Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease.

PURPOSE: Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. METHODS: A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). CONCLUSION: In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.

The Clinical and Laboratory Efficacy of HA 330 Treatment Combined with Continuous Renal Replacement Therapy in Septic Shock Patients: A Case Series.

INTRODUCTION: Blood purification therapy is a method used to enable cytokine removal and to improve disturbed immune homeostasis in patients with sepsis or septic shock. This study aimed to evaluate the impact of HA 330 treatment on biochemical and hemodynamic parameters and cytokine levels in adult patients with septic shock. METHODS: Critically ill patients with septic shock who received continuous veno-venous hemodiafiltration and HA 330 treatment were included in this prospective observational study. Biochemical and hemodynamic parameters were followed throughout HA 330 treatment. Serum interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, high-mobility group box1 (HMGB-1) protein, IL-10 levels were analyzed by ELISA method, before and after each HA 330 session. RESULTS: A total of 18 critically ill patients were included in this study. The median APACHE 2 score was 22.2 ± 7.49 and median SOFA score 9.6 ± 5.44 on intensive care unit admission. SOFA scores were significantly decreased on the 3rd day of HA 330 treatment, compared to 2nd day scores (p = 0.017). Median leukocyte value was significantly decreased (p = 0.027 and p = 0.024), while hemodynamic parameters remained unchanged throughout the HA 330 treatment. Median CRP and procalcitonin levels were significantly reduced at day 3 of HA 330 treatment compared to the baseline (p = 0.015 and p = 0.033, respectively). Serum IL-1 ß, IL-6, IL-8, TNF-a, HMGB-1, and IL-10 levels decreased insignificantly by 11.5%, 26.4%, 11.4%, 37.9%, 0.02%, and 35.5%, respectively, at the end of the hemoperfusion treatment compared to the pre-treatment. CONCLUSION: The administration of HA 330-based hemoperfusion in septic shock patients revealed improvements in SOFA scores, leukocyte count, and CRP and procalcitonin levels. However, there was no statistically significant change in concentrations of inflammatory cytokines and hemodynamic parameters during HA 330 treatment.

Gastric ultrasound, citrulline, and intestinal fatty acid-binding protein as markers of gastrointestinal dysfunction in critically ill patients: A pilot prospective cohort study.

BACKGROUND: Gastrointestinal (GI) dysfunction is common in the intensive care unit (ICU), although there is no consensus on biomarkers of GI dysfunction. We aimed to evaluate ultrasound-based gastric antrum measurements and serum intestinal fatty acid-binding protein (IFABP) and citrulline levels in relation to GI dysfunction in critically ill patients. METHODS: Adult critically ill patients receiving enteral nutrition and stayed for in the ICU for ≥48 h was included. GI dysfunction was described using Gastrointestinal Dysfunction Score (GIDS). Gastric antrum measurements, including craniocaudal (CC) diameter, anteroposterior diameter, and antral-cross sectional area (CSA), as well as serum levels for IFABP and citrulline, were prospectively recorded at baseline and on day 3 and day 5 of enteral nutrition. The receiver operating characteristic (ROC) analysis was performed to evaluate gastric ultrasound parameters, serum IFABP, and citrulline concentrations in predicting GI dysfunction. RESULTS: Thirty-nine participants with a median age of 60 years were recruited and 46.2% of participants had GI dysfunction. ROC analysis revealed that the cutoff value of CSA score to predict GI dysfunction was 4.48 cm2 , which provided 72.7% sensitivity and 77.2% specificity (area under the curve = 0.768, 95% CI: 0.555-0.980). At baseline, gastric residual volume was highly correlated with CC diameter and CSA (r = 0.764, P < 0.001 and r = 0.675, P < 0.001, respectively). Serum IFABP and citrulline levels had no correlation with GI dysfunction or gastric ultrasound parameters (P > 0.05). CONCLUSION: CSA was associated with GI dysfunction in critically ill patients. Serum IFABP and citrulline concentrations were poor in predicting GI dysfunction.

New Avenues to Explore in SARS-CoV-2 Infection: Both TRIM25 and TRIM56 Positively Correlate with VEGF, GAS6, and sAXL in COVID-19 Patients.

The ongoing COVID-19 pandemic poses a significant threat to human health. Many hypotheses regarding pathogenesis have been proposed and are being tried to be clarified by experimental and clinical studies. This study aimed to reveal the roles of the innate immune system modulator GAS6/sAXL pathway, endothelial dysfunction markers vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α, and antiviral effective TRIM25 and TRIM56 proteins in pathogenesis of COVID-19. The study included 55 patients with COVID-19 and 25 healthy individuals. The serum levels of GAS6, sAXL, VEGF, HIF-1α, TRIM25, and TRIM56 were measured using commercial ELISA kits and differences between COVID-19 patients and healthy controls, and the relationship to severity and prognosis were evaluated. GAS6, sAXL, TRIM56, and VEGF were found to be higher, while TRIM25 was lower in patients. There were strong positive correlations between GAS6, sAXL, TRIM25, TRIM56, and VEGF. None of the research parameters other than HIF-1α was associated with severity or prognosis. However, HIF-1α was positively correlated with APACHE II. We speculate that the antiviral effective TRIM25 and TRIM56 proteins, as well as the GAS6/sAXL pathway, act together as a defense mechanism in COVID-19. We hope that our study will contribute to further studies to elucidate the molecular mechanism associated with TRIM56, TRIM25, GAS6, sAXL, and VEGF in COVID-19 patients.

SAHA induce hippo pathway in CCA cells without increasing cell proliferation.

BACKGROUND: Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells. Since tumor metastasis is associated with poor prognosis and short-term survival of patients, there is an urgent need for alternative therapeutic approaches for CCA. Because of that reason, we aimed to investigate effect of SAHA which is known as HDAC inhibitor on extrahepatic cholangiocarcinoma cell line (TFK-1). METHODS: Cell cycle was measured by Muse Cell Analyzer. YAP, TAZ, TGF-ß protein levels were determined by western-blotting method. TEAD (1-3), TIMP2 and TIMP3 genes level were determined by real-time PCR analysis. RESULTS: We have seen the positive effects of SAHA on the TFK-1 cell line as it reduces cell viability and arresting cells in the G0/G1 phase. We also observed the negative effects of SAHA, as it increases the expression levels of YAP, TAZ, TGF-ß protein and TEAD (1-3) gene. We also found that SAHA reduced the expression levels of TIMP2 and TIMP3 in TFK-1 cells, but was not statistically significant. CONCLUSIONS: Although observing its antiproliferative effects, these negative effects may be related to the cells being resistant to the drug or the remaining cells having a more aggressive phenotype. Therefore, we think that caution should be exercised in the use of this drug for CCA treatment.

Measurement of serial serum total and acylated ghrelin levels in critically ill patients: A prospective and observational pilot study.

BACKGROUND: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. METHODS: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. RESULTS: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651-3995), 3485.20 (1379-4071), 3359 (1167-3919), and 3355 pg/ml (2207-3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0-673), 50 (0-730), 73 (0-808), and 125 pg/ml (0-689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P > .05). ICU mortality was 30%. CONCLUSION: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality .

If AFP is elevated, where is cancer? The case report on hereditary persistence of Alpha-fetoprotein.

Alpha-fetoprotein (AFP) is expressed by tumors with a high mitotic index such as hepatocellular carcinoma and germ cell tumors, therefore it is used as a tumor biomarker. Interestingly, although there is no underlying cause, elevated AFP has been reported in some genetically predisposed individuals. This is a very rare and benign condition called "hereditary persistence of AFP (HPAFP)" and an inherited in an autosomal dominant manner. To our knowledge, only 28 families have been reported to date. Some of the reported cases received inappropriate treatments such as chemotherapy and surgery. The possibility of HPAFP should be kept in mind in patients with high AFP in the absence of radiological evidence of hepatocellular carcinoma or germ cell tumor to avoid harmful procedures. It can be easily confirmed by analyzing AFP levels in other family members. We report a case of HPAFP with surprisingly higher AFP levels than previously reported cases and this is the first case reported from Turkey.

Macrolipasemia secondary to colon cancer chemotherapy: a case report.

We reported macrolipasemia in a colon cancer patient during the chemotherapy period without any evidence of pancreatitis. A 52-year-old man formerly treated for papillary thyroid carcinoma had elevated a carcinoembryonic antigen (CEA) concentration in the latest control and was diagnosed with colon cancer. Xelox chemotherapy (oxaliplatin and capecitabine) protocol was planned for six months. Interestingly, the lipase activities gradually increased from 30 U/L to 434 U/L, and exceeded three times the upper limit of the reference range (13-60 U/L). There were no symptoms of pancreatitis, and the abdominal computed tomography (CT) scan was also normal. Polyethylene glycol (PEG) recovery % values of serum samples gradually decreased and were 27% in the recent sample before the end of chemotherapy. Interestingly, the serum lipase activity fell a month after chemotherapy, and PEG recovery % increased (39%). We considered the following possibilities: (1) macrolipasemia due to chemotherapy drugs, (2) macrolipasemia due to antibodies against chemotherapy drugs.

The Effect of EZH2 Inhibition through DZNep on Epithelial-Mesenchymal Transition Mechanism.

Although the molecular pathogenesis of hepatocellular carcinoma (HCC) is uncertain, it is known that the epithelial-mesenchymal transition (EMT) mechanism and epigenetic changes have an important role. This study was focused on evaluating the relationship of 3-Deazaneplanocin A (DZNep) with the EMT mechanism, which is a histone methyltransferase inhibitor on HCC and is also known as an enhancer of zeste homolog 2 (EZH2) inhibitor. Cell viability of HepG2 cells (HCC cell line) assessed for DZNep over 72 hours with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, colony-forming assay, apoptosis assay, RNA isolation, cDNA synthesis, and real-time PCR (RT-PCR) were performed to see the effect of DZNep on HepG2 cells. DZNep reduced cell proliferation for 72 hours, also significantly reduced colony formation in addition it increased the total apoptosis. DZNep on EZH2, E-cadherin, N-cadherin, and Vimentin (Vim) gene expressions was given different results by either decreasing or increasing the expressions. In this study, we observed a positive effect of DZNep on apoptosis and TIMP3 expression level and decreased colony formation. However, it gave complicated results with the level of gene expression E-cadherin and TIMP2, increase the level of Vim and MMP2 expression. Therefore, we think that further studies are necessary to clarify the role of DZNep.

Suberoylanilide Hydroxamic Acid (SAHA) Reduces Fibrosis Markers and Deactivates Human Stellate Cells via the Epithelial-Mesenchymal Transition (EMT).

Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial-mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell lymphoma is under investigation for the treatment of lung and renal fibrosis. Experimental modeling for hepatic fibrosis can be constructed with an LX2 cell line isolated from human hepatic stellate cells (HSCs). In this study, we aimed to investigate the modulation of SAHA in the pathogenesis of liver fibrosis by detecting the levels of proteins; (E-cadherin (E-cad), N-cadherin (N-cad), Vimentin (Vim), and genes; E-cad, N-cad, Vim, transforming growth factor-beta (TGF-ß), alpha-smooth muscle actin (α-SMA), type 1 collagen (COL1A1), type 3 collagen (COL3A1)) that play a significant role in EMT with the LX2 cell line. We also evaluated the action of SAHA with cell proliferation, clonogenic, and migration assay. Cell proliferation was performed by flow cytometry. All the protein levels were determined by Western blot analysis, and gene expression levels were measured by Real-Time PCR. Our study observed that SAHA treatment decreased cell viability, colony formation and migration in LX2 cells. We found that SAHA increased E-cad expression level, while it decreased N-cad, Vim, COL1A1, COL3A1, α-SMA TGF-ß genes expression levels. SAHA decreased the level of E-cad, N-cad, and Vim protein levels. We thought that SAHA possesses potent antifibrotic and anti-EMT properties in LX2.

Chromosomal and oxidative DNA damage in non-functioning pituitary adenomas.

INTRODUCTION: Clinically non-functioning pituitary adenomas (NFPA) are common tumours of the pituitary gland and are mainly considered as benign. The primary aim of this study was to research the effects of NFPA on genome instability in patients with non-functioning pituitary adenoma by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay and 8-hydroxy- 2'-deoxyguanosine (8-OHdG) assay. The second objective of this study was to assess whether there is a relationship between age, pituitary adenoma diameters, 8-OHDG levels, CBMN site assay parameters, and tumour aggressiveness. MATERIAL AND METHODS: The study was performed on 30 patients who had been diagnosed with NFPA and were admitted to the Department of Endocrinology and Metabolism, and 20 healthy subjects of similar age and sex. RESULTS: Micronucleus (MN), nucleoplasmic bridges (NPBs), nuclear bud (NBUD) frequencies, and apoptotic and necrotic cell frequencies in patients with NFPA were found to be significantly higher than in control subjects, and plasma 8-OHdG levels in patients with NFPA were statistically significantly lower than control subjects in this study. CONCLUSIONS: It is believed that this is the first study to evaluate the aggressiveness of tumour with chromosome/oxidative DNA damage in patients with NFPA. However, further studies are needed in order to understand the cause of NFPA aggression and to evaluate these patients in terms of risk of cancer.

Systemic oxidative stress in non-arteritic anterior ischemic optic neuropathy.

PURPOSE: To investigate whether the serum total oxidant status (TOS), total antioxidant status (TAS), advanced oxidation protein products (AOPP), and thiol parameters could play a role in the pathogenesis of non-arteritic anterior ischemic optic neuropathy (NA-AION). METHODS: In this study, 18 newly diagnosed NA-AION patients and 17 healthy subjects (control group) were included. Serum plasma TOS and TAS, AOPP, and thiol parameters were measured by spectrophotometric method and the results were compared. RESULTS: Mean age of the patients and the controls were 60.8 ± 8.4 and 61.9 ± 9.4 years, respectively (p = 0.729). There were no significant differences between the patients and the control group with regard to the values of TAS, TOS, AOPP, and thiol (p = 0.869, p = 0.863, p = 0.040, p = 0.314; respectively). There was a positive correlation between TOS and thiol (p = 0.002, r = 0.681). CONCLUSION: We found no significant relationship between systemic oxidative parameters and NA-AION. However, this study should be accepted as a pilot investigation and needs to be validated.

Evaluation of chromosomal DNA damage, cytotoxicity, cytostasis, oxidative DNA damage and their relationship with endocrine hormones in patients with acute organophosphate poisoning.

Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage. Secondary aim of this study was also to assess whether a relation exists between endocrine hormones and the genome damage in acute OPs poisoning. In the study, blood samples were analysed of 13 patients before and after treatment admitted to the Department of Intensive Care Unit with acute OPs poisoning and of 13 healthy subjects of similar age and sex. The present study demonstrates that genome damage (micronucleus; MN and nucleoplasmic bridges; NPBs frequencies), apoptotic and necrotic cell frequencies increased in lymphocytes of patients with acute OPs poisoning before treatment and decreased after treatment. The present study also show that CBMN cyt assay parameters and 8-OHdG levels could be affected by some endocrine hormones such as E2, fT3, fT4, GH, IGF-1, FSH, LH, TSH, PRL, but not be related to ACTH and tT levels in acute OPs poisoning. In conclusion, it is believed that this is the first study to evaluate the chromosomal/oxidative DNA damage, cell proliferation, cell death and their associations with endocrine hormones in acute OPs poisoning. These preliminary findings need to be supported by further studies with larger sample sizes.

Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock.

PURPOSE: Reactive oxygen species (ROS) has a key role in the pathogenesis of sepsis. We wanted to evaluate ROS-associated lymphocyte necrosis and apoptosis. MATERIALS AND METHODS: A total of 51 patients were included in the study, 29 in the patient group and 22 in the control group. Blood samples were taken from patients in the patient group during severe sepsis or septic shock, then again once they had recovered. Oxidative DNA damage was evaluated by 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Peripheral blood lymphocytes from patients were evaluated with a microscope immediately. The rate of apoptosis and necrosis of lymphocytes were evaluated according to the number of cells in the peripheral. RESULTS: The level of 8-OHdG increased with severe sepsis or septic shock. There were significant differences between the pre- and post-treatment values for apoptotic cell frequency (4.21±3.15 vs. 3.82±3.07, P<0.05) and necrotic cell frequency (4.75±3.61 vs. 4.09±3.37, P<0.05). Apoptosis and necrosis was increased during severe sepsis and septic shock, and apoptosis increase also continued after recovery, but necrosis decreased following disease recovery. CONCLUSiONS: In patients with severe sepsis or septic shock, apoptosis and necrosis were increased along with increased 8-OHdG level.

Role of osteocalcin, tumor necrosis factor-alpha and adiponectin in polycystic ovary syndrome patients with insulin resistance.

OBJECTIVE: Insulin resistance (IR) seems to be the main pathogenic factor in polycystic ovary syndrome (PCOS). Adiponectin and tumor necrosis factor-alpha (TNF-α) are important in IR. The aim of this study was to evaluate the correlations of osteocalcin, adiponectin, and TNF-α with IR in PCOS. MATERIALS AND METHODS: A total of 60 women were divided into two groups. The first group constituted 44 patients with PCOS and the control group comprised 16 healthy women. Osteocalcin, adiponectin, TNF-α levels, body mass index (BMI), and IR in the fasting state were assessed and correlations of these parameters were evaluated. RESULTS: Homeostasis model assessment (HOMA)-IR, adiponectin, osteocalcin, and androstenedione levels were significantly increased in the PCOS group. A moderate positive correlation between BMI and HOMA-IR, a moderate negative correlation between TNF-α and osteocalcin, and a mild negative correlation between adiponectin and BMI were detected in PCOS. CONCLUSION: Osteocalcin may have impact on adiponectin, TNF-α, and IR levels in PCOS. Different osteocalcin levels in patients with PCOS may be responsible for explaining PCOS heterogeneity.

Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer.

Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.

Plasma apelin level in patients with restless legs syndrome and its association with periodic leg movements.

OBJECTIVES: Apelin is an antioxidant and anti-inflammatory molecule secreted by adipose tissue and has a protective effect on cardiac and neuronal tissue. Recent studies have reported that the risk of vascular disease is increased in restless legs syndrome (RLS). We aimed to measure plasma levels of apelin in patients with RLS. Additionally, we wanted to determine if there is any relationship between apelin levels and RLS disease severity and the periodic leg movement index (PLMI). METHOD: A total of 14 RLS patients with moderate-to-severe symptoms and 14 age- and body mass index (BMI)-matched healthy controls participated in the study. All participants had no concomitant medical disorder nor took medications. The international RLS rating scale (IRLSS) was used to determine disease severity. Polysomnography (PSG) served to exclude other sleep disorders such as sleep-related breathing disorders and to measure sleep parameters. RESULTS: The mean plasma apelin level was significantly lower in the patient group compared to the control group independent of IRLSS score and PSG findings (p = 0.004). After comparison between the RLS patient group and control group, the patient group was divided into two subgroups based on a PLMI above or below 15 events per hour. A reduced mean apelin level was observed in the patient group having a PLMI above 15 compared to the patient group with PLMI below 15 and the control group (p = 0.003). There was no correlation between plasma apelin levels and disease severity and PLMI in the two patient subgroups. CONCLUSIONS: RLS patients especially those with a PLMI above 15 have low plasma apelin levels independent of disease severity and sleep parameters such as sleep duration and quality. Decreased apelin levels may explain the increased risk for vascular diseases in those patients.

Effects of ursodeoxycholic acid therapy on carotid intima media thickness, apolipoprotein A1, apolipoprotein B, and apolipoprotein B/A1 ratio in nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease that is increasingly being associated with cardiovascular disease. Ursodeoxycholic acid (UDCA) may have antioxidant and anti-inflammatory activities, and may reduce liver injury in NASH. To date, no studies have assessed the efficacy of UDCA in carotid intima media thickness (CIMT), serum lipids, apolipoprotein A1 (apo A), apolipoprotein B (apo B), and apolipoprotein B/A1 (apo B/A1) ratios in patients with NASH. PATIENTS AND METHODS: In this prospective study, 30 patients with biopsy-proven NASH and 25 healthy adults as a control group were evaluated. None of the participants had diabetes, hypertension, or hyperlipidemia. Patients with NASH received UDCA 15 mg/kg/day for 6 months. BMI, waist circumference, homeostasis model assessment, lipids, apo A1, apo B, apo B/A1 ratios, and CIMT were analyzed before and after the treatment period. RESULTS: At the end of the study, there were no statistically significant changes in BMI or waist circumference. Liver enzymes decreased gradually. The homeostasis model assessment decreased from 3.4 ± 1.89 to 2.06 ± 1.68 (P < 0.001). No significant changes in the mean triglyceride, total cholesterol, low-density lipoprotein, or apo B levels were observed. The mean high-density lipoprotein (42.9 ± 7.1 vs. 45.5 ± 9.8; P = 0.037) and apo A1 (127.6 ± 17.7 vs. 135.9 ± 22.2; P = 0.02) increased significantly. Apo B/A1 ratios tended to decrease, but this decrease was not statistically significant. The mean CIMT decreased significantly (0.56 ± 0.15 vs. 0.47 ± 0.12; P = 0.001). CONCLUSION: UDCA treatment in NASH patients resulted in statistically significant reductions in the mean CIMT over a 6-month period. We believe that this benefit of UDCA may have resulted from decreased insulin resistance and increased serum high-density lipoprotein-apo A1 levels. However, larger, longer-term studies are needed to confirm this effect of UDCA in NASH.

Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly.

OBJECTIVE: The objectives of this study were to assess cytokinesis-block micronucleus cytome (CBMN Cyt) assay parameters and also oxidative DNA damage in patients with active acromegaly and controls and to assess the relationship between age, serum insulin-like growth factor 1 (IGF-1) levels, pituitary adenoma diameters, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and CBMN Cyt assay parameters in patients with active acromegaly. DESIGN: The study population included 30 patients with active acromegaly and 30 age- and sex-matched healthy controls. CBMN Cyt assay parameters in peripheral blood lymphocytes of patients with active acromegaly and controls were evaluated and plasma 8-OHdG levels were measured. RESULTS: Frequencies of micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001, p<0.001, p<0.001, respectively). The frequencies of apoptotic and necrotic cells in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p<0.001 and p<0.001 respectively). No statistically significant differences in the number of cells in metaphase, the number of bi-nucleated cells (M2), the number of tri-nucleated cells (M3), the number of tetra-nucleated cells (M4) and nuclear division index (NDI) values were observed between patients and controls (p>0.05). Plasma 8-OHdG (ng/ml) levels in patients with acromegaly were found to be significantly higher than those in controls (p<0.005). MN frequency in the lymphocytes of patients with acromegaly increased with elevated serum IGF-1 levels (p<0.05), whereas the number of NPBs and the frequency of apoptotic cells decreased with elevated serum IGF-1 levels (p<0.01 and p<0.05 respectively). CONCLUSIONS: Both the increase in chromosomal/oxidative DNA damage and the positive association between MN frequency and serum IGF-1 levels may predict an increased risk of malignancy in acromegalic patients. Long-term follow-up of patients with acromegaly will be necessary to establish the degree of cancer risk in this population.

Advanced oxidation protein products, total thiol levels and total oxidant/antioxidant status in patients with nash.

BACKGROUND/AIMS: In this study we aim to evaluate the relationship of advanced oxidation protein products (AOPP), total thiol, total antioxidant status (TAS), total oxidant status (TOS) levels and oxidative stress index (OSI) in patients with nonalcoholic steatohepatitis (NASH). MATERIALS AND METHODS: A total of 28 patients with NASH and 19 age-and-gender-matched healthy subjects were enrolled in the study as control group. Plasma AOPP and thiol levels were determined by spectrophotometric methods. Plasma TAS and TOS levels were measured using commercially available kits and OSI was calculated. RESULTS: Plasma AOPP (256.7 vs. 125.8 µmol/L) and TOS levels (8.9 vs. 5.9 µmol H2O2 equiv/L) were higher in patients with NASH than the controls (p<0.019 and p<0.041 respectively). Plasma total thiol levels (235.0 vs. 291.6 µmol/L) were lower in patients with NASH than the controls (p<0.001). TAS levels (1.14 vs. 1.14 mmol Trolox equiv/L) were not significantly different in patients with NASH than the controls (p>0.900). OSI values (8.0 vs. 5.5) were higher in patients with NASH than the controls (p<0.039). CONCLUSION: Our findings indicate that oxidative stress increases in patients with NASH as shown by increases in TOS level. We think effective antioxidant therapy to inhibit protein oxidation and also to increase of TAS and total thiol levels may be a therapeutic option in patients with NASH who have under increased oxidative stress.