ABSTRACT
A insuficiência cardíaca aguda (ICA) é uma das causas mais comuns de internação hospitalar, associada a um alto risco de mortalidade. O tratamento atual é principalmente sintomático, sendo os exames laboratoriais realizados, a fim de complementar a avaliação clínica no diagnóstico e auxiliar no estabelecimento do perfil de risco admissional e prognóstico. Este estudo teve como objetivo caracterizar o perfil clínico, farmacoterapêutico e laboratorial de pacientes internados com insuficiência cardíaca aguda em hospital referência regional. Trata-se de um estudo transversal retrospectivo, descritivo, de abordagem quantitativa. Os participantes do estudo foram aqueles com alta médica por ICA pela classificação Internacional de Doenças (CID-10), admitidos na sala de emergência. Excluindo-se a participação de pacientes com tempo de internação inferior a 24 horas, menores de 18 anos. Para análise estatística foi usado o programa SPSS versão 21.0. Quanto ao perfil farmacoterapêutico, os medicamentos mais frequentes foram os que atuam no aparelho cardiovascular e aparelho digestivo e metabolismo, sendo a furosemida o fármaco mais frequente. A análise entre as alterações laboratoriais e a escala de ADHERE, revelou diferença estatística significativa entre os pacientes com risco baixo e risco intermediário/alto nos valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), ureia (p=0,000), potássio (p=0,004), TTPA (p=0,004) e RNI (p=0,021). Concluiu-se que os medicamentos frequentemente corresponderam ao tratamento recomendado no manejo inicial de pacientes com ICA. O risco de mortalidade intra-hospitalar intermediário/alto de acordo com a escala de ADHERE estavam associados com alterações laboratoriais dos pacientes com ICA.
Acute heart failure (AHF) is one of the most common causes of hospitalization, associated with a high risk of mortality. The current treatment is mainly symptomatic, and laboratory tests are carried out in order to complement the clinical evaluation in the diagnosis and help in establishing the admission and prognostic risk profile. This study aimed to characterize the clinical, pharmacotherapeutic and laboratory profile of patients hospitalized with acute heart failure in a regional reference hospital. This is a retrospective, descriptive, cross-sectional study with a quantitative approach. Study participants were those discharged due to AHF according to the International Classification of Diseases (ICD-10), admitted to the emergency room. Excluding the participation of patients with hospitalization time of less than 24 hours, under 18 years old. For statistical analysis, SPSS version 21.0 was used. As for the pharmacotherapeutic profile, the most frequent drugs were those that act on the cardiovascular and digestive systems and metabolism, with furosemide being the most frequent drug. The analysis between laboratory changes and the ADHERE scale revealed a statistically significant difference between patients at low risk and intermediate/high risk in hemoglobin (p=0.005), TGO (p=0.001), creatinine (p=0.000) values, urea (p=0.000), potassium (p=0.004), APTT (p=0.004) and INR (p=0.021). It was concluded that the medications often corresponded to the recommended treatment in the initial management of patients with AHF. Intermediate/high risk of in-hospital mortality according to the ADHERE scale were associated with laboratory alterations in patients with AHF.
La insuficiencia cardiaca aguda (ICA) es una de las causas más frecuentes de hospitalización, asociada a un alto riesgo de mortalidad. El tratamiento actual es principalmente sintomático y se realizan pruebas de laboratorio para complementar la evaluación clínica en el diagnóstico y ayudar a establecer el perfil de riesgo de ingreso y pronóstico. Este estudio tuvo como objetivo caracterizar el perfil clínico, farmacoterapéutico y de laboratorio de pacientes hospitalizados con insuficiencia cardíaca aguda en un hospital regional de referencia. Se trata de un estudio retrospectivo, descriptivo, transversal con enfoque cuantitativo. Los participantes del estudio fueron los dados de alta por ICA según la Clasificación Internacional de Enfermedades (CIE-10), ingresados en urgencias. Se excluye la participación de pacientes con tiempo de hospitalización menor a 24 horas, menores de 18 años. Para el análisis estadístico se utilizó SPSS versión 21.0. En cuanto al perfil farmacoterapéutico, los fármacos más frecuentes fueron los que actúan sobre los sistemas cardiovascular, digestivo y el metabolismo, siendo la furosemida el fármaco más frecuente. El análisis entre los cambios de laboratorio y la escala ADHERE reveló una diferencia estadísticamente significativa entre los pacientes de riesgo bajo e intermedio/alto en los valores de hemoglobina (p=0,005), TGO (p=0,001), creatinina (p=0,000), urea (p =0,000), potasio (p=0,004), APTT (p=0,004) e INR (p=0,021). Se concluyó que los medicamentos correspondían muchas veces al tratamiento recomendado en el manejo inicial de pacientes con ICA. El riesgo intermedio/alto de mortalidad hospitalaria según la escala ADHERE se asoció con alteraciones de laboratorio en pacientes con ICA.
ABSTRACT
Leishmaniasis are endemic diseases caused by different species of intracellular parasites of the genus Leishmania. Due to the high toxicity and drug resistance of current antileishmanial drugs, it is necessary to identify new and more effective drugs. Previously, we investigated the immunomodulatory and anti-Trypanosoma cruzi action of BA5, a derivative of betulinic acid. In the present study, we investigated the in vitro activity of BA5 against different species of Leishmania and their action mechanism. BA5 exhibited low cytotoxicity against macrophages and inhibited the proliferation of promastigote forms of Leishmania amazonensis (IC50 = 4.5 ± 1.1 µM), Leishmania major (IC50 = 3.0 ± 0.8 µM), Leishmania braziliensis (IC50 = 0.9 ± 1.1 µM) and Leishmania infantum (IC50 = 0.15 ± 0.05 µM). Incubation with BA5 reduced the percentage of Leishmania amazonensis-infected macrophages and the number of intracellular parasites (IC50 = 4.1 ± 0.7 µM). To understand the mechanism of action underlying BA5 antileishmanial activity (incubation at IC50/2, IC50 or 2xIC50 values of the drug), we investigated ultrastructural changes by scanning electron microscopy and evaluated cell cycle, membrane mitochondrial potential, and cell death against promastigote forms of Leishmania amazonensis by flow cytometry. Promastigotes incubated with BA5 presented membrane blebbing, flagella damage, increased size, and body deformation. Flow cytometry analysis showed that parasite death is mainly caused by apoptosis-like death, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of Leishmania amazonensis. Surprisingly, the combination of BA5 and amphotericin B, an assay used to determine the degree of drug interaction, revealed synergistic effects (CI = 0.15 ± 0.09) on promastigotes forms of Leishmania amazonensis. In conclusion, BA5 compound is an effective and selective antileishmanial agent.
ABSTRACT
Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, which has very limited treatment options and affects poor and underdeveloped populations. The current treatment is plagued by many complications, such as high toxicity, high cost and resistance to parasites; therefore, novel therapeutic agents are urgently needed. Herein, the synthesis, characterization and in vitro leishmanicidal potential of new complexes with the general formula [RuCl3(TMP)(dppb)] (1), [PtCl(TMP)(PPh3)2]PF6 (2) and [Cu(CH3COO)2(TMP)2]·DMF (3) (dppb = 1,4-bis(diphenylphosphino)butane, PPH3 = triphenylphosphine and TMP = trimethoprim) were evaluated. The complexes were characterized by infrared, UV-vis, cyclic voltammetry, molar conductance measurements, elemental analysis and NMR experiments. Also, the geometry of (2) and (3) were determined by single crystal X-ray diffraction. Despite being less potent against promastigote L. amazonensis proliferation than amphotericin B reference drug (IC50 = 0.09 ± 0.02 µM), complex (2) (IC50 = 3.6 ± 1.5 µM) was several times less cytotoxic (CC50 = 17.8 µM, SI = 4.9) in comparison with amphotericin B (CC50 = 3.3 µM, SI = 36.6) and gentian violet control (CC50 = 0.8 µM). Additionally, complex (2) inhibited J774 macrophage infection and amastigote number by macrophages (IC50 = 6.6 and SI = 2.7). Outstandingly, complex (2) was shown to be a promising candidate for a new leishmanicidal therapeutic agent, considering its biological power combined with low toxicity.
