RESUMO
Proton pump inhibitors (PPIs) are the most commonly used anti-acid drugs worldwide, including among cancer patients. However, drug-drug interactions between PPIs and other agents may lead to decreased drug absorption with possible reduced therapeutic benefit, or even increased toxicity. Unfortunately, only scarce data exist regarding the safety of concomitant PPI use with anti-cancer agents. We aim at reviewing current evidence on this possible interaction by dividing anti-cancer agents by class. Until further data is available, we encourage healthcare providers to limit unnecessary PPI overuse.
Assuntos
Oncologistas , Inibidores da Bomba de Prótons , Interações Medicamentosas , Humanos , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
Antibiotics have been extensively used to treat infectious diseases over the past century and have largely contributed to increased life expectancy over time. However, antibiotic use can impose profound and protracted changes to the diversity of the microbial ecosystem, affecting the composition of up to 30% of the bacterial species in the gut microbiome. By modifying human microbiota composition, antibiotics alter the action of several oncologic drugs, potentially leading to decreased efficacy and increased toxicities. Whether antibiotics interfere with cancer therapies or even increase the risk of cancer development has been under investigation, and no randomised trials have been conducted so far. The aim of the current review is to describe the possible effects of antibiotic therapies on different oncologic treatments, especially immunotherapies, and to explore the link between previous antibiotics use and the development of cancer.
RESUMO
Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.
RESUMO
This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Ácidos Graxos/química , Isoniazida/análogos & derivados , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Isoniazida/síntese química , Testes de Sensibilidade Microbiana , Rifampina/farmacologiaRESUMO
Several quinonoid and phenazine compounds were synthesized in moderate to high yields and showed activity against H(37)Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The cytotoxity of the compounds were evaluated against human peripheral blood mononuclear cells (PBMC) and these substances emerge as promising antitubercular prototypes.
Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Fenazinas/síntese química , Quinonas/síntese química , Antituberculosos/química , Células Cultivadas , Resistência Microbiana a Medicamentos , Isoniazida/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Modelos Moleculares , Fenazinas/química , Fenazinas/farmacologia , Quinonas/química , Quinonas/farmacologia , Rifampina/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Difração de Raios XRESUMO
Three crude extracts of Aplysina caissara, a marine sponge endemic to Brazil, were tested against a hepatoma cell line and Mycobacterium tuberculosis. The results demonstrate that all extracts are toxic and capable of inhibiting cellular growth. Additionally, the extracts produced morphological aberrations and inhibited cell attachment to culture substrates. These effects were dose/time dependent. Our results also suggest that reactive oxygen species (ROS) production is not involved in the cytotoxic processes levied by the extracts employed in this study and that active metabolites are likely to be present in the polar fractions of the crude extracts. Finally, our results indicate that all three extracts exhibit a moderate anti-tuberculosis capacity, and that the removal of an extract's lipid fraction appears to diminish this activity.