RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese and Korean traditional medicinal books reported that the use of C. paniculatum in the treatment of psychotic symptoms, such as hallucinations and delusions. AIM OF THE STUDY: In this study, we aimed to investigate whether C. paniculatum could improve sensorimotor gating disruption in mice with MK-801-induced schizophrenia-like behaviors. We also aimed to identify the active component of C. paniculatum that could potentially serve as a treatment for schizophrenia and found that paeonol, the major constituent compound of C. paniculatum, showed potential as a treatment for schizophrenia. MATERIALS AND METHODS: To assess the effect of paeonol on mice with MK-801-induced schizophrenia-like behaviors, we carried out a series of behavioral tests related with symptoms of schizophrenia. In addition, we utilized Western blotting and ELISA techniques to investigate the antipsychotic actions of paeonol. RESULT: C. paniculatum extract (100 or 300 mg/kg) and paenol (10 or 30 mg/kg) significantly reversed MK-801-induced prepulse deficits in acoustic startle response test. In addition, paeonol (10 or 30 mg/kg) attenuated social novelty preference and novel object recognition memory on MK-801-induced schizophrenia-like behaviour in mice. Furthermore, the phosphorylation levels of PI3K, Akt, GSK3ß and NF-κB, as well as related pro-inflammatory cytokine, such as IL-1ß and TNF-α, were significantly reversed by the administration of paeonol (10 or 30 mg/kg) in the prefrontal cortex of MK-801-treated mice. CONCLUSIONS: Collectively, these data show that paeonol can potentially be used as an agent for treating sensorimotor gating deficits, negative symptoms, and cognitive deficits, such as those observed in schizophrenia with few adverse effects.
Assuntos
Cynanchum , Esquizofrenia , Animais , Camundongos , NF-kappa B/metabolismo , Maleato de Dizocilpina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases , Reflexo de Sobressalto , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Glicogênio Sintase Quinase 3 betaRESUMO
The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1ß, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK/JNK/NF-κB signaling cascades and production of IL-6.
Assuntos
Interleucina-6/metabolismo , Lamiaceae/química , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Transcrição RelA/metabolismo , Animais , Etanol/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Células RAW 264.7RESUMO
OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.
Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Programas Nacionais de Saúde , Intervenção Coronária Percutânea/efeitos adversos , República da Coreia/epidemiologia , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , Resultado do TratamentoRESUMO
BACKGROUND: Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. METHODS: We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1-year follow-up provocation test. RESULTS: The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1-year follow-up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1-year follow-up was significantly lower in the high-dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. CONCLUSIONS: Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up.
Assuntos
Angina Pectoris/tratamento farmacológico , Vasoespasmo Coronário/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Succinatos/administração & dosagem , Adulto , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/etiologia , Angiografia Coronária , Vasoespasmo Coronário/complicações , Vasoespasmo Coronário/diagnóstico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão/métodos , Antagonistas da Serotonina/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Optimal treatment of spontaneous isolated celiac artery dissection (SICAD) is not well established because the natural history of this rare disease is poorly understood. We analyzed the natural history of patients who underwent conservative treatment. METHODS: The study included 28 patients with SICAD from December 2008 to January 2017. Our institutional policy of first-line treatment for SICAD patients was conservative, and invasive procedures were reserved for unstable complications such as severe persistent pain, significant organ malperfusion, rapid aneurysmal change, and rupture or concealed rupture. Demographics, clinical features, morphologic characteristics on computed tomography, treatment modalities, and follow-up results of these patients were retrospectively reviewed. RESULTS: Mean age was 52 years, and 89% of patients were male; 86% presented with pain, mostly abdominal, and 14% of cases were detected incidentally on abdominal imaging. None of these patients had unstable complications on admission, and all underwent initial conservative treatment. During the follow-up period (22 ± 20 months), aneurysmal change and propagation of thrombosis were noted in one patient and two patients, respectively, all of whom were managed conservatively without adverse clinical events. No difference in clinical and morphologic outcomes was noted between patients who were treated with antihypertensive therapy and those who were not. Patients with intramural hematoma on initial images showed dynamic vascular remodeling (partial to complete resorption) during the follow-up period compared with patients who had dominant intimal flap on initial images. CONCLUSIONS: The clinical course of patients with SICAD was benign. Even progressive vascular changes during follow-up did not require invasive treatment. Antihypertensive therapy might not modify the clinical course. The short-term results of conservative management are encouraging, but further evaluation with long-term follow-up in a large population is needed.
Assuntos
Dissecção Aórtica/terapia , Artéria Celíaca , Dor Abdominal/etiologia , Dor Abdominal/terapia , Adulto , Idoso , Algoritmos , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Artéria Celíaca/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Procedimentos Clínicos , Feminino , Hematoma/etiologia , Hematoma/terapia , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Trombose/etiologia , Trombose/terapia , Fatores de Tempo , Resultado do Tratamento , Remodelação VascularRESUMO
It is uncertain that atorvastatin pretreatment can reduce myocardial damage in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the effects of atorvastatin pretreatment on infarct size measured by contrast-enhanced magnetic resonance imaging (CE-MRI) in STEMI patients. Patients undergoing primary PCI for STEMI within 12 hr after symptom onset were randomized to an atorvastatin group (n=30, 80 mg before PCI and for 5 days after PCI) or a control group (n=37, 10 mg daily after PCI). The primary end point was infarct size evaluated as the volume of delayed hyperenhancement by CE-MRI within 14 days after the index event. The median infarct size was 19% (IQR 11.1%-31.4%) in the atorvastatin group vs. 16.3% (7.2%-27.2%) in the control group (P=0.27). The myocardial salvage index (37.1% [26.9%-58.7%] vs. 46.9% [39.9-52.4], P=0.46) and area of microvascular obstruction (1.1% [0%-2.0%] vs. 0.7% [0%-1.8%], P=0.37) did not differ significantly between the groups. Frequency of the hemorrhagic and transmural infarctions was not significantly different in the 2 groups. Pretreatment with a high-dose atorvastatin followed by further treatment for 5 days in STEMI patients undergoing primary PCI failed to reduce the extent of myocardial damage or improve myocardial salvage.
Assuntos
Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Imageamento por Ressonância Magnética , Infarto do Miocárdio/terapia , Miocárdio/patologia , Intervenção Coronária Percutânea , Adulto , Idoso , Eletrocardiografia , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Estudos ProspectivosRESUMO
AIMS: To evaluate the efficacy of high-dose atorvastatin on contrast-induced nephropathy (CIN) occurrence in patients with ST-elevation myocardial infarction undergoing primary angioplasty. METHODS: We studied whether 80â mg atorvastatin loading and its subsequent use for 5 days (high-dose group) could prevent CIN as compared to those who received 10â mg atorvastatin (regular-dose group) in patients with ST-elevation myocardial infarction undergoing primary angioplasty. The primary endpoint was incidence of CIN, defined as an at least 25% or at least 0.5â mg/dl increase in baseline serum creatinine within 5 days after contrast administration. The secondary endpoint was an in-hospital 1 and 6-month renal function change, and a composite of all-cause mortality, myocardial infarction, renal failure requiring dialysis, heart failure, and target vessel revascularization. RESULTS: One hundred and ten patients were allocated to high dose and 108 to regular dose from August 2007 to February 2009. CIN incidence was 5.5% (6/110) in the high-dose group and 10.2% (11/108) in the regular-dose group, which is a nonsignificant difference (Pâ=â0.193). CIN occurred significantly less in the high-dose than in the regular-dose group in subgroups of renal insufficiency (creatinine clearance ≤60 âml/min) [0% (0/28) vs. 16.7% (5/30); Pâ=â0.024] and in the elderly patients who were at least 70 years old [4% (1/25) and 23.1% (6/26); Pâ=â0.048]. Serum creatinine level tended to decrease in the high-dose group and increase in the regular-dose group, but the change was not statistically different (Pâ=â0.093). The composite of clinical outcomes at 6 months was comparable in the high-dose and regular-dose groups (7.9 and 13.1%; Pâ=â0.26). CONCLUSION: High-dose atorvastatin pretreatment does not seem to prevent CIN in patients receiving primary angioplasty. However, it has the potential to lower CIN in patients with renal insufficiency and in the elderly.
Assuntos
Atorvastatina/administração & dosagem , Meios de Contraste/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Nefropatias/prevenção & controle , Intervenção Coronária Percutânea , Idoso , Feminino , Humanos , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Atorvastatin pretreatment has been reported to reduce myocardial damage in patients undergoing percutaneous coronary intervention (PCI). We sought to investigate the effect of atorvastatin pretreatment on infarct size in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients undergoing primary PCI for ST-segment elevation myocardial infarction within 12 hours after symptom onset were randomized to an atorvastatin group (80 mg before PCI and for 5 days after PCI [n = 89]) or a control group (10 mg daily after PCI [n = 84]). The primary end point was infarct size measured by technetium Tc 99m tetrofosmin single-photon emission computed tomography between days 5 and 14. RESULTS: Baseline clinical, angiographic, and procedural characteristics were not significantly different between groups except for age and current smoking status. There was no significant difference in infarct size (as a percentage of the left ventricle) between groups (22.2% ± 15.5% in the atorvastatin group vs 21.6% ± 15.4% in the control group, P = .79). The median infarct size was 19.0% (interquartile range 9.0-32.0) in the atorvastatin group and 18.0% (9.3-32.5) in the control group (P = .76). Achievement of myocardial blush grade 2/3 and complete ST-segment resolution at 60 minutes after PCI occurred with similar frequency (72.8% vs 81.9%, P = .33 and 43.2% vs 47.5%, P = .57, respectively). CONCLUSIONS: Pretreatment with high-dose atorvastatin followed by further treatment for 5 days did not reduce infarct size measured by single-photon emission computed tomography in patients undergoing primary PCI.
Assuntos
Angioplastia Coronária com Balão , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Infarto do Miocárdio/terapia , Pirróis/administração & dosagem , Adulto , Idoso , Atorvastatina , Quimioprevenção , Esquema de Medicação , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Estudos Prospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do TratamentoRESUMO
BACKGROUND: Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI), but initial treatment delay to intervention is the main limitation of this strategy. HYPOTHESIS: Upstream use of high-dose tirofiban could reduce myocardial infarct size, using analysis of contrast-enhanced magnetic resonance imaging (CE-MRI). METHODS: Patients with STEMI within 12 hours after symptom onset were randomized to a facilitated PCI group (n = 19) or to a primary PCI group (n = 20). The primary endpoint was myocardial infarct size evaluated by the volume of delayed hyperenhancement on CE-MRI at 1 month after index procedure. RESULTS: The baseline clinical characteristics were not significantly different between the 2 groups. Although the incidence of pre-PCI thrombolysis in myocardial infarction (TIMI) flow grade 2 to 3 was significantly higher in the facilitated PCI group than in the primary PCI group (47.4% vs 15.0%, P = 0.03), the achievement of myocardial blush grade 2 to 3 or ST-segment resolution at 30 minutes after procedure was not significantly different between the facilitated PCI and the primary PCI group (36.8% vs 40%, P = 0.84 and 31.6% vs 20%, P = 0.41, respectively). Infarct size on CE-MRI was similar in the facilitated PCI group and the conventional primary PCI group (22.1% +/- 11.7% vs 25.2% +/- 13.2%, P = 0.44). At 6 months, the left ventricular ejection fraction (LVEF) on echocardiography was 52.6% +/- 10.4% in the facilitated PCI group and 50.9% +/- 9.8% in the primary PCI group (P = 0.68). CONCLUSION: Despite the improvement of initial TIMI flow grade, the upstream use of high-dose tirofiban did not reduce myocardial infarct size measured by CE-MRI.