The usability of neopterin in determining disease course in COVID-19.

OBJECTIVES: To investigate the usability of neopterin in demonstrating the progression of COVID-19. As a result of uncontrolled activation of COVID-19 monocytes and macrophages, IFN gamma increases and the resulting inflammatory response causes organ damage. IFN released from T cells causes an increase in gamma neopterin levels. Therefore, measurement of neopterin levels can be used to indicate immune system activation and disease progression. METHODS: The study was carried out prospectively in two different centers. The patients were divided into two groups (mild-moderate and severe) and clinical, laboratory, imaging findings and neopterin levels at hospitalization were compared. RESULTS: 100 patients were included in our study, 41 of these patients were male. Forty-six patients were identified as severe COVID-19. C-reactive protein, lymphocyte count, fibrinogen, D dimers, lactate dehydrogenase, procalcitonin, troponin and neopterin levels were significant in indicating disease severity. (p<0.05). In ROC analysis, 0.642 for neopterin, 0.698 C-reactive protein, 0.331 lymphocyte count, 0.679 procalcitonin, 0.633 fibrinogen, 0.667 D dimers, 0.655 troponin and 0.706 lactate dehydrogenase were detected and these values were significant. CONCLUSION: In our study, neopterin was detected as an important indicator in determining the course of COVID-19.

Dose-Dependent Effect of Hydrogen Sulfide in Cyclophosphamide-Induced Hepatotoxicity in Rats.

BACKGROUND: Cyclophosphamide is a commonly used anticancer and immunosuppressive agent; however, hepatotoxicity is one of its severe toxicities. Hydrogen sulfide is a gaseous signaling molecule that plays crucial regulatory roles in various physiological functions. This study aimed to evaluate the hepatoprotective effect of hydrogen sulfide against cyclo phosp hamid e-ind uced hepatic damage in rats. METHODS: Hepatotoxicity was induced by the single intraperitoneal administration of cyclophosphamide (200 mg/kg). Sprague-Dawley rats were treated by hydrogen sulfide donor, sodium hydrosulfide (25, 50, and 100 µmol/kg, intraperitoneal) 7 days before and 7 days after the administration of a single intraperitoneal injection of cyclophosphamide (200 mg/kg). Cyclo phosp hamide-ind uced hepatotoxicity was evaluated by serum and tissue biochemical and histopathological assessments. The levels of hydrogen sulfide, nitric oxide, cyclic guanosine monophosphate, interleukin 6, and interleukin 10 in liver homogenates were also determined by ELISA. One-way analysis of variance and Kruskal-Wallis tests were used as statistical analyses. RESULTS: Cyclophosphamide increased liver function enzymes (alanine aminotransferase and aspartate aminotransferase), immunoreactivity to caspase-3 and Apaf-1, and proinflammatory cytokines. Cyclophosphamide also induced histopathological alterations including pycnotic nucleus with eosinophilic cytoplasm, increased sinusoidal dilatation, congestion, and edema. Hydrogen sulfide cotreatment significantly reduced cyclo phosp hamid e-ind uced inflammation, histological alterations, and apoptosis in the liver. 50 mg/kg sodium hydrosulfide was more effective against cyclo phosp hamid e-ind uced hepatotoxicity. CONCLUSION: In conclusion, hydrogen sulfide with its anti-inflammatory and anti-apoptotic effects seems to be beneficial as an adjunct to cyclophosphamide treatment to reduce cyclo phosp hamid e-ind uced hepatotoxicity and thereby can be suggested as a promising agent to increase the therapeutic efficacy of cyclophosphamide.

Serum prolidase, malondialdehyde and catalase levels for the evaluation of oxidative stress in patients with peripheral vertigo.

PURPOSE: We aimed to evaluate oxidative stress in patients with peripheral vertigo by measuring serum prolidase, malondialdehyde (MDA) and catalase levels. METHODS: A total of 30 patients (age: 60 <) with peripheral vertigo and 30 healthy subjects were recruited. Blood samples were collected from both groups and serum prolidase levels were measured using enzyme-linked immunosorbent assay (ELISA). MDA and catalase levels were measured by the spectrophotometric method. RESULTS: The most common cause of vertigo was BPPV (53.3%), followed by Ménière's disease (16.6%), vestibular neuritis (13.3%), lateral semicircular canal fistula (3.3%), and idiopathic vertigo (13.3%). Mean serum prolidase activity and MDA levels were significantly higher in the vertigo patients than in the control subjects (P < 0.05); however, there was no statistically significant difference in mean serum catalase levels between the groups (P > 0.05). CONCLUSION: We concluded that serum prolidase and MDA levels may be used as markers of oxidative stress in patients with peripheral vertigo.

Effect of Hydrogen Sulfide on Kidney Injury in Rat Model of Crush Syndrome.

BACKGROUND: Acute kidney injury is the most serious complication of crush syndrome. Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule. It is involved in homeostatic functions, such as blood pressure control, apoptosis, oxidative stress, and inflammation. In this study, effects of H2S on kidney injury were investigated in a rat model of crush syndrome. METHODS: Rats were divided into six groups (n = 8): Sham (steril saline ip), crush (sterile saline ip), crush + NaHS (sodium hydrosulfide, an H2S donor) (100 µmol/kg ip). All these groups were also separated as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hindlimbs of anesthetized rats with blocks weighing 3.6 kg each sides, followed by 3 or 24 h of decompression. Kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-ß, tissue total oxidant status, and total antioxidant status levels were measured in kidney homogenates 3 and 24 h after decompression. Serum creatine kinase, blood urea nitrogen, and creatinine levels were also measured. Apoptosis was assessed by TUNEL method. Bcl-2 was assessed by immunohistochemistry. Glomerular and tubular structures were also examined histopathologically. RESULTS: NaHS reduced kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, tumor-necrotizing factor-α, transforming growth factor-ß, total oxidant status levels, and increased total antioxidant status levels in kidney 3 and 24 h after decompression. Serum urea, creatinine, and creatine kinase levels also reduced with NaHS. NaHS decreased renal damage and apoptosis in crush-related acute kidney injury. CONCLUSIONS: These results suggest that H2S could reduce crush-related acute kidney injury via anti-inflammatory, antioxidant, and antiapoptotic effects.

The Role of Serum Procalcitonin, Interleukin-6, and Fibrinogen Levels in Differential Diagnosis of Diabetic Foot Ulcer Infection.

AIMS: We aimed to evaluate the roles of interleukin-6 (IL-6), PCT, and fibrinogen levels in the differential diagnosis of the patients with infected diabetic foot ulcer (IDFU) and noninfected diabetic foot ulcer (NIDFU) and to compare those with C-reactive protein (CRP), white blood cell (WBC), and erythrocyte sedimentation rate (ESR). METHODS: Patients over 18 years with a diagnosis of type 2 diabetes mellitus and DFU who were followed up in our hospital between 1 January 2016 and 1 January 2017 were included in the study. In addition to this patient group, patients with diabetes but without DFU were determined as the control group. RESULTS: Thirty-eight patients with IDFU, 38 patients with NIDFU, and 43 patients as the control group were included in the study. Fifty-six point three percent of the patients who participated in the study were males, and the mean age was 61.07 ± 11.04 years. WBC, ESR, CRP, IL-6, and fibrinogen levels of the cases with IDFU were determined to be significantly higher compared to the cases in NIDFU (p < 0.01). The area under the ROC curve (AUROC) value was highest for CRP (0.998; p < 0.001), and the best cut-off value for CRP was 28 m/L. The best cut-off values for fibrinogen, IL-6, ESR, and WBC were 480 mg/dL, 105.8 pg/mL, 31 mm/h, and 11.6 (103 µ/L), respectively. CONCLUSION: Serum PCT levels were not found to be effective in the discrimination of IDFU and NIDFU. Serum IL-6 and fibrinogen levels seem to be two promising inflammatory markers in the discrimination of IDFU.

Investigation of dynamic thiol-disulphide homoeostasis in age-related cataract patients with a novel and automated assay.

PURPOSE: The aim of this study was to determine plasma thiol-disulphide homoeostasis in patients with age-related cataract (ARC) and compare the results of the patients with healthy subjects. Plasma malondialdehyde (MDA) levels and catalase (CAT) activity were also investigated. METHODS: The study included 53 cataract patients and 52 healthy volunteers. Native thiol-disulphide exchanges were determined using a novel and automated method. CAT activity was determined using the method described by Aebi, and MDA levels were calculated using the thiobarbituric acid method. RESULT: Native thiol and total thiol levels were significantly lower in the cataract patients compared with the controls (p < 0.001, p = 0.002, respectively). The disulphide levels of the cataract patients were significantly higher than the controls (p = 0.002). The ratios of disulphide/native thiol and disulphide/total thiol were statistically higher in the cataract patients compared with the control group (p < 0.001, p < 0.001, respectively). Furthermore, CAT activity was significantly lower in the cataract patient group compared with the control group (p < 0.001), and MDA levels were insignificantly higher in the patient group (p = 0.581). CONCLUSIONS: Our study showed that dynamic thiol-disulphide homoeostasis has shifted towards disulphide formation, as a result of thiol oxidation in ARC patients. The present study is the first to measure thiol-disulphide homoeostasis in ARC patients with a novel automated assay. This study supports the hypothesis that cataract is an oxidative disorder. Further studies are required in order to examine the relationship between oxidative stress and the development of cataract formation.

Thiol Disulfide Homeostasis in Pseudoexfoliation Syndrome.

PURPOSE: To determine the serum thiol disulfide homeostasis in patients with pseudoexfoliation (PEX) syndrome. METHOD: Thirty-five patients with PEX syndrome and forty healthy subjects were included in this observational case-control study. Serum native thiol, total thiol, disulfide, and native thiol/disulfide ratio were determined using a novel and automated assay. RESULTS: The mean serum total thiol and native thiol levels were significantly lower in patients with PEX syndrome compared to healthy controls (p = 0.001). The mean serum disulfide level was significantly higher in patients with PEX syndrome compared to healthy controls (p = 0.023). The serum native thiol/disulfide ratio was lower in patients with PEX syndrome compared to healthy subjects (16 ± 10.1 vs 22.3 ± 11.5, respectively, p = 0.014). CONCLUSION: Our findings provide evidence that the dynamic native thiol/disulfide ratio is lower in PEX syndrome, which shows a reduction in the natural cell reductive capacity reservoir.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

Effect of ukrain on ischemia/reperfusion-induced kidney injury in rats.

BACKGROUND: The aim of this study was to investigate the potential protective effect of ukrain on an experimental kidney injury model induced by ischemia and reperfusion (IR) in rats. MATERIAL AND METHODS: A total of 24 male Sprague-Dawley rats were equally and randomly separated into three groups as follows: group-1: controls (C; only laparotomy); group 2: renal ischemia-reperfusion (IR; occlusion of the renal artery for 30 min and 2 h of reperfusion); and group 3: ukrain treatment and IR applied group (U + IR; occlusion of the renal artery for 30 min and 2 h of reperfusion; ukrain was intraperitoneally administered 1 h before the IR process). RESULTS: Serum total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. The oxidative stress index was determined by calculating the TOS/TAS ratio. TAS serum levels significantly increased, and TOS serum levels also prominently decreased in U + IR group, when compared with the IR group (P < 0.001). Mean NGAL level was remarkably higher in IR group, when compared with the U + IR group (P < 0.001). Caspase-3 messenger RNA (mRNA) expression level increased in IR and decreased in U + IR group (P < 0.001). Bcl-xL serum and mRNA expression levels increased in the U + IR group (P < 0.001). In addition, serum iNOS and mRNA expression levels increased in IR group and decreased in U + IR group (P < 0.001). CONCLUSIONS: Data established from the present study suggest that ukrain may exhibit protective effect against IR-induced kidney injury and that antioxidant activity primarily modulates this effect.

Antioxidant, Antiapoptotic and Inflammatory Effects of Interleukin-18 Binding Protein on Kidney Damage Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1ß, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis. RESULTS: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups. CONCLUSIONS: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.

Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats.

AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS: All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE: Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.

Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics.

BACKGROUND/AIM: To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. MATERIALS AND METHODS: The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). RESULTS: At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. CONCLUSION: The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis.

The effects of caffeic acid phenethyl ester on inflammatory cytokines after acute spinal cord injury.

BACKGROUND: The purpose of this study was to investigate the effects of Caffeic Acid Phenethyl Ester (CAPE) on proinflammatory cytokines, IL-1ß and TNF-α, and explore its healing effect after acute spinal cord injury. METHODS: Forty-eight male Wistar-Albino rats were used in this study which was planned as three groups. All groups were divided into two sub-groups. Group 1a was the control group, in which only lower segment thoracic laminectomy was performed. In group 1b, spinal cord trauma was performed with aneurysm clip. In the second group, serum physiologic was given systemically thirty minutes after trauma, and rats were sacrificed after the first and sixth hour. In the third group, CAPE was given systemically thirty minutes after trauma, and rats were sacrificed after the first and sixth hour. Serum IL-1ß and TNF-α levels were analyzed by ELISA in the serum. Histopathological analysis was performed in damaged cord tissues. RESULTS: CAPE suppressed TNF-α and IL-1ß levels in the serum. In histopathological evaluation, it was detected that CAPE decreased hemorrhage and necrosis. CONCLUSION: CAPE suppresses the levels of proinflammatory cytokines, TNF-α and IL-1ß, after acute spinal cord injury in the early phase and contributes to the healing process.

Comparison of blood ethanol stabilities in different storage periods.

INTRODUCTION: Measurements of blood ethanol concentrations must be accurate and reliable. The most important factors affecting blood ethanol stability are temperature and storage time. In this study, we aimed to compare ethanol stability in plasma samples at -20 °C for the different storage periods. MATERIALS AND METHODS: Blood samples were collected from intoxicated drivers (N=80) and initial plasma ethanol concentrations were measured immediately. Plasma samples were then stored at -20 °C and re-assessed after 2, 3, 4, or 5 months of storage. Differences between the initial and stored ethanol concentrations in each group (N=20) were analyzed using Wilcoxon matched-pairs test. The deviation from the initial concentration was calculated and compared with Clinical Laboratory Improvement Amendments (CLIA'88) Proficiency Testing Limits. Relationships between the initial concentrations and deviations from initial concentrations were analyzed by Spearman's correlation analysis. For all statistical tests, differences with P values of less than 0.05 were considered statistically significant. RESULTS: Statistically significant differences were observed between the initial and poststorage ethanol concentrations in the overall sample group (P<0.001). However, for the individual storage duration groups, analytically significant decreases were observed only for samples stored for 5 months, deviations from the initial concentrations exceeded the allowable total error (TEa). Ethanol decreases in the other groups did not exceed the TEa. CONCLUSION: According to our results, plasma ethanol samples can be kept at -20 °C for up to 3-4 months until re-analysis. However, each laboratory should also establish its own work-flow rules and criterion for reliable ethanol measurement in forensic cases.

Ghrelin levels in chronic periodontitis patients.

Ghrelin is a peptide hormone that has modulatory effects on the immune system. This study was designed to evaluate plasma ghrelin levels in patients with chronic periodontitis and to investigate if a relationship exists between ghrelin and periodontal parameters, serum cytokines, and bone turnover markers. Thirty-five chronic periodontitis patients (CP) and periodontal healthy individuals (C) were included in this study. Periodontal parameters were recorded. Blood samples were obtained to determine the levels of total and acylated ghrelin, interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), the soluble receptor activator nuclear factor kappaB ligand (sRANKL), alkaline phosphatase (ALP), and osteocalcin (OSC). Plasma levels of total and acylated ghrelin were significantly elevated in the CP group compared with the C group (p < 0.05). The difference was significant only between males in the two groups (groups were compared with respect to gender) (p < 0.05). There was no difference between the groups regarding the levels of serum sRANKL, TNF-α, and ALP. A relative increase in the serum levels of IL-1ß and a decrease in the serum levels of OSC of the CP group were observed (p < 0.05). In addition, positive correlations between total ghrelin/ALP and total ghrelin/acylated ghrelin were discovered. We found no direct correlation between ghrelin levels and periodontal parameters. Our results indicate an increase of total and acylated ghrelin levels in patients with chronic periodontitis. Further, studies in larger populations (which could include ghrelin levels in gingival tissue, gingival crevicular fluid, and saliva) are needed in order to confirm the role of ghrelin in periodontal disease.

The gingival crevicular fluid levels of interleukin-11 and interleukin-17 in patients with aggressive periodontitis.

BACKGROUND: The balance (ratio) of anti-inflammatory and proinflammatory cytokines is thought to play an important role in the pathogenesis of chronic periodontitis. Moreover, the imbalance of anti-inflammatory/proinflammatory cytokines may modulate disease progression in aggressive periodontitis (AgP). This study aims to investigate the levels of interleukin (IL)-11 and IL-17 and their ratio in gingival crevicular fluid (GCF) in patients with AgP. METHODS: This study included 20 patients with generalized AgP (GAgP) and 18 healthy controls (HC). For each patient, the values of clinical parameters, such as gingival index, plaque index, probing depth, and clinical attachment level, were recorded. Levels of IL-11 and IL-17 in GCF samples were evaluated using enzyme-linked immunosorbent assay. The values of clinical parameters, cytokine levels, and the ratios of cytokines were evaluated. RESULTS: The values of all the clinical parameters were significantly higher in the GAgP group than in the HC group (P < 0.001). The total amount and concentration of IL-11 and the concentration of the IL-17 and IL-11/IL-17 ratio were significantly lower in the GAgP group than in the HC group (P < 0.001). The total amount of IL-17 was not significantly different between the groups (P = 0.317). CONCLUSIONS: The IL-11/IL-17 ratio was decreased in the GAgP group because of the decreased IL-11 levels. The IL-11/IL-17 axis and the link between IL-17 and neutrophil function disorders in AgP should be investigated to clarify the role of the IL-11/IL-17 axis and its balance and imbalance in the pathogenesis of AgP.