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Background. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in obese children. Early diagnosis and treatment are essential for curing or slowing down the disease progression. The aim of the study was to assess the prevalence of NAFLD in this population and to identify anthropometrical and metabolic risk factors for NAFLD prediction and its development. Material and Methods. The study included 108 obese children. Anthropometric measurements, NAFLD diagnosis (based on ALT level and/or liver ultrasound), and metabolic syndrome (MS) components were assessed in all patients. Patients were divided into groups with and without NAFLD. Results. NAFLD was diagnosed in 49 (45%) patients with similar prevalence in boys (27; 55.10%) and girls [22 (44.9%), p=0.089]. NAFLD patients had significantly greater waist circumference, WHR, and WHtR and significantly higher total cholesterol, triglyceride, and fasting insulin concentrations as well as higher glucose and insulin concentrations in 120 minutes of OGTT and higher HOMA-IR levels compared to group of patients without NAFLD. In NAFLD patients, MS was significantly more likely to be diagnosed than in group without NAFLD (40.82% versus 22.81%, p=0.04), but among the MS components only hypertriglyceridemia was significantly more frequently diagnosed in the group with NAFLD (p=0.002). Among analysed parameters the best independent risk factor for NAFLD was fasting insulin concentration with the cut-off point = 18,9 uIU/ml (AUC = 0.829). Conclusions. NAFLD is a very common disease in obese children. NAFLD predictive risk factors include increased waist circumference, elevated WHR and WHtR, and elevated total cholesterol, triglycerides, and fasting insulin as well as elevated glucose and insulin concentration in the OGTT and HOMA-IR index. NAFLD increases the risk of potential cardiovascular complications expressed by diagnosis of metabolic syndrome. The best independent predictive risk factor for diagnosing NAFLD in obese children is fasting insulin > 18.9 uIU/ml.

The aim of the study was to compare oxidative/antioxidative status in obese and sport trained children and to correlate obtained redox markers with anthropometrical measurements, body composition parameters, and adipokines levels. 78 (44 males) obese (SG) and 80 (40 males) normal weight sport trained (CG) children matched for age and Tanner stage were recruited for the study. Body composition parameters and basal metabolic rate (BMR) were assessed by bioelectrical impedance analysis (BIA). Oxidative/antioxidative status was evaluated in plasma by total oxidative status (PerOX), oxidized-LDL cholesterol (oxLDL), total antioxidative capacity (ImAnOx), and glutathione peroxidase activity (GPx). Leptin and adiponectin levels and adiponectin/leptin ratio (A/L) were also investigated. OxLDL was higher in SG versus CG (P P Z-score, WHR, WHtR, body composition parameters, leptin (in boys only), and A/L ratio (in boys only) in SG and in a whole studied population. PerOX significantly correlated with BMR in the CG. Antioxidative/oxidative status in obese children is significantly impaired and related adipose tissue excess and its hormonal activity. Oxidative status assessed by PerOx is also high in sport trained children but antioxidative defense is significantly more efficient with no overproduction of oxidized LDL.

Myeloperoxidase (MPO) is a major protein constituent of the primary granules of vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of halide ions to hypohalous acids, especially HOCl. These reactive oxygen species can participate in a variety of secondary reactions, leading to modifications of amino acids and many types of biological macromolecules. The classic paradigm views MPO as a component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus an important arm of the effector phase of innate immune responses. However, the limited immunodeficiency associated with lack of MPO in mouse and human models has challenged this paradigm. In this review we examine more recent information on the interaction between MPO, its bioreactive reaction products, and targets within the inflammatory microenvironment. We propose that two assumptions of the current model may require revisiting. First, many important targets of MPO modification are extracellular, rather than present only within the phagolysosome, such as various components of neutrophil extracellular traps. Second, we suggest that the pro-inflammatory pathological role of MPO may be a particular feature of chronic inflammation. In the physiological setting of acute neutrophil-mediated inflammation MPO may also form part of a negative feedback loop which down-regulates inflammation, limits tissue damage, and facilitates the switch from innate to adaptive immunity. This different perspective on this well-studied enzyme may usefully inform further research into its function in health and disease.

Cathepsin E is an aspartic endosomal proteinase, expressed at high levels in some epithelial and haemopoetic cells. The enzyme has been implicated in a variety of functions, including antigen processing. This study documents strain-specific variation in expression of cathepsin E in mice. The levels of cathepsin E protein and message are profoundly decreased in haemopoetic cells from C57BL/6J mice, compared to levels in 129S2/Sv or Balb/c. The deficiency is cell-type-specific, as protein levels in gut are not affected. Deficiency affects B cell, T cells, macrophages and dendritic cells. The low cathepsin E phenotype cosegregates with the C57BL/6J genotype in a panel of C57BL/6J x 129S2/Sv F2 mice. Analysis of the promoter region of cathepsin E reveals a polymorphism which destroys a previously described functional PU.1 transcription binding consensus sequence in the C57BL/6J genome. Antigen processing of ovalbumin by dendritic cells, which has previously been shown to require cathepsin E, is impaired in C57BL/6J-derived dendritic cells. C57BL/6J mice thus exhibit a profound tissue-specific deficiency in cathepsin E expression, which may have important implications for the immune phenotype of this mouse strain.

Diabetic ketoacidosis (DKA) is still the most dangerous acute complication of type 1 diabetes mellitus (T1DM). It is a life-threatening condition requiring intensive treatment. DKA may be the first symptom of previously undiagnosed diabetes, especially in children.Assessment of the incidence and clinical manifestation of diabetic ketoacidosis in children with newly diagnosed type 1 diabetes.We analyzed 535 medical files of children (aged 9 months to 17 years, mean age 4.41-9.96, 261 girls (48%)) hospitalized from 2006 to 2009 because of the newly diagnosed type 1 diabetes mellitus. DKA was diagnosed (according to ISPAD) in children with pH7.3, blood glucose level11 mmol/L (200 mg/dL) and/or blood concentration of bicarbonate15 mmol/L with ketonuria. Severe DKA was diagnosed in children with pH7.2.DKA was diagnosed in 123 patients (23%) (63 girls (51%)). The mean age of children with DKA was significantly lower than the age of the children without DKA (9.05-4.45 vs 9.48-4.39 years; p0.001). Mean pH was 7.21-1.03 (min. 6,82; max. 7,30). In 32.5% of children with DKA severe ketoacidosis (pH -7.2) was observed. The prevalence of acidosis was higher in the 0-4 age group compared to children over 4 years (28 vs. 22%, p0.001). Neither sex, nor symptoms duration were associated with the development of DKA. Polyuria (95%), polydipsia (95%), weight loss (85%) and abdominal pain (50%) were the most common symptoms reported by patients.Despite the typical symptomatology of type 1 diabetes mellitus, about 1/4 of newly diagnosed diabetes in children is accompanied by ketoacidosis. The risk of acidosis is greater in younger children.

The production of hypochlorous acid (HOCl) is a characteristic of granulocyte activation, a hallmark of the early phase of innate immune responses. In this study, we show that, in addition to its well-established role as a microbicide, HOCl can act as a natural adjuvant of adaptive immunity. HOCl enhances the T cell responses to the model Ag OVA, facilitating the processing and presentation of this protein via the class II MHC pathway. HOCl modification also enhances cross-presentation of the tumor Ag tyrosinase-related protein 2 via class I MHC. The adjuvant effects of HOCl are independent of TLR signaling. The enhanced presentation of HOCl-modified OVA is mediated via modification of the N-linked carbohydrate side chain rather than formation of protein aldehydes or chloramines. HOCl-modified OVA is taken up more efficiently by APCs and is degraded more efficiently by proteinases. Atomic force microscopy demonstrated that enhanced uptake is mediated via specific receptor binding, one candidate for which is the scavenger receptor lectin-like oxidized low-density lipoprotein receptor, which shows enhanced binding to chlorinated OVA. A function of HOCl is therefore to target glycoprotein Ags to scavenger receptors on the APC surface. This additional mechanism linking innate and adaptive immunity suggests novel strategies to enhance immunity to vaccines.

Precocious puberty (PP) requires a detailed diagnosis. It is concerned that the most useful parameter to differentiate central precocious puberty (CPP) from isolated mild variants is the bone age (BA). On the other hand, obesity can accelerate physical development. The aim of this study was to evaluate whether the coexistence of obesity in children with precocious puberty symptoms influences the diagnostic process. We retrospectively analyzed records of 200 children (F/M 164/36) hospitalized with PP suspicion. The analysis evaluated the nutritional status based on BMI percentile level, compatibility between the BA and the chronological age; and the final clinical diagnosis. In the analyzed group excessive body weight was found in 66 (33%) children – 34 were overweight, 32 obese. Children with excessive body weight were significantly more likely to have mild variants of precocious puberty (71% vs. 66.4%), despite the higher prevalence of accelerated bone age in this group (47% vs. 24.6%). In the group with mild variant of PP and accelerated BA (n = 41 (28.9%)) up to 75.6% of children were overweight or obese. In the group of CPP accelerated BA was observed only in 23 (52.3%) children. Frequently recognized variant of PP in obese children was premature pubarche (n = 20 (62.5%)). Obesity and overweight significantly modifies puberty, and by accelerating the BA can hinder the initial diagnosis of PP. The BA acceleration seems to be poor indicator of CPP, especially in obese children. Among overweight and obese children dominates mild variant of precocious puberty – premature pubarche.