Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infantile spasms is an epilepsy syndrome with several distinctive features, including age specificity during infancy, characteristic semiology (epileptic spasms), specific electroencephalographic patterns (interictal hypsarrhythmia and ictal voltage suppression), and responsiveness to the adrenocorticotropic hormone (ACTH). There is no adequate animal model of infantile spasms, perhaps due to these clinically unique features, that is specific for the developing human brain. An informative animal model would provide insights into the pathophysiology of this syndrome and form the basis for the development of innovative therapies. This chapter considers criteria for an "ideal" animal model of infantile spasms, as well as "minimal" criteria that we consider essential to yield useful information. Two animal models of infantile spasms have been described in rodents: seizures induced by corticotropin-releasing factor and N-methyl-D-aspartic acid. Neither of these models conforms exactly to the human analog, but each possesses intriguing similarities that provide testable hypotheses for future investigations.
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PMID:Infantile spasms: criteria for an animal model. 1204 Sep 4

Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY- and galanin-like immunoreactivities (LI) while NPY- and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.
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PMID:Topiramate normalizes hippocampal NPY-LI in flinders sensitive line 'depressed' rats and upregulates NPY, galanin, and CRH-LI in the hypothalamus: implications for mood-stabilizing and weight loss-inducing effects. 1270 Jun 90

The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism.
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PMID:Prospective preliminary analysis of the development of autism and epilepsy in children with infantile spasms. 1273 40

Blood concentrations of pituitary hormones adrenocorticotropin (ACTH), prolactin, growth hormone, and adrenal hormone-cortisol were measured in 36 autistic and 27 control individuals. Individuals with autism had significantly lower serum concentrations of cortisol (p < 10(-6)), and significantly higher concentrations of ACTH (p = 0.002) than control age- and sex-matched subjects. Also, prolactin concentrations in autistic patients with epilepsy were significantly higher when compared with normal subjects. The observed hormonal changes may indicate dysfunction of the hypothalamo-pituitary-adrenal axis in individuals with autism.
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PMID:Lower cortisol and higher ACTH levels in individuals with autism. 1295 23

Systemic adrenocorticotropic hormone (ACTH) administration is a first-line therapy for the treatment of infantile spasms, an age-specific seizure disorder of infancy. It is proposed that exogenous ACTH acts via negative feedback to suppress the synthesis of corticotropin-releasing hormone (CRH), a possible endogenous convulsant in infant brain tissue. The aim of this study was to determine whether systemic ACTH treatment in infant rats down-regulates the hippocampal CRH system, including CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R1 and CRH-R2). Daily i.p. injection of ACTH for 7 consecutive days (postnatal days 3-9) elevated serum corticosterone levels 20-fold measured on postnatal day 10, indicating systemic absorption and circulation of the ACTH. Semiquantitative reverse transcriptase-PCR demonstrated that both CRH and CRH-BP mRNA obtained from the hippocampi of ACTH-injected infant rats was significantly depressed relative to saline-injected animals. Comparable reductions in both CRH and CRH-BP synthesis were further demonstrated with radioimmunoassay. In contrast, neither CRH-R1 nor CRH-R2 mRNA was altered by ACTH treatment, relative to saline-injected rats. This latter finding was confirmed electrophysiologically by measuring the enhancement of hippocampal population spikes by exogenous CRH, also showing no differences between ACTH- and saline-injected rats. The results of this study support the proposal that systemic ACTH treatment down-regulates CRH expression in infant brain, perhaps contributing to the therapeutic efficacy observed during treatment of infantile spasms.
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PMID:Systemic adrenocorticotropic hormone administration down-regulates the expression of corticotropin-releasing hormone (CRH) and CRH-binding protein in infant rat hippocampus. 1471 94

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.
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PMID:Classical West "syndrome" phenotype with a subtelomeric 4p trisomy. 1537 35

Corticosteroids (predominantly prednisolone and hydrocortisone) and adrenocorticotropic hormone (ACTH) have been used in the treatment of the epilepsies for over 50 years. Over the past 30 years most reports have focused on epilepsy syndromes and epileptic encephalopathies resistant to treatment with the more conventional anticonvulsant and antiepileptic drugs (AEDs) and specifically West syndrome. There has been relatively little attention on the role of corticosteroids in treating other epilepsies.
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PMID:Corticosteroids in the management of the paediatric epilepsies. 1578 28

Ring chromosome 20 (r[20]) syndrome is characterized by mild to moderate learning disability*, behavioural disorders, epilepsy, and various dysmorphic features. Although still considered rare, r (20) syndrome is being increasingly diagnosed. More than 30 cases have been described in the literature since 1976. Here we report an additional case of a 14-year-old male with r (20). He had moderate to severe learning disability and epileptic seizures manifesting at about 18 months of age. During the 13 years' follow-up period he showed intractable epileptic seizures, behavioural disorders, and mild dysmorphological features including microcephaly, strabismus, micrognathia, down-slanting eyelids, and ear abnormalities. Frequent episodes of atypical absence or non-convulsive status associated with electroencephalogram changes were seen in follow-up. He was treated with several classical and new antiepileptic drugs, including intravenous immunoglobulin, corticotropin, and vagal nerve stimulation, with unsuccessful control of seizures. Finally, surgical treatment (corpus callosotomy) was performed at the age of 13 years; severity of tonic seizures was diminished, but frequency was unchanged. Although his behavioural problems, e.g. hyperactivity, were mild in early childhood they became more severe when he was 11 years old. Aggressiveness, compulsiveness with self-injury, and panic attacks developed at the age of 13 years, and were more pronounced after callosotomy. This case report provides the first description of deterioration in psychological situation in patients with r(20) intractable epilepsy. The patient was diagnosed with r(20) syndrome after 13 years of clinical follow-up. Karyotype analysis should, therefore, be performed in every patient with intractable epilepsy of unknown aetiology.
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PMID:Ring chromosome 20 syndrome with intractable epilepsy. 1635 3

Prenatal administration of corticosteroids is common in obstetrics to improve the outcome of premature deliveries. Many pregnant women receive multiple corticosteroid courses. Long-term follow-up studies in humans are limited, but those available suggest detrimental effects on the behavior of those children. Animal data also show adverse effects of prenatal corticosteroids mainly in the hippocampus, a structure sensitive to corticosteroid action. Several molecules involved in neuronal survival, seizure susceptibility, and behavior have been identified as possible targets of prenatal corticosteroid effects. These molecules include hippocampal glucocorticoid receptors, brain-derived neurotrophic factor, corticotropin-releasing hormone, and neuropeptide Y. Prenatal corticosteroid treatment permanently reprograms expression of these molecules. The future goals of research in this area include development of specific antagonists of corticosteroid activation pathways that would help differentiate between positive main effects and undesired adverse effects of prenatally administered corticosteroids.
Epilepsy Behav 2005 Aug
PMID:Prenatal corticosteroid impact on hippocampus: implications for postnatal outcomes. 1597 54

Nocturnal frontal lobe epilepsy up to now has been considered a channelopathy caused by mutations in the alpha(4) and beta(2) subunits of the neuronal nicotinic acetylcholine receptor. However, these mutations account for only a minority of patients, and the existence of at least a new locus for the disease has been demonstrated. In one Italian nocturnal frontal lobe epilepsy family, we identified two new putative loci on chromosomes 3 and 8, where several candidate genes are mapped. In particular, on chromosome 8, corticotropin-releasing hormone gene (CRH) appears to be a good candidate. We therefore searched for CRH mutations in the proband. The study allowed the identification of a nucleotide variation in the promoter that was subsequently detected in all affected and obligate carrier members of the same family, in two sporadic cases, in all affected members of an additional compliant family, and in the proband of a noncompliant family. Moreover, a different mutation in the promoter was detected in a familial case. In vitro experiments showed altered levels of gene expression. CRH alterations could explain several autosomal dominant nocturnal frontal lobe epilepsy clinical features.
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PMID:Frontal lobe epilepsy and mutations of the corticotropin-releasing hormone gene. 1622 69


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