The relation of saturated fatty acids with low-grade inflammation and cardiovascular disease.

The mantra that dietary (saturated) fat must be minimized to reduce cardiovascular disease (CVD) risk has dominated nutritional guidelines for decades. Parallel to decreasing intakes of fat and saturated fatty acids (SFA), there have been increases in carbohydrate and sugar intakes, overweight, obesity and type 2 diabetes mellitus. The "lipid hypothesis" coined the concept that fat, especially SFA, raises blood low-density lipoprotein-cholesterol and thereby CVD risk. In view of current controversies regarding their adequate intakes and effects, this review aims to summarize research regarding this heterogenic group of fatty acids and the mechanisms relating them to (chronic) systemic low-grade inflammation, insulin resistance, metabolic syndrome and notably CVD. The intimate relationship between inflammation and metabolism, including glucose, fat and cholesterol metabolism, revealed that the dyslipidemia in Western societies, notably increased triglycerides, "small dense" low-density lipoprotein and "dysfunctional" high-density lipoprotein, is influenced by many unfavorable lifestyle factors. Dietary SFA is only one of these, not necessarily the most important, in healthy, insulin-sensitive people. The environment provides us not only with many other proinflammatory stimuli than SFA but also with many antiinflammatory counterparts. Resolution of the conflict between our self-designed environment and ancient genome may rather rely on returning to the proinflammatory/antiinflammatory balance of the Paleolithic era in consonance with the 21st century culture. Accordingly, dietary guidelines might reconsider recommendations for SFA replacement and investigate diet in a broader context, together with nondietary lifestyle factors. This should be a clear priority, opposed to the reductionist approach of studying the effects of single nutrients, such as SFA.

Optimum Conditions for the Efficacy and Safety of Cryofiltration Apheresis: An Analysis of Circuit Temperatures Depending on Plasma Flow Rate and Cooling Coil Lengths/Turns.

A system providing both appropriate cooling and warming are needed for the efficacy and safety of cryofiltration (CF) plasmapheresis. We measured some points of CF circuit temperatures with varying plasma flow rates (QP = 10-40 mL/min) and the numbers of connecting cooling coils (one or two) under the conditions of blood flow rate (QB ) 100 mL/min with 7700-mm coil length, 19 turns, and 50-mL priming volume. We measured the respective temperatures of each point of starting/returning for an extracorporeal circuit (TA /TV ), intracooling coil (TC ), and post-plasma fractionator (PF) (TPF ). The subtraction of TV from TA (ΔT) was used as an indicator of safe return. There were no significant differences in TC , TPF , or ΔT in accordance with each QP between that of one and two coils. All of the Tc values under the condition QP ≤ 20 mL/min achieved <4°C. The TPF under the condition QP ≥ 20 mL/min was not significantly different compared to that of QP 30 mL/min (the lowest condition). Although the ΔT increased depending on the QP increase, the ΔT under the condition QP ≤ 15 mL/min was not significantly different from that of the control (one-way double-filtration plasmapheresis [DFPP]) group. We conclude that (i) one coil is enough for effective cooling in CF, and (ii) an ideal QP that fulfills the required conditions for both effective cooling and sufficient warming of returning fluid does not exist, but QP from 15 to 20 mL/min may be a relevant range.

Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes.

INTRODUCTION: Gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. We explored whether fetal exposure to a diabetic environment is associated with fetal endothelial progenitor cell dysfunction, and whether vitamin D can reverse the impairment. METHODS: Nineteen women with uncomplicated pregnancies and 18 women with GDM were recruited before delivery. Time to first appearance of endothelial colony forming cell (ECFC) colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined. Angiogenesis-related functions of ECFCs in vitro were tested in the presence or absence of vitamin D. RESULTS: Fetal ECFCs from GDM pregnancies formed fewer colonies in culture (P = 0.04) and displayed reduced proliferation (P = 0.02), migration (P = 0.04) and tubule formation (P = 0.03) compared to uncomplicated pregnancies. Fetal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P < 0.05) and less tubule formation (P < 0.05) than normoglycemic control. Vitamin D significantly improved the dysfunction of fetal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia. DISCUSSION: Fetal ECFCs from GDM pregnancies or ECFCs exposed to hyperglycemia in vitro exhibit reduced quantity and impaired angiogenesis-related functions. Vitamin D significantly rescues these functions. These findings may have implications for vascular function of infants exposed to a diabetic intrauterine environment.

Endothelial dysfunction and the effects of TNF inhibitors on the endothelium in psoriasis and psoriatic arthritis: a systematic review.

BACKGROUND: Epidemiologic data support the association of psoriasis and psoriatic arthritis with adverse cardiovascular outcomes. Shared pathogenesis in endothelial dysfunction may underlie psoriasis and atherosclerosis. Tumor necrosis factor (TNF) inhibitors may modulate endothelial dysfunction seen in patients with psoriasis and psoriatic arthritis. OBJECTIVE: To perform a systematic review that investigated endothelial function in psoriasis and psoriatic arthritis and the effect of TNF inhibitors on endothelial function in psoriasis and psoriatic arthritis. METHODS: MEDLINE (1980-October 2012), Web of Science, the EULAR abstract database, and the AAD annual meeting abstract archive were searched for cross-sectional or longitudinal studies that 1) examined endothelial function in patients with psoriasis or psoriatic arthritis, or 2) investigated the effect of TNF inhibitor therapy on endothelial function. RESULTS: Twenty articles and four abstracts with 2261 patients evaluated endothelial function in psoriasis and psoriatic arthritis, which was measured by pulse wave velocity, flow-mediated dilation, nitroglycerine-induced vasodilation, carotid intima-media thickness, peripheral arterial tonometry, or aortic stiffness parameters. The majority of the data suggests that patients with psoriasis and psoriatic arthritis have significantly increased arterial stiffness, impaired endothelial-dependent vasodilation, increased carotid intima-media thickness, and decreased aortic elasticity compared to the general population. Two out of three studies showed that TNF inhibitors improved endothelial function in psoriasis and psoriatic arthritis. LIMITATIONS: Measurements of endothelial function were not standardized across studies. CONCLUSIONS: The preponderance of literature suggests that endothelial function is significantly impaired in patients with psoriasis and psoriatic arthritis compared to the general population. Preliminary evidence suggests that TNF inhibitors may improve endothelial function in the psoriasis and psoriatic arthritis populations.