Capillary dynamics,interstitial fluid and the lymphatic system

The regulation of small blood vessels (arterioles, venules and capillaries) and the formation of interstitial fluid at the capillary beds is an important process in the understanding of the healthy circulation. Traditionally, the Starling forces have been at the very heart of our understanding of this system. However, more recent work shows that the transvascular fluid flux is significantly lower than what one would expect on the basis of Starling’s forces alone, and hence alternative explanations have been sought to understand the process of tissue fluid formation. In this context the role of the endothelial glycocalyx layer (or EGL) has drawn substantial interest. The EGL is a dynamic, active interface between the blood and the endothelial cells. It is formed by membrane-bound glycoproteins, proteoglycans and polysaccharides, producing a hydrated gel-like layer on the luminal surface of the vascular endothelium of approximately 500–2000 nm thickness. In this paper we review some of these emerging concepts and propose alternative ideas to understand some frequent clinical conditions and their treatment.     

Capillary dynamics,interstitial fluid and the lymphatic system

The regulation of small blood vessels (arterioles, venules and capillaries) and the formation of interstitial fluid at the capillary beds is an important process in the understanding of the healthy circulation. Traditionally, the Starling forces have been at the very heart of our understanding of this system. However more recent work shows that the trans-vascular fluid flux is significantly lower than what one would expect on the basis of Starling's forces alone and hence alternative explanations have been sought to understand the process of tissue fluid formation. In this context the role of the endothelial glycocalyx layer (or EGL) has drawn substantial interest. The EGL is a dynamic, active interface between the blood and the endothelial cells. It is formed by membrane-bound glycoproteins, proteoglycans and polysaccharides, producing a hydrated gel-like layer on the luminal surface of the vascular endothelium of approximately 500–2000 nm thickness. In this paper we review some of these emerging concepts and propose alternative ideas to understand some frequent clinical conditions and their treatment.     

Differences in the width of the intercellular spaces in the epithelial basal infolding and the renal glomerular filtration site between freeze-substitution and conventional fixation

After aldehyde prefixation, pretreatment with cryoprotectant and subsequent freeze-substitution with OsO₄ in acetone (AC-FS), extensive gap junction-like close membrane appositions are frequently found in the basal infolding of the salivary gland epithelium, although the desmosomal intercellular space had the same width as with conventional electron microscopy. The intercellular space between podocyte pedicles and endothelial cells at the renal glomerular filtration site was narrower by the total width of 2 laminae lucidae following AC-FS than with conventional electron microscopy and was occupied by a homogeneous lamina densa without a lamina lucida, although no marked difference was discernable in the thickness of the lamina densa itself between the 2 preparative procedures. In addition, a decrease in the thickness of the glycocalyx was evident in the intestinal epithelial microvilli following AC-FS. It is thus likely that osmication in acetone at freezing temperatures remove the glycocalyx and related structures to a variable extent, and that this loss is responsible for reducing the intercellular spaces at some of the simple appositions narrower to the dimensions of the gap junction. It is also responsible for disappearance of the lamina lucida of the basement membrane.     

血管内皮糖萼在炎症中的作用

血管内皮糖萼是血管内皮细胞腔侧面的多糖蛋白复合物层.在生理状态下,其主要功能是调节血管内皮通透性及血细胞与内皮细胞间相互作用,介导血流剪切力诱导一氧化氮的释放等.炎症条件下,多种炎症介质导致血管内皮糖萼脱落,削弱了其血管保护功能;同时血管内皮糖萼的组分硫酸乙酰肝素可调控炎症发展,包括作为L-选择素的配体调节白细胞的滚动,形成趋化因子浓度梯度调节白细胞在血管腔侧面的移行及其与内皮细胞的紧密黏附,调控趋化因子由组织向血管腔的转运等.动脉粥样硬化作为一种炎症性疾病,其多种危险因子与血管内皮糖萼联系密切.综述了血管内皮糖萼在炎症和动脉粥样硬化中的作用.     

The roles of mucus‐forming mucins,peritrophins and peritrophins with mucin domains in the insect midgut

Most insects have a gut lined with a peritrophic membrane (PM) consisting of chitin and proteins, mainly peritrophins that have chitin‐binding domains. The PM is proposed to originate from mucus‐forming mucins (Mf‐mucins), which acquired a chitin‐binding domain that interlocked with chitin, replacing mucus in function. We evaluated the expression of Mf‐mucins and peritrophins by RNA‐sequencing (RNA‐seq) throughout the midgut of four distantly related insects. Mf‐mucins were identified as proteins with high o‐glycosylation and a series of uninterrupted Pro/Thr/Ser residues. The results demonstrate that the mucus layer is widespread in insects, and suggest that insect Mf‐mucins are derived from those found in other animals by the loss of the cysteine knot and von Willebrand domains. The data also support a role of Mf‐mucins in protecting the middle midgut of Musca domestica against acidic buffers. Mf‐mucins may also produce a jelly‐like material associated with the PM that immobilizes digestive enzymes in Spodoptera frugiperda. Peritrophins with a domain similar to Mf‐mucins may be close to the ancestor of peritrophins. Expression data of peritrophins and chitin synthase genes throughout the midgut of M. domestica, S. frugiperda and Tenebrio molitor indicated that peritrophins were incorporated along the PM, according to their preferential sites of formation. Finally, the data support the view that mucus has functions distinct from the PM.     

The expression of Lewis(a) and Lewis(b) antigens reflects changes in fucosylation between normal and neoplastic cervical squamous epithelium

Antibodies against the carbohydrate antigens Lewisa (Lea) and Lewisb (Leb) allow further investigation into the changes in fucosylation of the glycocalyx occurring during the normal and neoplastic development of cervical squamous epithelium. Lea and Leb are expressed on a broad zone of suprabasal cells in normal cervical squamous mucosa often independent of individual Lewis gene and secretor status. A proportion of Lea is expressed in sialylated form. In cervical intraepithelial neoplasia, the progressive dedifferentiation of the squamous mucosa is mirrored by loss of both Lea and Leb expression. In invasive squamous carcinomas, Lea and Leb expression is seen only on cells in areas of differentiation. The expression of Lea and Leb in normal and neoplastic cervical squamous epithelium resembles that of the Lex antigen described by us previously. The structural similarity between these antigens is highlighted and evidence for a common functional role in maintaining the integrity of squamous mucosae is discussed.     

克拉霉素和乙酰螺旋霉素对铜绿假单胞菌生物被膜的作用

目的 :研究克拉霉素 (CAM)、乙酰螺旋霉素 (ASM)对铜绿假单胞菌生物被膜 (BF)合成的影响及其与环丙沙星 (CIP)的相互作用。方法 :色氨酸法测定BF中的多糖蛋白复合物 (GLX) ;高氯酸 蒽酮反应物法定量测定BF的己糖成分 ;噻唑兰法测定活菌数。结果 :1/ 16最低抑菌浓度 (MIC)、1/ 4MIC的CAM可抑制BF中GLX、己糖的合成 ,且可显著增强 1/ 4MIC、1/ 2MIC的CIP对有BF的铜绿假单胞菌的杀菌作用 (P <0 0 5 ) ,而ASM则无以上作用。结论 :CAM可抑制铜绿假单胞菌BF的形成 ,并可增强CIP对有BF的铜绿假单胞菌的杀菌作用 ;而ASM则无抑制铜绿假单胞菌BF的作用     

Pleural mesothelium lubrication after hyaluronidase,neuraminidase or pronase treatment

Coefficient of kinetic friction (μ) of pleural mesothelium has been found to increase markedly after mesothelial blotting and rewetting. This increase disappeared after addition of a solution with hyaluronan or sialomucin, though previous morphological studies showed that only sialomucin occurs in mesothelial glycocalyx. In this research we investigated whether μ of rabbit pleural mesothelium increased after hyaluronidase, neuraminidase or pronase treatment. Hyaluronidase and neuraminidase did not increase μ, though neuraminidase cleaved sialic acid from mesothelial glycocalyx of diaphragm specimens, and removed hystochemical stain of sialic acid from glycocalyx. Sialomucin treated with neuraminidase lowered μ of blotted mesothelium, though less than untreated sialomucin; this feature plus lubrication provided by other molecules could explain why μ did not increase after neuraminidase. Short pronase treatment (in order to affect only glycocalyx proteins) increased μ; this increase was removed by hyaluronan or sialomucin. After pronase treatment μ decreased with increase in sliding velocity, indicating a regime of mixed lubrication, as in blotted mesothelium.