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BACKGROUND: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.MethodsâandâResults: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. CONCLUSIONS: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.
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BACKGROUND: Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.MethodsâandâResults: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (r2=0.900, P<0.0001). The correlation coefficients between the actual and converted values of log NT-proBNP in the internal and external validation sets were 0.942 (P<0.0001) and 0.891 (P<0.0001), respectively. We applied this formula to samples obtained from patients administered with sacubitril/valsartan. After treatment initiation, NT-proBNP levels decreased and actual BNP levels increased. However, the calculated BNP levels decreased roughly parallel to the NT-proBNP levels. CONCLUSIONS: This new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.
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Insuficiência Cardíaca , Peptídeo Natriurético Encefálico , Humanos , Estudos de Coortes , Fragmentos de Peptídeos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , BiomarcadoresRESUMO
Intravenous ATP may induce atrial fibrillation (AF). ATP shares similar receptor-effector coupling systems with acetylcholine. However, the association between an ATP injection and the hyperactivity of the intrinsic cardiac autonomic nervous system, known as ganglionated plexi (GPs), is not well understood. We describe a series of patients with non-pulmonary vein (PV) trigger sites provoked by an ATP injection, and assess the feasibility of a ganglionated plexus (GP) ablation. We retrospectively analyzed 547 patients (69% male; mean age 67.4 ± 10.4 years; 38.5% non-paroxysmal AF) who underwent a total of 604 ablation procedures. Intravenous ATP was administered with an isoproterenol infusion during sinus rhythm after a pulmonary vein isolation in 21.3%, Box isolation in 78.6%, and SVC isolation in 52.0% of the procedures, respectively. We reviewed the incidence, the distribution of the foci, and the ablation outcomes in patients with ATP-induced AF. A total of seven patients (1.3%) had ATP-induced AF. Foci were identified in the coronary sinus (CS) in six patients, right atrial posterior wall (RAPW) adjacent to the interatrial groove in two, mitral annulus in two, ligament of Marshall in one, right septum below the foramen ovale in one and left atrial posterior wall in one, respectively. Among these trigger foci, we confirmed the vagal response by high-frequency stimulation in the CS and RAPW in six and two patients, respectively. After a median RF time of 2.9 min (range 2.5-11.3) targeting these foci, in five of six patients who received a repeat ATP injection, the AF became non-inducible. ATP-provoked trigger foci were distributed among certain sites that overlapped with the distribution of the GPs. The GP ablation was effective for this rare, but challenging situation.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Trifosfato de Adenosina , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: This study evaluated the prevalence and prognostic impact of lung function abnormalities in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).MethodsâandâResults:Of the 1,012 consecutive patients who were admitted to Nara Medical University with ADHF between 2011 and 2018, 657 routinely underwent spirometry (pulmonary function test [PFT]) before discharge. Lung function was classified as normal or abnormal (restrictive, obstructive, or mixed). Abnormal PFTs were seen in 63.0% of patients with ADHF (36.7%, 13.1%, and 13.2% for restrictive, obstructive, and mixed, respectively). The prevalence of abnormal PFT increased with age (P<0.001). Overall, abnormal PFT was an independent predictor of the composite endpoint of cardiovascular mortality or hospitalization for HF (adjusted hazard ratio [HR] 1.402; 95% confidence interval [CI] 1.039-1.914; P=0.027). Abnormal PFT (adjusted HR 2.294; 95% CI 1.368-4.064; P=0.001), as well as the restrictive (HR 2.299; 95% CI 1.322-4.175; P=0.003) and mixed (HR 2.784; 95% CI 1.399-5.581; P=0.004) patterns, were predictive of the composite endpoint in HFpEF, but not in HFrEF. CONCLUSIONS: Abnormal PFT was prevalent and associated with poor outcomes in ADHF. Spirometry may be a useful tool in patients with ADHF, especially in those with HFpEF, to identify those at higher risk of a poorer outcome.
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Insuficiência Cardíaca , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Prevalência , Prognóstico , Testes de Função Respiratória , Volume SistólicoRESUMO
BACKGROUND: Countermeasure development for early rehospitalization for heart failure (re-HHF) is an urgent and important issue in Western countries and Japan.MethodsâandâResults:Of 1,074 consecutive NARA-HF study participants with acute decompensated HF admitted to hospital as an emergency between January 2007 and December 2016, we excluded 291 without follow-up data, who died in hospital, or who had previous HF-related hospitalizations, leaving 783 in the analysis. During the median follow-up period of 895 days, 241 patients were re-admitted for HF. The incidence of re-HHF was the highest within the first 30 days of discharge (3.3% [26 patients]) and remained high until 90 days, after which it decreased sharply. Within 90 days of discharge, 63 (8.0%) patients were re-admitted. Kaplan-Meier analysis revealed that patients with 90-day re-HHF had worse prognoses than those without 90-day re-HHF in terms of all-cause death (hazard ratio [HR] 2.321, 95% confidence interval [CI] 1.654-3.174; P<0.001) and cardiovascular death (HR 3.396, 95% CI 2.153-5.145; P<0.001). Multivariate analysis indicated that only male sex was an independent predictor of 90-day re-HHF. CONCLUSIONS: The incidence of early re-HHF was lower in Japan than in Western countries. Its predictors are not related to the clinical factors of HF, indicating that a new comprehensive approach might be needed to prevent early re-HHF.
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Insuficiência Cardíaca/terapia , Readmissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.
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Cardiologistas/tendências , Vasoespasmo Coronário/terapia , Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica/tendências , Padrões de Prática Médica/tendências , Inquéritos e Questionários , Vasodilatadores/uso terapêutico , Tomada de Decisão Clínica , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/mortalidade , Morte Súbita Cardíaca/epidemiologia , Desfibriladores Implantáveis , Quimioterapia Combinada , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/instrumentação , Cardioversão Elétrica/mortalidade , Conhecimentos, Atitudes e Prática em Saúde , Disparidades em Assistência à Saúde/tendências , Humanos , Japão/epidemiologia , Resultado do Tratamento , Vasodilatadores/efeitos adversosRESUMO
BACKGROUND: Few biomarkers, even B-type natriuretic peptide (BNP), can predict the long-term outcome in patients with acute decompensated heart failure (ADHF) on the first day of admission. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family of cytokines, is a key molecule in cardiorenal syndrome and a predictor of adverse events in chronic kidney disease patients. However, its significance in ADHF patients remains poorly understood. MethodsâandâResults: We studied 408 ADHF patients admitted between April 2011 and December 2016 by measuring their PlGF levels on the first day of admission. Primary endpoints were all-cause and cardiovascular (CV) death. Patients were divided into 2 groups according to PlGF quartiles. Kaplan-Meier analysis revealed that the high PlGF group (quartile 4: ≥12.6 pg/mL) had a worse prognosis than the low PlGF group (quartiles 1-3; <12.6 pg/mL) in terms of all-cause (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.13-2.14; P<0.01) and CV death (HR, 1.68; 95% CI, 1.04-2.66; P<0.05). After adjustment for covariates, PlGF remained an independent predictor of all-cause and CV death. CONCLUSIONS: PlGF on the first day of admission was significantly associated with both all-cause and CV death, suggesting that it provides novel prognostic information in the acute phase of ADHF.
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Insuficiência Cardíaca/diagnóstico , Fator de Crescimento Placentário/sangue , Valor Preditivo dos Testes , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicaçõesRESUMO
Plants activate their immune system through intracellular signaling pathways after perceiving microbe-associated molecular patterns (MAMPs). Receptor-like cytoplasmic kinases mediate the intracellular signaling downstream of pattern-recognition receptors. BROAD-SPECTRUM RESISTANCE 1 (BSR1), a rice (Oryza sativa) receptor-like cytoplasmic kinase subfamily-VII protein, contributes to chitin-triggered immune responses. It is valuable for agriculture because its overexpression confers strong disease resistance to fungal and bacterial pathogens. However, it remains unclear how overexpressed BSR1 reinforces plant immunity. Here we analyzed immune responses using rice suspension-cultured cells and sliced leaf blades overexpressing BSR1. BSR1 overexpression enhances MAMP-triggered production of hydrogen peroxide (H2O2) and transcriptional activation of the defense-related gene in cultured cells and leaf strips. Furthermore, the co-cultivation of leaves with conidia of the blast fungus revealed that BSR1 overexpression allowed host plants to produce detectable oxidative bursts against compatible pathogens. BSR1 was also involved in the immune responses triggered by peptidoglycan and lipopolysaccharide. Thus, we concluded that the hyperactivation of MAMP-triggered immune responses confers BSR1-mediated robust resistance to broad-spectrum pathogens.
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Resistência à Doença , Oryza/imunologia , Oryza/metabolismo , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Peróxido de Hidrogênio/metabolismo , Magnaporthe/fisiologia , Modelos Biológicos , Oryza/genética , Oryza/microbiologia , Peptidoglicano/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Explosão RespiratóriaRESUMO
BACKGROUND: The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and ß-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of ß-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in ß-cells. METHODS: Mice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in ß-cells (ß GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. ß-cell size and number were measured by immunofluorescence-based islet morphometry. RESULTS: In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from ß GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in ß GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in ß-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and ß-cell morphology were similar in ß GC-A KO mice and control littermates. However, HFD-fed ß GC-A KO animals had accelerated glucose intolerance and diminished adaptative ß-cell proliferation. CONCLUSIONS: Our studies of ß GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate ß-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of ß-cells to HFD-induced obesity. Impaired ß-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.
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Fator Natriurético Atrial/metabolismo , Glicemia/metabolismo , Deleção de Genes , Intolerância à Glucose/etiologia , Células Secretoras de Insulina/enzimologia , Obesidade/complicações , Receptores do Fator Natriurético Atrial/deficiência , Animais , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Predisposição Genética para Doença , Intolerância à Glucose/enzimologia , Intolerância à Glucose/genética , Intolerância à Glucose/patologia , Insulina/sangue , Células Secretoras de Insulina/patologia , Camundongos Knockout , Peptídeo Natriurético Encefálico/metabolismo , Obesidade/enzimologia , Obesidade/genética , Fenótipo , Receptores do Fator Natriurético Atrial/genética , Transdução de Sinais , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: Intravenous immunoglobulin (IVIG) contains immunoglobulin G against various viruses, except those that have been screened, such as human immunodeficiency and hepatitis C viruses. Antivirus titers reflect the serostatus of the blood donor population in the collection region and are of clinical interest. STUDY DESIGN AND METHODS: During the past 10 years, measles, mumps, rubella, varicella-zoster, hepatitis A and B, Epstein-Barr, and human respiratory syncytial viruses; human parainfluenza viruses 1, 2, and 3; human herpes simplex viruses 1 and 2; human herpesvirus 6; cytomegalovirus (CMV); human adenoviruses (HAdVs) 1, 2, 3, 7, and 11; human parvovirus B19; and human echovirus 9 and 11 titers in IVIG lots have been measured by a commercial testing facility. A viral neutralizing assay for CMV has been used at our facility. Herein, we summarize the measurements and results of a regression analysis of the trends in virus antibody titers. RESULTS: IVIG lots contained significant titers against all of the above viruses, except for HAdV 7. Three patterns-stable, increasing, and decreasing-were observed, without any drastic changes. Although these trends reflect the seroprevalence in Japan, the titers were not obviously affected by the cycle of epidemics. On the other hand, the prevalence data suggest that titers against hepatitis A virus and other viruses will decrease in the near future, although they are currently stable. CONCLUSION: Monitoring the titer of IVIG lots and seroprevalence of donor populations is important for anticipating future changes in virus antibody titers of IVIG lots and can provide useful information of clinical interest.
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Anticorpos Antivirais/imunologia , Imunoglobulinas Intravenosas/imunologia , Adolescente , Adulto , Doadores de Sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Testes Sorológicos , Adulto JovemRESUMO
Rice (Oryza sativa) produces diterpenoid phytoalexins (DPs), momilactones and phytocassanes as major phytoalexins. Accumulation of DPs is induced in rice by blast fungus infection, copper chloride or UV light. Here, we describe a rice transcription factor named diterpenoid phytoalexin factor (DPF), which is a basic helix-loop-helix (bHLH) transcription factor. The gene encoding DPF is expressed mainly in roots and panicles, and is inducible in leaves by blast infection, copper chloride or UV. Expression of all DP biosynthetic genes and accumulation of momilactones and phytocassanes were remarkably increased and decreased in DPF over-expressing and DPF knockdown rice, respectively. These results clearly demonstrated that DPF positively regulates DP accumulation via transcriptional regulation of DP biosynthetic genes, and plays a central role in the biosynthesis of DPs in rice. Furthermore, DPF activated the promoters of COPALYL DIPHOSPHATE SYNTHASE2 (CPS2) and CYTOCHROME P450 MONOOXYGENASE 99A2 (CYP99A2), whose products are implicated in the biosynthesis of phytocassanes and momilactones, respectively. Mutations in the N-boxes in the CPS2 upstream region, to which several animal bHLH transcription factors bind, decreased CPS2 transcription, indicating that DPF positively regulates CPS2 transcription through the N-boxes. In addition, DPF partly regulates CYP99A2 through the N-box. This study demonstrates that DPF acts as a master transcription factor in DP biosynthesis.
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Diterpenos/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Sesquiterpenos/metabolismo , Fatores de Transcrição/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica de Plantas/fisiologia , Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Regulação para Cima , FitoalexinasRESUMO
In patients with acute decompensated heart failure (ADHF), sex differences considering clinical and pathophysiologic features are not fully understood. We investigated sex differences in left ventricular (LV) ejection fraction (LVEF), plasma B-type natriuretic peptide (BNP) levels, and prognostic factors in patients with ADHF in Japan. We studied 748 consecutive ADHF patients of 821 patients registered in the ADHF registry between January 2007 and December 2014. Patients were divided into four groups based on sex and LVEF [reduced (ejection fraction, or EF, <50%, heart failure with reduced EF, or HFrEF) or preserved (EF ≥50%, heart failure with preserved LVEF, or HFpEF)]. The primary endpoint was the combination of cardiovascular death and heart failure (HF) admission. The present study consisted of 311 female patients (50% HFrEF, 50% HFpEF) and 437 male patients (63% HFrEF, 37% HFpEF). There was significant difference between sexes in the LVEF distribution profile. The ratio of HFpEF patients was significantly higher in female patients than in male patients (P= 0.0004). Although there were no significant sex differences in median plasma BNP levels, the prognostic value of BNP levels was different between sexes. Kaplan-Meier analysis revealed that the high BNP group had worse prognosis than the low BNP group in male but not in female patients. In multivariate analysis, log transformed BNP at discharge predicted cardiovascular events in male but not in female HF patients (female, hazard ratio: 1.169; 95% confidence interval: 0.981-1.399;P= 0.0806; male, hazard ratio: 1.289; 95% confidence interval: 1.120-1.481;P= 0.0004). In patients with ADHF, the distribution of LV function and the prognostic significance of plasma BNP levels for long-term outcome were different between the sexes.
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Insuficiência Cardíaca/fisiopatologia , Caracteres Sexuais , Volume Sistólico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Histamine increases microvascular endothelial leakage by activation of complex calcium-dependent and -independent signaling pathways. Atrial natriuretic peptide (ANP) via its cGMP-forming guanylyl cyclase-A (GC-A) receptor counteracts this response. Here, we characterized the molecular mechanisms underlying this interaction, especially the role of cGMP-dependent protein kinase I (cGKI). APPROACH AND RESULTS: We combined intravital microscopy studies of the mouse cremaster microcirculation with experiments in cultured microvascular human dermal endothelial cells. In wild-type mice, ANP had no direct effect on the extravasation of fluorescent dextran from postcapillary venules, but strongly reduced the histamine-provoked vascular leakage. This anti-inflammatory effect of ANP was abolished in mice with endothelial-restricted inactivation of GC-A or cGKI. Histamine-induced increases in endothelial [Ca(2+)]i in vitro and of vascular leakage in vivo were markedly attenuated by the Ca(2+)-entry inhibitor SKF96365 and in mice with ablated transient receptor potential canonical (TRPC) 6 channels. Conversely, direct activation of TRPC6 with hyperforin replicated the hyperpermeability responses to histamine. ANP, via cGKI, stimulated the inhibitory phosphorylation of TRPC6 at position Thr69 and prevented the hyperpermeability responses to hyperforin. Moreover, inhibition of cGMP degradation by the phosphodiesterase 5 inhibitor sildenafil prevented the edematic actions of histamine in wild types but not in mice with endothelial GC-A or cGKI deletion. CONCLUSIONS: ANP attenuates the inflammatory actions of histamine via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels. The therapeutic potential of this novel regulatory pathway is indicated by the observation that sildenafil improves systemic endothelial barrier functions by enhancing the endothelial effects of endogenous ANP.
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Fator Natriurético Atrial/farmacologia , Cálcio/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Células Endoteliais/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos/farmacologia , Histamina/farmacologia , Microvasos/efeitos dos fármacos , Canais de Cátion TRPC/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Proteína Quinase Dependente de GMP Cíclico Tipo I/deficiência , Proteína Quinase Dependente de GMP Cíclico Tipo I/genética , Relação Dose-Resposta a Droga , Células Endoteliais/enzimologia , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Proteínas de Membrana , Camundongos , Camundongos Knockout , Microvasos/enzimologia , Inibidores da Fosfodiesterase 5/farmacologia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação , Receptores do Fator Natriurético Atrial/genética , Receptores do Fator Natriurético Atrial/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPC/deficiência , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Canal de Cátion TRPC6 , Fatores de Tempo , TransfecçãoRESUMO
This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75 years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.
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Injúria Renal Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Idoso , Prognóstico , Intervenção Coronária Percutânea/efeitos adversos , Volume Sistólico , Meios de Contraste/efeitos adversos , Fatores de Risco , Função Ventricular Esquerda , Infarto do Miocárdio/etiologia , Creatinina , Estudos RetrospectivosRESUMO
We identified a short-grain mutant (Short grain1 (Sg1) Dominant) via phenotypic screening of 13,000 rice (Oryza sativa) activation-tagged lines. The causative gene, SG1, encodes a protein with unknown function that is preferentially expressed in roots and developing panicles. Overexpression of SG1 in rice produced a phenotype with short grains and dwarfing reminiscent of brassinosteroid (BR)-deficient mutants, with wide, dark-green, and erect leaves. However, the endogenous BR level in the SG1 overexpressor (SG1:OX) plants was comparable to the wild type. SG1:OX plants were insensitive to brassinolide in the lamina inclination assay. Therefore, SG1 appears to decrease responses to BRs. Despite shorter organs in the SG1:OX plants, their cell size was not decreased in the SG1:OX plants. Therefore, SG1 decreases organ elongation by decreasing cell proliferation. In contrast to the SG1:OX plants, RNA interference knockdown plants that down-regulated SG1 and a related gene, SG1-LIKE PROTEIN1, had longer grains and internodes in rachis branches than in the wild type. Taken together, these results suggest that SG1 decreases responses to BRs and elongation of organs such as seeds and the internodes of rachis branches through decreased cellular proliferation.
Assuntos
Brassinosteroides/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/genética , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Proliferação de Células , Tamanho Celular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Dados de Sequência Molecular , Oryza/metabolismo , Fenótipo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Caules de Planta/crescimento & desenvolvimento , Caules de Planta/metabolismo , Interferência de RNA , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismoRESUMO
Epicuticular wax (bloom) plays important roles in protecting the tissues of sorghum (Sorghum bicolor (L.) Moench) plants from abiotic stresses. However, reducing wax content provides resistance to greenbug and sheath blight-a useful trait in agricultural crops. We generated a sorghum bloomless (bm) mutant by gamma irradiation. One bm population segregated for individuals with and without epicuticular wax at a frequency of 72:22, suggesting that the bm mutation was under the control of a single recessive nuclear gene. Genes differentially expressed in the wild-type and the bm mutant were identified by RNA-seq technology. Of the 31 downregulated genes, Sb06g023280 was the most differentially expressed and was similar to WBC11, which encodes an ABC transporter responsible for wax secretion in Arabidopsis. An inversion of about 1.4 Mb was present in the region upstream of the Sb06g023280 gene in the bm mutant; it is likely that this inversion changed the promoter sequence of the Sb06g023280 gene. Using genomic PCR, we confirmed that six independent F2 bm mutant-phenotype plants carried the same inversion. Therefore, we concluded that the inversion involving the Sb06g023280 gene inhibited wax secretion in the bloomless sorghum.