Khaled Saad

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children

Objectives: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. Methods: We performed a case–controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. Results: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. Conclusion: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. Trial registration number: UMIN-CTR Study Design: trial Number: R000016846.

Trace element, oxidant, and antioxidant enzyme values in blood of children with refractory epilepsy

Purpose: The aim of this study is to evaluate the serum levels of some trace elements, oxidants, and antioxidants in children with intractable epilepsy compared to healthy children. Patients and Methods: In a case–control study, 40 children (24 males and 16 females) suffering from refractory generalized epileptic seizures were compared with 40 sex- and age-matched healthy children serve as a control group. Serum selenium (Se), zinc (Zn), copper (Cu), and plasma malondialdehyde (MDA) as well as erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) values were measured in the patients and controls. Results: Plasma MDA values of the patient group were significantly ( p < 0.001) higher than those in control. Serum Zn, Se, and erythrocyte GSH-Px values of the patient group are significantly ( p < 0.001) lower than those in control, although there is no statistical difference in Cu and SOD values. Conclusion: Plasma MDA, erythrocyte GSH-Px, and trace elements Zn and Se may play an important role in the pathogenesis of intractable epilepsy in children.

A Randomized, Placebo-controlled Trial of Digestive Enzymes in Children with Autism Spectrum Disorders

Objective There is growing evidence for a gut-brain connection associated with autism spectrum disorders (ASDs). This suggests a potential benefit from introduced digestive enzymes for children with ASD. Methods We performed a double-blind, randomized clinical trial on 101 children with ASD (82 boys and 19 girls) aged from 3 to 9 years. ASD patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) diagnostic criteria. Structured interviews of at least one hour each both with the parents and the child were performed. Later on, another two hours-session was conducted applying the Childhood Autism Rating Scale (CARS). ASD patients were randomized to receive digestive enzymes or placebo. Results The ASD group receiving digestive enzyme therapy for 3 months had significant improvement in emotional response, general impression autistic score, general behavior and gastrointestinal symptoms. Our study demonstrated the usefulness of digestive enzyme in our population of ASD patients. Conclusion Digestive enzymes are inexpensive, readily available, have an excellent safety profile, and have mildly beneficial effects in ASD patients. Depending on the parameter measured in our study, we propose digestive enzymes for managing symptoms of ASD. Digestive enzyme therapy may be a possible option in treatment protocols for ASD in the future.

Leukocytes apoptosis and adipocytokines in children with beta thalassemia major.

Abstract β-Thalassemia is a significant public health problem in Egypt. Infectious complications represent the second most common cause of mortality and the major cause of morbidity in β-thalassemia major (BTM). The increased susceptibility of these patients to infectious diseases has been attributed to the abnormalities of the immune system, which is evident by systemic inflammation and immune deficiency. In a case control study, 35 patients with BTM were compared with 30 sex- and age-matched children who served as controls. Serum ferritin, high-sensitive CRP (hsCRP), leptin and adiponectin levels were determined in all subjects. Apoptosis of neutrophils and lymphocytes was measured by the Annexin V-fluoroisothiocyanate binding assay. Serum leptin was significantly lower in patients when compared to controls. In contrast, adiponectin and hsCRP levels were significantly higher in the patients than the controls. Positive correlation was found between adiponectin and hsCRP. BTM patients had significantly higher total leukocytes, neutrophils and lymphocytes compared with controls. BTM children exhibited a significantly increased apoptosis in T-lymphocytes; however, there was no significant difference in the percentage of apoptosis of B-lymphocytes and neutrophils between the patients and the controls. There was a significant negative correlation between serum leptin and the percentage of apoptotic T-lymphocytes. Our BTM patients had a high percentage of apoptotic T-lymphocyte in comparison with controls. In addition, they had disturbed serum levels of adipocytokines and inflammatory markers. These derangements could have a role in the immunological disturbance observed in thalassemic patients.

The role of probiotics in children with autism spectrum disorder: A prospective, open-label study

Objective: There are limited data on the efficacy of probiotics in children with ASD, therefore, this study aims to evaluate the efficacy and tolerability of probiotics in an Egyptian cohort of children with ASD. Methods: Gastrointestinal (GI) flora were assessed by quantitative real-time PCR of stool samples of 30 autistic children from 5 to 9 years old. GI symptoms of autistic children were assessed with a modified six-item Gastrointestinal Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with Autism Treatment Evaluation Checklist (ATEC) before and after 3 months of supplementation of probiotics nutritional supplement formula (each gram contains 100 × 106 colony forming units of three probiotic strains; Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacteria longum). Results: After probiotic supplementation, the stool PCR of autistic children showed increases in the colony counts of Bifidobacteria and Lactobacilli levels, with a significant reduction in their body weight as well as significant improvements in the severity of autism (assessed by the ATEC), and gastrointestinal symptoms (assessed by the 6-GSI) compared to the baseline evaluated at the start of the study. Conclusions: We concluded that probiotics have beneficial effects on both behavioral and GI manifestations of ASD. Probiotics (a non-pharmacological and relatively risk-free option) could be recommended for children with ASD as an adjuvant therapy. At this stage, this study is a single center with a small number of patients and a great deal of additional wide-scale randomized controlled trials are needed to critically confirm the efficacy of probiotics in ASD. Trial registration number: UMIN-CTR Study Design: Trial Number UMIN000026157

Plasma levels of neutrophil gelatinase-associated lipocalin in children with heart failure.

Introduction: Data about plasma levels of neutrophil gelatinase-associated lipocalin (NGAL) in children with heart failure (HF) are very limited. NGAL is used widely as a biomarker for the diagnosis of renal injury in numerous clinical studies. The aim of this study is to investigate the plasma NGAL in children with HF caused by idiopathic dilated cardiomyopathy (IDCM) and its relation to the severity of HF. Material and methods: In a case-control study, 30 nondiabetic children, aged –16 years (all have IDCM) recruited from the pediatric department of our institute together with 30 healthy children were prospectively enrolled in this study. Patients underwent a detailed history taking, clinical examination, New York Heart Association (NYHA) class assessment and echocardiographic evaluation. Plasma levels of NGAL were measured by enzyme-linked immunosorbent assay. Results: Plasma levels of NGAL were significantly higher in children with HF compared with healthy controls (mean: 290.97 versus 144.33, p < 0.0001). The relationship between NGAL and the severity of HF was investigated. However, we did not find any statistically significant relationship between plasma NGAL levels and indices of myocardial function. Conclusions: NGAL levels were significantly increased in children with HF caused by IDCM. However, there was no significant relationship between plasma NGAL levels and indices of myocardial function. Future multicenter clinical studies in a large population addressing the natural course of NGAL in HF and its potential as a treatment target are needed in the near future.

Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children.

Background: Bovine colostrum (BC) has direct antimicrobial and endotoxin-neutralizing effects throughout the alimentary tract, as well as other bioactivities that suppress gut inflammation and promote mucosal integrity and tissue repair under various conditions related to tissue injury. The precise role of BC in respiratory and gastrointestinal (GI) infections in children is not well defined. The aim of this study was to evaluate the efficacy and tolerability of BC administration in preventing recurrent upper respiratory tract infections (URTI) and diarrhea in children. Methods: One hundred sixty children (aged 1–6 years) having recurrent episodes of URTI or diarrhea received BC for 4 weeks. The number of episodes of URTI, diarrhea, and frequency of hospitalization required for URTI and diarrhea occurring during the study period were assessed at weeks 8 and 24. Results: From a total number of 160 children, 81 patients (50.63%) were males. The mean age (± SD) was 3.65 (± 2.01) years. The mean (± SD) total number of infections was significantly decreased after BC therapy from 8.6 ± 5.1 at baseline to 5.5 ± 1.2 after 2 months (P < 0.001) and to 5.7 ± 1.6 after 6 months (P < 0.001). The mean (± SD) total number of URTI (P < 0.0001), number of episodes of diarrhea (P < 0.001), and number of hospital admissions (P < 0.001) were significantly decreased after BC therapy. Conclusion: BC is effective in the prophylaxis of recurrent URTI and diarrhea as it reduces the number of episodes and the hospitalization due to these infections. Results of this study suggest that BC could be provided as a therapeutic option for children with recurrent URTI and diarrhea.

Effects of royal jelly supplementation on regulatory T cells in children with SLE.

Background and objective To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). Methods This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks. Results The percentages of CD4+ CD25+high FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+ regulatory T cells) were significantly increased after RJ treatment when compared with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased after RJ therapy when compared with baseline values and the control group. Conclusion This is the first human study on the effect of RJ supplementation in children with SLE. Our results showed improvements with 3-month RJ treatment with regard to the clinical severity score and laboratory markers for the disease. At this stage, it is a single study with a small number of patients, and a great deal of additional wide-scale randomized controlled studies are needed to critically validate the efficacy of RJ in SLE.

A comparison between plasmapheresis and intravenous immunoglobulin in children with Guillain–Barré syndrome in Upper Egypt

Objective: The aim of our study is to assess the clinico-electrophysiological profile of children with Guillain–Barré syndrome (GBS) in Upper Egypt and to compare the efficacy of plasmapheresis versus other treatment modalities. Patients and methods: This was a retrospective study of children from January 2010 to October 2014 diagnosed as GBS. It included 62 cases. Results: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) was the most prevalent type of GBS in our locality. As regards the treatment, 32 cases received plasmapheresis while 30 patients received intravenous immunoglobulin. We found a significant decrease in the duration of hospitalization and a significant increase in the number of children with complete recovery in cases treated with plasmapheresis. Conclusion: GBS is not uncommon in children of Upper Egypt, with AIDP the most prevalent type. Plasmapheresis is the best treatment modalities for GBS as it reduces the duration of hospital stay and hastens the recovery of those children.

Oxidative status in children and adolescents with autoimmune thyroiditis

AbstractOxidative status in autoimmune thyroiditis (AIT) has not been investigated previously in children and adolescents. We investigated oxidant and antioxidant systems in a cohort of Egyptian children and adolescents with AIT to explore these as biomarkers of autoimmunity and thyroid function. Our case control study included 32 children with AIT and 32 healthy subjects with matching age and sex as a control group. After a thorough history and physical examination, a thyroid ultrasound, measurements of thyroid-stimulating hormone (TSH), free thyroxin (FT4), antithyroid peroxidase antibodies (TPOAb), and antithyroglobulin antibody were done with assessment of malondialdehyde (MDA) and total antioxidant capacity (TAC) levels as oxidative stress markers. Overt hypothyroidism was detected in 23/32, while subclinical hypothyroidism was detected in nine of the 32 studied patients. MDA levels were significantly elevated, while TAC levels were significantly decreased in AIT patients compared with healthy controls. The difference was more evident in patients with overt hypothyroidism than those with subclinical hypothyroidism. We also observed significant positive correlations of TPOAb levels with age, TSH, MDA, and thyroid volume, finding a negative correlation with TAC and FT4. In conclusion, the high serum MDA and lower TAC levels in patients with AIT and the correlation of thyroid antibodies with biomarkers of oxidative stress may reflect the role of autoimmunity in the development of oxidative stress. Future studies are needed for evaluation of antioxidant therapy for AIT patients. ClinicalTrials.gov Identifier NCT02318160. https://clinicaltrials.gov/ct2/show/NCT02318160.