Superoxide dismutase activity in colostrum, transitional and mature human milk

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3(rd)-5(th) days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation

Isolated hypertransaminasemia in children up to two years old with classical celiac disease

© 2019, Serbia Medical Society. All rights reserved. Introduction/Objective Isolated hypertransaminasemia (IHTS) is a common, benign, and transient appearance in patients with celiac disease (CD). The aim of this study is to determine the frequency of IHTS in children up to two years old with clinically classical CD, as well as its connection with the onset of the first symptoms of the disease, the age of diagnosis, the clinical and laboratory nutritional parameters, and the degree of damage of small intestinal mucosa. Methods The study was based on a sample of 82 children, 55 female and 27 male, ages 7-24 (14.28 ± 4.41) months. The diagnosis of CD was based on the revised ESPGHAN criteria and the activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by standard laboratory methods. Results IHTS was found in 39 (47.56%) patients, 27 of whom (69.23%) had elevated levels of both transaminases and 12 of only one - eight of AST and four of ALT. The increase in relation to the aforementioned reference value for ALT was 1.1-10.08 (1.67 ± 1.73), and for AST it was 1.08-7.91 (1.56 ± 1.29) times. In patients with IHTS compared to those with normal transaminasemia, the age of onset of CD was significantly lower (9.83 ± 3.69 vs. 12.95 ± 4.43 months, p = 0.001), as well as the age of diagnosis (12.97 ± 3.88 vs. 15.47 ±4.56 months; p = 0.01), while the differences in the other observed parameters were not significant. Conclusions IHTS occurs in almost half of children up to two years old with classical CD. Hypertransaminasemia is in most cases mild and significantly more frequent in patients with earlier clinical expression of the CD

Influence of breastfeeding and timing of gluten introduction on the onset of celiac disease in infants

© 2019, Serbia Medical Society. All rights reserved. Introduction/Objective The classic type of celiac disease (CD) is most common in children under two years of age. The aim of this study was to investigate whether breastfeeding, particularly breastfeeding during gluten introduction, and timing of gluten introduction, influence the onset of CD at this age. Methods We retrospectively analyzed medical records of 93 children, 40 in the first and 53 in the second year, with a classic CD diagnosed at the University Children’s Hospital, Belgrade between 2000 and 2010. The diagnosis of CD was based on the criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) from 1989. Results Duration of breastfeeding reduced the onset of the CD in the first year p = 0.039 (OR = 1.43 95% CI 1.019–1.899). Also, breastfeeding at the time of gluten introduction significantly delayed the age at diagnosis (F = 1.671, t = 2.39, p = 0.029). The timing of gluten introduction did not affect the age of occurrence of CD in these group of children. Conclusion Longer breastfeeding, and breastfeeding at the time of gluten introduction, postponed the onset of classic CD in patients up to two years. The association between the occurrence of CD and the time of introduction of gluten in this age group of patients has not been established

Frequency, severity and type of anemia in children with classical celiac disease

© 2019 Serbia Medical Society. All rights reserved. Introduction/Objective Anemia is the most common extraintestinal manifestation of celiac disease (CD) in children. The aim of this study was to determine the frequency, severity and type of anemia in children with a classical CD, as well as the differences between anemic and non-anemic patients in their age, duration of illness, percentile body length or height, percentage of body weight (BW) deviation compared to ideal, and the degree of damage to the small intestine mucosa. Methods The study was based on a sample of 90 children, 56 females and 34 males, ages 7-90 (18.23 ± 12.7) months with classical CD. The diagnosis of CD is based on the ESPGHAN criteria from 1990 and 2012, and of anemia on the 2011 WHO reference values. Results Anemia was found in 47 (52.22%) patients, of which it was mild in 23 cases [hemoglobin (Hb) 100-109 g/L] and moderately severe in 24 (Hb 70-99 g/L), in 34 (72.34%) it was microcytic [mean cell volume (MCV) < 70 fl] and normocytic (MCV 70-87 fl) in 13 patients. Low serum iron levels (< 10.7 µmol/L) were found in 68 (75.56%), and hypoferritinemia (< 16 ng/ml) in 77 (85.56%) patients. Except for a greater deficit of BW in patients with anemia compared to those without anemia (-14.64 ± 9.60 vs. -8.56 ± 11.87%, p < 0.01), differences in other defined features were not significant. Conclusion Mild or moderate iron deficiency anemia occurs in slightly more than half of children with a classical type CD. In anemic compared to non-anemic patients, there is a significantly higher BW deficit, while differences in other characteristics typical for this type of disease are not significant

HLA genotyping in pediatric celiac disease patients

© 2014 ABMSFBIH Celiac disease (CD) is a chronic inflammatory disease in the small intestine triggered by gluten uptake that occurs in genetically susceptible individuals. HLA-DQ2 protein encoded by HLA-DQA1*05 and DQB1*02 alleles is found in 90-95% of CD patients. All of the remaining patients carry HLA-DQ8 protein encoded by HLA-DQA1*03 and DQB1*03:02 alleles. Specific HLA-DQ genotypes define different risk for CD incidence. Presence of susceptible HLA-DQ genotypes does not predict certain disease development, but their absence makes CD very unlikely, close to 100%. Here we presented for the first time the distribution of HLA-DQ genotypes in the group of pediatric celiac patients from the University Children’s Hospital, Belgrade, Serbia and estimated risk for CD development that these genotypes confer. Seventy three celiac disease patients and 62 healthy individuals underwent genotyping for DQA1, DQB1 alleles and DRB1 allele. 94.5% of patients carried alleles that encode DQ2 protein variant and 2.7% carried alleles that encode DQ8 protein variant. Two patients carried single DQB1*02 allele. No patients were negative for all the alleles predisposing to CD. The highest HLA-DQ genotype risk for CD development was found in group of patients homozygous for DQ2.5 haplotype, followed by the group of heterozygous carriers of DQ2.5 haplotype in combination with DQB1*02 allele within the other haplotype. The lowest risk was observed in carriers of a single copy of DQB1*02 or DQA1*05 allele or other non-predisposing alleles. HLA genotyping, more informative than serological testing commonly used, proved to be a useful diagnostic tool for excluding CD development

UGT1A1 (TA)n promoter genotype: Diagnostic and population pharmacogenetic marker in Serbia

The UGT1A1 enzyme is involved in the metabolism of bilirubin and numerous medications. Unconjugated hyperbilirubinemia, commonly presented as Gilbert syndrome (GS), is a result of decreased activity of the UGT1A1 enzyme, variable number of TA repeats in the promoter of the UGT1A1 gene affects enzyme activity. Seven and eight TA repeats cause a decrease of UGT1A1 activity and risk GS alleles, while six TA repeats contribute to normal UGT1A1 activity and non-risk GS allele. Also, the UGT1A1 (TA)n promoter genotype is recognized as a clinically relevant pharmacogenetic marker. The aim of this study was to assess diagnostic value of UGT1A1 (TA)n promoter genotyping in pediatric GS patients. Correlation of the UGT1A1 (TA)n genotypes and level of unconjugated bilirubin at diagnosis and after hypocaloric and phenobarbitone tests in these patients was analyzed. Another aim of the study was to assess pharmacogenetic potential of UGT1A1 (TA)n variants in Serbia. Fifty-one pediatric GS patients and 100 healthy individuals were genotyped using different methodologies, polymerase chain reaction (PCR) followed by acrylamide electrophoresis, fragment length analysis and/or DNA sequencing. Concordance of the UGT1A1 (TA)n promoter risk GS genotypes with GS was found in 80.0% of patients. Therefore, UGT1A1 (TA)n promoter genotyping is not a reliable genetic test for GS, but it is useful for differential diagnosis of diseases associated with hyperbilirubinemia. Level of bilirubin in pediatric GS patients at diagnosis was UGT1A1 (TA)n promoter genotype-dependent. We found that the frequency of pharmacogenetic relevant UGT1A1 (TA)n promoter genotypes was 63.0%, pointing out that UGT1A1 (TA)n promoter genotyping could be recommended for preemptive pharmacogenetic testing in Serbia

Novel genetic risk variants for pediatric celiac disease

Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G&gt;A, KIAA1109 c.2933T&gt;C and c.4268-4269delCCinsTA, HoxB6 c.668C&gt;A, HoxD12 c.418G&gt;A, and NCK2 c.745-746delAAinsG, from which NCK2 c.745-746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c.418G&gt;A is more prevalent in celiac disease patients in the Serbian population (P &lt; 0.01), while NCK2 c.745-746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0.03). SLC9A4 c.1919G&gt;A and KIAA1109 c.2933T&gt;C and c.4268-4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance. Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology. © 2016 The Author(s)