RESUMO
BACKGROUND: Most antiepileptic drug therapies are symptomatic and adversely suppress normal brain function by nonspecific inhibition of neuronal activity. In recent times, growing evidence has suggested that neuroinflammation triggered by epileptic seizures might be involved in the pathogenesis of epilepsy. Although the potential effectiveness of anti-inflammatory treatment for curing epilepsy has been extensively discussed, the limited quantitative data regarding spatiotemporal characteristics of neuroinflammation after epileptic seizures makes it difficult to be realized. We quantitatively analyzed the spatiotemporal changes in neuroinflammation in the early phase after status epilepticus in rats, using translocator protein (TSPO) positron emission tomography (PET) imaging, which has been widely used for the quantitative evaluation of neuroinflammation in several animal models of CNS disease. METHODS: The second-generation TSPO PET probe, [18F]DPA-714, was used for brain-wide quantitative analysis of neuroinflammation in the brains of rats, when the status epilepticus was induced by subcutaneous injection of kainic acid (KA, 15 mg/kg) into those rats. A series of [18F]DPA-714 PET scans were performed at 1, 3, 7, and 15 days after status epilepticus, and the corresponding histological changes, including activation of microglia and astrocytes, were confirmed by immunohistochemistry. RESULTS: Apparent accumulation of [18F]DPA-714 was observed in several KA-induced epileptogenic regions, such as the amygdala, piriform cortex, ventral hippocampus, mediodorsal thalamus, and cortical regions 3 days after status epilepticus, and was reversibly displaced by unlabeled PK11195 (1 mg/kg). Consecutive [18F]DPA-714 PET scans revealed that accumulation of [18F]DPA-714 was focused in the KA-induced epileptogenic regions from 3 days after status epilepticus and was further maintained in the amygdala and piriform cortex until 7 days after status epilepticus. Immunohistochemical analysis revealed that activated microglia but not reactive astrocytes were correlated with [18F]DPA-714 accumulation in the KA-induced epileptogenic regions for at least 1 week after status epilepticus. CONCLUSIONS: These results indicate that the early spatiotemporal characteristics of neuroinflammation quantitatively evaluated by [18F]DPA-714 PET imaging provide valuable evidence for developing new anti-inflammatory therapies for epilepsy. The predominant activation of microglia around epileptogenic regions in the early phase after status epilepticus could be a crucial therapeutic target for curing epilepsy.
Assuntos
Epilepsia , Estado Epiléptico , Animais , Anti-Inflamatórios/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/diagnóstico por imagem , Radioisótopos de Flúor , Humanos , Doenças Neuroinflamatórias , Tomografia por Emissão de Pósitrons/métodos , Pirazóis , Pirimidinas , Ratos , Receptores de GABA/metabolismo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/metabolismoRESUMO
We developed a practical synthetic method for fluorine-18 (18F)-labeled pitavastatin ([18F]PTV) as a positron emission tomography (PET) tracer to assess hepatobiliary transporter activity and conducted a PET scan as a preclinical study for proof-of-concept in rats. This method is a one-pot synthesis involving aromatic 18F-fluorination of an arylboronic acid ester followed by deprotection under acidic conditions, which can be reproduced in general clinical sites equipped with a standard radiolabeling system due to the simplified procedure. PET imaging confirmed that intravenously administered [18F]PTV was rapidly accumulated in the liver and gradually transferred into the intestinal lumen through the bile duct. Radiometabolite analysis showed that [18F]PTV was metabolically stable, and 80% of the injected dose was detected as the unchanged form in both blood and bile. We applied integration plot analysis to assess tissue uptake clearance (CLuptake, liver and CLuptake, kidney) and canalicular efflux clearance (CLint, bile), and examined the effects of inhibitors on membrane transport. Treatment with rifampicin, an organic anion transporting polypeptide inhibitor, significantly reduced CLuptake, liver and CLuptake, kidney to 44% and 64% of control, respectively. In contrast, Ko143, a breast cancer resistance protein inhibitor, did not affect CLuptake, liver but significantly reduced CLint, bile to 39% of control without change in [18F]PTV blood concentration. In addition, we found decreased CLuptake, liver and increased CLint, bile in Eisai hyperbilirubinemic rats in response to altered expression levels of transporters. We expect that [18F]PTV can be translated into clinical application, as our synthetic method does not need special apparatus in the radiolabeling system and PET scan with [18F]PTV can quantitatively evaluate transporter activity in vivo.
Assuntos
Radioisótopos de Flúor/química , Quinolinas/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Western Blotting , Cromatografia em Camada Fina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estrutura Molecular , Proteínas de Neoplasias/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos/efeitos dos fármacos , Transportadores de Ânions Orgânicos/metabolismo , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Rifampina/químicaRESUMO
Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90â¯min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (Pâ¯<â¯0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (Pâ¯<â¯0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (Pâ¯<â¯0.05) than that of [11C]UQN at 90â¯min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.
Assuntos
Antioxidantes/farmacocinética , Ubiquinona/análogos & derivados , Animais , Suplementos Nutricionais/análise , Masculino , Oxirredução , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Ubiquinona/farmacocinéticaRESUMO
Various positron emission tomography (PET) probes have been developed to assess in vivo activities in humans of drug transporters, which aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, sodium (3R, 5R)-3, 5-dihydroxy-7-((1S, 2S, 6S, 8S)-6-hydroxy-2-methyl-8- ((1-[11C]-(E)-2-methyl-but-2-enoyl) oxy) -1, 2, 6, 7, 8, 8a-hexahydronaphthalen-1-yl) heptanoate ([11C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps (gene symbol SLCO) and Mrp2 (gene symbol ABCC2) in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [11C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion. After intravenous injection, [11C]DPV rapidly distributed to the liver and kidney followed by secretion into the bile and urine. Rifampicin significantly reduced the liver distribution of [11C]DPV 3-fold, resulting in a 7.5-fold reduced amount of excretion into the bile and the delayed elimination of [11C]DPV from the blood circulation. The hepatic uptake clearance (CLuptake, liver) and canalicular efflux clearance (CLint, bile) of [11C]DPV (544 ± 204 and 10.2 ± 3.5 µl/min per gram liver, respectively) in humans were lower than the previously reported corresponding parameters in rats (1800 and 298 µl/min per gram liver, respectively) (Shingaki et al., 2013). Furthermore, rifampicin treatment significantly reduced CLuptake, liver and CLint, bile by 58% and 44%, respectively. These results suggest that PET imaging with [11C]DPV is an effective tool for quantitatively characterizing the OATP1Bs and MRP2 functions in the human hepatobiliary transport system.
Assuntos
Sistema Biliar/metabolismo , Transporte Biológico/fisiologia , Radioisótopos de Carbono/metabolismo , Fígado/metabolismo , Pravastatina/metabolismo , Adulto , Idoso , Animais , Bile/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Células HEK293 , Humanos , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Ratos , Rifampina/metabolismoRESUMO
BACKGROUND: Recent clinical studies have shown that increased serum levels of p-cresyl sulfate (PCS), a uremic toxin, are associated with the progression of chronic kidney disease (CKD) and cardiovascular outcomes. Using rat renal cortical slices, we previously reported that the rat organic anion transporter (OAT) could play a key role in the renal tubular secretion of PCS. However, no information is currently available regarding the transport of PCS via human OAT (hOAT) isoforms, hOAT1 and hOAT3. METHODS: Uptake experiments of PCS were performed using HEK293 cells, which stably express hOAT1 or hOAT3. RESULTS: PCS was taken up by hOAT1/HEK293 and hOAT3/HEK293 cells in a time- and concentration-dependent manner. The apparent K m for the hOAT1-mediated transport of PCS was 128 µM, whereas in hOAT3/HEK293, saturation was not observed at the highest tested PCS concentration of 5 mM. Probenecid, an OAT inhibitor, inhibited PCS transport by hOAT1 and hOAT3. The uptake of p-aminohippurate by hOAT1 and estron-3-sulfate by hOAT3 was decreased with increasing PCS concentration. The apparent 50 % inhibitory concentrations for PCS were 690 and 485 µM for hOAT1 and hOAT3, respectively. CONCLUSION: PCS is a substrate for hOAT1 and hOAT3, and hOAT1 and hOAT3 appear to play a physiological role as a high-capacity PCS transporter. Since hOATs are expressed not only in the kidneys, but also in blood vessels and osteoblasts, etc., these findings are of great significance in terms of elucidating the renal clearance, tissue disposition of PCS and the mechanism of its toxicity in CKD.
Assuntos
Cresóis/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Ésteres do Ácido Sulfúrico/metabolismo , Células HEK293 , Humanos , Uremia/metabolismoRESUMO
PURPOSE: To evaluate multiparametric MR imaging with combined use of apparent diffusion coefficients (ADCs) and time-signal intensity curves (TICs) for discriminating malignant thyroid nodules from benign ones. MATERIALS AND METHODS: ADCs and TICs of 7 benign and 16 malignant nodules were retrospectively analyzed on lesion-by-lesion (overall ADCs and TICs) and pixel-by-pixel (ADC and TIC mapping) bases. ADCs were determined using b-values of 500 and 1000 s/mm(2) . The TICs were classified into 5 patterns on the basis of increment ratio, peak time, and washout ratio. Stepwise approach based on ADC and TIC criteria was used to discriminate between benign and malignant nodules. RESULTS: Overall ADC discriminated undifferentiated carcinomas from papillary carcinomas at 91% accuracy (≤1.3 × 10(-3) mm(2) /s) and differentiated lymphomas from the other malignant nodules at 100% accuracy (≤0.65 × 10(-3) mm(2) /s). Most malignant thyroid nodules had large (≥45%) areas of rapid-uptake TIC profile with small (≤15%) areas of flat TIC profile, or had small (<45%) areas of rapid-uptake TIC profile with large (≥25%) areas of extremely low or low ADCs (≤1.2 × 10(-3) mm(2) /s). Stepwise approach discriminated malignant nodules from benign ones at 91% accuracy. CONCLUSION: The multiparametric MR imaging helps discriminating malignant thyroid nodules from benign ones.
Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Reconhecimento Automatizado de Padrão/métodos , Nódulo da Glândula Tireoide/patologia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/classificaçãoRESUMO
It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans. We recently developed a practical synthetic method for fluorine-18-labeled pitavastatin ([18F]PTV) as a PET probe for quantitative evaluation of hepatobiliary transport. In the present study, we conducted clinical PET imaging with [18F]PTV and compared the pharmacokinetic properties of the probe for healthy subjects with or without rifampicin pretreatment. Rifampicin pretreatment significantly suppressed the hepatic maximum concentration and biliary excretion of the probe to 52% and 34% of the control values, respectively. Rifampicin treatment markedly decreased hepatic uptake clearance (21% of the control), and moderately canalicular efflux clearance with regard to hepatic concentration (52% of the control). These results demonstrate that [18F]PTV is a useful probe for clinical investigation of the activities of hepatobiliary uptake/efflux transporters in humans.
Assuntos
Quinolinas , Rifampina , Transporte Biológico , Humanos , Fígado/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Quinolinas/metabolismo , Quinolinas/farmacologia , Rifampina/metabolismo , Rifampina/farmacologiaRESUMO
Paragangliomas (PGLs) are neural-crest-derived, non-epithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. Head-and-neck PGLs (HNPGLs) have been recognized as nonchromaffin, nonfunctional, parasympathetic tumors. By contrast, thoracoabdominal paragangliomas and pheochromocytomas (PPGLs) are chromaffin, functional, sympathetic tumors. Although HNPGLs and PPGLs have the same histological structure, the zellballen pattern, composed of chief and sustentacular cells surrounded by abundant capillaries, the pathobiological differences between these types of PGLs remain unclarified. To determine the phenotypic features of these PGLs, we performed an immunohistochemical study using specific antibodies against choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, and enzymes for the catecholamine-synthesis, tyrosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH), in 34 HNPGLs from 31 patients, 12 thoracoabdominal PGLs from 12 patients, and 26 pheochromocytomas from 22 patients. The expression of ChAT, TH, and DBH was 100%, 23%, and 10% in the HNPGLs; 12%, 100%, and 100% in the pheochromocytomas; and 25%, 67%, and 100% in the thoracoabdominal PGLs, respectively. These results designate HNPGLs as acetylcholine-producing parasympathetic tumors, in contrast to PPGLs being catecholamine-producing tumors. The other most frequently used neuroendocrine markers are synaptophysin and chromogranin A expressed 100% and 80%, respectively, and synaptophysin was superior to chromogranin A in HNPGLs. This is the first report of HNPGLs being acetylcholine-producing tumors. Immunohistochemistry of ChAT could be greatly useful for pathologic diagnosis of HNPGL. Whether measurement of acetylcholine levels in the blood or urine could be a tumor marker of HNPGLs should be investigated soon.
Assuntos
Colina O-Acetiltransferase/metabolismo , Dopamina beta-Hidroxilase/metabolismo , Paraganglioma Extrassuprarrenal/metabolismo , Feocromocitoma/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Neoplasias Abdominais/metabolismo , Neoplasias Abdominais/patologia , Adolescente , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Catecolaminas/biossíntese , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Japão , Masculino , Pessoa de Meia-Idade , Paraganglioma Extrassuprarrenal/patologia , Feocromocitoma/patologia , Neoplasias Torácicas/metabolismo , Neoplasias Torácicas/patologia , Adulto JovemRESUMO
PURPOSE: Otitis media with effusion (OME) commonly occurs and persists in young children. It can cause hearing impairment and damage to the tympanic membrane without treatment. We aimed to determine the prevalence and association of Streptococcus pneumoniae in the nasopharynx of healthy children before the introduction of a pneumococcal conjugate vaccine. METHODS: In October 2016, nasopharyngeal swabs collection and otoscope examinations by an otolaryngologist were conducted in children aged less than 24 months in Nha Trang, Vietnam. OME was diagnosed as the presence of middle ear fluid using a digital otoscope equipped with a pneumatic otoscope. Quantitative PCR targeting pneumococci-specific lytA (the major autolysis gene) and bacterial culture were performed to detect S. pneumoniae. The point prevalence of OME in the study area was estimated. The association between OME and S. pneumoniae in the nasopharynx was evaluated using a multivariable logistic regression model. RESULTS: Among the 274 children who underwent bilateral ear examinations and nasopharyngeal swab collections, 47 had OME (17.2%, 95% confidence interval [CI] 12.9-22.1%) and 96 were colonized with S. pneumoniae (35.0%, 29.4-41.0%). OME and nasopharyngeal S. pneumoniae carriage were positively associated in children aged less than 12 months (adjusted odds ratio [aOR] 3.83, 1.40-10.51). Day-care attendance and living in a rural area were independently associated with OME (aOR 5.87, 2.31-14.91, and aOR 3.77, 1.58-8.99, respectively). CONCLUSIONS: The nasopharyngeal pneumococcal carriage was associated with OME among children aged <12 months. A further study after introducing a pneumococcal conjugate vaccine (PCV) is required to better understand the effect of PCV and S. pneumoniae carriage on OME in young children.
Assuntos
Otite Média com Derrame , Infecções Pneumocócicas , Portador Sadio/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Nasofaringe , Otite Média com Derrame/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Prevalência , Vietnã/epidemiologiaRESUMO
Dog albumin contains a specific drug-binding site that binds most of the site II ligands of human albumin. This study was undertaken to elucidate the structural configuration of this binding site using a photoaffinity labeling technique. Dog albumin and albumins of other animal species were photolabeled with [(14)C]ketoprofen. The photolabeled albumins were cleaved with cyanogen bromide (CNBr) and analyzed autoradiographically after electrophoretic separation. A 11.6-kDa CNBr fragment of the photolabeled dog albumin was found to have incorporated most of the radioactivity. Site II ligands of human albumin inhibited photoincorporation of radioactivity to this fragment. The binding constants of human and dog albumins ranged from 10 to 12 x 10(5) M(-1), at least twice as high as those of rat, rabbit, and bovine albumins. Edman degradation was performed to elucidate the amino acid sequence of the photolabeled peptide derived from further digestion of the dog 11.6-kDa CNBr fragment with lysyl endopeptidase. The sequence was XXSESLVXRX, which corresponds to Cys(476)-Arg(485) of dog albumin. Dog albumin contains a binding site that may have a binding microenvironment similar to that of site II on human albumin. Therefore, dog may be a better experimental animal for data extrapolation from animal to human with regard to site II drug-drug interactions.
Assuntos
Fragmentos de Peptídeos/metabolismo , Albumina Sérica/metabolismo , Sequência de Aminoácidos , Animais , Autorradiografia , Sítios de Ligação , Radioisótopos de Carbono , Bovinos , Cromatografia Líquida de Alta Pressão , Cães , Eletroforese em Gel de Poliacrilamida , Humanos , Ligantes , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/química , Marcadores de Fotoafinidade , Ligação Proteica , Coelhos , Ratos , Albumina Sérica/química , Especificidade da EspécieRESUMO
There has been no attempt to clarify the status of patients with carotid body tumor (CBT) in Japan. This multi-institutional survey analyzed patients with CBT throughout Japan by gathering information on these patients from institutions that performed head and neck surgeries. Information from a total of 150 patients from 25 institutions from the past 20 years was employed in the present survey. There were 87 females and 63 males, and their mean age was 48.0 years old. The most common chief complaint was a neck mass and the mean suffering period was 46.1 months. Eighteen patients had a family history of paragangliomas and fifteen patients had bilateral CBTs. Among the 94 patients who underwent surgery to remove a CBT, 23 patients had tumors classified as Shamblin type I, 59 had type II and 12 had type III. The most frequent feeding artery of these CBTs was the ascending pharyngeal artery. Preoperative embolization of these arteries was effective in reducing blood loss; however, the operation time in Shamblin type I and II tumors was not improved. Thus these results revealed the status of patients with CBT and their treatment throughout Japan.
RESUMO
This report describes a very rare case of myasthenia gravis (MG) localized to the larynx, with the onset of dyspnea requiring tracheotomy. The vocal cords of this patient were fixed in the paramedian position. Under fiberscopic observation, improvement of laryngeal function was demonstrated after intravenous injection of edrophonium. However, no voice change occurred. The posterior crico-arytenoid muscle has the sole responsibility of abducting the vocal cord; thus, it is concluded that the dyspnea was caused by the selective paralysis of this muscle. We suggest that MG should be considered in cases of vocal cord paralysis of unknown etiology.
Assuntos
Doenças da Laringe/diagnóstico , Miastenia Gravis/diagnóstico , Paralisia das Pregas Vocais/etiologia , Idoso , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/prevenção & controle , Dispneia/etiologia , Dispneia/prevenção & controle , Edrofônio/uso terapêutico , Humanos , Doenças da Laringe/tratamento farmacológico , Laringoscopia , Masculino , Miastenia Gravis/tratamento farmacológico , Espectrografia do Som , Paralisia das Pregas Vocais/tratamento farmacológicoRESUMO
This study investigated the features of developmental difficulties combined with sensory defects in children with congenital rubella syndrome (CRS). Following a large rubella outbreak in Khanh Hoa Province, Vietnam, in 2011, we enrolled 41 children with CRS from September 2011 through May 2013. Fourteen participants died and six became untraceable by October 2013; the remaining 21 children were followed up from 2013 to 2015. Thirteen and seven participants had hearing and functional ophthalmological impairment, respectively. Developmental difficulties were suspected in 19 (95%) children who failed in at least one area of the Ages and Stages Questionnaire (ASQ) and/or Denver II in 2013 and/or 2015. Developmental difficulties were frequently identified in the ASQ communication domain (n = 14 in 2013) and Denver II language area (n = 13 in 2013). Seven (41%) participants were suspected of having autism spectrum disorder (ASD) in 2013 by the Modified Checklist for Autism in Toddlers. In 2015, proportions of children failing the problem-solving (62%) and personal-social (62%) domains had increased and two of 13 were diagnosed with ASD by the Childhood Autism Rating Scale, Second Edition. Developmental difficulties were suspected in most children with CRS, including autism largely combined with sensory dysfunction.
Assuntos
Transtorno do Espectro Autista , Deficiências do Desenvolvimento , Síndrome da Rubéola Congênita , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/patologia , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/patologia , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Síndrome da Rubéola Congênita/epidemiologia , Síndrome da Rubéola Congênita/patologia , Síndrome da Rubéola Congênita/fisiopatologiaRESUMO
The binding of flunitrazepam (FNZP) by human alpha1-acid glycoprotein (hAGP) and the relationships between the extent of drug binding and desialylation and the genetic variants of hAGP were examined. The photolabeling specificity of [3H]FNZP was confirmed by findings in which other hAGP-binding ligands inhibited the formation of covalent bonds between [3H]FNZP and hAGP. The photolabeling of asialo-hAGP suggested that sialic acid does not involve in the binding of [3H]FNZP. No difference in the labeling could be found between the F1*S variants and A variant. Similarly, FNZP did not show a difference in binding affinity to the two genetic variants of hAGP. Sequence analysis of the photolabeled peptide indicated a sequence corresponding to Tyr91-Arg105 of hAGP.
Assuntos
Sítios de Ligação , Flunitrazepam/metabolismo , Orosomucoide/química , Marcadores de Fotoafinidade/metabolismo , Sequência de Aminoácidos , Assialoglicoproteínas/metabolismo , Brometo de Cianogênio , Variação Genética , Humanos , Dados de Sequência Molecular , Orosomucoide/análogos & derivados , Orosomucoide/genética , Orosomucoide/metabolismo , Fragmentos de Peptídeos/química , TripsinaRESUMO
We examined cortical activation by speech in patients with moderate inner ear hearing loss using PET to investigate the response of the language network to insufficient speech input. We made two word lists, well-perceived words and poorly-perceived words, and measured rCBF during monaural presentation of these words. Well-perceived words activated bilateral temporal lobes, bilateral inferior frontal gyri (IFG) and left angular gyrus (AG) regardless of the ear stimulated, Poorly-perceived words activated contralateral temporal lobe and bilateral IFG, while little or no activation was observed in the ipsilateral temporal lobe and left AG. Insufficient activation of the temporal lobe ipsilateral to the ear stimulated might correlated with less accurate word comprehension in patients with inner ear hearing loss.
Assuntos
Orelha Interna/fisiopatologia , Perda Auditiva Bilateral/fisiopatologia , Lobo Temporal/fisiopatologia , Estimulação Acústica , Idoso , Idoso de 80 Anos ou mais , Limiar Auditivo , Velocidade do Fluxo Sanguíneo , Mapeamento Encefálico , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Discriminação da Fala , Lobo Temporal/irrigação sanguínea , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Comportamento VerbalRESUMO
Frequency tagging of magnetoencephalographic signals was recently introduced as a new tool to study binaural interaction in the human auditory cortex [Fujiki et al., J. Neurosci. 22 (2002) RC205]. As the method has potential value for assessing brain plasticity in patients with unilateral hearing deficits, we studied binaural interaction in 10 healthy adults at different intensity levels. Cortical steady-state fields were measured with a 306-channel whole-scalp neuromagnetometer to amplitude-modulated sounds (carrier frequency 1 kHz), presented monaurally or binaurally at 45, 60 and 75 dB SL. The modulation frequencies were 39.1 Hz for the right ear and 41.1 Hz for the left. During binaural stimulation, the ipsilateral responses were suppressed more than the contralateral ones in both hemispheres, and the hemispheric balance shifted towards the contralateral hemisphere for inputs from both ears. The patterns of binaural interaction were similar at all three stimulus intensities. These data could be useful in examining patients who suffer from auditory disorders as well as in revealing basic mechanism of human auditory processing.
Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/fisiologia , Potenciais Evocados Auditivos/fisiologia , Adulto , Feminino , Transtornos da Audição/fisiopatologia , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Magnetoencefalografia , Masculino , Plasticidade Neuronal/fisiologiaRESUMO
OBJECTIVE: Since 1990, we have performed steroid injections into the vocal fold under topical anesthesia using fiberoptic laryngeal surgery (FLS) in an outpatient clinic. The aim of this study was to retrospectively assess the usefulness of this treatment method in 44 patients with mild Reinke's edema. MATERIAL AND METHODS: Using fiberoptic monitoring of the larynx, a curved injection needle was inserted via the oral cavity and triamcinolone acetonide was injected into Reinke's space of the bilateral vocal fold. RESULTS: Remission or improvement was observed in almost all patients in terms of both patients' self-rating of hoarseness and endoscopic vocal fold findings The maximum phonation time was a mean of 9.0 s before operation and 11.4 safter operation, and this increase was significant (p < 0.01). Voice pitch also improved, from 168 to 181 Hz, in female patients, and this increase was also significant (p < 0.05). CONCLUSION: Steroid injection is considered to be useful for treating mild Reinke's edema.
Assuntos
Anti-Inflamatórios/administração & dosagem , Edema Laríngeo/terapia , Laringite/tratamento farmacológico , Laringoscopia/métodos , Triancinolona Acetonida/administração & dosagem , Adulto , Idoso , Feminino , Tecnologia de Fibra Óptica , Rouquidão/tratamento farmacológico , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Fonação , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Qualidade da Voz/efeitos dos fármacosRESUMO
From December 1994 to February 1995, 131 wild boars (Sus scrofa leucomysta) living in a mountainous area in Japan were examined for yersiniosis and listeriosis. Of 131 wild boars, 76 (58%) were males and 55 (42%) were females. Four Yersinia spp. including Y. pseudotuberculosis, Y. enterocolitica, Y. frederiksenii, and Y. aldovei, were isolated from 49 (37%) of 131 wild boars. Yersinia pseudotuberculosis was isolated from five (4%) of 131 wild boars. All Y. pseudotuberculosis isolates were serotype 4b and harbored virulence plasmids. Yersinia pseudotuberculosis was isolated only from boars under 2-yr-old. No human pathogenic Y. enterocolitica was isolated. Listeria monocytogenes was isolated from two (1%) of the wild boars and both isolates were serotype 4b. These findings indicated that wild boar could be a reservoir of Y. pseudotuberculosis and L. monocytogenes in Japan.
Assuntos
Listeriose/veterinária , Doenças dos Suínos/epidemiologia , Yersiniose/veterinária , Fatores Etários , Animais , Animais Selvagens , Fezes/microbiologia , Feminino , Japão/epidemiologia , Listeria/classificação , Listeria/isolamento & purificação , Listeria/patogenicidade , Listeriose/epidemiologia , Masculino , Sorotipagem/veterinária , Suínos , Doenças dos Suínos/microbiologia , Virulência , Yersinia/classificação , Yersinia/isolamento & purificação , Yersinia/patogenicidade , Yersiniose/epidemiologiaRESUMO
BACKGROUND: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy). MATERIALS AND METHODS: Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron (40 µg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80 mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group). RESULTS: For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant. CONCLUSIONS: This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.
Assuntos
Antieméticos/uso terapêutico , Cisplatino/efeitos adversos , Morfolinas/uso terapêutico , Náusea/tratamento farmacológico , Vômito/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Aprepitanto , Cisplatino/uso terapêutico , Dexametasona/uso terapêutico , Quimioterapia Combinada , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Granisetron/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
CONCLUSION: Negative middle ear pressure was observed in many patients and otitis media with effusion (OME) developed in 3.3% of ears after surgery under general anesthesia. Gas dynamics in the middle ear cavity induced by nitrous oxide inhalation anesthesia and transient blockage of the eustachian tube induced by surgery are considered to be involved in development of OME after surgery under general anesthesia. OBJECTIVES: The goal of this prospective study was to investigate middle ear pressure and the prevalence of middle ear effusion in patients after surgery under general anesthesia, to ascertain whether surgery under general anesthesia induces OME. METHODS: Otoscopic inspection and tympanometry were performed before surgery (Pre), 1-2 days after surgery (Post-1), and 5-9 days after surgery (Post-2) under general anesthesia in 180 ears of 97 adult patients. RESULTS: Effusion accumulated in the tympanum in six ears (3.3%) of five patients at Post-1. All patients were anesthetized with nitrous oxide. At Post-2, effusion disappeared in all cases. The mean middle ear pressure in all ears was -17.8 daPa at Pre and -60.6 daPa at Post-1, showing a significant reduction from Pre to Post-1 (p < 0.001). At Post-2, the pressure was -18.4 daPa, with no significant difference from that at Pre (p = 0.74).