The therapeutic use of biological molecules such as growth factors and monoclonal antibodies is challenging in view of their limited half-life in vivo. This has elicited the interest in delivery materials that can protect these molecules until released over extended periods of time. Although previous studies have shown controlled release of biologically functional BMP-2 and TGF-β from silica sol–gels, more versatile release conditions are desirable. This study focuses on the relationship between room temperature processed silica sol–gel synthesis conditions and the nanopore size and size distribution of the sol–gels. Furthermore, the effect on release of large molecules with a size up to 70 kDa is determined. Dextran, a hydrophilic polysaccharide, was selected as a large model molecule at molecular sizes of 10, 40 and 70 kDa, as it enabled us to determine a size effect uniquely without possible confounding chemical effects arising from the various molecules used. Previously, acid catalysis was performed at a pH value of 1.8 below the isoelectric point of silica. Herein the silica synthesis was pursued using acid catalysis at either pH 1.8 or 3.05 first, followed by catalysis at higher values by adding base. This results in a mesoporous structure with an abundance of pores around 3.5 nm. The data show that all molecular sizes can be released in a controlled manner. The data also reveal a unique in vivo approach to enable release of large biological molecules: the use more labile sol–gel structures by acid catalyzing above the pH value of the isoelectric point of silica; upon immersion in a physiological fluid the pores expand to reach an average size of 3.5 nm, thereby facilitating molecular out-diffusion. 相似文献
Epileptiform discharges (ED) can occur during sevoflurane induction, especially in young female patients and when high alveolar concentrations are used. The aim of this study was to evaluate whether low sevoflurane concentration reduces the occurrence of ED in female patients.
Methods
Thirty-four female patients scheduled for minor gynecological surgery were prospectively included and randomized in two groups. In group A, anesthesia was induced with sevoflurane inspired 8% manually set via the circuit of the Zeus® (Dräger Medical, Lübeck, Germany) anesthesia workstation (fresh gas flow 8 L.min−1) for 2 min and then 2.5%. In group B, induction was performed by target-controlled inhalation with a target end-tidal concentration of sevoflurane set at 2.5% (fresh gas flow in auto-control mode). Electroencephalogram (EEG) was recorded in the operating room throughout induction till two min after intubation and analyzed off-line by a neurophysiologist blinded to the randomization.
Results
ED occurred in five patients (15%): one in group A and four in group B (P > 0.05). ED occurred with a median delay of 303 s [25–75 interquartiles: 135–418] and the median duration of ED episode was 13 s [3–78]. Fifteen patients had abnormal movements without simultaneous EEG abnormality.
Conclusion
Induction of anesthesia with low target concentration of sevoflurane (2.5%) fails to totally prevent the occurrence of ED in young female patients and should be used carefully in this population. 相似文献
Dual-task designs have been used widely to study the degree of automatic and controlled processing involved in postural stability of young and older adults. However, several unexplained discrepancies in the results weaken this literature. To resolve this problem, a careful selection of dual-task studies that met certain methodological criteria are considered with respect to reported interactions of age (young vs. older adults) × task (single vs. dual task) in stable and unstable postural conditions. Our review shows that older adults are able to perform a postural dual task as well as younger adults in stable conditions. However, when the complexity of the postural task is increased by dynamic conditions (surface and surround), performance in postural, concurrent, or both tasks is more affected in older relative to young adults. In light of neuroimaging studies and new conceptual frameworks, these results demonstrate an age-related increase of controlled processing of standing associated with greater intermittent adjustments. 相似文献
目的 构建桃红四物汤干预腰椎间盘突出症的“药物- 靶基因- 疾病”预测模型,探究桃红四物汤治疗腰椎间盘突出症的核心靶点及作用通路。方法 〖JP3〗通过中药系统药理学数据库与分析平台收集桃红四物汤中有效的化学成分及靶点信息,运用UniProt蛋白质数据库实现基因靶点名称规范化;从GeneCards、疗效靶点数据库、人类孟德尔遗传在线、DRUGBANK数据库中查找腰椎间盘突出症的靶点。构建“成分- 靶点- 疾病”网络,并对蛋白相互作用(protein- protein interaction,PPI)网络进行可视化分析,分析排名前20个靶点的生物过程、分子功能、细胞组成和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)中信号通路。结果 筛选出69个桃红四物汤的有效化学成分,235个潜在基因靶点,其中与腰椎间盘突出症共同的基因靶点有82个。PPI网络分析显示,肿瘤坏死因子(tumor necrosis factor,TNF)、表皮生长因子(epidermal growth factor,EGF)、表皮生长因子受体(epidermal growth factor receptor, EGFR)、激活蛋白1(activator protein 1,JUN)、丝氨酸/苏氨酸蛋白激酶(serine/threonine- protein kinase 1,AKT1)是桃红四物汤干预腰椎间盘突出症的核心靶点。基因本体论的富集分析结果显示,桃红四物汤干预腰椎间盘突出症的过程涉及对DNA结合转录因子活性的调节、细胞对生物刺激的反应、氧化应激反应以及对脂多糖、细菌来源分子的调节;KEGG的通路富集分析结果显示,丝裂原活化蛋白激酶(mitogen- activated protein kinase,MAPK)通路、晚期糖基化终末产物(advanced glycation end product,AGE)- AGE受体(receptor for AGE,RAGE)通路、TNF通路的差异蛋白表达水平较高。结论 桃红四物汤可能是通过抗炎、提高免疫、调控激素、延缓细胞凋亡等作用多靶点、多通路调控腰椎间盘突出症。 相似文献
Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)–intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH–IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300?mg or 600?mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300?mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles. 相似文献
Diagnostic facet joint nerve blocks have been utilized in the diagnosis of cervical facet joint pain in patients without disk herniation or radicular pain due to a lack of reliable noninvasive diagnostic measures. Therapeutic interventions include intra-articular injections, facet joint nerve blocks and radiofrequency neurotomy. The diagnostic accuracy and effectiveness of facet joint interventions have been assessed in multiple diagnostic accuracy studies, randomized controlled trials (RCTs), and systematic reviews in managing chronic neck pain.
This assessment shows there is Level II evidence based on a total of 11 controlled diagnostic accuracy studies for diagnosing cervical facet joint pain in patients without disk herniation or radicular pain utilizing controlled diagnostic blocks. Due to significant variability and internal inconsistency regarding prevalence in a heterogenous population; despite 11 studies, evidence is determined as Level II. Prevalence ranged from 36% to 67% with at least 80% pain relief as the criterion standard with a false-positive rate ranging from 27% to 63%.
The evidence is Level II for the long-term effectiveness of radiofrequency neurotomy and facet joint nerve blocks in managing cervical facet joint pain. There is Level III evidence for cervical intra-articular injections. 相似文献