Intestinal lymphatics

  • 文章类型: Editorial
    肠淋巴管扩张症(IL)的特征是肠淋巴管扩张,这可能会破裂并导致淋巴流失到肠道中。由于蛋白质含量高,脂蛋白,和肠淋巴中的淋巴细胞,淋巴丢失可能导致低蛋白血症,低蛋白血症,低球蛋白血症,和淋巴细胞减少症.此外,可能会耗尽矿物质,脂质,和脂溶性维生素。IL可以是原发性的,由于淋巴系统固有的功能障碍,或者其次,可能直接或间接阻碍淋巴引流的各种因素的结果。这种情况已成为具有重要临床兴趣的主题。鉴于肠道淋巴系统在人体体液稳态中起着重要作用,适应性免疫,营养和药物吸收,肠道运输,和全身新陈代谢,它的功能障碍可能有更广泛的影响。虽然原发性IL是罕见的,具有不同的临床特征,并发症,治疗反应,和结果,继发性IL比以前认为的更常见。IL的明确诊断需要内窥镜检查发白的绒毛(通常类似于雪花)和小肠粘膜中扩张的乳的组织学确认。IL的治疗具有挑战性,涉及饮食调整,管理潜在的医疗条件,使用西罗莫司和奥曲肽等药物。认识到其患病率和不同的病因对于有针对性地管理这种具有挑战性的医疗状况至关重要。本文提供了与IL相关的临床意义的全面探索。此外,它为现有诊断和管理环境中的关键知识差距提供了宝贵的见解。
    Intestinal lymphangiectasia (IL) is characterized by the dilation of intestinal lymphatic vessels, which can rupture and cause loss of lymph into the intestine. Due to the high content of proteins, lipoproteins, and lymphocytes in the intestinal lymph, loss of lymph might result in hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and lymphocytopenia. In addition, there may be a depletion of minerals, lipids, and fat-soluble vitamins. IL can be primary due to inherent malfunctioning of the lymphatic system, or secondly, a result of various factors that may hinder lymphatic drainage either directly or indirectly. This condition has emerged as a subject of significant clinical interest. Given that the intestinal lymphatic system plays an important role in the body\'s fluid homeostasis, adaptive immunity, nutrient and drug absorption, intestinal transport, and systemic metabolism, its dysfunction may have wider implications. Although primary IL is rare, with varied clinical features, complications, treatment response, and outcomes, secondary IL is more common than previously believed. The definitive diagnosis of IL requires endoscopic demonstration of whitish villi (which frequently resemble snowflakes) and histological confirmation of dilated lacteals in the small intestinal mucosa. Treatment of IL is challenging and involves dietary modifications, managing underlying medical conditions, and using medications such as sirolimus and octreotide. Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition. This article provides a comprehensive exploration of the clinical implications associated with IL. In addition, it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.
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  • 文章类型: Journal Article
    在口服施用脂质后,可以实现高度亲脂性药物或前药向肠系膜淋巴结(MLN)的有效递送。然而,尚不清楚可以针对哪种特定的MLN以及在何种程度上。此外,药物递送至腹膜后淋巴结(RPLN)的效率尚未评估.这项研究的目的是评估高度亲脂性模型药物大麻二酚(CBD)的分布,已知在服用脂质后经历肠道淋巴运输,在给药后的不同时间点在大鼠中的特异性MLN和RPLN。体内研究表明,在给药后2小时,在MLN链顶端第二的区域中存在明显更高浓度的CBD。从给药后3小时开始,所有MLN中的浓度相似。在RPLN中也发现了大量的CBD。这项研究表明,特定MLN中的药物浓度是不同的,至少在吸收过程的峰值。此外,除了MLN,RPLN也可以通过口服给药途径靶向,这可能对一系列疾病的治疗有进一步的影响。
    Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the efficiency of drug delivery to the retroperitoneal lymph nodes (RPLN) has not been assessed. The aim of this study was to assess the distribution of a highly lipophilic model drug cannabidiol (CBD), known to undergo intestinal lymphatic transport following administration with lipids, into specific MLN and RPLN in rats at various time-points post dosing. In vivo studies showed that at 2 h following administration, significantly higher concentrations of CBD were present in the region second from the apex of the MLN chain. From 3 h following administration, concentrations in all MLN were similar. CBD was also found at substantial levels in RPLN. This study demonstrates that drug concentrations in specific MLN are different, at least at the peak of the absorption process. Moreover, in addition to the MLN, the RPLN may also be targeted by oral route of administration, which may have further implications for treatment of a range of diseases.
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  • 文章类型: Journal Article
    阿扎那韦(ATV)被广泛用作水溶性差的抗HIV剂,需要调节新型药物递送系统以提高治疗效率和安全性。本工作的主要目的是使用质量设计(QbD)方法来制造载有ATV的纳米结构脂质载体(NLC),以解决口服给药后的生物利用度及其安全性的挑战。在这里,主要目的是确定优质产品生产的影响变量。考虑到这个目标,分配了质量目标产品概况(QTPP),并进行了系统风险评估研究,以确定对关键质量属性(CQA)有影响的关键材料属性(CMA)和关键过程参数(CPP)。脂质浓度,表面活性剂浓度,高压均质机的压力分别为CMA和CPP。采用乳化-高压均质法制备ATV-NLCs,进一步冻干得到固态NLCs。配方变量(CMA和CPP)对响应的影响,如粒径(Y1),多分散指数(Y2),通过中心复合材料可旋转设计(CCRD)观察到zeta电位(Y3)。通过ANOVA对数据进行统计学评估以确认显著水平(p<0.05)。通过生成设计空间和期望值,获得了NLC的最佳条件。通过DSC表征冻干的ATV-NLC,粉末X射线衍射,和FT-IR分析。通过TEM和FESEM揭示了NLC的形态。体外研究表明,药物的缓释模式(92.37±1.03%)具有Korsmeyer-Peppas模型的机制(r2=0.925,n=0.63)。与使用乳糜微粒流动阻滞模型的ATV悬浮液相比,Wistar大鼠的体内评估显示ATV-NLC的血浆药物浓度显着更高(p<0.001)。获得ATV-NLCs的相对生物利用度为2.54倍。因此,成功开发了一种安全且有前景的药物靶向系统,以提高生物利用度,避免首过效应,确保规避肝脏的急性毒性.
    Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (p < 0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, powder X-ray diffraction, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37 ± 1.03%) with a mechanism of Korsmeyer-Peppas model (r2 = 0.925, and n = 0.63). In vivo evaluation in Wistar rats showed significantly higher (p < 0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.
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  • 文章类型: Journal Article
    Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal.
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