Yongsoon Park

Mean platelet volume as an indicator of platelet activation: methodological issues

Background: Mean platelet volume (MPV) is increased in patients at high risk for athero-thrombotic diseases. Thus, an elevated MPV may be a risk marker for platelet activation. Methods: Healthy subjects with normal triglyceride (TG) levels (90 - 6 mg/dl; n = 40) or mild hypertriglyceridemia (161 - 79 mg/dl; n = 32) were studied. MPV was measured in fasting blood samples before and after stimulation with collagen (10 w g/ml), and exposure to 4 or 37°C. Samples from the normotriglyceridemic subjects were tested again 4 h after consuming a high-fat drink. Results: Collagen and exposure to 4°C increased MPV, whereas incubation at 37°C lowered MPV regardless of TG level. There was no significant difference in unstimulated MPV between the fasting and the fed states in the normotriglyceridemic subjects (both 7.2 - 0.1 fl; mean - SEM), nor between the latter group and hypertriglyceridemic subjects (7.0 - 0.1 fl). There was a significant negative relation between MPV and fasting TG level. Conclusions: This study suggests that MPV response to low-dose collagen may be a useful indicator of platelet propensity to activation. Further studies are warranted to correlate MPV with classical platelet aggregation tests and with the use of platelet-active drugs.

Cardiovascular disease and long-chain omega-3 fatty acids.

Purpose of review Of all known dietary factors, long-chain omega-3 fatty acids may be the most protective against death from coronary heart disease. New evidence has confirmed and refined the cardioprotective role of these fatty acids. Recent findings Omega-3 fatty acid supplementation reduces the risk of sudden cardiac death and death from any cause within 4 months in post-myocardial infarction patients. Evidence continues to accrue for benefits in the primary prevention of coronary heart disease and stroke, and an anti-arrhythmogenic mechanism is emerging as the most likely explanation. Summary Current evidence suggests that individuals with coronary artery disease may reduce their risk of sudden cardiac death by increasing their intake of long-chain omega-3 fatty acids by approximately 1 g per day.

High-fat dairy product consumption increases Δ9c’ 11t−18∶2 (rumenic acid) and total lipid concentrations of human milk

Conjugated octadecadienoic acids (18∶2’ conjugated linoleic acids) have been shown to be anticarcinogenic and may influence growth and nutrient partitioning. The Δ9c’ 11t−18∶2 isomer (rumenic acid’ RA) is most common in both food sources and human tissues. To determine if maternal diet can influence milk RA concentration’ breastfeeding women (n=16) were enrolled in a 3-wk crossover study. Women initially consumed minimal amounts of food containing RA during week 1’ then were assigned randomly to consume diets rich in high-fat dairy foods (and thus RA) during week 2 or 3. Milk was collected by complete breast expression twice during each experimental week. Current and chronic RA intakes were estimated by 3-d dietary records and food frequency question-naires’ respectively. Estimated chronic RA intakes ranged from 49 to 659 mg/d. Dietary RA intake was greater during the high compared to the low dairy period (291±75 vs. 15±24 mg/d’ respectively; P<0.0001). Milk contained more RA during the high than the low dairy period (13.5±0.1 vs. 8.2±0.4 μmol/g lipid’ respectively; P<0.0001). Milk lipid concentration was influenced by diet’ such that lipid concentration was greater during the high than the low dairy period (46.6±5.0 vs. 38.3±1.6 mg/g milk’ respectively; P<0.05). Additionally’ multiple regression analyses suggested that body mass index was the primary predictor of milk RA and lipid concentrations. In summary’ these data indicate that both lipid and RA concentrations of human milk can be influenced by diet.

Conjugated linoleic acid concentrations of human milk and infant formula

Conjugated linoleic acid (CLA) is an anticarcinogen found in ruminant products. CLA may also act as a growth promotor in the neonate. Because of the potential importance of CLA to maternal and infant health, CLA concentration was quantified in human milk and infant formula. Human milk samples (n = 14) were collected by complete breast expression, and four brands of formula were analyzed; both powder and ready-to-feed products were studied. Although CLA was detected in only 31% of the formula samples, it was detectable in all human milk. Concentration of the biologically important isoform (c9,t11) of CLA in human milk ranged from 2.23 to 5.43 mg/g fat; that of formula from undetectable to 2.04 mg/g fat. Percent total CLA present as c9,t11 ranged from 83 to 100% in human milk and 80 to 100% in formula. Overall, human milk contained significantly more (P < 0.0001) CLA than did the samples of infant formula containing measurable concentrations (3.64 ± 0.93 vs. 1.35 ± 0.81 mg/g fat, respectively).

Central Obesity as a Risk Factor for Prostatic Hyperplasia

Objective: Obesity‐related metabolic diseases may influence prostatic hyperplasia. This study examined the impact of obesity on prostate volume in men without overt obesity‐related metabolic diseases.

EPA, but not DHA, decreases mean platelet volume in normal subjects

The first indication of platelet activation is an increase in mean platelet volume (MPV). n−3 FA are known to inhibit platelet function and to reduce the risk for coronary heart disease. The purpose of this study was to determine the effects of FPA and DHA on MPV. Healthy subjects received olive oil placebo for 4 wk and then were randomly assigned to receive 4g of ethyl esters of either safflower oil (n=11), EPA (n=10), or DHA (n=12) for 4 wk. At the end of placebo run-in and treatment periods, MPV (fL; mean±SEM) and platelet count (PLT-CT; 103/μL blood) were measured in the basal state and after ex vivo stimulation with collagen (10 μg/mL), cold (4°C), and heat (37°C). Unlike DHA, EPA lowered MPV as compared with safflower oil (7.2±0.1 vs. 7.5±0.1 fL; P<0.05) and raised PLT-CT (211±18 vs. 192±18 103/μL; P<0.05) in the fasting state. Collagen and cold significantly increased MPV whereas heat lowered MPV regardless of treatment. All stimuli decreased PLT-CT. EPA significantly increased platelet EPA (0.2±0.1 vs. 3.3±0.4%) and docosapentaenoic acid (DPA; 2.2±0.3 vs. 2.9±0.3%) concentrations, but not DHA. DHA treatment significantly increased DHA (1.4±0.2 vs. 4.1±0.5%) and DPA (2.0±0.4 vs. 3.0±0.4%) concentrations, but not EPA. In conclusion, EPA, but not DHA, reduces platelet activation, an early step in platelet aggregation.

Increase in Cell Migration and Angiogenesis in a Composite Silk Scaffold for Tissue-Engineered Ligaments

The purpose of this study was to evaluate the biocompatibility of silk and collagen‐hyaluronan (HA) in vitro by assessing anterior cruciate ligament (ACL) cell and T‐lymphocyte cultures on scaffolds. The use of composite scaffolds as artificial ligaments in ACL reconstruction and their effects on angiogenesis were evaluated in vivo. The silk scaffold was knitted by hand and dry coated with collagen‐HA, whereas the composite silk scaffold was made by covering a silk scaffold with a lyophilized collagen‐HA substrate. The initial attachment and proliferation of human ACL cells on the composite silk scaffold was superior to the attachment and proliferation observed on the silk scaffold. The immune response was higher in both scaffolds after 72 h (p < 0.05) compared with the control culture condition without scaffolding, as assessed by T‐lymphocyte cultures in vitro. There was no significant difference in the immune response in vitro between the silk and composite silk scaffolds. Silk and composite silk scaffolds were implanted as artificial ligaments in ACLs removed from the knees of dogs, and they were harvested 6 weeks after implantation. On gross examination, the onset of an inflammatory tissue reaction, such as synovitis, was seen in both the silk scaffold and the composite silk scaffold groups. An histological evaluation of the artificial ligament implants revealed the presence of monocytes in the silk composite scaffold and the absence of giant cells in all cases. MT staining in the composite silk scaffold‐grafted group showed granulation tissue consisting of fibroblasts, lymphocytes, monocytes, and collagen fibers. In addition, CD31 staining revealed the formation of new blood vessels. On the other hand, no reparative tissues, such as blood vessels, collagen, and cells, were observed in the silk scaffold‐grafted group. These results suggest that the lyophilized collagen‐HA substrate is biocompatible in vitro and enhances new blood vessel and cell migration in vivo.

Novel genetic variations associated with salt sensitivity in the Korean population

Salt sensitivity is a risk factor for cardiovascular morbidity and mortality. To date, only a few genetic variations have been identified as being associated with salt sensitivity. This study aimed to estimate the prevalence of salt sensitivity in the Korean population and to identify genetic variants affecting its development. A total of 101 Korean participants consumed a low-salt diet for 7 days followed by a high-salt diet for 7 additional days. Salt sensitivity was determined by noting any significant elevation in the 24-h mean arterial blood pressure. To determine genetic variants affecting salt sensitivity, 36 single-nucleotide polymorphisms (SNPs) that were previously reported to be associated with hypertension were tested for any associations with salt sensitivity. Of the 101 subjects, 28 (27.7%) were determined to have salt sensitivity. Out of the 36 SNPs tested, four were significantly associated with salt sensitivity after adjusting for confounding factors: rs2681472 in ATPase, Ca++ transporting, plasma membrane 1 (ATP2B1), rs7961152 in branched chain aminotransferase 1 (BCAT1), rs16998073 in fibroblast growth factor 5 (FGF5) and rs2398162 in LOC100132798. For rs3754777 in serine threonine kinase 39 (STK39) and rs1937506, associations with salt sensitivity were observed before adjusting for confounding factors. Haplotype analysis revealed that the A-C haplotype of rs3754777–rs6749447 in STK39 was more frequent in the salt-sensitive group compared with the salt-resistant group, and was associated with salt sensitivity. This study estimates the prevalence of salt sensitivity in the Korean population and demonstrates a novel association between salt sensitivity and the ATP2B1, BCAT1, FGF5, LOC100132798 and STK39 genetic variations.

Low level of n-3 polyunsaturated fatty acids in erythrocytes is a risk factor for both acute ischemic and hemorrhagic stroke in Koreans

Evidence suggesting an association between n-3 polyunsaturated fatty acids (PUFA) and stroke risk has been inconsistent, possibly because previous studies have not differentiated between different stroke types. The present study investigated the hypothesis that tissue levels of n-3 PUFA are positively associated with hemorrhagic stroke and negatively associated with ischemic stroke. We recruited 120 subjects for this case-control study, with 40 cases each of hemorrhagic stroke, ischemic stroke, and unaffected controls. Patients with a family history of hemorrhagic stroke had a significantly increased risk for hemorrhagic stroke. Omega-3 Index (20:5n3 + 22:6n3 in erythrocytes) and 22:6n3 were negatively (P < .01) associated with the risk of both hemorrhagic and ischemic stroke in multivariate analyses. Saturated fatty acids 16:0 and 18:0 were positively associated, whereas 18:2n6 and 18:3n6 were negatively (P < .05) associated with risk of ischemic stroke. Monounsaturated fatty acid, 18:1n9, increased (P = .03) the odds of hemorrhagic stroke. Omega-3 Index and docosahexaenoic acid were significantly lower in patients with both subtypes of hemorrhagic stroke, subarachnoid and intracerebral hemorrhage, but only in one subtype of ischemic stroke, small-artery occlusion. Saturated fatty acids 16:0 and 18:0 were significantly higher, but 20:4n6 was significantly lower, in patients with small-artery occlusion. Linoleic acid was significantly lower in patients with small-artery occlusion and large-artery atherosclerosis, whereas 18:1n9 was higher in both subgroups of hemorrhagic stroke. In conclusion, the results of our case-control study suggest that erythrocyte n-3 PUFA may protect against hemorrhagic stroke and ischemic stroke, particularly in the case of small-artery occlusion.

Erythrocyte fatty acid profiles can predict acute non-fatal myocardial infarction.

The risk of CHD has been linked to n-3 and trans-fatty acids. The purpose of the present study was to evaluate the hypothesis that lower n-3 fatty acids and higher trans-fatty acids in erythrocytes are associated with an increased risk of acute non-fatal myocardial infarction (MI), and that fatty acid profiles can discriminate MI cases from controls. Fifty cases with acute non-fatal MI and fifty age- and sex-matched controls without MI were recruited. The Omega-3 Index (the sum of EPA and DHA in erythrocytes) was significantly lower in cases than controls (9.57 (SEM 0.28) v. 11.81 (SEM 0.35) %; P < 0.001), while total trans-fatty acids were significantly higher (1.01 (SEM 0.04) v. 0.56 (SEM 0.03) %; P < 0.001). The Omega-3 Index was associated with decreased risk of MI (OR 0.08 (95 % CI 0.02, 0.38); P = 0.001), while total trans-fatty acids were associated with an increased risk of MI (OR 72.67 (95 % CI 6.68, 790.74); P < 0.001). The area under the receiver operating characteristic curve of fatty acid profiles was larger than that for traditional risk factors, suggesting that fatty acid profiles make a higher contribution to the discrimination of MI cases from controls compared with modified Framingham risk factors. In conclusion, a higher Omega-3 Index and lower trans-fatty acids in erythrocytes are associated with a decreased risk of MI. Furthermore, fatty acid profiles improve discrimination of acute non-fatal MI compared with established risk factors.