Persistence of the benefit of an antioxidant therapy in children and teenagers with Down syndrome

This study examined the effect of an antioxidant intervention in biomarkers of inflammation and oxidative stress (OS) in the blood of Down syndrome (DS) children and teenagers during four different stages. A control group was composed by healthy children (n = 18), assessed once, and a Down group composed by DS patients (n = 21) assessed at the basal period (t₀), as well as after 6 months of antioxidant supplementation (t₁), after 12 months (after interruption of the antioxidant intervention for 6 months) (t₂), and again after further 6 months of antioxidant supplementation (t₃). Biomarkers of inflammation (myeloperoxidase activity – MPO and levels of IL-1β and TNF-α) and OS (thiobarbituric acid reactive substances – TBARS, protein carbonyls – PC), reduced glutathione (GSH), uric acid (UA) and vitamin E levels, as well as antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and gamma-glutamyltransferase (GGT) activities, were measured after each period. After the antioxidant supplementation, the activities of SOD, CAT, GPx, GR, GGT and MPO were downregulated, while TBARS contents were strongly decreased, the contents of GSH and vitamin E were significantly increased, and no changes in G6PD and GST activity as well as in UA and PC levels were detected. After the interruption of the antioxidant therapy for 6 months, DS patients showed elevated GPx and GGT activities and also elevated UA and TBARS levels. No changes in SOD, CAT, GR, GST, G6PD and MPO activities as well as in GSH, vitamin E, PC, TNF-α and IL-1β levels were detected. The results showed that the antioxidant intervention persistently attenuated the systemic oxidative damage in DS patients even after a relatively long period of cessation of the antioxidant intervention.     

In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex

Sulfite oxidase (SOX) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation and high urinary excretion of sulfite and thiosulfate. Affected patients present severe neurological dysfunction accompanied by seizures, whose pathophysiology is poorly known. In the present study we evaluated the in vitro effects of sulfite and thiosulfate on important parameters of glutamatergic neurotransmission and redox homeostasis in rat cerebral cortex slices. We verified that sulfite, but not thiosulfate, significantly decreased glutamate uptake when cerebral cortex slices were exposed during 1 h to these metabolites. We also observed that thiosulfate inhibited glutamine synthetase (GS) activity. A pronounced trend toward GS inhibition induced by sulfite was also found. Regarding redox homeostasis, sulfite, at the concentration of 10 μM, increased thiobarbituric acid-reactive substances and decreased glutathione concentrations after 1 h of exposure. In contrast, thiosulfate did not alter these parameters. We also found that 500 μM sulfite increased sulfhydryl group content in rat cerebral cortex slices and increased GSH levels in a medium containing oxidized GSH (GSSG) and devoid of cortical slices, suggesting that sulfite reacts with disulfide bonds to generate sulfhydryl groups. Moreover, sulfite and thiosulfate did not alter the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) after 1 h of incubation. However, sulfite inhibited the activities of GPx, GST and G6PDH when cortical slices were exposed for 3 h to sulfite. We finally verified that sulfite did not induce cell death after 1 h of incubation. Our data show that sulfite impairs glutamatergic neurotransmission and redox homeostasis in cerebral cortex. Therefore, it may be presumed that these pathomechanisms contribute, at least in part, to the seizures observed in patients affected by SOX deficiency.     

Enteral nutrition feeding alters antioxidant activity in unstimulated whole saliva composition of patients with neurological disorders

Patients with neurological disorders have an increased risk of oral and systemic diseases due to compromised oral hygiene. If patients lose the ability to swallow and chew food as a result of their disorder, enteral nutrition is often utilized. However, this type of feeding may modify salivary antioxidant defenses, resulting in increased oxidative damage and the emergence of various diseases. The aim of this study was to evaluate the effects of enteral nutrition on biochemical parameters in the unstimulated whole saliva composition of patients with neurological disorders. For this, enzymatic (superoxide dismutase – SOD; glutathione peroxidase – GPx) and non-enzymatic (uric acid; ferric ion reducing antioxidant power – FRAP) antioxidant activity, as well as a marker for oxidative damage (thiobarbituric acid reactive substances – TBARS) were analyzed. Unstimulated whole saliva was collected from 12 patients with neurological disorders and tube-feeding (tube-fed group – TFG), 15 patients with neurological disorders and normal feeding via the mouth (non-tube-fed group – NTFG), and 12 volunteers without neurological disorders (control group – CG). The daily oral hygiene procedures of TFG and NTFG patients were similar and dental care was provided monthly by the same institution's dentist. All patients exhibited adequate oral health conditions. The salivary levels of FRAP, uric acid, SOD, GPx, TBARS, and total protein were compared between studied groups. FRAP was increased (p < 0.05) in the NTFG (4651 ± 192.5 mmol/mL) and the TFG (4743 ± 116.7 mmol/mL) when compared with the CG (1844 ± 343.8 mmol/mL). GPx values were lower (p < 0.05) in the NTGF (8.24 ± 1.09 mmol/min/mg) and the TFG (8.37 ± 1.60 mmol/min/mg) than in the CG (15.30 ± 2.61 mmol/min/mg). Uric acid in the TFG (1.57 ± 0.23 mg/dL) was significantly lower than in the NTFG (2.34 ± 0.20 mg/dL) and the CG (3.49 ± 0.21 mg/dL). Protein was significantly lower in the TFG (5.35 ± 0.27 g/dL) than in the NTFG (7.22 ± 0.57 g/dL) and the CG (7.86 ± 0.54 g/dL). There was no difference in the salivary flow rate and SOD between groups. Enteral nutrition in patients with neurological disorders was associated with lower oxidative damage, resulting in increased salivary antioxidant capacity. These results emphasize the importance of oral care for this population to prevent oral and systemic diseases.     

Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-α in intestinal lymphocytes

Acute exercise in mice induces intestinal lymphocyte (IL) apoptosis. Freewheel running reduces apoptosis and forced exercise training increases splenocyte antioxidant levels. The purpose of this study was to examine the effect of freewheel running and acute exercise on mouse IL numbers and concentrations of apoptosis and antioxidant proteins and pro-inflammatory cytokines in IL. Female C57BL/6 mice had access to in-cage running wheels (RW) or cages without wheels (NRW) for 16 weeks and were randomized at the end of training to no exercise control (TC) or to treadmill exercise with sacrifice after 90 min of running (TREAD; 30 min, 22 m min^?1; 30 min, 25 m min^?1; 30 min, 28 m min^?1; 2° slope). IL were analyzed for pro-(caspase 3 and 7) and anti-(Bcl-2) apoptotic proteins, endogenous antioxidants (glutathione peroxidase: GPx; catalase: CAT) and the pro-inflammatory cytokine, TNF-α. RW mice had higher cytochrome oxidase (p < 0.001) and citrate synthase (p < 0.01) activities in plantaris and soleus muscles and higher GPx and CAT expression in IL (p < 0.05) (indicative of training) compared with NRW mice. TNF-α expression was lower (p < 0.05) and IL numbers higher (p < 0.05) in RW vs. NRW mice. No training effect was observed for apoptotic protein expression, although TREAD resulted in higher caspase and lower Bcl-2. These results suggest that freewheel running in mice for 16 weeks enhances antioxidant and reduces TNF-α expression in IL but does not reduce pro-apoptotic protein expression after acute exercise. Results are discussed in terms of implications for inflammatory bowel diseases where apoptotic proteins and TNF-α levels are elevated.     

Pro-oxidative effects of aggregated transthyretin in human Schwannoma cells

Neurotoxicity mechanisms of amyloidogenic polypeptides such as transthyretin (TTR) are not well understood. Misfolded and aggregated TTRs (agTTR) lead to age-related diseases such as senile systemic amyloidosis and familial amyloid polyneuropathy (FAP). Among other clinical manifestations in TTR amyloidic disease, peripheral nerve tissue, including Schwann cell, degeneration has been observed. In this study, we examined potential toxic effects of agTTR in human Schwannoma cells (sNF94.3 peripheral nerve sheath line). Cells were treated with agTTR (2.4 μM pre-aggregation concentration) or, as controls, normal, soluble TTR (2.4 μM) or no-TTR treatment, and then analyzed for different pro-oxidant and anti-oxidant markers: hydrogen peroxide (H₂O₂), catalase (CAT), glutathione (GSH), and more generalized cellular antioxidant capacity. In the latter case, cytosolic fractions were prepared after agTTR (or control) treatments and analyzed in oxidation assays. Relative to treatment with normal soluble TTR, cells treated with agTTR increase their release of H₂O₂. Residual CAT activity is decreased after agTTR treatment. The Schwannoma cells also exhibit significantly lower levels of GSH after agTTR treatment (p < 0.05, relative to controls). More generally, cytosols from agTTR-treated cells exhibited a lower capacity to prevent oxidation relative to those from control cells (TTR-treated, or non-TTR-treated). These results suggest that agTTR (a) stimulates production of reactive oxygen species, (b) leads to lower levels of endogenous antioxidants, and (c) decreases overall cellular antioxidant capacity, in Schwannoma cells.     

Gender-based differences in oxidative stress parameters do not underlie the differences in mood disorders susceptibility between sexes

The present study aimed to determine whether any gender-related difference exists concerning oxidative stress parameters in a population of 231 subjects, and if these changes might be related to gender-associated differences in major depressive disorder (MDD) or bipolar disorder (BD) vulnerability. This is a case-control nested in a population-based study. The initial psychopathology screen was performed with the Mini-International Neuropsychiatric Interview and the diagnostic was further confirmed with the Structured Clinical Interview for DSM-IV. Blood samples were obtained after the interview and the oxidative stress parameters such as uric acid, advanced oxidation protein product (PCC) and lipid hydroperoxides (TBARS) were determined. Our results indicated a higher prevalence of MDD and BD in women when compared to men. In addition, significant gender differences were found in the levels of PCC (0.27 ± 0.27 vs. 0.40 ± 0.31 nmol CO/mg protein, men vs. women, respectively; P = 0.02) and uric acid (4.88 ± 1.39 mg/dL vs. 3.53 ± 1.02 mg/dL, men vs. women, respectively; P = 0.0001), but not in TBARS (0.013 ± 0.01 nmol/mg of protein vs. 0.017 ± 0.02 nmol/mg of protein, men vs. women respectively; P = 0.243). After sample stratification by gender, no association was found between oxidative stress parameters and clinical diagnosis of MDD and BD for women (P = 0.516 for PCC; P = 0.620 for TBARS P = 0.727 for uric acid) and men (P = 0.367 for PCC; P = 0.372 for TBARS P = 0.664 for uric acid). In this study, women seem more susceptible to oxidative stress than male. However, these gender-based differences do not seem to provide a biochemical basis for the epidemiologic differences in mood disorders susceptibility between sexes.     

Methamphetamine decreases levels of glutathione peroxidases 1 and 4 in SH-SY5Y neuronal cells: Protective effects of selenium

Methamphetamine interferes with dopamine reuptake, and the resulting increased dopamine oxidation that creates oxidative stress can lead to degeneration of dopaminergic terminals. Previous studies have shown that the trace element selenium protects against methamphetamine toxicity. However, the specific selenoproteins responsible for protection have not been elucidated. Glutathione peroxidases 1 and 4 (GPx1 and GPx4) incorporate selenium into the amino acid selenocysteine, and their known antioxidant functions make them good candidates for protection from methamphetamine-induced oxidative damage. We differentiated SH-SY5Y neuronal cells in serum-free media with defined supplement containing 0, 10 and 100 nM selenium, and then challenged the cells with a 24-h exposure to methamphetamine. We found that 100 μM methamphetamine decreased GPx1 and GPx4 protein levels. However, both proteins were upregulated with increasing media selenium concentration. GPx enzymatic activity was also increased by selenium and decreased by methamphetamine and correlated with GPx protein levels. Total glutathione levels were reduced by methamphetamine at lower selenium conditions, while the oxidized fraction of GSH was increased at higher selenium levels. Additionally, we observed an increased generation of reactive oxygen species with methamphetamine exposure in media with 0 nM selenium, which was ameliorated by selenium supplementation. These results show that methamphetamine increases oxidative stress by reducing GPx levels, and this can be reversed with addition of selenium. These findings have important implications for treating patients with acute methamphetamine toxicity.     

Menstrual cycle and reproductive aging alters immune reactivity,NGF expression,antioxidant enzyme activities,and intracellular signaling pathways in the peripheral blood mononuclear cells of healthy women

Reproductive senescence in women is a process that begins with regular menstrual cycles and culminates in menopause followed by gradual development of diseases such as autoimmune diseases, osteoporosis, neurodegenerative diseases, and hormone-dependent cancers. The age-associated impairment in the functions of neuroendocrine system and immune system results in menopause which contributes to subsequent development of diseases and cancer. The aim of this study is to characterize the alterations in immune responses, compensatory factors such as nerve growth factor (NGF) and antioxidant enzyme activities, and the molecular mechanisms of actions in the peripheral blood mononuclear cells (PBMCs) of young (follicular and luteal phases), middle-aged, and old healthy women. Peripheral blood mononuclear cells were isolated from young women in follicular and luteal phases of the menstrual cycle (n = 20; 22.6 ± 2.9 yrs), middle-aged women (n = 19; 47.1 ± 3.8 yrs; perimenopausal) and old (n = 16; 63.2 ± 4.7 yrs; post-menopausal) women and analyzed for Concanavalin (Con A)-induced proliferation of lymphocytes and cytokine (IL-2 and IFN-γ) production, expression of NGF, p-NF-κB, p-ERK, p-CREB, and p-Akt, antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), glutathione-S-transferase (GST)], extent of lipid peroxidation, and nitric oxide (NO) production. Serum gonadal hormones (17β-estradiol and progesterone) were also measured. A characteristic age- and menstrual cycle-related change was observed in the serum gonadal hormone secretion (estrogen and progesterone), T lymphocyte proliferation and IFN-γ production. Salient features include the age-related decline observed in target-derived growth factors (lymphocyte NGF expression), signaling molecules (p-ERK/ERK and p-CREB/CREB ratios) and compensatory factors such as the activities of plasma and PBMC antioxidant enzymes (SOD and catalase) and NO production. Further, an age-associated increase in p-NF-κB expression and lipid peroxidation was observed. Also, serum 17β-estradiol levels were positively correlated with IFN-γ production, SOD activity and NGF expression in the PBMCs. These results suggest that alterations in the levels of gonadal hormones are associated with immunosenescence characterized by decreased IFN-γ production and proliferation of T lymphocytes, decline in NGF expression, SOD and catalase activities, NO production, and signaling mechanisms and thus, may increase the incidence of diseases and cancer in women.     

Biobehavioral and neuroendocrine correlates of antioxidant enzyme activity in ovarian carcinoma

Increased levels of reactive oxygen species (ROS) such as superoxide anions and hydrogen peroxide have been reported in many cancer cells and they have been implicated in carcinogenesis and tumor progression. Antioxidant enzymes, such as Manganese Superoxide Dismutase (MnSOD or SOD2) and Glutathione Peroxidase-1 (GPx1), act coordinately to neutralize ROS. These enzymes are also thought to contribute to cancer cell resistance to conventional radio-chemo-therapies. Although some relationships have been reported between psychosocial factors and the regulation of antioxidant enzymes, little is known about these relationships in the context of cancer progression.The current study investigated the levels of MnSOD and GPx1in confirmed serous, high-grade tumor tissue from 60 ovarian cancer patients, and explored the relationship between the activity of these enzymes, the levels of tumor norepinephrine (NE), and patient mood as determined via pre-operative questionnaires. MnSOD activity was positively related to depressed mood (p = 0.025) and tumor NE (p = 0.023). In contrast, GPx1 activity was inversely related to fatigue (p = 0.015) and tumor NE (p = 0.009), and was positively associated with vigor (p = 0.024). These findings suggest that psychological state and adrenergic signaling are linked with antioxidant enzyme activity in ovarian cancer and may have implications for patient treatments and outcomes.     

The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress

Sleep deprivation induces oxidative stress and impairs learning and memory processes. Vitamin E, on the other hand, is a strong antioxidant that has neuroprotective effect on the brain. In this study, we examined the potential protective effect of chronic administration of vitamin E on chronic sleep deprivation-induced cognitive impairment. In addition, possible molecular targets for vitamin E effects on chronic sleep deprivation-induced cognitive impairment were determined. Sleep deprivation was induced in rats using modified multiple platform model. Vitamin E (100 mg/kg) was administered to animals by oral gavage. Behavioral study was conducted to test the spatial learning and memory using the radial arm water maze (RAWM). In addition, the hippocampus was dissected out and antioxidant markers including glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) were assessed. The results of this project revealed that chronic sleep deprivation impaired both (short- and long-term) memories (P < 0.05), while vitamin E treatment prevented such effect. Additionally, vitamin E normalized chronic sleep deprivation-induced reduction in the hippocampus GSH/GSSG ratio, and activity of catalase, SOD, and GPx. In conclusion, sleep deprivation induces memory impairment, and treatment with vitamin E prevented this impairment probably through its antioxidant action in the hippocampus.     

Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress

Background:

Oxidative stress has been implicated in various disorders including epilepsy. We studied the antioxidant status in patients with epilepsy and aimed at determining whether there was any difference in the antioxidant levels between patients and controls, patients who are not on antiepileptic drugs (AEDs), and on treatment, between individual AEDs and patients on monotherapy and polytherapy.

Materials and Methods:

Antioxidant levels like catalase, glutathione peroxidase (GPx), vitamin E, glutathione (GSH), thiol group (SH), uric acid, and total antioxidant capacity (TAC) were compared between 100 patients with epilepsy and equal number of controls. Twenty-five patients who were not on AEDs were compared with patients on AEDs and the control group. Patients were divided into monotherapy and polytherapy group and antioxidant status was compared between the two groups and between individual drugs.

Results:

Catalase, SH, vitamin E, and TAC were significantly low in patients with epilepsy than those in the control group (P < 0.001). GSH and uric acid did not show any difference; GPx in patients was significantly higher than those in the control group There were no differences in the antioxidant levels between the treated and the untreated groups; however, it was lower in untreated patients than controls (P < 0.001), suggesting that AEDs do not modify the oxidative stress. Patients on Valproate (VPA) showed higher catalase and GPx levels. Catalase was higher in the monotherapy than polytherapy group (P < 0.04).

Conclusion:

Our study found significantly low levels of antioxidant in patients as compared to controls. AED did not influence the antioxidant status suggesting that seizures induce oxidative stress.     

Severity of depressive symptomatology and functional impairment in children and adolescents with temporal lobe epilepsy

ObjectiveDepression is a frequent psychiatric disorder in children with temporal lobe epilepsy (TLE). However, severity of depressive symptoms (DS) is frequently neglected in these patients. This study aimed to determine severity of DS and global functioning by using quantitative measures and to establish their correlation with patients’ demographics and clinical variables.Methods31 children (mean age of 11.8 ± 2.3 years) with TLE were assessed with K-SADS-PL for axis I DSM-IV diagnosis. Severity of DS was measured by Children Depression Rating Scale-Revised – CDRS-R. Global functional impairment was evaluated with Child Global Assessment Scale-CGAS.Results25 patients (56% boys; 12 ± 2.3 years) had current DS, moderate or severe in 84% according to CDRS-R T-Score. Severity of DS was not correlated with age (p = 0.377), gender (p = 0.132), seizure control (p = 0.936), age of onset (p = 0.731), duration of epilepsy (p = 0.602) and the presence of hippocampal sclerosis (p = 0.614). Patients had moderate to major functional impairment measured by CGAS (48.7 ± 8.8), being adolescents more impaired than children (p = 0.03). Impairment of global functioning was not associated with epilepsy variables (p > 0.05).ConclusionChildren with TLE had moderate to severe DS early in the course of their disease with a relevant impact on their global functional activities, especially considering adolescents. Epilepsy severity seems not to be correlated to the severity of DS, contradicting the idea of a cause–consequence relationship. More systematic research is needed to better understand the association of depressive disorders in children and adolescents with TLE.     

Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum

It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimer's disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AβPP female transgenic (Tg2576) (Tg) and wild‐type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild‐type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu‐ZnSOD, GR, and CAT was evaluated by real‐time RT‐PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro‐oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model. © 2009 Wiley‐Liss, Inc.     

Variability of cognitive development in children with Down syndrome: Relevance of good reasons for using the cluster procedure

The main goal of this cross-sectional study was to demonstrate that, in addition to a main change during childhood, the cognitive development of children with Down syndrome (DS) is characterized by interindividual variability in their cognitive functioning. Eighty-eight French children with DS took part in this experiment. They were divided into six chronological age groups: 6 years (N = 9), 7 years (N = 19), 8 years (N = 18), 9 years (N = 19), 10 years (N = 14) and 11 years (N = 9). They were assessed by means of the Differential Scales of Intellectual Efficiency. This test, composed of six independent scales, measures verbal abilities and nonverbal reasoning abilities. Initial analyses of the verbal and nonverbal subtest scores indicated a main change in cognitive skills. We then used a clustering approach to identify four cognitive profiles that distinguished the children with DS independently of age and gender. The results confirm that there is a growth in the cognitive skills of DS children. They also suggest that the cognitive functioning of DS children is characterized by different individual profiles. Implications for more fine-tuned research and intervention efforts are discussed.     

Changes in oxidative stress markers in patients with schizophrenia: The effect of antipsychotic drugs

The aim of this study was to investigate the serum levels or activities of oxidative stress markers in patients with schizophrenia in acute phase and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) after treatment. We consecutively enrolled 41 patients with schizophrenia in acute phase, and 27 patients were followed up with a 4-week antipsychotic treatment. Serum oxidative stress markers were measured with assay kits. We found that Positive and Negative Syndrome Scale (PANSS) total scores were significantly negatively correlated with serum GPx activity and GSH levels and positively correlated with serum SOD activity in patients with schizophrenia in acute phase. In addition, serum GPx activity had a positive correlation with GSH levels and negative correlation with SOD activity. We also found that serum SOD activity was significantly negatively correlated with TBARS levels in patients in acute phase. Furthermore, we found significantly increased changes only in GPx activity in female patients receiving the 4-week treatment (P=0.006). In conclusion, our results suggest that SOD, GPX and GSH might be indicators of schizophrenia severity in acute phase. Furthermore, antipsychotic drugs might affect serum GPx activity in female patients receiving the 4-week treatment.     

Household task participation of children and adolescents with cerebral palsy,Down syndrome and typical development

This cross-sectional study compared patterns of household task participation (e.g., performance, assistance and independence) of youth with cerebral palsy (CP), Down syndrome (DS) and typical development (TD). Parents of 75 children and adolescents were interviewed to report on their youths’ active engagement in daily self-care and family-care tasks, using the children helping out: responsibilities, expectations and supports (CHORES) questionnaire. Groups were equivalent in age (mean = 9.3 years; SD = 2.2 years), sex (male = 39; female = 36), respondent education, presence of maid, and number of siblings at home, but differed on child cognitive function and family socioeconomic status, with the DS and the CP groups scoring lower than the TD group but not different from each other. ANOVA revealed group differences on CHORES performance of self-care tasks (p = 0.004), on total participation score (p = 0.04) and on assistance scores (p < 0.02). Post hoc comparisons showed that TD group scored higher than CP and DS groups on performance and assistance in self-care tasks and total assistance; TD and CP groups were similar on total performance and assistance in family-care tasks. The groups also differed on independence indices; the TD index was greater than the CP and DS, and the CP index was greater than the DS. Parents from the three groups did not differ on ratings of importance regarding their children's household participation (p = 0.416). In spite of observed differences, children and adolescents with CP and DS are actively engaged in daily self-care and family-care tasks; their participation at home is not prevented by the presence of their disabilities.     

Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development

The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS + MLT10), DS with high-dose melatonin administered (DS + MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (p < 0.05). Although melatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (p < 0.05). At 20-weeks of age, myelinated axon number in the DS group was not only significantly lower than all other groups (p < 0.05) but also the cross-sectional area of these axons was smaller than all other groups (p < 0.05). There were no differences between the groups regarding the mean thickness of the myelin sheet. The current study indicates that prenatal exposure to DS decreases the number and the diameter of sciatic nerve axons and that melatonin prophylaxis can prevent these effects.     

Treadmill walking effects on grip strength in young men with Down syndrome

This study was aimed at investigating the relation between grip strength and anthropometric factors and the impact of an aerobic exercise on grip strength in young men with Down syndrome (DS). This study was a pre-post design. Twelve males with DS were assigned to an exercise group, who walked using an incremental protocol on a treadmill for 20 min at aerobic levels. Eight additional persons with DS were assigned to an attentional control group, who watched a video. Measure of grip strength was tested pre- and post-interventions. The results showed positively significant relationship among grip strength and age (r = .74, p < .01), weight (r = .52, p = .02), body mass index (r = .61, p = .01) and waist circumference (r = .54, p = .02). In addition, Grip strength was slightly improved after exercise (p = .03) but decreased after control condition. The results showed that anthropometric factors, such as age, weight, body mass index and waist circumference, were positively correlated with grip strength in young men with DS. Further, improvement in grip strength can be found even after a single exercise session. This finding emphasizes the importance of maintaining an active lifestyle in persons with DS for performing activities of daily living.     

Arterial stiffness response to exercise in persons with and without Down syndrome

This study compared arterial stiffness and wave reflection at rest and following maximal exercise between individuals with and without Down syndrome (DS), and the influence of body mass index (BMI), peak oxygen uptake (VO₂peak) on changes in arterial stiffness. Twelve people with DS (26.6 ± 2.6 yr) and 15 healthy controls (26.2 ± 0.6 yr) completed this study. Intima-media thickness (IMT) and stiffness of common carotid artery was examined. Hemodynamic and arterial variables were measured before and 3-min after exercise. Persons with DS had higher BMI and lower VO₂peak than controls. IMT did not differ between groups. At rest, carotid β stiffness was significantly higher in persons with DS (P < 0.05) but there was no difference in between groups for any of the other arterial stiffness measures. After exercise, persons with DS exhibited attenuated arterial stiffness responses in AIx-75, carotid β stiffness and Ep in contrast with controls (significant group-by-time interactions). When controlling for BMI and VO₂peak, the interactions disappeared. In both groups combined, BMI was correlated significantly with carotid Ep and β at rest. VO₂peak correlated significantly with AIx-75 and its pre-post change (r = ?0.45, P = 0.029; r = 0.47, P = 0.033, respectively). The arterial stiffness responses to maximal exercise in persons with DS were blunted, potentially reflecting diminished vascular reserve. Obesity and particularly VO₂peak influenced these findings. These results suggest impaired vascular function in people with DS.     

Nitrous oxide related behavioral and histopathological changes may be related to oxidative stress

Nitrous oxide (N₂O) toxicity can result in myelin loss and hyperhomocysteinemia similar to cobalamin (Cbl) deficiency. Studies on N₂O exposure can help in understanding the mechanism of demyelination. In view of paucity of studies on N₂O toxicity in rats this study was undertaken. Six male wistar rats were exposed to 1.5 L/min N₂O with 1:1 O₂ for 90 min daily for 1 month. After 1-month exposure blood homocysteine (HCY) and oxidative stress parameters glutathione (GSH) and total antioxidant capacity (TAC) were measured. Brain and spinal cord was subjected to histopathological examination. The neurobehavioral changes, oxidative stress parameters and histopathological changes were correlated with serum B12 and HCY level. After 1-month exposure, the rats appeared sluggish, lethargic and developed predominantly hind limb weakness for 1–1.5 h. In the exposed group, the total distance traveled (2001.66 ± 118.27 cm; p = 0.037), time moving (80.16 ± 5.7 s; p = 0.028), number of rearing (10.33 ± 1.45; p = 0.014) and grip strength (1042.40 ± 51.3 N; p = 0.041) were significantly decreased whereas, resting time significantly increased (219.83 ± 5.7 s; p = 0.030) compared to controls. Serum HCY level was significantly increased (20.56 ± 1.296 μm/ml; p = 0.0007) in the exposed group. However, serum B12 and folic acid levels were not significantly different. GSH significantly decreased (2.21 ± 0.60 mg/dl; p = 0.018) along with TAC (0.76 ± 0.16 Trolox_Eq_mmol/l; p = 0.036). The histopathological studies revealed shrinkage and vacuolation of neurons in cerebral cortex, focal myelin loss, vacuolation in subcortical white matter and spinal cord. N₂O exposure results in behavioral alterations, hyperhomocysteinemia, cortical and spinal cord demyelination which were associated with decrease GSH and TAC highlighting pathophysiological role of oxidative stress.