Airway major mucins in asthmatic children

Mucus is a protective coating secreted in the healthy airway. Structurally, mucins are complex glycoconjugates: their protein backbones are products of mucin [MUC] genes. Twenty mucin genes have been reported. MUC5AC and MUC5B are major gel-forming mucins in normal or pathologic airway secretions. Sputum production is a common symptom in asthma, especially during asthma exacerbations contributing to: airway hyperresponsiveness, airways obstruction, decreasing FEV[1] and fatal attacks of asthma. The aim of this study was to evaluate the expression and distribution of MUC5AC and MUC5B in the sputum and bronchial biopsies of mild and moderate asthmatic children. 2 9/12 years prospective study. Chest unit, Pediatric Department, ENT Department, Tanta University Hospital. 25 asthmatic children during and after acute attack, admitted and treated in chest unit;16 males and 9 females, aged 6-13 years [mean 9.4 +/- 3.6 yr.] On admission, the severity of the asthmatic paroxysm was mild persistent asthma [MiPA] in 14 patients and moderate Persistent asthma [MoPA] in 11. All were treated in chest ward. The study involved [1] sputum induction with RNAs extraction and direct Quantification of MUC5AC and MUC5B mucins of the sputum. [2] Bronchoscopy with mucosal biopsies from each subject for RNA extraction and immunohistochemical analysis. Semiquantitative reverse-transcription polymerase chain reaction [RT-PCR] was performed for MUC5AC and MUC5B to investigate their expression. On RT-PCR examination of the sputum sample, MUC5AC was significantly detected in 80%, 92% and MUC5B in 52%, 68% in MiPA and MoPA respectively compared with controls. MUC5AC and MUC5B mRNAs were amplified weekly in endobronchial mucosa of the controls, whereas they showed two- and threefold mRNA upregulation, in MiPA and MoPA respectively. In sputum samples there were significantly more mucins in MiPA and MoPA than in controls. In addition, there were significantly more mucins in MoPA than in MiPA. Also there was significantly more MUC5AC than MUC5B in each group. MUC5AC immunoreactivity in asthmatics was abundant in goblet cells with no staining of submucosal glandular cells. While immunoreactivity for MUC5B in asthmatics showed abundant signaling in submucosal glandular cells and moderately positive staining in epithelial goblet cells. Goblet cell number was significantly increased in MiPA and MoPA in comparison with controls with no difference between MiPA and MoPA. This study was designed to characterize mucin gene expression in tracheobronchial mucosa and sputum in asthmatic children. The present results suggest that upregulation of MUC5AC and MUC5B with the associated goblet cell hyperplasia [GCH] may play important role in the pathophysiology of asthma. We found that even mild asthma was associated with GCH and increased stored mucin in the airway epithelium. Moderate asthma has even more increased levels. Further elucidation of the regulation of specific airway mucin genes by relevant mediators and identification of the mechanisms that result in GCH is needed

Risk of epilepsy after electrographically proven neonatal seizures

Neonatal seizures often are manifestations of significant neurological disease and major predictors of adverse neurological outcome in the newborn. The present work aimed at estimation of outcomes of neonatal seizures especially the development of epilepsy. The present study was conducted on 30 patients [15 males and 15 females] with neonatal seizures, their ages ranged from one to 30 days. All patients were subjected to full history taking and through clinical examination. Laboratory investigations included: complete blood picture, metabolic screening tests [blood glucose, serum Ca, Mg and Na, blood urea, serum creatinine, serum bilirubin and ferric chloride test], sepsis screen [blood, CSF and urine culture, and TORCH titers], brain C. T. scan and EEG [interictal and follow up]. The etiologic diagnosis of neonatal seizures was based on positive clinical data, laboratory data and/or imaging data. Follow up for at least 6 months was performed with serial neurological evaluation and EEG. From this study, it was found that the seizures etiologies were diverse, hypoxic ischemic encephalopathy [HIE] was the most common cause 46.7%, meningitis 16.7%, cerebral dysgenesis 10%. Metabolic causes 13.3% and intracranial hemorrhage 13.3%. Etiology of seizures was significantly correlated with total outcome, subsequent development of epilepsy and developmental delay. There was significant correlation between findings of neurological examination and total outcome, epilepsy and developmental delay. Neonates with mildly abnormal neurological findings had favorable outcome in 100% of cases. Patients with severely abnormal neurological findings were associated with unfavorable outcome [mortality, epilepsy or developmental delay] in 81.8% of cases. Type of seizures was significantly correlated with the total outcome and mortality. Generalized tonic seizures had the worst prognosis. There was significant correlation between brain CT findings and total outcome, subsequent development of epilepsy and developmental delay. EEG findings were significantly correlated with the outcomes findings of neurological examination and frequency of seizures but insignificantly correlated with type of seizures, onset of seizures and brain CT findings. The 3-months follow up EEG was significantly correlated with the development of epilepsy. Seizure etiology, neurological evaluation of the newborn at birth [mildly, moderately and severely abnormal], clinical characteristics of seizures [onset, frequency and types], brain CT. and EEG findings [interdicted EEG background activity], 3-months follow-up EEG and meticulous follow-up clinical examination were the most important determinants for prediction of the neurological outcome of neonatal seizures. Epilepsy and developmental delay after neonatal seizures were more frequent in presence of one or more of the following: severely abnormal neurological examination at birth, cerebral dyesgenesis as an etiology of seizures, generalized tonic seizures, seizure frequency >/= 2 seizures/h, abnormal brain CT scan findings and abnormal inter-ictal EEG background. EEG is recommended to be performed for all cases with neonatal convulsions as a diagnostic and prognostic tool. Meticulous follow up [clinical examination, EEG] of cases with neonatal seizures is essential to predict the subsequent development of epilepsy and developmental delay