ABSTRACT
BACKGROUND: Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms. METHODS: Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed. RESULTS: Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats. CONCLUSIONS: This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.
Subject(s)
Adult , Animals , Child , Female , Humans , Infant, Newborn , Male , Rats , Autistic Disorder , Dexmedetomidine , Electroencephalography , gamma-Aminobutyric Acid , Gene Expression , Glutamic Acid , Models, Animal , N-Methylaspartate , Neurodevelopmental Disorders , Propofol , Rats, Sprague-Dawley , Receptors, GABA-A , Receptors, Glutamate , Reflex, Righting , Valproic AcidABSTRACT
BACKGROUND@#Autism is a challenging neurodevelopmental disorder. Previous clinical observations have suggested altered sedation requirements for children with autism. Our study aimed to test this observation experimentally in an animal model and to explore its possible mechanisms.@*METHODS@#Eight adult pregnant female Sprague-Dawley rats were randomly divided into two groups. Four were injected with intraperitoneal sodium valproate on gestational day 12 and four were injected with normal saline. On postnatal day 28, the newborn male rats were subjected to the open-field test to confirm autistic features. Each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). The times to loss of righting reflex (LORR) and to return of righting reflex (RORR) were recorded. On the following day, all rats were re-sedated and underwent electroencephalography (EEG). Thereafter, the rats were euthanized and their hippocampal gamma-aminobutyric acid type A (GABA(A)) and glutamate N-methyl-D-aspartate (NMDA) receptor gene expressions were assessed.@*RESULTS@#Autistic rats showed significantly longer LORR times and shorter RORR times than did the controls (median LORR times: 12.0 versus 5.0 min for dexmedetomidine and 22.0 versus 8.0 min for propofol; P < 0.05). EEG showed a low-frequency, high-amplitude wave pattern 2 min after LORR in the control rats. Autistic rats showed a high-frequency, low-amplitude awake pattern. Hippocampal GABA(A) receptor gene expression was significantly lower and NMDA gene expression was greater in autistic rats.@*CONCLUSIONS@#This study supports the clinical observations of increased anesthetic sedative requirements in children with autism and our biochemical analyses using and glutamate receptor gene expression highlight possible underlying mechanisms.
ABSTRACT
Objectives: The aim of this study was to evaluate the extent and patterns of antibiotic prescription in the outpatient and the emergency departments of a tertiary care center in Makkah, Kingdom of Saudi Arabia
Materials and Methods: A cross-sectional study was carried out by reviewing the pharmacy electronic database from March to May 2013. The World Health Organization core drug use indicators were used. A random sample of 200 OPD and ER antibiotic prescriptions was obtained for detailed patient file review
Results: A total of 3872 antimicrobial prescriptions were identified. This constituted 16.2% of all OPD and ER prescriptions; 10% of OPD prescriptions and 47% of ER prescriptions contained at least one antibiotic. More than 50% of antibiotic prescriptions were not associated with the type of infection on the database. Co-amoxiclav and fluoroquinolones were the most frequently prescribed antibiotics
Conclusions: The overall percentage of antibiotic prescriptions in the OPD and the ER at the tertiary care center in Makkah are acceptable, but the percentage in the ER far exceeded the overall rate. Guidelines are needed to rationalize the prescription of antibiotics in the OPD and the ER