Efficacy of tocilizumab treatment in cerulein-induced experimental acute pancreatitis model in rats.

BACKGROUND/AIMS: Acute pancreatitis (AP) is a disease that can cause local and systemic complications that may have high morbidity and mortality. Currently, there is not any specific treatment for AP. In this study, we created an experimental model of AP in rats, and we aimed to demonstrate the histological effectiveness of tocilizumab treatment that antagonizes interleukin-6 (IL-6), one of the key cytokines in the development of AP. MATERIALS AND METHODS: Forty-eight rats were divided into six groups for this study. AP model was created by subcutaneous injections of cerulein (20 µg/kg) four times at 1-h intervals. Tocilizumab 4 mg/kg was administered to one of the treatment groups and 8 mg/kg to the other treatment group intraperitoneally. The effects of tocilizumab were revealed by examining pancreatic tissue of the rats histopathologically according to the Schonberg scoring system. RESULTS: A comparison between tocilizumab treatment group and AP control group provides statistically significant improvement in AP (p<0.0001). Furthermore, the dose of 8 mg/kg is shown to be more effective than 4 mg/kg (p=0.004). CONCLUSION: Our study points out that tocilizumab may be an effective agent for pancreatitis treatment.

Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver disease: Association of selenoprotein P with carotid intima-media thickness and endothelium-dependent vasodilation.

BACKGROUND: In patients with NAFLD, there is an increased risk of cardiovascular disease (CVD). Selenoprotein P (SelP), a hepatokine, is associated with insulin resistance (IR) and serum SelP was found to be elevated in patients with NAFLD. AIM: This study aimed to determine the risk of CVD in NAFLD patients and the association of serum SelP levels with this NAFLD related CVD risk. METHODS: Ninety-three patients with NAFLD and 37 healthy controls were included in the study. Complete blood count, C-reactive protein (CRP), fasting glucose, serum lipid levels, and SelP levels were tested from fasting blood samples. Moreover, body mass index (BMI), HOMA-IR, carotid intima-media thickness (cIMT) and flow-mediated dilatation (FMD) were measured. RESULTS: In patients with NAFLD, the FMD ratio was significantly lower than in controls (P=0.027). cIMT measurements were similar in both groups (P=0.996). Serum SelP levels were significantly higher than controls (P<0.001). SelP levels were significantly correlated with BMI, fasting glucose, LDL-cholesterol and HOMA-IR (r=0.395, P<0.001; r=0.322, P=0.002; r=0.353, P<0.001; r=0.521, P<0.001, respectively). Also, SelP levels were significantly lower and correlated with FMD (r=-0.674, P<0.001). SelP, ESR and CRP were significantly higher (P<0.05) and FMD ratios were significantly lower (P<0.05) in patients with nonalcoholic steatohepatitis (NASH) when compared to patients with simple steatosis. CONCLUSION: These results suggest that in young NAFLD patients without additional comorbidities, there is an increased risk of CVD. FMD may be a better predictor for assessment of CVD risk when compared with cIMT. We assume that there could also be an important role of SelP in the pathogenesis of NASH.

Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima-media thickness and endothelium-dependent vasodilation.

It has been suggested that there is an ongoing subclinical inflammation in familial Mediterranean fever (FMF) patients also in attack-free periods as well. Due to this ongoing inflammation, endothelial dysfunction (ED) may develop. Previously, ED has been suggested to increase the risk of the atherosclerosis and cardiovascular disease (CVD). Endocan is recognized as a specific molecule of the endothelium and has been shown to increase in some cases associated with inflammation. However, there is not sufficient data whether those with FMF could develop ED in the early period of life. In this study, we aimed to investigate ED and its relation with endocan in young FMF patients. A total of 57 male patients diagnosed with FMF according to the Tel Hashomer criteria and a total of 33 healthy males with similar characteristics to the patient group were included in this research. Complete blood count, erythrocyte sedimentation rate (ESR), fibrinogen, serum glucose, serum LDL cholesterol (LDL-C) and triglyceride (TG), asymmetric dimethylarginine (ADMA), and endocan levels were tested from fasting blood samples. Moreover, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) were measured. The endocan levels of the FMF patients during an attack-free period were significantly higher than those of the control group (p < 0.001). On the other hand, FMD measurements were significantly lower among FMF patients (p < 0.001). ADMA levels were higher in the patient group; however, this difference was similar (p > 0.05). CIMT values were similar among FMF patients and healthy controls (p > 0.05). These results have suggested that ED may develop in the patients with FMF who have no additional CVD risk, even during young adulthood, and endocan may be a favorable biomarker at demonstration of ED than ADMA among FMF patients.