Krystyna Zwirska-Korczala

Serum chemerin and vaspin in non-alcoholic fatty liver disease.

Abstract Objective. Chemerin and vaspin are new adipokines which may modulate inflammatory response and insulin sensitivity in non-alcoholic fatty liver disease (NAFLD). The aims of this study were to assess: (1) circulating levels of chemerin and vaspin and their association with liver histology and markers of liver injury in NAFLD patients; and (2) the relationship between the analyzed adipokines and insulin resistance. Material and methods. A total of 41 NAFLD patients with body mass index (BMI) 30.4 ± 3.3 kg/m2 [20 with non-alcoholic steatohepatitis (NASH) and BMI 30.3 ± 3.3 kg/m2 and 21 with simple steatosis/uncertain NASH (SS/UN) and BMI 30.5 ± 3.4 kg/m2] and 10 healthy volunteers with BMI 24.0 ± 2.9 kg/m2 were included in the study. Results. Serum chemerin concentration was significantly higher in NAFLD patients compared to healthy volunteers (p = 0.009). Serum chemerin was significantly higher in patients with NASH compared to patients with SS/UN (p = 0.009). The homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in patients with NASH than in patients with SS/UN (p = 0.01). Serum chemerin and HOMA-IR were positively associated with NAFLD activity score (r = 0.40, p = 0.02; and r = 0.43, p = 0.008, respectively). Serum chemerin was associated with hepatocyte ballooning degeneration (r = 0.37; p = 0.03), total cholesterol (r = 0.45; p = 0.008) and diastolic blood pressure (r = 0.41; p = 0.02). HOMA-IR was related to fibrosis stage (r = 0.51; p = 0.001) and inflammatory activity grade in portal tracts (r = 0.40; p = 0.01). Serum vaspin correlated with hepatocyte ballooning degeneration (r = 0.31; p = 0.04), alanine aminotransferase and aspartate aminotransferase (r = 0.33, p = 0.03; and r = 0.32, p = 0.04, respectively) and diastolic blood pressure (r = 0.39, p = 0.01). Conclusions. This study shows for the first time that chemerin and vaspin serum concentrations are altered in patients with NAFLD. The analyzed adipokines appear to play a pivotal role in the pathogenesis of NAFLD, not only as regulators of insulin sensitivity, but also as mediators of the inflammatory process.

Chemerin, vaspin and insulin resistance in chronic hepatitis C

Summary.  Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 ± 11.6 vs 40.9 ± 11.8 years and 25.0 ± 4.1 vs 23.9 ± 3.3 kg/m2, respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro‐inflammatory grade (r = (–0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up‐regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

Influence of sodium fluoride and caffeine on the kidney function and free-radical processes in that organ in adult rats

An experiment was carried out on Sprague-Dawley rats (adult males) that for 50 days were administered, in the drinking water, NaF and NaF with caffeine (doses, respectively: 4.9 mg of NaF/kg body mass/24 h and 3 mg of caffeine/kg body mass/24 h). Disturbances were noted in the functioning of kidneys, which were, particularly noticeable after the administration of NaF with caffeine. Changes in the functioning of kidneys were also confirmed by such parameters as the level of creatinine, urea, protein, and calcium. Modifications of the enzymatic antioxidative system (superoxide dismutase, catalase, and glutathione peroxidase) and lipid peroxidation (malondialdehyde) were also observed. Changes in the contents of the above parameters as well as pathomorphological examinations suggest increased diuresis, resulting in dehydration of the rats examined.

The Comparison of Scoring Scales for Liver Biopsy Assessment in Morbidly Obese Patients Undergoing Bariatric Surgery

Background: Many scoring systems have been applied for the grading and staging of non-alcoholic fatty liver disease (NAFLD). There is no consensus according to semiquantitative scales for the assessment of steatosis, inflammatory grading, and fibrosis staging in NAFLD. Methods: We analysed 24 consecutive patients who underwent bariatric surgery. The grading for steatosis was estimated according to the systems proposed by Brunt and by Dixon. Brunts scale and Scheuers scale modified by Gabriel were used for inflammatory activity and fibrosis staging. Additionally, types of NAFLD disease were diagnosed according to Matteonis classification. Results: Steatosis was observed in 88% and steatohepatitis in 54% of patients. We observed portal, periportal and pericellular fibrosis. Neither bridging fibrosis nor cirrhosis were found. Extent of steatosis estimated according to Dixon and Brunts scales was positively associated with appearance of steatohepatitis. The comparison of Dixons and Brunts scales according to grade of steatosis demonstrated a statistically significant difference. Inflammatory activity grades and fibrosis stages assessed according to Scheuer and Brunt scales differ significantly. Inflammatory activity evaluated with the Brunt scale was associated with the extent of steatosis and occurrence of steatohepatitis. Conclusions: Non-advanced forms of liver fibrosis do not appear to be dependent on steatosis and inflammatory grade in NAFLD. It is necessary to find the precise estimation of extent of steatosis especially occupying less than 1/3 or 1/4 of the lobule area. Brunts scale seems to be more useful for the estimation of liver biopsy in NAFLD. It is essential to create a consensus for evaluation of steatosis and necroinflammatory grading and fibrosis staging in NAFLD.

Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity severalfold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum — reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

Interactions between the histaminergic and angiotensinergic systems in the central cardiovascular regulation in rats

No Abstract..

Pylorus preserving loop duodeno-enterostomy with sleeve gastrectomy - preliminary results

BackgroundBariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage. The pylorus can thereby be alternatively preserved or excluded. With the aim of performing a “pylorus-preserving gastric bypass”, we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step procedure.Methods16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy (DJOS). Total small intestinal length was determined to account for inter-individual differences.ResultsMean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation. The overall intestinal length was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS patients. The mean length of the common channel in DIOS patients measured 245.6 cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to 38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1 and 6 months, resp. No complication related to the duodeno-enterostomy occurred.ConclusionsLoop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation.

Role of melatonin receptor MT2 and quinone reductase II in the regulation of the redox status of 3T3-L1 preadipocytes in vitro

We have examined the role of melatonin receptor MT2 and quinone reductase II in the regulation of the redox status of preadipocytes (3T3‐L1) in vitro. 3T3‐L1 cells were treated with melatonin at a physiological concentration (10−9 mol/L) and a supraphysiological (pharmacological) concentration (10−3 mol/L) for 24 h. Luzindole (10−4 mol/L), an antagonist of MT2 receptor, and prazosin (10−5 mol/L), an inhibitor of quinone reductase II, were added 30 min before subsequent exposure of the cells to melatonin. The level of oxidative stress was determined by the analysis of activities of enzymes neutralising reactive oxygen species, and determination of the malondialdehyde (MDA) content. Melatonin increased activities of manganese and copper‐zinc superoxide dismutase (MnSOD, Cu/ZnSOD) and catalase (CAT) at both a physiological concentration (10−9 mol/L) and a pharmacological concentration (10−3 mol/L). MDA content was unchanged, whereas activities of glutathione peroxidase (GSH‐Px) and glutathione reductase (GSSG‐Rd) were increased only by the physiological concentration. Both effects were partially inhibited by luzindole, but not prazosin. These observations suggest that melatonin, acting at least partially via MT2 receptors, can increase antioxidant enzymes activities in 3T3‐L1 preadipocytes.

sPECAM-1 and sVCAM-1: role in pathogenesis and diagnosis of chronic hepatitis C and association with response to antiviral therapy:

Aim: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). Methods: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. Results: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<0.001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p = 0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<0.001) with no difference between responders and nonresponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<0.001), sVCAM-1 (r = 0.56, p<0.001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis — stage 0 versus stage 1—3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. Conclusions: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.

Central serotonin-induced pressor effect in rats is mediated in part via the histaminergic system

1 Department of Basic Medical Sciences, Faculty of Public Health, Medical University of Silesia, Piekarska 18, 41-902 Bytom, Poland 2 Department of Physiology, Faculty of Medicine and Dentistry, Medical University of Silesia, H. Jordana 19, 41-808 Zabrze, Poland, Fax: ++48 32 2722362, e-mail: jjochem@poczta.onet.pl 3 Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia