There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs.
Objectives. Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML. Methods. Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2. Results. VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component. Conclusions. Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.
Objective: Our study aimed to investigate the effect of mirtazapine on bone metabolism in the orchidectomized rat model. Methods: Rats were divided into three groups. A sham-operated control group (SHAM group) and a control group after orchidectomy (ORX group) received the standard laboratory diet (SLD). An experimental group after orchidectomy (ORX MIRTA group) received SLD enriched with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I, bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone homogenate. The femurs were used for biomechanical testing. Results: Compared with the control ORX group, we found a lower BMD in the ORX MIRTA group. The differences were statistically significant, although not in the lumbar vertebrae. BMD was lower in the MIRTA group, suggesting a preferential effect on cortical bone. However, although the thickness of the diaphyseal cortical bone was not different, the fragility in the femoral neck area was statistically significantly different between the groups in biomechanical testing. Regarding the bone metabolism markers, there was a significant decrease in OPG and BALP levels, suggesting a reduction in osteoid synthesis. Conclusions: The results suggest that prolonged use of mirtazapine may have a negative effect on the synthesis of bone and on its mechanical strength, especially in the femoral neck. Further studies are warranted to establish whether mirtazapine may have a clinically significant adverse effect on bone exclusively in the model of gonadectomized rats, or whether the effect occurs also in the model of gonadally intact animals and in respective human models.
Background. Transjugular intrahepatic portosystemic shunts (TIPS) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess glycogen phosphorylase BB (GPBB) concentration in relation to echocardiographic and haemodynamic parameters in patients before and after TIPS insertion. Methods. The study population consisted of 55 patients (38 men and 17 women, age 55.6±8.9 years, range 37-74 years) with liver cirrhosis treated with transjugular portosystemic shunting. GPBB, echocardiographic, and haemodynamic parameters were measured before TIPS insertion and 24 h after the procedure. GPBB concentrations were assessed using the Cardiac Array for Evidence Investigator protein biochip. Correlation between parameters was assessed using the Spearman's coefficient. Results. Serum post-procedural GPBB concentrations were increased in comparison with baseline (5.58 vs. 2.67 μg/L, P<0.001). GPBB concentration after TIPS significantly correlated with baseline systemic vascular resistence (r=0.330; P=0.017) and cardiac index (r=0.313; P=0.025). Conclusion. GPBB concentration measurement may be a useful tool for monitoring myocardial ischemia during a TIPS procedure.
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