Epigenetic insights into Familial Mediterranean Fever: Increased RGS10 expression and histone modifications accompanies inflammation in familial Mediterranean fever disease.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring fever, erythema, joint pain, and abdominal discomfort during acute episodes. While FMF patients typically share MEFV gene mutations, they display varying clinical manifestations, suggesting the involvement of modifying genes, epigenetic mechanisms, or environmental factors. G protein regulator signal 10 (RGS10), a member of the RGS protein family, exhibits anti-inflammatory effects in autoinflammatory diseases. There are no studies on the role of plays in FMF pathogenesis or histone modification in FMF. AIMS: This study aimed to shed light on the epigenetic regulation of FMF from several perspectives. The relationship between RGS10 DNA hypermethylation in FMF clinical parameters and the regulation of 22 histone modifications were examined in FMF attack patients and the control group. METHODS: Sixty FMF (remission/attack) and thirty healthy individuals were included in the study. First, RNA was isolated from the blood of patients/controls, and the expression of RGS10 was examined. Then, DNA was isolated from the patients, and gene-specific hypermethylation was investigated using the bisulfite conversion method. Finally, histone extraction was performed for FMF patients and controls and 22 histone H3 modifications were determined. In addition, using ADEX bioinformatics tools, RGS10 expression and methylation profiles were detected in different autoinflammatory diseases. RESULTS: This study indicate that RGS10 expression decreased in attack-free/attack patients than control, attributed to DNA methylation. In addition, there were a positive correlation between FMF patients and attack, WBC, neutrophil, MCHC and MPV. Moreover, higher H3K4 me3, H3K9 me2, and H3K14ac levels were observed in patients with FMF attacks. This research also showed a consistent decrease in RGS10 expression in patients with SjS, SSc, and T1D compared with controls. I also obtained five prognosis-related CpGs (cg17527393, cg19653161, cg20445950, cg18938673 and cg13975098) of RGS10 in patients with SjS, RA, SSc, SLE and T1D. CONCLUSION: The present study provides insights into the complex relationship between RGS10, epigenetic modifications, and immune responses in FMF. While RGS10 may initially enhance immune responses, genetic mutations and epigenetic changes associated with FMF acute episode may override this regulatory effect, resulting in increased inflammation and clinical symptoms. Moreover, our study revealed elevated levels of specific histone modifications in the context of FMF, suggesting significant epigenetic changes that could contribute to the disease pathogenesis. Understanding these associations opens new avenues for research and potential therapeutic interventions, potentially involving epigenetic therapies targeting histone modifications.

Association of eNOS gene 4a/4b VNTR and T786C polymorphism with Crimean-Congo hemorrhagic fever.

The most common viral hemorrhagic fever is Crimean-Congo hemorrhagic fever (CCHF). Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been linked to both hemorrhagic fevers and viral diseases. The study's goal is to evaluate if the eNOS gene 4a/4b and T786C polymorphisms are related to CCHF. The study included 54 CCHF RNA-positive patients and 60 control subjects. The Bosphore CCHF virus Quantification Kit v1 was used to obtain CCHF RNA, and the Magnesia 16 isolation device was used to isolate DNA (Anatolia Gene works, Turkey). Polymerase chain reaction and restriction fragment length polymorphism were used to genotype the samples. The frequency of the eNOS 4a/4a, 4a/4b, and 4 b/4b genotypes in patients and the control was 6.6% versus 1.7%, 37.0% versus 43.3%, and 57.4% versus 55%, respectively. 4a: 24.07% of patients and 23.33% of controls; and 4 b: 75.92% of patients and 76.66% of controls. The frequency of the eNOS-786 T/C, T/T, T/C, and C/C genotypes in patients and the control group was 35.2% versus 68.3%; 51.9% versus 26.73%; and 13.0% versus 5.0%, respectively. The allele and genotype frequencies of the eNOS T786C variant differ statistically between patients and the control (p < 0.05). The eNOS T786C variant could be a genetic determinant for susceptibility to CCHF. To our knowledge, this is the first study to figure out the association between eNOS gene T786C polymorphisms and CCHF disease.

NLRP13 inflammasome complex is hypermethylated in familial Mediterranean fever and global methylation correlates with the disease severity.

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by variations in the MEFV gene, which encodes the pyrin protein, a member of the inflammasomes. Despite the complex pathogenesis of FMF, epigenetic changes also play roles in the disease progression. In our previous study, we observed a relationship between NLRP13, which is one of the members of the inflammasome complex and has a pyrin domain in its structure, and the MEFV gene using the STRING database. In this study, we examined NLRP13 expression and methylation status in 40 patients with FMF attack and 20 healthy individuals. We then investigated the global DNA methylation status of patients with FMF in the attack period and control groups. We further examined the relationship between the clinical manifestation and global methylation as well as NLRP13 gene expression of patients with FMF and healthy individuals. As a result, we showed that hypomethylation in patients with FMF leads to different clinical outcomes in terms of disease severity. In addition, the data indicated that NLRP13 inflammasome is epigenetically controlled in patients with FMF and the presence of amyloidosis may affect the hypermethylation of this gene. Moreover, NLRP13 was silenced because of the hypermethylation of the promoter. The increase of methylation level at the promoter region participated in the inactivation of NLRP13. In the current study, we not only found a new gene that plays a role in the pathogenesis of FMF disease, but also new evidence for the epigenetic regulation of the disease.

Evaluation of clinical relationship of serum niacin and dopamine levels in patients with fibromyalgia syndrome.

Objectives: The aim of this study was to investigate the role of serum niacin and dopamine (DA) levels and their clinical importance in fibromyalgia syndrome (FMS) patients. Patients and methods: Between April 2018 and October 2018, a total of 53 female patients (mean age: 38.3±5.5 years; range, 21 to 45 years) with a clinical diagnosis of FMS and 35 healthy female controls (mean age: 36.7±5.2 years; range, 25 to 44 years) were included in this cross-sectional study. The Visual Analog Scale (VAS), Beck Depression Inventory (BDI), and Fibromyalgia Impact Questionnaire (FIQ) were applied to the patients. Serum levels of niacin and DA were measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) methods, respectively. Results: Niacin and DA levels of the patient group were significantly lower than those of control group (p=0.003 and p=0.02, respectively). A very strong positive correlation was found between niacin and DA levels (r=0.96 p<0.001). Evaluation of the diagnostic performance of niacin and DA by the receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.73 (p<0.001, 95% confidence interval [CI]: 0.62-0.85) and an AUC of 0.68 (p=0.004, 95% CI: 0.56-0.80), respectively. Conclusion: Serum niacin and DA levels decrease in FMS patients in relation to the tender point numbers. It can be suggested that the levels of these two markers can be considered additional tools in the diagnosis of FMS.

The Effect of Sun Light Exposure to the Level of Vitamin D in Elderly People Living in Nursing Home.

BACKGROUND: Elderly people are considered to be in the risk group for vitamin D deficiency. The aim of the present study was to determine the effect of nursing interventions and sunlight exposure to reach optimum 25-hydroxyvitamin D [25(OH)D] levels by individuals living in nursing homes. METHODOLOGY: Randomized controlled experimental study was carried out in June-August 2018 period in the nursing home. The question form, standardized mini mental test, Fitzpatrick skin typing questionnaire and Katz Index of activities of daily living were applied. Individuals in the intervention group (n=20) was exposed to sunlight five days a week for four weeks in July with an average duration of 21 ± 5 minutes (min 15 - max 30 minutes). For the participants in the control group (n=20), sunbathing was not offered. 25(OH)D, calcium, parathormone, phosphorus, alkaline phosphatase and albumin levels of all individuals were measured at the beginning and end of the study. RESULTS: At the end of the study, the 25(OH)D was significantly higher in the intervention group than in the control group (8.06 ng/ml and 0.96 ng/ml, respectively; p = 0.008). It was observed that in the intervention group, sunlight exposure increased the 25(OH)D regardless of gender and age. Increases were observed in intervention groups for calcium and albumin levels. At the beginning of the study, 25(OH)D was sufficient only in five elderly people in the intervention group, while at the end, 11 elderly people had sufficient levels of 25(OH)D. CONCLUSION: At the end of the study, it was concluded that sunlight exposure was a sufficient source to increase 25(OH)D in most elderly people living in the nursing home. Organizing sunbathing sessions as an independent nursing intervention is recommended for the elderly people living in nursing homes in order to prevent vitamin D deficiency and related consequences.

Prevalence of insulin resistance and identifying HOMA1-IR and HOMA2-IR indexes in the Middle Black Sea region of Turkey.

BACKGROUND: Insulin resistance (IR) is one of the most important etiological risk factors in the development of diabetes. However, there is no clear data regarding the prevalence of IR in the country. OBJECTIVE: This study evaluates the prevalence of IR and identifies the optimal threshold values for the HOMA indexes in Turkey. METHODS: This cross-sectional, population-based survey includes 2013 participants aged 20-84 years. The values of the anthropometric measurements and laboratory analysis were recorded. The 90th percentile in the non-obese and non-diabetic population was accepted as cut-off values for IR. RESULTS: The optimal threshold values for IR were 2.46 in HOMA1-IR and 1.40 in HOMA2-IR. Using the HOMA2-IR method, the overall prevalence of IR was 33.2%. The IR prevalence was higher in women (35.6%) compared to men (30.1%) [p=0.008]. There was a higher IR prevalence in men living in urban areas (p=0.001), not in women. The multivariate logistic regression analysis showed that gender, serum glucose level, serum levels of triglycerides and high-density lipoprotein cholesterol, bodymass index and income status were associated with insulin resistance. CONCLUSION: The cut-off values of HOMA1-IR and HOMA2-IR were determined in this study and we believe that these findings will be helpful to clinicians in the fight against health problems such as diabetes.

Serum Interleukin-23/17 Levels in Ankylosing Spondylitis Patients Treated with Nonsteroidal Anti-Inflammatory Drugs: A Prospective Cohort Study.

Etiopathogenesis of ankylosing spondylitis (AS), a major subtype of a group of chronic inflammatory diseases known as spondyloarthropathies, is not clearly understood yet. In this study, we aimed to investigate the interleukin 23 (IL-23)/interleukin-17 (IL-17) pathway, which is a new cytokine pathway in inflammatory diseases. We evaluated serum IL-17 and IL-23 levels after 1-year follow-up in AS patients using only nonsteroidal anti inflammatory drugs (at need or continue). Forty-four AS patients and 40 healthy controls were included in the study. Clinical evaluations of disease activity were performed. Serum tumor necrosis factor-α (TNF-α), IL-6, IL-17, and IL-23 levels were evaluated. IL-17 and IL-23 levels of the patient group at baseline and 12 months were lower than the control group. There was no significant difference between the baseline and 12th month evaluations of the patient group. TNF-α levels were similar in all groups (in the baseline and 12th month of the patient group and in the control group). Although our results are in contrast to the literature findings, the IL-23/IL-17 pathway is a newly discovered pathway, and there may still be unknowns. New studies involving larger patient groups are needed for the factors affecting serum IL-23/IL-17 levels in patients with AS. We also think that it will be useful to make more comprehensive and long-term studies about which patients will respond well to IL-23/IL-17 blockade.

Oxidative stress markers in laparoscopic vs. open appendectomy for acute appendicitis: A double-blind randomized study.

BACKGROUND: Oxidative stress is a complicated process, which was defined as an increase in prooxidants and decrease in antioxidants caused by various mechanisms, including inflammation and surgical trauma. The association between acute appendicitis and oxidative stress has been showed in previous studies. However, comparison of oxidative stress in laparoscopic or open appendectomy (OA) has not been established. PATIENTS AND METHODS: Patients who were diagnosed as acute appendicitis between October 2012 and January 2013 were randomized to open (OA, n = 50) and laparoscopic appendectomy (LA, n = 50). Blood samples for oxidative stress markers (total oxidant status [TOS] and total antioxidant status [TAS]), C-reactive protein (CRP) and white blood cells (WBC's) were collected just before the surgery and 24 h after surgery. RESULTS: There were no differences in preoperative values of WBC and CRP between LA and OA groups (P = 0.523 and 0.424), however, in postoperative 24(th) h, CRP was reduced in LA group (P = 0.031). There were no differences in preoperative levels of TOS, TAS, and oxidative stress index (OSI) between LA and OA groups. In the postoperative 24(th) h, TOS and OSI were found to be significantly higher in OA group when compared to LA group (P = 0.017 and 0.002) whereas no difference was detected in TAS level in the postoperative 24(th) h (P = 0.172). CONCLUSIONS: This double-blind, randomized clinical trial provides evidence that LA for uncomplicated appendicitis is associated with significantly lower oxidative stress compared with OA. Some of the advantages of LA may be attributed to the significant reduction of oxidative stress in these patients.

The Relationship Among the Level of Serum Amyloid A, High-Density Lipoprotein and Microalbuminuria in Patients With Familial Mediterranean Fever.

BACKGROUND: Serum amyloid A (SAA), which is produced in the liver, acts as an apoprotein of high-density lipoprotein (HDL) accumulation in extracellular matrix of tissues and organs. SAA elevations play a significant role in the development of amyloidosis. Microalbuminuria (MAU) is the early period of amyloidosis in patients with familial Mediterranean fever (FMF). We assessed the association between SAA as an important factor for the development of amyloidosis in patients with FMF and cytokines, HDL, and MAU. METHODS: A total of 40 FMF patients diagnosed with Tel-Hashomer criteria and making regular follow-up visits at the tertiary referral center from 2012 to 2013 were included in this study, besides 40 age- and sex-matched individuals as controls. RESULTS: Compared with controls, FMF patients had higher SAA (25.20 ± 45.78 vs. 1.68 ± 0.63 ng/ml; P = 0.002). Also, FMF patients had higher MAU than controls (23.20 ± 39.86 vs. 9.40 ± 5.32 mg/day; P = 0.036). HDL was significantly lower in the patient group than in controls (39.35 ± 10.45 vs. 47.82 ± 15.31 mg/dl; P = 0.023). Interleukin-1 beta (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) levels were higher in the FMF group than in controls (P < 0.0001, P = 0.009, P = 0.003, respectively). CONCLUSIONS: Our results suggest that IL-1, IL-6, TNF-α, SAA, and HDL may serve as markers of subclinical inflammation in FMF patients. Due to increased plasma HDL levels, antiinflammatory and antioxidant effects may elevate in FMF patients.

The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats.

The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1ß levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and 0.1% toluidine blue. TNF-α, IL-1ß, and MDA levels and hydroxyproline content significantly increased (p < 0.01) and GPx and SOD activities significantly decreased in bleomycin group (p < 0.01). Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1ß activity, hydroxyproline content, and MDA level (p < 0.01) and increased GPx and SOD activities (p < 0.05). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.

Alterations of serum brain type natriuretic peptide (BNP) in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is known to be associated with cardiac damage. Brain type natriuretic peptide (BNP) is secreted from stressed myocardium. OBJECTIVES: This study investigated that BNP levels in CCHF and its association with clinical course of disease. METHODS: Consecutive CCHF diagnosis confirmed patients were enrolled to the study. Results of patients were compared with age-sex-matched healthy volunteers. Blood samples for BNP levels were collected from the patients during emergency room applications. Mortality, hospitalization duration and other disease severity predictors (thrombocyte count, hemoglobin, white blood cell count, alanine aminotransferase, aspartate aminotransferase, prothrombin time, lactate dehydrogenase, international normalized ratio, activated partial thromboplastin time) were recorded. These parameters' correlations with BNP levels were analyzed. RESULT: Forty-three CCHF patients and 28 control subjects recruited to the study. Groups were similar for age and gender. There was no mortality. Levels of BNP were found to be significantly higher in patients than control subjects (100.4±45.4 vs. 78.0±40.4, P=0.033). But BNP levels were not correlated with duration of hospitalization and disease severity predictors (P > 0.05). CONCLUSIONS: This study showed that BNP levels are modestly increased in CCHF but this increase does not correlated with disease severity predictors.

Important of Angiopoietic System in Evaluation of Endothelial Damage in Children with Crimean-Congo Hemorrhagic Fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) causes endothelial activation and dysfunction by affecting the endothelium directly or indirectly. In maintaining the vascular integrity, vascular endothelial growth factor (VEGF-A) and its receptor (VEGFR1) and angiopoietin-2 (Ang-2) and its receptor (Tie-2) are very important mediators. For this reason, we aimed at studying the association of Ang-2 and VEGF and their receptors Tie-2 and VEGFR1 with CCHF infection. METHODS: Thirty one CCHF patients and 31 healthy controls (HC) were included in the study. CCHF patients were classified into 2 groups in terms of disease severity (severe and nonsevere). VEGF-A, VEGFR1, Ang-2 and Tie-2 levels were measured in all groups. RESULT: Serum levels of Tie-2, Ang-2, VEGF-A and VEGFR1 were significantly increased in CCHF patients compared with the HC. Furthermore, serum Tie-2, Ang-2, VEGF and VEGFR1 levels were found to be significantly higher in the severe group than in the nonsevere and HC groups (P < 0.05 and P < 0.001, respectively). Also, Tie-2, Ang-2, VEGF-A and VEGFR1 levels were significantly higher in the nonsevere group than in the HC group (P < 0.05). CONCLUSION: Having statistically significant higher Ang-2, Tie-2, VEGF-A and VEGFR1 levels in the severe group when compared with the other groups suggested that VEGF-related Ang-2/Tie-2 system played a critical role in the pathogenesis of the disease, and these markers could be used as the severity criteria.

Evaluation of endothelium functions by flow-mediated dilatation in pediatric patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a systemic viral disease that also affects the endothelium. Thrombocytopenia and hemorrhage are seen in this disease. But, the cause of thrombocytopenia is not clear. We hypothesized that endothelium dysfunction may be the cause of thrombocytopenia. We evaluated the endothelium functions by flow-mediated dilatation (FMD) in CCHF. METHODS: Consecutive children with suspected CCHF who applied to our hospital were evaluated for recruitment into the study. FMD analysis was done in the active and healing period of the disease. Diagnosis was confirmed or ruled out by polymerase chain reaction and/or ELISA test. Basal brachial artery diameter (BBAD) and dilated brachial artery diameter (DBAD) after ischemic period were measured and percent dilatations [(DBAD-BBAD)/BBAD, FMD%] were computed from all subjects. RESULTS: Fifty-four children (40 male, mean age 12.4 ± 4.4 years) were recruited into the study. CCHF diagnosis was confirmed in 28 children and ruled out in 26 children. Groups were similar for age and gender. FMD% was significantly decreased in CCHF patients when comparing this with the control patients in the active period (2.65 ± 2.76 vs. 13.76 ± 7.95, P < 0.001). FMD% was correlated with platelet count in the active period of the disease (r = 0.599, P = 0.004). FMD% was recovered in the healing period (2.65 ± 2.76 vs. 14.72 ± 2.66, P < 0.001) and was not significantly different from basal values of control patients (P > 0.05). CONCLUSIONS: FMD is significantly decreased in CCHF and recovers in the healing period. So, endothelium functions are disturbed, and disturbance is correlated with thrombocytopenia in CCHF.

Predictive role of neutrophil gelatinase-associated lipocalin in early diagnosis of platin-induced renal injury.

BACKGROUND: Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure. MATERIALS AND METHODS: Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury. RESULTS: Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/ mg (p=0.243) in the oxaliplatin group. CONCLUSIONS: Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine.

Evaluation of serum perforin, caspase-3, sFasL and M-30 levels as apoptotic markers in children with Crimean-Congo hemorrhagic fever.

BACKGROUND: Apoptosis is a main regulator in responses of cellular immunity throughout systemic viral infections. Perforin, soluble Fas ligand, caspase-3 and caspase-cleaved cytokeratin-18 (M-30) are mediators of apoptosis. The aim of this study is the evaluation of Crimean-Congo hemorrhagic fever (CCHF) disease changes in the levels of these apoptotic markers and the relation of these changes with disease severity. METHODS: Forty-nine hospitalized children with CCHF and 36 healthy controls were enrolled in this prospective study. The CCHF patients were classified into 2 groups based on disease severity (severe group and nonsevere group). Demographic characteristics and clinical and laboratory findings of all patients were recorded on admission. RESULTS: Serum perforin, caspase-3 and soluble Fas ligand levels were found to be significantly higher both in the severe and nonsevere CCHF groups than the healthy control group (P < 0.05), but there was no significant difference in these apoptotic markers between severe and nonsevere CCHF groups (P > 0.05). In addition, serum M-30 levels did not differ significantly among all groups (P > 0.05). There was a positive correlation between serum values for perforin, caspase-3 and M-30 and the disease's severity criteria such as aspartate aminotransferase and/or alanine aminotransferase. The serum levels of all these markers were negatively correlated with disease severity criteria such as the platelet count. CONCLUSIONS: In this study, we concluded that the interactions of cytolytic granules containing perforin and caspase cascade and Fas-FasL may play an important role in the pathogenesis of CCHF in children.

The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study.

BACKGROUND: Severe burn induces systemic inflammation and reactive oxygen species leading to lipid peroxidation which may play role in remote organs injury. Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil reduces oxidative stress and inflammation in distant organs. The aim of the present study was to evaluate the effects of different dosages of sildenafil in remote organs injury. METHODS: A total of thirty-two rats were randomly divided into four equal groups. The groups were designated as follows: Sham, Control, 10, and T20 mg/kg sildenafil treatment groups. Levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), VEGF receptor (Flt-1), activities of glutathione peroxidase (Gpx), levels of total antioxidative capacity (TAC), and total oxidant status (TOS) were measured in both tissues and serum, and a semi-quantitative scoring system was used for the evaluation of histopathological findings. RESULTS: Sildenafil increased levels of Gpx, and Flt-1, and decreased MDA and VEGF levels in tissues. Sildenafil also increased serum levels of TAC and Flt-1 and decreased TOS, OSI, and VEGF. CONCLUSION: Sildenafil decreased inflammation scores in remote organs in histopathological evaluation. It has protective effects in severe burn-related remote organ injuries by decreasing oxidative stress and inflammation.

Evaluation of cytokines as Th1/Th2 markers in pathogenesis of children with Crimean-Congo hemorrhagic fever.

Cytokine networks play a key role in the pathogenesis of the disease in Crimean-Congo Hemorrhagic Fever (CCHF) patients. Therefore, our aim was to study the effects of cytokine levels on the pathogenesis and severity of the disease in children with CCHF. Fifty-two patients diagnosed with CCHF and 34 healthy controls (HC) were included in the study. The patients with CCHF were divided into two groups (severe and non-severe). The levels of the Interleukin-10 (IL-10), IL-12, IL-6, Endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) were measured in all groups. IL-12 levels did not show any difference between the CCHF and HC groups and among the severe, non-severe and HC groups. IL-10 and ET-1 levels were significantly higher in the severe group when compared to the non-severe group and the HC group. Moreover, IL-10 and ET-1 levels were significantly higher in the non-severe group when compared to the HC group. In terms of IL-6 and TNF-α levels, there was no difference between the severe and non-severe groups while the said levels were significantly higher in the severe group when compared to the HC group. The results of the present study showing significantly higher IL-10 and ET-1 levels in the severe group suggest that Th2-mediated humoral immunity is more effective in the pathogenesis and severity of CCHF in children.

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

BACKGROUND: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). METHODS: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120 mL per minute and above 120 mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. RESULTS: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR < 120 mL per minute than in patients with eGFR ≥ 120 mL per minute. sNGAL, uIL-18, and uNGAL were correlated significantly with urinary albumin excretion, additionally, were inverse correlated with eGFR. The most remarkable findings of this study are of the higher values of sIL-18, sNGAL, uIL-18, and uNGAL in both normoalbuminuric FMF patients and patients with eGFR ≥ 120 mL per minute. CONCLUSIONS: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.

Evaluation of the serum levels of soluble IL-2 receptor and endothelin-1 in children with Crimean-Congo hemorrhagic fever.

We aimed to assess the association between serum levels of soluble IL-2 receptor (sIL-2r) and endothelin-1 and severe infection in children with Crimean-Congo hemorrhagic fever (CCHF). Fifty-two patients under 18 years of age with a laboratory- confirmed diagnosis of CCHF and 38 healthy controls were enrolled in the study. Patients were classified into two groups based on disease severity (severe group and non-severe group). The sIL-2r and endothelin-1 levels were observed to be significantly higher in patients with severe CCHF compared with those with non-severe CCHF and the control group (p < 0.05). In addition, those with non-severe CCHF were also found to have a significantly higher sIL-2r level relative to the control group (p < 0.001). Although there was a positive correlation between sIL-2r and endothelin-1 levels, serum levels of both sIL-2r and endothelin-1 were negatively correlated with the platelets count. In children with CCHF, serum levels of sIL-2r and endothelin-1 were increased, and this increase is related to the severity of the disease. In this study, we concluded through prognosis that serum levels of sIL-2r and endothelin-1 might be related, and that hemophagocytic lymphohistiocytosis and endothelial injury might contribute to a pathogenesis of the disease.

Red cell distribution width and hypertensive response to exercise in patients with type 2 diabetes mellitus.

OBJECTIVE: There is no study about hypertensive response to exercise (HRE), which is a marker of unborn hypertension (HT), and red cell distribution width (RDW) association, in diabetic normotensive patients. So, we aimed to investigate any correlation among RDW and HRE in normotensive type 2 diabetic patients. METHODS: Consecutive type 2 diabetic patients without history of HT and with normal blood pressure (BP) on ambulatory BP monitoring were included to the study. We divided the patients into two groups depending on their peak systolic BP on exercise; HRE (Group 1) or normal response to exercise (Group 2). RESULTS: Data of 75 diabetic patients (51.9 ± 9.7) were analyzed (31 male (48%)). Their mean RDW was 13.11 ± 0.46. Patients with HRE were significantly older than patients without HRE. Smoking was more frequent in Group 2. Gender distribution and body mass index were similar between the groups. Else hemoglobin, hematocrit, red blood cell count and RDW values were not significantly different. Office systolic BP and diastolic BP, daytime and 24-h systolic BP were significantly higher in Group 1 but heart rate was similar between the groups. CONCLUSIONS: This study revealed that RDW do not differ between diabetic normotensive patients with HRE or not.