RESUMO
OBJECTIVE: Although the pathogeneses of Alzheimer's disease (AD) and periodontal diseases have overlapping features, including ageing and chronic inflammation, the association between AD and periodontitis remains unclear. To explore the pathogenesis of periodontitis, a comprehensive gene expression/transcriptome analysis in periodontitis-affected gingival tissues found that the AD pathway was significantly up-regulated in periodontitis-affected gingival tissues. AD-related genes, amyloid beta precursor protein (APP), interleukin-1 beta and compliment 1QA, were significantly elevated in periodontitis. In the present study, balance between mRNA expression of APP and a potent amyloid degradation enzyme, neprilysin (NEP), as well as protein localisation of APP and NEP were analysed. DESIGN: Eighteen periodontitis-affected and 18 clinically healthy control gingival tissues were taken from patients with severe chronic periodontitis or undergoing tooth extraction. Total RNA was purified and used for quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR). The localisation of APP and NEP was analysed by immunohistochemistry (IHC). RESULTS: Both APP and NEP genes were up-regulated in periodontitis-affected gingival tissues. APP-expressing macrophages and NEP-expressing neutrophils and fibroblasts, reflecting inflammatory stages, were detected in inflamed gingival tissues by IHC. CONCLUSION: The up-regulation of APP and NEP mRNA levels in periodontitis-affected gingival tissues compared with healthy controls was confirmed by qRT-PCR analyses. Since NEP is one of the primary enzymes that degrades amyloid beta, increased NEP mRNA levels in periodontitis may act as an inhibitor of amyloid beta accumulation in gingival tissues, balancing increased APP mRNA expression. However, NEP has several effects including degradation of vasoactive substances; therefore, further sresearch is needed.
Assuntos
Periodontite Crônica/metabolismo , Gengiva/efeitos dos fármacos , Neprilisina/biossíntese , Neprilisina/farmacologia , Adulto , Idoso , Doença de Alzheimer , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Periodontite Crônica/diagnóstico por imagem , Periodontite Crônica/genética , Periodontite Crônica/patologia , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Gengiva/diagnóstico por imagem , Gengiva/patologia , Humanos , Imuno-Histoquímica , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Japão , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Neprilisina/genética , Neutrófilos/metabolismo , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaAssuntos
Toxinas Botulínicas/uso terapêutico , Paralisia Cerebral/tratamento farmacológico , Crianças com Deficiência , Toxinas Botulínicas/administração & dosagem , Paralisia Cerebral/diagnóstico , Criança , Crianças com Deficiência/estatística & dados numéricos , Prova Pericial , Humanos , Japão , Resultado do TratamentoAssuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral/tratamento farmacológico , Neurotoxinas/uso terapêutico , Adolescente , Adulto , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Paralisia Cerebral/diagnóstico , Pré-Escolar , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Neurotoxinas/administração & dosagem , Neurotoxinas/efeitos adversos , Ventilação Pulmonar/efeitos dos fármacos , Resultado do TratamentoAssuntos
Toxinas Botulínicas/uso terapêutico , Paralisia Cerebral/tratamento farmacológico , Toxinas Botulínicas/administração & dosagem , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Metanálise como Assunto , Guias de Prática Clínica como Assunto , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Antibody-mediated and cytotoxic T cell-mediated pathogenicity have been implicated as the autoimmune pathophysiologic mechanisms in Rasmussen's encephalitis. METHODS: The authors investigated autoantibodies against the NMDA glutamate receptor (GluR) epsilon2 subunit and their epitopes in serum and CSF samples from 15 patients with chronic epilepsia partialis continua (EPC), 17 with West syndrome, 10 with Lennox-Gastaut syndrome, and 11 control subjects. RESULTS: In 15 patients with chronic EPC, we detected NMDA-type GluR epsilon2 autoantibodies in histologically proven Rasmussen's encephalitis (3/3 patients), clinical Rasmussen's encephalitis (6/7 patients), acute encephalitis/encephalopathy (2/3 patients), and nonprogressive EPC (2/2 patients). Serum IgM autoantibodies were found in the early phase of EPC and became negative later in four patients. The autoantibodies were not detected in West syndrome, Lennox-Gastaut syndrome, or controls. Among 10 patients with histologically proven or clinical Rasmussen's encephalitis, epitope analyses showed that the autoantibodies were predominantly against C-terminal epitopes and rarely against N-terminal epitope, with inconsistency in profile during the courses of disease. Epitope recognition spectrum of autoantibodies was broader in CSF than in serum, and the serum or CSF profile showed an increase in number of epitopes as disease progressed in some patients. CONCLUSIONS: The presence of autoantibodies against NMDA GluR epsilon2 suggests autoimmune pathologic mechanisms but is not a hallmark of Rasmussen's encephalitis. Patients with Rasmussen's encephalitis may have autoantibodies against several neural molecules, and these autoantibodies may be produced in the CNS after cytotoxic T cell-mediated neuronal damage.
Assuntos
Autoanticorpos/sangue , Encefalite/imunologia , Epilepsia Parcial Contínua/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Espasmos Infantis/imunologia , Adolescente , Adulto , Autoanticorpos/líquido cefalorraquidiano , Criança , Pré-Escolar , Doença Crônica , Progressão da Doença , Encefalite/sangue , Encefalite/líquido cefalorraquidiano , Epilepsia Parcial Contínua/sangue , Epilepsia Parcial Contínua/líquido cefalorraquidiano , Epitopos/imunologia , Feminino , Humanos , Lactente , Masculino , Valor Preditivo dos Testes , Subunidades Proteicas/imunologia , Valores de Referência , Testes Sorológicos , Espasmos Infantis/sangue , Espasmos Infantis/líquido cefalorraquidiano , SíndromeRESUMO
Inositol 1,4,5-trisphosphate receptor (IP3R) is an intracellular Ca2+ channel that releases Ca2+ into the cytosol and its subcellular distribution is believed to have significant effects on Ca2+ signalling. We constructed a plasmid vector containing full-length rat type 3 IP3R linked to GFP (GFP-IP3R) for expression in mammalian cells. Western blot analyses revealed that the expressed fusion protein contained both GFP and full-length type 3 IP3R. Fluorescence confocal microscopy showed that the fluorescence of GFP-IP3R3 was distributed to reticular network structures, even after cell permeabilization with saponin. We further visualized intracellular membranes with DiOC6, a vital fluorescent marker for intracellular membranes, and provide evidence that the distribution of GFP-IP3R3 overlaps with the distribution of the endoplasmic reticulum. Our results indicate that GFP-IP3R3 can be used to visualize IP3R in living cells, and pave the way for subsequent mutational and functional studies.
Assuntos
Canais de Cálcio/análise , Vetores Genéticos , Proteínas Luminescentes/genética , Receptores Citoplasmáticos e Nucleares/análise , Sequência de Aminoácidos , Sequência de Bases , Western Blotting , Canais de Cálcio/genética , DNA Recombinante , Retículo Endoplasmático/metabolismo , Proteínas de Fluorescência Verde , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Microscopia Confocal , Dados de Sequência Molecular , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Recombinantes de Fusão/genética , Células Tumorais CultivadasRESUMO
This study examined the effects of matching participants to treatments on the basis of their preferences for either individual or group therapy for obesity. Seventy-five obese adults who expressed a clear preference for either individual or group therapy were randomly assigned to either their preferred or their nonpreferred treatment modality within a 2 (individual vs. group therapy) x 2 (preferred vs. nonpreferred modality) factorial design. At posttreatment, group therapy produced significantly greater reductions in weight and body mass than individual therapy, and no significant effects were observed for treatment preference or the interaction for treatment preference by type of therapy. All treatment conditions showed equivalent improvements in psychological functioning. These findings suggest that group therapy produces greater weight loss than individual therapy, even among those clients who express a preference for individual treatment.
Assuntos
Comportamento de Escolha , Obesidade/terapia , Psicoterapia de Grupo , Psicoterapia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Satisfação do Paciente , Redução de PesoRESUMO
This study compared 2 extended therapy programs for weight management with standard behavioral treatment (BT) without additional therapy contacts. Participants were 80 obese women who completed 20 weekly group sessions of BT and achieved a mean initial weight loss of 8.74 kg. Participants were randomly assigned to a no-further-contact condition (BT only) or to one of two extended interventions consisting of relapse prevention training (RPT) or problem-solving therapy (PST). No significant overall weight-change differences were observed between RPT and BT or between RPT and PST. However, participants who completed the PST intervention had significantly greater long-term weight reductions than BT participants, and a significantly larger percentage of PST participants achieved clinically significant losses of 10% or more in body weight than did BT participants (35% vs. 6%).
Assuntos
Assistência ao Convalescente , Terapia Cognitivo-Comportamental/métodos , Obesidade/terapia , Resolução de Problemas , Psicoterapia de Grupo/métodos , Adulto , Feminino , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Redução de PesoRESUMO
We presented 3 cases who exhibited important clinical or histopathological findings relevant to the pathogenesis of acute encephalopathy with shock syndrome (AESS). Hyperpermeability of the blood vesseles in the central nervous system was revealed by autopsy in case 1 and by enhancement CT scan in case 2, which implicated that the primary lesion of AESS was vascular damage. Although other cytokines than interleukin (IL)-6 were not evaluated, high value of IL-6 in case 3 might suggest that the some highly activated cytokines caused AESS.
Assuntos
Encefalopatias/etiologia , Choque/etiologia , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Masculino , SíndromeRESUMO
The ATP-induced oscillatory changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)) were analysed in HSY cells, a salivary ductal cell line from human parotid, using a fluorescence ratio imaging system. At concentrations higher than 1 microM, ATP caused sinusoidal [Ca(2+)](i) oscillations due to the periodic release and reuptake of Ca(2+) by intracellular Ca(2+) stores. The phorbol ester 4beta-phorbol 12,13-dibutyrate (PDBu) changed the [Ca(2+)](i) oscillations to a single spike. The inhibitory effect of PDBu on the [Ca(2+)](i) signals was reversed by protein kinase C (PKC) inhibitors such as staurosporine and chelerythrine chloride. However, preincubation of the cells with the PKC inhibitors did not affect the pattern of the ATP-induced [Ca(2+)](i) oscillations. The desensitization of the [Ca(2+)](i) response observed during prolonged stimulation with ATP was also not prevented by the PKC inhibitors. Incubation of HSY cells with the sulphydryl reagent thimerosal, which enhances the sensitivity of inositol 1,4,5-trisphosphate (IP(3)) receptors, caused repetitive Ca(2+) release from intracellular Ca(2+) stores resulting in baseline spikes of [Ca(2+)](i). The thimerosal-induced [Ca(2+)](i) oscillations did not change in the presence of PDBu and the phospholipase C inhibitor U73122. Thus, we could not provide evidence that negative feedback by PKC plays a central role in the regulation of ATP-induced [Ca(2+)](i) oscillations. These results suggest that the [Ca(2+)](i) oscillations, at least the baseline spikes, in HSY cells can be generated without stimulating the formation of IP(3).
Assuntos
Trifosfato de Adenosina/farmacologia , Cálcio/metabolismo , Ductos Salivares/efeitos dos fármacos , Timerosal/farmacologia , Cálcio/análise , Cátions Bivalentes , Linhagem Celular , Corantes Fluorescentes , Fura-2 , Humanos , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Ductos Salivares/metabolismo , Fatores de TempoRESUMO
The Ca2+ signaling mediated by activation of beta-adrenoceptors was studied in a purified preparation of ducts from rat submandibular glands. At concentrations above 1 nM, isoproterenol (ISO) caused a small but significant increase in cytosolic Ca2+ concentration ([Ca2+]i). The ISO-induced increase in [Ca2+]i was completely inhibited by the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Forskolin was able to mimic the Ca2+ response to ISO. These results suggest that the ISO-induced increase in [Ca2+]i in rat submandibular ducts is mediated by an accumulation of cAMP resulting from activation of beta-adrenoceptors. In the absence of extracellular Ca2+, ISO or forskolin caused a transient increase in [Ca2+]i, indicating Ca2+ mobilization from intracellular Ca2+ stores. Further, stimulation with ISO failed to mobilize Ca2+ after the depletion of intracellular Ca2+ stores by phenylephrine or carbachol, suggesting that the cAMP-mediated increase in [Ca2+]i is due to a Ca2+ release from inositol trisphosphate (IP3)-sensitive Ca2+ stores. As ISO did not stimulate a detectable production of IP3, the cAMP-mediated Ca2+ mobilization may be evoked by a mechanism different from activation of phosphoinositide hydrolysis.
Assuntos
Cálcio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Glândula Submandibular/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacosRESUMO
To reveal the functional organization of the somatosensory area in the dysgenetic cortex, somatosensory-evoked potentials were examined in seven patients with congenital brain anomalies diagnosed by magnetic resonance imaging, including six patients in whom multichannel recordings over the scalp were used. In four patients with polymicrogyria/pachygyria and two with lissencephaly, the early cortical responses, frontal P20 and parietal N20, were absent in the cortex contralateral to the stimulated side. The first cortical response was a positive wave that appeared predominantly over the centroparietal area in five patients, and in the frontal area in the other patient with polymicrogyria/pachygyria. These findings suggest that the differentiated somatosensory function is distributed normally in the centroparietal cortex in most cases of widespread cortical dysplasia. However, the absence of P20/N20 may indicate a hypoplastic central sulcus or functionally undifferentiated subdivision of the somatosensory cortex in these patients. The absence of cortical responses in the patient with holoprosencephaly may correspond with growth failure of the thalamocortical afferent projections in this disorder.
Assuntos
Dano Encefálico Crônico/congênito , Encéfalo/anormalidades , Potenciais Somatossensoriais Evocados/fisiologia , Adolescente , Adulto , Encéfalo/fisiopatologia , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/fisiopatologia , Mapeamento Encefálico , Criança , Dominância Cerebral/fisiologia , Feminino , Lobo Frontal/anormalidades , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/anormalidades , Lobo Parietal/fisiopatologia , Tempo de Reação/fisiologia , Córtex Somatossensorial/anormalidades , Córtex Somatossensorial/fisiopatologiaRESUMO
We treated two children with influenza-associated acute encephalopathy by a combination of mild hypothermia and steroid pulse therapy. Case 1, a 2-year-and-3-month-old boy, admitted to our hospital 7 days after the onset of central nervous symptoms. The brain MRI-CT revealed laminar cortical necrosis and severe brain edema. EEG showed very low voltage. Brain edema improved by the combination therapy. He had sequelae, but was able to eat. Case 2, a 1-year-and-10-month-old boy, admitted to our hospital 5 days after the onset of central nervous symptoms. Brain MRI showed frontal dominant cortical edema. EEG showed high voltage delta bursts. The combination therapy was effective, but he remained mental handicapped. The outcome was better compared to our previous cases of acute encephalopathy. The combination therapy is intended to counteract cytokines, and was considered to be an effective treatment against acute encephalopathy associated with an influenza virus infection.
Assuntos
Encefalite Viral/terapia , Hipotermia Induzida/métodos , Vírus da Influenza A , Influenza Humana/terapia , Metilprednisolona/administração & dosagem , Pré-Escolar , Humanos , Lactente , Masculino , Pulsoterapia , Resultado do TratamentoRESUMO
BACKGROUND: To establish a treatment strategy for acute encephalopathy and encephalitis associated with influenza virus infection, the pathophysiology of the disease was investigated through manifestations and laboratory findings of patients. PATIENTS AND METHODS: A child with central nervous system (CNS) complications during the course of influenza virus infection was analyzed in view of immunologic abnormalities. In addition, four children with acute encephalopathy and encephalitis were enrolled in the hypothermia treatment for the purpose of stabilizing the cytokine storm in the CNS. RESULTS: The CNS symptoms preceded the systemic progression to the failure of multiple organs (MOF) and disseminated intravascular coagulopathy (DIC). The mild hypothermia suppressed the brain edema on computed tomography (CT) scanning and protected the brain from the subsequent irreversible neural cell damage. CONCLUSION: The replicated viruses at the nasopharyngeal epithelium may disrupt the olfactory mucosa and gain access to the brain via the olfactory nerve system. The direct virus-glial cell interaction or viral stimulation of the glial cells induces the production and accumulation of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-alpha, in the CNS. The cytokine storm results in neural cell damage as well as the apoptosis of astrocytes, due to the TNF-alpha-induced mitochondrial respiratory failure. The disruption of the blood-brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF. Mild hypothermia appears promising in stabilizing the immune activation and the brain edema to protect the brain from ongoing functional, apoptotic neural and glial damage and the systemic expansion of the cytokine storm.
Assuntos
Encefalopatias/fisiopatologia , Encefalopatias/virologia , Encefalite Viral/fisiopatologia , Encefalite Viral/virologia , Influenza Humana/complicações , Doença Aguda , Encefalopatias/terapia , Pré-Escolar , Encefalite Viral/terapia , Humanos , Hipotermia Induzida , MasculinoRESUMO
Five patients with acute encephalopathy underwent methylprednisolone pulse (mPSL-P), hypothermia and their combination therapies (3 cases, 1 case and 1 case, respectively), with excellent outcome. Two cases with severe brain edema survived. One had severe brain damage as a sequelae. The remaining one recovered well after the combination therapy with mPSL-p and mild hypothermia, despite complete obstruction of the fourth ventricle on the first CT scan; the sequelae, hemiplegia and intelligent disturbance, was only mild. Four patients who received mPSL-P therapy within 6 hours after the onset of CNS symptoms recovered well though one was left with epilepsy. These results indicate that mPSL-P and/or hypothermia therapy will be chosen as the treatment of acute encephalopathy.
Assuntos
Anti-Inflamatórios/administração & dosagem , Encefalite/terapia , Hipotermia Induzida , Metilprednisolona/administração & dosagem , Doença Aguda , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Masculino , Pulsoterapia , Resultado do TratamentoRESUMO
We studied the clinical and CT findings of 3 children with acute encephalopathy associated with adenovirus type 7 (AD-7) infection. Seizures in all the patients developed from 8 to 10 days after the onset of pyrexia. The values of serum AST, LDH and CRP elevated and those of WBC and serum protein decreased at the onset of encephalopathy. None of the patients had CSF leukocytosis. CT showed mild brain atrophy in all patients. A steroid pulse therapy was effective in one patient. The pathogenesis of encephalopathy is unknown. However, its onset and the success of the steroid pulse therapy suggested that it is a post infectious encephalitis. These findings, as well as the data of blood examination and of previous reports, implicated adverse effects of cytokines in the pathogenesis of this encephalopathy.
Assuntos
Infecções por Adenovirus Humanos/complicações , Adenovírus Humanos/classificação , Encefalite/etiologia , Doença Aguda , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Anti-Inflamatórios/administração & dosagem , Atrofia , Encéfalo/patologia , Pré-Escolar , Citocinas , Encefalite/tratamento farmacológico , Encefalite/patologia , Feminino , Humanos , Lactente , Masculino , Metilprednisolona/administração & dosagem , Pulsoterapia , Resultado do TratamentoRESUMO
A 67-year-old female patient with biopsy proven AL systemic amyloidosis developed rapidly progressive dyspnea. Chest roentgenogram and CT scan revealed a large right pleural effusion in addition to nodular lesions with bilateral hilar lymphadenopathy. The patient's serum showed IgG lambda type monoclonal gammopathy and she also had Bence Jones proteinuria. The pleural effusion was an exudate that contained many mononuclear cells and a high concentration of protein. Cardiac function was not seriously disturbed. Except for amyloidosis, no other causes for the severe pleural effusion were found. This patient was treated with chemical pleurodesis using Picibanil and a low dose of prednisolone. Eighteen months after this treatment, her right pleural effusion did not recur. Bronchopulmonary tissues are known to be frequently involved by AL systemic amyloidosis, but a nodular pattern of pulmonary amyloid deposition and a unilateral large pleural effusion are rare clinical manifestations in this disease.