Homeostasis In Children Research Articles

Thiol-disulfide homeostasis in children with febrile neutropenia

Aim: The body’s antioxidant system processes rely on thiol-disulfide equilibrium to function correctly. The purpose of this study was to look into dynamic thiol/disulfide homeostasis (TDH) as an endogenous antioxidant indicator in febrile neutropenic (FN) children with acute lymphoblastic leukemia (ALL). Materials and methods: The study included 66 acute lymphoblastic leukemia patients, including 33 with FN and 33 controls. Both groups were compared for TDH and ischemia-modified albumin (IMA). TDH parameters were assessed using a unique spectrophotometric approach disclosed earlier by Neşelioğlu and Erel. Results: Total thiol, native thiol, disulfide, and native thiol/total thiol levels were significantly lower in patients with FN than in the controls (p< 0.05). Disulfide/total thiol, disulfide/native thiol, and IMA levels were significantly higher in the FN group than in controls (p<0.05). Conclusions: TDH could be a simple tool that could be used in routine screening as an indicator of thiol-specific oxidative stress, particularly in pediatric febrile neutropenia. Keywords: Thiol/disulfide homeostasis, oxidative stress, febrile neutropenia, acute lymphoblastic leukemia

The impact of modified fluid gelatin 4% in a balanced electrolyte solution on plasma osmolality in children-A noninterventional observational study.

Intravenous fluids for perioperative infusion therapy should be isotonic to maintain the body fluid homeostasis in children. Modified fluid gelatin 4% in a balanced electrolyte solution has a theoretical osmolarity of 284 mosmol L-1 , and a real osmolality of 264 mosmol kg H2 O-1 . Because both values are lower than those of 0.9% saline or plasma, gelatin would be expected to be hypotonic in-vitro and in-vivo. We thus hypothesized that the infusion of gelatin would be expected to decrease plasma osmolality. We performed an in-vitro experiment and an in-vivo study to evaluate the impact of gelatin on the osmolality in children. In the in-vitro experiment, full blood samples were diluted with gelatin 4% or albumin (50 g L-1 ) from 0% (pure blood) to 100% (pure colloid), and the osmolality was measured by freezing-point depression. In the in-vivo study, blood gas analyses from children undergoing major pediatric surgery were collected before and after gelatin infusion, and the osmolality was calculated by a modified version of Zander's formula. In the in-vitro experiment, 65 gradually diluted blood samples from five volunteers (age 25-55 years) were analyzed. The dilution with gelatin caused no significant changes in osmolality between 0% and 100%. Compared with gelatin, the osmolality in the albumin group was significantly lower between 50% and 100% dilution (p < .05). In the in-vivo study, 221 children (age 21.4 ± 30 months) were included. After gelatin infusion, the osmolality increased significantly (mean change 4.3 ± 4.8 [95% CI 3.7-4.9] mosmol kg H2 O-1 ; p < .01) within a normal range. Gelatin in a balanced electrolyte solution has isotonic characteristics in-vitro and in-vivo, despite the low theoretical osmolarity, probably caused by the (unmeasured) negative charges in the gelatin molecules contributing to the plasma osmolality. For a better evaluation of the (real) tonicity of gelatin-containing solutions, we suggest to calculate the osmolality (mosmol kg H2 O-1 ) using Zander's formula. ClinicalTrials.gov (ID: NCT02495285).

Disorders of phosphate homeostasis in children, part 1: primer on mineral ion homeostasis and the roles of phosphate in skeletal biology.

Phosphate has extensive physiological roles including energy metabolism, genetic function, signal transduction and membrane integrity. Regarding the skeleton, not only do phosphate and calcium form the mineral component of the skeleton, but phosphate is also essential in regulating function of skeletal cells. Although our understanding of phosphate homeostasis has lagged behind and remains less than that for calcium, considerable advances have been made since the recognition of fibroblast growth factor-23 (FGF23) as a bone-derived phosphaturic hormone that is a major regulator of phosphate homeostasis. In this two-part review of disorders of phosphate homeostasis in children, part 1 covers the basics of mineral ion homeostasis and the roles of phosphate in skeletal biology. Part 1 includes phosphate-related disorders of mineralization for which overall circulating mineral ion homeostasis remains normal. Part 2 covers hypophosphatemic and hyperphosphatemic disorders, emphasizing, but not limited to, those related to increased and decreased FGF23 signaling, respectively.

Disorders of phosphate homeostasis in children, part 2: hypophosphatemic and hyperphosphatemic disorders.

Phosphorus, predominantly in the form of inorganic phosphate PO4-3, has many essential physiological functions. In the skeleton, phosphate and calcium form the mineral component and phosphate is also essential in regulating function of skeletal cells. Considerable advances have been made in our understanding of phosphate homeostasis since the recognition of fibroblast growth factor-23 (FGF23) as a bone-derived phosphaturic hormone. This second part of a two-part review of disorders of phosphate homeostasis in children covers hypophosphatemic and hyperphosphatemic disorders that are of interest to the pediatric radiologist, emphasizing, but not limited to, those related to abnormalities of FGF23 signaling.

Evolution of glucose-insulin homeostasis in children with [beta] - thalassemia major ([beta] -TM): A twenty-year retrospective ICET- A observational analysis from early childhood to young adulthood

Evolution of glucose-insulin homeostasis in children with [beta] - thalassemia major ([beta] -TM): A twenty-year retrospective ICET- A observational analysis from early childhood to young adulthood

The Association between 25-(OH)D Level and Metabolic Control Status in Children with Type 1 Diabetes Mellitus at Dr. M. Djamil General Hospital Padang

Background. Type 1 diabetes mellitus (T1DM) is an autoimmune disease causing the destruction of pancreatic beta cells. This is an incurable condition, but with good metabolic control, an optimal quality of life can be achieved. Glycated hemoglobin (HbA1C) is still considered a reliable parameter of metabolic control. Studies showed vitamin D has a role in controlling glycemic homeostasis in children with T1DM. Calcidiol or 25-(OH)D is the best parameter to determine the level of vitamin D in the blood. This study aimed to evaluate the association between 25-(OH)D with metabolic control status in T1DM children at Dr. M. Djamil General Hospital Padang.&#x0D; Methods. A cross-sectional study was conducted on 43 pediatric patients with T1DM from July 2019-January 2021. Serum levels of 25-(OH)D were measured by direct CLIA method and classified into deficiency (≤ 20 ng/mL) and insufficiency (21–30 ng/mL). The HbA1C levels were calculated using the HPLC method and classified into good (&lt;7%), adequate (7-8%), and poor (&gt;8%) control. The Chi-square test and ANOVA were used for data analysis. The P-value of &lt; 0.05 was considered statistically significant.&#x0D; Results. The majority of respondents were girls (53.5%), with 90.7% having a good nutritional status. The mean age at diagnosis was 11.25±2.85 years, and had been known to suffer from T1DM for 2.95±1.74 years. All respondents had abnormal levels of 25-(OH)D (100%), i.e., insufficiency (28%), deficiency (72%), poor (65.1%) metabolic control, and 96.4% of respondents with poor metabolic control had a deficiency of 25-(OH)D. (P-value &lt;0.001).&#x0D; Conclusion. T1DM patients who have poor metabolic control have very low levels of 25-(OH)D.

Pediatric Carbon Monoxide Poisoning: Effects of Hyperbaric Oxygen Therapy on Thiol/Disulfide Balance.

Carbon monoxide (CO) poisoning remains the foremost cause of poisoning worldwide. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) and normobaric oxygen therapy (NBOT) on thiol/disulfide homeostasis in children with CO intoxication. Eighty-one children aged 0 to 18 years with CO intoxication were included in this cross-sectional study. No changes were made in the routine clinical evaluation and treatment practices of the patients. Thirty-two children who received HBOT and 49 children who received NBOT were compared for serum native thiol, disulfide, and total thiol levels, as well as for the changes in disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios before and after treatment. Antioxidant levels, such as native thiol and total thiol, were significantly decreased in patients who received HBOT and increased in those who received NBOT (P = 0.02 and P = 0.01, respectively). There was no statistically significant difference between the 2 groups concerning the change of native thiol/total thiol ratios (P = 0.07). In addition, there was no significant difference regarding changes in disulfide, disulfide/native thiol, and disulfide/total thiol levels before and after treatment (P = 0.39, P = 0.07, and P = 0.07, respectively). Although thiol-disulfide balance is maintained in patients treated with HBOT, antioxidant levels decrease significantly compared with NBOT. Despite efficiency of HBOT in CO intoxication, oxidative stress and reperfusion injury due to hyperoxygenation should be considered in the treatment of HBOT.

The evolution of glucose-insulin homeostasis in children with β-thalassemia major (β -TM): A twenty-year retrospective ICET- A observational analysis from early childhood to young adulthood.

Background:Thalassemia guidelines recommend oral glucose tolerance test (OGTT), starting from the age of 10 years, or earlier in the presence of iron overload.Objective:The aim of this retrospective study was to review and document the changes of glucose-insulin homeostasis from early childhood to young adulthood in β-thalassemia major (β -TM) patients with impaired fasting glucose (IFG) and normal OGTT.Methods:All data of the clinical patients’ records of 18 β -TM patients from September 1983 to September 2021 were included in the study. Annual or biennial OGTT results, for a duration of 15-20 years, were available for all patients.Results:The main findings are: a) IFG in children with β -TM represents a risk factor for the development of glucose dysregulation (GD) at later age; b) fluctuations of glucose homeostasis during follow-up were observed mainly in β-TM patients with IFG at baseline; and c) the primary defect of GD appears to be a low degree insulin resistance (IR), as estimated by HOMA-IR, followed by an insulin secretion defect.Conclusion:These results are noteworthy as they revealed that firstly, the baseline IFG predicts future development of GD, and secondly, that almost half of patients with IFG at the outset had normal glucose handling 15 years later. Understanding the sequence of abnormalities in the progression from normal glucose homeostasis to GD and identifying the risk factors for the glycometabolic defects in thalassemic patients might help in the formulation of interventions.

Utility of glycated haemoglobin in assessing abnormal glucose homeostasis in children and adolescents with obesity undergoing oral glucose tolerance test

Utility of glycated haemoglobin in assessing abnormal glucose homeostasis in children and adolescents with obesity undergoing oral glucose tolerance test

Predictors of polytrauma outcomes in the early period in children

BACKGROUND: The problem of anti-shock measures and stabilization of the general condition of the affected children with polytrauma at the stage of intensive care is an extremely urgent issue in pediatric traumatology. Various aspects, such as determining the most sensitive prognostic scale for assessing the severity of polytrauma, clinical and laboratory predictors of changes in the vector of development of the course of traumatic disease in the direction of thanatogenic orientation, remain actively discussed among clinicians.&#x0D; АIM: The aim of the study is to analyse the dynamics of changes in the indicators of internal homeostasis in children with polytrauma, indicating a favorable or thanatogenic direction of the course of the traumatic disease.&#x0D; MATERIALS AND METHODS: A retrospective analysis of the medical records of 49 patients diagnosed with polytrauma was performed. All patients were divided into two groups: the survivors group comprised 41 patients, and the deceased group consisted of 8 patients.&#x0D; All patients were examined for total blood count (Er, Tr, Ht, Hb, le, ESR), acid-base state (pH, SBC, BE), blood biochemical parameters (creatinine, urea, ALT, AST, K, Na, Ca), and C-reactive protein. The tests were performed daily during the first 10 days of the acute phase of the injury. The severity of the injury was determined by the NISS and pediatric trauma score scales, and in the case of a traumatic brain injury, the Glasgow coma scale was used.&#x0D; A logistic step-by-step regression analysis was performed to identify predictors of polytrauma outcomes. The statical significance was considered at p 0.05.&#x0D; RESULTS: The step-by-step logistic regression revealed significant predictors that determined the unfavorable outcome of polytrauma (death), already on the second day. They were the NISS score, the level of CRP, Hb, Er, Na, and creatinine. At the same time, the statistical significance in the dynamics of changes in red blood parameters (Er, Hb), blood ionic composition (Na, K), humoral activity (Le, ESR, CRP) remained up to 10 days, i.e., during the period of possible complications of the traumatic disease. Our data offered the possibility to derive an equation for calculating the risk of failure of compensatory mechanisms in polytrauma.&#x0D; CONCLUSIONS: The course of traumatic disease in children with polytrauma is characterized by morpho-functional changes in many organ systems. Predictors of failure of compensatory-adaptive mechanisms in response to polytrauma can be determined already in the early post-shock period.

Взаємозв’язки порушень біохімічного й імунологічного гомеостазу у хворих на ювенільний ревматоїдний артрит з урахуванням тривалості захворювання

Актуальність. Ювенільний ревматоїдний артрит (ЮРА) належить до довічних патологічних станів. Тому актуальними є дослідження, що вивчають закономірності його розвитку, функціонування метаболічних систем, розвиток дистрофічних змін на тлі запального процесу. Мета. Вивчення особливостей метаболізму сполучнотканинних структур відповідно до стану імунного гомеостазу на етапах еволюції ЮРА у хворих дитячого віку. Матеріали та методи. Вивчено особливості структурного складу компонентів сполучної тканини, вмісту мікроелементів, імунологічного гомеостазу у дітей із ЮРА. Проаналізовано 355 клінічних спостережень хворих на ЮРА з урахуванням ретро- і проспективних досліджень за 2012–2016 роки. Клінічна група становила 117 хворих на суглобову форму віком від 2 до 18 років (у середньому 6,0 ± 0,5 року). Результати. Дослідження імунного статусу визначило зниження рівня Т-загальних лімфоцитів (р &lt; 0,001), Т-лімфоцитів-хелперів (р &lt; 0,001), Т-супресорів/цитотоксичних (р &lt; 0,001), підвищення імунорегуляторного індексу (р &lt; 0,05), зменшення бактерицидної активності нейтрофілів (р &lt; 0,001), збільшення показників тесту з нітросинім тетразолієм і зниження показника індексу стимуляції нейтрофілів (р &lt; 0,001), підвищення рівня циркулюючих імунних комплексів (р &lt; 0,001). Аналіз умісту прозапальних цитокінів довів підвищення рівня інтерлейкіну-1 (р &lt; 0,05) та інтерлейкіну-6. Визначено залежність імунологічних показників від тривалості хвороби. Встановлено підвищення вмісту хондроїтин-4- та -6-сульфатів, кератан- і дерматансульфатів крові. Найбільші відхилення відзначались на перших етапах розвитку хвороби, що, безперечно, пов’язано з активністю патологічного процесу до призначення протизапального лікування або на перших етапах його отримання. У віддалені періоди захворювання відбувається зменшення рівня загальних глікозаміногліканів, хондроїтин-4- та -6-сульфатів, сповільнення екскреції уронових кислот (рt &lt; 0,05). Аналіз змін у вмісті неорганічних компонентів залежно від тривалості хвороби виявив незначне зниження втрати організмом фосфору у період 3–5 років ЮРА. Аналіз відхилень імунобіохімічних співвідношень на різних етапах еволюції патологічного процесу виявив зміни кількості та характеру взаємозв’язків між показниками сполучнотканинного метаболізму й імунологічного гомеостазу. Висновки. Висока активність захворювання є основним предиктором розвитку дистрофічних змін, що підтверджується численними кореляційними взаємозв’язками показників обміну сполучної тканини та імунологічних параметрів. Найбільш несприятливими періодами є перші 1,5 року і через 3–5 років від початку захворювання. Виявлені зміни є підставою для проведення медикаментозної корекції біохімічного складу сполучнотканинних структур з метою профілактики розвитку вторинних дистрофічних змін в уражених суглобах у дітей з ЮРА, а також можуть відображати недостатню ефективність проведеного лікування та збереження субклінічної активності запалення.

Thiol/Disulphide homeostasis in children with acute pyelonephritis and cystitis

Thiol/Disulphide homeostasis in children with acute pyelonephritis and cystitis

Profiling of Insulin-Like Growth Factor Binding Proteins (IGFBPs) in Obesity and Their Association With Ox-LDL and Hs-CRP in Adolescents.

Insulin-like growth factor binding proteins (IGFBPs) are critical modulators of metabolism. In adults, IGFBPs are associated with obesity and insulin resistance. However, the association of IGFBPs with metabolic homeostasis in children and adolescents is not yet fully characterized. In this study we investigated the association of plasma IGFBPs (IGFBP-1, 3 and 7) with weight, central adiposity and cardiovascular disease markers Hs-CRP and Ox-LDL. A total of 420 adolescents (age 11-14 years) were recruited from public middle schools in Kuwait. IGFBPs were measured using bead-based multiplexing while Hs-CRP and Ox-LDL were measured using ELISA. Results showed that levels of IGFBP-1 were significantly lower in obese and overweight children when compared to normal weight children. Correlation analysis showed negative association between the level of IGFBP-1 and waist circumference to height (WC/Ht) ratio. IGFBP-1 level was also negatively associated with Hs-CRP. It was also observed that the levels of IGFBP-3 and IGFBP-7 were negatively correlated with Ox-LDL. Our data demonstrate a strong negative association of IGFBP-1 with overweight/obesity, and the inflammatory marker Hs-CRP. This was not seen with the levels of IGFBP-3 and 7. The association of IGFBP-1 with central adiposity (WC/Ht ratio) was stronger than its association with BMI-for-age z-score. Therefore we suggest that IGFBP-1 could potentially be used as a sensitive biomarker for obesity and its subsequent effects in screening and monitoring of obesity-related metabolic complications in adolescents.

Взаємозв’язок показників обміну заліза і тиреоїдного гомеостазу у дітей із сидеропенією та йододефіцитом

Relationships between the iron metabolism indexes and thyroid homeostasis in children were investigated. For that purpose, 68 healthy children aged 6 to 11 years were examined (35 boys and 33 girls) with adequate iron and iodine supply (n =16), latent sideropenia (n = 16), mild iodine deficiency (n = 18) and combination of latent iron deficiency and mild iodine deficiency (n = 18). We found that in 13% of boys with latent sideropenia, 78% of boys and as many girls with mild iodine deficiency, 90% of boys and 88% of girls with combined iodine and iron deficiency, the thyroid-stimulating hormone (TSH) level in blood serum ranged from 2.5 to 4.2 mIU/l under the reference data of free triiodothyronine (fT3) and thyroxine (fT4). This observation points for development of minimal thyroid insufficiency (MTI). According to the TSH/fT4 index, MTI was found in 30% of boys and 38% of girls with combined iodine and iron deficiency. These children form the group of risk for development of subclinical hypothyroidism and require mandatory individual correction of MTI by administration of potassium iodide. We found direct moderate correlations between the contents of fT3 and fT4 in serum and the hemoglobin level (Hb) in blood, between the contents of the serum iron and ferritin (r from 0.42 to 0.64). We found also an inverse moderate correlation between the serum TSH content and indexes of iron metabolism (r from –0.56 to –0.61), and a direct moderate correlation between the TSH and total serum iron-binding capacity (r = 0.54). Therefore, iron deficiency can be considered a risk factor for the development of thyroid insufficiency, which requires control of functional capacity of thyroid gland in case of iron depot depletion. The most vulnerable period for the formation of thyroid dysfunction is a prepubertal age regardless of gender. The advisability of determining the indicators of iron metabolism and its correction under conditions of latent sideropenia, mild iodine deficiency and their combination for the prevention of MTI development was justified.

Asprosin serum levels and glucose homeostasis in children with obesity

PurposeAsprosin is a novel adipokine involved in glucose homeostasis, food intake regulation and energy homeostasis. However, the role of asprosin in glucose homeostasis regulation remains still controversial, especially in pediatrics. Aims of the study were to compare fasting serum asprosin levels between obese children and controls and to investigate the relationships of asprosin with body mass index (BMI) and biochemical markers of insulin resistance, insulin sensitivity, β-cell function and cardio-metabolic risk in obese non-diabetic children. MethodsThis cross-sectional, case-controlled, study included 43 obese children and 24 lean matched controls consecutively recruited. Children underwent clinical and biochemical assessments, including oral glucose tolerance test. Fasting asprosin serum levels were measured using an enzyme-linked immunosorbentassay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), Matsuda-index, Insulinogenic-index, Areas Under the Curves for glucose and insulin were calculated. Successively, asprosin variable was dichotomized according to mean value in order to create two ordered classes of values. ResultsFasting asprosin concentration was significantly lower in obese children compared to controls (331.9 ± 120.5 vs 358.1 ± 74.1 pg/ml; p = 0.013). Asprosin was lower in boys than in girls (313.7 ± 59.5 vs 361.1 ± 127.2 pg/ml; p = 0.044), while BMI standard deviation score (SDS) was higher in boys compared to girls (p = 0.024). Asprosin was negatively correlated with BMI (p = 0.024), BMI SDS (p = 0.044) and male sex (p = 0.043) in the entire cohort. No significant differences in asprosin levels were demonstrated between insulin resistant and non-insulin resistant obese children. Logistic regression models documented a significant negative association between BMI SDS and dichotomized asprosin. In particular, higher BMI SDS values were associated to lower asprosin serum levels class. A receiver operating characteristic (ROC) analysis showed existence of the best cut-off for BMI SDS (+2.7 SDS) variable into discriminating patients belonging to two asprosin classes in our cohort. ConclusionsIn conclusion, asprosin serum levels were significantly lower in obese children compared to control.Fasting asprosin decreased with increasing BMI, but it was not significantly affected by IR.

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.

Red blood cell homeostasis in children and adults with and without asymptomatic malaria infection in Burkina Faso

Asymptomatic malaria infections may affect red blood cell (RBC) homeostasis. Reports indicate a role for chronic hemolysis and splenomegaly, however, the underlying processes are incompletely understood. New hematology analysers provide parameters for a more comprehensive analysis of RBC hemostasis. Complete blood counts were analysed in subjects from all age groups (n = 1118) living in a malaria hyperendemic area and cytokines and iron biomarkers were also measured. Subjects were divided into age groups (<2 years, 2-4, 5-14 and ≥15 years old) and clinical categories (smear-negative healthy subjects, asymptomatic malaria and clinical malaria). We found that hemoglobin levels were similar in smear-negative healthy children and asymptomatic malaria children but significantly lower in clinical malaria with a maximum difference of 2.2 g/dl in children <2 years decreasing to 0.1 g/dl in those aged ≥15 years. Delta-He, presenting different hemoglobinization of reticulocytes and RBC, levels were lower in asymptomatic and clinial malaria, indicating a recent effect of malaria on erythropoiesis. Reticulocyte counts and reticulocyte production index (RPI), indicating the erythropoietic capacity of the bone marrow, were higher in young children with malaria compared to smear-negative subjects. A negative correlation between reticulocyte counts and Hb levels was found in asymptomatic malaria (ρ = -0.32, p<0.001) unlike in clinical malaria (ρ = -0.008, p = 0.92). Free-Hb levels, indicating hemolysis, were only higher in clinical malaria. Phagocytozing monocytes, indicating erythophagocytosis, were highest in clinical malaria, followed by asymptomatic malaria and smear-negative subjects. Circulating cytokines and iron biomarkers (hepcidin, ferritin) showed similar patterns. Pro/anti-inflammatory (IL-6/IL-10) ratio was higher in clinical than asymptomatic malaria. Cytokine production capacity of ex-vivo whole blood stimulation with LPS was lower in children with asymptomatic malaria compared to smear-negative healthy children. Bone marrow response can compensate the increased red blood cell loss in asymptomatic malaria, unlike in clinical malaria, possibly because of limited level and length of inflammation. Trial registration: Prospective diagnostic study: ClinicalTrials.gov identifier: NCT02669823. Explorative cross-sectional field study: ClinicalTrials.gov identifier: NCT03176719.

An Investigation of the Dynamic Thiol/Disulfide Homeostasis, As a Novel Oxidative Stress Plasma Biomarker, in Children With Autism Spectrum Disorders.

We aimed to investigate the role of impaired oxidant-antioxidant homeostasis on the etiopathogenesis of autism with a novel oxidative stress (OS) marker, dynamic thiol/disulfide homeostasis (DTDH), and relationship between the symptom severity and markers. A total of 60 children with ASD aged 3-10 years and 54 unaffected children were investigated for the plasma DTDH parameters. A sociodemographic-data form, K-SADS-PL, Childhood Autism Rating Scale, Abnormal Behavior Checklist, Autism Behavior Checklist, and a developmentally appropriate IQ test were administered to all participants. Distortion of DTDH to the OS-side in the autism group was determined with lower plasma levels of native and total thiol, in contrast to a higher disulfide and thiol oxidation-reduction ratio. However, biomarkers had no correlation with the symptom severity of autism. Cutoff values for each parameter on the ROC curve might be useful to predict ASD and each DTDH biomarker was detected as an independent predictor of ASD. The present study demonstrated a disturbed redox status and absence of an expected compensatory increase in antioxidant response in a pediatric sample of ASD by measuring dynamic oxidation/reduction shifts with a novel, practical and reproducible analytical technique, and contributes to data regarding oxidative hypothesis on autism and raises the question of the place of antioxidants in autism treatment. Our results may suggest predictive usefulness of the plasma DTDH biomarkers in ASD, despite the study being conducted with a modestly small sample size that makes further research with a larger replication sample necessary to substantiate the findings. LAY SUMMARY: Dynamic thiol/disulfide homeostasis is a novel plasma marker used to determine the oxidative stress which is a natural result of disequilibrium between the oxidants and antioxidants in the human body. There is increasing interest regarding a central biological linking role of oxidative stress among the other etiological factors of autism. Our findings on the disturbed plasma dynamic thiol/disulfide homeostasis in children with autism and the absence of an expected antioxidant response against increased oxidative stress supports the data concerning the role of oxidative stress on the etiology of autism and the need of further research on the place of antioxidants in autism treatment.

Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity.

Several studies identified genetic variants in FADS and ELOVL2 genes associated with obesity-related conditions, such as alterations in blood lipid parameters and insulin homeostasis. The aim of this cross-sectional study was to determine whether FADS and ELOVL2 genetic variants were associated with obesity and adiposity, besides dyslipidaemia and insulin resistance, in a large sample of obese children and adolescents. One thousand six hundred and forty-nine obese children underwent physical examination, anthropometry, fasting blood tests measuring plasma glucose, lipid and liver profile. Two genetic variants were genotyped: rs2236212 in ELOVL2 gene and rs1535 in FADS2, for the gene cluster FADS. In a subgroup of obese children (n = 105), erythrocyte fatty acid composition was measured. Generalized linear models were used to assess association between genotypes and variables. A positive association between zBMI and the minor allele of rs2236212 (p = 0.028), the major allele of rs1535 (p = 0.046) and the genetic score (p = 0.008), created by summing up both risk alleles, were found. The estimation of enzymatic activity revealed that minor alleles were associated significantly with a reduction of the enzymatic activity of elongase and desaturase (p = 0.048 and p = 0.0001, respectively). Common variants in the FADS2 and ELOVL2 genes were associated with BMI in a large population of obese Italian children. These SNPs were associated with alterations in LC-PUFAs homeostasis, not accompanied by modifications of plasma lipids or HOMA-IR. These findings provide additional support to the genetics accounting for BMI interindividual variability and the molecular basis of obesity.

Thiol-disulfide homeostasis in children with celiac disease.

Toxic gliadin peptide damages enterocytes in celiac disease by causing oxidative stress. Thiols are organic compounds that defend against oxidative stress. This study aimed to investigate the changes in thiol-disulfide homeostasis in children with celiac disease. The study included patients with celiac disease, children diagnosed with functional gastrointestinal disorders, and healthy children. Patients' serumnative and total thiol-disulfide amounts, disulfide/total thiol percentage ratios, disulfide / native thiol percentage ratios, and native thiol/total thiol percentage ratios were measured. The study involved 172 children, of whom 90 (52.3%) were girls. The mean participant age was 8.6 ± 4.2years. A total of 59 (34.3%) children had celiac disease, 56 (32.6%) had functional gastrointestinal disorders, and 57 (33.1%) were healthy. The total thiol and disulfide levels of patients with celiac disease (305 ± 87μmol/L and 25 ± 15μmol/L, respectively) were significantly lower than those of healthy children (349 ± 82μmol/L and 40 ± 15μmol/L, respectively) (P = 0.006 and P < 0.001, respectively). Native and total thiol levels (226 ± 85μmol/L and 279 ± 99μmol/L, respectively) in patients with celiac disease who consumed a gluten-containing diet were significantly lower than those of patients who consumed a gluten-free diet (278 ± 64μmol/L and 327 ± 69μmol/L, respectively) (P = 0.017 and P = 0.041, respectively). Thiol-disulfide homeostasis, an important antioxidant defense component of the gastrointestinal system, is disrupted in children with celiac disease. A gluten-free diet helped partially ameliorate this decline.