Effects of extracorporeal shockwave therapy on nanostructural and biomechanical responses in the collagenase-induced Achilles tendinitis animal model

The aim of this study was to quantitatively investigate the effects of extracorporeal shockwave therapy (ESWT) on the nanostructure and adhesion force of collagen fibrils in a rat model of collagenase-induced Achilles tendinitis (CIAT) using histology and atomic force microscopy. A total of 45 rats were divided into experimental groups of three rats each: a control group, 27 CIAT rats with nine time points, and 15 ESWT rats with five time points. Progressive changes in nanostructure including the fibrillary diameter and D-periodicity, and biomechanical properties including the fibrillary adhesion forces in each healing phase were investigated over a 5-week period after collagenase injection. On postoperative?day 3, CIAT rats showed granulomatous tissue associated with subacute inflammation, and a deterioration in nanostructure and mechanical properties compared to controls. On postoperative?day 12, the ESWT group showed increased vascularity, fibroblastic activity, lymphocyte and plasma cell infiltration, dense histocytes, and disorganization of the fibers compared to the CIAT group. The ESWT group showed and improvement in nanostructure and mechanical properties compared to controls, while the CIAT group showed a deterioration in nanostructure and mechanical properties compared to controls. On postoperative?day 26, the ESWT group showed 30% inflamed tissue and 70% fibrotic tissue, while the CIAT group showed chronic inflammation. By the end of the experiments, in both groups the changes had reversed and the tissues were similar in appearance to those in the control group. Following ESWT the deformed and irregular collagen network returned to a well-aligned normal collagen network nanostructure. These results suggest that ESWT may promote the healing response in Achilles tendinitis.     

Association between TGFBR2 gene polymorphism (rs2228048, Asn389Asn) and intracerebral hemorrhage in Korean population

Transforming growth factor, beta receptor II (TGFBR2) is mainly expressed by neurons in the central nervous system, and reduced neuronal TGFBR2 signaling results in accelerated age-dependent neurodegeneration. To investigate whether TGFBR2 polymorphisms are associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH), two single nucleotide polymorphisms (SNPs) of TGFBR2 gene (rs764522, -1444C/G; rs2228048, Asn389Asn) were selected and genotyped by direct sequencing in 247 stroke patients (120 IS and 127 ICH) and 655 control subjects (260 for IS and 395 for ICH). SNPStats, SNPAnalyzer, Helixtree, and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant, dominant, recessive, and log-additive) were performed to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and p values. The synonymous SNP rs2228048 was significantly associated with ICH (p = 0.032 in codominant 2 model, p = 0.024 in dominant model, p = 0.020 in recessive model, and p = 0.005 in log-additive model) and Fisher's exact test (p = 0.009). Allele frequencies of rs2228048 were different between ICH and controls (p = 0.006). In Bonferroni correction, these correlations were also significant. These results suggest that the synonymous SNP rs2228048 of TGFBR2 gene may be associated with development of ICH in Korean population.     

Hydrogen peroxide-induced alterations of tight junction proteins in bovine brain microvascular endothelial cells

Occludin and zonular occludens (ZO)-1 in tight junctions (TJs) and actin play an important role in maintaining blood-brain barrier (BBB) endothelial ion and solute barriers. Malfunction of BBB by reactive oxygen species (ROS) has been attributed to the disruption of TJs. This study examined H2O2 effects on changes of paracellular permeability, actin, and TJ proteins (occludin and ZO-1) using primary culture of bovine brain microvessel endothelial cells. The BBB permeability, measured as transendothelial electrical resistance (TER), decreased in a dose- and time-dependent manner when treated with H2O2. Cytotoxicity test revealed that H2O2 did not cause cell death at 0.01, 0.1, and 1.0 mM H2O2. H2O2 caused increased protein expression of occludin (1.17- to 1.29-fold) and actin (1.2- to 1.3-fold). ZO-1 maintained steady state levels of expression. H2O2 caused rearrangement of occludin and ZO-1 at tight junctions and formation of actin stress fiber. Although ZO-1 did not show significant change in protein expression, permeability changes shown in the current study correlate with alterations in expression and localization of occludin, actin, and ZO-1. These data suggest that H2O2 induces increased paracellular permeability of BBB that is accompanied with redistribution of occludin and ZO-1 and increased protein expression of occludin and actin.     

T Allele of nonsense polymorphism (rs2039381, Gln71Stop) of interferon-ε is a risk factor for the development of intracerebral hemorrhage

Interferons (IFNs) play key roles in various biologic responses including antiviral and immune reactions. We evaluated one possible risk factor in nonsense polymorphism (rs2039381, Gln71Stop) of interferon-ε (IFNE).     

Differentiation of Gut and Hepatic First-Pass Effect of Drugs: 1. Studies of Verapamil in Ported Dogs

Purpose. To investigate the relative contributions of the gut and liver to the first-pass loss of verapamil (VL) using anin vivo intestinal-vascular access port (IVAP) dog model. Methods. Basic pharmacokinetics of VL were determined after intravenous (IV: 0.5 mg/kg), portal venous (PV: 2 mg/kg), and duodenal (ID: 2 mg/kg) administration in IVAP dogs. Serial blood samples were collected for 8 h after dosing, and plasma was analyzed for unchanged drug by a high-performance liquid chromatography-fluorescence method. Extraction ratios in the liver and intestinal tract were determined from the area under the concentration-time curves for ID, PV, and IV administration. The functional role of CYP450 or secretory transporters such as P-gp on the gut and liver first-pass loss of VL was further studied using ritonavir, a known substrate or inhibitor of these processes. Results. The liver had a high intrinsic capacity for clearing VL because the absolute bioavailability (BA) of VL was 21.7% after PV administration. The BA of VL after ID administration was 23.5%; therefore, intestinal absorption was complete and intestinal extraction was negligible (ER_GI 0). The BA of VL increased from 23.5% to 66.2% in the presence of ritonavir primarily due to a reduction in hepatic extraction. Conclusions. Although the liver had a high intrinsic capacity for extracting VL, the contribution of gut to the first-pass loss of VL was negligible. Because of the additive effects of intestinal CYP3A-mediated metabolism and secretory transport, a significant gut first-pass effect was expected, but not observed in dogs. These studies demonstrate the utility of the in vivo IVAP dog model for evaluating the relative contribution of the gut and liver to the first-pass loss of drugs and for characterizing the functional role that CYP450 metabolism and/or secretory transporters play in drug-drug interactions and reduced oral bioavailability.     

Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke

To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.     

Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa

To study the status of oxidative DNA damage in Helicobacter pylori infection in more detail, we examined oxidative DNA damage to individual genes by determining the loss of PCR product of a targeted gene before and after gastric mucosal DNA was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8-hydroxyguanine residues. The results showed that, of the 5 genes tested, p53, insulin-like growth factor II receptor and transforming growth factor-beta receptor type II showed significant oxidative DNA damage in H. pylori-positive tissues and that the BAX and beta-ACTIN genes were relatively undamaged. These results suggest that in H. pylori infection, oxidative DNA damage does not occur homogeneously throughout the genomic DNA but, rather, in a gene-specific manner. We conclude that the progressive accumulation of preferential oxidative DNA damage in certain genes, such as p53, likely contributes to gastric carcinogenesis.     

Power quality control of an autonomous wind–diesel power system based on hybrid intelligent controller

Wind power generation is gaining popularity as the power industry in the world is moving toward more liberalized trade of energy along with public concerns of more environmentally friendly mode of electricity generation. The weakness of wind power generation is its dependence on nature—the power output varies in quite a wide range due to the change of wind speed, which is difficult to model and predict. The excess fluctuation of power output and voltages can influence negatively the quality of electricity in the distribution system connected to the wind power generation plant. In this paper, the authors propose an intelligent adaptive system to control the output of a wind power generation plant to maintain the quality of electricity in the distribution system. The target wind generator is a cost-effective induction generator, while the plant is equipped with a small capacity energy storage based on conventional batteries, heater load for co-generation and braking, and a voltage smoothing device such as a static Var compensator (SVC). Fuzzy logic controller provides a flexible controller covering a wide range of energy/voltage compensation. A neural network inverse model is designed to provide compensating control amount for a system. The system can be optimized to cope with the fluctuating market-based electricity price conditions to lower the cost of electricity consumption or to maximize the power sales opportunities from the wind generation plant.