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Immunological disorders, increased oxidative stress, and damage to the epithelial barrier play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). In the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC), it is increasingly common to use biological drugs that selectively affect individual components of the inflammatory cascade. However, administering the medicines currently available does not always result in obtaining and maintaining remission, and it may also lead to the development of resistance to a given agent over time. Metallothioneins (MTs) belong to the group of low molecular weight proteins, which, among others, regulate the inflammation and homeostasis of heavy metals as well as participating in the regulation of the intensity of oxidative stress. The results of the studies conducted so far do not clearly indicate the role of MTs in the process of inflammation in patients with IBD. However, there are reports that suggest the possibility of using MTs as a potential target in the treatment of this group of patients.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene

OBJECTIVES The aim of this study was to examine the role of ghrelin, obestatin, and glutamate and their receptors in the pathogenesis of children functional constipation. METHODS Children ages 4-17 were the subject of the study: 121 children with constipation (55 boys and 66 girls), 36 patients of the same age (26 boys and 10 girls) were the controls. Expression of ghrelin, obestatin, and glutamate receptors on gastric and colon specimens taken by endoscopy were assessed. The concentration of the above agents was estimated in serum by the enzyme-linked immunosorbent assay test. RESULTS The lower median serum concentrations of ghrelin, in the constipated children than in controls were confirmed (1.9 ng/mL vs 2.6 ng/mL, P

Immunological disorders, increased oxidative stress, and damage to the epithelial barrier play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). In the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC), it is increasingly common to use biological drugs that selectively affect individual components of the inflammatory cascade. However, administering the medicines currently available does not always result in obtaining and maintaining remission, and it may also lead to the development of resistance to a given agent over time. Metallothioneins (MTs) belong to the group of low molecular weight proteins, which, among others, regulate the inflammation and homeostasis of heavy metals as well as participating in the regulation of the intensity of oxidative stress. The results of the studies conducted so far do not clearly indicate the role of MTs in the process of inflammation in patients with IBD. However, there are reports that suggest the possibility of using MTs as a potential target in the treatment of this group of patients.

Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H—healthy pigs receiving PAF; P—EPI pigs receiving PAF+PERT; and L—EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H ( p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs ( p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs’ growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.

This study investigated the tolerance and safety of pasteurized donor human milk (PDHM) given either alone or together with commercially-used supplements in a porcine model of premature infants. A porcine model, mimicking human neonates at 30-32 weeks of gestational age, was used. The 7-day experiment was performed on 20 piglets. After birth, the piglets were infused with porcine immunoglobulins via the umbilical artery and surgically fitted with a stomach port. The piglets were then randomized into five groups and fed either PDHM, different variants of fortified PDHM or 'raw' human milk (RHM). Preterm piglets fed PDHM showed signs of gastrointestinal intolerance. Four piglets across the various PDHM-fed groups died, none of them were from the group fed PDHM supplemented with long-chain polyunsaturated fatty acids (LC PUFA). In all groups fed PDHM, macroscopic features of enterocolitis were observed, however, these pathological gut changes were less manifested in piglets receiving PDHM supplemented with LC PUFA. The piglets fed RHM had no specific signs of gut damage. The poor tolerance to PDHM suggests changes in milk composition caused by the Holder pasteurization. The supplementation with LC PUFA probably improves tolerance to PDHM.

Background Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components. Methods This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components. Results The study was conducted with 174 children/adolescents aged 6–17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score. Conclusions Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.

Background: Fibroblast growth factor 19 (FGF19), Fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the paediatric population the relationship between obesity, metabolic disorders and mentioned factors has not been clearly investigated. We analysed serum concentrations of FGF19, FGF21 and Klotho in children and adolescents with normal body weight as well as in overweight and obese subjects – and their associations with components of metabolic syndrome and insulin resistance (IR).Methods: The cross-sectional study conducted in the group of hospitalised children and adolescents. Laboratory investigation included serum ELISA tests for FGF19, FGF21, Klotho as well as lipid profile and oral glucose tolerance test for calculation of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. The clinical analysis included blood pressure measurement, body fat percentage estimation and assessing the prevalence of metabolic syndrome (MS) and its components. Results: The study was conducted on 174 children/adolescents aged 6-17 years divided into the following groups: with normal body weight (N=48), with obesity (N=92) and overweight subjects (N=34). Klotho levels were significantly higher in the group of subjects with obesity [median 168.6 pg/ml]) than those with overweight [131.3 pg/ml] and normal body weight [116.6 pg/ml] (p=0.0334). Median serum FGF21 level was elevated in the group of patients with MS in comparison to other subjects [136.2 pg/ml vs 82.6 pg/ml, p=0.0285]. Increased Klotho concentrations were noted in patients affected by IR compared with subjects with normal insulin sensitivity [185.3 pg/ml vs 132.6 pg/ml, p=0.0282]. Multivariable model for HOMA-IR showed FGF19 as an independent predictor for IR after adjusting for the pubertal stage and BMI Z-score.Conclusions: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and traits of MS.

Introduction The results of some previous studies suggested that maternal folate supplementation during pregnancy may contribute to allergy development in offspring. Aim This study was performed to examine the influence of maternal folic acid intake prior to and during pregnancy on the development of various types of allergy in children taking into account the timing and dosage of supplemented folate. Material and methods The retrospective study was performed between 2010 and 2014 in 307 child-mother pairs (203 allergic children and 104 children without allergy symptoms, aged 2–72 months). Allergy diagnosis was based on medical history, physical examination, positive results of allergic tests: specific IgE and/or skin prick tests and double-blind, placebo-controlled food challenge. The data concerning maternal folate supplementation prior to and during pregnancy were obtained based on a questionnaire. Results Mothers of allergic children used to take folic acid more frequently in the preconception period (42.9%), in the 1st (94.1%) and the 2nd/3rd (81.3%) trimester of pregnancy than mothers of the healthy ones (30.8%, 82.7% and 55.8%, respectively) (p < 0.05). Maternal intake of folate in a dosage higher than recommended (> 0.4 mg/day) was more often observed in the group of allergic subjects, especially in children with combined sensitization to food and inhalant allergens, than in the control group (p < 0.05). Conclusions Our results suggest an impact of maternal folic acid supplementation prior to and during pregnancy on allergy development in children. Further observations are required to establish the role of folate in fetal epigenetic modifications.

Aim of the study presentation of the uncommon paraneoplastic syndromes related to the gastrointestinal tract that may occur in children with neuroblastic tumors and their impact on the disease course. Material and methods Retrospective analysis of three cases of patients mainly with digestive tract-related symptoms, who were originally admitted to the gastroenterology department from 2013 to 2016 and were finally diagnosed with neuroblastic tumors. Results The clinical data analysis showed that the symptoms from gastrointestinal tract were dominant in analyzed subjects. The first case is a girl with weight loss, bloating and severe diarrhea, admitted to the hospital in a state of dehydration. The laboratory tests revealed severe hypokalemia. Finally, vasoactive intestinal peptide (VIP) secreting ganglioneuroblastoma was diagnosed and effective surgery was performed. The second case was also a girl who suffered from the incidents of watery diarrhea and flatulence. The tumor was detected by computerized tomography scan. The 3rd stage of ganglioneuroblastoma was diagnosed. The patient required chemotherapy, radiotherapy and surgery treatment. The third child was a boy, hospitalized due to abdominal pain, constipation and weakness. During the diagnostic process, the 4th stage of neuroblastoma was recognized. The chemotherapy, surgery, radiotherapy and immunotherapy were applied. Conclusions In children with common abdominal symptoms as chronic flatulence, diarrhea or severe constipation of unknown etiology, the neuroblastic tumors should be considered.

Aim To assess the prevalence of metabolic syndrome (MS) components in overweight or obese children and adolescents, as well as analyze the risk factors of its occurrence. Material and methods The study was conducted in a group of 70 children and adolescents aged 5-18 hospitalized in the Department of Gastroenterology, Allergology and Pediatrics, Polish Mother’s Memorial Hospital – Research Institute in Lodz (Poland) based on the results of medical histories, physical examination, biochemical investigation, and calculation of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Results MS was diagnosed in 14 children (20%). The most common abnormalities besides obesity included: decreased High Density Lipoprotein Cholesterol (HDL-C) levels (n=13, 92.9%), increased triglycerides (TG) concentrations (n=10, 71.4%) and arterial hypertension (n=10, 71,4%). Among all the children, insulin resistance was diagnosed in 29 subjects (41.4%). The results of univariate logistic regression showed that the occurrence of lipid disorders, obesity, hypertension and diabetes in their parents, as well as the duration of pregnancy, birth weight, or breastfeeding were not associated with the risk of MS development in the subjects (p>0.05). However, in the study group, 92.9% of subjects had one or more particular risk factor for MS development. Conclusions Besides visceral obesity, lipid disorders were the most frequently observed components of MS in the subjects analyzed, which may have prognostic significance. The occurrence of one or more MS risk factors in almost all of the children studied indicates the increased risk of cardiovascular diseases in the studied group in the future.

Purpose This study aimed to investigate early-life folate serum concentrations in children with food, inhalant or mixed type allergy. The influence of folate levels on the FoxP 3 expression in Treg (regulatory T) cells in the studied children, taking into account the MTHFR (5,10-methylenetetrahydrofolate reductase) genotypes was also analyzed. Material and methods The study was performed in 83 allergic children (study group) and 49 healthy children (control group), aged 2–72 months. Medical history of each child was obtained and laboratory tests (serum folic acid concentrations and MTHFR C677T polymorphism) were carried out. The percentage of Treg cells was evaluated in almost a half of the examined subjects (48.5%). Results Significantly higher serum folate levels in the group of children with food allergy than in those with inhalant allergy was confirmed ( P = 0.037). In the study group the TT homozygotes were characterized by significantly lower folate concentrations than CC homozygotes ( P = 0.045). A negative correlation was demonstrated between the FoxP 3 expression in CD4 + CD25 high FoxP 3 + peripheral blood lymphocytes and serum folic acid concentrations. The correlation was more pronounced in the group of allergic children and it was statistically significant ( r = −0.339, P Conclusions The results of the study indicate a possibility of some effects of folate status on Treg cells, thus suggesting their potential role in the development and course of allergy in children.

[b]Introduction[/b]. Environmental exposure to tobacco smoke is a significant threat for human health, where the higher is its degree, the more immature the human organism is. Therefore, the exposure to Tobacco smoke in foetal life exerts unfavourable effects on developing foetus and may cause early and distant results in children. [b]Material and methods.[/b] The study comprised 318 children in their first four years of life, treated for various medical conditions. The examined children were divided into two groups, Group 1 – children exposed to Tobacco smoke – and Group 2 – a control group with children from non-smoking families. History data were obtained on the basis of a specially designed questionnaire, used by the doctor in an individual conversation with parent. In each third child from the group 1 cotinine concentration in urine was assayed by the method of high performance liquid chromatography-UV-VIS and the cotinine/creatinine ratio was calculated. [b]Results of stud[/b][b]y[/b]. Results demonstrated environmental exposure to tobacco smoke in 173 children (Group 1). Out of them 31.2% were the children whose mothers had smoked also during pregnancy (Subgroup A). The other 119 children from Group 1 were accounted to Subgroup B, i.e., children, where other household members had been smoking cigarettes. A comparative group comprised 143 children from non-smoking families. The results demonstrated then that 17% of all the examined children were those, exposed to tobacco smoke effects already in their foetal life, predisposing them to prematurity and low birth weight. Moreover, it was observed that the young age and lower education level of their parents, together with worse housing conditions, may suggest a predisposing character and role of the mentioned factors.

Diagnostics of the digestive system carried out properly is becoming more and more important where patients' health status and lives are concerned. Current diagnostic methods include but are not limited to the following: radiodiagnostics, endoscopy, enteroscopy and capsule endoscopy. This article contains a brief presentation of these methods and it describes their main advantages and disadvantages. One of the main conclusions summarizing the description of diagnostic methods is to indicate any “blank spots” in the diagnosis and treatment of the digestive system. This article also presents studies of new devices that will eventually fill in the blank spots in the diagnosis of the digestive system. In the conclusions this article characterizes the most important parameter requirements that a device should possess to meet the expectations of physicians and allow for comprehensive diagnostic assessment of the intestines and taking of samples for further tests.

Preterm human neonates, contrary to preterm piglets, obtain immunoglobulins from their mothers via the placenta during intrauterine development. However, one should note that the majority of trans-placental transfer of immunoglobulins in humans takes place during the last trimester of pregnancy. It is also known that the feeding of limited amounts of colostrum or systemic infusion of small amounts of serum improves the survival of preterm and full-term piglets. Full-term piglets deprived of their mother’s immunoglobulins exhibit strong apathy and develop watery diarrhoea, often resulting in death. The aim of the current study was to determine if provision of immunoglobulins using different approaches would be beneficial for survival outcomes. To reach the immunological sufficient level we infused immunoglobulins intravenously in amount mimicking the blood level in piglets fed with sow colostrum. Intravenous infusion of immunoglobulins in both preterm and full-term newborn piglets fully ensured their survival, growth and blood immunoglobulin G and protein levels similar to those observed in piglets fed colostrum. Piglets completely deprived of immunoglobulins exhibited significantly lower blood levels of immunoglobulins and protein compared to colostrum-fed animals. Piglets infused with only serum exhibited significantly lower blood immunoglobulin G level compared to those infused with immunoglobulins. In conclusion, based on the data obtained, we suggest that passive immune support provided by colostrum intake or early systemic infusion of Ig’s in sufficient amounts is key to ensuring the general well-being of preterm and full-term new born piglets, used as an animal model for the human infant.

Introduction Gastroesophageal reflux disease (GERD) often occurs in children and characterizes with diverse clinical symptomatology. In small children symptoms mostly occur in digestive tract, but they can also occur as different symptoms in respiratory tract. Aim The evaluation of frequency and types of clinical symptoms from digestive and respiratory tract in children up to 3 years of age with suspicion of GERD. Material and methods The study included 285 children (age: 6–36 months) with suspicion of GERD. In every child medical investigation was carried out according to a designed questionnaire, which included the symptoms from digestive and respiratory tract. All children underwent 24-hour esophageal pH monitoring. The results were statistically elaborated. Results The that pathological gastroesophageal reflux was detected in 90 patients (31.6%). Among these children, isolated symptoms from respiratory tract were observed in 21.1% while from digestive tract in 30.0% of patients. Symptoms from both systems were more often observed in children with reflux disease (48.9%). The reflux index value in children with GERD showed its highest intensity in patients presenting symptoms from both systems. Conclusions 1. Diagnose of GERD in about 1/3 of patients shows the need for its confirmation with pH monitoring before application of anti-reflux therapy. 2. The conducted study showed common coexistence of symptoms from digestive and respiratory tract in children with GERD. 3. The occurrence of symptoms from both systems in children with GERD indicates significantly higher intensity of reflux in pH monitoring record.

The authors evaluated the frequency of exposure to tobacco smoke among children suffering from respiratory tract infections. The investigations comprised 141 children aged from 2 months to 6 years that were treated in the 2nd Department of Pediatric and Allergology of Polish Mother’s Memorial Hospital Research Institute in ?od? (Poland). 69 of them were exposed to tobacco smoke in their home environment. The remaining 72 children came from non-smoking families. 26 (37.7%) individuals among the passive smokers and 15 (20.83%) among the children from non-smoking families suffered from recurrent respiratory tract infections. Cotinine concentrations were evaluated in the group of 69 children using the HPLC-UV method. The determined average cotinine/creatinine index expressed as median was higher in passive smokers with recurrent respiratory infections than among passive smokers with non-recurrent respiratory infections. Moreover, it was stated that the exposure to cigarette smoke was more often among children of younger and less well educated parents as well as living in poor housing conditions. These studies clearly indicate that there is a need for extensive education on the harmful effects of passive smoking and the recurrence of infections.