[Clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in children].

Objective: To investigate the clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) in pediatric patients. Methods: Clinical data, laboratory examination, the initial best corrected visual acuity (BCVA), fundus, neuroelectrophysiological results, MRI imaging, treatment and prognosis of children diagnosed with MOG-ON from 2016 to 2019 were retrospectively analyzed. Results: A total of 29 eyes from 16 children were involved, with a male/female ratio of 1∶1, onset age of (7.0±2.9) years. Seven of 16 patients had prodromal infection, with a unilateral/bilateral ratio of 3∶13, and 2 cases had recurrent optic neuritis. Before treatment, BCVA of 19 eyes (65.5%) was ≤0.1, among them, 4 had no sense of light, 5 had light sense, 5 with sense of hands in front of eyes, and 5 with sense of fingers in front of eyes. There were 10 eyes (34.5%) with BCVA of 0.1-0.5. After treatment, there were 4 eyes (13.8%), 5 eyes (17.2%) and 20 eyes (69.0%) in groups with BCVA of 0.1-0.5, 0.5-1.0, and>1.0, respectively. Twelve of 16 patients had optic papillitis in fundus examination during acute phase. The latency was prolonged and the amplitude was decreased in P100 wave of all the children. Thirteen out of 16 children showed swelling and thickening of optic nerve in MRI T2WI. MRI images exhibited intracranial demyelinating lesions in 12 of 16 children and long segment spinal cord lesions in 3 of 16 children. Thirteen of 16 patients showed effective results after intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) treatment. There was no relapse after administration of mycophenolate mofetil in 2 recurrent children. No progression after administration of rituximab was found in 1 child with corticosteroid insensitivity. The average follow-up time was (16±9) months and no recurrence occurred. Ten of 16 patients had full recovery, 4 had significant improvement, and 2 showed no significant improvement. Conclusions: There is no significant gender difference in the incidence of pediatric MOG-ON. Bilateral involvement and severe visual impairment are common in acute phase. Most patients have good response to IVMP combined with IVIG treatment and hence have a good prognosis. Only a few of them have neurological sequelae.

[Clinical features and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody associated acute disseminated encephalomyelitis].

Objective: To analyze the clinical features, outcome and prognosis of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody associated acute disseminated encephalomyelitis (ADEM), and provide evidence for improving the diagnosis and treatment of this disease. Methods: This study involved 30 MOG antibody-associated ADEM patients in the Department of Neurology, Guangzhou Women and Children's Medical Center. Patients' clinical information were analyzed. Results: The mean onset age was (5.2±3.3) years old, the ration of male to female was 16∶14. Fifty percent of these patients had a history of precede infection or vaccination before onset. Encephalopathy and seizures were the most common clinical manifestations, followed by movement disorder. In addition, some patients had other positive autoantibodies. Brain Magnetic resonance imaging (MRI) showed extensive, asymmetrical, indefinite large patchy lesions in bilateral cortical and subcortical areas and the spinal cord was characterized by long segmental myelitis. In acute attack, the patients had a good response to corticosteroid combined immunoglobulin therapy. Most of these patients had a good prognosis and recurrence rate was about 20%. Conclusions: The onset age of MOG antibody-associated ADEM is around 5 years old. Encephalopathy and seizures were the most common clinical manifestations. Most patients have a good response to corticosteroid combined immunoglobulin therapy. Some patients may have a recurrent disease course.

[Property analysis of the finals mispronunciation in Chinese-speaking children with functional articulation disorder].

Objective: To characterize the finals mispronunciation in Chinese-speaking children with functional articulation disorder (FAD), in order to promote the standardized diagnosis. Method: A retrospective study was conducted. From January to December 2013, 90 FAD children, diagnosed by Dysarthria Rating Scale and Mandarin Finals scale, were included in this study. Among them, 22 were found to have finals mispronunciation; the average age was (6.56±0.26) years. According to the finals classification, six different finals (simple finals, front vowel compound finals, central vowel compound finals, back vowel compound finals, anterior nasal finals, and posterior nasal finals) were defined; the produced sound samples of those subjects were analyzed. Result: In all these children, 22 of 90 (24%) were found having finals mispronunciation, the occurring rates of which with omission and substitution errors were: 3% (4/132) for simple finals, 30% (26/88) for front vowel compound finals, 26% (23/88) for central vowel compound finals, 7% (8/110) for back vowel compound finals, 73%(128/176) for anterior nasal finals and 73% (112/154) for posterior nasal finals, respectively. In omission and substitution errors, the ratios of the finals above were 50% (150/301), 3% (10/301), 5% (14/301), 36% (107/301), 2% (5/301) and 5% (15/301), respectively. The most frequently occurred mispronunciation were omission, substitution and distortion, with rates of 37% (273/748), 4% (28/748) and 8% (61/748), respectively. Conclusion: The FAD children have remarkable mispronunciation of finals. Omission is the main error. The nasal finals are the most commonly involved, followed by front vowel and central vowel compound finals. The simple finals and the back vowel compound finals are most commonly produced in omission and substitution. These finals production features should be considered when making and implementing rehabilitation programs.

Exogenous nitric oxide induces apoptosis in Toxoplasma gondii tachyzoites via a calcium signal transduction pathway.

The mechanism by which nitric oxide (NO)-dependent cytotoxicity acts against Toxoplasma gondii tachyzoites is poorly understood. An NO donor, sodium nitroprusside (SNP), was used to induce death in T. gondii tachyzoites in vitro as a model for investigating (i) whether NO is capable of inducing apoptosis-like death in tachyzoites and (ii) whether a calcium signal transduction pathway is involved. Exposure to 2 mM SNP resulted in a pattern of tachyzoite death that shares many features with metazoan apoptosis and it may involve a calcium signal transduction pathway. Motility and cell survival in these parasites showed a gradual decline with increasing levels of SNP. Features common to metazoan apoptosis are observed after exposure to 2 mM SNP. Ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetra-acetic acid (EGTA), Verapamil and bis-(o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid/acetoxymethyl ester (BAPTA/AM) partially increased the cell survival concomitant with decreased [Ca2+]i in cells exposed to SNP. An NO scavenger (N-acetylcysteine), the analogue of SNP (devoid of NO), inhibited the rate of apoptosis after SNP treatment compared with SNP treatment without scavenger, but alone did not induce apoptosis. Taken together, the results indicate that SNP is capable of inducing apoptosis in T. gondii tachyzoites via a calcium signal transduction pathway.

[The effect of nitric oxide donor on the DNA content in Toxoplasma gondii tachyzoite].

OBJECTIVE: To determine the role of sodium nitroprusside (SNP) in regulating DNA synthesis of Toxoplasma gondii tachyzoites. METHODS: Hypodiploid peak of tachyzoite DNA induced by SNP was assessed according to DNA fragmentation. The effect of SNP on appearance of hypodiploid peak and the effect of Ca2+ on the growth of tachyzoites were evaluated. The intracellular Ca2+ chelator (BAPTA/AM), antagonist of Ca2+ channel (verapamil) and the extracellular Ca2+ chelator (EGTA) were used. The change of DNA content was measured by flow cytometry. RESULTS: SNP inhibited DNA synthesis of tachyzoites in a dose- and time-dependent pattern. The antiproliferative effect of SNP on tachyzoites was inhibited by verapamil, EGTA and BAPTA/AM. The inhibition of the growth of tachyzoites by SNP was associated with increased subploid peak through a Ca(2+)-dependent mechanism. CONCLUSION: SNP induced a hypodiploid peak in tachyzoites by altering the Ca2+ concentration in the plasma of tachyzoite, resulting in damages of the parasite.

[Modulation of GABA-activated currents by oxytocin in rat dorsal root ganglion neurons].

Experiments were performed on freshly isolated dorsal root ganglion (DRG) neurons of rat. GABA(A)-activated currents were recorded using the whole-cell patch clamp technique. The majority of the neurons (48/52, 90.5%) were sensitive to GABA (10( 6)~10( 3) mol/L). Application of oxytocin (OT) induced outward membrane responses in 51.3% (20/39) of the neurons, no apparent responses in 43.6% (17/39) and inward responses in 5.1% (2/39). 10( 12), 10( 11), 10( 10) and 10( 9) mol/L OT increased 10( 4) mol/L GABA-activated currents to 24.1+/-7.6% (n=6), 33.4+/-6.9% (n=9), 40.2+/-6.5% (n=13) and 67.2+/-14.8% (n=5), respectively. After preapplication of OT, the Kd value for GABA(A)-activated currents decreased, while the response obtained at the maximum concentration increased. The results suggest that the enhancement of GABA-activated currents by OT may suppress primary sensory transmission by potentiating pre-synaptic inhibition of GABA.

Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat.

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.

Liposome-entrapped antifibrotic agent prevents collagen accumulation in hypertensive pulmonary arteries of rats.

We studied the therapeutic efficacy of an intravenously injected antifibrotic agent encapsulated in liposomes on inhibiting collagen accumulation in hypertensive blood vessels. cis-4-Hydroxy-L-proline (cHyp) in liposomes was injected into rats exposed to 10% O2, and drug effect was evaluated by measuring right ventricular pressure and hydroxyproline content of the pulmonary artery. Right ventricular pressure was 11 +/- 1 mm Hg (mean +/- SEM) 5 days after a single intravenous injection of 200 mg/kg cHyp in liposomes compared with 14 +/- 1 mm Hg in rats injected with empty liposomes; hydroxyproline content was also reduced by cHyp treatment (87 +/- 6 versus 107 +/- 7 micrograms per vessel) (p less than 0.05 for both, n = 6-9). Injections of cHyp in liposomes every 5 days partially prevented hypertension and vascular collagen accumulation during a 3-week exposure to hypoxia, and the dose required was one tenth the dose of unencapsulated cHyp. Therapeutic doses of cHyp in liposomes injected for 6 months affected tensile properties of main pulmonary artery and aorta, but there were no apparent histological effects on other organs. Liposomes injected intravenously were identified in pulmonary artery endothelial cells. The prolonged effect of a single injection of cHyp in liposomes may be due to uptake of the liposomes by the endothelium. Liposome delivery of drugs to the arterial wall may be useful in the study and treatment of hypertensive vascular disease.