Paweł Kiciński

Association between Serum Selenium Concentrations and Levels of Proinflammatory and Profibrotic Cytokines—Interleukin-6 and Growth Differentiation Factor-15, in Patients with Alcoholic Liver Cirrhosis

According to some authors, serum selenium levels are strongly associated with the severity of liver diseases, including liver cirrhosis. The aim of this study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines—interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in the serum of 99 patients with alcoholic liver cirrhosis divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower, whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis

Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF) in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis (p < 0.05). The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A.

Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb) in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure.

Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea

Obstructive sleep apnoea (OSA) induces thrombophilia and reduces fibrinolysis. Alpha-2-antiplasmin (a-2-AP) and plasminogen activator inhibitor 1 (PAI-1) are major inhibitors of the fibrinolytic system. Increased concentrations of these factors are associated with a higher risk of cardiovascular diseases. The aim of this study was to assess plasma a-2-AP and PAI-1 in patients with OSA and evaluate correlations with the polysomnographic record and selected risk factors of cardiovascular diseases. The study group comprised 45 patients with OSA, and the control group consisted of 19 patients who did not meet the diagnostic criteria of OSA. Plasma a-2-AP and PAI-1 concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). In the study group, the median value of plasma a-2-AP was higher than that of the control group (157.34 vs. 11.89 pg/ml, respectively, P<0.0001). A-2-AP concentration increased proportionally to the severity of OSA. The concentration of a-2-AP was positively correlated with the apnoea-hypopnoea index (AHI), apnoea index (AI), respiratory disturbances time (RDT), and desaturaion index (DI), and negatively correlated with mean and minimal oxygen saturation (SpO2 mean, SpO2 min, respectively). The median value of PAI-1 was higher in the study group than the control group (12.55 vs. 5.40 ng/ml, respectively, P = 0.006) and increased along with OSA severity. PAI-1 concentration was positively correlated with AHI, AI, RDT, DI, and body mass index (BMI) and negatively correlated with SpO2 mean and SpO2 min. Higher plasma concentrations of a-2-AP and PAI-1 in patients with OSA indicated that these patients had increased prothrombotic activity. OSA increases the risk of cardiovascular complications as it enhances prothrombotic activity.

Reliability of the Epworth Sleepiness Scale and the Berlin Questionnaire for screening obstructive sleep apnea syndrome in the context of the examination of candidates for drivers

BACKGROUND The aim of the study has been to assess the usefulness of the Epworth Sleepiness Scale (ESS) and the Berlin Questionnaire (BQ) for obstructive sleep apnea syndrome (OSAS) screening. The capacity of both tests to discriminate between healthy individuals or with mild OSAS (apnea-hypopnea index (AHI) < 15/h) vs. patients with moderate or severe OSAS (AHI ≥ 15/h) was evaluated. MATERIAL AND METHODS The study encompassed 223 patients with a suspicion of the OSAS. The ESS and BQ were completed by patients unassisted. Screening polysomnography was performed using the Porti SleepDoc. The OSAS was diagnosed when AHI ≥ 15/h or AHI ≥ 5/h with simultaneous occurrence of clinical symptoms. RESULTS The ESS score was found to be significantly higher in the study group compared to the control group (8.9±5.9 vs. 11.6±5.2 pt, p < 0.0001). Otherwise, there were no significant inter-group differences in the percentage of high-risk individuals according to the BQ (83.7% vs. 92.3%, p > 0.05). Sensitivity of the ESS and BQ was 53.2% and 93.1%, respectively while specificity was 58.8% and 16.2%, respectively. Poor correlation between the ESS score and AHI and apnea index were noticed (r = 0.22, p = 0.001 and r = 0.24, p < 0.001, respectively). CONCLUSIONS Considering its low sensitivity, the ESS should not be used as a screening test for the OSAS diagnosis amongst candidates for drivers. The BQ is characterised by high sensitivity for the OSAS diagnosis with AHI ≥ 15/h, however, due to low specificity, the questionnaire may increase the number of healthy individuals referred for needless diagnostic procedures. Med Pr 2016;67(6):721-728.

Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

Abstract The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin), where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect), and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.

Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis

Objective Psoriasis and depression may have common mechanisms, such as systemic inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin D3 deficiency. Among men with psoriasis, this study examined whether depression severity was associated with serum concentrations of different metabolic and inflammatory markers. Methods The study included 85 men with psoriasis (mean age ± standard deviation [SD], 47 ± 14 years) and 65 men without psoriasis (mean age ± SD, 44 ± 13 years). In both groups, we measured the body mass index; blood pressure; and serum concentrations of lipids, uric acid, lipase, interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants completed the Beck Depression Inventory. Other variables analyzed included psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body surface area affected by psoriatic lesions. Results Compared with controls, patients with psoriasis had significantly greater depression severity, higher body mass indices, and higher serum concentrations of total cholesterol and interleukins 6 and 18; moreover, they had significantly lower serum 25-hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index, the percentage of body surface area affected by psoriatic lesions, and interleukin-18 concentration. In patients with psoriasis, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not correlate significantly with the serum concentrations of interleukin 6 and cortisol. Conclusions High concentrations of interleukin 18 and low concentrations of 25-hydroxyvitamin D3 may be associated with depression severity in men with psoriasis. Thus, further studies should examine whether effective anti-inflammatory treatments or vitamin D3 supplementation can improve depression outcomes in these patients.

Afamin and adropin in patients with alcohol-induced liver cirrhosis

The aim of the study was to determine serum concentrations of afamin and adropin in patients with alcoholic liver cirrhosis and to define their correlation with the stage of disease. The study included 99 patients with alcoholic cirrhosis from the region of Lublin, (Eastern Poland). Liver cirrhosis was diagnosed based on clinical features, history of heavy alcohol consumption, laboratory tests and abdominal ultrasonography. The control group consisted of 20 healthy individuals without liver disease who did not abuse alcohol. The serum afamin and adropin concentrations were determined using ELISA kits. The concentration of afamin was found to be significantly lower in patients with compensated alcoholic liver cirrhosis, i.e. P-Ch B (85.1±40.6 μg/ml) and P-Ch C (56.4±32.3 μg/ml) individuals, compared to the control group (135.9±43.6 μg/ml); p-value was <0.01 and <0.001, respectively. As far as adropin is concerned, a reverse relationship was demonstrated: the highest concentration was found in patients with P-Ch C (11.7±5.7 ng/ml) cirrhosis. Furthermore, the above concentration was significantly higher compared to patients with P-Ch A cirrhosis (7.2±2.8 ng/ml; p<0.05) and controls (7.5±2.6 ng/ml; p<0.05). The concentration of afamin decreases with the severity of alcoholic liver cirrhosis, which most likely results from impaired hepatic synthesis. Otherwise, the higher the stage of disease according to the Child-Pugh score, the higher the concentration of adropin.

Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis

Background. Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors – survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis. Material and methods. Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique. Results. The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001). Conclusion. In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.

Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis

INTRODUCTION AND OBJECTIVE Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG). MATERIAL AND METHODS The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples. RESULTS Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (p<0.001 for both). The highest concentration of FGF-19 was found in Child-Pugh stage C liver cirrhosis patients (806.9±650.3 pg/ml), and was significantly higher than observed in controls (p=0.005) and stage A patients (compensated cirrhosis) (p=0.02). The highest concentration of ENG was demonstrated in the control group (3.24±148 ng/ml) while the lowest in patients with decompensated cirrhosis (7.32±5.39 ng/ml and 7.92±4.18 ng/ml for stage B and C; p=0.03 and p=0.02, respectively). The use of the multiple-variable model demonstrated that the independent factors affecting the concentration of ENG were the concentration of bilirubin (p=0.02), INR (p=0.01) and duration of alcohol abuse (p=0.02). The independent determinants of FGF-19 concentrations were found to be the stage (severity) of liver cirrhosis (p=0.04) and INR (p=0.03). CONCLUSIONS Concentrations of zinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.