A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia

<p>Abstract</p> <p>Background</p> <p>Advances in intensive care support such as therapeutic hypothermia or new liver assist devices have been the mainstay of treatment attempting to bridge the gap from acute liver failure to liver transplantation, but the efficacy of the available devices in reducing mortality has been questioned. To address this issue, the present animal study was aimed to analyze the pure clinical effects of a simple extracorporeal dummy device in an anhepatic porcine model of acute liver failure.</p> <p>Methods</p> <p>Total hepatectomy was performed in ten female pigs followed by standardized intensive care support until death. Five animals (dummy group, n = 5) underwent additional cyclic connection to an extracorporeal dummy device which consisted of a plasma separation unit. The separated undetoxified plasma was completely returned to the pigs circulation without any plasma substitution or exchange in contrast to animals receiving intensive care support alone (control group, n = 5). All physiological parameters such as vital and ventilation parameters were monitored electronically; laboratory values and endotoxin levels were measured every 8 hours.</p> <p>Results</p> <p>Survival of the dummy device group was 74 ± 6 hours in contrast to 53 ± 5 hours of the control group which was statistically significant (p < 0.05). Body temperature 24 hours after hepatectomy was significantly lower (36.5 ± 0.5°C vs. 38.2 ± 0.7°C) in the dummy device group. Significant lower values were measured for blood lactate (1.9 ± 0.2 vs. 2.5 ± 0.5 mM/L) from 16 hours, creatinine (1.5 ± 0.2 vs. 2.0 ± 0.3 mg/dL) from 40 hours and ammonia (273 ± 122 vs. 1345 ± 700 μg/dL) from 48 hours after hepatectomy until death. A significant rise of endotoxin levels indicated the onset of sepsis at time of death in 60% (3/5) of the dummy device group animals surviving beyond 60 hours from hepatectomy.</p> <p>Conclusions</p> <p>Episodes of slight hypothermia induced by cyclic connection to the extracorporeal dummy device produced a significant survival benefit of more than 20 hours through organ protection and hemodynamic stabilisation. Animal studies which focus on a survival benefit generated by liver assist devices should especially address the aspect of slight transient hypothermia by extracorporeal cooling.</p

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds

LGBTQ parenting post heterosexual relationship dissolution

The chapter examines parenting among sexual and gender minorities post heterosexual relationship dissolution (PHRD). Reviewing the literature around intersecting identities of LGBTQ parents, we consider how religion, race, and socioeconomic status are associated with routes into and out of heterosexual relationships and variation in the lived experience of sexual and gender identity minorities, in particular how LGBTQ parents PHRD feel about being out. Further consideration is given to examining how family relationships change and develop as parental sexual and/or gender identity changes. We also explore the impact of PHRD identity and parenthood on new partnerships and stepfamily experiences. The chapter addresses the reciprocal relationship between research on LGBTQ parenting and policy and legal influences that impact upon the experience of LGBTQ parenting PHRD when custody and access are disputed. Finally, the chapter includes future research directions and implications for practice in an area that has been revitalized in recent years