined 1175 participants who underwent extensive cardiovascular health check-up including laboratory tests and speckle-tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th-75th percentile, 4.6-6.5 mg/dL). The prevalence of abnormal LVGLS (greater than -18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020). CONCLUSIONS: In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease.

9.
J Nat Med ; 74(3): 591-598, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32200514

RESUMEN

Three new steroidal saponins, aspiletreins A-C (1-3), together with 2H-chromen-2-one (4), and α-tocopherol (5), were isolated from whole Aspidistra letreae plants collected in Vietnam. Their structures were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR, IR, and HRESIMS, and by comparison with the reported data in the literature. Compounds 1-3 exhibited moderate cytotoxicities against the LU-1, HeLa, MDA-MB-231, HepG2, and MKN-7 human cancer cell lines, with IC50 values ranging from 7.69 ± 0.40 to 20.46 ± 3.11 µM.

10.
Chem Biodivers ; 17(5): e2000037, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32163220

RESUMEN

The ocotillol (OCT)-type saponins have been known as a tetracyclic triterpenoid, possessing five- or six-membered epoxy ring in the side chain. Interestingly, this type saponin was mostly found in Panax vietnamensis Ha et Grushv., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT-type saponins, majonoside R2, vina-ginsenoside R2, majonoside R1, pseudoginsenoside RT4, vina-ginsenoside R11, together with three protopanaxadiol (PPD)-type saponins and four protopanaxatriol (PPT)-type saponins from VG were evaluated for their antimelanogenic activity. All of isolates were found to be active. More importantly, the five OCT-type saponins inhibited melanin production in B16-F10 mouse melanoma cells, without showing any cytotoxicity. Besides ginsenoside Rd and ginsenoside Rg3 in PPD and notoginsenoside R1 in PPT-type saponins, majonoside R2 was the most potent melanogenesis inhibitory activity in OCT-type saponins. In this article, we highlighted antimelanogenic activity of OCT-type saponins and potential structure-activity relationship (SAR) of ginsenosides. Our results suggested that OCT-type saponins could be used as a depigmentation agent.

11.
Int J Cardiol ; 309: 1-7, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32220487

RESUMEN

BACKGROUND: Few studies have evaluated the therapeutic effect of long-term cardiac rehabilitation (CR) and no large-scale survey of cardiovascular outcomes after long-term CR is reported. METHODS: This cohort study included 9981 patients undergoing CR from 2004 to 2015. Patients who had supervised CR were divided into three groups according to CR duration: up to acute phase (until discharge, Phase I group), up to recovery phase (≤150 days, Phase II group), and up to maintenance phase (>150 days, Phase III group). Using propensity score matching, mortality and major adverse cardiovascular events (MACE) were compared among the groups. RESULTS: Follow-up period was 4.9 ± 3.0 years. Adult patients were divided into three groups (Phase I group: n = 4649, Phase II group: n = 3271, and Phase III group: n = 731). After propensity score matching, the risk of death and MACE was extremely lower in Phase III group than in Phase I or Phase II group (death: HR 0.47, P < 0.01, HR 0.64, P < 0.01, and MACE: HR 0.48, P < 0.01, HR 0.70, P < 0.01). Most patients in Phase II group had better survival than those in Phase I group. Subpopulations of female patients and those with dyslipidemia, smoking history, coronary artery bypass graft, or heart failure had better survival in Phase III group than in Phase II group. CONCLUSIONS: Long-term supervised CR for patients with cardiovascular diseases is more effective than short-term CR.

12.
Intern Med ; 2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32132339

RESUMEN

A 49-year-old man was diagnosed with acute cardiac insufficiency based on evidence of congestive heart failure. The non-invasive measurement of the cardiac output using an AESCULON® mini showed low cardiac output (CO, 3.9 L/min). We administered an intravenous diuretic for cardiac edema and dobutamine drip for low cardiac output. Soon after starting dobutamine at 3.2 γ (microg/kg/min), the CO improved to 6.8 L/min. Combination therapy of diuretic and dobutamine resolved the heart failure. CO measurement by an AESCULON® mini was safe, cost-effective, and convenient. Data output correlates with the CO by Swan-Gantz catheterization. The non-invasive measurement of the CO permitted a smooth recovery without recurrence in this patient.

14.
Circ J ; 84(4): 670-676, 2020 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-32132310

RESUMEN

BACKGROUND: Healthcare-associated infective endocarditis (HAIE) has become increasingly recognized worldwide because the underlying patient conditions are completely different from those of community-acquired infective endocarditis (CIE). However, data on HAIE in the Japanese population is lacking. We sought to clarify the patient characteristics and prognosis of HAIE in a Japanese population.Methods and Results:A retrospective study was conducted in 158 patients who were diagnosed with infective endocarditis, 53 of whom (33.5%) were classified as HAIE. Compared with patients with CIE, those with HAIE were older (median age 72 vs. 61 years; P=0.0002) and received surgical treatment less frequently (41.5% vs. 62.9%; P=0.01). Regarding causative microorganisms, staphylococci,including methicillin-resistant pathogens, were more common in patients with HAIE (32.1% vs. 14.3%; P=0.01). Patients with HAIE had higher in-hospital mortality (32.1% vs. 4.8%; P<0.0001) and Kaplan-Meier analysis showed worse prognosis for patients with HAIE than CIE (P<0.0001, log-rank test). On multivariate Cox analysis, HAIE (hazard ratio 3.26; 95% confidence interval 1.49-7.14), age ≥60 years, surgical treatment, stroke, and heart failure were independently associated with mortality. CONCLUSIONS: HAIE has different clinical characteristics and causative microorganisms, as well as worse prognosis, than CIE. Preventive strategies, and the prompt and appropriate identification of HAIE may improve the outcome of infective endocarditis.

15.
J Nat Prod ; 83(4): 1201-1206, 2020 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-32208696

RESUMEN

Six new chiro-inositol derivatives (1-6) were isolated from the leaves of Chisocheton paniculatus collected in Vietnam. Their chemical structures were elucidated by 1D and 2D NMR and HRESIMS analyses. All isolated compounds were evaluated for their inhibitory activity against lipopolysaccharide-induced nitric oxide (NO) production in the RAW 264.7 macrophage cell line. Compound 4 exhibited potent inhibitory activity for NO production with an IC50 value of 7.1 µM.

16.
Intern Med ; 59(8): 1093-1097, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32009099

RESUMEN

A 25-year-old woman had convulsions and disturbance of consciousness. Head magnetic resonance imaging (MRI) showed punctate areas in the occipital lobes with increased signals on T2-weighted imaging. The MRI abnormalities responded well to steroid pulse therapy, so we made a diagnosis of posterior reversible encephalopathy syndrome (PRES). Three months later, she developed a fever and dyspnea. Chest computed tomography revealed marked thickness of the tracheal and bronchial wall, and bronchoscopy showed a cobble-stone appearance of the tracheal mucosa, indicative of relapsing polychondritis (RPC). We consider that PRES had developed due to autoimmune vasculitis in the brain with RPC.

17.
J Nat Med ; 74(2): 487-494, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32006354

RESUMEN

Kaempulchraols B-D (2-4), isopimara-8(9),15-diene diterpenoids isolated from Kaempferia pulchra rhizomes collected in Myanmar, were identified as potent NF-κB inhibitors. These compounds were also effective as NO inhibitory agents, with IC50 values of 47.69, 44.97, and 38.17 µM, respectively, without showing any cytotoxicity against LPS-induced RAW264.7 cells. Investigations of the mechanisms of action of 2-4 revealed that they inhibit the NF-κB-mediated transactivation of a luciferase reporter gene, IL-6 production, and COX-2 expression, with an effective dose of 25 µM. Thus, isopimarane diterpenoids are suggested to be potent inhibitors of NF-κB pathways and could be further explored as potential anti-inflammatory lead compounds.

18.
Circ J ; 84(3): 371-373, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32062641

RESUMEN

The new Imperial era, Reiwa, started in May, 2019. After World War II, Reiwa is the third Imperial era following Showa and Heisei. In each era, we had specific healthcare problems in cardiovascular medicine and implemented preventive strategies against them. Furthermore, nationwide healthcare policies such as a universal healthcare insurance system (kaihoken) and health check-up system largely contribute to overcoming these problems. Here, we summarize the specific issues in cardiovascular medicine and nationwide strategies policies against them in each era. We also describe what we should do in the new Imperial era from the cardiovascular viewpoint.

19.
Fitoterapia ; 142: 104511, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32061911

RESUMEN

Four new polyacetylene amides, siphonellamides A-D (1-4), and one new fatty amide, siphonellamide E (5), together with a known indole fatty amide (6) and callyspongamide A (7), were isolated from the Red Sea marine sponge Siphonochalina siphonella. The structures of 1-5 were elucidated by extensive analyses of their 1D- and 2D-NMR spectra and MS. The isolated compounds were assessed for their cytotoxicity against HeLa, MCF-7, and A549 cancer cell lines. Compounds 1 and 2 exhibited cytotoxic activities with IC50 values ranging from 9.4 to 34.1 µM, while 5 was only cytotoxic to HeLa cells, with an IC50 value of 78.4 µM. Compound 7 showed moderate cytotoxicity against all tested cell lines.

20.
J Hypertens ; 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32004209

RESUMEN

OBJECTIVES: Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort. METHODS: We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS). RESULTS: CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P < 0.001), whereas weakly, but positively correlated with LA volume index and pump strain (r = 0.12 and 0.09, both P < 0.01). In multivariable analysis, CAVI was significantly associated with reservoir and conduit strain independent of traditional cardiovascular risk factors and LV morphology and function including LVGLS (standardized ß = -0.22 and -0.27, respectively, both P < 0.001), whereas there was no independent association with LA volume index and pump strain. In the categorical analysis, the abnormal CAVI (≥9.0) carried the significant risk of impaired reservoir and conduit strain (adjusted odds ratio = 2.61 and 3.73 vs. normal CAVI, both P < 0.01) in a fully adjusted model including laboratory and echocardiographic parameters. CONCLUSION: Arterial stiffness was independently associated with LA phasic function, even in the absence of overt cardiovascular disease, which may explain the higher incidence of atrial fibrillation in individuals with increased arterial stiffness.

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