Effect of Sesamin on the Composition of Eicosapentaenoic Acid in Liver and on Its Lymphatic Absorption in Rats

Changes in the hepatic concentration of n-3 fatty acids, e.g., eicosapentaenoic acid and linolenic acid, were significantly reduced by their simultaneous administration with sesamin, whereas there was no such effect of sesamin for n-6 and n-9 fatty acids. However, there was no significant difference in lymphatic absorption between eicosapentaenoic acid (n-3) and arachidonic acid (n-6), irrespective of the presence or absence of sesamin.     

Lymphatic biomarkers in primary melanomas as predictors of regional lymph node metastasis and patient outcomes

Recently developed lymphatic‐specific immunohistochemical markers can now be utilized to assess intratumoral and/or peritumoral lymphatic vessel density (LVD), to detect lymphatic vessel invasion (LVI) by melanoma cells and to identify lymphatic marker expression in melanoma cells themselves. We systematically reviewed the available evidence for the expression of lymphatic markers as predictors of regional node metastasis and survival in melanoma patients. The currently available evidence suggests that LVD (particularly in a peritumoral location) and LVI are predictors of sentinel node metastasis and poorer survival. Nevertheless, adherence to international guidelines in the conduct and reporting of the studies was generally poor, with wide methodologic variations and heterogeneous findings. Larger, carefully conducted and well‐reported studies that confirm these preliminary findings are required before it would be appropriate to recommend the routine application of costly and time‐consuming immunohistochemistry for lymphatic markers in the routine clinical assessment of primary cutaneous melanomas.     

金雀异黄素对不同淋巴转移能力的小鼠肝癌细胞株的抑制作用

MTT法检测大豆提取物金雀异黄素（genistein,Gen）对不同淋巴转移能力的腹水型小鼠肝癌细胞株HepA-H和HepA-L的生长抑制作用。应用电镜观察细胞形态和流式细胞术检测细胞凋亡。将HepA-H和HepA-L接种NIH小鼠,制备荷瘤动物模型,Gen腹腔给药后第14天取淋巴结观察,并计算转移率。TUNEL法检测淋巴结凋亡细胞,并计算凋亡指数。实验发现：（1）Gen对两株细胞均具有良好的生长抑制作用,且对HepA-H的抑制优于HepA-L;（2）Gen在体外诱导两株细胞发生凋亡,且HepA-H的凋亡率高于HepA-L,并呈量效关系;（3）Gen抑制荷瘤动物肿瘤生长和肿瘤淋巴转移,且对HepA-H的抑制强于HepA-L,实验组H的凋亡指数（3．87％）也显著高于实验组L（1．69％）。故研究认为Gen显著抑制HepA-H和HepA-L肝癌细胞淋巴转移的作用机制,可能与诱导细胞凋亡有关,对高淋巴转移细胞的抑制作用强于低淋巴转移细胞,提示Gen抗肿瘤作用具有一定的选择性。     

Successful Control of Lymphatic Filariasis in the Republic of Korea

A successful experience of lymphatic filariasis control in the Republic of Korea is briefly reviewed. Filariasis in the Republic of Korea was exclusively caused by infection with Brugia malayi. Over the past several decades from the 1950s to 2006, many investigators exerted their efforts to detection, treatment, and follow-up of filariasis patients in endemic areas, and to control filariasis. Mass, combined with selective, treatments with diethylcarbamazine to microfilaria positive persons had been made them free from microfilaremia and contributed to significant decrease of the microfilarial density in previously endemic areas. Significant decrease of microfilaria positive cases in an area influenced eventually to the endemicity of filariasis in the relevant locality. Together with remarkable economic growth followed by improvement of environmental and personal hygiene and living standards, the factors stated above have contributed to blocking the transmission cycle of B. malayi and led to disappearance of this mosquito-borne ancient disease in the Republic of Korea.     

Synapse Formation Activates a Transcriptional Program for Persistent Enhancement in the Bi-directional Transport of Mitochondria

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多烯磷脂酰胆碱对肝癌大鼠肝细胞保护作用的研究

探讨多烯磷脂酰胆碱(PPC)对肝癌大鼠肝脏细胞的保护作用.将72只Wistar大鼠随机分为正常对照组、肝癌模型组、联苯双酯阳性对照组、PPC低、中、高剂量组6组,模型组、阳性对照组及PPC低、中、高剂量组均采用二乙基亚硝胺(DEN)诱导构建肝癌大鼠模型,低、中、高剂量PPC组在模型组的基础上分别给予100、200、300 mg·(kg·d)-1ppC灌胃,治疗6周后,腹主动脉取血测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)以及总胆红素(TBIL)含量,然后处死大鼠,测定肝脏湿重,计算肝脏指数,同时测定肝匀浆中丙二醛(MDA),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平.结果显示,与正常对照组相比,DEN诱导的肝癌模型组中肝脏指数、AST、ALT、TBIL、MDA水平显著升高(p＜0.01);SOD、GSH-Px活力则显著下降(p＜0.01).PPC和联苯双酯能依耐性的逆转DEN所致的上述改变,表现为肝脏指数、AST、ALT、TBIL、MDA显著降低,SOD、GSH-Px活力则显著上升,PPC高剂量组作用最为明显,随着PPC摄入量的增加,PPC对肝癌大鼠肝细胞的保护作用也相应增强.     

Risk of Recrudescence of Lymphatic Filariasis after Post-MDA Surveillance in Brugia malayi Endemic Belitung District,Indonesia

Belitung district in Bangka-Belitung Province, Indonesia with a population of 0.27 million is endemic for Brugia malayi and 5 rounds of mass drug administration (MDA) were completed by 2010. Based on the results of 3 transmission assessment surveys (TAS), the district is declared as achieving elimination of lymphatic filariasis (LF) in 2017. The findings of an independent survey conducted by the National Institute of Health Research and Development (NIHRD) in the same year showed microfilaria (Mf) prevalence of 1.3% in this district. In 2019, NIHRD conducted microfilaria survey in 2 villages in Belitung district. Screening of 311 and 360 individuals in Lasar and Suak Gual villages showed Mf prevalence of 5.1% and 2.2% with mean Mf density of 120 and 354 mf/ml in the respective villages. Mf prevalence was significantly higher among farmers and fishermen compared to others and the gender specific difference was not significant. The results of a questionnaire based interview showed that 62.4% of the respondents reported to have participated in MDA in Lasar while it was 57.7% in Suak Gual village. About 42% of the Mf positive cases did not participate in MDA. Environmental surveys identified many swampy areas supporting the breeding of Mansonia vector species. Persistence of infection is evident and in the event of successful TAS3 it is necessary to monitor the situation and plan for focal MDA. Appropriate surveillance strategies including xenomonitoring in post-MDA situations need to be developed to prevent resurgence of infection. Possible role of animal reservoirs is discussed.     

肝移植术后肝脏淋巴回流淤滞发生的影响因素初步临床分析

目的:分析肝移植术后肝脏淋巴回流淤滞(Intrahepatic lymphatic stasis,IHLS)的影响因素。方法:收集我院自2004~2012年期间行肝移植手术并经增强计算机断层扫描(Computed tomography,CT)和/或磁共振(Magnetic resonance imaging,MRI)确诊的IHLS病人,分析正常肝移植组IHLS阳性率与肝移植术后静脉并发症、胆道并发症、乙肝复发、肝癌复发、动脉并发症、移植排斥、药物性肝损害、转移瘤组IHLS阳性率的差异。结果:正常移植肝组术后IHLS的阳性率分别与术后胆道并发症、静脉并发症、乙肝复发组肝移植术后IHLS的阳性率差异有统计学意义(P0.05),与其他并发症组IHLS的阳性率差异无统计学意义(P0.05)。结论:肝移植术后静脉并发症、胆道并发症及乙肝复发可影响肝移植术后IHLS发生。     

Morphological Findings in Lymphatic Tissues of Sheep Following Oral Application of the Immunosuppressive Mycotoxin Mycophenolic Acid

Mycophenolic acid (MPA) is applied in immunosuppressive therapy after organ transplantation. As a common contaminant in silage, this substance is also frequently fed to sheep unintentionally. In this study, the effect of MPA on the immune system of sheep was examined. Four groups of 9 sheep each were fed 0, 0.5, 1.2, or 5 mg of MPA per kg body weight per day for 6 weeks. Then, the animals were slaughtered and various organs were examined macroscopically, histologically, and immunohistochemically. No effect of MPA on general health was detected. With increasing dose of MPA, germinal centres in the retropharyngeal lymph nodes displayed an activated morphology with numerous centroblasts. In the highest dose group, the sheep showed shrinkage of thymic lobules. The numbers of IgG or IgM positive plasma cells decreased in the ileum with increasing MPA-doses. These results suggest, that MPA in a high concentration may affect the morphology of immune organs of sheep.     

Enhancement of phospholipid hydrolysis in vasopressin-stimulated BHK-21 and H9c2 cells

The hydrolysis of phospholipids in vasopressin-stimulated baby hamster kidney (BHK)-21 and H9c2 myoblastic cells was investigated. Phosphatidylcholine and phosphatidylethanolamine in these cells were pulse labelled with [³H]glycerol, [³H]myristate, [³H]choline or [³H]ethanolamine, and chased with the non-labelled precursor until linear turnover rates were obtained. When cells labelled with [³H]glycerol or [³H]myristate were stimulated by vasopressin, no significant decrease in the labelling of phosphatidylcholine was detected, but the labelling of phosphatidic acid was elevated. However, the labellings of phosphatidylethanolamine and its hydrolytic product were not affected by vasopressin stimulation. When the cells were pulse labelled with [³H]-choline, vasopressin stimulation caused a decrease in the labelled phosphatidylcholine with a corresponding increase in the labelled choline. The apparent discrepancy between the two types of labelling might be explained by the recycling of labelled phosphatidic acid back into phosphatidylcholine, thus masking the reduction in the labelled phospholipid during vasopressin stimulation. Alternatively, the labelled choline produced by vasopressin stimulation was released into the medium, thus reducing the recycling of label precursor back into the phospholipid and making the decrease in the labelling of phosphatidylcholine readily detectable. Further studies revealed that vasopressin treatment caused an enhancement of phospholipase D activity in these cells. The presence of substrate-specific phospholipase D isoforms in mammalian tissues led us to postulate that the differential stimulation of phospholipid hydrolysis by vasopressin was caused by the enhancement of a phosphatidylcholine-specific phospholipase D in both BHK-21 and the H9c2 cells.Abbreviations BHK-21 cells baby hamster kidney-21 cells     

Effects of Testosterone on Triglyceride Uptake and Mobilization in Different Adipose Tissues in Male Rats in Vivo

LI, MIN AND PER BJ4OURNTORP. Effects of testosterone on triglyceride uptake and mobilization in different adipose tissues in male rats in vivo. Obes Res. 1995;3:113–119. The effects of testosterone (T) on uptake and mobilization of orally administered triglyceride were examined in male rats. In order to attempt to explain regional differences, adipose tissue metabolism was studied in vivo. (U-14 C) oleic acid in sesame oil was given by gastric gavage to male, sham operated, castrated and castrated + T substituted rats, and accumulation and half-life of radioactivity measured. In castrated rats in comparisons with sham-operated and castrated + T rats, serum T was absent, and body weight lower (P< 0.05 or 0.01), but adipocytes in retroperitoneal and mesenteric tissues became significantly heavier. Radioactivity (dpm/mg triglyceride) was higher, in retroperitoneal tissue at 4 hours, 7, 30 days, and in mesenteric tissue at 4 hours, and at 30 and 60 days after oral label administration (0.1 > p > 0.05 or P< 0.05), no differences were seen in epididymal or inguinal depots at 4 hours. When radioactivity was expressed per adipocyte, the castrated group showed significantly higher radioactivity when compared to sham and castrated + T groups at 7 and 30 days in retroperitoneal and at 60 days in mesenteric adipocytes (P< 0.05 or 0.01). Half life (T 1/2) of radioactivity was longer in mesenteric tissue in the castrated rats than the other two groups (sham group, 33 days ± 2; castrated group, 58 days ± 6; and castrated + T group, 39 days ± 3, P< 0.05), but there were no differences between groups in retroperitoneal adipose tissue. It was concluded that T exerts important, multiple effects on triglyceride storage and mobilization in adipose tissue, with regional differences between adipose tissues.     

Physiological Effects of Water-soluble Soybean Fiber in Rats

Four-week-old rats were fed on diets containing either no dietary fiber (DF) or a DF source (WSSF, ISF or cellulose) for 4 weeks. The DF level was adjusted to 5%. The WSSF diet contained 3% and 2%, respectively, of WSSF and cellulose. No rat in any group experienced diarrhea, and none of the experimental diets suppressed the growth of rats, the apparent absorption of major nutrients being almost 100%. However, the rate of degradation of DF during the digestive process was significantly different (p<0.05, cellulose, 23.6%; WSSF with cellulose, 64.5% (WSSF degradation only was 91.8%); and ISF, 77.6%). The plasma and liver lipid levels were within normal ranges, although the liver cholesterol level in those rats fed on WSSF and ISF was significantly lower (p<0.05) than in those fed on cellulose. The cecal organic acid contents were in the order of WSSF>ISF>cellulose>DF-free. Furthermore, WSSF was effective in shortening the gastrointestinal transit time. The results indicate that WSSF seems to have favorable effects on the intestinal functions.     

Effect of N,N'-Diphenyl-p-phenyl-enediamine (DPPD) on Serum Triglyceride and Lipoprotein Cholesterol in Rats

Ancepsenolide (1a-s) and the enantiomer (1a-r) were respectively synthesized from (S)- and (R)-2-[(R)-O-MEM-mandeloyloxy]propanal (3a-s and 3a-r) and diisopropyl hexadecanedioate (5). The analogs (1b, 2a and 2b) were synthesized by a similar method.     

人EGFR显性负性突变体对胃癌细胞体内成瘤及淋巴结转移的影响

为了研究人表皮生长因子显性负性突变体(dominant negative mutant of EGFR, dnEGFR)对胃癌细胞体内成瘤及淋巴结转移的影响,用目的质粒pEGFPN1 dnEGFR,空质粒载体pEGFP N1分别转染胃癌细胞NCI-N87.筛选出稳定转染株,实验共分3组：NCI-N87细胞未转染组（untreated NCI-N87,UN组）,NCI-N87细胞pEGFP-N1转染组（EN组）;NCI-N87细胞pEGFPN1-dnEGFR转染组（DN组）.将3组细胞接种于裸鼠右后足垫,6周后测量移植瘤大小及对应腹股沟转移淋巴结数目,HE染色验证,real-time PCR和Western 印迹检测3组细胞中AKT1、MAPK3 mRNA和蛋白的表达改变.结果发现,DN组移植瘤较UN、EN组明显缩小（P<0.05）,且右腹股沟转移淋巴结数目较UN、EN组减少（P<0.05）.DN组细胞中,AKT1、MAPK3 mRNA和蛋白水平较UN、EN组降低（P<0.05）.提示pEGFPN1-dnEGFR可抑制裸鼠体内胃癌细胞成瘤及淋巴结转移,AKT1及MAPK3信号通路可能参与其中.     

Lymphangiogenesis in vitro: Formation of lymphatic capillary-like channels from confluent monolayers of lymphatic endothelial cells

Summary Lymphatic endothelial cells grown long term in culture form lymphatic capillarylike tubes. Examination by light and transmission electron microscopy showed that these structures were closed loops composed of one to several cells connected by intercellular junction to form a luminal space. This first demonstration of lymphangiogenesis in confluent monolayer cultures of lymphatic endothelial cells (a) showed that collagen type I accelerated lymphatic capillary tube formation, whereas fibronectin and matrigel had no effect; b) provided a model to study lymphatic endothelial cell function and differentiation; and c) offered a possibility to distinguish differences between the process of lymphangiogenesis and angiogenesis by testing various factors and conditions that effect endothelial cell behavior.     

Effects of triacylglycerol and diacylglycerol oils on blood clearance, tissue uptake, and hepatic apolipoprotein B secretion in mice

Prior studies have suggested that FAs liberated in the small intestine from ingested 1,3-diacylglycerol (DAG) are inefficiently incorporated into triglyceride (TG) in enterocytes, with less chylomicron TG entering the circulation postprandially. We found less TG, but more monacylglyerol and DAG, with similar total acylglycerol in newly secreted chylomicrons after oral DAG or triacylglycerol (TAG). However, clearance of DAG-chylomicrons was more rapid than that of TAG-chylomicrons; this was associated with more efficient in vitro LPL-mediated lipolysis of DAG-derived chylomicrons. Intravenously infused DAG was also cleared faster than TAG in normal mice, via both LPL-mediated lipolysis and apolipoprotein E (apoE)-dependent hepatic uptake. Infusions of TAG, but not DAG, increased plasma TG levels. Greater delivery of DAG-derived FA to the liver during infusion of DAG led to greater TG secretion versus TAG; this allowed the maintenance of similar hepatic TG levels after DAG and TAG infusions. Of note, apoB secretion was similar after DAG versus TAG, indicating the assembly of larger very low density lipoproteins after DAG. In conclusion, reduced plasma TG levels, after oral or intravenous DAG, result from more efficient clearance of DAG by both LPL lipolysis and apoE-mediated hepatic endocytosis. DAG emulsions may by useful for intravenous nutrition in people with preexisting hypertriglyceridemia.     

Survival of Rats Undergoing Continuous Bile Drainage Depends on Maintenance of Circadian Rhythm of Bile Secretion

It is very difficult to collect bile secretions from animals for extended periods of time. We compared the use of saline or water as drinking fluids to sustain the animals, which were being continuously drained of bile. Complete bile drainage was performed in 16 male Wistar rats by surgical intervention. After surgery, 8 rats were given tap water, and the other 8 were given normal saline for water. The rats that received water rapidly lost weight after bile drainage, and all died within 8 days after the operation. In contrast, all rats that drank saline maintained their body weight and survived 14 days or longer after surgery. Serum biochemistry of the rats with water intake on the third day after bile drainage revealed hyponatremia, hypochloremia, and acute renal failure resulting in hyperkalemia. In contrast, electrolyte balance and renal function were normal in the rats with saline intake, and bile was secreted continuously with a circadian rhythm. These results clearly demonstrate that saline as drinking water is essential to the replacement of lost fluids and loss of electrolytes due to bile drainage. Further, saline proved efficacious for sustaining experimental animals undergoing continuous bile collection.     

Hypersaline stress induces the turnover of phosphatidylcholine and results in the synthesis of the renal osmoprotectant glycerophosphocholine in Saccharomyces cerevisiae

The role of phosphatidylcholine turnover during hypersaline stress is investigated in Saccharomyces cerevisiae. In the wild-type strain, 2180-1A hypersaline stress induced the rapid turnover of phosphatidylcholine, a major membrane lipid. Yeast cells were grown in the presence of [14C]-choline to label phosphatidylcholine. Upon shifting the cells to medium with 0.8 M NaCl, phosphatidylcholine levels were diminished by c. 30% within 20 min to yield glycerophosphocholine, a methylamine osmoprotectant that has been previously identified in renal cells. High-performance liquid chromatography studies showed that osmotically mediated glycerophosphocholine production was enhanced if 10 mM choline was added as a supplement to synthetic dextrose medium with 1.6 M NaCl, but glycine betaine was not detected. Enhanced glycerophosphocholine production also correlated with improved growth in media containing 1.6 M NaCl and choline. Enhanced growth is specific to methylamines: salt-stressed cells supplemented with 10 mM choline or glycine betaine showed enhanced growth relative to unsupplemented control cultures, but other additives had no effect on growth or adversely affected it. Nutritional effects are ruled out because yeast cannot use choline or glycine betaine as carbon or nitrogen sources in normal or high-salt medium. Finally, enhanced growth in hypersaline media with choline or glycine betaine is dependent on the choline permease Hnm1. These results in yeast highlight a similarity with mammalian renal cells, namely that phosphatidylcholine turnover contributes to osmotic adaptation via synthesis of the osmoprotectant glycerophosphocholine.     

Effect of Bile Acids on the Intestinal Absorption of Endotoxin in Rats

The absorption of tritium-labeled Escherichia coli O89 Westphal-type endotoxin from the peritoneal cavity of rats was diminished by bile by 23% and by sodium deoxycholate by 47%, respectively. Practically, there is no endotoxin absorption from the intestinal tract of normal rats. The bile duct of rats was chronically cannulated for experimental purposes. A significant amount of perorally administered endotoxin absorbed from the intestinal canal into the blood in the rats treated thus. Absorption was demonstrated by the lethal effect of endotoxin on rats previously hypersensitized by lead acetate, and by the radioactivities found in the blood samples. The intestinal absorption of endotoxin in rats, rendered bile-deficient, may be prevented by sodium deoxycholate. Supported by their experimental findings, we emphasize the important role of bile acids in the defense mechanism of the macroorganism against bacterial endotoxins.