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Biomedical subjects

Yangsoo Jang

Publications and source records attributed to Yangsoo Jang.

At least 37 records · Page 2Linked to original sources

Delayed hyperenhancement magnetic resonance imaging is useful in predicting functional recovery of nonischemic left ventricular systolic dysfunction.

BACKGROUND: About 25% of the patients with nonischemic left ventricular (LV) systolic dysfunction improve spontaneously. However, the predictors for functional improvement are not known. We hypothesized that myocardial fibrosis, assessed by cardiac magnetic resonance (CMR) imaging, may predict the reversibility of nonischemic LV systolic dysfunction. METHODS AND RESULTS: CMR was performed in 46 patients. Baseline and follow-up echocardiography was performed to assess the recovery of LV function. There were 24 patients with absence of delayed hyperenhancement (group 1) and 22 patients with delayed hyperenhancement (group 2). There were significant difference for the follow-up LV end-diastolic dimension (56.2 +/- 7.3 versus 62.6 +/- 11.9), LV end-systolic dimension (43.2 +/- 9.2 versus 52.8 +/- 12.6), and LV ejection fraction (LVEF) (46.8 +/- 12.4% versus 31.6 +/- 11.3%). Follow-up echocardiography of 19/24 (79.2%) patients in group 1 showed functional recovery, whereas only 2/22 (9.1%) patient in group 2 showed functional recovery. The absence of delayed hyperenhancement was associated with sensitivity, specificity, positive predictive value, and negative predictive value of 90.5%, 79.2%, 80.0%, and 90.9%, respectively. CONCLUSION: Absence of delayed hyperenhancement demonstrated excellent sensitivity and negative predictive value in predicting functional recovery of nonischemic LV systolic dysfunction.

Cardiomyopathy, Dilated↗

Prediction of transmural extent of infarction with contrast echocardiographically derived index of myocardial blood flow and myocardial blood volume fraction: comparison with contrast-enhanced magnetic resonance imaging.

BACKGROUND: We sought to determine the accuracy of myocardial contrast echocardiography (MCE)-derived index of myocardial blood flow and myocardial blood volume fraction (MBVF) in predicting transmural extent of infarction and wall-motion recovery. METHODS: Low and high mechanical index MCE and contrast-enhanced magnetic resonance imaging were performed 5 to 7 days after successful percutaneous revascularization in 30 patients with acute myocardial infarction and regional wall-motion change was assessed 3 months later. The index of myocardial blood flow was calculated as A x beta (dB/s) using the equation y = A (1 - e(-beta t)), which fits the replenishment curve of low mechanical index MCE. The MBVF (mL/100 g myocardium) was calculated as 100 x 10(relative contrast intensity [CI]/10), using the relative CI by subtracting the cavity CI from the adjacent transmural CI using high mechanical index MCE. The contrast-enhanced magnetic resonance imaging-derived transmural extent of delayed hyperenhancement (DE) in 16 segments were measured and compared with corresponding MCE data. RESULTS: Among 480 segments, 382 measurable segments were subdivided into 5 groups as follows: no DE, 1% to 25% DE, 26% to 50% DE, 51% to 75% DE, and 76% to 100% DE. An increment of the extent of DE was significantly related to a decrement of A x beta (P < .001) and MBVF (P < .001). The optimal cut-off MBVF for predicting greater than 50% DE was 1.92 mL (sensitivity 82%, specificity 73%, P < .01), and persistently dysfunctional motion was 1.81 mL (sensitivity 74%, specificity 75%, P < .01). CONCLUSION: The MCE-derived A x beta and MBVF can be effective predictors of transmural extent of infarction and wall-motion recovery in the reperfused acute myocardial infarction.

Blood Flow Velocity↗

Abnormal longitudinal myocardial functional reserve assessed by exercise tissue Doppler echocardiography in patients with hypertrophic cardiomyopathy.

BACKGROUND: Previous studies have shown that mitral annular velocities are reduced in patients with hypertrophic cardiomyopathy (HCM). However, the response of systolic and diastolic velocities of the mitral annulus to exercise in patients with HCM has not been explored previously. Because pathologic left ventricular (LV) hypertrophy is associated with myocardial fibrosis, particularly in the subendocardium, we hypothesized that mitral annular systolic and diastolic velocities during exercise and at rest would be abnormal in patients with HCM. METHODS: Mitral septal annular systolic (S') and early diastolic (E') velocities were measured at rest and during graded supine bicycle exercise (25 W, 3-minute increments) in 40 patients with HCM (29 male, mean age 56 years) and 41 age- and sex-matched control subjects. LV diastolic and systolic longitudinal function reserve index were calculated using a new formula. RESULTS: There were no significant differences in mitral inflow velocities (early mitral filling velocity [E], E/A, deceleration time of E velocity [DT]) at rest between the two groups except late mitral filling (A) velocity, which was higher in control group. Increase in E' with exercise was significantly smaller in patients with HCM compared with control subjects (1.7 +/- 1.3 vs 3.4 +/- 2.5 cm/s from base to 25 W, P = .0006; 2.2 +/- 1.9 vs 4.5 +/- 2.8 cm/s from base to 50 W, P = .0002). Although LV ejection fraction at rest was significantly higher in patients with HCM compared with that of control subjects (71 +/- 7 vs 66 +/- 7, P = .0019), S' at rest (6.0 +/- 1.2 vs 6.8 +/- 1.1 cm/s, P = .011) was significantly lower in patients with HCM. Although a significant increase in S' was detected with exercise in control subjects, increase in S' with exercise was blunted in patients with HCM (6.4 +/- 1.4 vs 8.5 +/- 2.5 cm/s at 25 W, P = .0004; 7.0 +/- 1.4 vs 9.5 +/- 2.4 cm/s at 50 W, P < .0001). Longitudinal systolic (0.37 +/- 0.85 vs 1.47 +/- 1.75 cm/s at 25 W, P = .0034; 0.79 +/- 1.08 vs 2.32 +/- 1.66 cm/s at 50 W, P = .0001) and diastolic (1.29 +/- 1.06 vs 2.84 +/- 2.12 cm/s at 25 W, P = .0002; 1.63 +/- 1.46 vs 3.77 +/- 2.31 cm/s at 50 W, P < .0001) function reserve index was significantly lower in patients with HCM compared with that of control subjects. CONCLUSION: Augmentation of LV longitudinal function during exercise is blunted in patients with HCM, suggesting longitudinal functional reserve and resting longitudinal function is abnormal in these patients.

Cardiomyopathy, Hypertrophic↗

Triphasic mitral inflow velocity with mid-diastolic flow: the presence of mid-diastolic mitral annular velocity indicates advanced diastolic dysfunction.

Mitral inflow filling pattern usually consists of 2 forward flow velocities in sinus rhythm: early rapid filling (E) and late filling with atrial contraction (A). However, additional mid-diastolic flow velocity may be present resulting in triphasic mitral inflow filling pattern. When mitral inflow is triphasic, mitral annulus velocity recorded by tissue Doppler imaging (TDI) frequently demonstrates a mid-diastolic component (L'). The significance of L' has not been explored previously. The purpose of this study was to explore possible mechanisms and clinical implications of triphasic mitral inflow with or without L' using TDI and proBNP. Of 9004 patients who underwent transthoracic echocardiography from March to November 2003, 83 (0.9%) patients (33 male, 50 female; mean age, 63+/-10 years) with a triphasic mitral inflow velocity pattern, including mid-diastolic flow velocity of at least 0.2m/s, and sinus rhythm were prospectively identified in our clinical echocardiography laboratory. Peak velocity of E, mid-diastolic (L), and A, and deceleration time (DT) of the E wave velocity were measured. Diastolic mitral annular velocities were measured at the septal corner of the mitral annulus by TDI from the apical 4-chamber view. ProBNP was measured at the time of echocardiogram using a quantitative electrochemiluminescence immunoassay. Mean heart rate was 54+/-6 beats/min (range, 40-67). Mean left ventricular (LV) ejection fraction (EF) was 64+/-13% and LV systolic dysfunction (EF<40%) was present in only 6 (7%). Patients were classified into 2 groups: group 1 (n=47) included those who had L' and group 2 (n=36) included those without L'. Group 1 patients had significantly higher peak velocity (35+/-14 vs 26+/-6 cm/s, p=0.0002) and TVI (35+/-14 vs 26+/-6 cm/s, p=0.0002) of L, E/E' (18+/-8 vs 14+/-6, p=0.02), and left atrial volume index (42+/-14 vs 34+/-10 ml/m(2), p=0.0037). E' (4.7+/-1.3 vs 6.2+/-2.3 cm/s, p=0.001) and A' (6.2+/-2.0 vs 8.6+/-3.4 cm/s, p=0.0006) were significantly lower in group 1 compared with those of group 2. ProBNP was significantly higher in group 1 (847+/-1461 vs 438+/-1039 pmol/l, p=0.0012) and it was above normal in all except in 1 patient of group 1. In conclusion, the presence of L' in subjects with triphasic mitral inflow velocity pattern with mid-diastolic flow is associated with higher E/E', elevated proBNP and enlarged left atrium indicating advanced diastolic dysfunction with elevated filling pressures. This unique mitral annular velocity pattern should be helpful in identifying the patients with advanced diastolic dysfunction and increased LV filling pressures.

Adult↗

The SNP276G>T polymorphism in the adiponectin (ACDC) gene is more strongly associated with insulin resistance and cardiovascular disease risk than SNP45T>G in nonobese/nondiabetic Korean men independent of abdominal adiposity and circulating plasma adiponectin.

This study aimed to determine whether polymorphisms of the adiponectin (ACDC) gene independently contribute to insulin resistance (IR) and other cardiovascular disease (CVD) risk factors in nonobese, nondiabetic Korean men after adjusting for major environmental factors that influence IR. Among the 7 ACDC single-nucleotide polymorphisms (SNPs;C-11377G, T45G, G276T, H241P, Y111H, G90S, and R221S) prescreened in 48 subjects, we genotyped 333 subjects for SNP45 and SNP276, both of which showed an allele frequency of more than 2%. In Pearson correlation and multiple stepwise regression analyses, we found that waist circumference was the most important influencing factor (beta = .369, P < .001) in homeostasis model assessment (HOMA)-IR, whereas plasma adiponectin was the second most important (beta = -.217, P = .023). At position 276, T/T subjects showed significantly lower glucose concentrations (P = .043) and higher low-density lipoprotein particle sizes (P = .033) than the G/G and G/T subjects. The subjects also had lower serum triglycerides and HOMA-IR; however, these results were not statistically significant. After adjusting for waist circumference and plasma adiponectin, T/T subjects showed a significantly lower HOMA-IR than G/G or G/T subjects (P = .048). On the other hand, at position 45, only glucose concentrations were significantly lower in G carriers (P = .005). In the SNP45-SNP276 haplotype test, TT/TT subjects (having T/T at both SNP45 and SNP276) showed significantly lower IR before and after adjusting for waist circumference and adiponectin levels than did other carriers. In conclusion, we suggest that SNP276G>T, rather than SNP45T>G, is more strongly associated (both directly and indirectly) than with several components of metabolic syndrome and CVD risk, including IR, triglyceride concentration, and low-density lipoprotein particle size, in nonobese, nondiabetic men.

Abdomen↗

Insulin resistance, adipokines, and oxidative stress in nondiabetic, hypercholesterolemic patients: leptin as an 8-epi-prostaglandin F2alpha determinant.

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF(2alpha) excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF(2alpha) (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = -0.252, P < .05) and HOMA-IR (r = -0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF(2alpha) excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.

Adiponectin↗

Comparison of low-fat meal and high-fat meal on postprandial lipemic response in non-obese men according to the -1131T>C polymorphism of the apolipoprotein A5 (APOA5) gene (randomized cross-over design).

OBJECTIVE: The purpose of this study was to compare low-fat (LF) meal and high-fat (HF) meal on the postprandial lipemic responses according to the -1131T>C polymorphism of the APOA5 gene in a population usually consuming a LF diet and having a high frequency of the variant allele at the APOA5 -1131T>C SNP. METHODS: This study was conducted using a cross-over design and 49 non-obese healthy men (42.8 +/- 0.7 yrs, 23.9 +/- 0.25 kg/m(2)) participated in the meal tolerance test. They were randomly assigned to consume one of two types of experimental enteral formulae (LF vs HF) with a seven-day interval. Blood samples were collected at 0, 2, 3, 4 and 6h after ingestion and analyzed for total and chylomicron TG, glucose, insulin and free fatty acid. RESULTS: No differences were found in anthropometic parameter, calorie and macronutrient intakes and total energy expenditure between TT (n = 23) and TC + CC (n = 26) men. Fasting total TG were higher in TC + CC men than TT men, but fasting chylomicron TG were not significantly different between TT men and C carriers, TT subjects had no significant differences in postprandial responses of total TG and chylomicron TG and postprandial mean changes of chylomicron TG between LF and HF meal. On the other hand, C carriers had delayed peak time of total TG compared to TT subject and higher postprandial response and mean changes of chylomicron TG at HF meal compared to LF meal. CONCLUSION: The capacity to clear chylomicron-TG or hydrolyze TG might become a rate-limiting factor on HF diet in TC + CC men resulting in higher postprandial triglyceridemia. Therefore, HF diet for C carriers of the APOA5 gene may be one of important CVD risk factors.

Adult↗

Efficacy of subintimal angioplasty/stent implantation for long, multisegmental lower limb occlusive lesions in patients unsuitable for surgery.

PURPOSE: To investigate the feasibility and clinical outcomes of subintimal angioplasty combined with stent implantation in patients with long, multisegmental occlusive lesions unsuitable for surgical treatment. METHODS: Between 2003 and 2005, 30 patients (23 men; mean age 68 years, range 49-82) with severe claudication (Rutherford category 3, n=12) or critical limb ischemia (CLI; Rutherford category 4 or 5, n=18) underwent subintimal angioplasty with primary stenting for long (mean 28+/-11 cm) total occlusion in the lower limb arteries. Bypass surgery was considered unsuitable owing to inappropriate anatomy or poor distal runoff in 14 (47%) patients, severe coronary artery disease 14 (47%), or poor general condition in 2 (6%). RESULTS: Technical success was achieved in 27 (90%) of 30 cases. The 3 technical failures were due to inability to advance the wire, to re-enter the distal lumen, and vessel rupture, respectively. Three (10%) complications occurred (1 perforation, 2 hematomas) but did not require surgery. After a mean follow-up of 13+/-7 months (range 3-28), 10 (37%) cases of restenosis were found in 27 patients. At 12 months, the primary patency rate was 52%, and the limb salvage rate was 83%. CONCLUSION: Combined use of subintimal angioplasty and stent implantation was performed safely, with a relatively high success rate and acceptable intermediate-term clinical outcomes in patients with multisegmental, long occlusions of the lower limb arteries. Therefore, this strategy can be considered an option for symptomatic relief and limb salvage in patients unsuitable for bypass surgery due to various reasons.

Aged↗

Coronary artery intervention after cytostatics treatment in unstable angina patient with essential thrombocythemia. A case report and literature review.

Essential thrombocythemia (ET) is a clonal disorder of myeloid stem cells that causes thrombocytosis. As a result, ET can lead to vascular thrombosis and tissue ischemia; the association of coronary artery abnormalities such as myocardial infarction or unstable angina is rare. Here we describe a 45,-year-old male patient with essential thrombocythemia who presented with unstable angina. Elective coronary angiography showed total occlusion of mid right coronary artery and mid left anterior descending coronary artery. ET was confirmed by a bone marrow biopsy; treatment was started with antiplatelet therapy including aspirin and clopidogrel along with cytostatic therapy with hydroxyurea and anagrelide. After the initiation of the treatment, the platelet count decreased to 20 x 10(4)/microL. In addition, percutaneous coronary angioplasty was successfully performed with stent placement at the right coronary artery without hemorrhagic or thrombotic complications.

Angina, Unstable↗

Berberine inhibits the production of lysophosphatidylcholine-induced reactive oxygen species and the ERK1/2 pathway in vascular smooth muscle cells.

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.

Animals↗

Inflammatory and vasoactive factors in the aspirate from the culprit coronary artery of patients with acute myocardial infarction.

BACKGROUND: Besides distal embolization of thrombus and plaque debris, locally increased inflammatory markers at the site of ruptured plaque in acute myocardial infarction (AMI) are thought to have an adverse impact on myocardial reperfusion during primary percutaneous coronary intervention (PCI). However, there is lack of data on such factors. Therefore, we investigated the presence of locally increased inflammatory and vasoactive factors in culprit coronary artery. METHODS: We performed primary PCI with PercuSurge GuideWire system in 18 AMI patients. We collected blood samples from the femoral artery before PCI and from culprit coronary artery after first predilation while inflating the distal protection balloon and after completing PCI. We determined concentrations of C-reactive protein, soluble CD40 ligand, Interleukin (IL-6), serotonin, tissue factor, and factor VIIa. RESULTS: While the concentrations of soluble CD40 ligand (2.84+/-3.74 vs 0.98+/-0.63 ng/mL, p=0.004), IL-6 (33.67+/-32.63 vs 17.08+/-21.41 pg/mL, p<0.001), serotonin (2.05+/-0.76 vs 0.92+/-0.60 ng/mL, p<0.001), tissue factor (257.17+/-84.34 vs 154.60+/-87.99 pg/mL, p<0.001) and factor VIIa (34.30+/-27.30 vs 24.19+/-28.00 ng/mL, p=0.016) were significantly higher in the culprit coronary artery than in the femoral artery, CRP levels did not differ. The locally elevated concentrations of various factors were successfully reduced after multiple aspirations of blood using the PercuSurge GuideWire system. CONCLUSIONS: We found increased levels of soluble CD40 ligand, IL-6, serotonin, tissue factor and factor VII in the culprit coronary artery compared to those in peripheral blood. The clinical impact of such locally increased soluble factors in the culprit coronary artery needs to be investigated in further studies.

Aged↗

Cardiac expression profiles of the naked DNA vectors encoding vascular endothelial growth factor and basic fibroblast growth factor.

We investigated expression profiles and biological effects of the naked DNA vectors in the heart. To this end, naked DNA vector was injected into the apex of the beating rat heart after thorocotomy. When the expression of LacZ reporter was examined by reverse transcription-PCR and histochemical staining for beta-galactosidase, LacZ expression was detected only in the heart, suggesting limited dissemination of the injected vector in vivo. Even within the heart, LacZ expression was limited to the injection area (apex). Similar observations were made with other transgenes such as VEGF and basic fibroblast growth factor (bFGF), where 77% and 69% of the total transgene exprssion were detected in the heart segments containing the apex. Although VEGF and bFGF expressions were detected until 2 weeks after DNA injection, the highest levels of VEGF and bFGF were observed on day 5 and day 1, respectively. The optimal doses of the vectors were 10 microg and 25 microg for the VEGF and bFGF vectors, respectively. Interestingly, injection of bFGF vector led to 50% increase in the level of endogenous murine VEGF expression. Consistent with this finding, the number of vessels that stained positive for alpha-smooth muscle actin was increased in the bFGF vector-injected heart. These results suggest that simple injection of naked DNA vector may be sufficient to induce significant angiogenesis in the myocardium and that naked DNA gene therapy may be a feasible approach for the treatment of ischemic heart disease.

Animals↗

Comparison of effects of drug-eluting stents versus bare metal stents on plasma C-reactive protein levels.

After coronary stenting, inflammatory mechanisms play a crucial role in the pathogenesis of neointimal proliferation and in-stent restenosis. Drug-eluting stents (DESs) have been shown to decrease in-stent restenosis in different studies. We compared plasma C-reactive protein (CRP) levels after DES implantation with levels after bare metal stent (BMS) implantation. We performed percutaneous coronary intervention with a single stent in 67 patients (54 men; 59 +/- 9 years of age; n = 21 in the BMS group, n = 46 in the DES group) who had stable angina. Plasma CRP levels were determined before intervention and at 48 hours, 72 hours, and 2 weeks after coronary stenting. There was no difference in clinical and angiographic baseline characteristics except that the DES group had more patients with diabetes (34.8% vs 9.5%, p = 0.04), smaller reference vessels (2.95 +/- 0.53 vs 3.29 +/- 0.53 mm, p = 0.02), and smaller stent diameters (3.0 +/- 0.4 mm vs 3.4 +/- 0.5 mm, p <0.01). Plasma CRP levels at 48 hours (13.4 +/- 14.7 vs 5.9 +/- 4.9 mg/L, p <0.01) and 72 hours (16.7 +/- 19.8 vs 5.4 +/- 3.9 mg/L, p <0.01) after stent implantation were significantly higher in the BMS than in the DES group. In conclusion, DESs showed significantly lower plasma CRP levels after coronary stenting compared with BMSs. This may reflect the potent effects of DESs on acute inflammatory reactions induced by coronary intervention.

Aged↗

Sirolimus- versus paclitaxel-eluting stent implantation for unprotected left main coronary artery stenosis.

We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 +/- 0.44 vs. 0.65 +/- 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.

Adult↗

Novel monoclonal antibody that recognizes new neoantigenic determinant of D-dimer.

Our novel monoclonal antibody (mAb) B4 reacted with only D-dimer but not intact fibrinogen, or fibrinogen degradation products (FgDP) such as D-monomer, E fragment on ELISA. B4 didn't react with denatured D-dimer, while it reacted well with denatured D-monomer rather than the native form, indicating that B4 recognizes some neoconformational epitope in D-dimer. In our epitope study, B4 recognized the N-terminal (Bbeta134-142) of D-dimer, which corresponds to the most flexible segment of coiled coil backbone. It was confirmed by inhibition assay of B4 binding to D-dimer using the synthesized peptides with this sequence. As the other evidence, B4 didn't bind to some D-dimer species produced from a particular fibrinogen variant. This fibrinogen variant is mutated BbetaLys133 residue to Gln133 thus it doesn't produce the particular N-terminal epitope of D134 approximately by plasmin. Finally, our mAb was useful for clinical application. ELISA using our mAbs was well correlated with other commercial D-dimer ELISAs and in some clinical samples it was preferable to them. These results suggest that the epitope for B4 is another neoantigenic determinant in native D-dimer as distinct from native D-monomer.

Antibodies, Monoclonal↗

Micellar phytosterols effectively reduce cholesterol absorption at low doses.

BACKGROUND: The objective of this study was to evaluate the effects of micellar phytosterols on cholesterol absorption in humans. METHODS: 24 healthy adults (mean age 37 years, 16 women and 8 men) underwent four cholesterol-absorption tests to compare the effects of micellar phytosterols supplement containing 500, 300, 200 mg phytosterols and placebo on cholesterol absorption in a cross-over design. Individual absorption tests were separated by 2 weeks. Using the single oral isotope method, inhibition of cholesterol absorption was determined by gas-chromatography mass spectrometry measurement of the differences in plasma hexadeuterated cholesterol enrichment 4 days after test meals with or without phytosterols. Each test meal provided 500 kcal and 89 mg cholesterol including 40 mg tracer cholesterol. We used a general linear mixed model with SAS to test the significance of treatment effect. RESULTS: Micellar phytosterols had a significant overall effect on cholesterol absorption (p = 0.0002), reduced cholesterol absorption by 23.3% at a dose of 300 mg phytosterols (p = 0.0004) and by 32.0% at a dose of 500 mg phytosterols (p = 0.0001) compared with the placebo. The effect of 200 mg treatment did not reach statistical significance but there was a tendency (p = 0.052). CONCLUSION: Water-dispersible, micellar phytosterols reduced cholesterol absorption effectively at very low doses.

Adult↗

Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo. Berberine improves neointima formation in a rat model.

Berberine, an alkaloid isolated from Chinese medicinal herbs, long been known for its anti-microbial activity and used to treat various infectious disorders in traditional Chinese medicine. In the present study, we have tested the hypothesis that berberine could inhibit vascular smooth muscle cell (VSMC) proliferation as it did in endothelial cells or cancer cells. Our results show that berberine significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin binding epidermal growth factor (HB-EGF), induced VSMC proliferation and migration in vitro, and this effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway. Furthermore, we have examined its effect in vivo using a rat carotid artery injury model. A 28 days of chronic berberine treatment using an osmotic pump (100 microg kg(-1)d(-1), 2 weeks before and 2 weeks after the injury) improved neointima formation. The Neointima/Media ratio for control group and berberine treated group were 1.14+/-0.11 and 0.85+/-0.06 (p<0.05), respectively, and the reduction was approximately 25%. The result of the present study suggests a possibility of berberine being a potent agent to control restenosis after balloon angioplasty and warrants further study to gain a more complete understanding of its underlying mechanisms at a cellular level.

Angioplasty, Balloon↗