Free fatty acids exert a greater effect on ocular and skin blood flow than triglycerides in healthy subjects

BACKGROUND: Free fatty acids (FFAs) and triglycerides (TGs) can cause vascular dysfunction and arteriosclerosis. Acute elevation of plasma FFA and TG concentration strongly increase ocular and skin blood flow. This study was designed to discriminate whether FFA or TG independently induce hyperperfusion by measuring regional and systemic haemodynamics. METHODS: In a balanced, randomized, placebo-controlled, double-blind, three-way, crossover study nine healthy subjects received either Intralipid (Pharmacia and Upjohn, Vienna, Austria) with heparin, Intralipid alone or placebo control. Pulsatile choroidal blood flow was measured with laser interferometry, retinal blood flow and retinal red blood cell velocity with laser Doppler velocimetry, and skin blood flow with laser Doppler flowmetry during an euglycaemic insulin clamp. RESULTS: A sevenfold increase of FFA during Intralipid/heparin infusion was paralleled by enhanced choriodal, retinal, and skin blood flow by 17 +/- 4%, 26 +/- 5% (P < 0.001), and 47 +/- 19% (P = 0.03) from baseline, respectively. In contrast, a mere threefold increase of FFA by infusion of Intralipid alone did not affect outcome parameters, despite the presence of plasma TG levels of 250-700 mg dL(-1); similar to those obtained during combined Intralipid/heparin infusion. Systemic haemodynamics were not affected by drug infusion. CONCLUSIONS: Present findings demonstrate a concentration-dependent increase in ocular and skin blood flow by FFA independently of elevated TG plasma concentrations. As vasodilation of resistance vessels occur rapidly, FFA may play a role in the development of continued regional hyperperfusion and deteriorate microvascular function.     

Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development

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Clinical outcome of immunonutrition in a heterogeneous intensive care population

Objective To study the effect of a high-protein enteral formula enriched with arginine, glutamine, and antioxidants and containing 3 fatty acids and a mixture of fibers, on the clinical outcome of a heterogeneous intensive care (ICU) population.Design and setting A randomized, prospective, double blind, controlled, two-center clinical trial in two intensive care units in The Netherlands.Patients and participants A total of 597 adult ICU patients expected to require enteral tube feeding for more than 2 days were randomized to receive immunonutrition or an isocaloric control formula. Interventions Patients received either the immunonutrition or the control feed.Measurements and results Intention-to-treat and per-protocol analyses showed no statistically significant difference in clinical outcome parameters between the two groups. Results of the intention-to-treat analysis in control vs. immunonutrition were: median ICU length of stay in days, 8.0 (IQR 5.0–16.0) vs. 7.0 (4.0–14.0); median hospital length of stay in days, 20.0 (IQR 10.0–34.0) vs. 20.0 (10.0–35.0); median days of ventilation, 6.0 (IQR 3.0–12.0) vs. 6.0 (IQR 3.0–12.0); ICU mortality, 26.8% vs. 28.2%; in-hospital mortality, 36.4% vs. 38.5%; infectious complications, 41.7% vs. 43.0%Conclusions The results of this largest randomized, controlled trial found that in the general ICU population immunonutrition has no beneficial effect on clinical outcome parameters. These results are consistent with the literature that is currently available.This revised version was published online in February 2005 with corrections to the heading of a subsection of the Results (A priori subgroup analyses).     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.     

Growth hormone suppression and glutamine flux associated with cardiac surgery

Summary. Pharmacological doses of growth hormone (GH) in humans and rats increase plasma and muscle glutamine values. As major surgery results in a physiological rise in serum GH concentration, we investigated whether this physiological increase in GH altered glutamine metabolism. Eighteen patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive somatostatin, 100 μg subcu-taneously at induction of anaesthesia and 8 hourly for 48 h, or placebo. Somatostatin effectively blocked the physiological surge of GH following injury but did not affect plasma or muscle glutamine concentrations, which fell significantly in both groups. Plasma glutamine decreased by 31% (P<0–01) and 28% (P<0–01) in the control and somatostatin groups respectively. Muscle glutamine was reduced 45% (P<0–001) in the control group and 50% (P<0–001) in the somatostatin group. There was no difference in muscle or circulating glutamate, alanine or branched chain amino acid concentrations or in metabolite values between the somatostatin-treated patients and the control group. There was no relationship between the GH response to surgery and glutamine metabolism following major surgery.     

汉坦病毒M基因区核苷酸序列及G1膜蛋白部分氨基酸共享序列分析

目的对青岛地区31株汉坦病毒分离株M区基因序列测定及基因分型研究，为疫苗接种提供依据。方法从64例肾综合征出血热(HFRS)患者发热期血清标本中提取RNA，应用套式逆转录聚合酶链反应扩增汉坦病毒基因组M片段，G1基因区克隆并测定核苷酸序列和部分共享氨基酸序列，且对测定结果应用DNA Star和Prosis软件进行分析。结果64份标本中测出汉滩型(HTN)6份，占9％；汉城型(SEO)25份，占39％；总阳性率48％。SEO型汉坦病毒间核苷酸序列的差异相对较小，其基因的离散度为0．3％～8．9％。HTN型汉坦病毒变异率较高，基因的离散度为2．6％～11．2％。结论SEO型汉坦病毒基因型相对保守，而HTN型变异率较高；M区段可编码一个具有稳定的保守抗原表位。     

The effect of amino acid infusion on leg protein turnover assessed by L-[15N]phenylalanine and L-[1-13C]leucine exchange

A stable isotope technique depending on the use of [15N]phenylalanine and [1-13C]leucine to assess exchange was utilized to measure the components of protein turnover of the human leg and the effects of amino acid infusion. Eight healthy subjects (28.5 +/- 2.5 years) were studied when post-absorptive in the basal state and again during infusion of a mixed amino acid solution (55 g l-1, 1.52 ml kg-1 h-1). During the basal period leucine oxidation by the leg was 4.4 +/- 2.0 nmol 100 g-1 min-1 and this increased threefold during amino acid infusion (13.6 +/- 3.1 nmol 100 g-1 min-1, mean +/- SEM, P = 0.003). Amino acid infusion abolished the net negative balance between incorporation of leucine into, and release from, protein (basal, -31.8 +/- 5.8; during infusion, +3.1 +/- 7.1 nmol 100 g-1 P = 0.001). Phenylalanine exchange showed a similar pattern (basal, -13.7 +/- 1.8; during infusion, -0.8 +/- 3.0 nmol 100 g-1 min-1, P = 0.003). Basal entry of leucine into leg protein (i.e. protein synthesis) was 70.0 +/- 10.8 nmol 100 g-1 min-1 and this increased during amino acid infusion to 87.3 +/- 14.1 nmol 100 g-1 min-1 (P = 0.11). Phenylalanine entry to protein also increased with amino acid infusion (29.1 +/- 4.5 vs. 38.3 +/- 5.8 nmol 100 g-1 min-1, P = 0.09). Release from protein of leucine (101.8 +/- 9.1 vs. 84.2 +/- 9.1 nmol 100 g-1 min-1, P = 0.21) and of phenylalanine (42.8 +/- 4.2 vs. 39.1 +/- 4.2 nmol 100 g-1 min-1, P = 0.50) was unchanged by amino acid infusion. The results suggest that, in the post-absorptive state in man, infusion of mixed amino acids, without additional energy substrates; reverses negative amino acid balance by a mechanism which includes stimulation of muscle protein synthesis but which does not alter protein breakdown. Interpretation of the results obtained concurrently on whole-body protein turnover suggests that the increase in muscle protein synthesis contributes substantially to the whole-body increase, but the fall in whole-body breakdown with exogenous amino acids is independent of changes in muscle.     

Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review

Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.