Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study.

BACKGROUND: Children with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod. METHODS: The study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children's Hospital, in Rome. We reviewed the medical records of all children with a positive history for RI and who received oral prophylaxis of Pidotimod from September 2016 to February 2017. RESULTS: Thirty-three children met the inclusion criteria (males: 51.5%; average age: 6 years ±SD: 3). We found a significant decrease in the number of children with upper respiratory infections (82% at T0 vs 24% at T1; p = 0,0001) and with lower respiratory infections (36% at T0 vs 9% at T1; p = 0.003) after treatment with Pidotimod. We also demonstrated a significant decrease in the number of children hospitalized for respiratory infections (18% at T0 vs 3% at T1; p = 0.03). We measured T and B cells in the peripheral blood and B cell function in vitro at T0 and T1. We found that the response to CpG improved at T1. A significant increase of B cell frequency (p = 0.0009), B cell proliferation (p = 0.0278) and IgM secretion (p = 0.0478) were observed in children with DS after treatment. CONCLUSIONS: Our results provided evidence that Pidotimod may be able to prevent RI in children with Down syndrome.

Molecular Rescue of Dyrk1A Overexpression Alterations in Mice with Fontup® Dietary Supplement: Role of Green Tea Catechins.

Epigallocatechin gallate (EGCG) is an inhibitor of DYRK1A, a serine/threonine kinase considered to be a major contributor of cognitive dysfunctions in Down syndrome (DS). Two clinical trials in adult patients with DS have shown the safety and efficacy to improve cognitive phenotypes using commercial green tea extract containing EGCG (45% content). In the present study, we performed a preclinical study using FontUp®, a new nutritional supplement with a chocolate taste specifically formulated for the nutritional needs of patients with DS and enriched with a standardized amount of EGCG in young mice overexpressing Dyrk1A (TgBACDyrk1A). This preparation is differential with previous one used, because its green tea extract has been purified to up 94% EGCG of total catechins. We analyzed the in vitro effect of green tea catechins not only for EGCG, but for others residually contained in FontUp®, on DYRK1A kinase activity. Like EGCG, epicatechin gallate was a noncompetitive inhibitor against ATP, molecular docking computations confirming these results. Oral FontUp® normalized brain and plasma biomarkers deregulated in TgBACDyrk1A, without negative effect on liver and cardiac functions. We compared the bioavailability of EGCG in plasma and brain of mice and have demonstrated that EGCG had well crossed the blood-brain barrier.

Early Hyperbilirubinemia in Neonates with Down Syndrome.

OBJECTIVE: To compare total serum bilirubin (TSB) levels, phototherapy usage, and hospital readmission for jaundice among neonates with Down syndrome vs controls. STUDY DESIGN: A retrospective cohort study using 15 years of multihospital data. We created control reference intervals (5th, median, and 95th percentiles) for initial TSB values hourly during the first days after birth, and determined the proportion of neonates with Down syndrome whose TSB exceeded the 95th percentile control interval. We determined the proportion with an initial TSB exceeding the upper control reference interval, the highest TSB recorded, the percentage of neonates receiving phototherapy, and the rate of hospital readmission for jaundice treatment. RESULTS: We compared 357 neonates with Down syndrome with 377 368 controls. Compared with controls, those with Down syndrome had 4.7 times the risk (95% CI, 3.9-5.7; P < .0001) of an initial TSB exceeding the 95th percentile control interval (23.5% vs 5.0%), 8.9 times (95% CI, 8.1-9.8; P < .0001) the phototherapy usage (62.2% vs 7.0%), and 3.6 times (95% CI, 1.6-8.2; P = .0075) the readmission rate for jaundice (17.4 vs 4.8 per 1000 live births). CONCLUSIONS: Neonates with Down syndrome have a substantial risk of early hyperbilirubinemia. The American Academy of Pediatrics currently advises obtaining an early screening complete blood count from neonates with Down syndrome. We submit that assessing their TSB is also advisable.

Systematic review and meta-analysis shows a specific micronutrient profile in people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher salivary calcium and sodium.

Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na, and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na (SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.

Thyroid dysfunction in patients with Down syndrome: Results from a multi-institutional registry study.

The goals of this undertaking were to assess the outcomes of thyroid screening tests and adherence to thyroid screening guidelines across five Down syndrome (DS) specialty clinics in various states. Data related to thyroid screening were collected for 663 individuals across five clinics specializing in the comprehensive care of individuals with DS for a period of 1 year. Of the 663 participants, 47.7% of participants had a TSH and free T4 ordered at their DS specialty clinic visit. Approximately 19.0% (60/316) had a new thyroid disorder diagnosis made. We conclude that a sizable proportion of the patients with DS are not up-to-date on current guidelines when they present to a DS specialty clinic, while adherence to thyroid screening guidelines helps facilitate early diagnoses. Hypothyroidism is prevalent in the population, consistent with reported literature. DS specialty clinics can help patients stay current on screening guidelines.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects / Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos

Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002), while coenzyme Q10 was significantly decreased (p = 0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Resumo: Objetivo: Foram relatadas evidências de estresse oxidativo em indivíduos com a síndrome de Down. Há um interesse cada vez maior na contribuição do sistema imunológico na síndrome de Down. O objetivo deste estudo é avaliar a coenzima Q10 e marcadores pró-inflamatórios selecionados, como interleucina 6 e o fator de necrose tumoral α, em crianças com a síndrome de Down. Métodos: Foram inscritas neste estudo de caso-controle 86 crianças (5-8 anos) de duas instituições públicas. No momento da amostragem, os pacientes e os controles não sofriam de doença aguda ou crônica e não recebiam terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência. Resultados: Foram incluídas em oito meses (janeiro-agosto 2014) 43 crianças com síndrome de Down e 43 controles. Em comparação com o grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p = 0,002), ao passo que a coenzima Q10 apresentou significativa redução (p = 0,002). Além disso, o índice de massa corporal e a glicemia de jejum eram significativamente maiores nos pacientes. Houve uma correlação significativamente positiva entre os níveis de coenzima Q10 e do quociente de inteligência, bem como entre a interleucina 6 e o fator de necrose tumoral α. Conclusão: Os níveis de interleucina 6 e o fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser usados como biomarcadores, refletem o processo neurodegenerativo neles. A coenzima Q10 pode ter um papel como bom suplemento em crianças com síndrome de Down para melhorar os sintomas neurológicos.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

OBJECTIVE: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. METHODS: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. RESULTS: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. CONCLUSION: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Immunomodulating activity of Pidotimod in children with Down syndrome.

Acute respiratory tract infections (ARTIs) are the most frequent illnesses in pediatric age, frequently experienced in children with Down Syndrome (DS) due to the associated immune defects of both specific and non-specific immunity. Pidotimod, a synthetic immunostimulant, was shown to reduce the rates of ARTIs in children with DS, however the mechanisms associated with this effect is currently unknown. We analyzed immune parameters in DS children who received the seasonal 2011–2012 virosomal-adjuvanted influenza vaccine. Eighteen children aged 3-10 years (mean age 7.1+/-2.6 years) were randomly assigned (1:1 ratio) to receive Pidotimod 400 mg, administered orally once a day for 90 days or placebo. At the recruitment (T0) all children received a single dose of virosomal-adjuvanted influenza vaccine (Flu). Blood samples were collected at T0 and 3 months after the recruitment (T3) in order to evaluate innate and adaptative immune responses pathway. Flu-specific IgG1 and IgG3 levels in plasma samples were determined at pre-vaccination (T0), and 1 (T1) and 3 months (T3) post-vaccination. The use of Pidotimod was associated with the upregulation of a number of genes involved in the activation of innate immune responses and in antimicrobial activity. Interestingly the ratio of Flu-specific IgG1/IgG3 was skewed in pidotimod-treated individuals, suggesting a preferential activation of complement-dependent effector mechanisms. Although preliminary these data suggest that Pidotimod can potentiate the beneficial effect of immunization, possibly resulting in a stronger activity of both innate and adaptive immune responses.

Effect of zinc supplementation on thyroid hormone metabolism of adolescents with Down syndrome.

Studies have evidenced that zinc metabolism is altered in the presence of Down syndrome, and zinc seems to have a relationship with the metabolic alterations usually present in this syndrome. In this work, the effect of zinc supplementation on thyroid hormone metabolism was evaluated in adolescents with Down syndrome. A prospective study was carried out on 16 adolescents with Down syndrome (age: 10-19 years) who were randomized for treatment with 30 mg zinc daily for 4 weeks. Diet evaluation was accomplished y using a 3-day dietary record, and the analysis was performed by the NutWin program, version 1.5. Anthropometric measurements were performed for evaluation of body composition. The Zn-related nutritional status of the groups was evaluated by means of zinc concentration determinations in plasma and erythrocytes using the method of atomic absorption spectroscopy, and the thyroid hormone was obtained by radioimmunoassay. The diet of patients with Down syndrome, before and after the intervention presented reduced energy level and adequate zinc concentrations. Mean plasma zinc values were 59.2 +/- 13.2 and 71.0 +/- 21.9 microg/dL before and after the intervention, respectively. Erythrocyte concentrations of the mineral before supplementation, instead, were 51.5 microg/dL +/- 11.1 microg Zn/gHb, and at the end of the experiment, they were 42.9 +/- 8/5 microg Zn/gHb, with a significant statistical difference (p < 0.05). Serum concentrations of T(4) hormone before and after zinc supplementation were 1.26 +/- 0.20 and 1.54 +/- 0.63 pg/mL, respectively. Mean T(3) values before intervention were 2.47 +/- 037 pg/mL and, after supplementation, 2.25 +/- 0.67 pg/mL, without significant statistical difference (p > 0.05). Intervention with zinc showed to be effective in the stabilization of the concentrations of this mineral in plasma and erythrocytes, but had no influence on the metabolism of thyroid hormones.

Serum cholinesterases in Down syndrome children before and after nutritional supplementation.

INTRODUCTION: Down syndrome (DS) children have different degrees of developmental abnormalities associated with mental retardation. A cascade of pathological changes triggering alterations in cholinesterase-mediated functions seems to be the cause of neuronal and muscular dysfunctions, such as memory loss, disturbed cognitive skills, and language impairment in virtually all DS individuals, but there are currently no efficacious biomedical treatments for these central nervous system-associated impairments. The present study aimed to evaluate the effects of nutritional supplementation on cholinesterases in serum of DS children. METHODS: Activities of acetyl- and butyrylcholinesterase were analysed in the serum samples of 40 DS children, along with an equal number of age- and sex-matched controls under study. RESULTS: The activities of serum acetyl- and butyrylcholinesterase were found to be low in DS children before nutritional supplementation, compared to controls, and showed considerable improvement after six months of supplementation of zinc in combination with antioxidant vitamins and minerals. A significant improvement was also observed in cognitive skills and behavioural patterns after nutritional supplementation. CONCLUSION: The present pilot study suggests the significance of early intervention with nutritional supplementation in DS children to ameliorate the severity of this disorder.

[Biochemical alterations in patients with Down syndrome]. / Biokémiai eltérések Down-szindromás betegekben.

UNLABELLED: Down syndrome is a chromosome abnormality with specific clinical symptoms and mental retardation caused by trisomy of chromosome 21. The basic genetic change cannot be cured, the control of the associated symptoms, however, may improve the patients' quality of life. AIMS: Authors studied the possible correlations between the Down-specific genes and the related biochemical changes. Expression of superoxide dismutase, cystathionine-beta-synthase and S100 protein was investigated. Further aim of the study was to determine the total serum antioxidant capacity (transferrin, ferritin, total protein, albumin and bilirubin) along with the extracellular antioxidants as well as concentrations of homocysteine, folic acid, and vitamin B 12 . To assess the vascular damage, the activity of NAG and S100B level was measured. METHODS: Standard laboratory methods were used to determine the antioxidant capacity (Stocks, 1974), homocysteine (HPLC), folic acid (capture, IMX-Abbott), vitamin B 12 (MEIA, IMX-Abbott), S100 B protein (chemiluminescence sandwich immunoassay) levels, and N-acetyl-beta-D-glucosaminidase (spectrophotometry). RESULTS: Plasma homocysteine value proved to be lower in 7 of the 30 and higher in 6 of the 30 patients studied than the reference range. Plasma homocysteine was found 95 +/- 21% of the reference value. Relative value of plasma folic acid - expressed in percent of the normal value - was 85 +/- 51%, and that of B 12 was 78 +/- 30%. Deficiency of folic acid was detected in 2 of the 30, decreased level of B 12 in 2 of the 30 patients enrolled. No difference was found in antioxidant activity values between Down syndrome patients and healthy controls, however, neither of them reached the adult reference range. S100 protein concentration of 4-8 times higher values (average value: 0.68 +/- 0.27 microg/l) than upper limit of the reference range was observed (> 1 year: > 0.15 microg/l). Mean value of serum N-acetyl-beta-D-glucosaminidase remained within the reference range (10-30 U/l). No statistically significant correlation between the antioxidant activity and N-acetyl-beta-D-glucosaminidase values could be observed. CONCLUSION: The lower homocysteine, folic acid and B 12 values may be considered as the consequence of an increased cystathionine-beta-synthase activity ("atheroma free model"). There was no significant alteration in antioxidant activity level. It can be supposed that the hydrogene peroxide produced due to increased expression of superoxide dismutase is metabolized by the induced glutathione-peroxidase and catalase keeping by this the balance of the antioxidant system. This hypothesis is supported by the normal N-acetyl-beta-D-glucosaminidase values not indicating any vascular damage. The high S100 values, however, reflect certain brain damage which shows a progress with the age. Based on these experiences, regular control of these parameters is recommended. Furthermore authors think that folic acid supplementation is indicated in order to improve the patients' learning capacity, inhibit the development of Alzheimer symptoms and improve the quality of life.

Coenzyme Q10 absorption and tolerance in children with Down syndrome: a dose-ranging trial.

Controlled studies of coenzyme Q(10) dosing and tolerance have been reported in adults, but not in pediatric patients. This study compares low- and high-dose coenzyme Q(10) (LiQ-NOL syrup) absorption and tolerance in children with Down syndrome. After a 1-month low-dose (1.0 mg/kg/day) run-in period, all participants received high-dose coenzyme Q(10) (10.0 mg/kg/day) for two additional months (in randomized sequence as one daily dose or split into two daily doses). Chemistry profiles and complete blood counts were determined just before and at the study completion. Plasma coenzyme Q(10) concentrations were determined initially and at each study visit. Parents reported adverse events and study drug evaluations using standardized forms. Most of the 16 children who completed this study tolerated high-dose coenzyme Q(10) well. Uncooperative behavior resulted in premature withdrawal of two participants, and may have been treatment-related. Pre- and posttreatment laboratory test changes were considered to be clinically nonsignificant. Study results indicate that high-dose coenzyme Q(10) (10 mg/kg/day) is well-absorbed and well-tolerated by most children with Down syndrome, and appears to provide plasma concentrations which are comparable to previous adult studies administering much higher coenzyme Q(10) dosages.

Effect of vitamin D and calcium supplementation on bone turnover in institutionalized adults with Down's Syndrome.

OBJECTIVE: To assess the status of vitamin D and the effects of calcium and vitamin D3 supplementation on the bone metabolism in a group of adults with Down's syndrome (DS). DESIGN: Randomized, parallel, controlled and open clinical trial. SETTING: Institution for mentally handicapped: Fundación Uliazpi, Diputación Foral de Guipúzcoa, San Sebastián, Spain. SUBJECTS: A total of 23 persons with DS, residents at the Uliazpi Foundation were recruited and all completed the study. INTERVENTION: In all, 12 participants were randomly allocated to receive 1 g of calcium and 800 IU of vitamin D once daily for 1 year while 11 were assigned to the control group, receiving no supplementation. RESULTS: We found no differences between groups regarding serum calcium and phosphorous levels. The remaining parameters showed differences between the two groups consistent with a beneficial effect of the intervention: serum levels of parathyroid hormone, osteocalcin and crosslaps diminished while serum 25 OH vitamin D3 level increased. CONCLUSIONS: The results obtained allow to include people with DS as a risk group with regards to vitamin D deficit, which that can be corrected with vitamin D and calcium supplementation, and giving rise to an improvement of the biochemical markers related to the phospho-calcium metabolism and bone remodelling.

Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms.

BACKGROUND: The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown. OBJECTIVES: We aimed to determine the effects of orally administered folic acid and of folic acid combined with vitamin B-12, vitamin B-6, or both on tHcy in adults with trisomy 21. The study was also intended to analyze the possible influence of gene polymorphisms. DESIGN: One hundred sixty adults with trisomy 21 and 160 healthy, unrelated subjects aged 26 +/- 4 y were included. Plasma tHcy, red blood cell folate, serum folate, and vitamin B-12 were measured. Genotyping for the common methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C, cystathionine beta-synthase 844Ins68, methionine synthase 2756A-->C, methionine synthase reductase 66A-->G, and reduced folate carrier 80G-->A polymorphisms was carried out. RESULTS: The mean tHcy concentration (9.8 +/- 0.7 micromol/L) of cases who did not use vitamins was not significantly different from that of controls (9.4 +/- 0.3 micromol/L). Plasma tHcy concentrations (7.6 +/- 0.3 mmol/L) in cases who used folic acid were significantly lower than in cases who did not. Folic acid combined with vitamin B-12 did not significantly change tHcy concentrations compared with those in cases who used only folic acid. Folic acid combined with vitamins B-6 and B-12 significantly lowered tHcy (6.5 +/- 0.5 micromol/L). The difference in tHcy according to MTHFR genotype was not significant. However, tHcy concentrations were slightly higher in TT homozygotes among the controls but not among the cases. CONCLUSION: This study provides information on the relation between several polymorphisms in genes involved in homocysteine and folate metabolism in adults with trisomy 21.

Uptake of a prenatal screening test: the role of healthcare professionals' attitudes towards the test.

OBJECTIVE: To investigate the association between healthcare professionals' attitudes towards prenatal Down syndrome screening and screening uptake in the women who consult them. METHODS: The attitudes of 71 midwives and 18 obstetricians towards Down syndrome screening and screening uptake in the women who consulted them were assessed at two UK hospitals where uptake rates of Down syndrome screening differed (26 vs 61%). RESULTS: Healthcare professionals based at the hospital with higher screening uptake had more positive attitudes towards Down syndrome screening than healthcare professionals based at the hospital with lower screening uptake (19 vs 17, p = 0.03). Pooling across hospitals, obstetricians had more positive attitudes than midwives (20 vs 17, p = 0.004). In a sub-group of women who discussed screening with one healthcare professional, there was no significant association between individual healthcare professionals' attitudes and screening uptake (Spearman correlation coefficient = 0.13, p = 0.51). CONCLUSION: In this study powered to detect a correlation of 0.5 and over (i.e. a large effect), healthcare professionals' attitudes towards screening were unrelated to uptake of screening in the women consulting them. It remains to be determined if a smaller effect exists. The observed association between healthcare professionals' attitudes and uptake rates by hospitals raises the question of whether healthcare professionals' attitudes might influence systems of care, not just communication with pregnant women.

Socioeconomic barriers to informed decisionmaking regarding maternal serum screening for down syndrome: results of the French National Perinatal Survey of 1998.

OBJECTIVES: We sought to evaluate socioeconomic disparities in serum screening for Down syndrome and assess whether such disparities are more likely to reflect limits in access or information or, rather, informed decisionmaking. METHODS: A nationally representative sample of 12 869 French women completed interviews after giving birth. RESULTS: We found substantial disparities in the likelihood of (1) women not being offered screening, (2) screening not being offered as a result of late prenatal care, and (3) women not knowing whether or not they had undergone screening. Except in the case of nationality, there was essentially no evidence of differences in refusal of testing. CONCLUSIONS: Rather than representing informed decisionmaking, socioeconomic disparities in screening for Down syndrome are mostly due to limits in access or to information.

Aminoacid profile and oxidative status in children affected by Down syndrome before and after supplementary nutritional treatment.

Down syndrome is the most common autosomal aberration among liveborns, characterised by several clinical features and metabolic disturbances. Aminoacid pathways abnormalities and defective oxidative balance are the most common metabolic problems in Down Syndrome. To evaluate the biochemical responses of children with Down Syndrome to a nutritional regimen supplemented with aminoacids, vitamins and polyunsaturated fatty acids, we submitted 86 subjects divided in two groups (0-6 and 6-12 years) to the dosage of plasma levels of aminoacids, antioxidant enzymes activities and reactive oxygen species, before and after 12 months of such nutritional supplementation and in relation to normal controls. The results obtained showed a tendency towards the values of normal subjects with statistically significant differences. Although other studies must be performed to confirm and define such report, our experience supports the usefulness of a nutritional supplementation with aminoacids, vitamins and polyunsaturated fatty acids, also considering the absence of side effects.

Hypothalamic digoxin-mediated model for trisomy 21.

The isoprenoid pathway related cascade was assessed in trisomy 21. Membrane Na+, K(+)-ATPase activity, serum magnesium, and ubiquinone were decreased while hydroxy methyl glutaryl CoA (HMG) coenzyme A (CoA) reductase activity, serum digoxin, and dolichol levels were increased in trisomy 21. There were increased levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline, and morphine in trisomy 21. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycan (GAG) fractions, and lysosomal enzymes in trisomy 21. Reduced levels of ubiquinone, reduced glutathione, and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in trisomy 21. Hypothalamic digoxin and a disordered isoprenoid pathway are important in the pathogenesis of trisomy 21.

Redox balance in patients with Down's syndrome before and after dietary supplementation with alpha-lipoic acid and L-cysteine.

The aim of the present study was to investigate the possible normalizing effect of antioxidants on certain parameters indicative of oxidative stress in Down's syndrome (DS). The study was performed in pediatric patients with DS with proven redox imbalance, who were advised to take a dietary supplementation composed of alpha-lipoic acid and L-cysteine for several treatment cycles (one treatment cycle = 30 days dietary supplementation plus 30 days wash-out). Serum thiol groups, serum total and septic reactive oxygen species (ROS) and total antioxidant status of serum were determined before and after dietary supplementation, using commercially available kits. In all the evaluable patients (n = 20), after 3.8 +/- 1.1 treatment cycles, thiol group serum concentrations and total antioxidant status of serum significantly increased (p < 0.0001 for both parameters) in comparison with basal values, while serum total and septic ROS significantly decreased (p < 0.0001 for both parameters). On the basis of these results it is impossible to demonstrate the clinical effects of the biochemical normalization obtained in patients with DS after supplying alpha-lipoic acid and L-cysteine. These data suggest that delaying the clinical expression of redox imbalance in patients with DS might be feasible by normalizing their redox balance.

[Diminished zinc plasma concentrations and alterations in the number of lymphocyte subpopulations in Down's syndrome patients]. / Disminución de las concentraciones plasmáticas de cinc y alteraciones numéricas de subpoblaciones de linfocitos en pacientes con síndrome de down.

Alterations of plasma levels of zinc and in the immune system in Down's syndrome (DS) have been reported. These alterations have been associated with a high rate of infectious diseases, which represent the main cause of mortality in affected individuals. The objectives of this study were to determine plasma zinc levels and to evaluate the immune system in DS patients. Peripheral blood samples were obtained from 43 DS patients examined at the Unidad de Genética Médica, Universidad del Zulia in Maracaibo, Venezuela. Their mean age (+/- SD) was 2.3 +/- 2.0 years. As control group, 40 healthy children were studied (mean +/- SD 2.3 +/- 2.0 years). Karyotypes by a standard technique, the determination of plasma levels of zinc by atomic absorption spectrophotometry and the evaluation of the immune system by flow cytometry were carried out in the study groups. All DS patients had free trisomy 21. Significantly disminished zinc plasma levels, helper T lymphocyte (CD4) percentage, helper/cytotoxic (CD4/CD8) ratio and B-cells (CD19) were found in DS patients by matching with control group. An increase in CD8 was also found. No significative difference in the lymphocyte subpopulations between DS patients with disminished plasma levels of zinc and DS patients with normal zinc were found. These findings suggest that zinc deficiency is not the sole etiology involved in the disorders of immune system seen in DS patients. Other factors, such as thymic alterations and molecular abnormalities due to gene overexpression of loci located on chromosome 21 could be involved. Although, zinc supplementation is recommended in these patients with zinc deficiency, further studies with a double-blind, placebo versus zinc design are needed to evaluate the potentially beneficial effects of zinc treatment in DS patients.