Study of mitochondrial enzymes: cytochrome c oxidoreductase [complex III], and cytochrome oxidase [complex IV] with copper-zinc containing superoxide dismutase [SOD1] in children with down syndrome

Neither the pathogenesis nor the etiology of Down Syndrome [DS] are clearly understood. There is no evidence however that individual loci are responsible, or that the oxidative damage in DS could be solely explained by a gene dosage effect. Oxidative stress resulting from mitochondrial dysfunction may implicate the role of mitochondrial genome in DS pathogenesis and etiology. Moreover, the early Alzheimer's disease [AD] in DS is attributed to defective mitochondrial enzymes. The aim of the present work was to estimate the activity of mitochondrial electron transport enzymes cytochrome c oxidoreductase [complex III], cytochrome c-oxidase [complex IV] and copper-zinc containing superoxide dismutase [SOD-1] enzymes in children with Down syndrome and compare them with those of the normal children. The study was carried out on 30 Down syndrome children diagnosed by karyotyping and typical healthy children served as controls. Estimation of complex III, complex IV and Cu-Zn containing dismutase enzymes activities were done using spectrophotometeric methods. The results showed that there was a significant increase in the activity of SOD-1 in Down syndrome children compared to normal children with significant increase in DS children 5 years had significantly lower complex III activity than controls. DS children with epilepsy had significantly higher mean activity of SOD-1 than DS children without epilepsy. Both SOD-1 and complex III had significant inverse correlation with head circumference and there was no correlation between the three studied enzymes and the presence of congenital heart defects. Deficiency of the studied mitochondrial respiratory enzymes associated with increase in the activity of superoxide dismutase are a consequence of a generalized mitochondrial disturbance which may lie behind some pathogenetic aspects of Down syndrome and could contribute to impairment of energy metabolism and neurodegeneration, observed in DS

Assessment of the effect of inhaled corticosteroids on bone mineral content in asthmatic children

The use of inhaled corticosteroids [ICS] as a prophylaxis is now recommended in international guidelines for all patients using an inhaled bronchodilator more than once a day. We evaluated the effect of long term ICS therapy on bone mineral content of the lumbar spine, and the potential risk of impaired bone density in prepubertal children. The study was performed on two groups. Group I included 40 asthmatic children [mean age 8.3 +/- 0.5 years] on ICS in the form of beclomethasone dipropionate, 200 to 600 micro g/day [mean dosage 392 +/- 53.5 micro g/day]] for at least 6 months [mean 1.3 +/- 0.5 years]. Group II included 40 mild asthmatic children [mean age 8.2 +/- 0.6 years]. They are not receiving regular corticosteroids whether inhaled or systemic, but were treated only with inhaled beta[2]-stimulants whenever needed. The bone mineral density [BMD] was measured by dual energy X-ray absorptiometry [DEXA] densitometer. Measurements for the two groups were performed at the lumbar spine [L[2]-L[4]. Laboratory measurements included serum calcium, phosphorus and bone specific alkaline phosphatase. The study showed significantly higher BMD measurements in group II [mean 0.597 +/- 0.101 g/cm[2]] than group 1 [mean the 0.522 +/- 0.122 g/cm[2]] [P<0.05]. There were no statistically significant differences between level of serum calcium, phosphorus or bone specific alkaline phosphatase in both groups. A significant positive correlation was found between BMD and both weight and height of the children in both groups [r= 0.766, r= 0.859 in group I and 0.789, 0.825 in group II]. Our findings indicated that long term use of ICS slightly reduced the gain in bone mass in mild to moderately severe asthmatic prepubertal children. We recommended the use of lowest effective dose of ICS, the use of ICS with least oral bioavailability and follow up bone density of the lumbar spine at 6 months intervals

Impact of the swallowing dysfunction and gastroesophageal reflux on nutritional status of children with cerebral palsy

Undernutrition is a frequent problem in children with cerebral palsy who often have significant impairment of the eating and swallowing mechanism. A prevalence of oropharyngeal dysfunction and gastroesophageal reflux [GER] in 30 preschool children with cerebral palsy [CP] was studied using videofluoroscopy with barium contrast. The relation of their feeding dysfunction to their nutritional status was evaluated. Seventeen of these children had spastic tetraplegia, 10 had cerebral diplegia and only 3 had hemiplegia. Five children [16.7%] of our sample had no feeding dysfunction, they all had mild functional motor impairment and topographically, they had diplegia; 83.3% of these children had feeding dysfunction. Of these, 44% had combined dysfunction, 28% had isolated swallowing defect and 28% had isolated GER. Evidence of respiratory infection was present in 7 patients during radiological examination. Malnutrition, defined as triceps skin fold thickness [TSF] less than the third percentile for age and sex, was present in 50% of the cases. We found negative correlation between the degree of severity of cerebral palsy and both TSF and weight standard deviation score [r: -0.867, r: -0.748respectively]. Children with combined swallowing defect and GER had the lowest mean TSF and weight standard deviation score [3.26 +/- 0.52 mm and -3.4 +/- 0.87 respectively]. These findings were statistically significant [F= 2.83 and 3.12 respectively]. This study showed the value of using videofluoroscopy for assessment of feeding dysfunction in children with cerebral palsy. Assessment of secondary malnutrition and feeding dysfunction should be regarded as an important part of their general care. A multidisciplinary team should carry out this assessment

Combined ultrasonographic and clinical evaluation of high risk neonates for developmental dysplasia of hip: a prospective study

Developmental dysplasia of the hip [DDH] continues to be missed by routine physical screening examinations in the early months when treatment is most effective. Real time ultrasonography is valuable in detection of DDH in the young infants less than three months old. We performed a prospective study to evaluate the use of ultrasound screening that targets a select [high risk newborn] population for DDH aiming to increase the early diagnosis of this condition and decrease the incidence of late cases. From 2121 live births in our hospitals; we identified 188 [8.8%] newborns with risk factors for DDH. We followed these patients by clinical examination and ultrasound at birth, 6 weeks and 12 weeks of age. Initial ultrasound scan showed that 28% of the cases had findings suggestive of dysplastic hip, about half of them were clinically normal during neonatal examination. On subsequent scanning, the proportion of abnormal hip decreased gradually so that by 12 weeks, 80% had normal ultrasound appearance. Abnormality was more common in babies with breech presentation and family history of DDH. One female infant, not diagnosed by clinical examination at birth and with no risk factors, had abnormal clinical examination and ultrasound appearance of DDH by 12 weeks. From our study, we conclude that selective screening with ultrasound for the hip of newborns with specific physical and historical risk factors for DDH is more effective than clinical screening alone. It targets treatment to these infants who need it, and reveals a number of dislocated and subluxated hips that would otherwise be missed. It is better done when they are 4-6 weeks old. Clinical assessment cannot be restricted only to the first 2-3 days after birth but continued during the first year of life

Calcium regulating hormones in children with insulin dependent diabetes mellitus [IDDM]

Recent studies have revealed that altered mineral metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of calcium regulating hormones on calcium homeostasis and whether they are linked to glycemic control, we have designed this study. The study included 20 children with insulin dependent diabetes mellitus [IDDM] aged from 5.8 - 13 years and 20 age and sex matched normal children who served as control. Serum level of parathyroid hormone, 1,25 dihydroxy vitamin D, calcitonin, serum total and ionized calcium, phosphorus and magnesium were measured. The study included also measurement of biochemical bone remodeling markers [serum alkaline phophatase and osteocalcin]. Glycemic control was assessed in diabetic children by measurement of fasting blood sugar level and glycosylated hemoglobin. The levels of serum calcium, and magnesium were significantly lower in diabetic patients than control and they were significantly correlated with the fasting blood sugar level. In parallel, significant lower levels of 1,25 dihydroxy vitamin D were observed in diabetic patients than control group and were significantly correlated to glycosylated hemoglobin This may indicate that poor control of diabetes significantly affects the level of this active metabolite of Vitamin D. Serum level of calcitonin was slightly higher in diabetic children than control but this was not statistically significant. The levels of serum osteocalcin were significantly lower in diabetic patients than control and they were significantly correlated with the level of glycosylated hemoglobin This may indicate that the degree of metabolic control and duration of disease affected it. It was concluded that, in IDDM, an osteoblastic deficit appears to exist with decreased bone turnover and increased bone resorption. This deficit is aggravated by lower level of 1,25 dihydroxy vitamin D, increased levels of calcitonin and failure of activation of parathyroid hormone. Glucosuric induced osmotic diuresis may also be responsible for the negative calcium balance observed in these patients