RESUMO
The control of ticks through vaccination offers a sustainable alternative to the use of chemicals that cause contamination and the selection of resistant tick strains. However, only a limited number of anti-tick vaccines have reached commercial realization. In this sense, an antigen effective against different tick species is a desirable target for developing such vaccines. A peptide derived from the tick P0 protein (pP0) conjugated to a carrier protein has been demonstrated to be effective against the Rhipicephalus microplus, Rhipicephalus sanguineus, and Amblyomma mixtum tick species. The aim of this work was to assess the efficacy of this peptide when conjugated to the Bm86 protein against Dermacentor nitens and Ixodes ricinus ticks. An RNAi experiment using P0 dsRNA from I. ricinus showed a dramatic reduction in the feeding of injected female ticks on guinea pigs. In the follow-up vaccination experiments, rabbits were immunized with the pP0-Bm86 conjugate and challenged simultaneously with larvae, nymphs, and the adults of I. ricinus ticks. In the same way, horses were immunized with the pP0-Bm86 conjugate and challenged with D. nitens larva. The pP0-Bm86 conjugate showed efficacies of 63% and 55% against I. ricinus and D. nitens ticks, respectively. These results, combined with previous reports of efficacy for this conjugate, show the promising potential for its development as a broad-spectrum anti-tick vaccine.
RESUMO
CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation.
Assuntos
Antineoplásicos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Peptídeos Cíclicos/farmacologia , Peptídeos/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Peptídeos Penetradores de Células/síntese química , Técnicas de Química Sintética/métodos , Humanos , Neoplasias/tratamento farmacológico , Peptídeos/síntese química , Peptídeos Cíclicos/síntese química , Fosforilação/efeitos dos fármacosRESUMO
La insuficiencia mitral es una afección común que incide generalmente en 2 porceinto de la población, el prolapso valvular es el hallazgo más frecuente por la elongación o ruptura de las cuerdas tendinosas lo que ocasiona disímiles grados de regurgitación durante la contracción ventricular. A pesar de ello, la evaluación clínica de los pacientes asintomáticos con insuficiencia mitral severa, permanece en controversia y es motivo de debate entre los principales expertos. Se presentó un caso de insuficiencia mitral severa asintomática por rotura de cuerda tendinosa, al cual se le realizó sustitución valvular mitral debido al grado de deterioro del aparato valvular y sub-valvular, se logró buen resultado en el seguimiento
Mitral failure is a common disease that generally affects 2 percent of the population. The valvular prolapse is the most frequent finding due to elongation or rupture of tendinous cords that brings about different levels of regurgitation during the ventricular contraction. Despite the above-mentioned, the clinical evaluation of asymptomatic severe mitral failure patients remains controversial and is very much debated among outstanding experts. A case of asymptomatic severe mitral failure caused by rupture of the tendinous cord was presented. The mitral valve was replaced because the valvular and subvalvular systems were much deteriorated. The follow-up of the patient showed good results