Relationship between Vitamin D Level and Index of Cardio Electrophysiological Balance in Children.

BACKGROUND: Vitamin D deficiency has been found to be associated with various cardiovascular disorders, including hypertension, coronary artery disease, heart failure, peripheral vascular diseases, and sudden cardiac death. In the literature, it has been reported that many electrocardiographic parameters have been developed to predict ventricular arrhythmias. In recent studies, it is noteworthy that the index of cardio-electrophysiological balance (iCEB) and correct cardio-electrophysiological balance (iCEBc), which are electrocardiographic parameters, can be used as new, easy, cheap and non-invasive parameters to predict ventricular arrhythmias. OBJECTIVE: This study aimed to investigate the relationship between vitamin D deficiency and iCEB and iCEBc values in children. METHODS: A total of 186 patients were included in this study. Group 1 included 114 patients with vitamin D levels below 20 ng/ml; 50 patients with vitamin D levels of 21-29 ng/ml were included in Group 2; Group 3 consisted of 36 patients with a vitamin D level above 30 ng/ml. iCEB and iCEBc values were calculated by taking 12-lead ECG from all individuals and comparing them between groups. RESULTS: A total of 186 children, 114 subjects in Group 1, 36 subjects in Group 2, and 36 subjects in Group 3, were included in the study. Demographic characteristics and height-weight values of the groups were similar. Significant differences were found between the groups in terms of QT, QTc, QT/QRS, and QTc/QRS levels (p: 0.003, 0.028, 0.001, and 0.001, respectively). In the correlation analysis, a negative correlation was found between QTc/QRS and vitamin D level (r=-0.320, p=<0.001) and between QT/QRS and vitamin D level (r=-0.268, p=<0.001). Moreover, vitamin D level (ß=0.389, p<0.001) was determined as an independent predictor of QTc/QRS in multivariate logistic regression analysis. CONCLUSION: iCEB and iCEBc parameters increase significantly in children with low vitamin D levels. These parameters are also evaluated during the follow-up of children with vitamin D deficiency in terms of the risk of ventricular arrhythmia. iCEBc can be used as an easy, inexpensive, non-invasive, and reproducible parameter.

Toxoplasmosis: A Timeless Challenge for Pregnancy.

This study aimed to evaluate the prevalence of toxoplasmosis in pregnant women, as well as the general characteristics, clinical and laboratory findings, and pregnancy and fetal outcomes of pregnant women diagnosed with acute toxoplasma infection (ATI). The toxoplasma IgM, IgG, and IgG avidity test results of pregnant women who applied to our referral hospital between January 2016 and June 2022, and among them, those diagnosed with ATI, were analyzed. The 119 patients diagnosed with ATI during this time period were included for further analysis. The prevalence of toxoplasmosis in pregnant women was found to be 46.2%, and the rate of ATI was 4%. The total mother-to-child transmission rate was 5% (5/101). Congenital toxoplasmosis (CT) was observed in 1 (1.1%) child of the 87 pregnant women who received spiramycin prophylaxis, though it was found in 4 (30.8%) of the children of the 13 untreated mothers. With respect to prenatal treatment, CT rates were significantly higher in the children born to untreated mothers (p = 0.001). In conclusion, although toxoplasma seroprevalence was found to be high in our region, there was a paucity in diagnosis, follow-up, and treatment. Our findings support that prenatal spiramycin prophylaxis is effective in preventing the transmission of parasites from mother to child.

Amino acids profile in children with acute brucellosis.

BACKGROUND: Many new cases of brucella infections are seen in Turkey every year, especially in March, April, and May, due to the consumption of local unpasteurized cheese. Amino acids profiles have not been studied in brucellosis so far. INTRODUCTION: The amino acid profiles may be affected by infectious diseases. Our study aims to evaluate the plasma amino acid profile in the progression of acute brucellosis. METHODS: Plasma amino acid profile was performed by an 8045 LC-MS / MS device (Shimadzu 8045, Japan) using JASEM amino acid kit. RESULTS: Analysis of 45 amino acid profiles was made and results profiles showed significant differences in concentrations and types of amino acids in brucella patients. We observed a significant difference in terms of alanine, arginine, aspartic acid, glutamine, glutamic acid, glycine, isoleucine, ornithine, phenylalanine, proline, tyrosine, valine, alpha-aminoadipic acid, alpha-amino-pimelic acid, argininosuccinic acid, gamma-aminobutyric acid, thiaproline, 1-methylhistidine, 3-methylhistidine, hydroxylysine, hydroxyproline, cystine, serotonin, ethanolamine, and taurine (p-value <0.05 for each). No significant differences were determined regarding asparagine, citrulline, histidine, leucine, alloisoleucine, lysine, methionine, serine, threonine, tryptophan, anserine, alpha aminobutyric acid, beta aminoisobutyric acid, beta-alanine, cystathionine, histamine, and 5-oh-trp (p-value >0.05 for all). CONCLUSION: Patients with brucellosis have a specific profile of amino acids which may reflect sequelae of pathological and metabolic biochemical changes in the disease process due to the growth of Brucella spp. in the human body leading to an imbalance of amino acid levels.

The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature.

This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied. The variants detected by the exome sequencing analysis were verified by Sanger sequencing and analyzed using SeqScape Software 3. It was determined that both the father of the family and his 2 wives carried the same variant heterozygously. Of the children born to the first mother, 2 children were normal, 3 were heterozygous and 5 were homozygous. Four of these 5 homozygous children were diagnosed with Hodgkin lymphoma. Of the children born to the second mother, 1 child was normal, 3 children were heterozygous and 2 children were homozygous, and none of them had developed a malignant event. We also showed that CD27 deficiency may enhance Treg differentiation. According to our information, this study augmented the relationship of Hodgkin lymphoma and CD27 deficiency. The detection of homozygous CD27 variant in all siblings who developed lymphoma strengthened the place of this mutation in the etiology of Hodgkin lymphoma. In contrast, the presence of homozygous siblings with no malignant event suggested the possible contributions of environmental factors on the etiology.

Interleukin-33 and oxidative stress in epilepsy patients.

OBJECTIVE: Inflammation and oxidative stress plays an important role in the etiology of epilepsy. Interleukin-33 (IL-33), a new member of the cytokine family associated with interleukin-1 (IL-1), has been found to play a role in pathogenesis of central nervous system diseases and cause the production of proinflammatory cytokines and oxidative stress molecules. Our aim was to investigate IL-33 and oxidative stress values (total antioxidant capacity (TAS), total oxidant capacity (TOS), and oxidative stress index (OSI)) in patients with epilepsy and to evaluate their relationship with each other. METHODS: The study included 60 patients with epilepsy and 35 healthy controls. The group of patients with epilepsy consisted of 21 patients with treatment-resistant epilepsy and 39 patients with well-controlled epilepsy. The patients with epilepsy were also classified as monotherapy and polytherapy group according to the number of antiepileptic drugs they used, and focal and generalized epilepsy group according to the seizure type. Serum IL-33, TAS, TOS and OSI levels were measured in the patients with epilepsy and the control group. RESULTS: The mean serum TAS level was significantly lower in the all patients with epilepsy group compared to the control group, and the mean serum IL-33, TOS, and OSI levels were significantly higher. The mean serum TOS and OSI levels were significantly lower and TAS levels were significantly higher in the patients with well-controlled epilepsy than the patients with treatment-resistant epilepsy. While there was a positive correlation between serum IL-33 and OSI levels in the all patients with epilepsy group, a negative correlation was shown between IL-33 and TAS levels. CONCLUSION: The IL-33/ST2 pathway may represent a new promising therapeutic strategy both for the treatment and the prevention of the disease.

Impaired Thiol/Disulfide Homeostasis in Children Diagnosed with Autism: A Case-Control Study.

Although genetic factors occupy an important place in the development of autism spectrum disorder (ASD), oxidative stress and exposure to environmental toxicants have also been linked to the condition. The aim of this study was to examine dynamic thiol/disulfide homeostasis in children diagnosed with ASD. Forty-eight children aged 3-12 years diagnosed with ASD and 40 age- and sex-matched healthy children were included in the study. A sociodemographic data form was completed for all the cases, and the Childhood Autism Rating Scale (CARS) was applied to the patients. Thiol/disulfide parameters in serum were measured in all cases and compared between the two groups. Mean native thiol, total thiol concentrations (µmol/L), and median reduced thiol ratios were significantly lower in the ASD group than in the control group (p = 0.001 for all). Median disulfide concentrations (µmol/L), redox potential, and median oxidized thiol ratios were significantly higher in the ASD group than in the control group (p = 0.001, p = 0.001, and p = 0.001, respectively). ROC analysis revealed that area under the curve (AUC) values with "excellent discriminatory potential," for native thiol, total thiol, the reduced thiol ration, the oxidized thiol ratio, and redox potential and with "acceptable discriminatory potential" for disulfide were significantly capable of differentiating individuals with ASD from healthy individuals. No correlation was determined between the severity of autism and laboratory parameters. Impaired dynamic thiol/disulfide homeostasis was observed in children with ASD, suggesting that dynamic thiol/disulfide homeostasis in serum may be of diagnostic value in autism.

In Vitro Demonstration of Drug-Reagent Interactions Among Commonly Used Parenteral Drugs in Cardiology.

BACKGROUND: Drug-drug interactions are undesirable, as they reduce drug bioavailability. Drug-reagent interactions in biochemical tests may directly affect the accuracy of test results. OBJECTIVE: The aim of the present study was to investigate the impact of drug-reagent interactions of drugs used in cardiology on different cardiac markers (troponin I, Nt-proBNP, CK-MB mass, CK, AST, and LDH) and the D-dimer test. METHODS: Eleven drugs (enoxaparin, tirofiban hydrochloride monohydrate, diltiazem, glyceryl trinitrate, metoprolol, epinephrine, heparin sodium, atropine sodium, furosemide, norepinephrine tartrate, and amiodarone HCl) were tested in an interference study. The interference protocol was applied to the control material of troponin I, CK-MB mass, Nt-proBNP, CK, AST, LDH tests with 11 different drugs and performed with analyzers. Cardiac Markers Plus Control (Bio-Rad, Irvine, CA, USA; Lot: 23662) materials were used to assess the impact of drug-reagent interactions on the accuracy of tests of cardiac markers based on immunoassay methods. The bias rate, defined as the extent of deviation from the target value (bias %), in the interference study was calculated in each test. RESULTS: For all 11 drugs, positive interference in the range of 43.58% to 130.06% occurred in the CK-MB mass test, whereas positive interference in the range of 11.98% to 107.44% occurred in the troponin I test. All the drugs, except enoxaparin sodium, led to negative interference in the range of - 84.21 to -29.6% in the Nt-proBNP test. In the D-dimer test, amiodarone HCl and diltiazem caused interference (122.87% and 28.08%, respectively). The percentage of interference caused by the other drugs ranged from -1.27% to 11.44%. Minimal deviations in the target values (between -3.31% and 3.86%) were observed in the CK, AST, and LDH tests measured using spectrophotometric methods. CONCLUSION: Parenteral drugs used in cardiology can significantly interfere with troponin I, CK-MB mass, Nt-proBNP, and D-dimer tests in the analytical phase because of drug-reagent interactions. Minimal deviations in the CK, AST, and LDH tests were observed using spectrophotometric methods. Thus, changes in test results may be due to drug interference rather than the treatment itself. Clinicians should consider the possibility of drug interference in cases of doubtful cardiac test results that do not comply with the diagnosis.

False Measurement of Blood Amino Acids by LC-MS/MS in a Patient Dependent on Matrix Effect after Total Parenteral Nutrition Infusion.

BACKGROUND AND AIM: Although it is widely known that the total parenteral nutrition (TPN) used frequently in intensive care units has unwanted side effects, there is little known about how it interferes with the amino acid levels taken during the diagnosis of metabolic diseases. Amino acid can lead to inaccurate measurements with mass spectrometry due to its high molecular content of lipids and carbohydrates, which modifies the blood matrix. The purpose of this study was to emphasize the results of amino acid interference, measured with mass spectrometry, in patients administered with TPN. CASE PRESENTATION: Incorrect clinical interpretation resulted in the case of a pneumonia patient with false positive and negative blood amino acid levels caused by TPN infusion. The amino acid profile had been requested to rule out an amino acid metabolic defect in the two-year-old boy who arrived at the pediatric clinic complaining of respiratory distress, tachypnea and hypoxemia. He was monitored in the intensive care unit for further investigation. The personnel who had performed phlebotomy also carried out the sampling during the TPN infusion administration. This caused the amino acid results and an incorrect interpretation. The following deviation ratios were detected: phenylalanine 102%, leucine 86%, isoleucine 106%, GABA 200%, citrulline 238%, glutamine 178%, ornithine 216%, 1- methyl-l-histidine 1471%, serine 312%, alanine 163%, glycine 355%, homocitrulline and carnosine 444%. The amino acid blood level measurements taken for diagnosis and screening in suspected metabolic disease may lead to involuntary false low or elevated results in patients administered with TPN. CONCLUSION: This case demonstrates that TPN solutions affect the reference method of mass spectrometry measurement methods due to the concentration of ingredients. We suggest that inaccurate results can be avoided by carrying out the sampling prior to TPN infusion in patients whose plasma amino acid levels will be measured.

Investigating the Levels of Brain-Specific Proteins in Hydrocephalus Patients.

BACKGROUND: Hydrocephalus, a common brain disorder in children, can cause permanent brain damage. A timely diagnosis of this disorder is crucial. OBJECTIVE: The aim of this study was to evaluate the levels of S-100, CK-18, and NSE brainspecific proteins in patients with hydrocephalus. We examined the levels of these proteins in the blood samples of hydrocephalic patients. METHODS: The study was conducted on the hydrocephalus (n = 31) patients and a healthy control group (n = 30). A Receiver Operating Characteristic (ROC) curve was used to assess the validity of the NSE, CK-18, and S100B to differentiate between the hydrocephalus and the control groups. The suitability of the data to the normal distribution was tested with the Shapiro Wilk test, and the Student t-test was used to compare the characteristics of the normal distribution in two independent groups. The individuals in the hydrocephalus and control groups had similar values in terms of age, height, and weight. RESULTS: It was observed that NSE, CK-18, and S100B mean values of the individuals in the hydrocephalus group were significantly higher than NSE, CK-18, and S100B mean values of the control group. CONCLUSION: Experiments have shown that the levels of these proteins increase significantly in hydrocephalus patients compared to the healthy group. These three parameters can be considered as important markers in the diagnosis of hydrocephalus.

Relationship Between Oxidative Stress, Tau Level and Antioxidant Mechanisms of the KEAP-1/NRF-2/HO-1 in Children with Hydrocephalus.

BACKGROUND: Hydrocephalus is a complex neurologic disorder that has a widespread impact on the central nervous system and a multifactor disease which affects the CSF dynamics and causes severe neurological impairments in children. The pathophysiology of hydrocephalus is not fully understood. However, increasing evidence suggests that oxidative stress may be an important factor in the pathogenesis of hydrocephalus. OBJECTIVE: The purpose of this study is to investigate the relationship of the KEAP-1/NRF-2/HO-1 pathway, one of the main regulators of the antioxidant system in the hydrocephalus pathology, on oxidative stress and tau protein level. METHODS: The study included 32 patients with hydrocephalus and 32 healthy controls. KEAP-1, NRF-2, HO-1, TAU, and MPO levels are measured using ELISA method TAS, TOS, and Total THIOL colorimetric method. RESULTS: KEAP-1, TAS, and Total THIOL levels were found significantly lowerer in the hydrocephalus group than in the control group. Nevertheless, it was identified that in the hydrocephalus group that the NRF-2, HO-1, TAU, MPO, TOS, and OSI levels were significantly elevated. CONCLUSION: In conclusion, although the KEAP-1/NRF-2/HO-1 pathway is activated in patients with hydrocephalus, it is identified that the antioxidant defense system is insufficient and ultimately leads to elevated oxidative stress. The elevation in the tau level may be an indicator of oxidative stress induced neurodegenerative damage.

Increased ischemia-modified albumin levels in children with steroid-sensitive nephrotic syndrome.

OBJECTIVE: Growing evidence shows that oxidative stress plays an important role in the development and progression of nephrotic syndrome (NS). In this study, we aimed to examine serum IMA levels as an indicator of oxidative stress in children with steroid-sensitive NS (SSNS) in remission and relapse. METHODS: This cross-sectional study was carried out at the Pediatric Nephrology Unit of Sanliurfa Training and Research Hospital, Sanliurfa, Turkey, from April 2019 to December 2019. In this study Serum IMA and albumin levels were determined in 70 children with SSNS and 45 healthy controls. Among the children with SSNS, 50 were in remission and 20 were in relapse. Then, adjusted IMA levels were calculated from the IMA/albumin ratio. RESULTS: IMA and adjusted IMA levels significantly increased and albumin significantly decreased in children with SSNS in relapse and remission compared with those of the healthy controls. Moreover, these alterations were more prominent in the relapse group than in the remission group. IMA was inversely correlated with albumin in children with SSNS (r= -0.881, p= <0.001). CONCLUSIONS: Our findings demonstrated that elevated IMA and adjusted IMA levels observed in patients with SSNS were associated with increased oxidative stress and could indirectly reflect the degree of oxidative damage in glomerular structures.

Enzyme Replacement Therapy may Affect Blood Immunosuppressant Monitoring.

BACKGROUND: Although LC-MS/MS is preferred as a reliable method, therapeutic enzyme drugs in the blood matrix may lead to false results. OBJECTIVE: The purpose of this article is to experimentally investigate the effect of five different enzymes used in the treatment of metabolic diseases on blood immunosuppressant measurement. METHODS: Five different enzyme drugs (galsulfase, alglucosidase alfa, imiglucerase, elosulfase alfa, laronidase) were added to control materials containing tacrolimus, everolimus, sirolimus, and cyclosporine A drugs. Measurements were performed using an LC-MS/MS instrument (Shimadzu 8040, Japan). The amount of deviations from the target values was calculated. RESULTS: Blood Immunosuppressant levels significantly changed after the administration of enzyme drugs. Four different enzyme drugs led to false-positive results in the tacrolimus levels at a rate of 10.58% (95% CI, 9.83-11.32) to 37.28% (95% CI, 33.55-41.27). The highest deviations were observed with the administration of galsulfase and alglucosidase alpha in the sirolimus levels at rates of 336.54% (95% CI, 306.25-366.82) and 395.88% (95% CI, 360.25-431.50), respectively. Imiglucerase was the least effective enzyme for the sirolimus level (0.80% (95% CI, 0.71-0.89). Different deviations between the ratios of - 9.37% (95% CI, -10.40 - -8.33) and 8.33% (95% CI, 7.41-9.24) were determined at the cyclosporin A level. CONCLUSION: Galsulfase, alglucosidase alpha, imigluserase, elosulfase alpha and laronidase can significantly interfere with immunosuppressant measurements with LC-MS/MS. False immunosuppressant results associated with enzyme injection may result in immunosuppression failure, organ rejection. For the measurement of immunosuppressant levels, sampling should be done before the enzyme infusion. Clinicians should question the time of enzyme infusion and sampling when confounding results in immunosuppressant measurement.

The Serum Prolidase Enzyme Activity as a Biomarker for Evaluation of the Subclinical Vascular Damage in Children with Epilepsy.

BACKGROUD: Epilepsy is a chronic medical condition requiring long term or even lifelong therapy. Various researches have shown that epilepsy patients have vascular risk factors such as abnormal lipids, insulin, elevated oxidative stress, chronic inflammation, and subclinical atherosclerosis. OBJECTIVES: The purpose of the present study was to determine serum prolidase enzyme activity as a biomarker in children taking antiepileptic drug treatment through comparison with control cases. MATERIALS AND METHODS: The present study group consists of 61 children (20 females, 41 males) with epilepsy and a control group was formed of 32 healthy individuals (14 females, 18 males). Aspectrophotometric method was used to measure serum prolidase enzyme activity. RESULTS: The epilepsy group demonstrated statistically significantly higher prolidase enzyme activity values when compared with the control group (P = 0.003). It was measured that the serum TOS and OSI values were significantly elevated in patients with epilepsy compared to controls (P < 0.001). However, serum TAS values were significantly lower in the epilepsy group than in the control group (P = 0.032). CONCLUSIONS: These results supported that epileptic patients taking the antiepileptic treatment had increased serum prolidase enzyme activity, suggesting that it may show an increased risk of subclinical vascular damage related to both chronic inflammation and fibrotic process associated with degenerated collagen turnover. Therefore, serum prolidase enzyme activity could be considered a useful biomarker for evaluation of the subclinical vascular damage in children with epilepsy on some antiepileptic drugs.

Assessment of thiol/disulfide balance as an oxidative stress marker in children with ß-thalassemia major.

OBJECTIVE: We aimed to investigate the oxidative stress status in children with ß-thalassemia major (ß-TM) by measuring native thiol (SH), disulfide (SS) and total thiol (SH + SS) plasma levels. METHODS: This study was carried out from November 2017 to March 2018 at the Pediatric Hematology Clinic of the Harran University Medical Faculty Hospital. Blood specimens were collected from 100 participants, including 50 ß-TM patients and 50 controls, and SH, SS and SH+SS levels were detected through a newly developed method. RESULTS: SH, SS, SH+SS levels and SS/SH ratio were markedly higher in ß-TM patients than in controls. In ß-TM group, SH and SH+SS levels were positively correlated with age, albumin and total bilirubin. Serum ferritin level was positively correlated with SH, SH+SS, aspartate transaminase and alanine transaminase. CONCLUSIONS: We found that the SS/SH ratio was high in patients with ß-TM, which shows increased oxidative stress. This ratio may be considered as a tool for the determination of oxidative status in such patients due to easily calculate, suitable for routine use and economical.