Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Hepatic Ischemia Reperfusion Injury in a Rat Model

BACKGROUND: Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy. METHODOLOGY/PRINCIPAL FINDINGS: We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration

The clinical global impression scale and the influence of patient or staff perspective on outcome

<p>Abstract</p> <p>Background</p> <p>Since its first publication, the Clinical Global Impression Scale (CGI) has become one of the most widely used assessment instruments in psychiatry. Although some conflicting data has been presented, studies investigating the CGI's validity have only rarely been conducted so far. It is unclear whether the improvement index CGI-I or a difference score of the severity index CGI-S_difis more valid in depicting clinical change. The current study examined the validity of these two measures and investigated whether therapists' CGI ratings correspond to the view the patients themselves have on their condition.</p> <p>Methods</p> <p>Thirty-one inpatients of a German psychotherapeutic hospital suffering from a major depressive disorder (age M = 45.3, SD = 17.2; 58.1% women) participated. Patients filled in the Beck Depression Inventory (BDI). CGI-S and CGI-I were rated from three perspectives: the treating therapist (THER), the team of therapists involved in the patient's treatment (TEAM), and the patient (PAT). BDI and CGI-S were filled in at admission and discharge, CGI-I at discharge only. Data was analysed using effect sizes, Spearman's <it>ρ </it>and intra-class correlations (ICC).</p> <p>Results</p> <p>Effect sizes between CGI-I and CGI-S _difratings were large for all three perspectives with substantially higher change scores on CGI-I than on CGI-S _dif. BDI_difcorrelated moderately with PAT ratings, but did not correlate significantly with TEAM or THER ratings. Congruence between CGI-ratings from the three perspectives was low for CGI-S _dif(ICC = .37; Confidence Interval [CI] .15 to .59; <it>F</it>_30,60= 2.77, <it>p </it>< .001; mean <it>ρ </it>= 0.36) and moderate for CGI-I (ICC = .65 (CI .47 to .80; <it>F</it>_30,60= 6.61, <it>p </it>< .001; mean <it>ρ </it>= 0.59).</p> <p>Conclusions</p> <p>Results do not suggest a definite recommendation for whether CGI-I or CGI-S _difshould be used since no strong evidence for the validity of neither of them could be found. As congruence between CGI ratings from patients' and staff's perspective was not convincing it cannot be assumed that CGI THER or TEAM ratings fully represent the view of the patient on the severity of his impairment. Thus, we advocate for the incorporation of multiple self- and clinician-reported scales into the design of clinical trials in addition to CGI in order to gain further insight into CGI's relation to the patients' perspective.</p