Immunosuppressive effects of multipotent mesenchymal stromal cells on graft-versus-host disease in rats following allogeneic bone marrow transplantation.

OBJECTIVE: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. MATERIALS AND METHODS: The GVHD model was established by transplantation of Sprague Dawley rats' bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. RESULTS: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. CONCLUSION: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. CONFLICT OF INTEREST: None declared.

Effects of risperidone on development and expression of nicotine-induced locomotor sensitization in rats.

It has been shown that atypical antipsychotics significantly reduce smoking and alcohol consumption in schizophrenic patients. However, our knowledge about the effect of risperidone, especially on nicotine abuse is limited. We aimed to test the effects of risperidone in an animal model of nicotine-induced locomotor sensitization, which represents initial neuroadaptations and continued behavioral changes in nicotine-type dependence. To investigate the effect of risperidone on the development of nicotine-induced locomotor sensitization, rats were pretreated with risperidone (0.025 and 0.050 mg kg⁻¹) 30 min before the nicotine (0.5 mg kg⁻¹, base) treatment, and locomotor activity was recorded for 30 min. This procedure was repeated every day for eight sessions. After a 6-day drug-free period, rats were challenged with nicotine (0.5 mg kg⁻¹). To reveal the effect of risperidone on the expression of nicotine-induced locomotor sensitization, rats were injected with nicotine for eight sessions. After a 6-day drug-free period, rats were pretreated with risperidone (0.025 and 0.050 mg kg⁻¹) or vehicle 30 min before the nicotine (0.5 mg kg⁻¹) challenge injection. Repeated administration of nicotine generated robust locomotor sensitization in rats. Risperidone pretreatment (0.050 mg kg⁻¹) blocked the expression but not the development of nicotine-induced locomotor sensitization in rats. Our results suggest that risperidone blocks the continuation of nicotine-type addictive behavior, but it is ineffective on early adaptations in the initiation of nicotine addiction. Thus, this drug may have a limited beneficial effect in treatment of nicotine dependence.

Effects of sildenafil and tadalafil on ischemia/reperfusion injury in fetal rat brain.

OBJECTIVE: The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, sildenafil and tadalafil, in ischemia/reperfusion (I/R)-induced oxidative injury in fetal rat brain. METHODS: Timed pregnant adult Wistar rats were randomly assigned to the following groups (n = 6 for each group): saline + none I/R (1), saline + I/R (2), sildenafil + none I/R (3); sildenafil + I/R (4), tadalafil + none I/R (5) and tadalafil + I/R (6). Fetal ischemia was induced by clamping the utero-ovarian artery bilaterally. Fetuses were delivered and 268 fetal rats were decapitated. Malondialdehyde (MDA) levels and, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed in fetal brain tissue homogenates by spectrophotometric methods. RESULTS: In saline + I/R group, MDA levels were increased and, SOD and GSH-Px activities were decreased significantly comparing with saline + none I/R group. Both tadalafil and sildenafil treatment decreased the MDA levels significantly in ischemia/reperfusion groups, whereas this effect was significantly more potent with tadalafil. SOD levels were significantly decreased in all groups after I/R. Tadalafil seems to be more effective than sildenafil by means of increasing GSH-Px activity significantly after I/R. CONCLUSION: Our results indicate some beneficial effects of PDE5 inhibitory drugs, especially tadalafil, on oxidative I/R injury in fetal rat brains.