Impact of interleukin 13 (IL13) genetic polymorphism Arg130Gln on total serum immunoglobulin (IgE) levels and interferon (IFN)-γ gene expression.

This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in interleukin (IL)-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Gln576Arg, in the control of serum total and antigen-specific immunoglobulin (Ig)E levels. Furthermore, we analysed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response [IL-4, IL-13, interferon (IFN)-γ, IL-8 and IL-10]. Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1-8 years. TaqMan allelic discrimination, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphisms (RFLP) methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan gene expression assays. We found elevated total IgE levels in carriers of IL13 Arg130Gln variant allele [odds ratio (OR) = 1·84; 95% confidence interval (CI) = 1·16-2·93]. This effect was more apparent for boys (OR = 2·31; 95% CI = 1·25-4·28). However, no significant association was observed for the other four variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying the Arg130 allele (P = 0·005). No differences were found for IL4, IL8 or IL10, while IL13 gene expression was under the detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression.

Plasma concentrations of selected antioxidants in autistic children and adolescents.

Few studies have demonstrated an increased vulnerability to oxidative stress in autism. The results of previous studies have shown that endogenous antioxidant defence is insufficient, indicating that exogenous antioxidant could play a crucial role for oxidative stress prevention in autism. Plasma concentrations of vitamins C, E, A, carotenoids beta-carotene and lycopene were measured in 51 subjects with autistic spectrum disorders aged 5-18 years (27 children aged 5-10 years, 24 subjects aged 11-18 years). Older autistic group was compared with a group of healthy Slovak subjects aged 11-18 years. Older autistic subjects vs. healthy control showed significantly higher vitamin C and beta-carotene plasma values with 92% and 71% vs 54% and 13% of optimal over-threshold values, respectively. This indicates a reduced risk of free radical disease. In younger vs. older autistic group the similarly high plasma vitamin concentrations were recorded. Favourable values of these vitamins suggested that consumption of fruit and vegetables in autistic subjects is optimal. Autistic average vitamin E and A plasma concentrations (non-significantly changed in comparison to control group) were below-threshold with low percentage of over-threshold values. Insufficient vitamin E and A plasma values indicate lower consumption of food rich in vitamins A and E (e.g. whole-grain products, plant oils, oil seeds, nuts, fat spreads and dairy products). Autistic average lycopene concentration is lower in comparison to published non-Slovak data. Conclusions of this pilot study suggest that plasma concentrations of exogenous antioxidants, vitamins E and A, and lycopene in autistic subjects are insufficient (Tab. 1, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

The redox state of glutathione in erythrocytes of individuals with Down syndrome.

BACKGROUND: The redox state of glutathione has been used as indicator for the redox environment of the cell. OBJECTIVES: To investigate relationships between the redox environments, the SOD activity, total antioxidant status and the oxidation stress markers production (MDA and lipofuscin). METHODS: Individuals with Down syndrome and age-matched healthy controls were enrolled into a study. Some parameters of oxidative stress in serum were determined: reduced glutathione, oxidized glutathione, redox potential of this couple (Eh), activity of superoxide dismutase in the red blood cells as well as malondialdehyde and lipofuscin. RESULTS: In the group of persons with DS statistically significant decrease in the GSH concentration was found, however, no differences in the GSSG concentration versus controls was observed. The redox potential values for couple GSH/GSSG are a statistically significantly increased in DS individuals compared to controls. CONCLUSION: In this study we highlighted the different ways of view at the role of GSH in metabolism of persons with DS. It is useful to look at the GSH and GSSG concentrations separately as well as at redox potential value, which influence total redox state of organism (Tab. 2, Fig. 3, Ref. 30) Full Text (Free, PDF) www.bmj.sk.

Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of Down syndrome patients.

Thirty-seven individuals with Down syndrome (DS) were divided into four age categories: (i) 1 to < 6 years, (ii) 6 to < 13 years, (iii) 13 to < 20 years, and (iv) over 20 years. Activities of antioxidant enzymes found in individual age categories were different, but the differences between age groups were not statistically significant. We confirmed significantly higher activities of Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) in blood cells of people with DS as compared to 35 controls, which consisted, for the first time, of siblings of children with DS. No significant differences were found in activities of catalase and glutathione reductase in DS vs. controls. A significant difference was observed in serum concentration of malondialdehyde (MDA) in DS vs. controls (8.39 +/- 0.34 micromol/l vs. 7.34 +/- 0.27 micromol/l; p = .021) and concentration of MDA in erythrocytes of individuals with DS between the third and fourth age group (p = .05). In DS persons, an elevated ratio of SOD to catalase plus GPx with respect to the controls in all age categories was found, suggesting oxidative imbalance, potentially contributing to accelerated aging observed in these persons.

Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome.

Subjects with Down syndrome exhibit various types of cognitive impairment. Neuropathological and neurochemical studies revealed similarities between Down syndrome and Alzheimer's disease, cholinergic deficits being the most consistent findings. To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5-31 years) received placebo and a single dose of transdermal nicotine (5 mg patch) over 2h in a single-blind, within-subjects repeated measures design. Auditory event-related potentials (ERPs) and neuropsychological tests, comprising digit symbol performance subtest from WAIS-R and the Frankfurt Attention Inventory (FAIR) were performed. Effects of nicotine administration in Down syndrome individuals were a decrease of ERP-P3 latency in 7 of 8 subjects (electrode position Cz: 386.9+/-24.0 ms vs. 363.1+/-26.9.2 ms, placebo vs. nicotine, respectively; P = 0.058) and an increase of ERP-P3 amplitude in 6 of 8 subjects (electrode position Cz: 17.4+/-5.5 vs. 18.0+/-4.5 microV, placebo vs. nicotine respectively; P = 0.725). Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.

Serum lipid resistance to oxidation and uric acid levels in subjects with Down's syndrome.

In subjects with Down's syndrome (DS) increased oxidative stress and consequent oxidative cell damage have been reported. The aim of this study was to assess whether the excessive production of free oxygen radicals in these subjects can affect the copper-induced lipid oxidation resistance measured in fresh whole serum. Since a significant elevation of serum uric acid levels, which is an efficient hydrophilic antioxidant, has been repeatedly reported in subjects with DS, we studied the association between increased serum uric acid levels and lipid resistance to oxidation measured directly in serum samples by monitoring the change in absorbance at 234 nm. The group of subjects with Down's syndrome consisted of 25 individuals (aged 18+/-5 years). Control group included brothers and sisters of subjects with DS (n = 25, aged 17+/-7 years). In subjects with DS, the serum lipid resistance to oxidation (lag time) was significantly higher than in controls (p<0.05) and a concomitant increase in serum uric acid levels was observed (p<0.001). A significant positive correlation between lag time and serum uric acid concentration was found in subjects with DS (r = 0.48, p<0.05), while the positive correlation in the control group was not significant. The results suggest that increased serum uric acid levels repeatedly observed in subjects with DS may be associated with an enhanced resistance of serum lipids to oxidation which is thought to play an important role in the atherogenic process.

[Down's syndrome--effect of increased gene expression in chromosome 21 on the function of the immune and nervous system]. / Downov syndróm--dôsledky zvýsenej expresie génov 21. chromozómu na funkciu imunitného a nervového systému.

Down syndrome (DS) is associated with mental retardation, immune disorders and congenital heart diseases. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic phenotypic features may be caused by the presence of the band 21q22, called the "Down syndrome region". Many proteins important for the immune and nervous systems as CuZn-superoxide dismutase (SOD-1), CD18-beta chain of LFA-1, interferon receptor, APP-amyloid precursor protein, protein S-100 beta are coded by chromosome 21. Overexpression of these molecules may contribute to the thymic derangement that results in anomalous maturation leading to functionally impaired T cells. Many factors have been shown to contribute to the immune deficiency which results in high susceptibility to infections, high rate of malignancies, and autoimmune phenomena in persons with DS. The main disorders in the immune system include thymus abnormalities, changes in cell-mediated immunity, phagocytosis, antibodies-mediated immunity and a high prevalence of autoantibodies in persons with DS. Furthermore, the duplication of chromosome 21 genes may generate most of the pathological changes in the central nervous system. There is an increased prevalence of seizure disorders. Such widespread alterations in the cortical areas seem to account for specific impairments observed in short-term and long-term memory, language skills, and cognitive and learning processes. If all principles of optimal health care and adequate education were followed without exception for persons with DS, then the quality of their life could be improved significantly and they would be able to become productive citizens in the society. (Tab. 5, Fig. 3, Ref. 42.)

Changed serum trace element profile in Down's syndrome.

Being cofactors of important antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), which are significantly modified in Down's syndrome (trisomy 21), serum levels of microtrace elements zinc, copper, and selenium and of macroelement magnesium are reported in 16 subjects with Down's syndrome (DS) and their respective well age- and sex-matched controls. Serum zinc and selenium levels were significantly lowered in DS subjects, whereas copper levels were elevated. Consequently, a marked increase (40%) of the copper/zinc ratio in DS persons was observed. There were no differences in serum levels of magnesium between DS and control subjects.

Guidelines for optimal medical care of persons with Down syndrome. International League of Societies for Persons with Mental Handicap (ILSMH).

There are numerous clinical conditions observed in persons with Down syndrome, as described above, which should be taken into consideration in the course of their medical care and management. If provided with optimal medical services, pursuing specific evaluations and examinations, with a focus on preventive aspects and fostering well being in all areas of human functioning, the quality of life of individuals with Down syndrome can be enhanced significantly and their contribution to society substantial.

Thyroid function and plasma immunoglobulins in subjects with Down's syndrome (DS) during ontogenesis and zinc therapy.

Thyroid function parameters and immunoglobulin concentrations in sera of outpatients with Down's syndrome (DS, n = 110) of different ages (DS1 = 1-9 years; DS2 = 6-15; DS3 = 15-35) were compared with those of age-matched controls (n = 110). Although mean serum TSH was higher in all DS groups, thyroid hormone concentrations were significantly lower only in DS3. In DS1, a notable frequency rate of high T4 and T3 was found. Serum concentrations of thyroxine binding globulin (TBG) were significantly higher in all DS groups. Free T4 and T3 indexes, calculated as the ratio of total hormone: TBG concentrations, were lower in all DS groups. IgA serum concentrations were significantly higher in all DS groups, IgA was higher in DS1 and DS2. Serum zinc levels were lower in all DS groups. Repeated examination after one year revealed lower T4 and higher TSH in DS patients treated with zinc during this interval as compared to values observed before treatment. Our results suggest a high occurrence rate of complex immune and endocrine disorders with thyroid dysregulation in DS patients, with zinc deficiency playing a considerable role.

[Biostim in the treatment of recurrent respiratory diseases in children]. / Biostim v liecbe recidivujúcich respiracných chorôb u detí.

The authors treated with Biostim (Roussel Uclaf Co., France) 20 children aged 3 to 15 years with relapsing and chronic diseases of the respiratory system. A favourable clinical effect was observed in 45% and improvement in 40% of the patients. In the investigated immunological indicators the response to treatment Biostim was manifested in the antibody immunity by a reduction of IgE values (P < 0.01) and of IgM (P < 0.05). As to cellular immunity, there was a significant increase of the phagocytic activity (P < 0.05). The tolerance of the preparation was very good.

[The immune status in children with recurrent otitis media]. / Stav imunity u detí s opakovanými zápalmi stredného ucha.

The results of the research task revealed that the cause of relapsing otitis were in one third of the children various disorders of the immune system (primary and secondary). In the youngest children without disorders of immunity detectable by laboratory methods most probably retarded maturation of the specific antibody response is involved. In cases of confirmed immunity disorders, immunotherapy proved useful.