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Retinol dehydrogenase 11 (RDH11) is an 11-cis-retinol dehydrogenase that has a well-characterized, albeit auxiliary role in the retinoid cycle. Diseases caused by mutations in the RDH11 gene are very rare, and only one affected family with eye and intelligence involvement has been reported. In the present study, we describe the clinical and genetic findings in a Chinese patient with retinitis pigmentosa (RP), juvenile cataracts, intellectual disability, and myopathy. Trio-based whole-exome sequencing and whole genomic copy number variation detection were performed in this family, and compound heterozygous mutations were identified in RDH11 of the patient: c.938T>C (p.Leu313Pro) derived from the father and c.75-3C>A derived from the mother. Variant c.75-3C>A was confirmed to be a splice-site mutation by cDNA sequencing. It caused exon 2 skipping, resulting in a frameshift mutation and premature translation termination (p.Lys26Serfs*38). Moreover, we found mislocalization of RDH11 protein in muscle cells of the patient by using immunofluorescence staining. This is the first case reported in the Chinese population harboring mutations in RDH11 and revealing a new phenotype of syndromic RP with myopathy.
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Doenças Musculares , Oxirredutases/genética , Retinose Pigmentar , Oxirredutases do Álcool , Variações do Número de Cópias de DNA , Proteínas do Olho/genética , Humanos , Doenças Musculares/genética , Mutação , Linhagem , Fenótipo , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genéticaRESUMO
OBJECTIVE: To detect hot spot mutation of RYR1 gene in 15 cases of congenital myopathy with different subtypes, and to discuss the value of RYR1 gene hot spot mutation detection in the diagnosis of the disease. METHODS: Clinical data were collected in all the patients, including clinical manifestations and signs, serum creatine kinase, electromyography. Fourteen of the patients accepted the muscle biopsy. Hot spot mutation in the C-terminal of RYR1 gene (extron 96-106) had been detected in all the 15 patients. RESULTS: All the patients presented with motor development delay, and they could walk at the age of 1 to 3.5 years,but were always easy to fall and could not run or jump. There were no progressive deteriorations. Physical examination showed different degrees of muscle weakness and hypotonia.High arched palates were noted in 3 patients. The serum levels of creatine kinase were mildly elevated in 3 cases, and normal in 12 cases. Electromyography showed "myogenic" features in 11 patients, being normal in the other 4 patients. Muscle biopsy pathologic diagnosis was the central core disease in 3 patients, the central nuclei in 2 patients, the congenital fiber type disproportion in 2 patients, the nameline myopathy in 3 patient, the multiminicore disease in 1 patient, and nonspecific minimal changes in the other 3 patients; one patient was diagnosed with central core disease according to positive family history and gene mutation. In the family case (Patient 2) of central core disease, the c.14678G>A (p.Arg4893Gln) mutation in 102 extron of RYR1 was identified in three members of the family, which had been reported to be a pathogenic mutation. The c.14596A>G(p.Lys4866Gln) mutation in 101 extron was found in one patient with central core disease(Patient 1), and the c.14719G>A(p.Gly4907Ser) mutation in 102 extron was found in another case of the central core disease(Patient 3).The same novel mutation was verified in one of the patients' (Patient 3) asymptomatic father. CONCLUSION: Congenital myopathies in the different subtype have the similar clinical manifestations, signs, enzyme detection and electromyography changes. Muscle biopsy plays an important role in the selection of genes to be detected. Hot spot mutation in C-terminal of the RYR1 gene can only be identified in patients with central core disease, so we suggest this hot spot gene mutation screening apply to the suspicious patient with central core disease only.
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Miopatias Congênitas Estruturais/genética , Miopatia da Parte Central/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Biópsia , Análise Mutacional de DNA , Eletromiografia , Humanos , Mutação , LinhagemRESUMO
OBJECTIVE: To summarize the etiology and clinical characteristics of children with myopathic elevated creatine kinase (CK) levels. The degrees of elevated CK as well as lactic dehydrogenase (LDH) and aspartate aminotransferase (AST) levels in different myopathy were analyzed. METHODS: The clinical data of 235 cases characterized as myopathic hyper-CK-emia from January 2004 to December 2011 were collected and analyzed. A retrospective analysis of LDH and AST levels according to CK in part of the patients were reviewed. RESULTS: Of the 235 cases, 180 were male and 55 female. According to the age at which hyper-CK-emia was diagnosed, 64 cases were under 6 months, 90 between 6 months and 3 years, 50 between 3 and 6 years and 31 between 6 and 14 years. Their CK levels significantly increased in 162 cases, moderately increased in 31 cases, and slightly increased in 42 cases. The age at which hyper-CK-emia was diagnosed and the CK level had no correlation with muscle weakness and the severity. As to CK levels: Duchenne muscular dystrophy (DMD) > inflammatory myopathies > congenital muscular dystrophy (CMD) > metabolic myopathies. LDH and AST levels: DMD > inflammatory myopathies > metabolic myopathies > CMD. CONCLUSION: Unlike adults, the etiology of myopathic hyper-CK-emia in children is complicated and diverse. The onset type, the degree and duration of hyper-CK-emia are helpful to make the diagnosis. CK increases most significantly in DMD, then in inflammatory myopathies, CMD, and metabolic myopathies. Diagnostic flowchart of myogenic hyper-CK-emia should follow a certain process, and the indications of biochemical tests, metabolic screening, electrophysiological examination, muscle biopsy and genetic testing should be made. Finally, different treatments should be designed according to the etiology.
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Creatina Quinase/análise , Diagnóstico Diferencial , Doenças Musculares/enzimologia , Adolescente , Aspartato Aminotransferases/análise , Biópsia , Criança , Pré-Escolar , Feminino , Testes Genéticos , Humanos , L-Lactato Desidrogenase/análise , Masculino , Distrofia Muscular de Duchenne , Estudos RetrospectivosRESUMO
The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs. The most common clinical phenotype associated with TRNT1 is autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD). Muscle involvement has rarely been reported in TRNT1-related disorders. Here we report a Chinese patient with incomplete SIFD and hyperCKemia, and explored the skeletal muscle pathological changes. The patient was a 3-year-old boy with sensorineural hearing loss, sideroblastic anemia, and developmental delay since infancy. At the age of 11 months, significantly increased levels of creatine kinase were noted, accompanied by mild muscle weakness. Whole-exome sequencing revealed compound heterozygous variants of the TRNT1 gene, c.443C > T (p.Ala148Val) and c.692C > G (p.Ala231Gly), in the patient. Western blot showed a decreased expression of TRNT1 and cytochrome c oxidase subunit IV (COX IV) in the skeletal muscle of the patient. Electron microscopy observation of skeletal muscle pathology revealed abnormal mitochondria of various sizes and shapes, supporting a diagnosis of mitochondrial myopathy. The present case indicates that in addition to the classic SIFD phenotype, TRNT1 mutations can cause mitochondrial myopathy, a rare clinical phenotype of TRNT1-related disorders.
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This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.
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Complexo I de Transporte de Elétrons/genética , Doenças Mitocondriais/genética , Mutação , Adolescente , Encéfalo/patologia , Complexo I de Transporte de Elétrons/deficiência , Humanos , Doença de Leigh/genética , Imageamento por Ressonância Magnética , MasculinoRESUMO
OBJECTIVE: To investigate and analyze the clinical manifestations, classification, therapeutic approaches and follow-up of myasthenia gravis (MG) in children in order to improve its management and prognosis. METHODS: Clinical information of 135 children with MG, who were diagnosed between January 1993 to January 2008, were collected and retrospectively analyzed. And prospective following-up of these patients were conducted. RESULTS: Among the 135 cases, 59 were males and 76 females, giving the ratio of M/F around 1:1.3. Totally, 115 cases (85.2%) were type I MG (ocular type), of which only 4.2% developed to generalized type during the subsequent clinical course. Type II MG (generalized type)was found in 18 cases (13.4%) and type III MG in two cases(1.5%). The onset age ranged from 5 month to 15 years, with 50.3% before three years and 80.7% before seven years. Upper respiratory tract infection was presented in 26.7% (36/135) of the sick children before the onset of MG. Among the 106 children being followed up, recurrence of the disease identified in 50.9% and the number of relapse ranged from 1 to 9. Altogether, 40.19% (43/106) of the cases were positive for anti-acetylcholine receptor antibodies (AchR-Ab) on the initial examination, and the AchR-Ab postitive rate showed no difference among different clinical subtypes and states. However, during the follow-up, 53% (9/17) of the recurrent cases, who were negative at the first onset, turned to be positive, and 37.97% (30/79) were positive for repetitive nerve stimulation in electromyogram test. There were 71 % (45/63) of all the cases showed reduced levels of CD4+ and/or CD3+ and/or CD8+. Thymus proliferation was found in 5.93% (8/135) through CT scan and thymoma in 1.48% (2/135). Steroids and anti-cholinesterase administration were effective in most cases with good prognosis. CONCLUSION: Childhood MG, mainly type I, is relatively common in China, with specific characteristics which are different from western patients or adult MG in morbidity, sex distribution, progress, laboratory examination and treatment. The prevalence of myasthenia gravis crisis and mortality rate in MG children is low, and few are accompanied with thymoma. Most MG cases have a satisfied prognosis and few have neuropsychic sequela.
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Anticorpos/sangue , Miastenia Gravis/tratamento farmacológico , Neostigmina/uso terapêutico , Prednisona/uso terapêutico , Receptores Colinérgicos/imunologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Miastenia Gravis/sangue , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the value of cryptococcal latex agglutination test in the diagnosis and treatment of cryptococcal meningitis in children. METHODS: The clinical data of 10 children with cryptococcal meningitis were retrospectively studied. Cryptococcal meningitis was confirmed based on clinical manifestations, India ink stain, cryptococcal latex agglutination test or cryptococcal culture. The outcome of antifungal treatment and the changes of latex agglutination test titer were followed up for 2 to 4 years. RESULTS: Latex agglutination test and/or India ink stain were positive (titer 1 : 64-1 : 1024) in 8 patients in the first examination of cerebrospinal fluid. In the other 2 patients, latex agglutination test was positive (titer 1 : 256) in the fourth examination of cerebrospinal fluid in one, and India ink stain was positive in the eleventh examination in the other. After antifungal treatment, six patients were cured, two patients died, and two patients were lost to follow-up. The positive cryptococcal latex agglutination test (titer 1 : 2-1 : 16) was seen respectively in six, three, two and one cured patients 6 months, 1 year, 2 years and 4 years later. CONCLUSIONS: The cryptococcal latex agglutination test of cerebrospinal fluid is valuable for the quick and early diagnosis of cryptococcal meningitis; however, the decision of withdrawal of antifungal treatment should not rely on the results of the test.
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Testes de Fixação do Látex/métodos , Meningite Criptocócica/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/tratamento farmacológicoRESUMO
OBJECTIVE: Alpha-dystroglycanopathy (α-DGP) is a subtype of muscular dystrophy caused by defects in the posttranslational glycosylation of α-dystroglycan (α-DG). Our study aimed to summarize the clinical and genetic features of POMT2-related α-DGP in a cohort of patients in China. METHODS: Pedigrees, clinical data, and laboratory tests of patients diagnosed with POMT2-related α-DGP were analyzed retrospectively. The pathogenicity of variants in POMT2 were predicted by bioinformatics software. The variants with uncertain significance were verified by further analysis. RESULTS: The 11 patients, comprising eight males and three females, were from nine non-consanguineous families. They exhibited different degrees of muscle weakness, ambulation, and intellectual impairment. Among them, three had a muscle-eye-brain disease (MEB)-like phenotype, five presented congenital muscular dystrophy with intellectual disability (CMD-ID), and three presented limb-girdle muscular dystrophy (LGMD). Overall, nine novel variants of POMT2, including two non-sense, one frameshift and six missense variants, were identified. The pathogenicity of two missense variants, c.1891G > C and c.874G > C, was uncertain based on bioinformatics software prediction. In vitro minigene analysis showed that c.1891G > C affects the splicing of POMT2. Immunofluorescence staining with the IIH6C4 antibody of muscle biopsy from the patient carrying the c.874G > C variant showed an apparent lack of expression. CONCLUSION: This study summarizes the clinical and genetic characteristics of a cohort of POMT2-related α-DGP patients in China for the first time, expanding the mutational spectrum of the disease. Further study of the pathogenicity of some missense variants based on enzyme activity detection is needed.
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OBJECTIVE: To improve the diagnosis and management of Duchenne/Becker muscular dystrophy(DMD/BMD). METHODS: Clinical features of 90 cases of DMD/BMD were collected. Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes, and multiplex ligation-dependent probe amplification (MLPA) was applied to detect DMD gene to identify genetic mutation. For those patients whose deletion/duplication mutation was not identified, FKRP gene mutation analysis was performed using PCR-DNA direct sequence. All the cases were followed up. RESULTS: Among the 90 cases of clinically diagnosed DMD/BMD, exons deletion of DMD was detected in 58 cases (64.44%), and exons duplication in 9 (10.00%). Among the 34 mothers with an affected boy but without previous genetic conformation, 17 were confirmed to be carriers with gene deletion/duplication. None of the 23 cases, without detected DMD gene deletion/duplication, carried FKRP gene mutation. Fourteen children were given short-term intermittent prednisone therapy (0.75 mg/kg daily during the first 10 days of each month). The course was not long enough and the sample size was too small to conclude any benefits or side effects. Prenatal diagnosis was provided for one mother in her next pregnancy detecting a female carrier fetus. CONCLUSION: DMD gene deletions mainly occurs between exons 45 and 54, while duplications mostly at 5'-terminus. Identification of the characteristics and types of gene mutation may facilitate the recognition and prognosis prediction of DMD/BMD. MLPA is a non-complex and quick diagnostic tool for DMD/BMD and its carriers, and also helpful in genetic counseling.
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Deleção de Genes , Distrofia Muscular de Duchenne/genética , Mutação , Técnicas de Amplificação de Ácido Nucleico , Adolescente , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Seguimentos , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: To analyze the relationship between phenotype and genotype and the role of immune cells in the pathogenesis of X-linked Charcot-Marie-Tooth disease (CMT1X). METHODS: The probands of the two families with X-linked dominant inherited peripheral neuropathy were evaluated clinically, electrophysiologically, pathologically and genetically. The available family members were genetic analyzed and the novel mutations were compared with other known ones. RESULTS: (1) In both families, affected members presented progressive weakness and wasting of distal extremities and it seems that males suffered more severely than affected females with onset in the first decade of their life. Proband of family 1 showed moderately elevated CSF protein and marked increase of IgG-syn in CSF.(2) Nerve conduction velocity (NCV) of the peripheral nerves was intermediately slow in both motor and sensory nerves exhibiting the features of demyelination. Brain-stem auditory evoked potentials (BAEPs) was abnormal in the proband of family 1: delayed I-III interpeak intervals were recorded but with normal III-V interpeak intervals. (3) Sural nerve biopsy in the probands of the two families showed a prominent distinguished loss of myelinated fibers and a few clusters of regenerating axons without conspicuous onion-bulb formations. Thinly myelinated fibers was prominent in family 2 but not in family 1. Immunohistochemical staining showed that there were positive CD68 cells in the endoneurial space and lamellar sheath. (4) By genetic testing, we identified two novel missense mutations of GJB1 gene, which resulted in Ile127Phe amino acid substitution in family 1(located in the intracellular loop of connexin 32) and Asp178Gly amino acid substitution in family 2 (located in the 2(nd) extracellular loop of CX32), respectively. Both mutations were highly conserved in low species and were predicted to be possibly damaging through Polyphen prediction tool. CONCLUSION: The two novel GJB1 gene mutations cause a spectrum of clinical manifestations of CMT1X in both families. However, the mutations site of CX32 alone cannot predict these phenotypic variations in CMT1X fully. The immune system may be involved in the pathogenesis of the disease.
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Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Conexinas/genética , Mutação , Adolescente , Adulto , Idoso , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Proteína beta-1 de Junções ComunicantesRESUMO
Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.
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DNA Mitocondrial/genética , Complexo I de Transporte de Elétrons/deficiência , Doença de Leigh/genética , Mutação , Adolescente , Humanos , MasculinoRESUMO
Mercury intoxication is a rare cause of severe hypertension. A case of mercury intoxication presented with severe hypertension and erythromelalgia was reported. A 10-year- and -5-month-old girl presented with recurrent rash and painful hands for 2 months, with seizure attack and episodic loss of consciousness for one hand half months. The girl was found to have red painful hands, a blood pressure 170/120 mm Hg(1 mm Hg=0.133 kPa), tachycardia and hypokalemia (2.83-3.25 mmol/L, reference value 3.5-5.5 mmol/L). An extensive investigation ensued. Elevated renin-angiotensin and aldosterone were demonstrated in plasma. Cranial MRI T2 weighed images showed widespread white matter signal abnormalities, which particularly involved parietal, occipital and frontal lobes. With hypertension controlled, white matter signal abnormalities weakened. Other symptoms included insomnia, nausea and paroxysmal abdominal pain. The girl was found to have a raised concentration of mercury in urine (0.171 mg/L, reference value< 0.01 mg/L), and she had been exposed to elemental mercury for several days. After chelating therapy, the girl's blood pressure returned to normal, erythromelalgia ameliorated, all other symptoms disappeared. So, mercury intoxication should be considered in the differential diagnosis of hypertension with erythromelalgia.
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Eritromelalgia/diagnóstico , Hipertensão/diagnóstico , Intoxicação por Mercúrio/diagnóstico , Criança , Eritromelalgia/etiologia , Feminino , Humanos , Hipertensão/etiologia , Intoxicação por Mercúrio/complicaçõesRESUMO
Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.
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Doença de Leigh/genética , Mutação , Piruvato Desidrogenase (Lipoamida)/genética , Pré-Escolar , Diagnóstico Diferencial , Humanos , Doença de Leigh/diagnóstico , Doença de Leigh/terapia , MasculinoRESUMO
Febrile seizure (FS) is a frequently encountered seizure type in childhood. Changes of brain function following FS have clinical importance. The recently identified gamma-aminobutyric acid B receptor (GABA(B)R) is a metabotropic receptor of GABA. In this study, we used a rat model of recurrent FS to investigate the changes of GABA(B)R1a and GABA(B)R2 subunits in hippocampus after recurrent FS by using Western blot, quantitative RT-PCR, double immunofluorescence, in situ hybridization and immunoprecipitation/Western blot. After treatment of hyperthermia and the presence of induced seizures once every 2 days for 10 times, GABA(B)R1a and GABA(B)R2 subunits in hippocampus were decreased after 24 h of the last treatment. The decrease of GABA(B)R1a lasted for 15 days but that of GABA(B)R2 persisted for more than 30 days. The binding of GABA(B)R1a to GABA(B)R2 in hippocampus was also decreased significantly after 24 h of the last treatment and lasted for more than 30 days. In situ hybridization showed that GABA(B)R1a mRNA was significantly decreased in dentate gyrus, and GABA(B)R2 mRNA was considerably reduced in CA3 region. In H10 and FS1 groups in which hyperthermia treatment was the same but no (H10 group) or only one seizure (FS(1) group) was induced, the decrease of GABA(B)R1a and GABA(B)R2 subunits and the reduced binding capability between GABA(B)R1a and GABA(B)R2 subunits were also detected but with less severity, and the time recovering from these abnormalities was shorter. We conclude that GABA(B)R1a and GABA(B)R2 subunits and the binding of the 2 subunits decrease in hippocampus for a relatively long period of time after recurrent FS in immature rats. These changes may result in long-lasting imbalance of excitation/inhibition function in hippocampus, and are derived from the consequences of recurrent febrile seizures.
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Hipocampo/metabolismo , Subunidades Proteicas/metabolismo , Receptores de GABA-B/metabolismo , Convulsões Febris/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Modelos Animais de Doenças , Masculino , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Febrile seizure (FS) is the most common seizure disorders. Approximately one third of children with a febrile seizure have recurrent events. The mechanism of FS remains unclear. Heme oxygenase-1 (HO-1) is a member of the heat shock proteins family and can be induced in the brain by various stresses, including hyperthemia and seizure. This study aimed at investigating the changes of HO-1 in the cortex of rats after recurrent FS. METHODS: FS in rats was induced ten times, once every 2 days. In a bath of warm water, developing rats were randomly divided into two groups: control group (n = 16) and warm water-treated group (n = 50). The latter group was subdivided into hyperthermia group (n = 19) and FS group (n = 23). The expression and content of HO-1 mRNA in cortex were observed using in situ hybridization and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The content of HO-1 protein in cortex was measured using Western blotting. RESULTS: HO-1 mRNA expression of cortex neurons in FS group was markedly increased in comparison with those in hyperthermia and control groups (P = 0.00), however, there was no statistic difference between hyperthermia group and control group (P = 0.16). The relative amount of HO-1 mRNA in cortex in FS group was increased by 53.13% and 96% in comparison with those in hyperthermia group and control group respectively (P = 0.00), but there was no obvious difference between the later two groups (P = 0.051). Western blotting analysis showed that the HO-1 protein content in cortex in FS group was increased by 198% and 246% in comparison with those in hyperthermia group and control group respectively (P = 0.00). There was no obvious difference in HO-1 protein content between the later two groups (P = 0.09). CONCLUSIONS: Recurrent FS in rats can cause the increase of HO-1 mRNA and protein in cortex which may be involved in the mechanism of FS. The short-time recurrent hyperthermia can not induce the increase of HO-1 mRNA and protein.
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Córtex Cerebral/enzimologia , Febre/enzimologia , Heme Oxigenase-1/genética , Convulsões Febris/enzimologia , Animais , Heme Oxigenase-1/análise , Masculino , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , RecidivaRESUMO
OBJECTIVE: To explore the effect of gamma-aminobutyric acid B receptor (GABA(B)R)on nitric oxide (NO)/nitric oxide synthase (NOS) system during recurrent febrile seizures (FS). METHODS: Sprague-Dawley rats aged 21 days were randomly divided into four groups:control group, FS group, FS + baclofen group, FS + phaclofen group. FS in rats were induced ten times in a bath of warm water,once every 2 days. The plasma level of NO was detected by the spectrophotometer; the expression of nNOS mRNA was examined by in situ hybridization; the expression of nNOS protein was observed by immunohistochemistry. RESULTS: Compared with those in FS group,the plasma level of NO decreased [(19.02+/-9.31) micromol/L vs (40.03+/-9.12)micromol/L], and the expression of nNOS was down-regulated in FS + baclofen group; the plasma level of NO increased [(66.46+/-8.15) micromol/L vs (40.03+/-9.12) micromol/L] and the expression of nNOS was up-regulated in FS + phaclofen group. CONCLUSION: GABA(B)R modulated the expression of NO/NOS system during recurrent FS.
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Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/sangue , Receptores de GABA-B/metabolismo , Convulsões Febris/metabolismo , Animais , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Febrile seizure (FS) is the most common type of seizure disorders in children. Recurrent FS can cause hippocampal neurons injury. At the same time heme oxygenase/carbon monoxide (HO/CO) system and nitric oxide synthase/nitric oxide (NOS/NO) system were up-regulated and interacted each other. This study examined the effects of the two systems on the apoptosis of hippocampal neurons in rats with recurrent FS. METHODS: FS was induced in rats by exposure to warm water bath (45.2 degrees C), once every 2 days, 10 times in all. Sprague-Dawley (SD) rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS + ZnPP-IX (HO inhibitor) and FS + L-NAME (NOS inhibitor) groups. The apoptosis of hippocampal CA1 neurons was detected by TUNEL. RESULTS: After recurrent FS, the apoptotic cells in the hippocampal CA1 neurons increased by 225% compared with those in the Control group (P < 0.01). The apoptotic cells in the FS+ZnPP-IX group increased by 62% and 425% compared with those in the FS and the Control groups (both P < 0.01). The apoptotic cells in the FS + L-NAME group decreased by 38% compared with those in the FS group (P < 0.01) and increased by 100% compared with those in the Control group (P < 0.05). CONCLUSIONS: In recurrent FS, exogenous administration of HO inhibitor ZnPP-IX may induce an increase of apoptotic cells in hippocampal neurons, while NOS inhibitor L-NAME may decrease the apoptotic cells. The results suggest that the HO/CO system might alleviate neuronal damage, while NOS/NO system might augment neuronal damage.
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Apoptose/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Hipocampo/patologia , Óxido Nítrico/farmacologia , Convulsões Febris/patologia , Animais , Heme Oxigenase (Desciclizante)/fisiologia , Marcação In Situ das Extremidades Cortadas , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Ratos , Ratos Sprague-Dawley , Convulsões Febris/tratamento farmacológicoRESUMO
OBJECTIVE: Febrile seizure (FS) is one of the most common seizure types in children. Our previous studies have demonstrated that both gamma-aminobutyric acid B receptor (GABABR) and hydrogen sulfide (H2S) are involved in the pathogenesis of FS. This study was designed to explore the effect of GABABR on H2S/cystathionine-beta-synthase (CBS) system in recurrent FS. METHODS: Sixty-four Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37 degrees C water bath exposure), FS, FS+baclofen (GABABR excitomotor), and FS+phaclofen (GABABR inhibitor) groups (n=16 each). FS was induced by warm water bath exposure (45.2 degrees C, once every 2 days, 10 times in total. The plasma level of H2S was detected by the spectrophotometer. The expression of CBS mRNA was examined by in situ hybridization. The expressions of CBS protein was observed by immunohistochemistry. RESULTS: The plasma level of H2S increased in the FS+baclofen group (427.45 +/- 15.91 micromol/L) but decreased in the FS+phaclofen group (189.72 +/- 21.53 micromol/L) compared with that in the FS group (362.14 +/- 19.71 micromol/L). The expressions of CBS mRNA and protein were up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen group compared with those in the FS group. CONCLUSIONS: GABABR modulated the expression of H2S/CBS system in recurrent FS.
Assuntos
Cistationina beta-Sintase/fisiologia , Sulfeto de Hidrogênio/metabolismo , Receptores de GABA-B/fisiologia , Convulsões Febris/metabolismo , Animais , Baclofeno/farmacologia , Cistationina beta-Sintase/genética , Sulfeto de Hidrogênio/sangue , Ratos , Ratos Sprague-Dawley , RecidivaAssuntos
Síndrome de Fadiga Crônica , Narcolepsia , Síndrome da Taquicardia Postural Ortostática , Adolescente , Comorbidade , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/genética , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Síndrome da Taquicardia Postural Ortostática/genéticaRESUMO
OBJECTIVE: To study the alteration of hydrogen sulfide (H(2)S)/ cystathionine-beta-synthase (CBS) system during recurrent febrile seizures (FS) in the hippocampus of developing rats. METHODS: The rats were randomly divided into control group (n=8) and hyperthermia-treated group (n=22). Which was subdivided into FS group (n=8) and H group(no seizure occurred, n=9) according to whether seizures occurred. The plasma level of H(2)S was detected by the spectrophotometer. The expression levels of CBS gene and protein were examined by in situ hybridization and immunohistochemistry respectively. RESULTS: The plasma levels of H(2)S were increased significantly in FS group compared with those of control group or H group. The expression levels of CBS gene and protein were enhanced in FS group compared with those of control group or H group. CONCLUSION: The expression levels of H(2)S/ CBS system were up-regulated during recurrent FS.