Experimental study on the damage of immature brain induced by chronic treatment with exogenous glucocorticosteroid / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the possibility of brain damage induced by exogenous glucocorticosteroid (GC) at therapeutic level during early life.</p><p><b>METHOD</b>Totally 192 healthy Sprague-Dawley (SD) rats were selected and divided into three groups including PD7, PD15 and PD60 corresponding to three age-groups in human, i.e., the full-term newborn, one-year-old infant and adult, respectively. According to the therapeutic regime for infantile spasms, the dose of prednisone and ACTH was designed as 6 mg/(kg.d) and 150 U/(m(2).d) respectively. SD rats of different age-groups were treated with prednisone or ACTH and normal saline as the control for 4 days. The specimens were collected on Day 4 or 3 weeks after treatment. Body and brain weights were measured when the rats were sacrificed. Histological studies on the tissues of frontal lobe and hippocampus were performed by Nissl staining. Ultrastructural changes of brain were observed by the transmission electron microscopy. Expression of apoptosis-related proteins Bcl-2 and Bax in neurons was detected by immunohistochemistry. Neuronal apoptosis was detected by TUNEL. Mitochondria membrane potential of neurons in frontal lobe and hippocampus were detected by flow cytometry, and the Caspase-3 activity was detected by spectrophotometric assay.</p><p><b>RESULT</b>(1) Significant reduction of brain weight [prednisone group of PD7: (0.78 +/- 0.08) g, control group: (0.89 +/- 0.08) g] and decrease of neurons numbers [(77.7 +/- 4.7) neurons per VF, control group: (102.3 +/- 5.9) neurons per VF] with cellular ultrastructural abnormalities in the frontal cortex were observed in infantile rats, including PD7 and PD15 groups. However none of the differences in brain weight and frontal cerebral cortex neurons were detected 3 weeks after drug discontinuation in PD7 group. (2) Compared with NS control, the numbers of TUNEL-positive cell (prednisone group of PD7: (114.8 +/- 8.1) cells per VF, control group: (56.3 +/- 5.6) cells per VF], Caspase-3 activity (345.3 +/- 13.0, control group: 166.3 +/- 6.4) and Bax protein expression (0.27 +/- 0.02, control group: 0.15 +/- 0.06) in neurons of the infant rats increased significantly but their potentials of mitochondrial membrane (112.9 +/- 8.6, control group: 140.5 +/- 5.6) were reduced remarkably, especially in PD7 group.</p><p><b>CONCLUSION</b>(1) Long-term use of ACTH or prednisone could induce brain damage. The younger the rats were, the more liable they were to the damage and more severe the damages were, and the less possibly to recover completely from the damage. (2) The pathogenesis of the brain injury induced by GC is primarily due to up-regulated Bax protein expression resulted from the enhanced ratio of Bax to Bcl-2 and increased mitochondria membrane potential, followed by Caspase enzymes activation and irreversible excessive apoptosis.</p>

Polyneuro-electrophysiological studies of myoclonus in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical and neuroelectrophysiological characteristics of myoclonus of different origins in children.</p><p><b>METHOD</b>Thirty-two children with myoclonic seizure were analyzed by video electroencephalogram-electromyogram (VEEG-EMG) polygraphic recordings, jerk-locked back averaging (JLA) and short latency somatosensory evoked potential (SSEP). They were classified into cortical myoclonus (CM), subcortical myoclonus (SCM), and unidentified group according to their generating locations, and also were classified into epileptic and non-epileptic myoclonus based on their different properties.</p><p><b>RESULT</b>The 32 patients included 14 with CM, 14 with SCM and 4 with unidentified origin. (1) CM group: the myoclonic patients presented as focal and/or multifocal seizures in 11 cases and as generalized in another 3 patients besides focal myoclonus. Arrhythmic jerks were shown completely in 11 cases and rhythmic seizures were concomitant in another 3 patients. Myoclonus sensitivity to sensory stimulus was observed in 10 patients. The durations of EMG burst were 10-52 ms. Background EEGs were presented normal in 4 patients and slowing in 10 patients. The epileptiform discharges in interictal EEG were variable. The ictal EEG showed epileptic discharges with each clinical jerk in 9 cases but only with some jerks in 4 patients. Another one had no any EEG abnormality in each jerk. The myoclonus-related spikes were disclosed in 13 cases by JLA. Of the 10 cases who underwent SSEP, giant SSEPs were seen in 3 cases including the one with normal EEG and JLA analyses. (2) SCM group: myoclonus was presented as generalized in 8 cases and as focal in 6 cases. All the patients showed arrhythmic jerks and 14 cases were not sensitive to stimulus. The durations of EMG burst were from 60 ms to 400 ms. Normal background EEGs were presented in 6 patients and slowing in 8 patients. The interictal EEG showed no consistent abnormality. Epileptic discharges associated with myoclonus seizures were not found in any of 9 patients but were observed with some seizure changes in 5 cases. There was no myoclonus-related spike by JLA in this group. SSEPs were normal in all patients. (3) The group with unidentified origin: the durations of EMG were from 60 ms to 400 ms, and their EEG and SSEP recordings were normal. In addition, 32 patients could be classified as epileptic myoclonus in 14 cases and nonepileptic myoclonus in 18 cases by the polyneurophysiological tests.</p><p><b>CONCLUSION</b>(1) It is not reliable to identify myoclonus seizures and their clinical properties depending on their interictal and ictal EEGs only. (2) Polyneuroelectrophysiological tests, including EEG-EMG, JLA, and SSEP, seem to be valuable and useful to identify the generating locations and properties for different myoclonus in children.</p>

Peripheral nerve damage and its pathogenesis induced by antiepileptic drugs in rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the possibility of peripheral nerve damage induced by antiepileptic drugs (AEDs) in different age rats and its pathogenesis.</p><p><b>METHODS</b>Adult (2-month-old) and infant (7-day-old) rats were divided into 8 groups (n = 16 in each) and treated with the following 7 AEDs respectively: phenytoin [PHT, 62.5 mg/(kgxd)], phenobarbital [PB, 30.0 mg/(kgxd)], sodium valproate [VPA, 312.5 mg/(kgxd)], clonazepam [CZP, 1.25 mg /(kgxd)], carbamazepine [CBZ, 187.5 mg/(kgxd)], topiramate [TPM, 40 mg/(kgxd)], oxcarbazepine [OXC, 312.5 mg/(kgxd)], remaining one group was used as control. Four weeks later, 8 rats were sacrificed randomly from each group and serum, sciatic nerves and spinal cord samples were collected. The rest half rats were sacrificed 4 week after AEDs withdrawal. Histological observations were performed on the sciatic nerves samples, including teased fibers, semi-thin sections and electron microscopy. The activity of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and sciatic nerves were detected respectively. Expression of apoptosis-related proteins Bcl-2 and Bax was detected by immunohistochemistry. Neurons apoptosis in the anterior horns of spinal cord were detected by TUNEL.</p><p><b>RESULTS</b>(1) Except for TPM group, various incidence (7.2% - 20.2%) of teased fibers abnormalities were observed in all the other different age groups. PHT group showed the most serious changes followed by PB (adult) or VPA (infant), CBZ, CZP and OXC groups. The predominant abnormality of teased fibers was demyelination. (2) There was no significant difference in the incidence of pathologic changes in teased fibers between adult and infant groups. Four weeks after AEDs withdrawal, recovery of pathologic changes in teased fibers in infant groups was much better than adult. (3) Significantly increased expression of Bax protein and ratio of Bax/Bcl-2 was only found in infant rats treated with PB, CNP or VPA compared with control (P < 0.05), the results of TUNEL was in accordance with immunohistochemistry. (4) Compared with control, the activity of T-AOC and SOD decreased in both infant and adult rats treated with PHT, CZP, CBZ and OXC, and the reduction of SOD activity in serum and sciatic nerves samples was also found in PB groups. Serum activity of GSH-PX was decreased in both age groups treated with PHT, PB, VPA, CZP, CBZ and OXC. The reduction of GSH-PX activity in sciatic nerves samples was remarkably in both adult and infant rats treated with PHT, PB, CBZ, OXC as well as the infant rats treated with CZP.</p><p><b>CONCLUSIONS</b>Six AEDs (PHT, PB, CBZ, VPA, CZP, OXC) showed the potential to cause peripheral nerves damage. Demyelination was the predominant pathologic change. Both adult and infant rats had the same susceptibility. Recovery of pathologic changes in teased fibers in both age groups was slow, but infant rats were prone to revive more quickly. There was no significant correlation between spinal cord neuron apoptosis and peripheral nerves damages in rats treated with AEDs. Breakdown of oxidation-antioxidation balance was closely related to development of peripheral nerves damages caused by most AEDs.</p>

Clinical and polyneuroelectrophysiological characteristics of infantile spasm / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the characteristics of various seizure types in infantile spasm (IS) and to recognize the clinical and electrophysiological differences among spasm, myoclonic and tonic seizures.</p><p><b>METHODS</b>Totally 681 seizures of 8 infants with IS were analyzed, including 20 episodes of non-cortical myoclonus which were finally ruled out by video-electroencephalogram-electromyogram polygraphic recordings (VEEG-EMG) and off-line analysis of jerk-locked back averaging (JLA). As a control, the data of 58 myoclonic seizures collected from an infant with Aicardi syndrome within two months before his typical clinical presentations of IS were also analyzed.</p><p><b>RESULTS</b>Three types of seizures were recorded from the 8 infants, including spasm, myoclonic and tonic seizures with the incidence of 94.4%, 4.5%, and 1.1%, respectively. Spasms were mostly presented as body muscle contraction axially, which often occurred in clusters and evolved in a crescendo-decrescendo manner; 85.7% of them lasted for 0.4 - 3.0 s and 14.3% for 3 - 7 s. In addition, there were 273 seizures which were identified as subtle spasms according to their ictal EEG with high voltage slow wave (HVS) and fast wave bursts in most. There was no constantly time-locked EEG correlating to spasms even when JLA was applied for analysis. Myoclonic seizures were shock-like muscle constraction lasting for less than 400 ms with or without visible epileptic discharges in its ictal EEG. However, there was a time-locked cortical discharge discerned by JLA in epileptic myoclonus. Tonic seizures were consisted of sustained muscle contractions involving limbs and trunk, lasting for more than 3 s. Its ictal EEGs were more likely low amplitude fast waves and medium amplitude theta activities. Some spasms, named as tonic spasm, could be distinguished from tonic seizure according to the seizure duration which was always less than 2 s in tonic spasms and their different EEG patterns.</p><p><b>CONCLUSIONS</b>There were various seizure types in IS but spasm was the predominant one. With polyneuroelectrophysiological tests including EEG-EMG and JLA, it would be much helpful to precisely recognize the different common seizure types including spasm, tonic spasm, myoclonic and tonic seizure during infancy which is important for the diagnosis, classification and treatment of infantile epilepsy.</p>

Experimental study on the possibility of brain damage induced by chronic treatment with phenobarbital, clonazepam, valproic acid and topiramate in immature rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the possibility of brain damage induced by several anti-epileptic drugs (AEDs) at therapeutic level to immature brain of rat.</p><p><b>METHODS</b>Totally 160 healthy Spraque-Dawley (SD) rats selected for the study were divided into infant and adult groups. Each age group was treated with phenobarbital (PB), clonazepam (CZP), valproic acid (VPA), topiramate (TPM) or normal saline respectively for 2 or 5 weeks with 8 rats in each group. The steady-state plasma concentrations of AEDs at the experimental dosage were coincided with the range of clinical therapeutic concentrations. Drug levels in plasma were determined by fluorescence polarization. Body and brain weights were measured when the rats were sacrificed. Histological studies on the tissues of frontal lobes and hippocampus were performed by Nissl staining. And ultrastructural changes of brain were observed by the transmission electron microscopy. Plasma neuron-specific enolase (NSE) was determined by ELISA. Expression of apoptosis-related proteins Bcl-2 and Bax in neurons was detected by immunohistochemistry. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL).</p><p><b>RESULTS</b>(1) There were no significant differences in brain weight among all adults groups. While remarkable reduction of brain weight was observed in immature rats exposed to CZP or PB (P < 0.01) for long term. (2) Significant neurodegeneration, neuronal necrosis and decrease in the number of neurons can be observed in the immature rats exposed to CZP or PB for long period. (3) For immature rats, concentration of plasma NSE was increased even after short-term treatment with PB [(8.84 +/- 2.10) nmol/L] compared with control group [(6.27 +/- 1.27) nmol/L] (P < 0.01). And it was increased in immature rats exposed to CZP [(8.15 +/- 1.67) nmol/L] or PB [(8.07 +/- 1.27) nmol/L] for long term compared with controls [(6.02 +/- 1.20) nmol/L] (P < 0.01). But there were no significant differences between AEDs-treated adult rats and control rats. (4) The expression of Bcl-2 and Bax protein in mature brain did not change at therapeutic level. In contrast, expression of Bax protein in the frontal lobe was increased significantly in immature rats receiving CZP and PB for long period compared with control. (5) The number of TUNEL positive cells in immature rats exposed to CZP or PB for long term was obviously increased.</p><p><b>CONCLUSIONS</b>PB and CZP may result in remarkable histological abnormalities, neuronal apoptosis and necrosis in immature brain. The brain damage induced by PB was more serious and persistent than that induced by CZP.</p>

Experimental study on the chitosan-DNA vaccines against campylobacter jejuni invasion / 中华预防医学杂志

<p><b>OBJECTIVE</b>The immunogenicity and protective efficacy of an experimental Campylobacter jejuni (C. jejuni) chitosan-DNA vaccines were evaluated in mice.</p><p><b>METHODS</b>The chitosan-DNA vaccines were prepared by embedding pcDNA3.1(+)-cadF and pcDNA3.1(+)-peblA with chitosan respectively. BALB/c mice were intranasally immunized in a four-dose primary series (7 d intervals) at doses of 60 microg chitosan-DNA vaccines each time. The comparative immunogenicities of nine formulations were assessed on the basis of the generation of antigen-specific antibodies in serum and intestinal secretions. Mice were attacked repeatedly through intragastric administration of C. jejuni HS:19 at the 8th week after the immunization and protective efficacy was determined by detecting the degrees of protection afforded against C. jejuni invaded.</p><p><b>RESULTS</b>The mice immunized with chitosan-DNA vaccines have generated high levels of IgA and IgG from the sera and IgA from the intestinal secretions and the P/N value went up to 20.58, 30.13 and 6.87 respectively. Meanwhile, the expression of intestinal SIgA increased correspondingly. Moreover the chitosan-DNA vaccines induced strongest level of protection in BALB/c mice against challenge with C. jejuni HS:19 strain and the protective efficacies was 93.70.</p><p><b>CONCLUSION</b>The results of this study indicate that the chitosan-DNA vaccines could induce significant protective immunity against C. jejuni challenge in the mice model.</p>

Comparative study on the role of parent Campylobacter jejuni and galE mutant in inducing experimental peripheral nerve damage / 中华儿科杂志

<p><b>OBJECTIVE</b>A comparative study on the role of Campylobacter jejuni (CJ) HB9313 and galE mutant in inducing experimental sciatic nerve damage was conducted in guinea pigs in order to explore whether CJ lipo-oligosaccharide (LOS) is critical component associated with peripheral nerve lesions and find experimental evidence for the presumption of molecular mimicry on the pathogenesis of Guillain-Barre syndromes (GBS) with CJ antecedent infection.</p><p><b>METHODS</b>A total of 32 guinea pigs were randomly divided into four groups: parental strain group (n = 10), galE mutant group (n = 10), control group (n = 6) and PBS group (n = 6), and immunized with the whole cell antigens of CJ HB9313 with Freund's adjuvant (FA), the whole cell antigens of galE mutant (without ganglioside-like structure) with FA, PBS with FA, and PBS alone, respectively. Enzyme-linked immunosorbent assay (ELISA) was employed to detect anti-LOS and anti-ganglioside GM1 antibodies in sera of these animals, and comparative morphologic studies of pathologic changes were carried out on the sciatic nerves, including examination of teasing fibers, examination of semithin sections made from epon-embedded tissue blocks under light microscope and transmission electron microscope.</p><p><b>RESULTS</b>ELISA results indicated that after immunization, the levels of anti-LOS IgG antibody were significantly elevated in animals from parental strain group and galE mutant group as compared with those before immunization (P < 0.01). No statistically significant difference was found between the two groups. However, the mean optical densities (ODs) of IgG antibody against GM1 at 14 and 28 day after immunization, in parental strain group, were 0.661 +/- 0.290 and 0.984 +/- 0.025, respectively, significantly higher than those of galE mutant group, which were 0.193 +/- 0.078 and 0.180 +/- 0.063 (P < 0.01). The results of morphologic examination on sciatic nerves showed that for teased-fiber study, incidence of pathologic abnormalities of teased fibers from animals of galE mutant group was 4.9% (98/2000), significantly lower than that from parental strain group, which was 16% (320/2000), characterized by predominantly axonal degeneration. The difference between them was highly significant statistically (P < 0.01). Examination of semithin sections of sciatic nerves also revealed that obvious pathological changes occurred in the animals from parental strain group, while only minimal abnormalities could be seen from galE mutant group, there was a significant differences between them (P < 0.01). In parental strains group, the predominant pathologicanl change was axonal degeneration with considerable variation in severity. These morphologic changes were confirmed by electron microscopy.</p><p><b>CONCLUSION</b>Compared with parental strain, galE mutant without ganglioside-like structure no longer could induce anti-GM1 antibodies, nor induce obvious immune damage of peripheral nerves in experimental guinea pigs. The results of this study provide a strong support to the hypothesis of molecular mimicry as a pathogenesis in patients with GBS following CJ antecedent infection.</p>

Animal and clinical studies on rectal administration of a mixed solution of ibuprofen and diazepam / 中华儿科杂志

<p><b>OBJECTIVE</b>Seizure is a common emergency in children with complicated pathogeny. Seizures are usually caused by complicated etiology and fever and febrile seizure are the commonest causes. Repeated and permanent seizures can damage the brain. So it is important to take active and effective measures to control seizure and high fever. Because most seizures and fever take place at home or out of hospital and it is difficult to administer drugs intravenously, it is important to explore an easy, safe, quick and effective way to control and prevent both seizure and fever. The present study aimed to explore the efficacy and safety of rectal administration of mixed ibuprofen and diazepam (IBU-DZP) solution.</p><p><b>METHODS</b>(1) Animal study on the pharmacokinetics in rabbits and pharmacodynamics in rats after rectal administration with the mixed solution and on the irritability of the mixed solution to rectum. (2) Clinical study: Pharmacokinetics of the mixed solution in children after rectal administration were investigated.</p><p><b>RESULTS</b>(1) Animal study: IBU and DZP were both rapidly absorbed from rectum with a peak blood level of (11.7 +/- 1.2) min and (9.4 +/- 2.7) min in rabbits, respectively. The mixed solution could effectively prevent the severity of seizures induced by pentetrazole and significantly suppressed fever induced by yeast. There were no remarkable pathological changes in rectal tissues after repeated rectal administration of the mixed solution. (2) Clinical study: IBU and DZP rapidly reached their peak blood levels at about 30 min and 15 min respectively after rectal administration to the children. The peak values were (57.8 +/- 7.9) mg/L and (450.1 +/- 158.7) microg/L, respectively. In fact, both of them reached levels that were much higher than their therapeutic levels in serum just at 5 min after administration, their blood levels were (41.4 +/- 5.5) mg/L and (321.8 +/- 53.9) microg/L, respectively.</p><p><b>CONCLUSIONS</b>IBU-DZP mixed solution administered rectally is an easy, safe, quick and effective way to control and prevent both seizure and fever.</p>

Immunopathological evidence of terminal residues containing sialic acid in Campylobacter jejuni lipopolysaccharide as the critical antigen to induce peripheral neuropathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the important role of the terminal residues containing sialic acid (SA) in Campylobacter jejuni (CJ) lipopolysaccharide (LPS) as the critical antigen to induce nerve damage, and also to identify immunopathological evidence for the hypothesis of molecular mimicry and cross-immunity between CJ LPS and gangliosides.</p><p><b>METHODS</b>A mutant of Pen O:19 CJ with neuB1 gene inactivated and LPS outer core terminal residues losing SA was to be constructed. PCR and RT-PCR were used to confirm the mutant. Capability of CJ LPS binding to cholera toxin B subunit (CTB) was tested. Guinea pigs were systematically immunized with LPS of the wild and the mutant strains, respectively. Titers of anti-LPS and anti-ganglioside GM(1) IgG antibodies in sera of immunized guinea pigs were detected by ELISA. Pathological study for sciatic nerves of both Guinea pigs either immunized systematically or perineural injection with their immunized serum was finished.</p><p><b>RESULTS</b>(1) The mutant of CJ O:19 strain with inactivated neuB1 gene was successfully constructed and lost transcriptional activity of neuB1 gene in the mutant strain was confirmed by PCR and RT-PCR. SA was well demonstrated by both acidic ninhydrin reaction and periodate-resorcinol reaction in the LPS of wild strain but not in the mutant LPS; (2) Compared with the titers before immunization, the titers of anti-GM(1) IgG antibody increased in sera of guinea pigs immunized with LPS of the wild strain. However there were no detectable anti-GM(1) IgG antibody in sera of the animals immunized with mutant LPS and PBS. (3) The incidence of pathological fibers of sciatic nerves in wild CJ LPS group (17.3%) was significantly higher than the mutant CJ LPS group (chi(2) = 125, P < 0.01); the difference between the mutant CJ LPS group and control group was not statistically significant (chi(2) = 1.633, P > 0.05). (4) After perineural injection with immunized serum, the incidence of pathological fibers of sciatic nerves in wild strain group (67.8%) was also significantly higher than the incidence of mutant group (P < 0.01).</p><p><b>CONCLUSION</b>A mutant of CJ O:19 strain neuB1 gene inactivated and SA component of terminal structure of LPS lost was successfully constructed. And it no longer expressed SA component which is the normal terminal structure of LPS in wild strain. The capability of the wild strain to induce increased titers of anti-GM(1) antibody and immune-mediated nerve damage was simultaneously lost for the mutant strain. It could be a strong immunopathologic evidence to identify the molecular mimicry hypothesis between CJ LPS and ganglioside epitope in nerve on the pathogenesis of CJ related GBS. The terminal residues containing SA should be as the basic GM1-like structure in CJ LPS.</p>

Long-Term Effect of Topiramate Treatment on 24 Cases of Lennox-Gastaut Syndrome / 实用儿科临床杂志

Objective To explore the effect and adverse reaction of topiramate(TPM) on treating Lennox-Gastaut syndrome(LGS)(including therapeutic alliance or single ). Methods Twenty-four cases with LGS whose attacks could not be controlled by re-(gular) therapy were selected.TPM was gradually increased from low dosage till its showing effect or untolerant adverse reaction.Results Two cases were excluded because of adverse reaction and increase of attacks. The remained cases were followed up from 6 months to 15 months (average: 9 months). The total effective rate was 82.6%, 11 cases accounting for 45.8% free of attack. The tonic-clonic seizure reduced more than 50% accounting for 82.2%, the full control accounting for 66.7%. The myoclonic seizure reduced more than 50% accounting for 81.8%,the full control accounting for 58.8%.The atypical absence seizure reduced more than 50% accounting for 81.8%, the full control accounting for 63.6%. The maximum effect occurred about 2-40 weeks following TPM used, the dosage about 2-10 mg/(kg?d).The adverse reaction included anorexia (8 cases), language disorder (5 cases), drowsiness (4 cases), decrease of anamnesis (3 cases), weight loss or unchanged(3 cases), inattention (3 cases), depression (3 cases), mental bradypraxia (2 cases ), skin damage (1 case), stupor (1 case), gross hematuria(1 case).The hepatic and renal function were normal during therapy. Conclusion TPM is a new, broad-spectrum, effective and safe antiepileptics drug on treating LGS.

Role of free radicals in brain edema induced by endotoxin in infant rats and the therapeutic effect of dexamethasone and IVIG / 中华儿科杂志

<p><b>OBJECTIVE</b>Glucocorticoid is considered as an effective drug for prevention and treatment of brain edema and reducing the blood-brain barrier (BBB) permeability. Intravenous immunoglobulin (IVIG) is frequently used to treat neurological diseases with immune abnormality, its function and potential mechanism on brain edema have not been reported. In this study, the roles of the total hydrosulfide group (TSH), non-protein hydrosulfide group (NPSH) and malondialdehyde (MDA) in etiology of the endotoxin brain edema in infant rats and the interfering effects of dexamethasone (DEX) and IVIG were investigated.</p><p><b>METHODS</b>In 35 infant rats, 10 mg/kg lipopolysaccharide (LPS) was intraperitoneally injected. The same volume of normal saline was injected to 24 control rats. Ten mg/kg DEX and 400 mg/kg IVIG were intravenously injected respectively to 36 and 24 infant rats instantly following LPS injection. The TSH, NPSH and MDA concentrations and the brain Evans blue contents were detected at different time in the brain tissue. The brain water content was measured by drying method.</p><p><b>RESULTS</b>The brain water, EB and MDA contents after endotoxin injection were significantly higher than those of control group, while the brain TSH, NPSH content were significantly lower than those of control group (P < 0.05 or P < 0.01); After treatment with DEX or IVIG, the brain EB, MDA and water content significantly decreased with the peak at 6 h (P < 0.05 or P < 0.01), TSH and NPSH significantly increased compared with LPS group. However, the NPSH content in IVIG treatment group did not change significantly (P > 0.05).</p><p><b>CONCLUSION</b>Free radicals play a role in the brain edema induced by LPS in infant rats. The primary results suggested that DEX and IVIG have therapeutic effect for the endotoxin-induced brain edema by affecting the free radicals.</p>

Damage to peripheral nerves induced by Campylobacter jejuni exotoxin / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the pathogenesis of the damage to peripheral nerves induced by Campylobacter jejuni exotoxin (CJT).</p><p><b>METHODS</b>(1) Animal models: (1) The CJT was extracted from PEN 19-CJ and injected perineurally and intravenously to Wistar rats. (2) The sera and the supernatants of peripheral blood mononuclear cells (PBMCs), taken from the rats immunized with the CJT, were injected perineurally at sciatic nerves of experimental rats and intravenously, respectively. (2) Histopathologic study of sciatic nerves: the animals were sacrificed and their sciatic nerves were examined for tease fibers, transverse section with toluidine blues staining and electron microscopy. (3) Immunohistochemistry: sections of sciatic nerves of either normal rats or human which were incubated with CJT and the sciatic nerves with pathological changes induced by CJT were obtained for observation of the binding capability of CJT with peripheral nerves by SABC and FITC-immunofluorescence methods, and nucleic acid hybridization techniques for detection of TNF-alpha mRNA expression in pathological sciatic nerves samples.</p><p><b>RESULTS</b>(1) Remarkable peripheral neuropathies with axon degeneration and/or demyelination were found in the nerves induced by both CJT injection perineurally and intravenously. The axon degeneration was more obvious. Pathological changes were identified in 76.8% (2,763/3,600) of teasing fibers after perineural injection, but only 9.6% (230/2,400) of fibers were damaged in control group (P < 0.01). The peak severity of fiber damage was found on the 3rd day after CJT intravenous injection with the incidence of abnormal fibers was 19.5% (390/2,000), and abnormalities of 15.5% (310/2000) on the 14th day. However, no abnormal changes were demonstrated in control group (P < 0.01). So was in the groups injected with anti-CJT sera and the supernatants of PBMCs compared with control (P > 0.05). (2) Binding of CJT to the nerve was found dominant in the sciatic nerves taken from normal rats or human either incubated with CJT or in the pathological sciatic nerves induced by CJT to various degrees. The binding of CJT to all these nerves was determined. (3) After intravenous injection with CJT, no histopathologic change could be found in the other viscera of the rats, with the exception of remarkable pathological change in peripheral nerves.</p><p><b>CONCLUSIONS</b>(1) CJT could remarkably damage the peripheral nerves in rats. Specific pathogenicity of CJT to peripheral nerves was well shown, because no histopathologic abnormalities could be found in the other viscera, such as brain, liver and kidney etc. although there was remarkable pathological change along the peripheral nerve in the animals. (2) No immunological pathogenicity of CJT could be demonstrated in the nerves of rats after immunization with CJT.</p>

Experimental study on the therapeutic mechanism of high dose intravenous immunoglobulin in treatment of immune-mediated peripheral neuropathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the therapeutic basis of high dose intravenous immunoglobulin (IVIg) in treatment of peripheral neuropathy induced by Campylobacter jejuni lipopolysaccharide (CJ LPS).</p><p><b>METHOD</b>(1) IVIg (400 mg/kg x d) was given to the rats on the different days respectively during the immunization with CJ LPS. Histological study of sciatic nerve was performed on the 35 th day after immunization. The titer of anti-CJ LPS antibody in sera of immunized rats was measured by ELISA; IgG deposition was detected by immunohistochemistry and expression of TNF-alpha mRNA in the pathological nerves by in situ hybridization histochemistry. (2) When PBMCs were stimulated by CJ LPS in vitro, IVIg was added into culture medium at the doses of 1, 2.5, 5, and 10 mg/ml, respectively. Pathological examination of sciatic nerve was performed on the 7th day after perineural injection of the supernatants. Expression of TNF-alpha mRNA in PBMCs stimulated by CJ LPS in medium was detected by in situ hybridization histochemistry after adding IVIg.</p><p><b>RESULTS</b>(1) The rate of abnormal fibers appearance in IVIg group (1.0%) was much lower than that of the control group (15.0%) after immunization with CJ LPS, P < 0.01. The titer of antibody in control group was 9 times higher than that of IVIg group. There was no expression of immunoglobulin and TNF-alphamRNA in peripheral nerves in IVIg group, but high expression was found in control group in which no IVIg was injected. (2) The expression rates of TNF-alphamRNA on the PBMCs in IVIg group (1.0%) was much lower than that of control group (9.5%). (3) When the PBMCs of normal rats were stimulated by CJ LPS, the expression rates of TNF-alphamRNA in PBMCs of 5 mg/ml IVIg group (3.0%) or 10 mg/ml IVIg group (2.0%) were much lower than that of 1 mg/ml IVIg group (15.0%) or 2.5 mg/ml IVIg group (11.5%), P < 0.01. The rate of abnormal fibers appearance in 5 mg/ml IVIg group (9.8%) or 10 mg/ml IVIg group (8.5%) was much lower than that of 1 mg/ml IVIg group (50.0%), 2.5 mg/ml IVIg group (41.0%) or control group (50.8%) after the perineural injection with the supernatants, respectively, P < 0.01.</p><p><b>CONCLUSION</b>The therapeutic effect of high dose IVIg might be associated with inhibition of the humoral and cellular immunity simultaneously in peripheral neuropathy induced by CJ LPS.</p>

Influence of antiepileptic drugs at therapeutic level to immature brain / 中华神经科杂志

Objective To explore the different influence of antiepileptic drugs(AEDs)at therapeutic levels to the maturation of brain.Methods 180 healthy Sprague-Dawley(SD)rats were divided into infant and adult group.Each age group was administered with PB,CNP,VPA,TPM or normal saline respectively in persistent 5 weeks.The steady-state plasma concentrations of AEDs at the experimental dosage were coincided with the range of clinical therapeutic concentrations.After AEDs withdrawed,the effects of AEDs on cognitive function were assessed by Morris water maze and two-way shuttle box at different time points.Body and brain weight were got immediately when the rats were sacrificed.Histological changes of brain were observed by HE staining,Nissl staining and transmission electron microscopy.Results(1) For immature rats,1 day or 14 days after AEDs withdrawed,there were significant differences between groups exposed to PB or CNP and control group in escape response latency(ERL)in the two-way shuttle box.Even after one month ERLs of immature rats receiving CNP((6.05?2.04)s)or PB((5.81? 1.75)s)were still longer than that of untreated controls((4.75?2.43)s,P

Children's motor nerve conduction: the normal value and developmental regular rule / 实用儿科临床杂志

Objective To search for the normal value and developmental regular rule of motor norve conduction in children.Methods One hundred and fourty-nine children aged from 0 to 14 years old were divided into 7 groups in accordance with age. There were 19 pecrsons aged from 20 to 35 years old in adult group. The motor nerve conduction function of median nerve, ulnar perve, tibial nerve and peroneal nerve of every suhject was determined by nerve evoked potential meter.Results The terminal latency of action potential of every nerve is decreased along with growing up of age before 6 years old and increased after 6 years old. The conduction velocity of ulnar nerve is the fastest,then the peroneal nerve and median nerve, that of tibial nerve is the slowest. Median nerve development quicken after 3 months of birth and approch ulnar nerve at the time of 3 years old. Tibial nerye get into fast development period from 3 months to 1 years old and catch up peroneal nerve. The conduction velocity of every nerve extend to adult level in th period of 3~6 years old.Conclusion The every parameler of nervous conduction has a great difference of age in the period of child,particularly in that of infancy. therefore, the normal values should be set up in accordance with proper age groups. This study shows that it's suitable to divide groups in accordance with new-born, 3 and 6 months, 1, 3 and 6 years old. Adult criterion should be used in the children dbove 6 years old.

Protection of Co-administration with Vitamin E and Coenzyme Q10 to Valproate-Associated Hepatotoxicity in Infantal Rats / 实用儿科临床杂志

Objective To study the protection and mechanism of co-administration of vitamin E with coenzyme Q10(CoQ10) to valproate-associated hepatotoxicity in infantal rats.Methods The rat models were established by oral administration of valproic acid(VPA) in ablactation(21 days) Wistar rats,at doses of 500 mg/(kg?d) during 30 days,other groups received the same amount of VPA with phemobarbitone(PB) and co-administration with vitamin E and CoQ10.The changes of liver cell morphology and the blood coagulation test,as well as the contents of succinic dehydrogenase(SDH),cytochrome oxidase(CCO),cytochrome,the levels of glutothione(GSH) and malondial dehyde(MDA) in rat liver mitochondria were detected by chromatometry,HPLC,Oil-Red-O staining and electron microscope,respectively.Results 1.Average content of cytochrome aa3 in liver mitochondria of infantal rats were reduced by 58.80% and(61.80%) because of administration of VPA and VPA added with PB.The protection against the loss of cytochrome aa3 by coadministration of VitE and CoQ10 was obvious.As for activities of SDH and CCO,which affected by VPA and VPA added with PB in rats,were significantly lowered compared with control group(P