Halef Okan Doğan

The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients

Abstract Background. Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. Methods. The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Loks model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. Results. Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Loks model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. Conclusions. Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.

INCREASED IRISIN CONCENTRATIONS IN PATIENTS WITH CRIMEAN-CONGO HEMORRAGIC FEVER

Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening viral infection. The pathogenesis of the disease is not well understood. The aim of this study was to determine the change in irisin concentrations in patients with CCHF. The study included a total of 30 patients with CCHF and 30 control participants. Irisin concentrations were determined using a commercial ELISA kit. Median irisin concentrations were 9.03 (5.81-12.22) μg/mL and 4.2 (3.39-7.62) μg/mL, respectively, in each group. There was no correlation between irisin and disease severity. Any correlations between irisin, and lactate dehydrogenase (LDH), international normalization ratio (INR), Alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, activated partial thromboplastin time (aPTT), D-dimer and hemoglobin, were also investigated. There were statistically significant positive correlations between the values of irisin, and platelet (p = 0.005, r: 0.369), ALT (p = 0.049, r: 0.261), INR (p = 0.006, r: 0.359) and aPTT values (p = 0.002, r: 0.405). A negative correlation was also found between the values of irisin and LDH (p = 0.008, r: －0.348). No correlations were determined between the values of irisin, and AST, hemoglobin and D-dimer. These results suggest that irisin may have a role in CCHF.

Decreased Chitotriosidase Activity and Levels in Familial Mediterranean Fever

Different studies have demonstrated changes in chitotriosidase (ChT) activity and concentrations in multiple diseases. However, changes in ChT activity and concentrations have not been concurrently evaluated in patients with Familial Mediterranean Fever (FMF). In this study, we analyzed the changes in serum ChT activity and concentrations in patients with FMF. The study included a total of 80 patients with FMF and 80 healthy controls. ChT enzyme activity and concentrations were measured and then compared between the groups. ChT activity was measured by using fluorometric ELISA and ChT concentrations were measured by using colorimetric ELISA methods. The median ChT activity was 10.00 (6.00–15.00) nmol/mL/hr in the patients and 14.00 (6.25–20.75) nmol/mL/hr in the controls. There was a statistically significant difference in the ChT activity between the controls and patients (P = 0.027). The median ChT concentrations were 65.40 (46.20–84.92) pg/mL and 125.00 (75.72–143.95) pg/mL in the patients and controls, respectively (P < 0.001), which were expressed as median percentiles (25th–75th). Additionally, we found no correlation between C-reactive protein and ChT activity (P = 0.978, r = 0.003) and concentrations (P = 0.446, r = −0.87). Serum ChT enzyme activity and concentrations may not be considered as a biomarker in FMF patients taking colchicine. New studies are needed to evaluate the changes of enzyme activity and concentration in colchicine-negative patients.

The protective effect and diagnostic performance of NOX-5 in Crimean–Congo haemorrhagic fever patients

Introduction. Crimean‐Congo haemorrhagic fever (CCHF) is an acute viral haemorrhagic disease. Reactive oxygen species that are mainly generated by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzyme family have a pivotal role in the pathophysiology of many diseases. The serum levels of NOX isoforms in patients with CCHF have yet to be assessed. Methods. This prospective study was conducted at Cumhuriyet University, Turkey. Only patients with CCHF confirmed by the National Reference Virology Laboratory were enrolled in the study. The study subjects comprised 67 CCHF patients and 70 healthy control subjects. The quantitative sandwich ELISA technique was used for the determination of serum NOX 1, 2, 4 and 5. Results. Higher median median NOX‐1 (P=0.001) and NOX‐5 (P<0.001) levels were found in patients compared to the control group. Higher median serum NOX‐5 levels were found in the low‐grade disease group compared to the intermediate‐high disease group according to two different severity scores (P=0.003). Negative correlations were also found between the serum NOX‐5 levels and the severity scores [(P<0.05, r=‐0.259), (P<0.01, r=‐0.417)]. The area under the curve (AUC) values for the NOX‐1 and NOX‐5 were 0.67 (confidence interval: 0.58‐0.75) and 0.99 (confidence interval: 0.95‐1.00), respectively. Lower NOX‐5 levels were found in patients receiving thrombocyte suspension (P=0.004) Conclusions. NOX‐5 may have a protective effect on CCHF patients and the measurement of serum NOX‐5 levels may be used as a novel biochemical test in the diagnosis of CCHF.

An Investigation of the Effects of Curcumin on the Changes in the Central Nervous System of Rats Exposed to Aroclor 1254 in the Prenatal Period

BACKGROUND & OBJECTIVE Aroclor 1254 is a widespread toxic compound of Polychlorinated Biphenyls (PCBs), which can create significant nervous problems. No remedies have been found to date. The aim of this study was to reveal the damage that occurs in the central nervous system of rat pups exposed to Aroclor 1254 in the prenatal period and to show the inhibiting effect of curcumin, which is a strong anti-oxidant and neuroprotective substance. METHOD The study established 3 groups of adult female and male Wistar albino rats. The rats were mated within these groups and the offspring rats were evaluated within the group given Aroclor 1254 only (n=10) and the group was given both Aroclor 1254 and curcumin (n=10) and the control group (n=10). The groups were compared in respect of pathomorphological damage. The immunohistochemical evaluation was made of 8-hydroxdeoxyguanosine (8-OHdG), 4-hydroxynoneal (4HNE), myelin basic protein (MBP) expressions and TUNEL reaction. The biochemical evaluation was made of the changes in the TAS-TOS and Neuron Specific Enolase (NSE) levels. Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels. Consequently, it was understood that Aroclor 1254 caused damage in the central nervous system of the pup in the prenatal period, and curcumin reduced these negative effects, particularly in the forebrain and the midbrain. CONCLUSION It was concluded that curcumin could be a potential neuroprotective agent and would be more effective at higher doses.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs

Objective Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. Methods Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. Results The TAS (p=0.001), total thiol, and native thiol levels (p<0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p<0.001). Conclusion These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs.

The Protective effect of P7C3 against DNA and neuron damage in rat pups with congenital hypothyroidism

Congenital hypothyroidism (CH) is defined as congenital thyroid hormone deficiency. The aim of this study was to examine the DNA and neuron damage in rat pups with CH and to evaluate the beneficial effects of 3.6-Dibromo-α-[(phenylamino) methyl]-9H-carbazole-9-ethanol (P7C3). Rat pups were assigned to four groups as Group 1: CH, Group 2: CH treated with P7C3, Group 3: CH treated with P7C3 and L-thyroxine, and Group 4: control group. Plasma 8-(OH)DG and neuron-specific enolase (NSE) concentrations were determined in all groups. For histopathological examinations haematoxylin-eosin staining was applied. Increased NSE concentrations were found in the CH group compared to the control group. The 8-(OH)DG concentrations were found to be higher in Group 2 and Group 3 than in the control group. Neuronal degenerations localized in the hippocampus and brain cortex were found in histopathological examinations in Group 1. The distribution of neuronal degeneration was less in Group 2 and Group 3 than Group 1 and lesser in Group 3 than in Group 2. DNA damage might have a role in CH pathogenesis. P7C3 compounds have a protective effect in CH.

Evaluation of the associations between endothelial dysfunction, inflammation and coagulation in Crimean-Congo hemorrhagic fever patients

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease. The aim of this study was to evaluate the association between inflammation, coagulation and endothelial dysfunction in CCHF. The study population consisted of 40 patients and 50 healthy controls. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), endocan, high sensitive C-reactive protein (hsCRP), international normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets values were determined in blood samples. Median hsCRP (p < 0.0001), ALT (p < 0.001), AST (p < 0.001) and aPTT (p < 0.001) values were found to be higher in CCHF patients than in the healthy control subjects. In contrast, median endocan (p = 0.0006) and platelet (p < 0.001) concentrations were found to be lower in CCHF patients than in healthy controls. Serum hsCRP concentrations positively correlated with PT, aPTT and INR in CCHF patients, whereas serum endocan levels were not correlated with hsCRP, PT, aPTT and INR. In conclusion, endothelial dysfunction is one of the key steps in CCHF disease development and serum endocan may be used as a biomarker to evaluate endothelial dysfunction in patients. There is no relationship between increased inflammation and endothelial dysfunction. Coagulation abnormalities might be related to the impaired hepatic synthetic function of coagulation factors. Increased hsCRP concentrations may have a compensatory role in restoring impaired hemostasis in CCHF. Further research is needed to confirm these findings and to examine possible explanations.

Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism

In this study, it was aimed to show the cannabinoid receptor‐2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase‐3, caspase‐9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used. In the first two groups, the mothers were treated with 0.025% MMI during the critical period of the pregnancy. In the third group, as the control group, the mothers and pups were not treated. Euthanasia was applied to the pups in Group I on Day 10, and to the pups in Groups II and III on Day 21. In the biochemical analyses, total T4 levels of both mothers and pups in Group I and II were found to be lower than those of the control group. Histopathologically, karyopyknosis in migrating neurons and demyelinization were observed in both groups. Caspase‐3 and −9 expressions and TUNEL reactions showed parallelism to these findings. eNOS and iNOS activities were also increased in Groups I and II. CB2 receptor activity was observed in the fore and mid brain in Group I, and in the whole brain in Group II. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period.

Vitamin D status, serum lipid concentrations, and vitamin D receptor (VDR) gene polymorphisms in Familial Mediterranean fever

Vitamin D (VitD) is critical for the regulation of inflammatory processes, and VitD deficiency has been linked to several chronic inflammatory disorders. We aimed to investigate the concentrations of serum 25(OH)D3, lipid parameters, and three known VDR polymorphisms (BsmI, FokI, and TaqI) in patients with Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease. The study included 123 FMF patients and 105 controls. Seventy patients had no attack (group 1), 30 had 1-2 attacks (group 2), and 23 had 3 or more attacks (group 3) within last three months. Serum 25(OH)D3 concentrations were determined using liquid chromatography-tandem mass spectrometry. BsmI, FokI, and TaqI polymorphisms were analyzed by a competitive allele specific polymerase chain reaction assay (KASPar). Serum lipid parameters were measured with enzymatic colorimetric methods. 25(OH)D3 concentrations were lower in FMF patients compared to controls (p < 0.001). No difference was observed in 25(OH)D3 concentration between groups 1, 2, and 3. The distributions of FokI and TaqI genotypes were not significantly different between FMF patients and controls. There was a significant difference in the distribution of AA BsmI genotype between male FMF patients and male controls. Increased concentrations of triglycerides (p = 0.012) and decreased concentrations of high-density lipoprotein cholesterol [HDL-C] (p = 0.006) were found in FMF patients compared to controls. Although lower 25(OH)D3 concentrations were observed in FMF patients versus controls, no association was determined between FMF attack frequency and 25(OH)D3 concentrations. We showed that the AA genotype of BsmI polymorphism is associated with FMF in males but not in females. The effects of decreased HDL-C and increased triglyceride concentrations on cardiovascular events in FMF patients should be further investigated.