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1.
Eur J Case Rep Intern Med ; 9(9): 003564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299841

RESUMO

Eosinophilic myocarditis (EM) is a rare cause of acute heart failure. It can occur secondary to drug hypersensitivity, autoimmune diseases such as vasculitis, idiopathic hypereosinophilic syndrome (HES) or malignancy, but is often under-recognized and underdiagnosed, being confused with other causes of heart failure. While EM is associated with various clinical symptoms, it is rarely associated with cardiac tamponade that requires urgent pericardiocentesis. Here we describe a patient with EM who presented with cardiac tamponade and decompensated heart failure likely secondary to autoimmune disease. LEARNING POINTS: Work-up for hypereosinophilia should include the identification of treatable causes as well as end-organ dysfunction requiring urgent treatment.In patients presenting with acute heart failure and cardiac tamponade of unclear aetiology, eosinophilic myocarditis should be considered whether or not hypereosinophilia is present on presentation.When invoking the diagnosis of eosinophilic myocarditis, extensive efforts should be made to identify primary causes, such as autoimmune conditions including vasculitis.

2.
Molecules ; 23(7)2018 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-29966296

RESUMO

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0⁻15% cytotoxicity at 5⁻100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0⁻12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the peptides through the cell membrane. Thus, we synthesized seven fatty acyl derivatives of the linear (HR)4 peptide. The peptides were synthesized using Fmoc/tBu solid phase peptide chemistry, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption/ionization (MALDI) spectrometry. The fatty acyl peptides containing C8, C12, C14, and C18 alkyl chain did not show cytotoxicity on SK-OV-3 or CCRF-CEM cell lines up to 50 µM concentration; however, at higher concentration (100 µM), they showed mild cytotoxicity. For example, C16-(HR)4 was also found to reduce the proliferation of SK-OV-3 cells by 11% at 50 µM and C20-(HR)4 showed mild toxicity at 10 µM, reducing the proliferation of SK-OV-3 cells by 21%. Increase in the length of alkyl chain showed cytotoxicity to the cell lines. C20-(HR)4 peptide showed better efficiency in translocation of F'-GpYEEI to SK-OV-3 than the phosphopeptide alone. Further investigation of C20-(HR)4 peptide efficacy showed that the peptide could deliver doxorubicin and epirubicin into SK-OV-3 and also improved the drug antiproliferative ability. These studies provided insights into understanding the structural requirements for optimal cellular delivery of the fatty acyl-(HR)4 peptide conjugates.


Assuntos
Arginina , Histidina , Peptídeos Cíclicos/química , Peptídeos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Arginina/química , Transporte Biológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/síntese química , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/farmacologia , Sistemas de Liberação de Medicamentos , Histidina/química , Humanos , Peptídeos/síntese química , Peptídeos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia
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