Increased Levels of VEGF-A and HIF-1α in Turkish Children with Crimean-Congo Hemorrhagic Fever.

BACKGROUND: Crimean-Congo Hemorrhagic Fever (CCHF) is a disease characterized by serious course, including acute viral fever, ecchymosis, thrombocytopenia, liver dysfunction and high rate of mortality. Hypoxia Inducible Factor-1α (HIF-1α) and Vascular Endothelial Growth Factor-A (VEGF-A) play an important role both in the inflammatory process and plasma leakage. The aim of this study was to define HIF-1α and VEGF-A serum levels obtained from CCHF patients and control group and to investigate whether these factors were correlated with the pathogenesis of this disease. METHODS: Thirty cases younger than 17yr confirmed by RT-PCR and/or ELISA for CCHF were included in this study. Thirty age and sex matched healthy peoples were enrolled as controls. Blood samples collected from the patient and control groups. Serum levels of HIF-1α and VEGF-A were measured with ELISA. RESULTS: Levels of HIF-1α and VEGF-A were statistically significantly increased in CCHF patients compared to the control group (P< 0.05). A significant positive correlation was found between the levels of HIF-1α and VEGF-A in the patient group (P< 0.01). The levels of ALT, AST, CK, aPTT, WBC and Thrombocyte count were significantly higher in the patients than in the control group (P< 0.001). A positive correlation was found among the levels of AST and CK from biochemical parameters and VEGF and HIF-1α in the patient group (P< 0.05). CONCLUSION: HIF-1α and VEGF-A might play an important role in CCHF pathogenesis.

SDF-1/CXCL12 and CXCR4 gene variants, and elevated serum SDF-1 levels are associated with preeclampsia.

OBJECTIVE: We aimed to compare the frequencies of stromal cell-derived factor-1 (SDF-1) 3'A and CXCR4 single-nucleotide polymorphisms (SNPs) and serum SDF-1 levels in patients with preeclampsia (PE). METHODS: In total, 89 women with PE and 89 control women were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. Enzyme-linked immunosorbent assay method was used to measure serum SDF-1 level. RESULTS: For SDF-1 3'A SNP, the frequency of GA genotype, total number of GA and AA genotypes, and the A allele frequency was higher in PE patients than controls (p = 0.04, 0.023, and 0.029, respectively). For CXCR4 SNP, the frequency of CT genotype, total number of CT and TT genotypes, and the T allele frequency were higher in PE patients than controls (p = 0.04, 0.006, and 0.005, respectively). SDF-1 serum level was detected higher in preeclamptic women compared with controls (p = 0.001). In PE patients, there was no significant association between serum SDF-1 levels and genotypes of SDF-1 3'A SNP. SDF-1 level was significantly higher in patients bearing CXCR4 CT genotype than CC genotype (p = 0.001). Furthermore, SDF-1 levels in patients bearing CT+TT genotype were found higher than that of patients with CC genotypes (p = 0.001). CONCLUSION: Results of our study suggest that SDF-1 3'A and CXCR4 polymorphisms and elevated serum SDF-1 levels may have a role in the development of PE.

Angiotensin-Converting Enzyme (ACE) I/D and Alpha-Adducin (ADD1) G460W Gene Polymorphisms in Turkish Patients with Severe Chronic Tinnitus.

OBJECTIVE: Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. MATERIALS AND METHODS: The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. RESULTS: With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (p<0.01) and allele frequencies (p=0.021) of the ADD1 G460W gene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (p<0.01). CONCLUSION: Our results demonstrate an association between ADD1 G460W gene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.

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 Maternal Serum 25-Hydroxyvitamin D, Paraoxonase 1 Levels, and Neutrophil-to-Lymphocyte Ratio in Spontaneous Preterm Birth.

BACKGROUND The aim of this study was to evaluate the association of maternal serum 25-hydroxyvitamin D, paraoxonase 1, and neutrophil-to-lymphocyte ratio in women having early spontaneous preterm birth without clinical chorioamnionitis. MATERIAL AND METHODS This study was prospectively administered in women referred to our obstetrics service with preterm labor that resulted in preterm birth (n=35) and term labor that ended in term birth (n=44). The maternal serum levels of 25-hydroxyvitamin D and paraoxonase 1 were measured and neutrophil-to-lymphocyte ratio was calculated. RESULTS The 25-hydroxyvitamin D and paraoxonase 1 levels of the preterm group were significantly lower than those of the term group (p<0.05). The neutrophil-to-lymphocyte ratio value of the preterm group was significantly higher than that of the term group (p<0.05). There was a significant but small positive correlation between the serum levels of 25-hydroxyvitamin D and paraoxonase 1 in the preterm group (r=0.35; p=0.021). CONCLUSIONS Decreased maternal serum 25-hydroxyvitamin D and paraoxonase 1 levels and increased neutrophil-to-lymphocyte ratio may have a role in the etiology of spontaneous preterm birth.

Elevated Serum CD95/FAS and HIF-1α Levels, but Not Tie-2 Levels, May Be Biomarkers in Patients With Severe Endometriosis: A Preliminary Report.

STUDY OBJECTIVE: To evaluate serum values of cluster of differentiation 95 (CD95/FAS), hypoxia-inducible factor 1-alpha (HIF-1α), and tyrosine kinase receptor 2 (Tie-2) as possible biomarkers of disease presence and severity in women with endometriosis, and to characterize the changes in these values in women with stage I/II and stage III/IV endometriosis. DESIGN: Prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Thirty women with endometriosis and 30 healthy women without endometriosis. INTERVENTION: For the diagnosis of endometriosis and prediction of its severity, we measured the serum levels of CD95/FAS, which assess apoptotic conditions, and of HIF-1α and Tie-2, which assess angiogenesis. Endometriosis was diagnosed and staged through surgical laparoscopy and later confirmed histologically. During the surgery, the patients with endometriosis were divided into 2 groups based on disease stage. Eleven patients had stage I/II endometriosis, and 19 had stage III/IV endometriosis. MEASUREMENTS AND MAIN RESULTS: Endometriosis was associated with increased serum CD95/FAS and HIF-1α levels, but not Tie-2 levels. We also determined that stage III/IV endometriosis was associated with higher serum CD95/FAS and HIF-1α levels, but not Tie-2 levels, compared with stage I/II endometriosis. CONCLUSION: Endometriosis, in accordance with its severity, increases serum CD95/FAS and HIF-1α levels, but not Tie-2 levels. These biomarkers may be useful for reproductive surgeons to improve the quality of counseling women about the presence and severity of endometriosis.

Serum levels of ET-1, M30, and angiopoietins-1 and -2 in HELLP syndrome and preeclampsia compared to controls.

PURPOSE: We aimed to compare the serum levels of ET-1, M30, and Angs-1 and -2 in patients with preeclampsia or HELLP syndrome, and normal controls. METHODS: In this cross-sectional study of 74 pregnant women, serum levels of ET-1, M30, and Angs-1 and -2 were measured in preeclamptic patients with or without HELLP syndrome. 74 pregnant women; 37 had healthy pregnancies, 25 had preeclampsia (PE), and 12 had HELLP syndrome. RESULTS: The age, body mass index, gravidity, and parity of patients with normal pregnancy, PE, and HELLP syndrome were comparable (p > 0.05). In HELLP syndrome, compared to healthy or preeclamptic pregnancies, platelet count was lower (p < 0.05) and the values of hepatic function tests were higher (p < 0.05). In HELLP syndrome, ET-1, M30, and Ang-2 were higher compared to healthy or preeclamptic pregnancies (p < 0.05); however, they increased in preeclamptic pregnancies compared to healthy pregnancies though not significant (p > 0.05). In PE or HELLP syndrome, Ang-1 was higher compared to a healthy pregnancy (p < 0.05); however, in HELLP syndrome, it was also higher than in PE though not significant (p > 0.05). We found no significant correlation among these biomarkers and hematological and biochemical parameters (p > 0.05). CONCLUSION: For the diagnosis of HELLP syndrome, increased levels of ET-1, M30, and Angs-1 and -2 appear as promising biomarkers after determination of their standardized threshold levels after further studies. As an apoptosis-related biomarker, serum M30 level has a merit to be the most promising test for prediction or differential diagnosis of HELLP syndrome in PE patients.

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.

Value of ABO blood group in predicting the severity of children with Crimean-Congo hemorrhagic fever.

PURPOSE: The aim of this study was to assess the role of ABO blood groups in predicting disease severity and bleeding potential in children with Crimean-Congo hemorrhagic fever (CCHF). METHODS: One hundred fifty-one hospitalized patients with CCHF were enrolled in this retrospective study. The patients were divided according to O- and non-O- (A, B and AB) blood groups (n=91 and n=60, respectively). They were also classified into two groups (severe and non-severe) based on disease severity (n=29 and n=122, respectively). Demographic characteristics, clinical findings, and hematologic and biochemical parameters of all patients were recorded on admission and discharge. RESULTS: Although, in all cases, compared to the non-O blood group, the ratio of the blood group O was considerably higher (60% vs. 40%) and similarly so in severe cases (58.6% vs. 41.4%), this difference was not statistically significant (p>0.05). The aPTT at discharge and fever duration of the O-blood group were significantly higher than those of the non-O-blood group (p=0.042, p=0.034, respectively). The factor VIII level of the O-blood group was significantly lower than that of the non-O-blood group (p=0.040). Although the ratios of bleeding and severity were higher in the O-blood group compared to the other group, statistical significance was not reached (p>0.05). CONCLUSIONS: Consideration of the ABO blood group is important during diagnostic follow-up to assess the severity of CCHF. In clinical practice, pediatric CCHF patients with the O blood group need to be followed closely for tendency to bleed.

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.

Evaluation of renal involvement in children with Crimean-Congo hemorrhagic fever.

The aim of the present study was to evaluate renal involvement in children with Crimean-Congo hemorrhagic fever (CCHF). Forty-four children infected with CCHF virus and 30 controls were enrolled in the study. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine protein levels were measured in the patient and control groups. Clinical and laboratory findings of the patient and control groups were compared. uNGAL levels were higher in the patient group than that in the control group (P < 0.001). Of the 44 patients, 26 (59.1%) were proteinuric. uNGAL levels in proteinuric patients were higher than those in non-proteinuric patients (P = 0.035). There was a positive correlation between uNGAL and urine protein levels in the patient group. (R = 0.614, P < 0.001). Due to renal involvement, increased proteinuria and increased uNGAL levels were observed in children with CCHF. In these children, measuring urine total protein and uNGAL levels can be useful to monitor renal involvement due to CCHF.

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.