Abnormal circadian rhythm and cortisol excretion in autistic children: a clinical study

Aim To determine the circadian rhythm alteration of cortisol excretion and the level of corticosteroids in children with different grades of autism severity. Methods The study included 45 children with different grades of autism severity (low [LFA], medium [MFA], and high functioning autism [HFA]), 15 in each group, and 45 age/sex-matched children with typical development. The urinary levels of free cortisol (at three phases of 24-hour cycle), corticosteroids, vanilylmandelic acid, and 5-hydroxyindole acetic acid were determined. Results Alteration in the pattern of cortisol excretion (Phases I, II, and III) was observed in children with LFA (Phase I: 43.8 ± 4.43 vs 74.30±8.62, P = 0.000; Phase II: 21.1±2.87 vs 62±7.68, P < 0.001; Phase III: 9.9 ± 1.20 vs 40 ± 5.73, P < 0.001) and MFA (Phase I: 43.8 ± 4.43 vs 52.6±7.90, P < 0.001; Phase II: 21.1±2.87 vs 27.4±4.05, P < 0.001; Phase III: 9.9 ± 1.20 vs 19 ± 2.50, P < 0.001) compared to the control group. The corticosteroids excretion levels were higher in all the groups of children with autism than in the control group. The level of 5-hydroxyindole acetic acid was significantly higher in children with LFA (8.2±1.48 vs 6.8±0.85, P < 0.001) and MFA (8.2±1.48 vs 7.4± 0.89, P = 0.001) and not significantly higher in children with HFA than in the control group. The changes were correlated with degrees of severity of the disorder. Conclusion These data suggest that altered cortisol excretion pattern and high level of corticosteroids in urine may probably be a consequence of altered hypothalamic-pituitary- adrenal axis function, which may contribute to the pathogenesis and affect the severity of autism

ANALYSIS OF SALIVARY COMPONENTS TO EVALUATE THE PATHOGENESIS OF AUTISM IN CHILDREN

Objective: Autism is a neurodevelopmental disorder affecting the cognitive and social skills with severe implications on the affected individual'sability to lead productive and independent life. The present study is focused on evaluating the alteration in the levels of salivary components includingantioxidants, in children with different grades of severity of autism.Materials and Methods: Unstimulated whole saliva sample was collected from normal, and autistic children grouped as medium functioning autism(MFA) and low functioning autism (LFA) based on childhood autism rating scale score (n-20 in each group). Concentration of protein, cholesterol,thiocyanate (SCN¯), mucin, uric acid, lipid peroxides (LPO), reduced glutathione (GSH), α-amylase and antioxidant enzymes activity were determinedin saliva.Results: LFA group showed elevated levels (p=0.000) of protein, SCN¯, mucin, uric acid, α-amylase and LPO when compared to MFA group andnormal children. Antioxidant enzymes, cholesterol and GSH levels were significantly decreased (p=0.000) in LFA than in MFA and normal children.Significant elevation in the levels of SCN¯ (p=0.001) and mucin (p=0.004) was observed in LFA than in MFA. The electrophoretic pattern revealed thatprotein corresponding to 52-63 kD are significantly elevated, and 63-76 kD are decreased in autistic children. Western blot of salivary glutathione-Stransferase-2 (GST-2) showed decreased activity in LFA than in MFA and normal children.Conclusion: The results showed that alteration in salivary components, including antioxidant enzymes, especially GST was proportional to theseverity of autism, which can act as biological marker for diagnosing autism and also saliva can be considered as a non-invasive specimen to study thepathogenesis of autism like other biological specimen.Keywords: Antioxidants, Autism, Glutathione-2, Low functioning autism, Medium functioning autism, Protein marker, Unstimulated saliv

Distribution of the different genotypes of HCV among patients attending a tertiary care hospital in South India

Background: Genotyping of the hepatitis C virus (HCV) and assessment of viral load is important for designing therapeutic strategies and region specific diagnostic assays. Objectives: To determine the distribution of HCV genotypes among patients attending a tertiary care hospital in south India, and to correlate this with viral load. Study design: Ninety HCV RNA positive patients were recruited for the study. HCV genotyping was carried out using type-specific primers from the core region of the viral genome [J. Clin. Microbiol. 35 (1997) 201]. Viral load estimations were carried out using the Amplicor HCV Monitor (Versions 1.5 and 2, Roche Diagnostics, Branchburg, NJ, USA). Clinical details were elicited from patients' hospital records. Results: Genotype 3 was detected most frequently (62.2%) followed by infection with HCV genotype 1 (18.8%). There was no significant difference seen in alanine aminotransferase (ALT) values between the two genotypes. Genotype 1 was associated with a significantly higher viral load as compared with genotype 3 (P=0.001). Parenteral transmission accounted for 61% of all infection caused. Infection with genotype 1 was significantly associated with a history of haemodialysis (P=0.01). Genotype 3 was detected more frequently in patients from east India, as compared with its detection in patients from south India (P=0.004). Similarly, genotype 1 was detected with greater frequency in individuals from south India as compared with patients from east India (P=0.004). The concordance between Ohno's genotyping assay and nucleotide sequencing, for genotypes 1 and 3, was 75%. Conclusions: HCV genotypes 1 and 3 accounted for 81% of HCV infections in patients from this geographical region. HCV genotype distribution showed regional differences and genotype 1 was associated with higher viral loads. Parenteral transmission was the major route for acquisition of HCV infection. Ohno's type-specific primer based genotyping assay can be used for distinguishing between HCV genotype 1 and non-1 HCV genotypes in laboratories that do not possess nucleotide sequencing facilities

Immunochromatography in CSF improves data on surveillance of S. pneumoniae meningitis in India

Introduction: Streptococcus pneumoniae is a significant cause of childhood bacterial meningitis in India. The United States Food and Drug Administration has licensed an immunochromatographic (ICT) test, Binax®NOW™, to detect the C polysaccharide antigen of S. pneumoniae in cerebrospinal fluids (CSF). Accurate etiological diagnosis of bacterial meningitis in India is essential for effective treatment strategies and preventive interventions. Materials and methods: CSF samples from 2081 children admitted, with clinically suspected bacterial meningitis at 11 sentinel sites of hospital based sentinel surveillance network for bacterial meningitis in India between September 2009 and December 2016 were tested with ICT. Concurrent CSF cultures were processed using standard procedures. Results and discussion: S. pneumoniae was detected thrice the number of times by ICT than by CSF culture, with a sensitivity and specificity of 100% and 95.3% respectively. This rapid ICT test proves to be of immense use as a diagnostic test for meningitis patients with/without prior antibiotic treatment, especially in facilities with limited laboratory infrastructure in resource limited settings. Keywords: India, Pneumococcal meningitis, Binax, Rapid tes