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CELSR1 gene, encoding cadherin EGF LAG seven-pass G-type receptor 1, is mainly expressed in neural stem cells during the embryonic period. It plays an important role in neurodevelopment. However, the relationship between CELSR1 and disease of the central nervous system has not been defined. In this study, we performed trios-based whole-exome sequencing in a cohort of 356 unrelated cases with partial epilepsy without acquired causes and identified CELSR1 variants in six unrelated cases. The variants included one de novo heterozygous nonsense variant, one de novo heterozygous missense variant, and four compound heterozygous missense variants that had one variant was located in the extracellular region and the other in the cytoplasm. The patients with biallelic variants presented severe epileptic phenotypes, whereas those with heterozygous variants were associated with a mild epileptic phenotype of benign epilepsy with centrotemporal spikes (BECTS). These variants had no or low allele frequency in the gnomAD database. The frequencies of the CELSR1 variants in this cohort were significantly higher than those in the control populations. The evidence from ClinGen Clinical-Validity Framework suggested a strong association between CELSR1 variants and epilepsy. These findings provide evidence that CELSR1 is potentially a candidate pathogenic gene of partial epilepsy of childhood.
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Epilepsias Parciales , Humanos , Epilepsias Parciales/genética , Cadherinas/genética , Alelos , Heterocigoto , Mutación Missense/genéticaRESUMEN
OBJECTIVE: The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.
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Anticonvulsivantes/uso terapéutico , Encéfalo/fisiopatología , Epilepsia Mioclónica Juvenil/diagnóstico , Convulsiones/diagnóstico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Niño , Preescolar , China , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Epilepsia Mioclónica Juvenil/fisiopatología , Convulsiones/diagnóstico por imagen , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Adulto JovenRESUMEN
OBJECTIVES: Jeavons syndrome (JS) is one of the underreported epileptic syndromes and is characterized by eyelid myoclonia (EM), eye closure-induced seizures or electroencephalography (EEG) paroxysms, and photosensitivity. In the Western populations, it has been reported to be characterized by focal posterior, occipital predominant epileptiform discharges (OPEDs) or frontal predominant epileptiform discharges (FPEDs) followed by generalized EDs in both interictal and ictal EEG recordings. However, it is not clear if there are different clinical manifestations between OPEDs and FPEDs. The clinical and electrographic presentations in the Chinese population are largely unknown. Here, we report the clinical and electroencephalographic features of 50 Chinese patients with JS and evaluate for the presence of different clinical features between patients with OPEDs and patients with FPEDs. METHODS: We identified 50 cases who met the Jeavons syndrome criteria from 4230 patients with epilepsy at Xijing Hospital, Xi'an, China from the period of January 2010 to November 2011. These patients underwent long-term 24-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI) or computerized tomography (CT). Webster IQ testing was performed to determine intellectual development. We reviewed and described the interictal abnormalities, ictal EEG pattern, and demographic, clinical, and neuroimaging findings of these 50 Chinese patients in Xi'an. We divided the 50 patients into two groups according to the predominance of EDs and analyzed their clinical features. RESULTS: Twenty-five of these 50 patients were male. Twenty-two out of 32 patients in the group with FPEDs were male, and 3/18 patients in the group with OPEDs were male. The median age of EMA-EM onset in FPEDs was 8years and that in OPEDs was 5.8years. Eyelid myoclonia occurred in all the 50 patients. Twenty-one out of 32 patients in the group with FPEDs had EM with absences, and 14/32 of them had EM with eyeball rolling up. Two out of 18 patients in the group with OPEDs had EM with absences, and only 1 of 18 had EM with eyeball rolling up. CONCLUSION: Eyelid myoclonia with or without absences or JS diagnosis is easily missed and underreported in China. As an IGE, either the frontal or the occipital lobe may initiate generalized spike-and-wave discharges (GSWDs) and generalized seizures (GSs). There may be two subtypes of JS with distinctive clinical and electroencephalogrphic features: a predominantly male group with frontal predominant epileptiform discharges, eyelid myoclonia, and eyes rolling up and a predominantly female group with occipital predominant epileptiform discharges with eyelid myoclonia alone.
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Epilepsia Tipo Ausencia/complicaciones , Epilepsia/diagnóstico , Párpados/fisiopatología , Mioclonía/diagnóstico , Mioclonía/fisiopatología , Adolescente , Adulto , Anciano , Encéfalo/patología , China , Electroencefalografía , Epilepsia/fisiopatología , Epilepsia Tipo Ausencia/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Occipital/fisiopatología , Convulsiones/fisiopatología , Síndrome , Grabación en VideoRESUMEN
The pathogenesis of temporal lobe epilepsy (TLE) was originally considered to be acquired. However, some reports showed that TLE was clustered in some families, indicating a genetic etiology. With the popularity of genetic testing technology, eleven different types of familial TLE (FTLE), including ETL1-ETL11, have been reported, of which ETL9-ETL11 had not yet been included in the OMIM database. These types of FTLE were caused by different genes/Loci and had distinct characteristics. ETL1, ETL7 and ETL10 were characterized by auditory, visual and aphasia seizures, leading to the diagnosis of familial lateral TLE. ETL2, ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities, indicating a mesial temporal origin. Febrile seizures were common in FTLEs such as ETL2, ETL5, ETL6 and ETL11. ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura. Considering the diversity and complexity of the symptoms of TLE, neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully. Most FTLE patients had a good prognosis with or without anti-seizure medication treatment, with the exception of patients with heterozygous mutations of the CPA6 gene. The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development, differentiation and synaptic signaling. In this article, we describe the research progress on eleven different types of FTLE. The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.
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Epilepsy is a paroxysmal brain disorder that results from an imbalance between neuronal excitation and inhibition. Gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the brain and plays an important role in the occurrence and development of epilepsy. Abnormalities in all aspects of GABA metabolism, including GABA synthesis, transport, genes encoding GABA receptors, and GABA inactivation, may lead to epilepsy. GABRA1, GABRA2, GABRA5, GABRB1, GABRB2, GABRB3, GABRG2 and GABBR2 are genes that encode GABA receptors and are commonly associated with epilepsy. Mutations of these genes lead to a variety of epilepsy syndromes with different clinical phenotypes, primarily by down regulating receptor expression and reducing the amplitude of GABA-evoked potentials. GABA is metabolized by GABA transaminase and succinate semi aldehyde dehydrogenase, which are encoded by the ABAT and ALDH5A1 genes, respectively. Mutations of these genes result in symptoms related to deficiency of GABA transaminase and succinate semi aldehyde dehydrogenase, such as epilepsy and cognitive impairment. Most of the variation in genes associated with GABA metabolism are accompanied by developmental disorders. This review focuses on advances in understanding the relationship between genetic variation in GABA metabolism and epilepsy to establish a basis for the accurate diagnosis and treatment of epilepsy.
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Epilepsia , Receptores de GABA-A , 4-Aminobutirato Transaminasa/genética , 4-Aminobutirato Transaminasa/metabolismo , Aldehído Deshidrogenasa/genética , Epilepsia/diagnóstico , Epilepsia/genética , Humanos , Mutación/genética , Receptores de GABA/metabolismo , Receptores de GABA-A/genética , Succinatos , Ácido gamma-AminobutíricoRESUMEN
OBJECTIVE: Continuous spike-and-wave during slow wave sleep (CSWS) syndrome is one of the presentations of electrical status epilepticus during sleep (ESES). The purpose of this study was to investigate the characteristics of CSWS syndrome in children. METHODS: Between 2007 and 2009, a total of 778 nocturnal long-term or 24-hr video-EEG records were included. The EEG, clinical and neuroimaging characteristics were studied in children who met standard criteria for CSWS. RESULTS: Nine children met standard criteria for CSWS in video-EEGs. Their ages ranged 6 to 13 years. Their EEGs were characterized by continuous spike-and-wave (SW) discharges during non-rapid eye movement (NREM) sleep, accounting for 85%-100% of the period of NREM sleep. Clinically, these children had various types of epileptic seizures and exhibited different degrees of neuropsychiatric impairments, language dysfunction, and/or behavioral disturbances. Neuroimaging abnormalities were found in 6 cases, including atelencephalia or atrophy, gray matter heterotopia and leucomalacia. CONCLUSIONS: This study indicates the characteristics of CSWS syndrome in clinical manifestations, EEG and neuroimaging examinations. This will be helpful in understanding CSWS syndrome.
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Sueño/fisiología , Estado Epiléptico/fisiopatología , Adolescente , Niño , Electroencefalografía , Humanos , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , SíndromeRESUMEN
OBJECTIVE: To compare and rank the efficacy and acceptability of new antiepileptic drugs (AEDs) for patients with focal drug-resistant epilepsy. METHODS: PubMed, EMBASE, Cochrane databases and Clinicaltrials.gov were systematically searched from their inception through January 1, 2020, to identify trials evaluating AEDs for focal drug-resistant epilepsy. We included randomized controlled clinical trials (RCTs) comparing new AEDs with placebo or with other AEDs as adjunctive therapy for focal drug-resistant epilepsy. A Bayesian network meta-analysis was performed to determine efficacy and acceptability, as reflected by odds ratios (ORs), 95 % credible intervals (CrIs) with random-effects and consistent models. RESULTS: Sixty-two RCTs were included, involving 12,739 patients with focal drug-resistant epilepsy. Regarding the seizure-free rate (40 RCTs involving 9,136 patients), 8 AEDs were more efficacious than placebo, with lnORs ranging between 1.69 for brivaracetam (95 % CrI, 0.56-2.81) and 0.72 for pregabalin (95 % CrI, 0.12-1.32). Regarding the responder rate, all AEDs except oxcarbazepine were more efficacious than placebo, with lnORs ranging between 1.31 for levetiracetam (95 % CrI, 0.92-1.71) and 0.66 for carisbamate (95 % CrI, 0.17-1.14). Regarding acceptability (60 RCTs comprising 12,139 patients), 9 AEDs were inferior to placebo. Estimated from seizure-free rate, brivaracetam was ranked as the most efficacious AED based on cumulative probability plots and SUCRAs, with fatigue as the main adverse event. CONCLUSION: The results indicate that, based on seizure-free rate and all-cause discontinuation rate, brivaracetam is the most efficacious and acceptable AED, with mild adverse events and acknowledgement of potential publication bias.
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Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada , Pirrolidinonas/uso terapéutico , Quimioterapia Combinada/métodos , Humanos , Levetiracetam/uso terapéutico , Metaanálisis en Red , Oxcarbazepina/uso terapéutico , Preparaciones Farmacéuticas , Pregabalina/uso terapéuticoRESUMEN
N-myc downstream-regulated gene 2 (NDRG2) has been implicated in the development of central nervous system and brain diseases such as brain tumors, ischemic stroke and neurodegenerative disorders. However, it remains unclear that the spatiotemporal distribution of NDRG2 in the human fetal brain. In this study, we examined the expression pattern of NDRG2 in different regions of human fetal brain at 16-28 gestational weeks (GWs) by using RT-PCR, western blot and immunohistochemistry. Firstly, RT-PCR revealed that mRNA of NDRG2 was detected in the human brain regions of fetuses at 16-28 GWs such as medulla oblongata (MdO), mesencephalon (MeE), cerebellum (Cbl), frontal lobe (Fr), ventricular (VZ)/subventricular zone (SVZ) and hippocampus (hip), and the expressions of NDRG2 mRNA in these human fetal brain regions were increased with gestational maturation. Furthermore, western blot and immunohistochemistry results revealed that at 28 GWs, the expression of NDRG2 protein was restricted to the MdO's olivary nucleus, MeE's aqueduct, cerebellar internal granular layers, cerebral cortex of the Fr, VZ/SVZ of lateral ventricle, and hippocampal dentate gyrus, and highest expression in the VZ/SVZ, and lowest in the MeE. Finally, double immunohistochemistry results showed that NDRG2 in the MdO, Cbl and VZ/SV at 28 GWS was mainly expressed in neurons (NeuN positive cells), and in some astrocytes (GFAP positive cells). Taken together, these results suggest that NDRG2 is mainly expressed in human fetal neurons of various brain regions during development, which may be involved in neuronal growth and maturation.
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Encéfalo/metabolismo , Feto/anatomía & histología , Proteínas Supresoras de Tumor/metabolismo , Encéfalo/embriología , Edad Gestacional , Humanos , Análisis Espacio-TemporalRESUMEN
Status epilepticus (SE) can cause severe neuronal loss and oxidative damage. As peroxisome proliferator-activated receptor gamma (PPARgamma) agonists possess antioxidative activity, we hypothesize that rosiglitazone, a PPARgamma agonist, might protect the central nervous system (CNS) from oxidative damage in epileptic rats. Using a lithium-pilocarpine-induced SE model, we found that rosiglitazone significantly reduced hippocampal neuronal loss 1 week after SE, potently suppressed the production of reactive oxygen species (ROS) and lipid peroxidation. We also found that treatment with rosiglitazone enhanced antioxidative activity of superoxide dismutase (SOD) and glutathione hormone (GSH), together with decreased expression of heme oxygenase-1 (HO-1) in the hippocampus. The above effects of rosiglitazone can be blocked by co-treatment with PPARgamma antagonist T0070907. The current data suggest that rosiglitazone exerts a neuroprotective effect on oxidative stress-mediated neuronal damage followed by SE. Our data also support the idea that PPARgamma agonist might be a potential neuroprotective agent for epilepsy.
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Hipocampo/efectos de los fármacos , Degeneración Nerviosa/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , PPAR gamma/agonistas , Estado Epiléptico/tratamiento farmacológico , Tiazolidinedionas/farmacología , Animales , Benzamidas/farmacología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Convulsivantes , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Litio , Masculino , Agonistas Muscarínicos , Degeneración Nerviosa/etiología , Degeneración Nerviosa/fisiopatología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/fisiología , PPAR gamma/antagonistas & inhibidores , PPAR gamma/metabolismo , Pilocarpina , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Rosiglitazona , Estado Epiléptico/inducido químicamente , Estado Epiléptico/fisiopatología , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1RESUMEN
BACKGROUND: This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. METHODS: This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. RESULTS: Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treatment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among different seizure types, OXC was effective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects experienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. CONCLUSION: This study, reporting the real-world data, further confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.
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Anticonvulsivantes/uso terapéutico , Carbamazepina/análogos & derivados , Epilepsia Tónico-Clónica/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Administración Oral , Factores de Edad , Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Preescolar , China , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Epilepsia Tónico-Clónica/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oxcarbazepina , Estudios Prospectivos , Convulsiones/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
We used immunohistochemical methods to examine the distribution of the calcium channel alpha2 (CCalpha2) subunit in the chicken spinal cord and dorsal root ganglion (DRG) neurons and determine its relationship with calbindin-D28k (CB) in the DRG neurons. In the spinal cord, CCalpha2 subunit was detected in nerve terminals, which were observed as dot-like structures, and in laminae I, II, III and Lissauer's tract in the dorsal horn. In the DRG neurons, approximately 65% of the total neurons were CCalpha2 subunit positive, and most (86%) of these neurons were small to medium sized, suggesting that the CCalpha2 subunit and/or a complex of the CCalpha2 and delta subunits is possibly localized in a number of nociceptive neurons. A majority (77%) of the positive neurons showed CB immunoreactivity and most (88%) of these neurons were small to medium sized. This may indicate a close correlation between the CCalpha2 subunit and CB in the nociceptive neurons. Thus, it is postulated that the mode of nociceptive transmission may involve a cellular Ca(2+)-regulating system that consists of both Ca(2+) entry via calcium channels with the alpha2delta subunit and intracellular Ca(2+)-binding activity of CB in the nociceptive neurons of the DRG.
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Canales de Calcio/metabolismo , Ganglios Espinales/metabolismo , Células del Asta Posterior/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Médula Espinal/metabolismo , Vías Aferentes/metabolismo , Vías Aferentes/ultraestructura , Animales , Calbindina 1 , Calbindinas , Canales de Calcio Tipo L , Recuento de Células , Pollos , Femenino , Ganglios Espinales/citología , Inmunohistoquímica , Neuronas Aferentes/citología , Neuronas Aferentes/metabolismo , Nociceptores/citología , Nociceptores/metabolismo , Dolor/metabolismo , Dolor/fisiopatología , Células del Asta Posterior/citología , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Subunidades de Proteína/metabolismo , Médula Espinal/citología , Raíces Nerviosas Espinales/metabolismo , Raíces Nerviosas Espinales/ultraestructuraRESUMEN
Decreased sweat secretion is a primary side effect of topiramate in pediatric patients, but the mechanism underlying this effect remains unclear. This study aimed to better understand how topiramate decreases sweat secretion by examining its effect on the expression of carbonic anhydrase (CA) II and aquaporin-5 (AQP5), total CA activity, as well as on tissue morphology of sweat glands in mice. Both developing and mature mice were treated with a low (20 mg/kg/day) and high dose (80 mg/kg/day) of topiramate for 4 weeks. Sweat secretion was investigated by an established technique of examining mold impressions of hind paws. CA II and AQP5 expression levels were determined by immunofluorescence and immunoblotting and CA activity by a colorimetric assay. In mature mice, topiramate treatment decreased the number of pilocarpine reactive sweat glands from baseline in both the low and high dose groups by 83% and 75%, respectively. A similar decrease was seen in developing mice. Mature mice with reactive sweat glands that declined more than 25% compared to baseline were defined as anhidrotic mice. These mice did not differ from controls in average secretory coil diameter, CA II expression and CA activity. In contrast, anhidrotic mice did show a reduction in membrane AQP5 expression in sweat glands after topiramate delivery. Thus, sweat secretion and membrane AQP5 expression in mouse sweat glands decreased following topiramate administration. These results suggest dysregulation of AQP5 may be involved in topiramate-induced hypohidrosis and topiramate may serve as a novel therapy for hyperhidrosis.
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Anticonvulsivantes/farmacología , Acuaporina 5/metabolismo , Fructosa/análogos & derivados , Regulación de la Expresión Génica/efectos de los fármacos , Glándulas Sudoríparas/metabolismo , Sudor/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Anhidrasa Carbónica II/metabolismo , Colorimetría , Relación Dosis-Respuesta a Droga , Técnica del Anticuerpo Fluorescente , Fructosa/farmacología , Immunoblotting , Ratones , TopiramatoRESUMEN
Epilepsia partialis continua (EPC) is a rare variant of epilepsy. Cases from China are rare. We present a case series of seven patients to analyze its clinical features, imagining findings, etiology, drug use, and long-term outcome in a single epilepsy center. We made assessments of drug effects twice (Stage I - when they left our hospital; Stage II in March 2017 - by telephone interviews to rate their long-term outcome). The mean duration of the second follow-up was 4.8years. Of the seven patients, four patients characterized motor and sensory EPC and three motor EPC. Local distributions of EPC were: the left face (2 patients), right face (1 patient), left leg (3 patients), right leg and arm (1 patient). CT/MR was abnormal in four, normal in two, and not available in one patient. EEG abnormalities commonly consisted of spike-waves, sharp-waves (or) slow wave activity, and periodic lateralized epileptiform discharges. They were all nonprogressive EPC (encephalitis: 2; tumor: 2; head trauma: 1; and not found in 2 cases). In our observations, topiramate might be effective in patients with facial muscles continuous jerking, while carbamazepine in cases of limbs continuous myotonia. Our cases had favorable long-term outcome. Thus, our cases' etiology differentiated from other regions. Some drugs used by referring to EPC distributions might help to control EPC and their outcome were usually favorable.
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Epilepsia Parcial Continua/etiología , Adolescente , Adulto , Niño , China , Traumatismos Craneocerebrales/complicaciones , Electroencefalografía , Encefalitis/complicaciones , Epilepsia Parcial Continua/diagnóstico , Epilepsia Parcial Continua/tratamiento farmacológico , Femenino , Humanos , MasculinoRESUMEN
UNLABELLED: Potent effects of Flt3 ligand (FL) on the development of the immune system have generated much interest in application of FL in cancer immunotherapy. OBJECTIVE: To evaluate the effects of Pichia pastoris secreted rhFL on the growth of mouse EL-4 lymphoma and C26 colon adenocarcinoma injected in syngeneic mice for the first time. METHODS: Mice were placed into one of two treatment groups. 2 x 10(5) EL-4 or C26 cells were injected subcutaneously (SC.) into mice on day 0. Group 1 received subcutaneous PBS injections from Day -7 to Day 14 and group 2 received subcutaneous rhFL injections at 30 microg/day from Day -7 to Day 14. Serial tumor areas were measured. On Day 22, mice from each group were sacrificed, and weight of tumors and spleens were evaluated. Data analysis used Student t tests. RESULTS: Pichia pastoris secreted rhFL resulted in tumor growth delay for both EL-4 lymphoma and C26 colon adenocarcinoma compared with control (P < 0.01). Tumors from rhFL-treated mice were smaller (P < 0.01) than controls while spleens larger (P < 0.01) than controls. Histological examination of tumor sections revealed an obvious increase in regions composed largely of infiltrating cells in the rhFL-treated tumors. Infiltrating cells could be detected in clusters among tumors from mice treated with rhFL whereas these cells were only occasionally detected in sections of control tumors. CONCLUSION: Treatment of rhFL expressed from Pichia pastoris resulted in an antitumor response against EL-4 and C26 tumors injected in syngeneic mice.
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Adenocarcinoma/tratamiento farmacológico , Adyuvantes Inmunológicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Proteínas de la Membrana/farmacología , Pichia/química , Adenocarcinoma/patología , Animales , Neoplasias del Colon/patología , Inmunoterapia , Linfoma/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
NDRG2, one of the new N-Myc downstream-regulated gene (NDRG) gene families, is believed to be involved in cell growth event. However, the exact function is still unknown. Identification of the tissue or cell types expressing this gene in vivo will provide clues in clarifying its physiological roles. Using RT-PCR and Western blot, we analyzed the expression level of NDRG2 mRNA and protein in human fetal tissues from different gestational ages. The anti-NDRG2 monoclonal antibody, which has been proved to react specifically with NDRG2 protein, was further used to analyze the cellular location of NDRG2 protein in various human fetal tissues by immunohistochemistry. We found that NDRG2 expression was developmentally dynamic, being generally lower in the early stages of development and markedly increasing during the later stages. NDRG2 mRNA and protein distribution were generally consistent in heart and lung. One of the differences was that NDRG2 protein appeared later than mRNA in kidney. Another unmatched expression was found in liver. NDRG2 mRNA appeared later than protein in liver. In human fetal tissues at sixteen and twenty-eight weeks of gestation, NDRG2 protein immunoreactions could be seen in epithelium of small intestine, epithelium of large intestine, superficial layer of epidermis, whisker follicles, epithelium of small bronchus, hepatocytes, cardiac myocytes, thymus corpuscles and epithelium of renal tubule, and the immunoreactions in those tissues from twenty-eight weeks of gestation was stronger than that from sixteen weeks of gestation. In the present study, we demonstrate the expression pattern and cellular location of NDRG2 protein in a large set of human fetal tissues. This is the first demonstration of NDRG2 protein expression in human fetal tissues. Taken together, the results suggest that NDRG2 protein found in a variety of tissues is not a tissue-specific protein, and may play important roles in histogenesis and organogenesis.
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Regulación del Desarrollo de la Expresión Génica , Proteínas Supresoras de Tumor/metabolismo , Feto , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Tisular , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: To express the first three immunoglobulin-like domains of human stem cell factor receptor (c-Kit/Ig1-3) in E. coli and HEK293 ET cells and study their binding activity for stem cell factor (SCF). METHODS: In prokaryotic expression system, a double mutant form of c-Kit /Ig1-3 (c-Kit /Ig1-3(DM) was produced by overlap PCR and cloned into pET16b. The recombinant protein was expressed in E. coli BL21 (DE3) and refolded by dilution. In eukaryotic expression system, the gene of c-Kit/Igl13 with eight histidine segments was cloned into pEAK12 and the recombinant plasmid was transfected into HEK293 ET cells. The fusion protein was harvested from the growth medium and purified on Ni-NTA agarose column. The recombinant protein was tested for the receptor binding activity with his-tag pull-down and enzyme-linked immunosorbent binding assay. RESULTS: In E. coli c-Kit /Ig1-3(DM) as produced as an inclusion body and showed low binding activity for SCF after refolding. Two HEK293 ET cell clones that express high levels of c-Kit/Ig1-3 were produced and each clone secreted 2p micro/ml of recombinant protein, whose relative molecular mass was about 58,000. Eukaryotically expressed c-Kit/Ig1-3 had specific binding activity for SCF, and the dissociation constant (Kd) was 9.39 nmol/L. CONCLUSION: c-Kit/Ig1-3 with high receptor binding activity is successfully produced in HEK293 ET cells.
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Inmunoglobulinas/biosíntesis , Inmunoglobulinas/aislamiento & purificación , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Proteínas Proto-Oncogénicas c-kit/aislamiento & purificación , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/aislamiento & purificación , Células Cultivadas , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Inmunoglobulinas/genética , Ligandos , Plásmidos , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Recombinantes de Fusión/genética , TransfecciónRESUMEN
Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system. There is no consensus regarding reported associations between human leukocyte antigen DQB1 (HLA-DQB1) polymorphisms and the risk for developing GBS. Here, we evaluated possible associations between HLA-DQB1 polymorphisms and the risk for GBS using a meta-analysis. We searched PubMed for case-control genetic association studies for HLA-DQB1 polymorphisms (*020x, *030x, *040x, *050x, and *060x) and the risk for GBS. Fixed-effect meta-analytical methods were used for the outcome measure and subgroup analyses. Estimated odds ratios (ORs) and 95% confidence intervals (CIs) were used to investigate the associations between HLA-DQB1 polymorphisms and the risk for GBS. Nine case-control studies involving 780 cases of GBS and 1353 controls were identified in the current study. The meta-analysis demonstrated no significant associations between HLA-DQB1 polymorphisms and the risk for GBS in Asian and Caucasian populations. There were two associations that approached significance: HLA-DQB1*030x in Asian patients (P = 0.07; OR: 0.76, 95% CI: 0.57-1.03) and HLA-DQB1*060x in all patients (P = 0.08; OR: 1.48, 95% CI: 0.96-2.29). Additional studies with larger sample sizes are required to establish a definitive assessment of the contribution of HLA-DQB1 polymorphisms to GBS risk.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Síndrome de Guillain-Barré/genética , Cadenas beta de HLA-DQ/genética , Polimorfismo Genético , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/etnología , Síndrome de Guillain-Barré/etnología , Humanos , Oportunidad Relativa , Población Blanca/genéticaRESUMEN
AIM: To investigate the expression of NDRG2 and mutation of the entire coding region of NDRG2 in human liver and pancreatic cancers, and to further discuss the possible causes of NDRG2 distinct expression patterns. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze the expression of NDRG2 mRNA in 37 fresh cancer specimens (including 8 cases of pancreatic cancer and 29 cases of liver cancer) and adjacent normal tissues collected from clinical operation. In addition, mutation analysis of the whole coding region of NDRG2 in these cancers was examined by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). RESULTS: Compared with adjacent normal tissues, the expression levels of NDRG2 mRNA in corresponding cancer tissues reduced significantly (pancreatic cancer: 0.680+/-0.112 vs 2.089+/-0.214, P<0.01) (liver cancer: 0.894+/-0.098 vs 1.345+/-0.177, P<0.05). Using PCR-SSCP, the mutation of the whole coding region of NDRG2 was not found in those cancer tissues where the expression of NDRG2 mRNA reduced markedly. CONCLUSION: NDRG2 gene might express differently between normal tissues and cancer tissues, and might play an important role in the development of pancreatic cancer and liver cancer. Low expression of NDRG2 might be unrelated to the mutation of coding region of NDRG2.
Asunto(s)
Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/fisiopatología , Proteínas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Polimorfismo Conformacional Retorcido-Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Supresoras de TumorRESUMEN
Altered microRNA-205 (miR-205) expression has been found in glioma tissue samples and cell lines; however, the clinical significance of this is unclear. The aim of this study was to confirm the miR-205 expression pattern in human glioma and to investigate its clinical relevance. Quantitative reverse-transcription polymerase chain reaction assays showed that miR-205 expression was significantly lower in glioma tissues than in non-neoplastic brain tissues (P<0.001). Statistical analysis revealed a significant correlation between low miR-205 expression and both high grade glioma (World Health Organization [WHO] criteria, P=0.008) and a low Karnofsky performance status score (P=0.02). Survival analysis demonstrated that the cumulative 5-year overall survival rate of patients with glioma in the high miR-205 expression group was significantly higher than that in the low miR-205 expression group (P<0.001). Multivariate Cox regression analysis further indicated that miR-205 expression (P=0.01) and WHO grade (P=0.01) were independent prognostic indicators of the overall survival of patients with glioma. Moreover, subgroup analyses revealed that the cumulative 5-year overall survival rate of patients with high grade (III-IV) glioma was significantly worse for the low miR-205 expression group than for the high miR-205 expression group (P<0.001), but no significant difference was found for patients with low grade (I-II) glioma (P=0.09). In conclusion, down-regulation of miR-205 was associated with glioma progression. Our data are the first to suggest that miR-205 holds potential as a prognostic factor for glioma, especially for patients with advanced disease.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Glioma/genética , MicroARNs/análisis , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Estimación de Kaplan-Meier , Estado de Ejecución de Karnofsky , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TranscriptomaRESUMEN
OBJECTIVE: Epileptic patients have a higher relapse risk when EEGs before the initiation of anti-epileptic drug (AED) withdrawal show epileptiform activity. The purpose of this study is to assess the characteristics of ambulatory EEGs before the decision to withdraw AEDs and to clarify potential influencing factors for abnormal EEGs. METHODS: 214 epileptic patients were included in the study. These patients were seizure-free for 3-5 years on AED medication. Ambulatory 24-h EEGs were performed before the decision to withdraw AEDs. The demographical data and clinical information of the patients were used for the analysis of influencing factors for EEG findings. RESULTS: Ambulatory EEGs showed abnormalities in 41.1% of the patients (88/214). Of 88 patients with abnormal EEGs, 43 had unequivocal epileptic discharges; and 45 only had nonspecific EEG abnormalities. In our analysis, the potential factors for abnormal EEGs included female, delayed therapy, longer duration of intractability/treatment response time and medications failed. CONCLUSIONS: In many patients ambulatory EEGs remain abnormal even after seizure-free for 3-5 years; and many factors influenced the characteristics of the EEGs. The findings can assist in establishment of therapeutic principles.