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1.
J Thromb Thrombolysis ; 52(3): 934-940, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33258102

RESUMO

Although P2Y12 receptor blockers have become a standard, adjunctive therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the optimal regimen has not been established. We performed a prospective, open-label, randomized study to investigate the effect of cangrelor administration on platelet function and inflammation in patients with primary PCI (PPCI). Twenty-two patients were randomized to receive either cangrelor and ticagrelor or ticagrelor alone (standard group) before PPCI. Platelet reactivity was evaluated at baseline (before PCI), 10 min and the end of the procedure. At baseline, there was no significant difference in platelet reactivity between both groups, whereas platelets were significantly inhibited at 10 min after initiating cangrelor vs. standard (adenosine-diphosphate-induced aggregation 102.2 ± 24.88 vs. 333.4 ± 63.3, P < 0.05 and thrombin-receptor-activating-peptide-induced aggregation 285.8 ± 86.1 vs. 624.8 ± 106.0, P < 0.05). Lower platelet aggregation in the cangrelor group persisted but the difference was reduced by the end of the procedure. Circulating inflammatory cells, pro-inflammatory cytokines, total elastase, and surrogates of neutrophil extracellular traps (total elastase-myeloperoxidase complexes) were significantly lower in the cangrelor compared to the standard therapy group at 6 h after randomization. There was a trend towards reduction in cardiac damage in the cangrelor group as reflected by the changes in late gadolinium enhancement between 48 h and 3 months after STEMI. Early administration of cangrelor in STEMI patients was associated with more effective platelet inhibition during PPCI and significantly dampened the deleterious inflammatory response compared to standard therapy (NCT03043274).


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Monofosfato de Adenosina/análogos & derivados , Meios de Contraste , Gadolínio , Humanos , Elastase Pancreática , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ticagrelor/uso terapêutico , Resultado do Tratamento
2.
Front Chem ; 8: 561052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324607

RESUMO

A low-cost, simple, and highly selective method was used for the assessment of total prostate specific antigen (tPSA) in the serum of prostate cancer patients. This method is based on quenching the intensity of luminescence displayed by the optical sensor Eu (TTA)3 phen/poly methylmethacrylate (PMMA) thin membrane or film upon adding different concentrations of tPSA. The luminescent optical sensor was synthesized and characterized through absorption, emission, scanning electron microscopy (SEM), and x-ray diffraction (XRD), and is tailored to present red luminescence at 614 nm upon excitation at 395 nm in water. The fabricated sensor fluorescence intensity is quenched in the presence of tPSA in aqueous media. The fluorescence resonance energy transfer (FRET) is the main mechanism by which the sensor performs. The sensor was successfully utilized to estimate tPSA in the serum of patients suffering prostate cancer in a time and cost effective way. The statistical results of the method were satisfactory with 0.0469 ng mL-1 as a detection limit and 0.99 as a correlation coefficient.

3.
J Mol Cell Cardiol ; 149: 95-114, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33017574

RESUMO

OBJECTIVE: Acute myocardial infarction (AMI) initiates pathological inflammation which aggravates tissue damage and causes heart failure. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), promotes inflammation and the development of atherosclerosis. The role of ATX/LPA signaling nexus in cardiac inflammation and resulting adverse cardiac remodeling is poorly understood. APPROACH AND RESULTS: We assessed autotaxin activity and LPA levels in relation to cardiac and systemic inflammation in AMI patients and C57BL/6 (WT) mice. Human and murine peripheral blood and cardiac tissue samples showed elevated levels of ATX activity, LPA, and inflammatory cells following AMI and there was strong correlation between LPA levels and circulating inflammatory cells. In a gain of function model, lipid phosphate phosphatase-3 (LPP3) specific inducible knock out (Mx1-Plpp3Δ) showed higher systemic and cardiac inflammation after AMI compared to littermate controls (Mx1-Plpp3fl/fl); and a corresponding increase in bone marrow progenitor cell count and proliferation. Moreover, in Mx1- Plpp3Δ mice, cardiac functional recovery was reduced with corresponding increases in adverse cardiac remodeling and scar size (as assessed by echocardiography and Masson's Trichrome staining). To examine the effect of ATX/LPA nexus inhibition, we treated WT mice with the specific pharmacological inhibitor, PF8380, twice a day for 7 days post AMI. Inhibition of the ATX/LPA signaling nexus resulted in significant reduction in post-AMI inflammatory response, leading to favorable cardiac functional recovery, reduced scar size and enhanced angiogenesis. CONCLUSION: ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury.


Assuntos
Inflamação/patologia , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Remodelação Vascular , Animais , Benzoxazóis/farmacologia , Contagem de Células , Movimento Celular/efeitos dos fármacos , Feminino , Deleção de Genes , Humanos , Inflamação/genética , Interferon-alfa/metabolismo , Interferon beta/metabolismo , Lisofosfolipídeos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mielopoese , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/genética , Miocárdio/patologia , Fosfatidato Fosfatase/metabolismo , Piperazinas/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Regulação para Cima/genética , Cicatrização
5.
Environ Sci Pollut Res Int ; 26(30): 30836-30846, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446598

RESUMO

This study aims to identify the analytical and radiological characterization of scale TENORM waste produced from oil and natural gas productions in the western desert in Egypt and evaluates their radiological impacts. The mean activity concentration of 238U, 226Ra, 210Pb, 228Ra, 224Ra, and 40K measured in scale TENORM samples is 660 ± 63, 1979 ± 435, 1399 ± 211, 645 ± 104, 794 ± 116, and 556 ± 86 Bq/kg, respectively. Radiological hazard parameters (Raeq, Hex, Hin, etc.) were estimated form the scale TENORM waste sample. All the calculated hazard parameters were found greater than the permissible and recommended safe levels. So the exposure to radiations released from the accumulation of the petroleum scale TENORM waste may cause health risks to the operators and who inhale radioactive radon gases and/or ingest contaminants by radiotoxic nuclides of U, Th, Ra, and Pb. Also, the risks may be extended to the near and/or the general environment.


Assuntos
Resíduos Industriais/análise , Campos de Petróleo e Gás , Poluentes Radioativos/análise , Radiação de Fundo , Egito , Radioisótopos de Chumbo/análise , Gás Natural , Radioisótopos de Potássio/análise , Monitoramento de Radiação , Rádio (Elemento)/análise , Tório/análise , Urânio/análise
6.
Mediators Inflamm ; 2019: 2872607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341419

RESUMO

BACKGROUND: Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. METHODS: MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. RESULTS: Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P < 0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P = 0.14 and OR 1.23; CI: 0.96-1.58, P = 0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P = 0.0048 and 4.88: 95% CI 0.756 to 9.0133, P = 0.0204, respectively). CONCLUSIONS: Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients.


Assuntos
Síndrome Coronariana Aguda/enzimologia , Peroxidase/sangue , Síndrome Coronariana Aguda/diagnóstico , Arritmias Cardíacas/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Insuficiência Cardíaca/sangue , Humanos , Inflamação , Masculino , Infarto do Miocárdio/sangue , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Recidiva , Análise de Regressão , Medição de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Transdução de Sinais , Fumar , Resultado do Tratamento
7.
Catheter Cardiovasc Interv ; 94(5): 714-721, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074100

RESUMO

OBJECTIVE: We sought to perform a systematic review and meta-analysis of the available literature comparing fractional flow reserve (FFR) measurements after administration of adenosine using intracoronary (IC) bolus versus standard continuous intravenous (IV) infusion. BACKGROUND: FFR is considered the gold standard for invasive assessment of coronary lesions of intermediate severity. IV adenosine is recommended to induce hyperemia; however, IC adenosine is widely used for convenience. The difference between IV and IC administration in lesions assessment is not well studied. METHODS: We systematically searched MEDLINE and relevant databases for studies comparing IV with IC adenosine administration for FFR measurement. We reviewed data pertaining to adenosine doses, side effects, and FFR values. RESULTS: Eight studies addressing the primary question were identified. Dose of IC adenosine varied between 36 and 600 µg. Compared to IV adenosine infusion, the sensitivity of IC administration is 0.805 (95% confidence interval [95% CI]: 0.664-0.896; p < .001), specificity is 0.965 (95% CI: 0.932-0.983; p < .001), positive likelihood ratio is 24.218 (95% CI: 12,263-47.830; p < .001), negative likelihood ratio is 0.117 (95% CI: 0.033-0.411; p < .01), and diagnostic odds ratio is 274.225 [95% CI: 92.731-810.946; p < .001]. Overall, hemodynamic side effects and symptoms were reported more frequently with IV adenosine. CONCLUSIONS: The available literature suggests that IC adenosine is well tolerated and may provide equivalent diagnostic accuracy compared to IV administration. However, variability in dosing regimens does not allow definitive conclusions regarding noninferiority of IC approach compared to IV administration.


Assuntos
Adenosina/administração & dosagem , Cateterismo Cardíaco , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Reserva Fracionada de Fluxo Miocárdico , Hiperemia/fisiopatologia , Vasodilatadores/administração & dosagem , Adenosina/efeitos adversos , Idoso , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença
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