The effects of fish or fish oil on the omega‐3 index

Aim: To compare the impact of recommended intakes of fish and fish oil supplements on the omega‐3 index and selected risk factors in patients with coronary heart disease. Methods: A 12‐week crossover intervention comparing the impact of 1 g/day of long‐chain omega‐3 polyunsaturated fatty acids from fresh salmon or fish oil capsules on the omega‐3 index and cardiovascular risk factors. Eleven patients with coronary heart disease, recruited from St. Vincent's Hospital, Melbourne, participated in the study. Results: A decrease in blood pressure (>5 mmHg; P < 0.05) was observed after the fish but not the fish oil. The change in waist to hip ratio also favoured the fish intervention. Resting heart rate fell by a similar amount on both interventions, and the omega‐3 index increased significantly on both; from 6% to 7–8% (P < 0.01). Blood lipids did not improve on either arm. Conclusions: In Australians with coronary heart disease, 1 g/day of long‐chain omega‐3 polyunsaturated fatty acid from fish or supplements over 12 weeks was effective in increasing the omega‐3 index. Fish intake may have additional cardiovascular benefits beyond the omega‐3 effect as evidenced by the substantial blood pressure reduction following the fish arm warranting examination in a larger study.     

Use of microencapsulated fish oil as a means of increasing n-3 polyunsaturated fatty acid intake

Background: The successful incorporation of fish oil into foods may provide a means of increasing intakes of n-3 polyunsaturated fatty acids (n-3 PUFA). The aim of the present study was to evaluate the bioavailability of n-3 PUFA in microencapsulatd fish oil compared with a fish oil capsule. Methods: Twenty-eight healthy volunteers were recruited to take part in this randomized controlled trial. Volunteers were supplemented with 0.9 g n-3 PUFA daily for 4 weeks, delivered either as microencapsulated fish oil in a milkshake or as a fish oil capsule. Plasma fatty acid composition and plasma total cholesterol levels were measured at baseline and after supplementation. In addition, volunteers completed a questionnaire on fish consumption, use of supplements and exercise. Results: Responses to the questionnaire indicated that the males who took part in this study took more physical exercise, consumed less fish and were less likely than the females to take supplements. Plasma n-3 PUFA concentrations were raised significantly and by a similar level by both fish oil supplements. Furthermore, no significant difference was observed in plasma n-3 PUFA concentrations following supplementation with either form of fish oil. Plasma total cholesterol levels were not significantly altered by n-3 PUFA supplementation in either group. The results of this study indicated that there was no difference in the bioavailability of n-3 PUFA given as microencapsulated fish oil compared with n-3 PUFA delivered as a fish oil capsule. Fortification of foodstuffs with microencapsulated fish oil therefore offers the potential to increase intakes of n-3 PUFA in line with current recommendations.     

Rapid Incorporation of ω‐3 Fatty Acids Into Colonic Tissue After Oral Supplementation in Patients With Colorectal Cancer

Background: The purpose of the study was to examine whether a preoperative supplement with ω‐3 fatty acids (FAs) leads to their incorporation into colonic tissue in patients scheduled for colorectal cancer surgery. This would be of interest because ω‐3 FAs have potential beneficial (local) immunological effects that might benefit these patients. Methods: In a randomized, double‐blind, prospective, placebo‐controlled, single‐center intervention trial, patients referred for elective colorectal cancer surgery received either an ω‐3 FA–enriched oral nutrition supplement (ONS) (200 mL twice daily) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for 7 days before surgery. Tissue samples from healthy colonic tissue (mucosa and muscular layer) were obtained during surgery, and tissue fatty acid composition was analyzed by gas chromatography. Results: EPA was significantly higher in colonic mucosa (P = .001) and in the colonic muscular layer (P = .004) in the ω‐3 FA group compared with controls. Patients in the ω‐3 FA group also tended to have higher docosapentaenoic acid and DHA levels in colonic tissue. Conclusions: EPA is incorporated rapidly into colonic mucosa and colonic muscular layer in patients given 3 g of ω‐3 FA daily for 7 days before surgery for colorectal cancer. This may lead to potential beneficially effects on (local) immune function, which might benefit these patients.     

Enrichment of n‐3 fatty acids and conjugated linoleic acid in beef: ProSafeBeef

ProSafeBeef is a 5‐year integrated project funded by the European Commission under the sixth Framework Programme. The overall aim is to advance beef safety and quality across Europe and the work programme spans seven integrated “pillars”. Pillar 3 is concerned with producing safe beef and beef products with enhanced nutritional and eating quality characteristics. A particular focus is on the development of strategies to enhance the concentrations in beef of those fatty acids considered to be of benefit to human health, without causing a detrimental effect on the appearance, shelf‐life or eating quality of the beef. There is accumulating evidence of the importance of long‐chain n‐3 (omega‐3) polyunsaturated fatty acids (PUFAs) for human health and disease prevention, and also evidence from experimental studies that has shown anticarcinogenic, antiatherogenic, and anti‐obesity effects of two isomers of conjugated linoleic acid (CLA). Based on this evidence, the major focus of research efforts to improve the nutritional value of beef has been on increasing the concentration of the n‐3 PUFAs and CLA. Considerable progress has been made within pillar 3 of ProSafeBeef to meet this aim, primarily by manipulating the diet of cattle. Fundamental information on ruminal lipid metabolism and on the control and/or prevention of ruminal hydrogenation of dietary lipids arising from research within ProSafeBeef will facilitate the production of beef with a ‘healthier’ fatty acid profile. Moreover, strategies will be defined for industry on how to optimise nutritional and sensory properties and oxidative quality of beef products, by combining the nutritional enhancement made in the live animal together with target levels of functional ingredients to be added during processing.     

Genetically modified plants are an alternative to oily fish for providing n‐3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project

The n‐3 polyunsaturated fatty acids (PUFA) present primarily in oily fish, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important components of cell membranes and that are needed for normal development and cell function. Humans have very limited capacity for EPA and DHA synthesis from α‐linolenic acid and so they must be obtained pre‐formed from the diet. However, perceived unpalatability of oily fish and fish oil concerns about contamination with environmental pollutants, dietary choices that exclude fish and animal products, and price limit the effectiveness of recommendations for EPA and DHA intakes. Moreover, marine sources of EPA and DHA are diminishing in the face of increasing demands. Therefore, an alternative source of EPA and DHA is needed that is broadly acceptable, can be upscaled and is sustainable. This review discusses these challenges and, using findings from recent nutritional trials, explains how they may be overcome by seed oils from transgenic plants engineered to produce EPA and DHA. Trials in healthy men and women assessed the acute uptake and appearance in blood over 8 hours of EPA and DHA from transgenic Camelina sativa compared to fish oil, and the incorporation of these PUFA into blood lipids after dietary supplementation. The findings showed that postprandial EPA and DHA incorporation into blood lipids and accumulation in plasma lipids after dietary supplementation was as good as that achieved with fish oil. The oil derived from this transgenic plant was well tolerated. This review also discusses the implications for human nutrition, marine ecology and agriculture.     

Design, synthesis and anti-tubercular evaluation of new 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives. Part 1

A series of 2-acylated and 2-alkylated amino-5-(4-(benzyloxy)phenyl)thiophene-3-carboxylic acid derivatives were synthesized and evaluated for anti-tubercular activity. Among these compounds, 10d, 15, 12h and 12k inhibited Mycobacterium tuberculosis (Mtb) growth with MIC values between 1.9 and 7.7 μM and low toxicity against VERO cells. The four compounds were also tested against multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) clinical strains, which were found to show moderate activity. In addition, molecular docking simulation was performed to position compounds 10d, 15, 12h and 12k into mtFabH active site to predict the probable binding mode. These studies thus suggest that the designed 2-amino-5-phenylthiophene-3-carboxylic acid scaffold may serve as new promising template for further elaboration as anti-TB drugs.     

Linseed oil and marine oil as sources of (n-3) fatty acids in rat heart

Rats were fed a fat mixture containing a low level of (n-3) polyunsaturated fatty acids, linseed oil or marine oil. The arachidonic acid in cardiac tissue was depressed by (n-3) linolenic acid and further depressed by (n-3) polyunsaturated fatty acids of marine oil. Docosahexaenoic acid was the principal replacement for arachidonic acid.     

Effects of Perioperative Supplementation with Omega-3 Fatty Acids on Leukotriene B4 and Leukotriene B5 Production by Stimulated Neutrophils in Patients with Colorectal Cancer: A Randomized,Placebo-Controlled Intervention Trial

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B₅ (LTB₅) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B₄ (LTB₄) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB₄ values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.     

Administration of an Intravenous Fat Emulsion Enriched with Medium-Chain Triglyceride/ω-3 Fatty Acids is Beneficial Towards Anti-Inflammatory Related Fatty Acid Profile in Preterm Neonates: A Randomized,Double-Blind Clinical Trial

Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age < 32 weeks, birth weight < 1500 g) were assigned to receive either MCT/ω-3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time; the MCT/ω-3 PUFA-IVFE group showed higher ω-3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower ω-6/ω-3 PUFAs ratio (p = 0.001) and ω-6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/ω-3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/ω-3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.     

Synthesis and aldose reductase inhibitory activity of a new series of 5-[[2-(ω-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives

Anew series of 5-[[2-(ω-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives was synthesized and evaluated for their potency as aldose reductase inhibitors (ARIs). Their activities were examined in terms of their inhibitory effect on rat lens aldose reductase in vitro and in terms of the preventive effect on sorbitol accumulation in the sciatic nerve of streptozotocin (STZ)-induced diabetic rats in vivo. Of these compounds, some of the naphthylmethylene thiazolidine derivatives were comparable to Zenarestat in the inhibitory potency in vitro and in vivo. In particular, compound 30 was 1.5 times more potent than Zenarestat in the in vivo activity, and had an adequate potency for clinical development.     

Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3’s (RRIPP-3) Study

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.     

Synthesis, anti-hypertensive and β-adrenoreceptor antagonist activities of 3-[4-[3-(4-aryl-1-piperazinyl)-isopropanoloxy]-phenyl]-4(3H quinazolones

The synthesis of seven 2-substituted 3-[4-[3-(4-aryl-1-piperazinyl)-isopropanoloxy]-phenyl]-4(3H)quinazolones is described. Pharmacological tests showed that some of the synthesized compounds (3a–c and 3e) possessed pronounced and sustained hypotensive effects, as tested in anesthetized normotensive rabbits, adrenoreceptor antagonist properties with respect to the α- and β-receptors and central nervous system depressant effect.     

Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: synthesis, molecular docking and structure-activity relationship analysis of 3-aryl-4-arylaminofuran-2(5H)-ones

Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one (35) was the most active with IC₅₀ of 0.09 ± 0.02 μM. The structure-activity relationship revealed that introduction of chlorine atoms at both meta positions of aniline moiety significantly increased the enzyme inhibitory activity. The results of antibacterial assay revealed that the tested compounds showed good activity against Gram-positive bacteria, with 35 being the most potent with MIC₅₀ of 0.06 μg/mL against Staphylococcus aureus ATCC 25923. Molecular docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also performed. The inhibitor snugly fitting the active site may well explain its excellent inhibitory activity.     

甲状腺激素干扰物二巯基敌枯双生物作用的实验研究I观察指标的探讨

目的 :研究二巯基敌枯双所致甲状腺的形态改变 ,探讨二巯基敌枯双是否属甲状腺激素干扰物。方法 :Wistar大鼠 60只 ,随机分为正常对照组和实验组。正常对照组给予溶剂二甲基亚砜 ,实验组给予二巯基敌枯双二甲基亚砜溶液 ,剂量为 5 0 mg/kg体重。于实验组的给药第 5 d、第 10 d和第 2 0 d,分别放血处死两组动物。测定血清中 T4,TSH的浓度 ;取动物甲状腺称重 ,常规 HE染色 ,光镜下观察。结果 :各时间点实验组血清 T4,TSH的浓度和对照组相比无显著变化 (P>0 .0 5 ) ;实验组动物的甲状腺脏器系数显著高于对照组 ,(P<0 .0 5 ) ;组织学观察到实验组在第 5 d甲状腺滤泡上皮增生 ,有的滤泡出现局灶性增生斑块 ,第 10 d复层化的甲状腺滤泡上皮细胞继续增生 ,并向间质突出 ,形成实心芽 ,第 2 0 d实心芽向继发滤泡分化 ,出现了滤泡腔。结论 :二巯基敌枯双引起甲状腺增生 ,提示具有甲状腺激素干扰物的可能性     

右旋反式氯丙炔菊酯的合成及其药效研究

目的研制一种新型卫生杀虫剂--右旋反式氯丙炔菊酯.方法采用右旋反式DV菊酸与S-炔丙醇酮为原料,经化学拆分、酰氯化及酯化等反应合成右旋反式氯丙炔菊酯,并采用GB/T13917.1-1992和GB/T17322.2-1998标准方法测定了对致倦库蚊和德国小蠊的药效.结果右旋反式氯丙炔菊酯对致倦库蚊及德国小蠊的KT50值分别为8.5 min和3.46min.结论右旋反式氯丙炔菊酯对蚊虫和蟑螂等害虫具有良好的击倒作用和杀灭能力,可以作为一种新型卫生杀虫剂加以推广和应用.     

Synthesis and biological evaluation of a novel human stem/progenitor cells proliferation activator: 4-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl) thiosemicarbazide (Stemazole)

Stem/progenitor cells are crucial for cell-based therapy and regenerative medicine, and their application in clinical and basic research requires a large supply of cells. To identify effective stem/progenitor cell proliferation activators, we synthesised a series of new 4-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl) thiosemicarbazide (named Stemazole) derivatives. Preliminary evaluation of the structure-activity relationship (SAR) and the biological activities of the compounds were determined with a luminescent cell viability assay. The identified leading compound, Stemazole, exhibited remarkable proliferation-promoting activity in human hippocampal stem/progenitor cells (HSCs) in a time-dependent and concentration-dependent manner. The proliferation-promoting activity of Stemazole was further confirmed against a panel of human stem/progenitor cells derived from each of the three blastoderm layers. In conclusion, Stemazole is a novel activator of stem cells proliferation.