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1.
Sensors (Basel) ; 22(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35591180

RESUMO

The majority of digital sensors rely on von Neumann architecture microprocessors to process sampled data. When the sampled data require complex computation for 24×7, the processing element will a consume significant amount of energy and computation resources. Several new sensing algorithms use deep neural network algorithms and consume even more computation resources. High resource consumption prevents such systems for 24×7 deployment although they can deliver impressive results. This work adopts a Computing-In-Memory (CIM) device, which integrates a storage and analog processing unit to eliminate data movement, to process sampled data. This work designs and evaluates the CIM-based sensing framework for human pose recognition. The framework consists of uncertainty-aware training, activation function design, and CIM error model collection. The evaluation results show that the framework can improve the detection accuracy of three poses classification on CIM devices using binary weights from 33.3% to 91.5% while that on ideal CIM is 92.1%. Although on digital systems the accuracy is 98.7% with binary weight and 99.5% with floating weight, the energy consumption of executing 1 convolution layer on a CIM device is only 30,000 to 50,000 times less than the digital sensing system. Such a design can significantly reduce power consumption and enables battery-powered always-on sensors.


Assuntos
Algoritmos , Redes Neurais de Computação , Humanos
2.
J Photochem Photobiol B ; 201: 111607, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710927

RESUMO

This study investigated and compared the behaviour of two types of natural waxes, beeswax and Chinese wax, by means of two different ageing tests: an artificial accelerated ageing test using UV light and a simulated natural ageing test (indoors conditions) based on the action of natural, window-filtered light. The same tests were employed to evaluate the influence of wax finishing on the ageing behaviour of Chinese Ash (Fraxinus mandshurica) wood surfaces. Ageing effects were evaluated by direct and microscopic observation, colour measurements in the CIELab system and FTIR investigations. The results yielded by both accelerated UV ageing (72 h) and simulated indoors natural ageing (6 months) indicate that the waxes under analysis here are materials with a good ageing resistance. FTIR investigation revealed only minor chemical changes following ageing, more evident with beeswax than with Chinese wax. Finishing Chinese Ash wood surfaces with the two types of waxes influenced their ageing behaviour in terms of colour and surface chemistry changes. For both UV and natural ageing the maximum colour differences occurred for the samples finished with Chinese wax. The colour differences ΔE after 72 h accelerated UV ageing were in all the cases higher than those occurring after 6 months of indoors simulated natural ageing. Acceleration indexes for UV exposure compared to exposure to natural window-filtered sunlight, of about 40X-60X, were calculated. Both UV accelerated ageing and natural simulated ageing resulted in significant surface chemistry changes for the unfinished Chinese ash wood samples, consisting mostly in lignin degradation and formation of carbonyl containing chromophores. FTIR investigation of wax finish wood samples revealed only very minor chemical changes of the top wax layers, although chemical changes occurring beneath the coating layer on the wood surface are highly probable. Overall, the experiments presented in this paper indicate that Chinese wax seems slightly more resistant to ageing than beeswax.


Assuntos
Fraxinus/química , Raios Ultravioleta , Ceras/química , Cor , Fraxinus/metabolismo , Fotólise , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Fatores de Tempo , Ceras/efeitos da radiação , Madeira/química
3.
Sci Rep ; 5: 16125, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26530454

RESUMO

In order to overcome drug resistant and enhance antitumor activity of DOX, a new pH-sensitive micelle (DOX/DQA-DOX@DSPE-hyd-PEG-AA) was prepared to simultaneously deliver DOX to nucleus and mitochondria. Drug released from DOX/DQA-DOX@DSPE-hyd-PEG-AA showed a pH-dependent manner. DOX/DQA-DOX@DSPE-hyd-PEG-AA induced the depolarization of mitochondria and apoptosis in MDA-MB-231/ADR cells and A549 cells, which resulted in the high cytotoxicity of DOX/DQA-DOX@DSPE-hyd-PEG-AA against MDA-MB-231/ADR cells and A549 cells. Confocal microscopy confirmed that DOX/DQA-DOX@DSPE-hyd-PEG-AA simultaneously delivered DQA-DOX and DOX to the mitochondria and nucleus of tumor cell. After DOX/DQA-DOX@DSPE-hyd-PEG-AA was injected to the tumor-bearing nude mice by the tail vein, DOX was mainly found in tumor tissue. But DOX was widely distributed in the whole body after the administration of free DOX. Compared with free DOX, the same dose of DOX/DQA-DOX@DSPE-hyd-PEG-AA significantly inhibited the growth of DOX-resistant tumor in tumor-bearing mice without obvious systemic toxicity. Therefore, dual subcellular compartment delivery of DOX greatly enhanced the antitumor activity of DOX on DOX-resistant tumor. DOX/DQA-DOX@DSPE-hyd-PEG-AA has the potential in target therapy for DOX-resistant tumor.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/uso terapêutico , Antibióticos Antineoplásicos/toxicidade , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Distribuição Tecidual , Transplante Heterólogo
4.
Asian Pac J Cancer Prev ; 15(22): 9699-706, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25520091

RESUMO

BACKGROUND: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. MATERIALS AND METHODS: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). CONCLUSIONS: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Compostos Organoplatínicos/uso terapêutico , Polimorfismo Genético/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Humanos , Oxaliplatina , Prognóstico , Fatores de Risco
5.
Asian Pac J Cancer Prev ; 15(19): 8383-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25339033

RESUMO

BACKGROUND: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. MATERIALS AND METHODS: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. CONCLUSIONS: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Compostos Organoplatínicos/uso terapêutico , Polimorfismo Genético/genética , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/mortalidade , Humanos , Oxaliplatina , Prognóstico , Fatores de Risco , Taxa de Sobrevida
6.
Arch Pharm Res ; 37(12): 1617-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24691829

RESUMO

Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicity metabolite, and it is a substrate of MRP-2. Using CBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used for the protected hepatic injury. This study investigated the acute and chronic effects of SF on the pharmacokinetics of CBZ in rats. The concentrations of CBZ and CBZE in plasma and tissues were determined by HPLC method. The results showed that SF which significantly decreased the AUC0-t of CBZ, increased CBZE conversely. Tissue analysis showed that the concentrations of CBZ and CBZE in brain and liver were decreased by SF. In addition, the distribution of CBZE in kidney was reduced significantly, which influenced the CBZE excretion and increased the drug toxic potentially. Results in the current study suggest that patients using CBZ might be cautioned in the use of SF extract or Sophora-derived products. Meanwhile, patients receiving drugs which are substrates of CYP 3A4 and/or MRP-2 should be advised of the potential herb-drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy.


Assuntos
Carbamazepina/análogos & derivados , Extratos Vegetais/farmacologia , Sophora/química , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Área Sob a Curva , Carbamazepina/administração & dosagem , Carbamazepina/sangue , Carbamazepina/farmacocinética , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Masculino , Extratos Vegetais/administração & dosagem , Raízes de Plantas/química , Ratos Sprague-Dawley , Especificidade por Substrato , Fatores de Tempo , Distribuição Tecidual
7.
Zhong Yao Cai ; 34(8): 1288-92, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22233047

RESUMO

OBJECTIVE: To optimize the formulation of Chinese herbs' volatile oil micro emulsion. METHODS: Sreened the formulation of blank micro-emulsion and the formulation of micro-emulsion contained volatile oil by means of pseudo-ternary phase diagram. RESULTS: System of isopropyl myristate, polyoxyethylene hydrogenated castor oil, absolute ethyl alcohol and water could formed the largest area of micro-emulsion. The optimal formulation of micro-emulsion contained volatile oil was: volatile oil consisted of 2.852%, isopropyl myristate 6.65%, polyoxyethylene hydrogenated castor oil 30.42%, absolute ethyl alcohol 7.605% and water 52.47%. CONCLUSIONS: Using pseudo-ternary phase diagram to optimize the formulation of Chinese herbs' micro-emulsion is scientific and feasible. The volatile oil's solubility is also increased by made of oil-in-water type micro-emulsion and insured the stability.


Assuntos
Medicamentos de Ervas Chinesas/química , Emulsões/química , Óleos Voláteis/química , Tensoativos/química , Química Farmacêutica , Estabilidade de Medicamentos , Excipientes/química , Miristatos/química , Tamanho da Partícula , Solubilidade , Solventes/química , Tecnologia Farmacêutica/métodos , Temperatura , Água/química
8.
Bioorg Med Chem Lett ; 19(9): 2579-84, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19329312

RESUMO

The synthetic DOX-LNA conjugate was characterized by proton nuclear magnetic resonance and mass spectrometry. In addition, the purity of the conjugate was analyzed by reverse-phase high-performance liquid chromatography. The cellular uptake, intracellular distribution, and cytotoxicity of DOX-LNA were assessed by flow cytometry, fluorescence microscopy, liquid chromatography/electrospray ionization tandem mass spectrometry, and the tetrazolium dye assay using the in vitro cell models. The DOX-LNA conjugate showed substantially higher tumor-specific cytotoxicity compared with DOX.


Assuntos
Química Farmacêutica/métodos , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Ácido alfa-Linolênico/química , Linhagem Celular Tumoral , Cromatografia Líquida/métodos , Doxorrubicina/toxicidade , Desenho de Fármacos , Endocitose , Citometria de Fluxo/métodos , Humanos , Concentração Inibidora 50 , Microscopia de Fluorescência/métodos , Modelos Químicos , Espectrometria de Massas por Ionização por Electrospray/métodos , Sais de Tetrazólio/química , Tiazóis/química
9.
Biopharm Drug Dispos ; 29(9): 485-94, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19085951

RESUMO

The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has disadvantages including photodegradation and a short half-life. Several newer 1,4-DHPs, including m-nifedipine and its analogs at the C3, C5 position such as MN9201, MN9202 and MN9203, have been designed to offset these problems. The aim of this study was to investigate the pharmacokinetic characteristics of these derivatives to provide reference for their further evaluation and modification. Derivatives were intravenously bolus administered to beagle dogs. The drug concentration in the plasma was determined by the HPLC method. The pharmacokinetic parameters were calculated by the non-compartmental method. The analysis of variance (ANOVA) was used to compare the pharmacokinetic parameters of the derivatives. The results showed that the area under the curve from time zero to the last sampling time (AUC(0-t)) of m-nifedipine, MN9201, MN9202 and MN9203 was 45.1 +/- 13.6, 51.7 +/- 15.2, 70 +/- 16 and 62 +/- 12.4 micromol/l*min, respectively. The elimination half-life (t(1/2)) was 98 +/- 24, 129 +/- 55, 190 +/- 21 and 92 +/- 25 min, respectively. The t(1/2) of MN9202 was significantly longer than those of the others (p<0.05 or p<0.01). These results suggest that the length of the carbon chain at the C3 or C5 position in the derivatives had a marked effect on its metabolism, and M9202 is a promising new drug candidate worth further evaluation.


Assuntos
Nifedipino/análogos & derivados , Animais , Área Sob a Curva , Cães , Masculino , Estrutura Molecular , Nifedipino/sangue , Nifedipino/química , Nifedipino/farmacocinética , Reprodutibilidade dos Testes
10.
Biol Pharm Bull ; 30(9): 1628-33, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17827711

RESUMO

Emodin has numerous biochemical and pharmacological activities, though information about its intestinal absorption and first-pass metabolism is scarce. The purpose of this study was to evaluate intestinal absorption and metabolism of luminally administered emodin in an isolated rat small intestine using the method of LC/MS/MS. About 22.55% of the administered emodin appeared at the vascular side, chiefly as free emodin (12.01%), but some emodin glucuronide (8.69%) and sulfate (1.84%) were also detected. Free glucuronide (5.23%) and sulfate (1.08%) moieties were found in the luminal perfusate. This model serves as a valuable tool for understanding intestinal handling of emodin, and our results confirm absorption and first-pass metabolism of emodin in the rat small intestine. Phase II metabolic enzymes such as glucuronyl transferase or sulfate transferase may also play an important role in the first-pass metabolism of emodin in the small intestine, which may ultimately reduce the bioavailability (and thus the efficacy) of orally administered emodin.


Assuntos
Catárticos/metabolismo , Emodina/metabolismo , Intestino Delgado/metabolismo , Animais , Disponibilidade Biológica , Cromatografia Líquida , Glucuronídeos/metabolismo , Técnicas In Vitro , Absorção Intestinal , Masculino , Perfusão , Ratos , Ratos Sprague-Dawley , Circulação Esplâncnica/fisiologia , Sulfatos/metabolismo , Espectrometria de Massas em Tandem
11.
Biosci Biotechnol Biochem ; 71(7): 1636-43, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17617731

RESUMO

The intestinal absorption characteristics of anthraquinones emodin and chrysophanol were observed by measuring the intracellular accumulation across Caco-2 cells by the reverse-phase high performance liquid chromatography. The intracellular accumulation of chrysophanol was much greater than that of emodin, the maximum absorption of emodin and chrysophanol being 414.02+/-15.28 and 105.56+/-11.57 nmol/l x mg x protein, respectively. The absorption of each anthraquinone was significantly lower at 4 degrees C than that of 37 degrees C. The effects of the transport inhibitors, verapamil, cyclosporine and phloridzin, on the intracellular accumulation were also examined. Verapamil and cyclosporine increased the absorption of emodin and chrysophanol, while phloridzin inhibited their absorption, all in a dose-dependent manner. These results suggest that the absorption characteristics of emodin and chrysophanol were closely related to their special structure with the hydroxy groups. It is also likely that a specific transport system mediated the intracellular accumulation of emodin and chrysophanol across the Caco-2 cells.


Assuntos
Antraquinonas/farmacocinética , Emodina/farmacocinética , Inibidores Enzimáticos/farmacocinética , Mucosa Intestinal/metabolismo , Mutagênicos/farmacocinética , Células CACO-2 , Humanos , Intestinos/citologia
12.
Yao Xue Xue Bao ; 41(8): 752-5, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17039782

RESUMO

AIM: To study the biliary excretion of genistein and its metabolite at different doses in rats. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography. RESULTS: The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION: The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.


Assuntos
Bile/metabolismo , Genisteína/metabolismo , Genisteína/farmacocinética , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Genisteína/química , Masculino , Estrutura Molecular , Fitoestrógenos/administração & dosagem , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacocinética , Ratos , Ratos Sprague-Dawley
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