RESUMEN
Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.
Asunto(s)
Síndrome Hepatorrenal , Trasplante de Hígado , Síndrome Hepatorrenal/complicaciones , Síndrome Hepatorrenal/terapia , Humanos , Riñón , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , TacrolimusRESUMEN
The development of nanotechnology in the last two decades has led to the use of silver nanoparticles (AgNPs) in various biomedical applications, including antimicrobial, anti-inflammatory, and anticancer therapies. However, the potential of the medical application of AgNPs depends on the safety of their use. In this work, we assessed the in vitro cytotoxicity and genotoxicity of silver nanoparticles and identified biomolecules covering AgNPs synthesized from actinobacterial strain SH11. The cytotoxicity of AgNPs against MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264.7 was studied by MTT assay, cell LDH (lactate dehydrogenase) release, and the measurement of ROS (reactive oxygen species) level while genotoxicity in Salmonella typhimurium cells was testing using the Ames test. The in vitro analysis showed that the tested nanoparticles demonstrated dose-dependent cytotoxicity against RAW 264.6 macrophages and MCF-7 breast cancer cells. Moreover, biosynthesized AgNPs did not show a mutagenic effect of S. typhimurium. The analyses and identification of biomolecules present on the surface of silver nanoparticles showed that they were associated with proteins. The SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis revealed the presence of 34 and 43 kDa protein bands. The identification of proteins performed by using LC-MS/MS (liquid chromatography with tandem mass spectrometry) demonstrated their highest homology to bacterial porins. Capping biomolecules of natural origin may be involved in the synthesis process of AgNPs or may be responsible for their stabilization. Moreover, the presence of natural proteins on the surface of bionanoparticles eliminates the postproduction steps of capping which is necessary for chemical synthesis to obtain the stable nanostructures required for application in medicine.