RESUMO
PURPOSE: Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated. METHODS: CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated. RESULTS: When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the Cmax was markedly higher, and the mean residence time was longer than when CuGTSM was administered for both CuGTSM and GTSM in both mouse strains. With macular mice, the AUC ratio (GTSM/CuGTSM) was markedly higher and the plasma CuGTSM concentration was lower than with C3H/HeNCrl mice when either CuGTSM or nCuGTSM was administered. CONCLUSION: Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.
Assuntos
Complexos de Coordenação/farmacocinética , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Tiossemicarbazonas/farmacocinética , Administração Oral , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C3H , Tamanho da PartículaRESUMO
We report a patient with a 6q22.1 deletion, who presented with a rare syndrome of generalized epilepsy, myoclonic tremor, and intellectual disability. There was no clinical progression after follow-up for more than 10 years. Our report presents the genetic basis for a phenotype involving a non-progressive generalized epilepsy with tremor. The efficacy of valproic acid for seizure control and the partial efficacy of deep brain stimulation with propranolol for myoclonic tremor is detailed.
RESUMO
BACKGROUND: Menkes disease is a copper metabolism disorder caused by mutations in ATP7A, a copper-transporting P-type ATPase. In this study, oral copper supplementation via glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) (CuGTSM), a lipophilic copper complex, was investigated in male hemizygous macular (MoMl/y) mice, a mouse model of Menkes disease. METHODS: CuGTSM was administered by oral gavage on postnatal days 5, 8, 11, 17, 23, and 32. The copper levels in the organs and serum, copper-dependent enzyme activities in the brain, and ceruloplasmin (Cp) activity in the serum were measured at 15 days and 3 and 8 months of age. Histological analysis of the intestines and the rotarod test were also performed. RESULTS: CuGTSM treatment extended the lifespan of MoMl/y mice and partly restored the copper concentrations and cytochrome oxidase and DBH activities in the brain; however, the rotarod test showed impaired motor performance. The treatment also increased copper concentrations and Cp activity in the serum. In suckling MoMl/y mice, CuGTSM treatment transiently induced diarrhea accompanied by copper accumulation and altered villus morphology in the ileum. CONCLUSION: Oral administration of CuGTSM extended the lifespan of MoMl/y mice. Oral administration is attractive, but pharmaceutical studies are needed to reduce the adverse enteral effects.
Assuntos
Complexos de Coordenação/uso terapêutico , Cobre/farmacocinética , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Tiossemicarbazonas/uso terapêutico , Administração Oral , Animais , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/farmacologia , Cobre/sangue , ATPases Transportadoras de Cobre/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Mutação , Taxa de Sobrevida , Tiossemicarbazonas/administração & dosagem , Tiossemicarbazonas/farmacologia , Distribuição Tecidual , Aumento de Peso/efeitos dos fármacosRESUMO
Menkes disease (MD) is a neurodegenerative disorder characterized by copper deficiency. It is caused by defective intestinal absorption of copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. We investigated the effects of combination therapy with copper and disulfiram, a known lipophilic chelator. We synthesized a copper-disulfiram complex (Cu-DSF) and determined its crystal structure by X-ray crystallographic analysis. Unfortunately, Cu-DSF was not orally bioavailable due to its lipophilicity. We therefore planned to use cyclodextrin as a solubilizing agent to increase the water solubility of Cu-DSF. After comparisons of the effects of cyclodextrins (α, ß, γ), it was found that addition of ß-cyclodextrin (ß-CyD) increased the solubility of Cu-DSF. Moreover, the modified ß-CyD, hydroxypropyl-ß-cyclodextrin, was yet more effective as a solubilizing agent. For the development of a convenient method to determine the concentration of Cu-DSF included by ß-cyclodextrins, a standard curve based on UV-visible(VIS) absorption was derived.
Assuntos
Cobre/química , Dissulfiram/química , Cristalografia por Raios X , Ciclodextrinas/química , SolubilidadeRESUMO
We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n=20) and influenza virus-associated encephalopathy (IE) (n=18) to understand the underlying mechanism of IE. We found that IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n=20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.
Assuntos
Encefalite Viral/imunologia , Influenza Humana/imunologia , Elastase de Leucócito/sangue , Criança , Pré-Escolar , Citocinas/sangue , Selectina E/sangue , Encefalite Viral/sangue , Encefalite Viral/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Lactente , Influenza Humana/sangue , Influenza Humana/metabolismo , Influenza Humana/virologia , Interleucina-10/sangue , Interleucina-13/sangue , Interleucina-1beta/sangue , Interleucina-2/sangue , Interleucina-5/sangue , Interleucina-6/sangue , Interleucina-7/sangue , Interleucina-8/sangue , Masculino , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy (¹H-MRS). In six patients with cryptogenic WS, we performed single-voxel ¹H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Lobo Occipital/metabolismo , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/metabolismo , Hormônio Adrenocorticotrópico/uso terapêutico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Colina/metabolismo , Cosintropina/farmacologia , Eletroencefalografia , Feminino , Humanos , Lactente , Inositol/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Espasmos Infantis/fisiopatologiaRESUMO
The recent findings on subtraction ictal SPECT and ictal near-infrared spectroscopic topography in patients with West syndrome were summarized and its availability for presurgical evaluation was discussed. The subtraction ictal SPECT study in patients with West syndrome demonstrated the cortical epileptic region and subcortical involvement, which may consist of epilepsy networks related to the spasms. Moreover, subtraction ictal SPECT may have predictive power for short-term seizure outcome. Patients with a symmetric hyperperfusion pattern are predicted to have a better seizure outcome, whereas patients with asymmetric hyperperfusion pattern may develop poor seizure control. Importantly, asymmetric MRI findings had no predictive power for seizure outcome. Multichannel near-infrared spectroscopic topography applied to the patients with West syndrome detected an increase in regional cerebral blood volume in multiple areas which were activated either simultaneously or sequentially during spasms. Topographic changes in cerebral blood volume were closely correlated with spasm phenotype, suggesting that the cortex is involved in the generation of spasms. In conclusion, subtraction ictal SPECT may be considered as a useful tool for presurgical evaluation of patients with West syndrome and investigation of the pathophysiology of spasms. The ictal near-infrared spectroscopic topography should be more investigated to see if this is useful tool for presurgical evaluation.
Assuntos
Espasmos Infantis/diagnóstico , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Lactente , Fluxo Sanguíneo Regional , Espasmos Infantis/diagnóstico por imagem , Espasmos Infantis/patologiaRESUMO
Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged unilateral hemisphere with cortical malformation comprising abnormal hypertrophic cells. To address the proliferative status of HMG, Ki-67 immunoreactivity was investigated in HMG specimens obtained during epilepsy surgery. Nine HMG tissues were stained with a Ki-67 antibody and Ki-67 labeling index in the malformed cortex, and the underlying white matter was measured separately and compared with tissues from focal cortical dysplasias and normal brains from autopsy. In HMG tissues, Ki-67-positive cells were scattered in both the gray and white matter, with a significantly higher Ki-67 labeling index in the white matter compared with gray matter. No dysmorphic neuron or balloon cell was stained for Ki-67. As Ki-67 immunoreactivity overlapped with that of ionized calcium-binding adaptor protein-1, Ki-67-positive cells were identified as microglia. In HMG, microglia were activated and entered into a proliferative status with higher distribution in the white matter, implying an ongoing neuroinflammatory process involving the white matter.
Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Malformações do Desenvolvimento Cortical/metabolismo , Malformações do Desenvolvimento Cortical/patologia , Microglia/metabolismo , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Microglia/patologia , Distribuição TecidualRESUMO
BACKGROUND: Menkes disease (MD) is a disorder of copper transport caused by ATP7A mutations. Although parenteral copper supplements are partly effective in treating MD, the copper level in the brain remains insufficient, whereas copper accumulates in the kidney. We investigated the copper-trafficking efficacy of copper-pyruvaldehyde bis(N4-methylthiosemicarbazone) (Cu-PTSM), a lipophilic copper complex, in macular mice, an animal model of MD. METHODS: Macular mice were treated with cupric chloride (CuCl2) or Cu-PTSM on postnatal days 4, 10, and 17. At 4 wk of age, the copper levels in major organs and cytochrome oxidase (CO) activity in brain tissue were measured. Hematology, blood biochemistry, and urinary ß2-microglobulin (ß2-M) secretion were also assessed. RESULTS: The copper levels in the brains of the Cu-PTSM-treated group remained low, but CO activity in the cerebral and cerebellar cortices in the Cu-PTSM-treated group were higher than those in the CuCl2-treated group. There were no significant differences in hematological or biochemical findings or in urinary ß2-M secretion among the groups. CONCLUSION: Although the copper-trafficking efficacy of Cu-PTSM was limited, the improved CO activity in the brain suggests that Cu-PTSM delivered copper more effectively to neuronal CO than did CuCl2. Reduced renal copper accumulation may be beneficial in prolonged copper supplementation.
Assuntos
Cobre/metabolismo , Modelos Animais de Doenças , Síndrome dos Cabelos Torcidos/metabolismo , Compostos Organometálicos/metabolismo , Tiossemicarbazonas/metabolismo , Animais , Transporte Biológico , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Microglobulina beta-2/metabolismoRESUMO
The authors present a 14-year-old girl with 18q- syndrome combined with cyclic vomiting syndrome. Since the age of 5 years, she has been admitted to hospital 30 times. Despite trying many prophylactic treatments, no medication has inhibited the vomiting attacks successfully. Intranasal sumatriptan was effective at halting the vomiting attacks. This is the first case of 18q- syndrome combined with cyclic vomiting syndrome successfully treated with sumatriptan. This report may allow us to consider sumatriptan use in patients suffering from misery attack of cyclic vomiting syndrome combined with chromosomal abnormality of 18q- syndrome.
Assuntos
Transtornos Cromossômicos/complicações , Malformações do Sistema Nervoso/complicações , Agonistas do Receptor de Serotonina/administração & dosagem , Sumatriptana/administração & dosagem , Vômito/tratamento farmacológico , Administração Intranasal , Adolescente , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/fisiopatologia , Cromossomos Humanos Par 18/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/fisiopatologia , Síndrome , Resultado do Tratamento , Vômito/genética , Vômito/fisiopatologiaRESUMO
We measured the levels of pro- and anti-inflammatory cytokines in the cerebrospinal fluid (CSF) of 24 patients with West syndrome to clarify whether inflammatory cytokines were involved in the pathophysiology of West syndrome. There was no significant elevation of any of the three pro-inflammatory cytokines, interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha, in patients with West syndrome as compared with those in controls. However, level of anti-inflammatory cytokine, IL-1 receptor antagonist was significantly decreased in the CSF of patients with West syndrome. Further study is needed to elucidate whether an immune system disturbance is involved in the pathophysiology of West syndrome.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1/líquido cefalorraquidiano , Espasmos Infantis/líquido cefalorraquidiano , Citocinas/líquido cefalorraquidiano , Feminino , Humanos , Lactente , Interleucina-1beta/líquido cefalorraquidiano , Interleucina-6/líquido cefalorraquidiano , Masculino , Meningite Asséptica/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidianoRESUMO
Currently, various formulas with different fatty acid compositions are used for enteral nutrition (EN). All formulas contain various concentrations of essential fatty acids: linoleic acid (LA) and alpha-linolenic acid (ALA); LA is biotransformed into arachidonic acid (AA) and ALA into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vivo. Some formulas contain preformed EPA and DHA. However, the effects of the differences in the fatty acid composition on the fatty acid status of patients receiving long-term EN is not clear. We measured serum fatty acid concentrations in 50 patients with neurological diseases receiving long-term EN. The data were then compared retrospectively with reference to the fatty acid compositions of the formulas used. All of the patients received almost their entire nutritional intake via EN for at least 1 year. Blood samples were obtained just before injecting the EN solution. Among the formulas that did not include EPA or DHA, formulas with low ALA concentrations were associated with low serum EPA and DHA. Conversely, the ALA-enriched formulas with reduced LA concentrations significantly increased EPA and DHA levels, although the levels remained lower than the control values. With the formula containing EPA and DHA, the EPA and DHA levels reached control values. Therefore, the fatty acid composition of the EN formulas affected the fatty acid status of patients receiving long-term EN. Formulas containing preformed EPA and DHA with suitable amounts of essential fatty acids may benefit these patients.
Assuntos
Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Nutrição Enteral , Ácidos Graxos/sangue , Alimentos Formulados , Adulto , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
PURPOSES: The aims of the study were to evaluate the detectability of focal leading activity in three cases of West syndrome having focal abnormal activity on EEG by comparing subtraction ictal images and raw ictal images, and to interpret the results in 16 cases. METHODS: Subtraction images were constructed using iNeurostat (revision 2). RESULTS: In three cases with focal abnormal activity on EEG, subtraction ictal images reflected the EEG findings; in contrast, raw ictal images did not. Diverse degrees of cortical hyperperfusion, ranging from zero to 10 sites, seen in the other 13 cases seemed to reflect spasm pathophysiology and rapid spasm propagation. Subtraction ictal images also allowed the ready detection of hyperperfusion of subcortical structures and of a tight cortico-subcortical relationship in a subset of cases. CONCLUSIONS: We showed the superiority of subtraction ictal images in detecting the focal epileptic region and in showing propagation pathways from the cortex to subcortical structures. A subset of spasms in WS may be focal cortical-onset secondarily generalized seizures. We believe that subtraction analysis is valuable in patients with complex WS who have partial seizures and spasms simultaneously along with focal epileptic EEG activity, as they will likely be candidates for epilepsy surgery.
Assuntos
Espasmo/diagnóstico por imagem , Espasmo/etiologia , Espasmos Infantis/complicações , Espasmos Infantis/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Mapeamento Encefálico , Circulação Cerebrovascular , Eletroencefalografia/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
beta-Phenylethylamine (beta-PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. beta-PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but beta-PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which beta-PEA induces convulsions, we examined the effect of beta-PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of beta-PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 muM. These currents suppressed by beta-PEA consisted of two K(+) currents: a time- and voltage-dependent K(+) current (M-current) and a leakage K(+) current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K(+) current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose beta-PEA.
Assuntos
Neocórtex/fisiologia , Neurônios/fisiologia , Fenetilaminas/farmacologia , Canais de Potássio/efeitos dos fármacos , Convulsões/induzido quimicamente , Animais , Relação Dose-Resposta a Droga , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Modelos Biológicos , Neocórtex/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fenetilaminas/efeitos adversos , Psicotrópicos/efeitos adversos , Ratos , Ratos WistarRESUMO
A considerable amount of 7-aminoclonazepam (ACZP), a major metabolite of clonazepam (CZP), is present in the brain during CZP treatment, yet the pharmacological properties of ACZP remain unknown. We investigated the effects of ACZP on the GABA(A) receptor-mediated currents (I(GABA)) in neurons from the nucleus reticularis thalami (NRT) of the rat, using a nystatin-perforated patch technique. Neurons in which CZP (10 nM) exerted prominent augmentation (>100% augmentation) of I(GABA), which comprised 32% of the neurons tested, were included for the analysis of ACZP. In these neurons, ACZP augmented I(GABA), which was blocked by 10 microM flumazenil, a benzodiazepine receptor (BZR) antagonist. The half-maximal effective concentration of ACZP was 124 nM, whereas that of CZP was 1.8 nM. The maximal enhancements induced by ACZP and CZP were 38% and 170%, respectively. In neurons from the ventrobasal complex of the thalamus, the effect of ACZP was negligible. Our results suggest that ACZP was a weak partial BZR agonist and that ACZP may competitively modify the effect of CZP, leading to clinical consequences for patients with high levels of ACZP.
Assuntos
Clonazepam/análogos & derivados , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Receptores de GABA/fisiologia , Núcleos Talâmicos/citologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Clonazepam/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Estimulação Elétrica/métodos , Feminino , Moduladores GABAérgicos/farmacologia , Masculino , Potenciais da Membrana/efeitos da radiação , Técnicas de Patch-Clamp/métodos , Ratos , Ratos Wistar , Ácido gama-Aminobutírico/farmacologiaRESUMO
Patients with severe neurological disorders often require enteral nutrition (EN). Since long-term EN can cause multiple complications, reinstating the oral intake of food is beneficial. Olfactory stimulation using black pepper oil (BPO), a strong appetite stimulant, was reported to facilitate swallowing in older people. Therefore, the effects of olfactory stimulation with BPO were investigated in pediatric patients receiving long-term EN due to neurological disorders. The effects of scenting with BPO for 1 min immediately before every meal were evaluated in ten patients: 4 boys and 6 girls, aged 19-97 months (51 +/- 26 months). The neurological disorders included periventricular leukomalacia (3 patients), hypoxic ischemic encephalopathy (3), Costello syndrome (1), Russell-Silver syndrome (1), Miller-Dieker syndrome (1), and cerebral palsy of unknown etiology (1). In eight of these patients, BPO intervention was continued for 3 months. Five of these eight patients showed increases in the amount of oral intake with desirable effects including facilitated swallowing movement, although complete elimination of the need for EN was not achieved. In the other three patients, BPO intervention was not effective; severe cerebral tissue loss, profound malformation or intractable seizures seemed to reduce the efficacy of BPO. In two cases, BPO intervention was discontinued due to cough or because the odor of BPO was unbearable to the family. In conclusion, olfactory stimulation with BPO facilitated oral intake in a subset of patients on long-term EN. BPO stimulation may be useful for facilitating oral intake when used in combination with conventional methods.
Assuntos
Estimulantes do Apetite/administração & dosagem , Nutrição Enteral , Doenças do Sistema Nervoso/dietoterapia , Piper nigrum , Olfato/efeitos dos fármacos , Administração Oral , Criança , Pré-Escolar , Doença Crônica , Deglutição , Ingestão de Alimentos , Feminino , Humanos , Lactente , Masculino , Sialorreia , Estimulação QuímicaRESUMO
PURPOSE: To examine the distribution of KCC2, a neuron-specific K(+)-Cl(-) cotransporter, in human cortical dysplasia (CD). METHODS: The immunohistochemical expression of KCC2 was investigated in 18 CD specimens obtained during epilepsy surgery. The histopathologic diagnoses were focal CD (FCD) type I (eight cases), FCD type II (six cases), and hemimegalencephaly (HME; four cases). Tissue sections were immunostained for KCC2 and compared with control sections. RESULTS: In the mature nondysplastic cortex, all the layers showed diffuse neuropil staining for KCC2. The somata were stained much less, although subcortical ectopic neurons displayed dense staining in the cytosol (intrasomatic staining). In FCD type I, the cortex showed neuropil staining for KCC2 with less-stained somata. Aberrant giant pyramidal neurons were also less stained at the soma, whereas immature neurons showed intrasomatic staining. Increased numbers of ectopic neurons with intrasomatic staining were noted in the subcortical white matter. In FCD type II, dysmorphic neurons displayed dense intrasomatic staining with reduced staining of the neighboring neuropils. Balloon cells did not stain for KCC2. Dysmorphic neurons in HME also showed intrasomatic staining. CONCLUSIONS: Neurons in CD tissues expressed KCC2. However, the subcellular distribution of KCC2 was altered, which might have affected the ionic homeostasis of Cl(-) and K(+) involved in epileptic activity within CD tissues.
Assuntos
Córtex Cerebral/anormalidades , Córtex Cerebral/patologia , Epilepsia/metabolismo , Epilepsia/patologia , Neurônios/metabolismo , Simportadores/metabolismo , Adolescente , Adulto , Idoso de 80 Anos ou mais , Córtex Cerebral/metabolismo , Criança , Pré-Escolar , Cloretos/metabolismo , Corantes , Feminino , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Imuno-Histoquímica , Lactente , Masculino , Neocórtex/anormalidades , Neocórtex/metabolismo , Neocórtex/patologia , Neurônios/química , Neurônios/patologia , Neurópilo/metabolismo , Neurópilo/patologia , Potássio/metabolismo , Células Piramidais/metabolismo , Células Piramidais/patologia , Frações Subcelulares/metabolismo , Frações Subcelulares/patologia , Simportadores/análise , Distribuição Tecidual , Cotransportadores de K e Cl-RESUMO
The exposure to mercury (Hg) of various groups of people with different dietary backgrounds has been assessed because of its hazardous effects, but little is known about that in patients receiving enteral nutrition. Therefore, we studied the Hg exposure in 25 patients with severe motor disabilities, who received liquid enteral feedings for more than one year, by determining total mercury (T-Hg) in their hair samples with inductively coupled plasma-mass spectrometry. The geometric mean of the T-Hg level in hair from the patients was 88 ng/g hair (+/- 1 geometric standard deviation [GSD], 34 - 228 ng/g), whereas that for the control group on a normal diet was 1,900 ng/g (+/- 1 GSD, 1,022 - 3,531 ng/g). The T-Hg levels in the patients' hair were far lower than those in the controls (p < 0.001). The T-Hg levels in the enteral feedings used were below the detection limit of cold-vapor atomic absorption spectrophotometry (< 10 ng/g). The present study has shown that Hg exposure is low in patients receiving enteral nutrition, indicating that food is a primary source of Hg exposure.
Assuntos
Nutrição Enteral , Monitoramento Ambiental/métodos , Cabelo/química , Mercúrio/toxicidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Intoxicação por Mercúrio/diagnóstico , Transtornos das Habilidades Motoras , Espectrofotometria AtômicaRESUMO
We report the first infant case with hepatosplenic gammadelta T-cell lymphoma after recurrent acute disseminated encephalomyelitis-like, which were rapidly resolved with steroid pulse therapy. The patient had a history of recurrent bronchitis, intractable diarrhea, and failure to thrive since 4 months of age. Immunologic analysis revealed higher percentage of circulating gammadelta T-cells with markedly reduced numbers of CD3TCRalphabetaCD8 T-cells. The patient developed gammadelta T-cell lymphoma at the age of 15 months. Clinical course of the patient suggests the importance of immunological background for the development of hepatosplenic gammadelta T-cell lymphoma.