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1.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34404749

RESUMO

In recent years there has been extensive research on malformations of cortical development (MCDs) that result in clinical features like developmental delay, intellectual disability, and drug-resistant epilepsy (DRE). Various studies highlighted the contribution of microtubule-associated genes (including tubulin and kinesin encoding genes) in MCD development. It has been reported that de novo mutations in KIF2A, a member of the kinesin-13 family, are linked to brain malformations and DRE. Although it is known that KIF2A functions by regulating microtubule depolymerization via an ATP-driven process, in vivo implications of KIF2A loss of function remain partly unclear. Here, we present a novel kif2a knock-out zebrafish model, showing hypoactivity, habituation deficits, pentylenetetrazole-induced seizure susceptibility and microcephaly, as well as neuronal cell proliferation defects and increased apoptosis. Interestingly, kif2a -/- larvae survived until adulthood and were fertile. Notably, our kif2a zebrafish knock-out model demonstrated many phenotypic similarities to KIF2A mouse models. This study provides valuable insights into the functional importance of kif2a in zebrafish and phenotypical hallmarks related to KIF2A mutations. Ultimately, this model could be used in a future search for more effective therapies that alleviate the clinical symptoms typically associated with MCDs.

2.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445171

RESUMO

Tauopathy refers to a group of progressive neurodegenerative diseases, including frontotemporal lobar degeneration and Alzheimer's disease, which correlate with the malfunction of microtubule-associated protein Tau (MAPT) due to abnormal hyperphosphorylation, leading to the formation of intracellular aggregates in the brain. Despite extensive efforts to understand tauopathy and develop an efficient therapy, our knowledge is still far from complete. To find a solution for this group of devastating diseases, several animal models that mimic diverse disease phenotypes of tauopathy have been developed. Rodents are the dominating tauopathy models because of their similarity to humans and established disease lines, as well as experimental approaches. However, powerful genetic animal models using Drosophila, zebrafish, and C. elegans have also been developed for modeling tauopathy and have contributed to understanding the pathophysiology of tauopathy. The success of these models stems from the short lifespans, versatile genetic tools, real-time in-vivo imaging, low maintenance costs, and the capability for high-throughput screening. In this review, we summarize the main findings on mechanisms of tauopathy and discuss the current tauopathy models of these non-rodent genetic animals, highlighting their key advantages and limitations in tauopathy research.


Assuntos
Modelos Animais de Doenças , Tauopatias/genética , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Drosophila/genética , Drosophila/fisiologia , Humanos , Tauopatias/fisiopatologia , Peixe-Zebra/genética , Peixe-Zebra/fisiologia , Proteínas tau/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-34444526

RESUMO

Patient-controlled epidural analgesia is widely used to control postoperative pain following major intra-abdominal surgeries. However, determining the optimal infusion dose that can produce effective analgesia while reducing side effects remains a task to be solved. Postoperative pain and adverse effects between variable-rate feedback infusion (VFIM group, n = 36) and conventional fixed-rate basal infusion (CFIM group, n = 36) of fentanyl/ropivacaine-based patient-controlled epidural analgesia were evaluated. In the CFIM group, the basal infusion rate was fixed (5 mL/h), whereas, in the VFIM group, the basal infusion rate was increased by 0.5 mL/h each time a bolus dose was administered and decreased by 0.3 mL/h when a bolus dose was not administered for 2 h. Patients in the VFIM group experienced significantly less pain at one to six hours after surgery than those in the CFIM group. Further, the number of patients who suffered from postoperative nausea was significantly lower in the VFIM group than in the CFIM group until six hours after surgery. The variable-rate feedback infusion mode of patient-controlled epidural analgesia may provide better analgesia accompanied with significantly less nausea in the early postoperative period than the conventional fixed-rate basal infusion mode following open gastrectomy.


Assuntos
Analgesia Epidural , Amidas , Analgésicos Opioides/uso terapêutico , Anestésicos Locais , Retroalimentação , Fentanila , Gastrectomia/efeitos adversos , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Ropivacaina
4.
Int J Mol Sci ; 22(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34281244

RESUMO

Olfaction is an important neural system for survival and fundamental behaviors such as predator avoidance, food finding, memory formation, reproduction, and social communication. However, the neural circuits and pathways associated with the olfactory system in various behaviors are not fully understood. Recent advances in optogenetics, high-resolution in vivo imaging, and reconstructions of neuronal circuits have created new opportunities to understand such neural circuits. Here, we generated a transgenic zebrafish to manipulate olfactory signal optically, expressing the Channelrhodopsin (ChR2) under the control of the olfactory specific promoter, omp. We observed light-induced neuronal activity of olfactory system in the transgenic fish by examining c-fos expression, and a calcium indicator suggesting that blue light stimulation caused activation of olfactory neurons in a non-invasive manner. To examine whether the photo-activation of olfactory sensory neurons affect behavior of zebrafish larvae, we devised a behavioral choice paradigm and tested how zebrafish larvae choose between two conflicting sensory cues, an aversive odor or the naturally preferred phototaxis. We found that when the conflicting cues (the preferred light and aversive odor) were presented together simultaneously, zebrafish larvae swam away from the aversive odor. However, the transgenic fish with photo-activation were insensitive to the aversive odor and exhibited olfactory desensitization upon optical stimulation of ChR2. These results show that an aversive olfactory stimulus can override phototaxis, and that olfaction is important in decision making in zebrafish. This new transgenic model will be useful for the analysis of olfaction related behaviors and for the dissection of underlying neural circuits.


Assuntos
Channelrhodopsins/metabolismo , Percepção Olfatória/genética , Olfato/genética , Animais , Animais Geneticamente Modificados/genética , Channelrhodopsins/genética , Sinais (Psicologia) , Larva/fisiologia , Luz , Rede Nervosa/metabolismo , Neurônios/metabolismo , Odorantes , Optogenética/métodos , Estimulação Luminosa , Regiões Promotoras Genéticas/genética , Natação , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
5.
Nat Commun ; 12(1): 3291, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078905

RESUMO

The formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer's disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.


Assuntos
Doença de Alzheimer/genética , Proteínas de Drosophila/genética , MicroRNAs/genética , Ubiquitina-Proteína Ligases/genética , Proteínas tau/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Autofagia/genética , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Olho/metabolismo , Olho/patologia , Humanos , Lisossomos/metabolismo , Camundongos , MicroRNAs/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína Pós-Traducional , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Proteínas tau/metabolismo
6.
Cells ; 10(3)2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807650

RESUMO

The microbiota-gut-brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota-gut-brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer's disease.

7.
Anesth Analg ; 130(2): 480-487, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30320644

RESUMO

BACKGROUND: Age-related changes in upper airway anatomy may affect the overall performance of supraglottic airways significantly. The clinical performance of the i-gel and the self-pressurized air-Q intubating laryngeal airways with noninflatable cuffs for elderly populations remains unknown, unlike in children. Thus, we performed a prospective, randomized comparison of these 2 supraglottic airways in elderly patients undergoing general anesthesia. METHODS: We recruited 100 patients, 65-90 years of age, who were scheduled for elective surgery under general anesthesia with muscle relaxation. The enrolled patients were allocated to the i-gel or self-pressurized air-Q group. We assessed oropharyngeal leak pressure as the primary outcome and fiberoptic view after placement and fixation of the airway and at 10 minutes after the initial assessment. The fiberoptic view was scored using a 5-point scale as follows: vocal cords not visible; vocal cords and anterior epiglottis visible, >50% visual obstruction of epiglottis to vocal cords; vocal cords and anterior epiglottis visible, <50% visual obstruction of epiglottis to vocal cords; vocal cords and posterior epiglottis visible; and vocal cords visible. We also investigated success rate and ease of insertion, insertion time, and manipulations during insertion as insertion variables, complications during maintenance and emergence periods, and postoperative pharyngolaryngeal complications including sore throat, dysphagia, and dysphonia. RESULTS: After assessing for eligibility, 48 patients were allocated to each group. Oropharyngeal leak pressures were significantly higher in the i-gel group than in the self-pressurized air-Q group (P < .001) at the 2 measurement points. The raw mean difference at initial assessment and the median difference after 10 minutes were 5.5 cm H2O (95% confidence interval, 3.3-7.6 cm H2O) and 5.0 (95% confidence interval, 2.0-7.0 cm H2O), respectively. The initial scores of fiberoptic view were similar in the 2 groups. However, the self-pressurized air-Q supraglottic airway provided a significantly improved fiberoptic view at 10 minutes after initial assessment (P = .030). We found no statistically significant differences in insertion variables and complications between the 2 groups. CONCLUSIONS: The i-gel provided better sealing function than the self-pressurized air-Q supraglottic airway according to the high oropharyngeal leak pressures in elderly patients during general anesthesia. The self-pressurized air-Q supraglottic airway had improved fiberoptic views in elderly patients during general anesthesia.


Assuntos
Manuseio das Vias Aéreas/normas , Anestesia Geral/normas , Intubação Intratraqueal/normas , Máscaras Laríngeas/normas , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas/instrumentação , Anestesia Geral/instrumentação , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Estudos Prospectivos
8.
J Clin Med ; 8(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484445

RESUMO

Unlike 5-hydroxytryptamine (5-HT, serotonin) 1 and 5-HT2, the effect of 5-HT3 receptors on tumor cells is poorly understood. We conducted this study to determine whether the perioperative use of 5-HT3 receptor antagonists, which are widely used antiemetics, impacts the recurrence and mortality after lung cancer surgery and related anti-tumor mechanisms. From data on 411 patients, propensity score matching was used to produce 60 1:2 matched pairs of patients, and variables associated with the prognosis after open lung cancer surgery were analyzed. Additionally, the effects of 5-HT3 receptor antagonists were confirmed in vitro on A549 human lung adenocarcinoma cells. Cancer recurrence occurred in 10 (8.2%) and 14 (22.95%) patients (p = 0.005), treated or untreated, with palonosetron or ramosetron. Perioperative usage of palonosetron or ramosetron was also associated with lower recurrence rate after lung cancer surgery (hazard ratio (HR), 0.293; 95% confidence interval (CI) 0.110-0.780, p = 0.0141). Our in vitro experiments also showed that palonosetron and ramosetron inhibited cell proliferation and colony formation and reduced migration, which was associated with autophagic cell death via the extracellular signal-regulated kinase (ERK) pathway. Palonosetron and ramosetron may have anti-tumor potential against lung cancer cells, suggesting the need to consider these drugs as first-choice antiemetics in patients undergoing lung cancer surgery.

9.
Dis Model Mech ; 12(5)2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31043432

RESUMO

DYRK1A is a major causative gene in Down syndrome (DS). Reduced incidence of solid tumors such as neuroblastoma in DS patients and increased vascular anomalies in DS fetuses suggest a potential role of DYRK1A in angiogenic processes, but in vivo evidence is still scarce. Here, we used zebrafish dyrk1aa mutant embryos to understand DYRK1A function in cerebral vasculature formation. Zebrafish dyrk1aa mutants exhibited cerebral hemorrhage and defects in angiogenesis of central arteries in the developing hindbrain. Such phenotypes were rescued by wild-type dyrk1aa mRNA, but not by a kinase-dead form, indicating the importance of DYRK1A kinase activity. Chemical screening using a bioactive small molecule library identified a calcium chelator, EGTA, as one of the hits that most robustly rescued the hemorrhage. Vascular defects of mutants were also rescued by independent modulation of calcium signaling by FK506. Furthermore, the transcriptomic analyses supported the alterations of calcium signaling networks in dyrk1aa mutants. Together, our results suggest that DYRK1A plays an essential role in angiogenesis and in maintenance of the developing cerebral vasculature via regulation of calcium signaling, which may have therapeutic potential for DYRK1A-related vascular diseases.


Assuntos
Vasos Sanguíneos/patologia , Sinalização do Cálcio , Técnicas de Inativação de Genes , Proteínas Quinases/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Vasos Sanguíneos/efeitos dos fármacos , Encéfalo/irrigação sanguínea , Encéfalo/embriologia , Encéfalo/patologia , Encéfalo/ultraestrutura , Hemorragia Cerebral/patologia , Ácido Egtázico/farmacologia , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Desenvolvimento Embrionário/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Harmina/farmacologia , Espaço Intracelular/metabolismo , Mutação/genética , Fenótipo , Transcriptoma/genética , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/antagonistas & inibidores
10.
Nat Commun ; 10(1): 1357, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902983

RESUMO

A fundamental question in biology is how vertebrates evolved and differ from invertebrates, and little is known about differences in the regulation of translation in the two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated translation initiation machinery that specifically interacts with eIF4E homologous protein, and forms machinery that is structurally analogous to the eIF4F-mediated translation initiation machinery via the recruitment of other translation initiation components. Biochemical and RNA immunoprecipitation analyses coupled to sequencing suggest that this machinery emerged as a gain-of-function event in the vertebrate lineage, and it positively regulates the translation of mRNAs required for vertebrate development. Collectively, our findings demonstrate that TRS evolved to regulate vertebrate translation initiation via its dual role as a scaffold for the assembly of initiation components and as a selector of target mRNAs. This work highlights the functional significance of aminoacyl-tRNA synthetases in the emergence and control of higher order organisms.


Assuntos
Iniciação Traducional da Cadeia Peptídica , Treonina-tRNA Ligase/metabolismo , Sequência de Aminoácidos , Animais , Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/metabolismo , Fator de Iniciação 4E em Eucariotos , Fator de Iniciação 4F em Eucariotos/metabolismo , Fator de Iniciação 4G em Eucariotos/metabolismo , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Ligação Proteica , Proteínas de Ligação ao Cap de RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade da Espécie , Treonina-tRNA Ligase/química , Vertebrados/crescimento & desenvolvimento , Vertebrados/metabolismo , Peixe-Zebra
11.
Int J Med Sci ; 16(3): 376-383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30911271

RESUMO

Background: Combination of dexmedetomidine and opioid may be an alternative to high-dose opioid in attenuating cough during emergence from anesthesia, while also reducing the adverse effects of high-dose opioid. We tested the hypothesis that a single-dose of dexmedetomidine combined with low-dose remifentanil infusion during emergence would not be inferior to high-dose remifentanil infusion alone in attenuating cough after thyroidectomy. Methods: One hundred sixty-nine patients undergoing thyroidectomy were enrolled and randomized in a 1:1 ratio into group DR or group R. Each patient received an infusion of dexmedetomidine (0.5 µg/kg) and low-dose remifentanil infusion of effect-site concentration (Ce) at 1 ng/mL or normal saline and high-dose remifentanil infusion of Ce at 2 ng/mL for 10 min at the end of surgery. Remifentanil was maintained until tracheal extubation. Primary endpoint was the severity of coughing, which was assessed for non-inferiority using a four-point scale at the time of extubation. For comparison of coughing incidence during emergence, coughing grade was also measured at three times: before extubation, at extubation, and after extubation. Time to awakening, hemodynamic and respiratory profile, pain, and postoperative nausea and vomiting were also evaluated for superiority. Results: The 95% confidence intervals for differences in cough grade during tracheal extubation were <0.9, indicating non-inferiority of the single dose of dexmedetomidine combined with low-dose remifentanil infusion. The incidence of coughing was similar in the two groups. Hemodynamic changes during tracheal extubation were attenuated, but emergence from anesthesia was delayed, in group DR. Use of rescue antiemetic was similar in both groups, but the incidence of vomiting was less in group DR. Conclusion: A single-dose of dexmedetomidine (0.5 µg/kg) combined with low-dose remifentanil infusion at 1 ng/mL of Ce during emergence from sevoflurane-remifentanil anesthesia was not inferior to high-dose remifentanil infusion alone at 2 ng/mL of Ce with regard to suppressing cough.


Assuntos
Anestesia Geral/efeitos adversos , Tosse/tratamento farmacológico , Dexmedetomidina/administração & dosagem , Remifentanil/administração & dosagem , Adulto , Analgésicos não Narcóticos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestesia Geral/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Remifentanil/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Nat Commun ; 10(1): 708, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755616

RESUMO

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies.


Assuntos
Encefalopatias/genética , Microcefalia/genética , Valina-tRNA Ligase/genética , Alelos , Animais , Encefalopatias/enzimologia , Encefalopatias/patologia , Linhagem Celular , Modelos Animais de Doenças , Epilepsia/enzimologia , Epilepsia/genética , Epilepsia/patologia , Feminino , Fibroblastos , Técnicas de Inativação de Genes , Predisposição Genética para Doença , Humanos , Mutação com Perda de Função , Masculino , Microcefalia/enzimologia , Microcefalia/patologia , Modelos Moleculares , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Linhagem , Prosencéfalo/patologia , Peixe-Zebra
13.
Nanoscale ; 11(7): 3396, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30608099

RESUMO

Correction for 'Bioaccumulation of polystyrene nanoplastics and their effect on the toxicity of Au ions in zebrafish embryos' by Wang Sik Lee et al., Nanoscale, 2019, DOI: 10.1039/c8nr09321k.

14.
Microb Pathog ; 127: 56-59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30508625

RESUMO

Streptococcus parauberis is the major infectious agent of streptococcosis in the olive flounder (Paralichthys olivaceus), causing serious economic damage. In this study, we identified potential vaccine candidates against S. parauberis by reverse vaccinology. In total, the 2 out of 21 proteins were identified as vaccine candidates from two available S. parauberis genomes. The membrane-anchored protein SEC10/PgrA and the metal ABC transporter substrate-binding lipoprotein mtsA were potent antigenic proteins based on western blotting with mouse-derived antiserum against whole bacteria of S. parauberis serotypes I and II. In particular, metal ABC transporter substrate-binding lipoprotein (mtsA) showed similar protective immunity to that of whole-cell bacterins against S. parauberis in a zebrafish model. These results suggest that mtsA may be considered as a novel candidate in the development of vaccines against S. parauberis.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus/imunologia , Vacinologia/métodos , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/isolamento & purificação , Modelos Animais de Doenças , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Análise de Sobrevida , Peixe-Zebra
15.
Nanoscale ; 11(7): 3173-3185, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30534785

RESUMO

As nano- and micro-sized plastics accumulate in the environment and the food chain of animals, including humans, it is imperative to assess the effects of nanoplastics in living organisms in a systematic manner, especially because of their ability to adsorb potential toxicants such as pollutants, heavy metals, and organic macromolecules that coexist in the environment. Using the zebrafish embryo as an animal model, we investigated the bioaccumulation and in vivo toxicity of polystyrene (PS) nanoplastics individually or in combination with the Au ion. We showed that smaller PS nanoplastics readily penetrated the chorion and developing embryos and accumulated throughout the whole body, mostly in lipid-rich regions such as in yolk lipids. We also showed that PS nanoplastics induced only marginal effects on the survival, hatching rate, developmental abnormalities, and cell death of zebrafish embryos but that these effects were synergistically exacerbated by the Au ion in a dose- and size-dependent manner. Such exacerbation of toxicity was well correlated with the production of reactive oxygen species and the pro-inflammatory responses synergized by the presence of PS, supporting the combined toxicity of PS and Au ions. The synergistic effect of PS on toxicity appeared to relate to mitochondrial damage as determined by ultrastructural analysis. Taken together, the effects of PS nanoplastics were marginal but could be a trigger for exacerbating the toxicity induced by other toxicants such as metal ions.


Assuntos
Embrião não Mamífero/metabolismo , Ouro/toxicidade , Nanopartículas/toxicidade , Poliestirenos/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/patologia , Íons/toxicidade
16.
Sensors (Basel) ; 18(11)2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30424510

RESUMO

We report the electrical characteristics and pH responses of a Si-nanonet ion-sensitive field-effect transistor with ultra-thin parylene-H as a gate sensing membrane. The fabricated device shows excellent DC characteristics: a low subthreshold swing of 85 mV/dec, a high current on/off ratio of ~107 and a low gate leakage current of ~10-10 A. The low interface trap density of 1.04 × 1012 cm-2 and high field-effect mobility of 510 cm²V-1s-1 were obtained. The pH responses of the devices were evaluated in various pH buffer solutions. A high pH sensitivity of 48.1 ± 0.5 mV/pH with a device-to-device variation of ~6.1% was achieved. From the low-frequency noise characterization, the signal-to-noise ratio was extracted as high as ~3400 A/A with the lowest noise equivalent pH value of ~0.002 pH. These excellent intrinsic electrical and pH sensing performances suggest that parylene-H can be promising as a sensing membrane in an ISFET-based biosensor platform.

17.
Nanomaterials (Basel) ; 8(9)2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30142912

RESUMO

A silver nanoparticle is one of the representative engineered nanomaterials with excellent optical, electrical, antibacterial properties. Silver nanoparticles are being increasingly used for medical products, water filters, and cosmetics, etc. However, silver nanoparticles are known to cause adverse effects on the ecosystem and human health. To utilize silver nanoparticles with minimized negative effects, it is important to understand the behavior of silver nanoparticles released to the environment. In this study, we compared toxicity behaviors of citrate-stabilized silver nanoparticles with polyethylene glycol coated silver nanoparticles in two different ionic environments, which are aquatic environments for developing zebrafish embryo. Depending on the composition of the ionic environment, citrate-stabilized silver nanoparticles and polyethylene glycol coated silver nanoparticles exhibited different behaviors in dissolution, aggregation, or precipitation, which governed the toxicity of silver nanoparticles on zebrafish embryos.

18.
World J Surg ; 42(10): 3150-3157, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29915988

RESUMO

BACKGROUND: While carbohydrate loading is an important component of enhanced patient recovery after surgery, no study has evaluated the effects of preoperative carbohydrate loading after laparoscopic cholecystectomy (LC) on patient satisfaction and overall recovery. Thus, we aimed to investigate the impact of preoperative oral carbohydrates on scores from the quality of recovery 40-item (QoR-40) questionnaire after LC. METHODS: A total of 153 adults who underwent LC were randomized into three groups. Group MN-NPO was fasted from midnight until surgery. Group No-NPO received 400 mL of a carbohydrate beverage on the evening before surgery, and a morning dose of 400 mL was ingested at least 2 h before surgery. Group Placebo received the same quantity of flavored water as for group No-NPO. The quality of recovery after general anesthesia was evaluated using QoR-40 questionnaire. Intraoperative hemodynamics were also evaluated. RESULTS: There were no significant differences among the groups in terms of the pre- and postoperative global QoR-40 scores (P = 0.257). Group MN-NPO had an elevated heart rate compared to patients who ingested a preoperative beverage (groups No-NPO and Placebo; P = 0.0412). CONCLUSIONS: The preoperative carbohydrate beverage did not improve quality of recovery using the QoR-40 questionnaire after general anesthesia for laparoscopic cholecystectomy compared to placebo or conventional fasting. However, the preoperative fasting group had a consistently increased heart rate during changes in body position that induced hypotension, which is likely a result of depletion of effective intravascular volume caused by traditional fasting over 8 h. TRIAL REGISTRATION: Clinical trial.gov identifier: NCT02555020.


Assuntos
Colecistectomia Laparoscópica/reabilitação , Carboidratos da Dieta/administração & dosagem , Doenças da Vesícula Biliar/cirurgia , Adulto , Protocolos Clínicos , Método Duplo-Cego , Jejum , Feminino , Doenças da Vesícula Biliar/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Cuidados Pré-Operatórios , Recuperação de Função Fisiológica
19.
Medicine (Baltimore) ; 97(26): e11138, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952958

RESUMO

There is a growing interest in research aimed at better understanding the disease status or predicting the prognosis of patients with simple blood tests associated with systemic inflammation. The neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and mean platelet volume (MPV) can be used as factors to determine the prognosis of patients in various clinical situations. However, reference values for these attributes based on large, healthy populations have yet to be determined.From January 2014 to December 2016, data from routine blood analyses were collected from healthy patients in the checkup center of a tertiary hospital in Seoul, South Korea. Retrospective data review was then performed on an electronic medical record system. Data were treated anonymously as only age, sex, body mass index, medical history including cancer diagnosis, medications, and smoking status were considered. After the initial screen, we had a collection of 12,160 samples from patients without any medical history, including cancer treatment. This patient pool consisted of 6268 (51.5%, median age 47 years) and 5892 (48.5%, median age 46 years) male and female patients, respectively. The mean NLR across all ages was 1.65 (0.79), and the values for men and women were 1.63 (0.76) and 1.66 (0.82), respectively. The mean LMR, PLR, and MPV were 5.31 (1.68), 132.40 (43.68), and 10.02 (0.79), respectively. This study provides preliminary reference data on LMR, PLR, and MPV from different age and sex groups in South Korea. The results suggest that different cutoff values should be applied to the various patient populations.


Assuntos
Contagem de Leucócitos/métodos , Volume Plaquetário Médio/métodos , Contagem de Plaquetas/métodos , Adulto , Plaquetas/citologia , Feminino , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Valores de Referência , República da Coreia , Estudos Retrospectivos
20.
J Nanosci Nanotechnol ; 18(9): 6598-6601, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29677841

RESUMO

The analog figure-of-merits (FOMs) of conventional inversion-mode (IM) and junctionless (JL) NanoWire Field Effect Transistor (NWFET) have been investigated, considering the gate Work-Function Variability (WFV) and Random Discrete Dopant (RDD) using 3-dimensional (3D) TCAD simulation. While the JL-NWFET shows higher immune to WFV on analog FOMs, it can be easily affected by RDD due to higher channel doping level. On the other hand, the IM-NWFET shows stronger correlation between transconductance (gm) and gate capacitance (Cgg), leading to similar variation in cut-off frequency (ft) even though it shows larger gm and Cgg variation compared to JL-NWFET.

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