Exploring altered free amino acids and metabolites: Insights into the metabolic landscape of preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a complex disease that poses a risk for maternal and perinatal morbidity and mortality. This study aimed to investigate the role of maternal serum amino acids (AAs) levels in PE. MATERIALS AND METHODS: A total of 56 pregnant women (26 with PE and 30 controls) were included in the study. The participants had a confirmed gestational age between 24 and 37 weeks. The mean body mass index (BMI) for the PE group was 33.1 kg/m2, while the control group had a mean BMI of 29.6 kg/m2. AAs levels were quantified, and statistical analyses were performed to identify significant differences between the two groups. Receiver Operating Characteristic (ROC) curve analysis was employed the diagnostic potential of specific AAs. RESULTS: We observed significantly elevated levels of multiple AAs in the PE group, including citrulline, lysine, ethanolamine, ornithine and histidine. Citrulline exhibited exceptional predictive power for PE with 100.0% sensitivity and specificity at a cutoff of 7.79 µmol/L, reflected in an area under the curve (AUC) of 1.000. DISCUSSION: Our study highlights the crucial involvement of altered amino acid levels, specifically in the urea cycle, disruptions in lysine and ethanolamine metabolism in PE development. Exploring these changes may reveal new therapeutic targets, providing insights into the disease's molecular mechanisms. Understanding amino acid metabolism in PE not only informs therapeutic strategies but also holds the potential to revolutionize early diagnosis and intervention.

Exploring free amino acid profiles in Crimean-Congo hemorrhagic fever patients: Implications for disease progression.

This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus infection and alterations in amino acid metabolism. The primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Exploring free amino acid profiles in CCHF patients: Implications for disease progression.

This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Analysis of liver fibrosis equations as a potential role of predictive models in Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) is a formidable global health concern, characterized by its rapid onset and high fatality rate. Distinguishing between patients at different stages remains challenging because of overlapping clinical features. This study aimed to evaluate the diagnostic efficacy of 14 hepatic fibrosis indices for distinguishing fatal cases and intensive care unit requirement (ICU) in CCHF. This study enrolled 194 patients with confirmed CCHF. Laboratory measurements were performed using auto analyzers. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas. Time-dependent receiver operating characteristic (tdROC) curve analyses were employed to evaluate the predictive effects of hepatic fibrosis indices on both intensive care unit requirement and overall survival among patients. Regarding the tdROC analyses results, the highest area under the curve statistics were obtained for the baseline S-INDEX, KING, and GPRI scores (0.920, 0.913, and 0.909 respectively) in the estimation of ten-day survival, and the baseline KING, Goteborg University cirrhosis index (GUCI), and gamma-glutamyl transferase to platelet ratio index (GPRI) scores (0.783, 0.773, and 0.769 respectively) in the estimation of intensive care requirements for up to ten days. S-index and KING index emerged as early predictors of ten-day survival, while KING, GUCI, and GPRI indices demonstrated predictive capabilities for ICU admission on the first day. The identified indices have the potential to assist healthcare providers in making timely and informed decisions regarding patient management and treatment strategies. Further research and validation are warranted to solidify the role of these hepatic fibrosis indices in the clinical setting and enhance their broader applicability in the management of CCHF.

Maternal serum amino acid levels as predictors of premature rupture of membranes: A comprehensive analysis.

INTRODUCTION: The aim of this study is to investigate the association between altered maternal serum amino acids (AAs) levels and premature rupture of membranes (pPROM) in pregnant women. METHODS: We conducted a case-control study involving 60 pregnant women diagnosed with pPROM and 60 healthy pregnant women as controls. Amino acid levels were quantified using high-performance liquid chromatography. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive capability of specific AAs for pPROM. RESULTS: Our findings revealed that lysine, glycine, and glutamic acid levels were significantly elevated in the pPROM group compared with the control group. Lysine, with a threshold value exceeding 137.90 µmol/L, exhibited the highest predictive accuracy, with an area under the curve (AUC) of 0.796 (p < 0.001), sensitivity of 66.7 %, and specificity of 80.0 %. Glycine, with a cut-off value of >242.48 µmol/L, had an AUC of 0.789 (p < 0.001), sensitivity of 83.3 %, and specificity of 65.0 %. Glutamic acid, at a threshold of 111.40 µmol/L, demonstrated an AUC of 0.787 (p < 0.001), sensitivity of 88.3 %, and specificity of 65.0 %. These AAs could effectively predict the occurrence of pPROM. CONCLUSION: Elevated blood levels of lysine, glycine, and glutamic acid were found to be associated with pPROM. These AAs serve as potential predictive biomarkers for pPROM, with lysine showing the highest AUC and sensitivity. Identifying such biomarkers may contribute to the development of non-invasive diagnostic tools for pPROM risk assessment, enabling timely interventions and improved maternal and fetal outcomes.

Validation of low-density lipoprotein cholesterol equations in pediatric population.

Several studies have shown a high prevalence of dyslipidemia in children. Since childhood lipid concentrations continue into adulthood, recognition of lipid abnormalities in the early period is crucial to prevent the development of future coronary heart disease (CHD). Low density lipoprotein cholesterol (LDL-C) is one of the most used parameters in the initiation and follow-up of treatment in patients with dyslipidemia. It is a well known fact that LDL-C lowering therapy reduces the risk of future CHD. Therefore, accurate determination of the LDL-C levels is so important for the management of lipid abnormalities. This study aimed to validate different LDL-C estimating equations in the Turkish population, composed of children and adolescents. A total of 3,908 children below 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included in this study. LDL-C was directly measured by direct homogeneous assays, i.e., Roche, Beckman, Siemens and estimated by Friedewald's, Martin/Hopkins', extended Martin-Hopkins' and Sampson's formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both overall and separately for the LDL-C, triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) sublevels. Linear regression analysis was performed and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R 2) and mean absolute deviations were also evaluated. The overall concordance of Friedewald, Sampson, Martin-Hopkins and the extended Martin-Hopkins formula were 64.6%, 69.9%, 69.4%, and 84.3% for the Roche direct assay, 69.8%, 71.6%, 73.6% and 80.4% for the Siemens direct assay, 66.5%, 68.8%, 68.9% and 82.1% for the Beckman direct assay, respectively. The extended Martin-Hopkins formula had the highest concordance coefficient in both overall and all sublevels of LDL-C, non-HDL-C, and TG. When estimating the LDL-C categories, the highest underestimation degrees were obtained with the Friedewald formula. Our analysis, conducted in a large pediatric population, showed that the extended Martin-Hopkins equation gives more reliable results in estimation of LDL-C compared to other equations.

Assessment of semaphorin 3A and semaphorin 7A levels in primary Sjogren's syndrome.

Sjogren's syndrome (SS) is a chronic autoimmune connective tissue disease. Varying rates of system involvements may be seen in the course of the disease. Semaphorins has multifunctions in several physiological and pathological processes such as immune system regulation. The association of Semaphorin 3A (Sema3A) and Semaphorin 7A (Sema7A), which are immune semaphorins, with autoimmune diseases is interesting for researchers. We aimed to compare serum Sema3A and Sema7A levels between primary SS and control subjects, and investigated Sema3A and Sema7A levels in disease subgroups and associated system involvements. 50 consecutive primary SS patients and 40 healthy subjects followed in the Rheumatology clinic of Cumhuriyet University Medical Faculty between 2017 and 2018 were included in the study. Inclusion criteria of patients were diagnosis of primary SS according to the 2016 ACR/EULAR classification criteria. Serum Sema3A and Sema7A levels were measured by commercial ELISA kit. Both groups were similar in terms of age, gender, and body mass index. Serum Sema3A and Sema7A levels were significantly lower in SS than in the controls (p = 0.001 and p = 0.005, respectively). Serum Sema3A levels were significantly lower in patients with renal involvement than in patients without (p = 0.03). Sema3A and Sema7A may play a role in the etiopathogenesis of SS and may be a potential serological marker for the diagnosis of SS and may be a target for treatment.

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats.

BACKGROUND: Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats. METHODS: The animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion+uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion+uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes. RESULTS: In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups. CONCLUSION: Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.

Metabolomic profiling in ankylosing spondylitis using time-of-flight mass spectrometry.

BACKGROUND & AIMS: Ankylosing spondylitis (AS) is an inflammatory disease associated with destructive changes in the skeleton and joints. The exact molecular mechanism of the disease has not been fully elucidated. This study aimed to determine metabolic differences between active AS patients and healthy controls to understand the molecular mechanism of AS. PATIENTS AND METHODS: The study included 38 subjects, comprising 18 patients with active AS and 20 healthy controls. Metabolic profiling of the plasma was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS). Data acquisition, classification, and identification were achieved with the METLIN (https://metlin.scripps.edu/) database and XCMS (https://xcmsonline.scripps.edu). RESULTS: Significant alterations were identified in the unsaturated fatty acids (FA), linoleic acid, alpha-linolenic acid, FA degradation, and FA biosynthesis pathways. Down -regulations were observed in phosphatidylcholine (PC) (16:0/0:0), beta-d-Fructose, stearic acid, trimipramine N-Oxide and muconic acid, and up-regulation were detected in PC (18:2/0:0), 3-Methylindole, palmitic acid (PA), alpha-Tocotrienol, and beta-d-glucopyranoside in active AS patients compared to the healthy control subjects. CONCLUSION: Pathway analysis revealed that dysregulation in FA metabolism is associated with AS, and therefore, modulation of diet according to PA and PC may be potential therapeutic targets.

Validation of Friedewald, Martin-Hopkins and Sampson low-density lipoprotein cholesterol equations.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important biomarker for determining cardiovascular risk and regulating lipid lowering therapy. Therefore, the accurate estimation of LDL-C concentration is essential in cardiovascular disease diagnosis and prognosis. Sampson recently proposed a new formula for the estimation of LDL-C. However, little is known regarding the validation of this formula. OBJECTIVES: This study aimed to validate this new formula with other well-known formulas in Turkish population, composed of adults. METHODS: A total of 88,943 participants above 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included to this study. LDL-C was directly measured by homogeneous assays, i.e., Roche, Beckman and Siemens and estimated by Friedewald's, Martin-Hopkins', extended Martin-Hopkins' and Sampson's formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both in general and separately for the LDL-C, TG and non-HDL-C sublevels. Linear regression analysis was applied and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R2) and mean absolute deviations were also calculated. RESULTS: The results showed that the extended Martin-Hopkins approach provided the most concordant results with the direct assays for LDL-C estimation. The results also showed that the highest concordances were obtained between the direct assays with the extended Martin-Hopkins formula calculated with the median statistics obtained from our own population. On the other hand, it was observed that the results of the methods may differ in different assays. The extended Martin-Hopkins approach, calculated from the median statistics of our population, gave the most concordant results in patients with "low LDL-C level (LDL-C levels < 70 mg/dL) or hypertriglyceridemia (TG levels ≥ 400 mg/dL)". CONCLUSIONS: Although the results of the formulas in different assays may vary, the extended Martin-Hopkins approach was the best one with the highest overall concordances. The validity of the Martin Hopkins' and Sampson's formulas has to be further investigated in different populations.

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice.

BACKGROUND: The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. OBJECTIVES: To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. MATERIAL AND METHODS: Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. RESULTS: The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. CONCLUSIONS: We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

Different threshold levels of circulating total and free 25-hydroxyvitamin D for the diagnosis of vitamin D deficiency in obese adolescents.

The total serum 25-hydroxyvitamin D [25(OH)DT] level is lower in obese individuals than in their nonobese peers, despite similar bone turnover markers and bone mineral density. This study aimed to investigate whether the threshold level of 25(OH)D for the diagnosis of vitamin D deficiency (VDD) in obese adolescents was lower than that in controls and to compare 25(OH)DT, free [25(OH)DF] and bioavailable [25(OH)DB] vitamin D with VDBP levels in obese individuals and their controls. A total of 173 adolescents (90 obese individuals and 83 controls) aged 12-18 years were included in the study. The metabolic and anthropometric parameters of the participants were recorded, the 25(OH)DT, 25(OH)DF, and VDBP levels were measured, and the 25(OH)DB levels were calculated. The cutoff values for VDD were estimated according to the level of 25(OH)D below which parathyroid hormone begins to rise. The obese subjects had lower 25(OH)DT (12.1 ± 5.8 vs. 16.4 ± 9.3 ng/mL, p < 0.001), 25(OH)DF (12.6 ± 4.2 vs. 16.7 ± 7.6 pg/mL, p < 0.001), 25(OH)DB [4.8 (2.3) vs. 6.1 (5.2) ng/mL, p = 0.012], and VDBP [112.2 (51.3) vs. 121.9 (95.5) µg/mL, p < 0.001] levels than the controls. The cutoff values for 25(OH)DT and 25(OH)DF levels for VDD were lower in the obese group than in the control group (9.4 vs. 14.1 ng/mL; 12.2 vs. 16.8 pg/mL, respectively).Conclusion: The vitamin D cutoff values for the diagnosis of VDD were different in the obese and control groups. Using the same cutoff value for VDD may cause overtreatment in obese adolescents. What is Known: • Vitamin D deficiency is more prevalent in obese children than nonobese controls, despite the same bone turnover markers and bone mineral density • The cutoff value of vitamin D level for the diagnosis of VDD is based on the PTH elevation What is New: • In obese adolescents, total and free vitamin D cutoff value for the diagnosis of VDD was lower than nonobese peers • Using the same cutoff value for vitamin D deficiency in both obese and nonobese adolescents may cause overtreatment.

Can Calprotectin Show Subclinical Inflammation in Familial Mediterranean Fever Patients?

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease that has self-limiting inflammatory attacks during polyserositis. Hepcidin is a protein, and interleukin-6 stimulation increases hepcidin levels. Calprotectin (CLP) is a recently defined cytokine released from monocytes and neutrophils in response to tissue trauma and inflammation. There are studies in the literature showing that it can be used as a biomarker in rheumatic diseases such as ankylosing spondylitis and rheumatoid arthritis. Here, we compared the levels of hepcidin and CLP in healthy individuals and FMF patients during an attack-free period and show its relation to genetic mutations. METHODS: This is a cross-sectional study. Between July 2017 and December 2017, 60 patients diagnosed with FMF an admitted to the Cumhuriyet University Faculty of Medicine Department of Internal Medicine Rheumatology as well as 60 healthy volunteers without any rheumatic, systemic, or metabolic diseases were enrolled in this study. Blood was collected from a peripheral vein to measure serum CLP and hepcidin levels. Blood tests were examined by ELISA; the study protocol was approved by the local ethics committee. RESULTS: Median serum hepcidin level was 468.1 (210.3-807.8) pg/mL in FMF group and 890.0 (495.0-1,716.9) pg/mL in the healthy control (HC) group. There was a statistically significant difference between the two groups (P < 0.001). The median serum levels of CLP in the FMF group were measured as 1,331.4 (969.3-1,584.6 pg/mL and 73.8(45.0-147.9) pg/mL in the HC group. There was a statistically significant difference between the two groups (P < 0.001). Receiver operating characteristic analysis showed that the sensitivity was 66.7% and the specificity was 71.7% at serum hepcidin < 581.25 pg/mL (P < 0.05); the sensitivity was 96.7% and specificity was 100% at CLP > 238 pg/mL (P < 0.05). There was no significant difference between serum hepcidin and CLP levels in FMF patients with M694V homozygous and M694V heterozygous (P > 0.05). There was no significant difference in serum hepcidin levels between FMF patients with and without arthritis, proteinuria, and amyloidosis (P < 0.05). There was no significant correlation between laboratory findings, gender, age, and serum CLP and hepcidin levels (P > 0.05, r < 0.25). CONCLUSION: Serum CLP levels in FMF patients during an attack-free period are significantly higher than in the HC groups. Serum hepcidin levels in FMF patients are significantly lower than in the HC group. Low levels of hepcidin may be explained by including FMF patients during an attack-free period in the study. CLP may be an important biomarker in FMF. A better understanding of the role of these biomarkers in the diagnosis of FMF is needed to evaluate the results in a more comprehensive way.

Evaluation of Serum Glucagon-Like Peptide 1 and Vitamin D Levels in Elderly Patients with Bone Fractures.

OBJECTIVES: To evaluate the correlation between levels of serum vitamin D and glucagon-like peptide-1 (GLP-1) in elderly patients with bone fractures. MATERIALS AND METHODS: This study included 56 patients and 31 control subjects. The patients included were those aged ≥65 years who were admitted to our hospital with a diagnosis of bone fracture. The control group comprised age-matched, healthy individuals. Levels of serum vitamin D and GLP-1 were measured and compared between the 2 groups. RESULTS: Significant differences were noted between the groups in terms of serum levels of vitamin D (p < 0.001) and serum levels of GLP-1 (p < 0.001). A positive correlation was observed between serum levels of vitamin D and GLP-1. CONCLUSION: Serum levels of GLP-1 were found to be significantly lower in elderly patients with bone fracture compared to healthy adults. In addition, a significant correlation was found between decreased vitamin D and GLP-1 levels. These results may therefore demonstrate the protective effects of GLP-1 on bone structure and metabolism, similar to those of vitamin D.

High prolidase levels in patients with Familial Mediterranean Fever (FMF).

INTRODUCTION: Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group. METHODS: Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study. RESULTS: Median serum prolidase levels were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1α in the FMF group was 482.0 (292.0-3967.0) pg/mL and 632.0 (362.0-927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05). CONCLUSION: Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.

Does mammalian target of rapamycin or sestrin 1 protein signaling have a role in bone fracture healing?

Background/aim: Fracture healing is a complex physiological process that involves a well-orchestrated series of biological events. The mammalian target of rapamycin (mTOR) and sestrin 1 (SESN 1) play a central role in cell metabolism, proliferation, and survival. The aim of our study is to present serum mTOR and SESN 1 levels by comparing patients with or without bone fractures. It is also a guide for further research on the roles of these proteins in fracture healing. Materials and methods: A total of 34 patients (10 females, 24 males) with bone fractures and 32 controls (10 females, 22 males) participated in this study. After collecting serum venous blood samples, the quantitative sandwich ELISA technique was used for the determination of serum mTOR and SESN 1 levels. Results: The mean serum mTOR level was significantly higher in the fracture group compared to the control group (P = 0.001). However, SESN 1 levels did not significantly differ between groups (P = 0.913). Conclusion: We found that serum mTOR levels increased on the first day after fracture compared to the control group. However, we obtained no significant difference between groups in terms of SESN 1 levels. This study may guide further clinical studies investigating the potential role of mTOR signaling in the bone healing process.

Serum NADPH oxidase concentrations and the associations with iron metabolism in relapsing remitting multiple sclerosis.

BACKGROUND: Overproduction of reactive oxygen species (ROS) and impaired iron metabolism are considered to be possible factors in the pathogenesis of Multiple sclerosis (MS). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the primary sources of regulated ROS production. The NADPH oxidase (NOX) family consists of seven catalytic homologues, NOX1-5 and two dual oxidases. NOX1 and NOX5 are associated with endothelial dysfunction and inflammation but NOX4 has a protective effect on vascular function. The aims of this study were to investigate the status of NOX1, NOX4 and NOX5 and its relationship with serum iron metabolism biomarkers in relapsing-remitting MS patients. METHODS: The study included 53 RRMS patients and 45 control subjects. Serum NOX1,4,5, ferritin, iron, unbound-iron binding capacity, C-reactive protein (CRP), white blood count (WBC) and erythrocyte sedimentation rate (ESR) levels were measured in all the study subjects. RESULTS: Higher serum NOX5 (p < 0.0001), CRP (p = 0.014), ferritin (p = 0.040) and lower serum NOX4 (p < 0.0001) and iron (p = 0.013) concentrations were found in the patients than in controls. No correlation was found between NOXs, CRP, WBC, ESR and iron metabolism biomarkers in patients. CONCLUSION: Our data suggest that increased NOX5 expression and decreased levels of NOX4 might be related with oxidative stress related vascular changes in MS patients. These findings provide future opportunities to combat MS with separately target individual NOX isoforms.

Low levels of pannexin-1 in Behçet's syndrome.

OBJECTIVE: Behçet's syndrome (BS) is a chronic, multisystemic and inflammatory syndrome. In our study, we aimed to compare the initiator, effector and inflammatory caspases and pannexin channel protein, which is thought to have an activity in inflammation, in the inflammatory process of BS, with healthy subjects, to investigate their level in patients and their relationship with the clinical findings. METHOD: Forty-six patients who were under follow-up for BS in the Sivas Cumhuriyet University Medical Faculty Department of Internal Diseases, Rheumatology Unit, between January 2017 and June 2017 and 44 healthy controls (HC) who did not have any rheumatic, systemic or metabolic diseases, were enrolled in this study. RESULTS: The mean serum pannexin-1 level was 6.36 (4.21-527.2) pg/mL in the BS group and 255.8 (5.38-2000) pg/mL in the HC group. Serum pannexin-1 levels were statistically significantly lower in the BS group (P < 0.0001). The measured mean serum caspase-3 level was 12.04 (11.25-43.69) pg/mL in the group with BS and 12.1 (11.19-484.3) pg/mL in the HC group (P = 0.143), mean serum caspase-9 level was 22 (5.14-29.33) pg/mL in the BS group and 22.01 (11.23-850) pg/mL in the HC group (P = 0.593), mean serum caspase-14 level was 6 (5.2-8.21) pg/mL in the BS group and 6.15 (5.7-353) pg/mL in the HC group (P = 0.053). CONCLUSION: Comparison of serum caspase-3, caspase-9 and caspase-14 levels in subjects with BS and in the HC group did not reveal any statistically significant differences. On the other hand, serum pannexin-1 levels were statistically significantly lower in the BS group.

An evaluation of the different biomarkers to discriminate bleeding in Crimean-Congo Hemorrhagic Fever.

Crimean-Congo Hemorrhagic Fever (CCHF) is an acute viral hemorrhagic disease. In this study, an evaluation was made of the potential use of iron metabolism and liver function biomarkers to estimate the bleeding status in CCHF patients. This prospective study was conducted in Cumhuriyet University, Turkey. Only patients with confirmed CCHF were enrolled in the study. The study subjects comprised 40 CCHF patients and 37 healthy control subjects. Serum iron, unsaturated iron binding capacity (UIBC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined using the colorimetric method. Serum ferritin levels were measured using the electrochemiluminescent method. The serum ferritin (p = 0.037), AST (p = 0.0002), ALT (p = 0.002), LDH (p = 0.0005) and aPTT (p = 0.001) values were higher in patients with bleeding than in patients without bleeding. Receiving operating characteristic analyses were applied for the area under the curve (AUC) values for ferritin, aPTT, and AST to discriminate the bleeding status in patients, an these were determined as 0.717, 0.819, and 0.882, respectively. A cut-off value of 149 U/L for AST was obtained to discriminate the bleeding condition in CCHF patients. Higher ferritin (p < 0.0001) levels were determined in patients compared to the control group. The iron (p = 0.180) and UIBC (p = 0.0017) values were lower in patients than in the control group. Cytokine storm due to an increase in ferritin levels may contribute to the increased inflammation and coagulation abnormalities in CCHF patients. It was concluded that routine screening of the AST level would be helpful to estimate the bleeding status in addition to screening liver damage in CCHF patients.