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视网膜色素变性(retinitis pigmentosa,RP)的治疗目前仍处于探索阶段。胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)是目前研究中重要的神经营养因子,但其传统给药方式生物利用度相对较低。近年来GDNF安全有效的给药方式成为研究热点,包括经病毒载体或非病毒载体的基因工程法释药技术、经聚合物释放系统释药技术、经细胞移植释药技术、小分子触发器诱导产生GDNF等。本文就GDNF干预RP的给药方式进行综述。 相似文献
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Victoria A. Chang Dawn M. Meyer Brett C. Meyer 《Journal of stroke and cerebrovascular diseases》2019,28(1):163-166
Background
Acute stroke codes may be activated for anisocoria, but how often these codes lead to a final stroke diagnosis or alteplase treatment is unknown. The purpose of this study was to assess the frequency of anisocoria in stroke codes that ultimately resulted in alteplase administration.Methods
We retrospectively assessed consecutive alteplase-treated patients from a prospectively-collected stroke registry between February 2015 and July 2018. Based on the stroke code exam, patients were categorized as having isolated anisocoria [A+(only)], anisocoria with other findings [A+(other)], or no anisocoria [A?]. Baseline demographics, stroke severity, alteplase time metrics, and outcomes were also collected.Results
Ninety-six patients received alteplase during the study period. Of the 94 who met inclusion criteria, there were 0 cases of A+(only). There were 9 cases of A+(other) (9.6%). A+(other) exhibited higher baseline National Institutes of Health (NIH) Stroke Scale scores compared to A? (17 versus 7; P?=?.0003), and no additional differences in demographics or alteplase time metrics. Final stroke diagnosis and other outcome measures were no different between A+(other) and A?. Of the A+ patients without pre-existing anisocoria, 5 of 6 (83%) had posterior circulation events or diffuse subarachnoid hemorrhage.Conclusions
In this exploratory analysis, zero patients with isolated anisocoria received alteplase treatment. Anisocoria as a part of the neurologic presentation occurred in 10% of alteplase patients, and was strongly associated with a posterior circulation event. Therefore, we conclude that anisocoria has a higher likelihood of leading to alteplase treatment when identified in the presence of other neurologic deficits. 相似文献24.
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Gudrun Aspelund Elaa M Mahdi David H Rothstein Derek S Wakeman 《Journal of gastroenterology and hepatology》2019,34(6):966-974
Choledochal cysts (CDCs) and biliary atresia (BA) are rare pediatric hepatobiliary anomalies that require surgical intervention due to increased risk of malignancy and liver failure, respectively. The underlying disease and operative procedures place patients at risk for long‐term complications, which may continue to affect them into adulthood. Lack of a transitional care model in the health‐care system potentiates the challenges they will face following aging out of their pediatric providers' care. We sought to elucidate the long‐term complications and challenges patients with CDCs and BA face, review the current literature regarding transitioning care, and propose guidelines aiding adult providers in continued care and surveillance of these patients. A literature review was performed to assess short‐term and long‐term complications after surgery and the current standards for transitioning care in patients with a history of CDCs and BA. While transitional programs exist for patients with other gastrointestinal diseases, there are few that focus on CDCs or BA. Generally, authors encourage medical record transmission from pediatric to adult providers, ensuring accuracy of information and compliance with treatment plans. Patients with CDCs are at risk for developing biliary malignancies, cholangitis, and anastomotic strictures after resection. Patients with BA develop progressive liver failure, necessitating transplantation. There are no consensus guidelines regarding timing of follow up for these patients. Based on the best available evidence, we propose a schema for long‐term surveillance. 相似文献
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《Journal of pharmaceutical sciences》2019,108(8):2661-2667
In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders. 相似文献
29.
In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion 下载免费PDF全文
Yajie Yin Xiaofei Zhang Zheng Cui Wei Qu Bing He Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang 《中国药学》2019,28(5):329-338
Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia®350 (S350) and pH sensitive material Eudragit® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS. 相似文献
30.
Lauren A. Eberly Emmanuel Rusingiza Paul H. Park Gedeon Ngoga Symaque Dusabeyezu Francis Mutabazi Cyprien Gahamanyi Evariste Ntaganda Gene F. Kwan Gene Bukhman 《Journal of the American College of Cardiology》2019,73(8):977-980
Nurse-led delivery care models have the potential to address the significant burden of heart failure in sub-Saharan Africa. Starting in 2006, the Rwandan Ministry of Health, supported by Inshuti Mu Buzima (Partners In Health–Rwanda), decentralized heart failure diagnosis and care delivery in the context of advanced nurse-led integrated noncommunicable clinics at rural district hospitals. Here, the authors describe the first medium-term survival outcomes from the district level in rural sub-Saharan Africa based on their 10-year experience providing care in rural Rwanda. Kaplan-Meier methods were used to determine median time to event for: 1) composite event of known death from any cause, lost to follow-up, or transfer to estimate worst-case mortality; and 2) known death only. Five-year event-free rates were 41.7% for the composite outcome and 64.3% for known death. While death rates are encouraging, efforts to reduce loss to follow-up are needed. 相似文献