Tratamiento de la infección del torrente sanguíneo por pseudomona aeruginosa con resistencia a carbapenemicos / Bloodstream infección treatment by carbapenem-resistant pseudomonas aeruginosa

La Pseudomona aeruginosa es una bacteria gramnegativa con gran capacidad de adaptación a ambientes hostiles, uno de ellos, el medio hospitalario, donde ha surgido como germen a temer por el papel preponderante que ha tenido en los pacientes que cursan con infecciones del torrente sanguíneo, dado por el desarrollo de mecanismo de resistencia a diferentes antimicrobianos que hace complejo el manejo terapéutico, incrementando de esta manera la morbimortalidad, la estancia hospitalaria y los gastos en atención sanitaria de estos paciente. Se realizó una revisión sistemática de la literatura disponible para establecer el estado actual del manejo antimicrobiano de la infección del torrente sanguíneo por Pseudomona aeruginosa

Pseudomonas aeruginosa is a gram-negative bacteria, possesses a great adaptability to hostile environ-ments, one of them is the clinical environment, where it has emerged as a fearful germ which performs a leading role in patients who present bloodstream infections, due to its development resistance mechanisms to different antimicrobial it makes therapeutic management complex, increases mortality and morbidity, hospital stay and health care expenses for these patients are high. A systematic review of available literature was performed to establish the current status of antimicrobial management of bloodstream infection by Pseudomonas aeruginosa

Overview of P-glycoprotein inhibitors: a rational outlook

P-glycoprotein (P-gp), a transmembrane permeability glycoprotein, is a member of ATP binding cassette (ABC) super family that functions specifically as a carrier mediated primary active efflux transporter. It is widely distributed throughout the body and has a diverse range of substrates. Several vital therapeutic agents are substrates to P-gp and their bioavailability is lowered or a resistance is induced because of the protein efflux. Hence P-gp inhibitors were explored for overcoming multidrug resistance and poor bioavailability problems of the therapeutic P-gp substrates. The sensitivity of drug moieties to P-gp and vice versa can be established by various experimental models in silico, in vitro and in vivo. Ever since the discovery of P-gp, the research plethora identified several chemical structures as P-gp inhibitors. The aim of this review was to emphasize on the discovery and development of newer, inert, non-toxic, and more efficient, specifically targeting P-gp inhibitors, like those among the natural herb extracts, pharmaceutical excipients and formulations, and other rational drug moieties. The applications of cellular and molecular biology knowledge, in silico designed structural databases, molecular modeling studies and quantitative structure-activity relationship (QSAR) analyses in the development of novel rational P-gp inhibitors have also been mentioned.

Glicoproteína-p (P-gp), uma glicoproteína de transmembrana permeável, é um membro da superfamília (ABC) de cassete de gene de ligação de ATP que funciona especificamente como um carreador mediado pelo transportador de efluxo ativo primário. É amplamente distribuído por todo o corpo e apresenta uma gama diversificada de substratos. Diversos agentes terapêuticos vitais são substratos para P-gp e sua biodisponibilidade é reduzida ou a resistência é induzida devido ao efluxo de proteínas. Portanto, os inibidores da P-gp foram explorados para a superação da resistência a múltiplas drogas e problemas de biodisponibilidade deficiente dos substratos terapêuticos da P-gp. A sensibilidade das moléculas da droga à P-gp e vice-versa, pode ser estabelecida por vários modelos experimentais in silico, in vitro e in vivo. Desde a descoberta da P-gp, diversas pesquisas identificaram várias estruturas químicas como inibidores da P-gp. O objetivo deste presente estudo foi o de enfatizar a descoberta e desenvolvimento de inibidores mais novos, inertes, atóxicos e mais eficazes, visando especificamente os da P-gp, como aqueles entre os extratos vegetais, excipientes e formulações farmacêuticas, e outras moléculas racionais de droga. As aplicações do conhecimento de biologia celular e molecular, bancos de dados estruturais in silico, estudos de modelagem molecular e análises da relação quantitativa estrutura-atividade (QSAR) no desenvolvimento de novos inibidores racionais da P-gp também foram mencionados.

The mechanism of multicellular resistance mediated by NF-?B signaling pathway in colonic carcinoma cells / 解放军医学杂志

Objectives To explore the effect of NF-?B signaling pathway on multicellular resistance(MCR) to 5-Fu in colon carcinoma cells.Methods The multicellular spheroids(MCS) of colon carcinoma HT-29 cell line were cultured by using liquid overlay technique,and the monolayer cells by using routine procedure.The morphology of MCS was observed with light microscope and scanning electronmicroscope(SEM).The expression of proliferating cell nuclear antigen(PCNA) was determined by immunohistochemistry.24 hours after adding 50?g/ml SN50 to spheroids cells,the 50% inhibiting concentration(IC50) for 5-Fu was determined by using radial outgrowth assay.The activity of NF-?B was measured by using electrophoretic mobility shift assay(EMSA) and the specific bands were observed.Apoptosis of spheroids cells,which were pretreated with 5?g/ml 5-Fu for 24 hours,was identified by TUNEL,the apoptosis related proteins caspase-3,Bcl-2 and Bax were detected by Western blotting and analyzed by semi-quantitative method.Results A necrotic core formed in the centre of MCS,and the peripheral cells were actively proliferating.Compared with the monolayer cultured cells,the activity of NF-?B was increased in MCS.When the activity of NF-?B in spheroid cells was inhibited by SN50,5-Fu readily induced cells to apoptosis(15.75%?1.02% vs 8.71%?0.73%,P