Enver Sancakdar

Is Neutrophil/Lymphocyte Ratio Associated with Subclinical Inflammation and Amyloidosis in Patients with Familial Mediterranean Fever?

Background. The purpose of the present study is to determine the association between neutrophil/lymphocyte ratio and both subclinical inflammation and amyloidosis in familial Mediterranean fever. Methods. Ninety-four patients with familial Mediterranean fever and 60 healthy volunteers were included in the study. Of the patients, 12 had familial Mediterranean fever related amyloidosis. The neutrophil/lymphocyte ratio of the patients was obtained from the hematology laboratory archive. Results. The neutrophil/lymphocyte ratio was significantly higher among persons with familial Mediterranean fever compared to healthy individuals (P < 0.0001). Also, neutrophil/lymphocyte ratio was significantly higher in patients with amyloidosis than in amyloidosis-free patients (P < 0.0001). Since NLR was evaluated in nonamyloid and amyloid stages of the same patient population (type 1 phenotype), we obtained significant statistical differences (1.95 ± 0.30 versus 2.64 ± 0.48, P < 0.05, resp.). With the cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (P = 0.009), it was a reliable marker in predicting the development of amyloidosis. Conclusion. The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in patients with familial Mediterranean fever in attack-free periods. The neutrophil/lymphocyte ratio may be a useful marker in predicting the development of amyloidosis.

Bradycardia seen in children with Crimean-Congo hemorrhagic fever.

INTRODUCTION Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease with a high mortality rate. In clinical practice, we observed bradycardia in some pediatric patients with CCHF during the clinical course. So we aimed to report CCHF cases that presented bradycardia during the clinical course and the relation of bradycardia with the clinical findings and ribavirin therapy. METHODS Charts of all hospitalized pediatric CCHF patients were reviewed with respect to age, sex, history of tick bite or history of removing a tick, other risk factors for CCHF transmission, and interval between the tick bite and the onset of symptoms. Outcomes and clinical and laboratory findings and medications were recorded for each patient. We searched the patient records for information regarding the existence of bradycardia. Bradycardia was accepted as the heart rate 2 standard deviations (SD) lower than the suspected heart rate based on age. RESULTS Fifty-two patients (mean age 11.2 ± 4.4 years, 31 female) were enrolled into the study. Bradycardia was seen in seven patients. Six patients with bradycardia were male and only one was female, and the mean age was 13.1 ± 1.6 years. It was observed that male gender is frequent among patients with bradycardia, as compared with those without bradycardia (p=0.01). Bleeding was found to be more frequent in patients with bradycardia (p=0.02). There were significant differences between the bradycardia and nonbradycardia groups with regard to the requirements for fresh frozen plasma transfusion, the number of platelet suspension given, requirement for intravenous immune globulin (IVIG) and in the days of stay in hospital (p=0.01, p=0.03, p=0.03, p=0.04, respectively). CONCLUSION Reversible bradycardia might be seen in the clinical course of pediatric CCHF patients, and the clinicians must be aware of this finding. The possibility that ribavirin may potentiate bradycardia cannot be assessed without a placebo-control study. So further studies may help to reveal the cause of the bradycardia, the disease itself, or the ribavirin therapy. Hence this study supports the need for a randomized, placebo-controlled study to assess intravenous ribavirin in treating CCHF and to support approval of the drug.

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.

Renalase gene polymorphism is associated with increased blood pressure in preeclampsia

BACKGROUND Renalase is a novel enzyme that degrades circulating catecholamines. We aimed to investigate the role of rs2576178 and rs10887800 polymorphisms of the renalase gene in preeclampsia (PE) patients METHODS This case-control study consisted of 110 women with PE and 102 normotensive controls. PCR-RFLP method was used for determination of renalase gene polymorphisms. RESULTS Allele frequency and genotype distribution of rs10887800 polymorphism were found statistically significantly higher in women with PE (p<0.05). Also G allele and GG genotype of rs10887800 polymorphism were found higher in women with severe PE than that of mild PE (p<0.05). There was no significant difference for rs2576178 polymorphism in terms of allele frequency and genotype distribution (p>0.05). In PE patients, systolic blood pressure (SBP) means according to rs10887800 genotypes were found statistically significantly higher (GG vs AA; p=0.001) and (GG vs GA; p=0.001). Similarly, diastolic blood pressure (DBP) means were found statistically significantly higher in PE patients (GG vs GA: p=0.001); (GG vs AA: p=0.004). For rs2576178 polymorphism, SBP means were found as (GG vs AA; p=0.012, GG vs GA; p>0.05) in PE patients. DBP means were not significant according to rs2576178 genotypes in PE patients (p>0.05). CONCLUSIONS The findings of the present study suggest that blood pressure may be increased by GG genotype and G allele of rs10887800 polymorphism and the polymorphism may increase the susceptibility to PE.

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.

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

Abstract 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 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.

Serum adiponectin, leptin, and interleukin 6 levels as adipocytokines in children with febrile seizures The role of adipose tissue in febrile seizures

Proinflammatory and anti-inflammatory cytokines have an important role in the pathogenesis of febrile seizures (FS). Adipocytokines like interleukin 6 (IL-6), leptin, and adiponectin released from adipose tissue play a role in inflammation. This study aimed to assess the probable role of adipose tissue in children with FS. We measured serum IL-6, leptin, and adiponectin levels and evaluated clinical and laboratory findings in children with FS (n = 32) and compared the results with the values of children of the same age with febrile illness without seizures (febrile control, FC; n = 26) and healthy control group (HC; n = 29). The serum levels of white blood cells, C-reactive protein, IL-6, leptin, and adiponectin were found to be significantly higher, while serum hemoglobin (Hb) levels were found to be significantly lower in FS and FC groups than in the HC group (p < 0.001). When we compared the FS with the FC group, the serum Hb levels were significantly lower in the FS group than those in the FC group (p = 0.001). There was no significant difference between the FS and FC group with regard to the serum levels of these adipocytokines (p > 0.05). Our data showed that elevated levels of these adipocytokines as acute phase reactants in FS and FC groups did not contribute to the development of FS.

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.

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.