Effects of omega-3 fatty acid supplementation on tumor-bearing rats

BACKGROUND: Dietary fish oil (rich in omega-3 fatty acids: eicosapentaenoic acid and docosahexaenoic acid) suppresses synthesis and activity of proinflammatory cytokines that induce anorexia. We hypothesized that dietary fish oil reverses the feeding pattern of tumor anorexia, increasing food intake and retarding tumor growth. STUDY DESIGN: Thirty-two Fischer rats were placed in Automated Eater Meter cages and randomly divided into four groups: tumor bearing (TB) rats eating normal chow diet (TB-Chow); TB rats eating chow diet supplemented with omega-3 fatty acids (TB-omega-3FA); Controls, non-tumor bearing (NTB) rats eating normal chow (NTB-Chow); and NTB rats with omega-3 fatty acid supplementation (NTB-omega-3FA). Doses of 10(6) methylcholanthrene (MCA) sarcoma cells were subcutaneously injected in TB rats. Daily food intake, meal size (MZ), meal number (MN), body weight, and tumor volume were measured, and rats were euthanized at onset of anorexia. Data were statistically analyzed using analyses of variance (ANOVA) and t-tests. Data are reported as mean +/- SE. RESULTS: Tumor appeared significantly earlier in TB-Chow than in TB-omega-3FA rats (7.5 +/- 0.3 days versus 11.6 +/- 0.8 days, p < 0.05). Daily food intake declined significantly in TB-Chow versus TB-omega-3FA rats 18 days after tumor inoculation and, at onset of anorexia, was 9.41 +/- 1.77 g/day versus 13.32 +/- 0.81 g/day, p < 0.05. Food intake decreased initially by decrease in meal number (at day 15) followed by a decrease in meal size (at day 18). At onset of anorexia, meal size and meal number were significantly decreased in TB-Chow versus TB-omega-3FA rats (0.75 +/- 0.067 g/meal versus 1.05 +/- 0.08 g/meal, p < 0.05) and (9.5 +/- 1.32 versus 12.79 +/- 0.93 meals/day, p < 0.05), respectively. Tumor volume was significantly smaller in TB-omega-3FA versus TB-Chow rats (7.6 +/- 0.6 cm(3) versus 16.5 +/- 1.0 cm(3), p < 0.05), as was tumor weight (7.5 +/- 2.2 g versus 18.1 +/- 1.6 g, p < 0.05). CONCLUSIONS: In TB rats, omega-3FA improved food intake; restored normal eating pattern, delayed onset of anorexia, tumor appearance, and growth; and prevented body weight loss. Supplementation of omega-3 fatty acids has therapeutic potential in cancer anorexia.     

大鼠肝移植术后输注ω-3多不饱和脂肪酸对T淋巴细胞的影响

目的 探讨大鼠肝移植术后应用ω-3多不饱和脂肪酸对移植肝脏功能、受体T淋巴细胞和急性排斥反应的影响.方法 行BN(RTln)大鼠到Lewis(RT11)二袖套法大鼠肝移植18例,术后颈内静脉插管,微量泵匀速输注液体.生理盐水NS组(n=6)输注生理盐水,肠外营养PN组(n=6)输注营养液,脂肪酸OM组(n=6)输注营养液+ω-3脂肪乳.术后第7天处死大鼠,留取肝组织标本病理检查,取血清检测生化指标.取抗凝血0.5 ml,流式细胞仪检测CD4+、CD8+、CD4+CD25+T细胞和CD8+CD28-T细胞.结果 大鼠肝移植术后输注ω-3脂肪酸的OM组CD4+、CD8+、CD4+CD25+和CD8+CD28-T细胞下降,与Ns组比较差异有统计学意义(t=4.28,P<0.01;t=2.63,P<0.05;t=2.59,P<0.05;t=8.86,P<0.01).OM组CD4+、CD8+、CD4+CD25+和CD8+CD28-T细胞下降,与PN组比较差异有统计学意义(分别t=8.06,t=3.57,t=5.35.t=7.98,均P<0.01).OM组CD4+/CD8+比值下降,与NS组和PN组比较差异有统计学意义(分别t=2.41,t=8.74,均P<0.01).病理学检查移植肝排斥反应强度(rejection activity index,RAI)评分,NS组为7.17±0.98,PN组为6.17±0.75,OM组为4.33±0.52,OM组与NS组、PN组比较排斥反应减轻(分别t=6.25,t=4.92,均P<0.01).结论 静脉输注ω-3多不饱和脂肪酸可以抑制T淋巴细胞,显著降低CD4+辅助性T细胞比例,减轻排斥反应.抑制性T细胞和调节性T细胞与ω-3脂肪酸减轻大鼠肝移植排斥反应的效应无关.     

Arteriovenous grafts for vascular access in haemodialysis.

The outcome of 68 arteriovenous grafts placed in 46 patients requiring haemodialysis was studied over a period of 3.5 years. The biological grafts included autogenous saphenous vein, modified bovine carotid artery and human umbilical cord vein allograft, whereas the synthetic grafts comprised Sparks Dacron mandril, expanded reinforced polytetrafluoroethylene and knitted Dacron velour. These subcutaneous grafts were arranged as looped or straight configurations in the forearm or thigh. Of 59 grafts evaluated in patients with end-stage renal failure, only 48 per cent of the forearm grafts performed well, compared with 85 per cent of the thigh grafts. Although only 38 per cent of the looped grafts were successful, 78 per cent of the straight grafts functioned satisfactorily. Synthetic grafts suffered less serious complications than the commercial biological grafts.     

Assessment of stenosis in vascular access grafts

The major complication that occurs with grafts used as vascular access for hemodialysis, is stenosis at the venous anastomosis or in the draining vein. 75% area stenosis is considered significant as thrombotic occlusion may occur. The aim of this experimental study was to evaluate invasive and noninvasive indices to detect significant stenoses in a vascular access graft. A compliant underarm loop graft in vitro model was built and studied with 50, 65, 80, and 90% stenosis at flow rates of 500, 1000, and 1500 mL/min. Flow in the system was pulsatile. Velocity was measured with ultrasound Doppler and the pressure was measured invasively. The resistance index (RI), p(venous line)/MAP, and the newly introduced pressure ratio (PR) were calculated and compared. A stenosis can be suspected when a high frequency ultrasound velocity signal develops at the venous anastomosis. RI > 1 confirms a very severe stenosis (90%). The parameter PR < 8% confirms significant stenoses showing its clinical relevancy.     

Effects of omega-3 fatty acids on acute necrotizing pancreatitis in rats

The aim of this study was to investigate the influence of omega-3 fatty acids (omega3FA) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increases in mortality rate, intestinal permeability, bacterial infection in pancreas and extrapancreatic organs, and serum activity of urea and amylase, alanine transferase (ALT), interleukin (IL)-6, tumor necrotizing factor-alpha (TNF-alpha), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and a considerable decrease of concentrations of calcium, protein and albumin. The use of omega3FA reduced mortality, phenol sulfophthalein excretion in urine, bacterial infection in pancreas, liver, spleen, MPO and MDA levels in pancreatic and lung tissue, LDH level in BAL fluid and serum IL-6 and TNF-alpha values. Serum triglyceride increased only in the omega3FA groups. Serum amylase, ALT, calcium, urea, protein, IL-1, and degree of pancreatic damage indicated no difference between the pancreatitis groups. Increased intestinal permeability and cytokine levels, and free radical damage play an important role during the course of acute pancreatitis. The treatment with omega3FA improves these effects. omega3FA may be useful in the treatment during ANP in rats. Therefore, it can be beneficial in patients with pancreatitis.     

ω-3多不饱和脂肪酸对改善荷瘤大鼠营养状况的作用

目的:通过建立大鼠肿瘤动物模型,比较含ω-3多不饱和脂肪酸(PUFA)和ω-6 PUFA的不同肠外营养支持对大鼠肿瘤及机体营养状况的影响.方法:实验动物随机分为4组,对其中3组用Walker 256肉瘤细胞株建立肿瘤动物模型,通过颈静脉置管分别对其中2组实施含ω-3 PUFA及ω-6 PUFA的营养支持.最终测定血清IL-6、TNF-α及白蛋白浓度,使用Western印迹法测定Atrogin-1基因蛋白的表达量.研究期间隔日记录大鼠体重改变.结果:ω-3 PUFA组大鼠的体重丢失少于荷瘤大鼠组[(-21.30±2.95)g比(-26.80±1.03)g;P=0.009)].ω-3 PUFA组大鼠的血清IL-6浓度明显低于ω-6 PUFA组[(71.63±39.50)pg/mL比(141.72±98.32)pg/mL;P=0.002].ω-3 PUFA组大鼠的血清TNF-α浓度低于ω-6 PUFA组[(131.67±22.10)pg/mL比(167.26±37.98)pg/mL;P=0.007].ω-3 PUFA组大鼠Atrogin-1蛋白质的表达低于ω-6 PUFA组.结论:①运用ω-3 PUFA干预,可降低荷瘤大鼠的血清IL-6、TNF-α浓度;②运用ω-3 PUFA干预,可改善荷瘤大鼠体重、减轻荷瘤大鼠的体重丢失;③运用ω-3 PUFA干预,可使荷瘤大鼠的Atrogin-1基因蛋白质表达减少,改善机体的骨骼肌蛋白消耗.     

Homocysteine and vascular access thrombosis in hemodialysis patients

BACKGROUND: Vascular access remains the Achilles' heel of successful hemodialysis, and thrombosis is the leading cause of vascular access failure. Hyperhomocystinemia is common in hemodialysis patients and is associated with venous and arterial thrombosis in patients without end-stage renal disease. SUBJECTS AND METHODS: In the study, 65 hemodialysis patients with native arteriovenous fistula were included. Two groups of patients were defined: group A including 45 patients with their vascular access either never or only once thrombosed, and group B including 20 patients with two or more thromboses of their vascular access. We determined serum concentrations of total homocysteine (immunoassay, Abbott) in our patients. RESULTS: In 63 (96.9%) patients, hyperhomocystinemia was presented. There was no statistically significant difference between group A and B regarding age, gender and duration of hemodialysis treatment. Total homocysteine concentrations were higher in group A (42.1 +/- 18.6 micromol/l) than in group B (36.1 +/- 18.1 micromol/l) patients but the difference was small and not statistically significant. CONCLUSION: We found no significant differences in total homocysteine concentrations between group A (thrombosis non-prone) and group B (thrombosis prone) patients. Our results suggest that thrombosis of native arteriovenous fistulas may not be caused by hyperhomocystinemia in these patients.     

Forecasting thrombosis of vascular access with Doppler color flow imaging.

A noninvasive technique, color Doppler flow imaging, was used to study the predictive value for future episodes of thrombosis in vascular access (polytetrafluoroethylene [PTFE] grafts and radial-cephalic fistulae) in a series of chronic hemodialysis patients. Patients with grafts were classified into three groups based on maximum constriction of the vascular access diameter: narrowing of greater than 50% (group I), narrowing of 30% to 50% (group II), and no narrowing or narrowing less than 30% (group III). More than half of the patients in group I suffered vascular access thrombosis within 6 months, while only 9% to 13% of patients in groups II and III had episodes of thrombosis during the same time interval. Decreased access volume flow (AVF) also correlated with episodes of thrombosis in these patients. No correlation could be demonstrated between recirculation and future thrombosis. No patient with a fistula had narrowing greater than 30% and none had vascular access thrombosis during the 6-month follow-up.     

Transluminal angioplasty of venous stenoses in polytetrafluoroethylene vascular access grafts

Since 1984, percutaneous transluminal angioplasty (PTA) utilizing high pressure balloon catheters has been used as an initial approach to restore patency of PTFE (polytetrafluoroethylene, GORE-TEX) hemodialysis vascular access grafts. Seventeen stenotic lesions detected by fistulogram underwent elective PTA. Twelve of these lesions were detected after thrombectomy and five were detected because of increased venous pressures during dialysis. Fourteen attempts at PTA were completely successful in restoring functional patency to the vascular graft. Three attempts were unsuccessful; two of these three grafts were subsequently repaired surgically. Venous stenoses that extended far greater than 6 cm were not considered for PTA. We conclude that PTA is a technique of promise in the non-surgical salvage of failing PTFE grafts. PTA can prolong the useful life of PTFE vascular access grafts and can be performed on an outpatient basis, eliminating the hospitalization that is usually required for surgical revision.     

Randomization of autogenous vein and polytetrafluorethylene grafts in femoral-distal reconstruction

A randomized, prospective, controlled study comparing autogenous saphenous vein and polytetrafluoroethylene (PTFE) grafts in infrainguinal arterial reconstructions has been initiated in three different institutions. A total of 446 operative procedures were divided into six groups, depending on the site of distal bypass insertion into the popliteal or an infrapopliteal artery and on whether the patient received a randomized vein or PTFE graft or an obligatory PTFE graft. The randomized saphenous vein graft patency to infrapopliteal arteries was significantly better (P less than 0.005) at 2 1/2 years than the patency of randomized or obligatory PTFE grafts to the same level. No significant differences between randomized vein grafts and randomized or obligatory PTFE grafts in the femoropopliteal position could be demonstrated up to 2 1/2 years, either above or below the knee. The need for such a study and the limitations of this preliminary report are discussed. The requirement for longer observation of greater numbers of cases is stressed. A current plan for usage of the PTFE graft in the lower extremity is presented.     

Plasma fatty acid composition in continuous ambulatory peritoneal dialysis patients: an increased omega-6/omega-3 ratio and deficiency of essential fatty acids

Patients with end-stage renal disease, including those treated with peritoneal dialysis, have a high risk for death, particularly from cardiovascular causes. Plasma fatty acid (FA) composition is used as an indicator of disease risk, because its alteration has been related to metabolic disease and cardiovascular disease. For this purpose, we have measured plasma FA composition in continuous ambulatory peritoneal dialysis (CAPD) patients and compared them with those of healthy subjects. This study was performed on 51 (21 M, 30 F) CAPD patients at least 6 months under dialysis, aged 20-75 years (mean 47.81 ± 11.8 years) and 45 (25 M, 20 F) healthy control subjects aged 20-60 years (mean 38.62 ± 12.9 years). Plasma 10-cis-pentadecanoic acid, 10-cis-heptadecanoic acid, heneicosanoic acid, tricosanoic acid, nervonic acid, saturated fatty acid, and monounsaturated FA levels and delta 9 desaturase activity were significantly higher whereas linoleic acid, linolenic acid, 11,14-eicosedienoic acid, arachidonic acid, docosahexaenoic acid, and omega-3 FA levels were significantly lower in the CAPD group than those in the healthy group. Our results show that there are FA abnormalities and especially a depletion in essential FA levels and a high level of omega-6/omega-3 ratio in CAPD patients, the underlying mechanism of which is not known and needs to be investigated. Therefore, we believe that essential FA supplementation should be encouraged for CAPD patients.     

Omega-3 fatty acid supplementation in primary nephrotic syndrome: effects on plasma lipids and coagulopathy.

The effect of fish oil dietary supplementation on the dyslipidemia and coagulopathy of seven patients with nephrotic syndrome and hypoalbuminemia due to primary kidney disease was studied. Plasma lipids, platelet aggregation studies, simplate bleeding time, and fibrinogen levels were determined before and after 6 wk of treatment with fish oil (15 g/day of MaxEPA; 2.7 g of eicosapentenoic acid (EPA) and 1.8 g of docosahexenoic acid. Urea kinetics were determined from urine-urea concentration, urinary proteina, and urine volume. A 3-day dietary intake record was obtained from each patient before and after 6 wk of fish oil supplementation. There was no significant dietary change in protein, fat, or carbohydrate intake over the time period of the study. At study end, total triglycerides decreased from 2.98 +/- 1.31 to 2.18 +/- 1.14 mmol/L (P = 0.002), and very low-density lipoprotein-triglycerides decreased from 2.35 +/- 1.34 to 1.28 +/- 1.07 mmol/L (P = 0.01). Low-density lipoprotein (LDL) cholesterol increased from 5.18 +/- 1.74 to 7.35 +/- 2.83 mmol/L (P = 0.005). No significant changes occurred in bleeding time, platelet count, hematocrit, red blood cell flexibility, or whole blood viscosity. Platelet aggregation responses to collagen and arachidonic acid were consistently reduced after treatment, but there was no change in platelet response to ADP. The platelet membrane phospolipids showed a significantly increased incorporation of EPA after the fish oil diet (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

A new technique for measuring blood flow in polytetrafluorethylene grafts for hemodialysis.

A method has been described for the measurement of blood flow in non branching grafts using the isotope dilution principle. The technique is simple, reproducible and consistent and can be performed in less than ten minutes.