The clinical pattern of nephrotic syndrome in children has no effect on the concentration of soluble urokinase receptor (suPAR) in serum and urine.

Concentration of soluble urokinase receptor (suPAR) was regarded as viable marker to differentiate the focal segmental glomerulosclerosis (FSGS) from other glomerulopathies and also as predictive parameter for progression of renal disease. AIM: The aim of this study was to evaluate serum and urine (s)(u)suPAR concentration in steroid-sensitive and steroid-resistant nephrotic children treated with different (double and triple-drug) regimens. MATERIALS AND METHODS: Overall 43 children were evaluated including 14 patients with steroid-resistant nephrotic syndrome (SRNS) aged 9±6 years and 29 with steroid-sensitive nephrotic syndrome (SSNS) aged 9±5 years, as well as control group (n=59). The concentration of suPAR was measured with ELISA kit (R∧D Systems Inc.). RESULTS: There was no difference in serum suPAR level between SRNS (6404, range: 4613-9575 pg/mL) and SSNS (5745, range: 4666-8246 pg/mL) patients, and also in urinary suPAR: SRNS (2877, range: 847- 19121 pg/mL) and SSNS (2854, range: 328-7434 pg/mL), respectively. There was no statistically significant difference in serum biomarker concentrations between patients with severe course of the disease, in combination therapy, with three drugs: CsA + MMF + Pred (5968, range: 4613-9575 pg/mL) in comparison with patients receiving double therapy: CsA + Pred or MMF + Pred (5449, range: 4666-6623 pg/mL, 5905, range: 5102-6730 pg/mL, respectively). SuPAR concentration in the urine of patients treated with Pred + MMF was lower (1493, range: 328-4444 pg/mL) than in patients receiving Pred + CsA (3193, range: 629-7434 pg/mL), as well as lower than in patients with triple combination of drugs (3318, range: 448-5570 pg/mL), however the difference was not statistically significant. CONCLUSIONS: Serum and urine concentration of suPAR did not different between different clinical patterns of nephrotic syndrome in children, regardless the immunosuppressive treatment used.

Evaluation of the immunoradiometric and electrochemiluminescence method for the measurement of serum insulin in children.

Human insulin is a polypeptide hormone produced, stored, and secreted by the ß-cells in the pancreatic islets of Langerhans. Its secretion is stimulated by an increase of the glucose concentration in circulation. Non-radioactive assays are frequently used in many laboratories to measure hormone concentrations, as an alternative to the traditional "gold standard" radioimmuno- and immunoradiometric assays. The precise and reliable determination of the insulin concentration is an important concern in numerous diagnostic procedures. The aim of this study was to compare two commercially available assays (manual and automated) for measurement of serum insulin concentrations. Aliquots of the 86 randomly selected serum samples were measured by Elecsys Insulin Assay (cobas e411 immunoassay analyzer, Roche Diagnostics GmbH, Mannheim, Germany) and DIAsource INS-IRMA Kit (DIAsource ImmunoAssays S.A., Louvain-la-Neuve, Belgium). Compared assays exhibit good correlation (r = 0.996). Insulin concentrations were on average 4.2 µ IU/mL lower (p < 0.05) with the cobas e411 immunoassay analyzer when compared to those measured with DIAsouce Immunoassay. Our findings suggest that electrochemiluminescence method on the cobas e411 analyzer and manual IRMA method offered by the DIAsource for the serum insulin determination could be considered interchangeable.

Neutrophil gelatinase-associated lipocalin in blood in children with inflammatory bowel disease.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa glycoprotein present in the bodily fluids and tissues. It is secreted by neutrophils, epithelial cells, hepatocytes and adipocytes, and its expression is highly increased in response to cellular stress. The role of NGAL in the pathophysiology of inflammatory bowel disease including Crohn's disease and ulcerative colitis in children has thus far not been studied. METHODS: The following groups of children were included: (i) inflammatory bowel disease group, n = 36, aged from 1 to 18 years with Crohn's disease (n = 19) and ulcerative colitis (n = 17); (ii) control group, n = 126; and (iii) disease control group, n = 27, without inflammatory bowel disease, with a food and/or inhalant allergy. RESULTS: Healthy children aged from 1 to 8 years exhibited lower NGAL level than those of 9 to 18 years old (39.0; 18.1-83.7 ng/mL vs 57.6; 28.7-107 ng/mL, P = 0.001). In the younger, but not in the older children, the serum NGAL level correlated with their age, r = 0.334, P = 0.001. In children with inflammatory bowel disease, serum NGAL level was higher (108; 37.3-245 ng/mL) than in healthy (42.0; 18.1-107 ng/mL) and allergic, noninflammatory bowel disease children (49.3; 19.3-107 ng/mL), P = 0.001. Serum NGAL levels in Crohn's disease and ulcerative colitis children did not correlate with age, gender, disease activity, and indices of the inflammation. CONCLUSION: Serum NAGL levels are highly elevated in Crohn's disease and ulcerative colitis in children compared to the healthy control group. Systematic studies are needed to explain the role of this protein in the inflammatory bowel disease.

Selected Serum Markers Associated with Pathogenesis and Clinical Course of Type 1 Diabetes in Pediatric Patients-The Effect of Disease Duration.

Biochemical abnormalities in the course of type 1 diabetes (T1D) may cause the production/activation of various proteins and peptides influencing treatment and causing a risk of complications. The aim of this study was to assess concentrations of selected serum substances involved in the pathogenesis and course of T1D and to correlate their concentrations with the duration of T1D. The study included patients with T1D (n = 156) at the age of 3-17, who were divided according to the duration of the disease into those newly diagnosed (n = 30), diagnosed after 3-5 (n = 77), 6-7 (n = 25), and over 7 (n = 24) years from the onset of T1D, and age-matched healthy controls (n = 30). Concentrations of amylin (IAPP), proamylin (proIAPP), catestatin (CST), chromogranin A (ChgA), nerve growth factor (NFG), platelet-activating factor (PAF), uromodulin (UMOD), and intestinal fatty acid binding protein (I-FABP) were measured in sera using immunoenzymatic tests. There were significant differences in concentrations of all the substances except UMOD and NGF between T1D patients and healthy children. The duration of the disease affected concentrations of CST, ChgA, PAF, and NGF, i.e., proteins/peptides which could have an impact on the course of T1D and the development of complications. In long-term patients, a decrease in concentrations of CST and ChgA, and an increase in PAF concentrations were found. In the case of NGF, a decrease was observed after the initial high values, followed by an increase over 7 years after T1D diagnosis. Concluding, the results show that concentrations of selected serum indicators may change in the course of T1D. Further studies are needed to establish whether these indicators could be used in the context of predicting long-term complications.

Healthy Food Pyramid as Well as Physical and Mental Activity in the Prevention of Alzheimer's Disease.

The ageing of the population is resulting in neurodegenerative diseases, including Alzheimer's disease (AD), which are an increasing social, economic and medical problem. Diet and physical activity are now considered as important modifiable factors that help prevent or delay the development of AD and other dementia-related diseases. The pyramid of healthy nutrition and lifestyle is a way of presenting the principles, the implementation of which gives a chance for proper development and a long healthy life. The basis of the pyramid, in the first place, is physical activity. Our review of the literature in the PubMed database supports the hypothesis that complementary factors, such as proper diet, physical exercise and mental activity, have a positive impact on the prevention of neurodegenerative diseases. The nutritional recommendations for healthy adults primarily include the consumption of vegetables, fruits, cereals, legumes, vegetable oils and fishes. Therefore, the introduction of Mediterranean and Asian diets may reduce the risk of the neurodegenerative diseases associated with dementia, whereas dairy products and meat-the main sources of L-carnitine-should be consumed in moderate amounts. The aim of our work is to provide up-to-date knowledge about the appropriate dietary model and healthy lifestyle elements and their impact on good health and the long life of people.

Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre.

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Potential Role of L-Carnitine in Autism Spectrum Disorder.

L-carnitine plays an important role in the functioning of the central nervous system, and especially in the mitochondrial metabolism of fatty acids. Altered carnitine metabolism, abnormal fatty acid metabolism in patients with autism spectrum disorder (ASD) has been documented. ASD is a complex heterogeneous neurodevelopmental condition that is usually diagnosed in early childhood. Patients with ASD require careful classification as this heterogeneous clinical category may include patients with an intellectual disability or high functioning, epilepsy, language impairments, or associated Mendelian genetic conditions. L-carnitine participates in the long-chain oxidation of fatty acids in the brain, stimulates acetylcholine synthesis (donor of the acyl groups), stimulates expression of growth-associated protein-43, prevents cell apoptosis and neuron damage and stimulates neurotransmission. Determination of L-carnitine in serum/plasma and analysis of acylcarnitines in a dried blood spot may be useful in ASD diagnosis and treatment. Changes in the acylcarnitine profiles may indicate potential mitochondrial dysfunctions and abnormal fatty acid metabolism in ASD children. L-carnitine deficiency or deregulation of L-carnitine metabolism in ASD is accompanied by disturbances of other metabolic pathways, e.g., Krebs cycle, the activity of respiratory chain complexes, indicative of mitochondrial dysfunction. Supplementation of L-carnitine may be beneficial to alleviate behavioral and cognitive symptoms in ASD patients.

Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial.

INTRODUCTION: The gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D. RESEARCH DESIGN AND METHODS: Children aged 8-17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they received L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal. RESULTS: Ninety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported. CONCLUSIONS: L. rhamnosus GG and B. lactis Bb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D. TRIAL REGISTRATION NUMBER: NCT03032354.

Preventive Role of L-Carnitine and Balanced Diet in Alzheimer's Disease.

The prevention or alleviation of neurodegenerative diseases, including Alzheimer's disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life.

Relation of plasma carnitine and aminotransferases to alcohol dose and time of dependence.

BACKGROUND: Serum aspartate, alanine aminotransferases (AST, ALT), and plasma carnitine are all indirect biomarkers of alcohol abuse. Carnitine transfers long-chain fatty acids from cytoplasm to mitochondria for ß-oxidation. The aim of the study was to determine the relationship between daily alcohol intake, time of alcohol dependence, plasma carnitine, and serum aminotransferases. PATIENTS: We studied 26 men who were addicted for 2-30 years, consuming ethanol from 75 to 700 g/day (alcoholic group), as well as 17 healthy men (control group). RESULTS: In alcoholics, compared to the controls, we found: a significant increase in serum: AST (p = 0.0014), ALT (p = 0.0071), AST/ALT ratio (p < 0.000); significantly lower plasma free carnitine (FC) (p = 0.0316) and total carnitine (TC) (p = 0.0349); and a significant negative correlation between FC (r = -0.6200; R2 = 0.3844; p = 0.0007), TC (r = -0.4365; R2 = 0.1905; p = 0.0258), and time of alcohol dependence, suggesting carnitine as an indirect marker of alcohol abuse. We did not find any significant correlation between FC, TC, and levels of alcohol or aminotransferase activity. CONCLUSION: In the alcoholic group, there was an increase in serum activity of AST, ALT, and AST/ALT ratio that confirms liver injury. In addition, we found low plasma FC and TC, which may indicate damage to mitochondrial ß-oxidation caused by alcohol metabolites. The significantly higher plasma FC and TC in patients consuming the most, compared to patients consuming smaller doses of alcohol, may be caused by a lower carnitine demand of injured liver cells, decreased urinary carnitine excretion by impaired renal tubules, and leakage of carnitine into the blood from damaged muscles by the higher quantities of alcohol. The negative correlation between carnitine concentration and time of alcohol dependence may suggest the potential use of carnitine for treatment of alcohol abuse.