Maciej Kaczmarski

Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease

PURPOSE Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in patomechanism of this disease is not clear. The aim of the study was to evaluate the serum levels of leptin, adiponectin and resistin in obese children with NAFLD. MATERIAL/METHODS The fasting serum levels of adipokines were determined in 44 consecutive obese children with suspected liver disease and in 24 lean controls. The degree of the ultrasound liver steatosis was graded according to Saverymuttu. RESULTS The fatty liver was confirmed in 33 children by ultrasonography (16 of them also showed an increased ALT activity). The serum leptin level was significantly higher and adiponectin level was lower in the obese children with NAFLD when compared to controls. Only adiponectin correlated with homeostasis model assessment of insulin resistance (HOMA-IR). Significant negative correlations were found between the ultrasonographic grades of liver steatosis and adiponectin and resistin levels. Serum adiponectin and resistin levels were lower in children with an advanced liver steatosis (grade 3, n=10) compared to patients with a mild steatosis (grade 1-2, n=23). The ability of serum adiponectin and resistin to differentiate children with an advanced liver steatosis from those with mild steatosis was significant. CONCLUSIONS These data suggest a role of both adiponectin and resistin in the pathogenesis of NAFLD in obese children and confirm the association between adiponectin and insulin resistance. Adiponectin and resistin may be suitable serum markers in predicting an advanced liver steatosis in children with NAFLD.

Transport of μ-opioid receptor agonists and antagonist peptides across Caco-2 monolayer

Milk is the source of beta-casomorphins--biologically active peptides with opioid activity--which are suspected to play various roles in the human body. The local influence of exogenous opioid peptides on gastrointestinal functions has been widely reported. After passing the gut barrier, beta-casomorphins may affect the functions of immunological system, as well as dopaminergic, serotoninergic and GABA-ergic systems in brain, regulate the opioid receptor development and elicit behavioral effects. However, possibilities and mechanisms of the intestinal transport of beta-casomorphins in human body in vivo have not been reported so far. In our research, the transepithelial transport of micro-opioid receptor agonists--human beta-casomorphin-5 and 7(BCM5, BCM7) and antagonist--lactoferroxin A (LCF A) have been investigated using Caco-2 monolayer. In order to determine the pathway of investigated peptide transport across Caco-2 monolayer, two directions of the transport (apical to basolateral and basolateral to apical) have been studied. All investigated peptides were transported across the human intestinal cell line Caco-2 and the curves of cumulative amount of transported peptides in time were linear in each case. In addition, the hydrolysis of beta-casomorphins during 60 min of experiment by dipeptidyl peptidase IV was observed. The data suggest the possibility of transport of opioid peptides derived from food across human intestinal mucosa.

Changes of β-casomorphin content in human milk during lactation

Milk is the best, complete food important for the development and nourishment of a neonate. Except for nutrients, milk contains biologically active opioid peptides derived from beta-casein, named beta-casomorphins (BCMs), which can exert effects in the gastrointestinal tract as well as in the whole body of neonates. The content of beta-casomorphins in human milk during maturation phases has not been studied so far. The aim of this study was to determine the content of beta-casomorphin-5 and -7 in human milk in different phases of lactation. A significantly higher concentration of both beta-casomorphins was found in colostrum than in mature milk. The concentration of beta-casomorphin in milk collected in the second month of lactation was similar to the level obtained in the fourth month of lactation. The content of beta-casomorphins in human milk was observed with the period of lactation. The level of opioid peptides may depend on the function of these peptides in neonates body and may be associated with the maturation process.

Seroprevalence of Helicobacter pylori infection in Polish children and adults depending on socioeconomic status and living conditions

PURPOSE Helicobacter pylori (H. pylori) is one of the causes of gastritis, peptic ulcer disease, gastric cancer and MALT-lymphoma. The frequency of H. pylori infection is different in various regions of the world and dependent on age, socioeconomic and hygiene status. The objective of this study was to assess seroprevalence and the associated socioeconomic and sociodemographic characteristics influencing H. pylori infection in children and adults in Polish population. MATERIAL/METHODS In multicenter epidemiological studies, H. pylori infection occurrence was assessed in Poland in the years 2002 and 2003. The seroprevalence of H. pylori infection diagnosis was based on IgG anti-H. pylori antibodies concentration above 24 UI/ml, which was measured using ELISA test. The study included 6565 subjects: 3307 adults (50.37%) and 3258 children (49.63%). RESULTS Positive result was observed in 3827 subjects (58.29%), i.e. 1043 children (32.01%) and 2784 adults (84.19%). H. pylori infection prevalence was greater in children of poor economic status, who were born in a rural area, lived in crowded houses with no running tap water and with toilet outside the house, and who did not observe hygiene rules. In adults, the factors predisposing to higher probability of being H. pylori infected included: being born in a rural area, having low family income and elementary education, smoking tobacco, drinking high proof alcohols as well as not observing of hygiene rules. CONCLUSIONS Improvement of socioeconomic status, sanitary and hygienic conditions and the education of the society might decrease H. pylori infection prevalence in children and in adults.

Serum fibrosis markers as predictors of an antifibrotic effect of interferon alfa in children with chronic hepatitis B.

Objective Interferon alfa (IFN-&agr;) may retard hepatic fibrogenesis in adults with chronic hepatitis C. We evaluated prospectively four selected serum fibrosis markers before, immediately after and 12 months after IFN treatment of children with chronic hepatitis B (CHB). Methods Forty-seven children (mean age 8 years, range 4–16) with CHB underwent IFN-&agr; treatment (3 MU t.i.w.) for 5 months. Fibrosis and inflammation were assessed blindly before and 12 months after the end of treatment. Serum laminin-2, collagen IV, MMP-2 and MMP-9/TIMP-1 complex were determined using automated assays. Results Twelve months after treatment had been discontinued levels of laminin-2, collagen IV and MMP-2 were decreased, and serum MMP-9/TIMP-1 complex was increased. Levels did not differ between sustained responders (42.5%) and non-responders. Similarly, fibrosis did not progress in both groups, whereas histological inflammation improved only in responders. Conclusions A 5 month IFN-&agr; treatment has no marked effect on histological liver fibrosis in children with CHB, irrespective of virological response. The evolution of serum fibrosis markers suggests they may be more sensitive to detect minor antifibrotic effects than semiquantitative follow-up histology.

Eosinophilic esophagitis in children: frequency, clinical manifestations, endoscopic findings, and seasonal distribution

PURPOSE Eosinophilic esophagitis (EoE) is a chronic disease characterized by eosinophilic infiltration of the esophageal mucosa, which is associated with clinical and endoscopic manifestations. The objective of our study was to determine the frequency of EoE and to outline the clinical manifestations of EoE in Polish children. MATERIAL/METHODS Ten large regional pediatric gastroenterology centers participated in the study. A database of endoscopy reports from January 2004 till December 2009 was reviewed. A total of 35,631 esophagogastroduodenal endoscopy studies in children, aged from 4 months to 18 years, were performed. Data pertaining to the childrens age, gender, indications for endoscopy, clinical findings and histopathology diagnosis were made. RESULTS In 84 children (20 girls and 64 boys), aged between 4 months and 18 years, EoE was diagnosed. This constituted one case per 424 endoscopic studies. In children with changes in the esophageal mucosa the frequency of EoE was higher and reached one case per 73 children. The most frequent symptoms of EoE differed between the younger (1-6 years old) and older children (aged 13-18 years old). Feeding aversion, vomiting and/or regurgitation were most frequently observed in the younger children, while in older children: abdominal pain, dysphagia and chest pain. Granular mucosa, longitudinal furrows, and mucosal rings belong to the findings most often observed in endoscopic studies. EoE was more frequently diagnosed in the spring (45.2%) and summer (28.5%). CONCLUSIONS EoE was diagnosed in every age, with frequency of 1/424 gastrointestinal endoscopies, more frequently in boys than in girls.

Atopy patch test in the diagnosis of food allergy in children with gastrointestinal symptoms.

PURPOSE To evaluate the diagnostic accuracy of the atopy patch test (APT) in detection of delayed-type sensitization to different food allergens, in children with digestive symptoms and with/or without cows milk allergy. MATERIAL AND METHODS 28 children suspected of food allergy-related gastrointestinal symptoms were underwent diagnostic procedures as skin prick test (SPT), specific immunoglobulin E (sIgE), APT, oral food challenge and then divided into two groups according to the results of oral food challenge: A - 17 children with cows milk allergy, B - 11 children without cows milk allergy. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of APT were calculated. RESULTS A positive challenge response to milk was found in 60,7% of examined children. No statistical difference in the prevalence of positive SPT and sIgE to milk has been found between the groups. The prevalence of positive APT to other food allergens was significantly higher in children with allergy to milk (p<0,005). No statistical difference of positive APT to other food allergens has been found in children with/or without cows milk allergy. APT sensitivity and specificity in children with cows milk allergy obtained on 77%/73%; where PPV obtained on 71%. CONCLUSIONS High sensitivity and specificity of APT confirm its accuracy in diagnostics of delayed-type reactions in children with gastrointestinal symptoms. Combined atopy patch test and oral food challenge is essential for avoidance of unnecessary elimination diet. Delayed-type sensitization to other food allergens is common in children with cows milk allergy.

Serum fetuin A concentration is elevated in children with non-alcoholic fatty liver disease

PURPOSE To assess the serum fetuin A concentration as a potential marker of subclinical atherosclerosis in obese children with NAFLD. MATERIAL/METHODS A prospective analysis of 45 obese children initially diagnosed with liver pathology (elevated serum ALT activity and/or ultrasonographic liver brightness and/or hepatomegaly) was conducted. The diagnosis of NAFLD was established in the children with elevated serum ALT activity and liver steatosis on ultrasound examination. Viral hepatitis, autoimmune, metabolic liver diseases (Wilson disease, alpha-1-antitrypsin deficiency, cystic fibrosis) and drug and toxin-induced liver injury were excluded in all children. The degree of liver steatosis was graded according to Saverymuttu scale and the total liver lipids concentration was assessed using proton magnetic resonance spectroscopy ((1)H MRS). RESULTS Serum fetuin A concentration was significantly higher in examined children compared to the control group (n=30) (p=0.00002). Higher serum fetuin A concentration was also observed in children with NAFLD (n=19) in comparison to the controls (p=0.000026). Additionally, higher BMI values, waist circumferences, ALT and GGT activity, intensity of liver steatosis on ultrasound and total concentration of lipids in the liver in (1)H MRS were found in children with NAFLD compared to the rest of the examined obese patients (n=26). There was not found any correlation of the investigated glycoprotein with any other assessed parameters both in children with NAFLD and obese children without NAFLD. CONCLUSION Higher serum fetuin A concentration found in children with NAFLD compared to the control group support the hypothesis that atherosclerotic processes may develop faster in hepatopatic obese patients.

Content of β-casomorphins in milk of women with a history of allergy

The prevalence of food allergies increased over the past decade. Most symptoms of food allergy appear during the first 2 yr of life. The aim of this study was to determine the β‐casomorphin‐5 and ‐7 (BCMs) in colostrum and milk of 12 breast‐feeding women with a history and clinical manifestation of food allergy. The results were compared with the data obtained from a control group of healthy age‐matched breast‐feeding women. The level of BCM in women with food allergy was constant during lactation, whereas the highest level of opioid peptides was found in colostrums of healthy women with a subsequent rapid decrease in mature milk. These differences in BCMs profile between allergic and healthy breast‐feeding women suggest that BCM content in the human milk may be an indicator of allergic conditions.

Cow's-milk-induced infant apnoea with increased serum content of bovine β-casomorphin-5.

772 S uddenly occurring life-threatening events with symptoms such as apnoea, changes in skin colour (eg, blue or cyanotic), altered muscle tone (eg, floppy, stiff), coughing, choking, or gagging are called apparent life-threatening events (ALTE). About 7.4% to 10% of infants with ALTE, mostly in its recurring form, cannot be saved and they die of sudden infant death syndrome (SIDS) (1–3). A number of different and independent causes of ALTE pathogenesis have been described. Those causes include diseases of various organs and systems, infections, nonaccidental traumas, and Münchausen syndrome by proxy (1,4,5). A coexistence of digestive tract disorders is also diagnosed in >50% of infants with ALTE. Gastro-oesophageal reflux is 1 of the most often diagnosed disorders; however, its role in the genesis of infantile apnoea has not been fully explained (6). ALTE aetiology is explainable and diagnosable only in half of all of the cases (2,3). The causes of ALTE described before do not include an opioid action of the exogenous peptides released from milk b-caseins. We report a case of a breast-fed infant with recurrent apnoea episodes, which have always been preceded by his mother’s consumption of fresh cow’s milk. A biochemical examination has revealed a high level of b-casomorphin-5 (BCM-5) in the child’s serum. We speculate that it is an opioid activity that may have a depressive effect on the respiratory centre in the central nervous system and induce a phenomenon called milk apnoea. A full-term male infant from a rural family, age 7 weeks, was referred to a macroregional SIDS prevention centre to diagnose the cause of his recurrent ALTE. Apnoea had been occurring since the child was 3 weeks old and its clinical course kept getting more serious. The infant’s mother noticed that those events occurred only after her consumption of cow’s milk, particularly when she had consumed large amounts of it (up to 2 L/d). Before and during her pregnancy, the mother drank milk with no adverse effects. The boy’s ALTE occurred during breast-feeding or directly after that, and was manifested as sudden, 20-, 30-, or 40-second-long apnoea with generally lowered muscle tone. Most of the episodes required