Effect of repetitive lysine–tryptophan motifs on the bactericidal activity of antimicrobial peptides

Previous studies identified lysine- and tryptophan-rich sequences within various cationic antimicrobial peptides. In the present study, we synthesized a series of peptides composed of lysine (K)-tryptophan (W) repeats (KW)(n) (where n equals 2, 3, 4 or 5) with amidation of the C-terminal to increase cationicity. We found that increases in chain length up to (KW)(4) enhanced the peptides’ antibacterial activity; (KW)(5) exhibited somewhat less bactericidal activity than (KW)(4). Cytotoxicity, measured as lysis of human red blood cells, also increased with increasing chain length. With (KW)(5), reduced antibacterial activity and increased cytotoxicity correlated with greater hydrophobicity and self-aggregation in the aqueous environment. The peptides acted by inducing rapid collapse of the bacterial transmembrane potential and induction of membrane permeability. The mode of interaction of the peptides and the phosphate groups of lipopolysaccharide was dependent upon the peptides’ ability to permeate the membrane. Longer peptides [(KW)(4) and (KW)(5)] but not shorter peptides [(KW)(2) and (KW)(3)] strongly bound and partially inserted into negatively charged, anionic lipid bilayers. These longer peptides also induced membrane permeabilization and aggregation of lipid vesicles. The peptides had a disordered structure in aqueous solution, and only (KW)(4) and (KW)(5) displayed a folded conformation on lipid membranes. Moreover, (KW)(4) destroyed and agglutinated bacterial cells, demonstrating its potential as an antimicrobial agent. Collectively, the results show (KW)(4) to be the most efficacious peptide in the (KW)(n) series, exhibiting strong antibacterial activity with little cytotoxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00726-012-1388-6) contains supplementary material, which is available to authorized users

Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in patients with coronary artery disease: A retrospective virtual histology-intravascular ultrasound study

Background: The associations between statin and coronary plaque compositional changes were re­ported according to the use of high dose or not. An evaluation of the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using real world dosages of statin on coronary plaque composition was undertaken. Methods: The study subjects consisted of 61 patients (mean 59.9 years old, 45 males) who underwent percutaneous coronary intervention, baseline and follow-up (F/U; mean 8.4 months) virtual histology- -intravascular ultrasound (VH-IVUS) examination. Change of plaque composition at peri-stent area, which was selected in order to measure the identical site at F/U study, was compared according to the F/U LDL-C level. Results: Body mass index, prevalence of dyslipidemia, baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL-C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ≥ 70 mg/dL group (79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR 1.06, 95% CI 1.00–1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97–12.17, p = 0.056) showed strong tendency of regression of necrotic core volume (NCV) ≥ 10%. In multivariable logis­tic regression analysis, F/U HDL-C (OR 1.07, 95% CI 1.01–1.14, p = 0.020) and F/U LDL-C < 70 mg/dL (OR 8.02, 95% CI 1.58–40.68, p = 0.012) were the independent factors for regression of NCV ≥ 10%. Conclusions: Follow-up LDL-C level < 70 mg/dL with any types of statins and increase of HDL-C were associated with regression of NCV ≥ 10% in patients with coronary artery disease

A case of anemia caused by combined vitamin B12 and iron deficiency manifesting as short stature and delayed puberty

Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake is rare in children in the modern era because of improvements in nutritional status. However, such anemia can be caused by decreased ingestion or impaired absorption and/or utilization of vitamin B12. We report the case of an 18-year-old man with short stature, prepubertal sexual maturation, exertional dyspnea, and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small bowel resection from 50 cm below the Treitz ligament to 5 cm above the ileocecal valve necessitated by midgut volvulus in the neonatal period. Laboratory tests showed deficiencies of both vitamin B12 and iron. A bone marrow examination revealed dyserythropoiesis and low levels of hemosiderin particles, and a cytogenetic study disclosed a normal karyotype. After treatment with parenteral vitamin B12 and elemental iron, both anemia and growth showed gradual improvement. This is a rare case that presented with short stature and delayed puberty caused by nutritional deficiency anemia in Korea

Association of factor XIII Val34Leu polymorphism and coronary artery disease: A meta-analysis

Background: Factor XIII plays an important role in the stabilization of the linkage between fibrins and in the pathophysiology of coronary artery disease (CAD). The association between factor XIII Val34Leu polymorphism and CAD risk remains controversial. Methods: We conducted a meta-analysis of 36 studies involving 26,940 cases and 34,694 controls. Subgroup analyses were performed with division of data into disease (myocardial infarction [MI], CAD without MI), age, and sex. Results: Factor XIII Val34Leu polymorphism was significantly associated with ove all CAD risk (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.03–1.06, p = 0.004) and MI risk (OR = 1.15, 95% CI 1.07–1.25, p = 0.0003), but not with CAD without MI risk (OR = 1.00, 95% CI 0.87–1.15, p = 0.96). In the subgroup analysis by age and sex, there was no association between Val34Leu polymorphism and CAD. Conclusions: This meta-analysis found that factor XIII Val34Leu polymorphism was associated with CAD risk, especially MI, but not with CAD without MI. In addition, age and sex did not affect the relationship between factor XIII Val34Leu polymorphism and CAD risk.

In-stent restenosis-prone coronary plaque composition: A retrospective virtual histology-intravascular ultrasound study

  Background: The mechanism of in-stent restenosis (ISR) is multifactorial, which includes biological, mechanical and technical factors. This study hypothesized that increased inflammatory reaction, which is known to be an important atherosclerotic process, at a culprit lesion may lead to higher restenosis rates. Methods: The study population consisted of 241 patients who had undergone percutaneous coronary intervention with virtual histology-intravascular ultrasound (VH-IVUS) and a 9-month follow-up coronary angiography. Compared herein is the coronary plaque composition between patients with ISR and those without ISR. Results: Patients with ISR (n = 27) were likely to be older (66.2 ± 9.5 years vs. 58.7 ± 11.7 years, p = 0.002) and have higher levels of high-sensitivity C-reactive protein (hs-CRP, 1.60 ± 3.59 mg/dL vs. 0.31 ± 0.76 mg/dL, p < 0.001) than those without ISR (n = 214). VH-IVUS examination showed that percent necrotic core volume (14.3 ± 8.7% vs. 19.5 ± 9.1%, p = 0.005) was higher in those without ISR than those with ISR. Multivariate analysis revealed that hs-CRP (odds ratio [OR] 3.334, 95% con­fidence interval [CI] 1.158–9.596, p = 0.026) and age (OR 3.557, 95% CI 1.242–10.192, p = 0.018) were associated with ISR. Conclusions: This study suggests that ISR is not associated with baseline coronary plaque composition but is associated with old age and increased expression of the inflammatory marker of hs-CRP. (Cardiol J 2018; 25, 1: 7–13

Synthesis of High Crystalline Al-Doped ZnO Nanopowders from Al 2

High crystalline Al-doped ZnO (AZO) nanopowders were prepared by in-flight treatment of ZnO and Al2O3 in Radio-Frequency (RF) thermal plasma. Micron-sized (~1 μm) ZnO and Al2O3 powders were mixed at Al/Zn ratios of 3.3 and 6.7 at.% and then injected into the RF thermal plasma torch along the centerline at a feeding rate of 6.6 g/min. The RF thermal plasma torch system was operated at the plate power level of ~140 kVA to evaporate the mixture oxides and the resultant vapor species were condensed into solid particles by the high flow rate of quenching gas (~7000 slpm). The FE-SEM images of the as-treated powders showed that the multipod shaped and the whisker type nanoparticles were mainly synthesized. In addition, these nanocrystalline structures were confirmed as the single phase AZO nanopowders with the hexagonal wurtzite ZnO structure by the XRD patterns and FE-TEM results with the SAED image. However, the composition changes of 0.3 and 1.0 at.% were checked for the as-synthesized AZO nanopowders at Al/Zn ratios of 3.3 and 6.7 at.%, respectively, by the XRF data, which can require the adjustment of Al/Zn in the mixture precursors for the applications of high Al doping concentrations