Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ann Lab Med ; 41(3): 277-284, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303712

RESUMO

Background: We recently introduced the Barricor (BD, Franklin Lakes, NJ, USA) plasma separation tube, which uses a mechanical separator instead of a gel. We evaluated the effects of using the Barricor tube in a stat (statin) laboratory on the results and turnaround time (TAT) of routine chemical tests. We verified the impact of Barricor tube on reducing TAT and providing results similar to those obtained using serum separator tubes (SSTs). Methods: We collected venous blood samples from 166 outpatients in Barricor tubes and SSTs and measured 28 routine analytes using an AU5800 instrument (Beckman Coulter, Brea, CA, USA). TAT indexes were compared before and after using Barricor tube. Results: Mean percent differences were <5%, except for alanine aminotransferase , total CO2, high-density lipoprotein, phosphate, total protein, and direct bilirubin. The median TAT decreased from 45 to 38 minutes, and the rate of a TAT >60 minutes decreased from 7.84% to 2.66%, which was approximately one-third of that for SST. The reduction in TAT was attributable to a decrease in centrifugation time. Incomplete clotting and repeated centrifugation, which occurred frequently when using SST, also decreased after using the Barricor tubes. Conclusions: The Barricor tube is an alternative to SST for routine chemical tests in institutions aiming to reduce TAT, with clinically allowable differences in test results.

2.
Carbohydr Polym ; 253: 117187, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278965

RESUMO

Chondroitin sulfate-hybridized zein nanoparticles (zein/CS NPs) were developed for targeted delivery of docetaxel, which exhibited mean diameters of 157.8 ± 3.6 nm and docetaxel encapsulation efficiency of 64.2 ± 1.9 %. Docetaxel was released from the NPs in a sustained manner (∼72 h), following first-order kinetics. The zein/CS NPs showed improved colloidal stability, maintaining the initial size in serum for 12 h. The pre-treatment of CS reduced the uptake efficiency of the NPs by 23 % in PC-3 cells, suggesting the involvement of CD44-mediated uptake mechanism. The NPs showed 2.79-fold lower IC50 values than free docetaxel. Enhanced tumor accumulation of the NPs was confirmed in PC-3 xenograft mice by near-infrared fluorescence imaging (35.3-fold, versus free Cy5.5). The NPs exhibited improved pharmacokinetic properties (9.5-fold longer terminal half-life, versus free docetaxel) and anti-tumor efficacy comparable to Taxotere with negligible systemic toxicity, suggesting zein/CS NPs could be a promising nanoplatform for targeted cancer therapy.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4306-4309, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018948

RESUMO

There is an increasing demand for real-time neural signal monitoring from a large number of electrode contacts to provide adequate spatial and temporal resolution for brain mapping and high-resolution neural interface. This paper proposes a novel multi-channel neural recording system that records neural signals from a large number of electrodes with a smaller number of recording channels. The system utilizes an adaptive electrode selection technique to automatically scan the electrode arrays and record from selected electrodes where neural spikes are detected. The proposed neural recording IC was fabricated in CMOS 180 nm process and tested with in vitro environments. Experiment results with pre-recorded neural data indicate that neural spikes can be separated and amplified with the proposed system and counted in real-time.


Assuntos
Mapeamento Encefálico , Registros , Eletrodos
4.
Pharmaceutics ; 12(10)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987920

RESUMO

In our previous study, Hwang-Ryun-Hae-Dok-Tang, which contains berberine (BBR) as a main active ingredient, inhibited cytochrome P450 (CYP) 2D6 in a quasi-irreversible manner. However, no information is available on the detailed mechanism of BBR-induced CYP2D6 inhibition. Thus, the present study aimed to characterize the inhibition mode and kinetics of BBR and its analogues against CYP2D6 using pooled human liver microsomes (HLM). BBR exhibited selective quasi-irreversible inhibition of CYP2D6 with inactivation rate constant (kinact) of 0.025 min-1, inhibition constant (KI) of 4.29 µM, and kinact/KI of 5.83 mL/min/µmol. In pooled HLM, BBR was metabolized to thalifendine (TFD), demethyleneberberine (DMB), M1 (proposed as demethylene-TFD), and to a lesser extent berberrubine (BRB), showing moderate metabolic stability with a half-life of 35.4 min and a microsomal intrinsic clearance of 7.82 µL/min/mg protein. However, unlike BBR, those metabolites (i.e., TFD, DMB, and BRB) were neither selective nor potent inhibitors of CYP2D6, based on comparison of half-maximal inhibitory concentration (IC50). Notably, TFD, but not DMB, exhibited metabolism-dependent CYP2D6 inhibition as in the case of BBR, which suggests that methylenedioxybenzene moiety of BBR may play a critical role in the quasi-irreversible inhibition. Moreover, the metabolic clearance of nebivolol (ß-blocker; CYP2D6 substrate) was reduced in the presence of BBR. The present results warrant further evaluation of BBR-drug interactions in clinical situations.

5.
J Vis Exp ; (162)2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32925887

RESUMO

In vivo real-time monitoring of neuronal activities in freely moving animals is one of key approaches to link neuronal activity to behavior. For this purpose, an in vivo imaging technique that detects calcium transients in neurons using genetically encoded calcium indicators (GECIs), a miniaturized fluorescence microscope, and a gradient refractive index (GRIN) lens has been developed and successfully applied to many brain structures1 , 2 , 3 , 4 , 5 , 6. This imaging technique is particularly powerful because it enables chronic simultaneous imaging of genetically defined cell populations for a long-term period up to several weeks. Although useful, this imaging technique has not been easily applied to brain structures that locate deep within the brain such as amygdala, an essential brain structure for emotional processing and associative fear memory7. There are several factors that make it difficult to apply the imaging technique to the amygdala. For instance, motion artifacts usually occur more frequently during the imaging conducted in the deeper brain regions because a head-mount microscope implanted deep in the brain is relatively unstable. Another problem is that the lateral ventricle is positioned close to the implanted GRIN lens and its movement during respiration may cause highly irregular motion artifacts that cannot be easily corrected, which makes it difficult to form a stable imaging view. Furthermore, because cells in the amygdala are usually quiet at a resting or anesthetized state, it is hard to find and focus the target cells expressing GECI in the amygdala during baseplating procedure for later imaging. This protocol provides a helpful guideline for how to efficiently target cells expressing GECI in the amygdala with head-mount miniaturized microscope for successful in vivo calcium imaging in such a deeper brain region. It is noted that this protocol is based on a particular system (e.g., Inscopix) but not restricted to it.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Comportamento Animal/fisiologia , Cálcio/metabolismo , Microscopia/instrumentação , Miniaturização/instrumentação , Estimulação Acústica , Animais , Artefatos , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Cabeça , Lentes , Camundongos Endogâmicos C57BL , Movimento , Neuroimagem , Neurônios/metabolismo , Refratometria , Reprodutibilidade dos Testes , Técnicas Estereotáxicas
6.
Pharmaceutics ; 12(8)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751591

RESUMO

PEGylated Eudragit L100 (ELP)-containing proliponiosomes (PLNs) were developed for improved oral delivery of celecoxib (CXB). The successful introduction of PEG 2000 or 5000 to Eudragit L100 (EL) was confirmed via proton nuclear magnetic resonance analysis of which calculated molar substitution ratio of PEG to EL was 36.0 or 36.7, respectively. CXB, ELP, phospholipid, and non-ionic surfactants were dissolved in dimethyl sulfoxide and lyophilized to produce CXB-loaded PLNs (CXB@PLNs). The physical state of CXB@PLNs was evaluated using differential scanning calorimetry and powder X-ray diffractometry, which revealed that crystalline CXB was transformed into amorphous form after the fabrication procedure. The reconstitution of CXB@PLNs in aqueous media generated CXB-loaded liponiosomes with nano-sized mean diameters and spherical morphology. CXB@PLNs displayed enhanced dissolution rate and permeability compared to CXB suspension. In vivo pharmacokinetic studies performed on rats demonstrated the improved oral bioavailability of CXB@PLNs compared to that of CXB suspension. No serious systemic toxicity was observed in the blood biochemistry tests performed on rats. These results suggest that the developed PLNs could be promising oral delivery systems for improving the bioavailability of poorly water-soluble drugs, such as CXB.

7.
Asian J Pharm Sci ; 15(3): 292-310, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32636948

RESUMO

Currently, sixty-five original sprinkle drug products are available in various dosage forms including tablets, powders, granules, immediate-release capsules, extended-release capsules, delayed-release capsules, and multiparticulate drug delivery systems. By sprinkling on soft food vehicles, these products provide dosing flexibility and convenience of administration, which potentially improve the compliance of patients with dysphagia. Due to these advantages, the growth of sprinkle products picked up since the 1990s, and several regulatory issues regarding this dosage form have been raised and documented. In this article, the types of sprinkle formulations were discussed by dividing them into seven categories, and the commercial products were summarized in terms of the drug substance, pharmaceutical excipients, storage conditions and administration methods. In addition, several US Food and Drug Administration guidelines related to the regulatory issues of sprinkle formulations were reviewed, which led to the conclusion that the future development of this promising dosage form demands integrated guidance for industry rather than scattered information in various documents.

8.
Biomed Pharmacother ; 126: 110068, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32203888

RESUMO

Cisplatin (CP) is a chemotherapeutic drug used to treat cancerous solid tumors, but it causes serious side effects, including ototoxicity. The major cause of CP-induced ototoxicity is increased levels of mitochondrial reactive oxygen species (ROS). In this study, we examined the effect of 2-Isopropyl-3H-naphtho(1,2-d)imidazole-4,5-dione (KL1333), a ß-lapachone derivative, on CP-induced ototoxicity using ex vivo organotypic culture system of cochlea. Hair cell damages in CP-treated cochlear explants with or without KL1333 were compared by immunohistochemistry. CP-induced oxidative stress and the preventive effect of KL1333 were analyzed by measuring intracellular ROS levels and depolarization of mitochondrial membrane potential. Activation of apoptosis signaling pathway was detected using TUNEL assay and immunostaining of cleaved caspase-3. As the results, it was found that KL1333 pretreatment significantly decreased stereocilia degeneration and hair cell loss, and prevented an increase in mitochondrial ROS levels in response to CP. Immunohistochemical examinations of cochlear explants revealed greater caspase-3 immunopositivity in the CP group than in controls, while the KL1333 + CP group showed significantly less immunopositivity than the CP group (P < 0.05). Thus, it appeared that KL1333 protected hair cells in the organ of Corti from CP-induced apoptosis by decreasing mitochondrial damages due to the production of mitochondrial ROS. This study is the first report showed the preventive effect of KL1333 against CP-induced ototoxicity. Although further studies should be performed to determine if KL1333 could maintain anticancer effect of CP, our data cautiously suggests that the antioxidant KL1333 can be used as an effective anti-apoptotic agent to prevent ototoxicity caused by CP-induced oxidative stress, and may prove useful in preventing hearing loss caused by CP.

9.
IUCrJ ; 7(Pt 2): 193-206, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32148848

RESUMO

SMC complexes play a central role in chromosome organization in all domains of life. The bacterial Smc-ScpAB complex is a three-subunit complex composed of Smc, ScpA and ScpB. ScpA bridges the two ATPase domains of the Smc homodimer, while ScpB, which belongs to the kite family of proteins, interacts with ScpA. The three subunits are known to be equally important for the function of Smc-ScpAB in bacteria. From crystallographic and biochemical studies, evidence is provided that six archaeal ScpA proteins are unable to interact with the only putative ScpB found in these species. Structure-based sequence alignment reveals that these archaeal ScpAs lack the ScpB-binding segment that is commonly present in the middle of bacterial ScpA sequences, which is thus responsible for their inability to interact with ScpB. ScpA proteins lacking the ScpB-binding segment are found to prevail in archaea. Moreover, two archaeal ScpA proteins with a longer middle region also failed to bind their putative ScpB partner. Furthermore, all or most species belonging to five out of 14 euryarchaeotal orders contain Smc and ScpA but not a detectable ScpB homologue. These data support the notion that archaeal Smc-based complexes generally function as a two-subunit complex composed of only Smc and ScpA.

10.
Nutr Rev ; 78(9): 699-708, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073633

RESUMO

CONTEXT: Krill oil is a good source of n-3 phospholipids and has greater bioavailability than fish oil, which contains n-3 triglycerides. However, it is unclear whether krill oil affects circulating lipid concentrations more beneficially than fish oil. OBJECTIVE: A network meta-analysis was conducted to compare the lipid-modifying effects of krill oil and fish oil. DATA SOURCES: PubMed and Embase databases were searched. STUDY SELECTION: A total of 64 randomized controlled trials that determined the lipid-modifying effects of krill oil or fish oil were selected. DATA EXTRACTION: The MetaXL program was used for meta-analysis. A subgroup analysis and a network meta-regression were conducted to investigate the dose-response effect of the n-3 fatty acid content of fish oil and krill oil. RESULTS: Krill oil was associated with significantly lower triglyceride levels than control supplements (weighted mean difference [WMD] -23.26 [95%CI, -38.84 to -7.69]). However, the net differences in triglycerides (WMD -4.07 [95%CI, -15.22 to 7.08]), low-density lipoprotein cholesterol (WMD 3.01 [95%CI, -5.49 to 11.51]), high-density lipoprotein cholesterol (WMD 1.37 [95%CI, -3.73 to 6.48]), and total cholesterol (WMD 1.69 [95%CI, -6.62 to 10.01]) were not significantly different between the krill oil and fish oil groups. One gram of n-3 fatty acids contained in fish oil and krill oil lowered median triglycerides by 8.971 mg/dL (95% credible interval [CrI], 2.27 to 14.04) and 9.838 mg/dL (95%CrI, 0.72 to 19.40), respectively. CONCLUSIONS: The lipid-modifying effects of krill oil and fish oil do not differ. The reduction in triglycerides depends on the dose of n-3 fatty acids consumed.

11.
Arch Pharm Res ; 43(1): 1-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31989476

RESUMO

The term "single enzyme nanoparticle" (SEN) refers to a chemically or biologically engineered single enzyme molecule. SENs are distinguished from conventional protein nanoparticles in that they can maintain their individual structure and enzymatic activity following modification. Furthermore, SENs exhibit enhanced properties as biopharmaceuticals, such as reduced antigenicity, and increased stability and targetability, which are attributed to the introduction of specific moieties, such as poly(ethylene glycol), carbohydrates, and antibodies. Enzyme replacement therapy (ERT) is a crucial therapeutic option for controlling enzyme-deficiency-related disorders. However, the unfavorable properties of enzymes, including immunogenicity, lack of targetability, and instability, can undermine the clinical significance of ERT. As shown in the cases of Adagen®, Revcovi®, Palynziq®, and Strensiq®, SEN can be an effective technology for overcoming these obstacles. Based on these four licensed products, we expect that additional SENs will be introduced for ERT in the near future. In this article, we review the concepts and features of SENs, as well as their preparation methods. Additionally, we summarize different types of enzyme deficiency disorders and the corresponding therapeutic enzymes. Finally, we focus on the current status of SENs in ERT by reviewing FDA-approved products.


Assuntos
Adenosina Desaminase/uso terapêutico , Fosfatase Alcalina/uso terapêutico , Terapia de Reposição de Enzimas , Imunoglobulina G/uso terapêutico , Nanopartículas/química , Fenilalanina Amônia-Liase/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Humanos
12.
Carbohydr Polym ; 230: 115568, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887874

RESUMO

Chondroitin sulfate A-deoxycholic acid-polyethylene glycol-maleimide (CSA-DOCA-PEG-MAL; CDPM) nanostructures were designed for the transient binding of MAL with thiol in blood components and cell membranes, in addition to the CD44 receptor targeting, for the therapy of breast cancer. The spontaneous binding of free thiol groups in plasma proteins and blood cells with the MAL group of CDPM was significantly higher than that of CSA-DOCA-PEG (CDP). Enhanced cellular uptake and the in vitro antiproliferation efficacy of docetaxel (D)-loaded CDPM (CDPM/D) nanoparticles (NPs) in MCF-7 cells indicated dual-targeting effects based on MAL-thiol reactions and CSA-CD44 receptor interactions. Following intravenous injection in rats, reduced clearance and an elevated half-life of the drug was observed in the CDPM/D NPs compared to the CDP/D NPs. Taken together, MAL modification of CDP NPs could be a promising approach not only to enhance tumor targeting and penetration but also to extend the blood circulation time of anticancer drugs.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sulfatos de Condroitina/farmacologia , Receptores de Hialuronatos/antagonistas & inibidores , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Sulfatos de Condroitina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Maleimidas/química , Maleimidas/farmacologia , Nanopartículas/uso terapêutico , Tamanho da Partícula , Polietilenoglicóis/química , Ratos
13.
J Infect Dis ; 221(2): 256-266, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31693113

RESUMO

BACKGROUND: Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. METHODS: We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. RESULTS: We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.


Assuntos
Vírus da Influenza A/metabolismo , Influenza Humana/metabolismo , Metaloproteinase 13 da Matriz/biossíntese , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/virologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Aterosclerose/patologia , Western Blotting , Colágeno/metabolismo , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Humanos , Vírus da Influenza A/genética , Influenza Humana/virologia , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/patologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
14.
Small ; 15(38): e1901793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31379110

RESUMO

Band-like transport behavior of H-doped transition metal dichalcogenide (TMD) channels in field effect transistors (FET) is studied by conducting low-temperature electrical measurements, where MoTe2 , WSe2 , and MoS2 are chosen for channels. Doped with H atoms through atomic layer deposition, those channels show strong n-type conduction and their mobility increases without losing on-state current as the measurement temperature decreases. In contrast, the mobility of unintentionally (naturally) doped TMD FETs always drops at low temperatures whether they are p- or n-type. Density functional theory calculations show that H-doped MoTe2 , WSe2 , and MoS2 have Fermi levels above conduction band edge. It is thus concluded that the charge transport behavior in H-doped TMD channels is metallic showing band-like transport rather than thermal hopping. These results indicate that H-doped TMD FETs are practically useful even at low-temperature ranges.

15.
Exp Ther Med ; 18(1): 833-840, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31281457

RESUMO

Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.

16.
Molecules ; 24(10)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121831

RESUMO

Aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)-derived peptide (AdP) has been developed as a cosmeceutical ingredient for skin anti-aging given its fibroblast-activating (FA) and melanocyte-inhibiting (MI) functions. However, a suitable strategy for the topical delivery of AdP was required due to its low-permeable properties. In this study, FA and MI domains of AdP (FA-AdP and MI-AdP, respectively) were determined by functional domain mapping, where the activities of several fragments of AdP on fibroblast and melanocyte were tested, and a hydrosol-based topical delivery system for these AdP fragments was prepared. The excipient composition of the hydrosol was optimized to maximize the viscosity and drying rate by using Box-Behnken design. The artificial skin deposition of FA-AdP-loaded hydrosol was evaluated using Keshary-Chien diffusion cells equipped with Strat-M membrane (STM). The quantification of the fluorescent dye-tagged FA-AdP in STM was carried out by near-infrared fluorescence imaging. The optimized hydrosol showed 127-fold higher peptide deposition in STM than free FA-AdP (p < 0.05). This work suggests that FA- and MI-AdP are active-domains for anti-wrinkle and whitening activities, respectively, and the hydrosol could be used as a promising cosmetic formulation for the delivery of AdPs to the skin.


Assuntos
Cosmecêuticos/farmacologia , Citocinas/química , Proteínas de Neoplasias/química , Peptídeos/farmacologia , Proteínas de Ligação a RNA/química , Envelhecimento da Pele/efeitos dos fármacos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cosmecêuticos/química , Doxorrubicina , Humanos , Melanócitos/citologia , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Camundongos , Modelos Biológicos , Imagem Óptica , Peptídeos/química , Viscosidade
17.
J Clin Virol ; 115: 47-52, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30978620

RESUMO

BACKGROUND: Influenza C virus has been largely neglected, compared to influenza A orB viruses, and is not routinely tested in clinical practices. However, several studies have indicated that influenza C virus causes severe acute respiratory illness and pneumonia in all ages. OBJECTIVE: We conducted a study to identify influenza C virus among young children in South Korea. STUDY DESIGN: From October 2013 to September 2016, 973 young children with influenzalike illness (ILI) were enrolled at three university hospitals. We tested nasopharyngeal samples for 16 types of respiratory viruses. Among the tested samples, 564 were positive for one or more respiratory viruses. Except for the samples where 16 types of respiratory viruses were found, 409 negative samples were examined for the presence of influenza C virus, using a matrix gene specific primer set. RESULTS: Among 409 nasopharyngeal samples, five influenza C viruses were detected. The manifestation of influenza C virus infection in young children was observed acute respiratory illness, such as fever, rhinorrhea, and cough, but no pneumonia or severe respiratory illness. Nucleotide sequencing was conducted and a phylogenetic tree was generated. We found that C/Sao Paulo/387/82-like lineage viruses circulated in South Korea, and the fully sequenced virus (C/Seoul/APD462/2015) was closely related to C/Victoria/2/2012 and C/Tokyo/4/2014 strains. CONCLUSIONS: This study was the first report of influenza C virus detection in South Korea. Although severe illness was not observed in this study, we suggest the necessity for influenza C virus testing in pediatric patients with ILI, considering other reports of severe illnesses caused by influenza C virus infections.


Assuntos
Influenza Humana/diagnóstico , Influenza Humana/virologia , Influenzavirus C/isolamento & purificação , Nasofaringe/virologia , Infecções Respiratórias/diagnóstico , Hospitais Universitários/estatística & dados numéricos , Humanos , Lactente , Influenza Humana/epidemiologia , Filogenia , RNA Viral/genética , República da Coreia/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estações do Ano , Análise de Sequência de DNA
18.
Future Med Chem ; 10(22): 2659-2674, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30499740

RESUMO

Due to the impermeable structure and barrier function of the blood-brain barrier (BBB), the delivery of therapeutic molecules into the CNS is extremely limited. Nanodelivery systems are regarded as the most effective and versatile carriers for the CNS, as they can transport cargo molecules across the BBB via various mechanisms. This review emphasizes the multi-functionalization strategies of nanodelivery systems and combinatorial approaches for the delivery of therapeutic drugs and genes into the CNS. The characteristics and functions of the BBB and underlying mechanisms of molecular translocation across the BBB are also described.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Nanotecnologia , Animais , Portadores de Fármacos/química , Humanos
19.
Nat Commun ; 9(1): 2744, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-30013065

RESUMO

Prefrontal brain areas are implicated in the control of fear behavior. However, how prefrontal circuits control fear response to innate threat is poorly understood. Here, we show that the anterior cingulate cortex (ACC) and its input to the basolateral nucleus of amygdala (BLA) contribute to innate fear response to a predator odor in mice. Optogenetic inactivation of the ACC enhances freezing response to fox urine without affecting conditioned freezing. Conversely, ACC stimulation robustly inhibits both innate and conditioned freezing. Circuit tracing and slice patch recordings demonstrate a monosynaptic glutamatergic connectivity of ACC-BLA but no or very sparse ACC input to the central amygdala. Finally, our optogenetic manipulations of the ACC-BLA projection suggest its inhibitory control of innate freezing response to predator odors. Together, our results reveal the role of the ACC and its projection to BLA in innate fear response to olfactory threat stimulus.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Clássico/fisiologia , Medo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Odorantes/análise , Animais , Comportamento Animal , Coiotes/fisiologia , Eletrodos Implantados , Eletrochoque , Medo/fisiologia , Feminino , Raposas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Optogenética , Córtex Pré-Frontal/fisiologia , Técnicas Estereotáxicas , Urina/química
20.
Artigo em Inglês | MEDLINE | ID: mdl-30031944

RESUMO

Herein we have developed an optimized analytical method for the simultaneous quantification of a fungicide, thiophanate-methyl, and its metabolite, carbendazim, in pear cultivated under open-field conditions using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Due to the problem of partitioning associated with using acetonitrile and salts, methanol was used for sample extraction; the extract was then filtered using a vacuum filter, and cleaned-up using C18 QuEChERS bulk sorbent following dispersive solid-phase extraction (d-SPE) procedure. Since a common problem, "matrix effect", associated with the matrix was observed in LC-MS/MS, calibration curves for both thiophanate-methyl and carbendazim were constructed in the matrix using seven different concentration levels. Excellent linearity was observed, with determinant coefficient (R2) ≥ 0.9990. The limits of quantification (LOQs) were ≤0.02 mg/kg, satisfactory in terms of the maximum residue limits. Methods were validated at two fortification concentrations (10 × LOQ and 50 × LOQ); the experiments were repeated three times for each level and the average recoveries were 75.00-84.92%, with the coefficient of variation (CV) being ≤5.78%. The developed analytical method was applied to pear samples previously sprayed with commercial thiophanate-methyl formulation four times on different days during pre-harvest treatment. The parent compound was converted to its metabolites and the total residues degraded continuously until harvest. The data obtained in this study could help set safety guidelines for thiophanate-methyl in pear.


Assuntos
Benzimidazóis/análise , Carbamatos/análise , Cromatografia Líquida/métodos , Fungicidas Industriais/análise , Resíduos de Praguicidas/análise , Pyrus/química , Tiofanato/análise , Frutas/química , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...