Treatment Of Acute Liver Research Articles

Site-Specific Biomimicry of Antioxidative Melanin Formation and Its Application for Acute Liver Injury Therapy and Imaging.

Biocompatible nano-antioxidants composed of natural molecules/materials, such as dopamine and melanin, are of great interest for diverse biomedical applications. However, the lack of understanding of the precise structure of these biomaterials and thus the actual dose of effective components impedes their advancement to translation. Herein, a strategy to mimic in situ melanin formation and explore its antioxidative applications is reported, by developing a PEGylated, phenylboronic-acid-protected L-DOPA precursor (PAD) that can self-assemble into well-defined nanoparticles (PADN). Exposure to oxidative species leads to deprotection of phenylboronic acids, transforming PADN to PEG-L-DOPA, which, similar to the biosynthetic pathway of melanin, can be oxidized and polymerized into an antioxidative melanin-like structure. With ultrahigh stability and superior antioxidative activity, the PADN shows remarkable efficacy in prevention and treatment of acute liver injury/failure. Moreover, the in situ structure transformation enables PADN to visualize damaged tissue noninvasively by photoacoustic imaging. Overall, a bioinspired antioxidant with precise structure and site-specific biological activity for theranostics of oxidative stress-related diseases is described.

Evaluation of a novel hybrid bioartificial liver based on multi-layer fiat-plate bioreactor

Objective To evaluate the efficacy of a novel hybrid bioartificial liver based on multilayer flat-plate bioreactor in treatment of acute liver failure.Methods The animals were divided into the hybrid bioartificial liver (HBAL) treatment group (n =8 ),the bioartificial liver (BAL) treatment group (n =8),the non-bioartificial liver (NBAL) treatment group (n =8),and the control group (n =8).Biochemical parameters and survival time were determinedt.The levels of xenoantibodies ( IgG,IgM) were determined by using enzyme linked immunosorbent assay ( ELISA ).The PERV mRNA expression in the plasma was detected by using reverse transcription-polymerase chain reaction (RT-PCR).Results Biochemical parameters were significantly decreased in all treatment groups. Analysis of survival curves showed that the 7-day survival rate was 37.5％ (3/8) in the control group,50.0％ (4/8) in the NBAL group,62.5％ (5/8) in the BAL group and 87.5％ (7/8) in the HBAL group respectively.Survival time was significantly prolonged by HBAL treatment ( P ＜ 0.05 ).Conclusion The hybrid bioartificial liver showed a great efficiency in the treatment of acute liver failure. Key words: Bioartificial liver; Acute liver failure

Development of formaldehyde-free agar/gelatin microcapsules containing berberine HCl and gallic acid and their topical and oral applications

The safety issues of biomedical applications have been a major concern in recent years. Drug delivery associated with microencapsulation technology has been focused on as microencapsulated drugs are believed to promote comparative therapeutic efficiency on human absorption and prolong the life cycle of drugs. The most commonly applied crosslinker is formaldehyde in a gelatin microencapsulation system, which is considerably toxic to the human body. To reduce the risks involved when using formaldehyde, agar was associated with gelatin as the wall matrix materials of microcapsules as it could crosslink with gelatin to give a gel network in the microcapsules formation. Here we report the development, characterization and safe use of agar–gelatin microcapsules. We further demonstrate that both oral and topical applications are possible using the berberine HCl and gallic acid loaded microcapsules respectively. Microcapsules containing both drugs were prepared combining the optimal parameters identified. The mean drug loading efficiency and the mean particle sizes of the berberine HCl loaded microcapsules were 78.16% and 16.75 μm respectively, while those of gallic acid loaded microcapsules were 70.28% and 21.98 μm respectively. The compositions and surface morphology of berberine HCl and gallic acid containing microcapsules were examined using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The in vitro controlled release models demonstrated that the drugs could be gradually released from the microcapsules. The minimum inhibitory concentrations (MICs) and anti-Staphylococcus aureus activity also proved that the berberine HCl loaded microcapsules exhibited better antibacterial activity towards Staphylococcus aureus when compared with those of the original drugs. The in vitro drug delivery model also demonstrated the delivery of berberine HCl from microcapsule treated textiles into nude mice skin. The in vivo mice disease model also showed that gallic acid loaded microcapsules were helpful in the treatment of acute liver and kidney toxicity after an overdose administration of acetaminophen. The development of agar–gelatin microcapsules was demonstrated to be an efficient, deliverable tool for both oral and topical applications.

Prolonged function of extracorporeal hDAF transgenic pig livers perfused with human blood.

The development of genetically modified pigs has renewed interest in the use of porcine liver perfusion in the treatment of acute liver failure. A previously developed model of extracorporeal perfusion has been used to test the function of porcine livers transgenic for human decay accelerating factor when perfused with fresh, whole, human blood. Three experimental groups were studied: alloperfusions (normal pig livers perfused with pig blood) and xenoperfusions of both unmodified and transgenic pig livers with human blood. All livers were perfused for up to 72 hr. Alloperfusion resulted in the maintenance of good function and histological structure. Stable hemodynamic, synthetic, and metabolic parameters were demonstrated in both unmodified and transgenic liver xenoperfusions; hyperacute rejection was not seen. In both groups, however, the measured parameters of liver function deteriorated toward the end of the 72 hr perfusion period; deterioration was more marked in the nontransgenic group. Xenoperfusions were characterized by a progressive and marked decrease in hematocrit of the circulating blood. Histologically, patchy necrosis was noted in both groups and more retained erythrocytes were seen in the sinusoids of nontransgenic livers, but no other consistent differences were apparent. These studies have demonstrated that porcine liver xenoperfusions can be performed for prolonged periods while maintaining good liver function. The use of organs from animals transgenic for a human complement regulator protein confers improvement in some measures of liver function. This preclinical model provides evidence that extracorporeal liver xenoperfusion may be effective in temporary liver support for patients in acute liver failure.

Large scale cryopreservation of porcine hepatocytes for the clinical treatmentof acute liver failure

Large scale cryopreservation of porcine hepatocytes for the clinical treatmentof acute liver failure