RESUMO
BACKGROUND: Blood pressure is a critical therapeutic goal in intensive care unit (ICU). One important factor influencing blood pressure are analgesia and sedation. Analgesic and sedative drugs are commonly used in critically ill patients. These drugs affect blood pressure by reducing the tension of the venous system, the cardiac preload, and cardiac output and inhibiting cardiac functions. Consequently, vasoactive agents are commonly used to increase blood pressure. The indications for the usage of vasoactive agents are unequivocal. However, opinions on when to stop raising blood pressure vary. This study explored the relationship between blood pressure and sedation. METHODS: Patients in the Multiparameter Intelligent Monitoring in Intensive Care-III (MIMIC) database who had received mechanical ventilation, had been administered sedative analgesics during their ICU stay, and met the inclusion criteria were included in this study. The mean arterial pressure (MAP) tendency patterns were identified using spectral clustering and visualized using the t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm. The 28-day mortality rates of patients with different MAP patterns during their first 24 hours in the ICU and their sedation levels were calculated in the crosstab. RESULTS: Fourteen thousand seven hundred and eighty-five patients from the MIMIC-III database were included in this study. Three MAP patterns were identified by spectral clustering. The median MAP of the low, moderate, and high MAP groups was 71.2, 80.4, and 97.6 mmHg, respectively. The 28-day mortality rate of patients in the moderate MAP group (13.0%) was lower than that of patients in the low (16.6%) and high (15.6%) MAP groups. No difference was found in the 28-day mortality rate between the low and high MAP groups. Dynamic changes in blood pressure at different sedation depths were also examined. Notably, compared with light and moderate sedation level, patients in the deep sedation group, especially those in the high MAP group (48.5%), had a higher 28-day mortality rate (36.5%). CONCLUSIONS: Low MAP in the first 24 hours in ICU indicates a high possibility of poor prognosis for critically ill patients on mechanical ventilation. For patients under deep sedation, maintaining a high mean arterial pressure also indicates poor prognosis. A personalized MAP target should be determined according to the severity of illness and level of sedation for each patient.
RESUMO
We report dual pH-responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)-shell (chitosan) structure with dual pH-responsive drug release function. The fabricated core-shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core-shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core-shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core-shell microcapsules were a potential candidate of dual-drug carriers.
Assuntos
Modelos Químicos , Nanocápsulas/química , Alginatos/química , Ampicilina/química , Ampicilina/farmacocinética , Ampicilina/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Diclofenaco/química , Diclofenaco/farmacocinética , Diclofenaco/toxicidade , Liberação Controlada de Fármacos , Desenho de Equipamento , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Concentração de Íons de Hidrogênio , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Nanocápsulas/toxicidadeRESUMO
Two rare 7,8-seco-lignans (1, 2), three new lignan glycosides (3, 4a, 4b), and 10 known lignans (5-14) were isolated from the fruit of Schisandra glaucescens Diels. The absolute configurations of 1 and 2 were determined by comparing their experimental and calculated electronic circular dichroism spectra. The molecular structures of the new compounds (3, 4a, and 4b), including their absolute configurations, were determined using various spectroscopic methods and hydrolysis reactions. The antioxidant activities of the isolated compounds were tested using 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Compounds 4, 7, 8, 10, 11, and 12 exhibited antioxidant activities of varying potential in both assays. Of these compounds, 7 showed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, with IC50 values of 15.7 (150 µM DPPH) and 34.6 µM (300 µM DPPH), respectively, and 4, 12, and 7 displayed higher total antioxidant activities than Trolox in the ferric reducing antioxidant power assay. The neuroprotective effects of these compounds against Aß25-35-induced cell death in SH-SY5Y cells were also investigated. Compounds 1, 2, 6, 7, 8, 11, and 12 exhibited statistically significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell death compared with the group treated only with Aß25-35.
Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Schisandra/química , Peptídeos beta-Amiloides/farmacologia , Antioxidantes/química , Compostos de Bifenilo/farmacologia , Cromanos , Medicamentos de Ervas Chinesas/química , Frutas/química , Glicosídeos/química , Concentração Inibidora 50 , Lignanas/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Ressonância Magnética Nuclear Biomolecular , Oxirredução , Fragmentos de Peptídeos/farmacologia , Picratos/farmacologia , Extratos Vegetais/químicaRESUMO
Two new tetrahydrofuran lignans, schiglaucin A and B (1-2), together with eight known analogues (3-10), were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated on the basis of spectroscopic techniques (HRESIMS, UV, IR, NMR, and CD experiments). All of the compounds were tested for their neuroprotective activities against H2O2- and CoCl2-induced cell injuries in SH-SY5Y cells, respectively. Compounds 1-10 showed significant neuroprotective effects against H2O2-induced SH-SY5Y cell death, while compounds 1-5 and 8-10 exhibited significant neuroprotective effects against CoCl2-induced SH-SY5Y cell injury.
Assuntos
Lignanas/farmacologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Schisandra/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobalto , Humanos , Peróxido de Hidrogênio , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Caules de Planta/química , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Honglian (HL) is one of the three major types of cytoplasmic male sterility (CMS) of rice (Oryza sativa L) that has been commercially used in hybrid production. In previous studies, the CMS in HL is shown to be associated with a chimeric gene orfH79 that is cotranscribed with an extra atp6 in mitochondria. This study demonstrated that the intact F0F1-ATPase in HL CMS line was specifically reduced in both of its protein quantity and enzyme activity, whereas its F1 sector was not affected. It implies that the F0 sector presents a labile linkage with F1. In the presence of fertility restorer gene, F0F1-ATPase can be recovered. Furthermore, orfH79 transcripts were preferentially polyadenylated, and consequently degraded rapidly in florets of the restored hybrid plants, indicating that the atp6-orfH79 is involved in the sterile phenotype. With inhibition of cytochrome pathway of electron transfer chain, the biomass of the sterile plants grown in dark was significantly lower than that of the fertile lines. However, the respiration measurements showed an increase in the electron transferring capacity in the sterile plants, suggesting that the reduction of biomass in sterile line was caused by the disruption of F0F1-ATPase.
Assuntos
Oryza/classificação , Oryza/enzimologia , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/genética , ReproduçãoRESUMO
Small non-coding RNAs play important roles in regulating cell functions by controlling mRNA turnover and translational repression in eukaryotic cells. Here we isolated 162 endogenous small RNA molecules from Oryza sativa, which ranged from 16 to 35 nt in length. Further analysis indicated that they represented a diversity of small RNA molecules, including 17 microRNAs (miRNAs), 30 tiny non-coding RNAs (tncRNAs) and 20 repeat-associated small interfering RNAs (rasiRNAs). Among 17 miRNAs, 13 were novel miRNA candidates and their potential targets were important regulatory genes in the rice genome. We also found that a cluster of small RNAs, including many rasiRNAs, matched to a nuclear DNA fragment that evolutionarily derived from chloroplast. These results demonstrate clearly the existence of distinct types of small RNAs in rice and further suggest that small RNAs may control gene regulation through diverse mechanisms.
Assuntos
Oryza/genética , RNA de Plantas/genética , RNA não Traduzido/genética , Sequência de Bases , Sondas de DNA/genética , Variação Genética , Genoma de Planta , MicroRNAs/química , MicroRNAs/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA de Plantas/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA não Traduzido/químicaRESUMO
BACKGROUND AND AIMS: Rice (Oryza sativa) is one of the most important cereal plants in the world. Wild-abortive (WA) and Honglian (HL) cytoplasmic male sterility (CMS) have been used extensively in the production of hybrid seeds. Although a variable number of fertility-restorer genes (Rf) for WA and HL-CMS have been identified in various cultivars, information on Rf in Oryza species with the AA-genome is sparse. Therefore the distribution and heredity of Rf for WA and HL-CMS in wild rice species of Oryza with the AA-genome were investigated. METHODS: Fertility-restorer genes for WA and HL-CMS in wild rice species with the AA-genome were investigated by following the fertility of microspores identified by I2-KI staining and by following the seed-setting rate of spikelets. A genetic model of Rf in some selected restorer accessions was analysed based on the fertility segregation of BC1F1 populations. KEY RESULTS: Fertility analysis showed that 21 out of 35 HL-type F1s, and 13 out of 31 WA-type F1s were scored as fertile. The frequency of Rf in wild rice was 60% for HL-CMS and 41.9% for WA-CMS, respectively. The fertility-restorer accessions, especially those with complete restoring ability, aggregated mainly in two species of O. rufipogon and O. nivara. The wild rice accessions with Rf for HL-CMS were distributed in Asia, Oceania, Latin American and Africa, but were centered mainly in Asia, whilst the wild restorer accessions for WA-CMS were limited only to Asia and Africa. Apart from one restorer accession that possessed two pairs of Rf for WA-CMS, all of the other nine tested wild restorer accessions each contained only a single Rf for WA-CMS or HL-CMS. Allele analysis indicated that there existed at least three Rf loci for the WA and HL-CMS systems. CONCLUSIONS: These data support the hypothesis that fertility-restorer genes exist widely in Oryza species with the AA-genome, and that Rf in Oryza sativa originated from the Oryza rufipogon/Oryza nivara complex, the ancestor of cultivated rice in Asia. The origin and evolution of Rf is tightly linked to that of CMS in wild rice, and fertility of a given CMS type is controlled by several Rf alleles in various wild restorer accessions.
Assuntos
Genoma de Planta , Oryza/genética , Alelos , Cruzamentos Genéticos , Evolução Molecular , Fertilidade/genética , Variação Genética , Proteínas de Plantas/genéticaRESUMO
A typical fractured rock mass is intersected by several sets of discontinuities, which provide the main flowpath for ground water. Due to the limitations of data obtained by conventional field measurements, it is often difficult to estimate the anisotropic permeability tensor associated with the joints existing in the rock mass. For that reason, determining permeability tensors for fractured rocks is an important topic in rock mass hydraulics. Based on field surveys, joint parameters can be analyzed by using probabilistic and statistical tools, and three-dimensional mapping of the jointed rock mass. Through analysis of a single joint's hydraulic characteristics, the principal value of the permeability tensor for the jointed rock mass can be determined by using Monte Carlo methods and the searching percolation trace method, which is developed in this paper. The study reports on practical examples demonstrating that results from the methods discussed in this paper are in agreement with those from field hydrogeological surveys and measurements.