Changes in hepatic lymph vessels in endotoxaemia.

This study was undertaken into rats to investigate changes in the hepatic lymph vessels and the space of Disse in endotoxaemia and to examine their relationship with the development of endotoxin-induced hepatic injury. Lymph stasis, namely dilatation of the lymph vessels and oedema, developed rapidly in the medium-sized portal canals, the large portal canals, and the liver hilum after endotoxin injection, but not in the small portal canals. Such changes reached their maximum 4-8 h after endotoxin injection and had recovered markedly by 16 h after the injection. The space of Disse remained within normal limits during this period. These findings suggest that the intrahepatic lymph stasis in endotoxaemia may be caused by a reduction in the pumping activity of the extrahepatic and the intrahepatic large lymph vessels rather than by an increase of lymph formation in the liver lobules. There was no evidence suggesting a direct relationship between the disturbance of hepatic lymph flow and the development of hepatic injury in endotoxaemia.     

大鼠直肠壁内淋巴管的微细分布和形态特征

目的观察大鼠直肠壁内淋巴管的分布和形态、结构特点，为探讨直肠癌淋巴道转移的机制，提供形态学依据。方法用半薄、超薄切片、光镜和电镜下观察大鼠淋巴管的微细分布。结果大鼠直肠壁的黏膜固有层深部可见毛细淋巴管，黏膜下层、肌层和浆膜层均有毛细淋巴管和淋巴管。结论直肠壁各层内均有毛细淋巴管，除黏膜层外，还存有淋巴管。     

Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyaluronan receptors.

Endothelial cells (ECs) display distinct structural and functional characteristics depending on the tissue and developmental stage; however, the development of tissue-specific ECs remains poorly understood. Here, we describe the development of hepatic sinusoids in mice based on the expression of hyaluronan receptors Stab2 and Lyve-1. Flk-1(+) cells in and around the liver bud begin to express Stab2 at embryonic day (E) 9.5, before the formation of vascular lumen. Hepatic sinusoidal endothelial cells (HSECs) begin to express Lyve-1 at E10.5, and both markers continue to be expressed in HSECs thereafter. Although HSECs and lymphatic ECs (LECs) are known to share functional and phenotypic characteristics, we clearly show that HSECs can be distinguished from LECs by the expression of molecular markers and higher endocytotic activity. Our results provide new insight into the development of tissue-specific ECs and phenotypic criteria to distinguish HSECs from other types of ECs, including LECs.     

Lymphoid cells in afferent and efferent intestinal lymph: lymphocyte subpopulations and cell migration.

Gut wall emigrating cells have been characterized in the intestinal lymph. The intestinal lymph duct was cannulated in 6-month-old minipigs. Under non-restraining conditions the efferent lymph from the mesenteric lymph nodes was collected in seven normal animals. Lymph coming directly from the gut (afferent lymph) was also collected in 18 pigs after resection of the mesenteric lymph node chains 3 months previously. The intestinal lymph flow was similar in both groups (around 18 ml/h). The lymphoid cell yield was 1.2 +/- 1.0 x 10(6)/h in control animals, while in mesenteric lymph node resected pigs it was around 20 times higher (26.2 +/- 17.6 x 10(6)/h). In the gut-derived lymph 76.5 +/- 8.8% T lymphocytes were observed (CD4+, 48.1 +/- 15.5%; CD8+, 53.6 +/- 12.7%). The percentage of immunoglobulin-positive cells was lower (IgM+, 10.1 +/- 4.5; IgA+, 1.7 +/- 1.1). In 14 mesenteric lymph node resected pigs a mean of 5.6 +/- 3.1 x 10(8) lymphocytes from the gut lymph were labelled in vitro with a fluorescent dye and retransfused. The labelling index of fluorescent cells in the intestinal lymph increased rapidly and remained at a high level until 44 h after cell transfusion. A four-to-ten times lower labelling index was found in the spleen, various lymph nodes and Peyer's patches. Most of the recovered lymphocytes were T cells. This model provides access to the cell pool leaving the gut wall, thus allowing an examination of its role in the gastrointestinal tract and other mucosal-lined organs.     

Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival

Background: Clearance of large molecules from the interstitialspace is an important function of lymphatics andis affected by local pathologic changes.Objective: To determine if the clearance rate ofinterstitially injected albumin is correlated to tumour characteristicsand outcome in women with invasive breast cancer.Method: In a consecutive series of women comingto biopsy for suspected breast cancer, technetium-tagged albuminwas injected into the tissue adjacent to thepalpable mass. The isotope disappearance rate was measuredover two hours. Also assessed were the maximumvessel density (MVD – using Factor VIII polyclonalantisera), the proliferation rate (using Ki-67 antisera), nodestatus, tumour size, histologic and nuclear grade, mitoticrate, and p53 and c-erbB-2 oncoproteins. All patientswere followed until relapse and for a minimumof 10 years.Results: In multivariate analysis, an association between relapse-freesurvival and isotope clearance rate was suggested (p= 0.024). The best outcome was seen inpatients with the least isotope clearance. Node status,size, histologic and nuclear grade, and mitotic ratecorrelated with survival. MVD did not correlate withsurvival and was inversely related to the isotopeclearance rate. Tumour proliferation rate, and the c-erbB-2and p53 oncoproteins did not relate to outcome.Conclusion: The role of lymphatics in breast canceris difficult to study. Measurement of interstitial clearancemay be a useful technique and could bea prognostic factor.     

The peritoneal microcirculation in peritoneal dialysis.

This paper deals with the peritoneal microcirculation and with peritoneal exchange occurring in peritoneal dialysis (PD). The capillary wall is a major barrier to solute and water exchange across the peritoneal membrane. There is a bimodal size-selectivity of solute transport between blood and the peritoneal cavity, through pores of radius approximately 40-50 A as well as through a very low number of large pores of radius approximately 250 A. Furthermore, during glucose-induced osmosis during PD, nearly 40% of the total osmotic water flow occurs through molecular water channels, termed "aquaporin-1." This causes an inequality between 1 - sigma and the sieving coefficient for small solutes, which is a key feature of the "three-pore model" of peritoneal transport. The peritoneal interstitium, coupled in series with the capillary walls, markedly modifies small-solute transport and makes large-solute transport asymmetric. Thus, although severely restricted in the blood-to-peritoneal direction, the absorption of large solutes from the peritoneal cavity occurs at a high clearance rate ( approximately 1 mL/min), largely independent of molecular radius. True absorption of macromolecules to the blood via lymphatics, however, seems to be occurring at a rate of approximately 0.2 mL/min. Several controversial issues regarding transcapillary and transperitoneal exchange mechanisms are discussed in this paper.     

Alteration of epicardial lymphatics in lymphostatic canine hearts

Summary This study was conducted in an attempt to establish a method for evaluation of cardiac lymphostasis in autopsy cases and animal experiments. Ten mongrel dogs were operated on to induce cardiac lymphostasis in terms of ligation of coronary lymphatics. From the following day to 6 months after surgery, epicardial lymphatics were visualized to measure the volumes and densities of the lymphatics. The mean volume, measured after 1 week (0.27±0.09), 2 weeks (0.32±0.04), and 6 months (0.23±0.05) continued to be higher than that on the first day (0.16±0.04) (P<0.05). The density, measured after 1 week (2.6±0.3) and 2 weeks (3.7±0.7), also showed higher values, than that on the 1st day (1.7±0.7) (P<0.01). However, 6 months later, the measured value (1.9±0.03) showed no statistical difference compared to that of the 1st day. Observation under a binocular microscope revealed impressions of a progressive increase in both number and thickness of the lymphatics as late as 2 weeks after the induction. However, 6 months later, there was marked dilatation and a relative decrease in the number of lymphatics.     

Sympathectomy decreases size and invasiveness of tongue cancer in rats

The sympathetic nervous system plays a role in carcinogenesis wherein locally released sympathetic neurotransmitters affect proliferation, angiogenesis, vessel permeability, lymphocyte traffic and cytokine production. The present in vivo study was designed to investigate whether surgical sympathectomy, both unilateral and bilateral, had an effect on tumor growth, interstitial fluid pressure (IFP) and lymphatics in rat tongue cancer. We used 4-nitroquinoline-1-oxide (4-NQO) in drinking water for 19 weeks to induce tongue cancer in 20 Dark Agouti rats. After 11 weeks, one group underwent unilateral sympathectomy and another underwent bilateral sympathectomy, while the third group underwent sham surgery. By 19 weeks, tumors in the bilaterally sympathectomized (BL-SCGx) rats were significantly smaller (P<0.05), more diffuse in appearance and less invasive (P<0.05) compared with the large exophytic tumors in the sham-operated rats. The relative lymphatic area was significantly decreased (P<0.05) in tumors in the BL-SCGx rats compared with the sham group. Interestingly, the tumors in rats that underwent unilateral or bilateral sympathectomy had a significantly lower (P<0.05) IFP than those in sham rats. Lack of tyrosine hydroxylase (TH) immunoreactive nerves and few neuropeptide Y (NPY) positive fibers indicate absence of sympathetic nerve fibers in the bilateral sympathectomized group. The peritumoral lymph vessel area was correlated with the tumor size (P<0.001), depth of invasion (P<0.001), weight of rats (P<0.005) and IFP (P<0.05). In conclusion, the present study presents evidence that deprivation of sympathetic nerves decreases tumor growth in rat tongue, probably caused by decreasing IFP and lymph vessel area.     

雌激素增强失血性休克大鼠肠系膜淋巴管的收缩功能

目的:观察17β-雌二醇(E2)对失血性休克大鼠肠系膜淋巴微循环和离体肠系膜淋巴管收缩性的作用及其与淋巴管平滑肌细胞(LSMCs)内外钙离子浓度([Ca2+])差的关系.方法:雄性Wistar大鼠随机均分为假手术组、休克组和休克+E2组,建立失血性休克模型[(40±2)mmHg维持1.5 h,液体复苏],休克+E2组在...     

Rare adipose disorders (RADs) masquerading as obesity

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum''s disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations.