Original article
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
Moushira E. Zakia, Hala T. El-Bassyounib, Angie M.S. Tossonc,
, Eman Younessd, Jihan Husseind
Corresponding author
a National Research Centre, Medical Research Division, Biological Anthropology Department, Cairo, Egypt
b National Research Centre, Human Genetics and Genome Research Division, Clinical Genetics Department, Cairo, Egypt
c Cairo University, Faculty of Medicine, Pediatrics Department, Cairo, Egypt
d National Research Centre, Medical Research Division, Medical Biochemistry Department, Cairo, Egypt
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"apellidos" => "Tosson" "email" => array:1 [ 0 => "amstosson@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:3 [ "nombre" => "Eman" "apellidos" => "Youness" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Jihan" "apellidos" => "Hussein" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "National Research Centre, Medical Research Division, Biological Anthropology Department, Cairo, Egypt" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "National Research Centre, Human Genetics and Genome Research Division, Clinical Genetics Department, Cairo, Egypt" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cairo University, Faculty of Medicine, Pediatrics Department, Cairo, Egypt" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "National Research Centre, Medical Research Division, Medical Biochemistry Department, Cairo, Egypt" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Trisomy 21 is the most frequent chromosomal abnormality, which characteristically has significant cognitive disability and neurologic deficiencies. It affects 1/700 to 1/1000 live births.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> Excess inhibition in the brain of patients with an extra chromosome 21 could be responsible for cognitive deficits noticed throughout their lives.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a> Oxidative stress is known to have a substantial role in the pathology because of genetic and epigenetic factors, which suggests that oxidative imbalance contributes to the clinical manifestations in Down syndrome (DS).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">3</span></a> In Down syndrome the oxidative damage has a major role in the neurodegenerative processes.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> Coenzyme Q10 (CoQ10) works as a reactive oxygen species (ROS) scavenger. Possibly, in addition, it stimulates oxidative damage repair enzymes and has a role in the regulation of gene expression. It also might work as a modulator of DNA repair mechanisms.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5,6</span></a> The effect of CoQ10 has been studied in some neurological disorders where mitochondrial dysfunction was detected.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a> This could explain the biochemical process by which exogenous CoQ10 improves the bioenergetic impairment in some mitochondrial myopathies and in cardiomyopathy.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8,9</span></a> Coenzyme Q10 has been administered in patients affected by DS, attempting to counteract the oxidative imbalance present due to its secondary deficiency, with promising results.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">10,11</span></a> Individuals having DS are more prone to infections and autoimmune disorders. Ineffective immune responses in DS lead to recurrent viral/bacterial infections and contribute to the development of various pathophysiological symptoms, including cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The dysfunction of the immune system in DS has been attributed to decreased number of B-lymphocytes, T-cell subset modifications, as well as changes in the levels of anti- and pro-inflammatory cytokines. Tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) have been implicated as key components of immune and also inflammatory processes.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a> An improved and better understanding of the relationship between these different elements may help in the discovery of new approaches to ameliorate the progression of dementia in trisomy 21 patients.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of the study was to evaluate the level of some pro-inflammatory markers (IL-6 and TNFα) and CoQ10 in 5–8 year-old children with DS.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This prospective study included all Down syndrome patients presenting to the Clinical Genetics Clinic, National Research Centre, and outpatient clinic of New Children's Hospital, who met the inclusion criteria over a period of eight months. Both the centre and hospital are general governmental establishments serving middle- and low-income patients.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">The patients’ inclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">Cytogenetically proven Down syndrome patients, having no congenital anomalies or chronic diseases, aged 5–8 years old, who consented to participate in this investigation, were enrolled in the study. The age group 5–8 years was selected, according to the frequency of young DS cases fulfilling the inclusion criteria. At the time of blood sampling, they had no acute illnesses and were not on any type of medications or supplements for at least one month. The study period was determined by availability of kits. The control group consisted of healthy children of similar age and sex fulfilling the inclusion criteria.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">IQ assessment and determination of plasma CoQ10 and cytokines levels</span><p id="par0030" class="elsevierStylePara elsevierViewall">This study was blinded. All samples were coded and numbered by the investigator responsible for collection of clinical data and only she had access to the full data on the subjects. Intelligence quotient (IQ) assessments were done using the 4th edition of Wechsler Intelligence Scale for Children (WISC-IV).<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> Levels of CoQ10 were assayed by a dedicated high-performance liquid chromatography (HPLC) system with electrochemical detector (ECD) produced by Shiseido Co. Ltd. (Tokyo, Japan). CoQ10 levels in plasma were measured as μmol/L. Cytokine quantification was conducted by ELISA using commercial kits for human TNFα and IL-6 (eBio-Science, CA, USA), according to the manufacturer's instructions. The presence and concentration of cytokines were identified by the intensity of the color measured by spectrometry in a micro ELISA reader. Plasma levels of human TNFα and IL-6 were expressed in pg/mL. An Olympus AU400 automatic analyzer (Olympus Corporation, Tokyo, Japan) was used to measure fasting blood glucose with commercial kits (Roche Diagnostics, IN, USA).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The recruitment and experimental protocols of the study were conducted in compliance with the Declaration of Helsinki (as revised in Edinburgh, 2000) and approved by local ethical committee. All legal guardians of participants consented to the study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">All data are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation. Correlation analyses were performed by calculating the Pearson correlation coefficient (<span class="elsevierStyleItalic">r</span>) to assess the relationships between the studied parameters. Statistical analysis was performed using SPSS Statistics 20.0 for windows (IBM SPSS Statistics for Windows, Version 20.0, NY, USA). The results were considered statistically significant at the 0.05 significance level.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">Forty-three Down syndrome patients and 43 controls were enrolled in a prospective study from January 2014 to August 2014. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes clinical data, BMI, and investigations on the studied individuals.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">DS patients had significantly higher body mass index (BMI) than controls (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001). Also, TNFα and IL-6 levels were significantly higher in DS patients compared to controls, with <span class="elsevierStyleItalic">p</span>-values of 0.002 and 0.001, respectively. The CoQ10 level was significantly lower DS patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002). The redox status of CoQ10 (% of oxidized/total CoQ10) was found to be in the range of 28–35% in the plasma of DS children compared to 8–12% in controls. The level of fasting blood glucose was significantly higher in DS patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.004), while the IQ score significantly lower (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001) than controls. The mean IQ score of DS patients was in the range of mild mental disability. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes the results of Pearson correlation coefficients <span class="elsevierStyleItalic">r</span> between CoQ10, pro-inflammatory cytokines, and BMI. There was a significant positive correlation between CoQ10 levels and IQ scores, as well as between IL-6 and TNFα levels.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">It has been postulated that a triplicated chromosome 21 causes a 50% increase in the expression of trisomic genes as a primary dosage effect, which translates directly into biochemical aberrations.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13,15</span></a> A number of studies have shown that trisomy 21 related increase of oxidative stress might be involved in different aspects of DS phenotypes.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4,16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In this study the inflammatory markers and oxidative stress mechanisms in children with Down syndromes are evaluated and compared to controls. In the present study, all patients showed significant decrease in plasma CoQ10, a potent endogenous antioxidant, which may be an important factor associated with oxidative imbalance in children with trisomy 21. Miles et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> found significant decrease of CoQ10 in DS patients. Another study by Tiano et al.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a> concluded that lymphocyte and platelet CoQ10 content were significantly lower in DS patients, a fact which probably underlie oxidative imbalance at the cellular level. However, the present study included a larger number of patients, with an age range of 4 years (5–8 years of age). The CoQ10 redox mechanism is possibly related to maintaining the mitochondrial homeostasis and prevention of free radical production. However, studies comparing data on oxidative DNA damage and systemic oxidative stress parameters in CoQ10-treated DS patients concluded that CoQ10 does not simply work as an ROS scavenger. This is because of the absence of a measurable plasma antioxidant response, which could be masked by the hyperuricemia usually found in DS, together with unchanged DNA levels.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The cytokines IL-6 and TNFα are considered major orchestrators of both immune and inflammatory responses.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">18</span></a> The present study's data showed significant increase in the pro-inflammatory markers IL-6 and TNFα level in serum collected from DS subjects, when compared to the control group, a similar finding to other studies.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">13,19</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">High rates of overweight and obesity among children worldwide and the range of health problems associated with them from psychosocial to adverse metabolic findings warrant development of a number of action plans and setting of global targets for the prevention of obesity in children and adolescents. New preventive strategies, highlighting the important role of physical activity and nutrition education, are necessary. Individual, family, and community variations can affect having a healthy lifestyle.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">20,21</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">High BMI is associated with a specific pattern of low-grade immune activation.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> The present study's data confirm previously described associations between DS and high BMI.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">23,24</span></a> The mean IQ score of the studied DS patients was 60.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.2. Gardiner, in 2014,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a> delineated that although intellectual disability in DS can be only mild delay, the most frequently reported IQ is in the range of 40–50 (mild to moderate delay). Shukla et al.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a> reported that the IQ score of the DS patients had moderate mental disability in 31% and mild mental disability 52% of their patients. The correlation of CoQ10 levels to IQ scores in DS patients signifies the CoQ10 effect on neurodevelopment that may be due to its protective role against nuclear DNA damage, in addition to its redox role.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> It is well-known that diabetes mellitus has a higher prevalence in DS than in the general population,<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">27,28</span></a> while in the present findings the blood glucose level was within normal, which may be explainable by the young age of the patients. The importance of these results from clinical and therapeutic points of view is that it emphasizes the importance of a proper follow-up strategy for DS individuals, and aids to outline novel strategies for the treatment of patients with DS.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion, the levels of Il-6, TNFα, and CoQ10 in young DS patients might represent a key-contributing factor to the neurodegenerative process that culminates in DS. Coenzyme Q10 should be considered a good supplement in young children with trisomy 21 to ameliorate the neurological symptoms.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres794458" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec792769" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres794459" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec792768" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "The patients’ inclusion criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "IQ assessment and determination of plasma CoQ10 and cytokines levels" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-28" "fechaAceptado" => "2016-04-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec792769" "palabras" => array:5 [ 0 => "Coenzyme Q10" 1 => "Down syndrome children" 2 => "Interleukin 6" 3 => "Oxidative stress" 4 => "Tumor necrosis factor α" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec792768" "palabras" => array:5 [ 0 => "Coenzima Q10" 1 => "Crianças com síndrome de Down" 2 => "Interleucina 6" 3 => "Estresse oxidativo" 4 => "Fator de necrose tumoral α" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">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.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">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.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">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 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002), while coenzyme Q10 was significantly decreased (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>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.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">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.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">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 fator de necrose tumoral α, em crianças com a síndrome de Down.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">86 crianças (5-8 anos de idade) de duas instituições públicas foram inscritas neste estudo de caso-controle. No momento da amostragem, os pacientes e os controles não sofriam de nenhuma doença aguda ou crônica e não recebiam nenhuma terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">43 crianças com síndrome de Down e 43 controles foram incluídos em um período de 8 meses (janeiro-agosto 2014). Em comparação ao grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,002), ao passo que a coenzima Q10 apresentou significativa redução (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>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.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusão</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os níveis de interleucina 6 e fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser utilizados como biomarcadores, refletindo 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.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Zaki ME, El-Bassyouni HT, Tosson AM, Youness E, Hussein J. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects. J Pediatr (Rio J). 2017;93:100–4.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; CoQ10, coenzyme Q10; DS, Down syndrome; IL-6, interleukin 6; IQ, intelligence quotient; TNFα, tumor necrosis factor α.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Trisomy 21 group<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>43 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>43 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (y) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender (F/M) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23/20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21/22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TNFα (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6 (pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CoQ10 (μmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">103.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328831.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Clinical data and investigations of studied DS children and controls.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index; CoQ10, coenzyme Q10; DS, Down syndrome; IL-6, interleukin 6; IQ, intelligence quotient; TNFα, tumor necrosis factor α.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">CoQ10 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNF α \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IQ \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BMI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Glucose \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CoQ10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TNF α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328832.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Significant positive correlation between CoQ10 levels and IQ scores.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Significant positive correlation between IL-6 and TNF α levels.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Correlation matrix of CoQ10, pro-inflammatory cytokines, and various parameters in DS children.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 1 | 3 |
| 2024 October | 21 | 24 | 45 |
| 2024 September | 25 | 31 | 56 |
| 2024 August | 45 | 28 | 73 |
| 2024 July | 53 | 34 | 87 |
| 2024 June | 56 | 15 | 71 |
| 2024 May | 70 | 14 | 84 |
| 2024 April | 45 | 21 | 66 |
| 2024 March | 37 | 17 | 54 |
| 2024 February | 37 | 16 | 53 |
| 2024 January | 21 | 17 | 38 |
| 2023 December | 12 | 19 | 31 |
| 2023 November | 23 | 32 | 55 |
| 2023 October | 24 | 28 | 52 |
| 2023 September | 29 | 40 | 69 |
| 2023 August | 19 | 11 | 30 |
| 2023 July | 22 | 10 | 32 |
| 2023 June | 23 | 7 | 30 |
| 2023 May | 25 | 11 | 36 |
| 2023 April | 22 | 9 | 31 |
| 2023 March | 34 | 15 | 49 |
| 2023 February | 20 | 12 | 32 |
| 2023 January | 22 | 29 | 51 |
| 2022 December | 55 | 30 | 85 |
| 2022 November | 24 | 18 | 42 |
| 2022 October | 56 | 26 | 82 |
| 2022 September | 32 | 32 | 64 |
| 2022 August | 31 | 38 | 69 |
| 2022 July | 33 | 26 | 59 |
| 2022 June | 29 | 33 | 62 |
| 2022 May | 48 | 30 | 78 |
| 2022 April | 37 | 29 | 66 |
| 2022 March | 37 | 40 | 77 |
| 2022 February | 11 | 27 | 38 |
| 2022 January | 18 | 19 | 37 |
| 2021 December | 8 | 21 | 29 |
| 2021 November | 6 | 13 | 19 |
| 2021 October | 9 | 21 | 30 |
| 2021 September | 4 | 7 | 11 |
| 2021 August | 6 | 10 | 16 |
| 2021 July | 4 | 1 | 5 |
| 2021 June | 11 | 12 | 23 |
| 2021 May | 8 | 18 | 26 |
| 2021 April | 22 | 9 | 31 |
| 2021 March | 16 | 7 | 23 |
| 2021 February | 3 | 2 | 5 |
| 2021 January | 9 | 7 | 16 |
| 2020 December | 10 | 12 | 22 |
| 2020 November | 7 | 8 | 15 |
| 2020 October | 5 | 9 | 14 |
| 2020 September | 14 | 9 | 23 |
| 2020 August | 1 | 0 | 1 |
| 2020 July | 4 | 7 | 11 |
| 2020 June | 3 | 3 | 6 |
| 2020 May | 3 | 5 | 8 |
| 2020 April | 8 | 9 | 17 |
| 2020 March | 2 | 4 | 6 |
| 2020 February | 14 | 12 | 26 |
| 2020 January | 14 | 14 | 28 |
| 2019 December | 8 | 27 | 35 |
| 2019 November | 8 | 31 | 39 |
| 2019 October | 11 | 34 | 45 |
| 2019 September | 7 | 8 | 15 |
| 2019 August | 8 | 9 | 17 |
| 2019 July | 20 | 9 | 29 |
| 2019 June | 8 | 9 | 17 |
| 2019 May | 7 | 13 | 20 |
| 2019 April | 18 | 15 | 33 |
| 2019 March | 6 | 8 | 14 |
| 2019 February | 13 | 8 | 21 |
| 2019 January | 14 | 10 | 24 |
| 2018 December | 6 | 7 | 13 |
| 2018 November | 14 | 4 | 18 |
| 2018 October | 93 | 10 | 103 |
| 2018 September | 33 | 8 | 41 |
| 2018 August | 19 | 5 | 24 |
| 2018 July | 16 | 5 | 21 |
| 2018 June | 6 | 3 | 9 |
| 2018 May | 14 | 11 | 25 |
| 2018 April | 5 | 0 | 5 |
| 2018 March | 6 | 1 | 7 |
| 2018 February | 8 | 1 | 9 |
| 2018 January | 4 | 2 | 6 |
| 2017 December | 5 | 1 | 6 |
| 2017 November | 3 | 4 | 7 |
| 2017 October | 8 | 2 | 10 |
| 2017 September | 3 | 3 | 6 |
| 2017 August | 5 | 3 | 8 |
| 2017 July | 9 | 5 | 14 |
| 2017 June | 8 | 10 | 18 |
| 2017 May | 8 | 6 | 14 |
| 2017 April | 14 | 5 | 19 |
| 2017 March | 17 | 25 | 42 |
| 2017 February | 19 | 14 | 33 |
| 2017 January | 3 | 9 | 12 |
| 2016 December | 3 | 11 | 14 |
| 2016 November | 0 | 23 | 23 |
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