Dong Hwan Yun

Naringin Protects against Rotenone-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells

Rotenone, a mitochondrial complex I inhibitor, can induce the pathological features of Parkinsons disease (PD). In the present study, naringin, a grapefruit flavonoid, inhibited rotenone-induced cell death in human neuroblastoma SH-SY5Y cells. We assessed cell death and apoptosis by measuring mitogen-activated protein kinase (MAPKs) and caspase (CASPs) activities and by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Naringin also blocked rotenone-induced phosphorylation of Jun NH2-terminal protein kinase (JNK) and P38, and prevented changes in B-cell CLL/lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) expression levels. In addition, naringin reduced the enzyme activity of caspase 3 and cleavages of caspase 9, poly (ADP-ribose) polymerase (PARP), and caspase 3. These results suggest that naringin has a neuroprotective effect on rotenone-induced cell death in human neuroblastoma SH-SY5Y cells.

Balance Control and Knee Osteoarthritis Severity

Objective To investigate balance control according to the severity of knee osteoarthritis (OA) using clinical tests and Tetra-ataxiometric posturography (Tetrax®). Method A total 80 patients with primary knee OA classified according to American College of Rheumatology criteria, and 40 age-matched controls were enrolled in this study. Of those with OA, 39 patients had mild OA (Kellgren-Lawrence [KL] grade 1, 2) and the other 41 had moderate to severe OA (KL grade 3, 4). The postural control capabilities of the subjects were assessed using the timed up and go test (TUG), Berg balance scale (BBS), and Tetrax®, which utilizes two paired force plates to measure vertical pressure fluctuations over both heels and forefeet. The subjects were checked for their stability index (ST), Fourier index, weight distribution index (WDI), and synchronization index (SI) in eight positions using Tetrax®. Results Patients with moderate to severe OA exhibited significantly higher stability indices in all positions than patients with mild OA. The Fourier index was also higher in patients with moderate to severe OA than in patients with mild OA. However, the weight distribution index and synchronization of both heels and forefeet were not significantly different in the three groups. Conclusion These findings suggest that patients with moderate to severe OA have more deficits in balance control than those with mild disease. Therefore, evaluation of balance control and education aimed at preventing falls would be useful to patients with knee OA.

Efficacy of ultrasonography-guided injections in patients with facet syndrome of the low lumbar spine.

Objective To investigate the efficacy of ultrasonography (US)-guided injections in patients with low lumbar facet syndrome, compared with that in patients who received fluoroscopy (FS)-guided injections. Method Fifty-seven subjects with facet syndrome of the lumbar spine of the L4-5 and L5-S1 levels were randomly divided into two groups to receive intraarticular injections into the facet joint. One group received FS-guided facet joint injections and the other group received US-guided facet joint injections. Treatment effectiveness was assessed using a visual analogue scale (VAS), physicians and patients global assessment (PhyGA, PaGA), and the modified Oswestry Disability Index (MODI). All parameters were evaluated four times: before injections, and at a week, a month, and three months after injections. We also measured, in both groups, how long it took to complete the whole procedure. Results Each group showed significant improvement from the facet joint injections on the VAS, PhyGA, PaGA, and MODI (p<0.05). However at a week, a month, and three months after injections, no significant differences were observed between the groups with regard to VAS, PhyGA, PaGA, and MODI (p>0.05). Statistically significant differences in procedure time were observed between groups (FS: 248.7±6.5 sec; US: 263.4±5.9 sec; p=0.023). Conclusion US-guided injections in patients with lumbar facet syndrome are as effective as FS-guided injections for pain relief and improving activities of daily living.

Association between interleukin 15 receptor, alpha (IL15RA) polymorphism and Korean patients with ossification of the posterior longitudinal ligament

OBJECTIVES Recently, a number of evidences have been reported concerning the genetic factor involved in the development of ossification of the posterior longitudinal ligament (OPLL). The purpose of this study was to investigate single nucleotide polymorphisms (SNPs) of the interleukin 15 receptor, alpha (IL15RA) gene as a risk factor in Korean patients with OPLL. DESIGN To investigate the genetic association, two coding SNPs (rs2296139, Thr73Thr; rs2228059, Asn182Thr) in IL15RA were genotyped in 166 OPLL patients and 230 control subjects. SNPStats, SNPAnalyzer, and Helixtree programs were used for association analysis. RESULTS In the present study, we found the association between a missense SNP (rs2228059) and the risk of OPLL in codominant (p = 0.0028, OR = 1.58, 95% CI = 1.17-2.14), dominant (p = 0.0071, OR = 1.82, 95% CI = 1.17-2.82), and recessive models (p = 0.036, OR = 1.79, 95% CI = 1.04-3.09). The frequency of rs2228059 allele was significantly associated with the susceptibility of OPLL (p = 0.0043, OR = 1.52, 95% CI = 1.14-2.02). After Bonferroni correction, the missense SNP (rs2228059, Asn182Thr) still had significant correlations (p = 0.0056 in codominant model; p = 0.0142 in dominant model; p = 0.0086 in allele analysis). Haplotype variation in IL15RA was associated with OPLL (global haplotype test, p = 0.025). CONCLUSIONS These results suggest that IL15RA polymorphism may be associated with the susceptibility of OPLL in Korean population.

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.

Matrix metalloproteinase-3 gene polymorphisms are associated with ischemic stroke.

Stroke is a heterogeneous disease caused by different pathogenic mechanisms. Several candidate genes for stroke have been proposed, but few have been replicated. Matrix metalloproteinases (MMPs) are expressed following stroke. We investigated the association of single nucleotide polymorphisms (SNPs) of the MMP3 gene with stroke in the Korean population. This study included 186 stroke patients [116 ischemic stroke (IS) and 70 intracerebral hemorrhage (ICH)] and 668 age-matched control subjects (267 for IS and 401 for ICH). Three SNPs [rs520540 (Ala362Ala), rs602128 (Asp96Asp), and rs679620 (Lys45Glu)] in the coding region of MMP3 were selected and genotyped by direct sequencing. HelixTree, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant, dominant, and recessive models) were conducted to evaluate odds ratio, 95% confidence interval, and P value. Three SNPs in the MMP3 gene were significantly associated with IS (P<0.05). The genotype distribution of 3 SNPs differed between the IS and control subjects. However, there was no association of the SNPs between the ICH and control. In analysis of gender, 3 SNPs were also associated with IS in female group (P<0.05). These SNPs remained significantly associated with IS after the Bonferroni correction for multiple testing (P(c)<0.05). Haplotype analysis revealed that no haplotypes were associated with IS or ICH. Overall, the results of our study demonstrate an association of the MMP3 gene with development of IS, and no association of MMP3 with ICH.

Association of Toll-like Receptor 2 Polymorphisms with National Institute of Health Stroke Scale Scores of Ischemic Stroke Patients

Toll-like receptor 2 (TLR2) has been shown to have an important role in the postischemic inflammatory response and to contribute to ischemic brain damage. In this study, we investigated whether coding region single nucleotide polymorphisms (SNPs) of the TLR2 gene were associated with ischemic stroke (IS) and with clinical phenotypes in IS patients. We genotyped two SNPs (rs3804099 [Asn199Asn] and rs3804100 [Ser450Ser]) using direct sequencing in 202 IS patients and 291 control subjects. No SNPs of the TLR2 gene were found to be associated with IS. However, in analysis of clinical phenotypes, we found that rs3804099 was associated with the National Institute of Health Stroke Scale (NIHSS) scores of IS patients in codominant (TC vs. TT, p = 0.0005; CC vs. TT, p = 0.0007) and dominant models (TC/CC vs. TT, p = 0.0001). Also, rs3804100 revealed significant association in codominant (TC vs. TT, p = 0.0002; CC vs. TT, p = 0.008) and dominant models (TC/CC vs. TT, p < 0.0001). In allele frequency analysis, we also found that the C alleles of rs3804099 and rs3804100 were associated with higher NIHSS scores (p = 0.0003 in rs3804099; p = 0.0001 in rs3804100). Our results suggest that TLR2 may be related to severe IS.

Efficacy of Ultrasonography Guided Stellate Ganglion Blockade in the Stroke Patients with Complex Regional Pain Syndrome

Objective To compare the efficacy of ultrasonography guided stellate ganglion block (US-SGB) with that of blind SGB in management of the stroke patients with complex regional pain syndrome (CRPS) type 1. Method Forty-two patients with post-stroke CRPS were randomly assigned to either US-guided SGB (22 patients) or blind SGB group (20 patients). The mean age of US-guided SGB and blind SGB groups was 61.3±5.6 years and 59.1±4.5 years. We performed two blockades at 7-day intervals on the affected side of patients with CRPS. Pain intensity, using a visual analog score (VAS), score of CRPS clinical severity, and the amounts of affected hand swelling with a hand volumeter were assessed before, 2 weeks and 4 weeks after treatment. Results In both groups, VAS and the amount of hand swelling were significantly decreased after 2 weeks and after 4 weeks. Between two groups, VAS difference of US-guided SGB group and that of blind SGB group were 2.61±1.09, 1.88±0.62 at 2 weeks and 3.67±1.03, 3.13±0.62 at 4 weeks, respectively. US-guided SGB group showed more significant improvement in mean change of VAS compared to the blind SGB group (p-value<0.05). Conclusion Both US-guided SGB and blind SGB techniques were effective in relieving pain in subacute stroke patients with CRPS. US-guided SGB was better in pain relief but has no advantages in reduction of hand swelling in this study.

The Relationship Between Tongue Pressure and Oral Dysphagia in Stroke Patients

Objective To evaluate the relationships between tongue pressure and different aspects of the oral-phase swallowing function. Methods We included 96 stroke patients with dysphagia, ranging in age from 40 to 88 years (mean, 63.7 years). Measurements of tongue pressure were obtained with the Iowa Oral Performance Instrument, a device with established normative data. Three trials of maximum performance were performed for lip closure pressure (LP), anterior hard palate-to-tongue pressure (AP), and posterior hard palate-to-tongue pressure (PP); buccal-to-tongue pressures on both sides were also recorded (buccal-to-tongue pressure, on the weak side [BW]; buccal-to-tongue pressure, on the healthy side [BH]). The average pressure in each result was compared between the groups. Clinical evaluation of the swallowing function was performed with a videofluoroscopic swallowing study. Results The average maximum AP and PP values in the intact LC group were significantly higher than those in the inadequate lip closure group (AP, p=0.003; PP, p<0.001). AP and PP showed significant relationships with bolus formation (BF), mastication, premature bolus loss (PBL), tongue to palate contact (TP), and oral transit time (OTT). Furthermore, LP, BW, and BH values were significantly higher in the groups with intact mastication, without PBL and intact TP. Conclusion These findings indicate that the tongue pressure appears to be closely related to the oral-phase swallowing function in post-stroke patients, especially BF, mastication, PBL, TP and OTT.

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). We recruited stroke [119 ischemic stroke (IS) and 145 intracerebral hemorrhage (ICH)] and control (401), respectively. The nonsense SNP (rs2039381, Gln71Stop) of IFNE was selected. We identified individual genotype using sequencing. SNPStats and SPSS 18.0 programs were used to analyze genetic data. Genotype frequencies (C/C:C/T:T/T) in the ICH group and control group were 59.3:37.9:2.8 and 73.6:23.4:3.0, respectively. We found that rs2039381 was associated with ICH (OR = 2.01, 95% CI = 1.33-3.03, p = 0.001 in codominant1 model; OR = 1.91, 95% CI = 1.28-2.84, p = 0.0016 in dominant model; OR = 1.60, 95% CI = 1.14-2.26, p = 0.0074 in log-additive model). T allele frequency of rs2039381 was significantly higher in ICH than in controls. The nonsense SNP (rs2039381, Gln71Stop) of IFNE was associated with ICH (OR = 1.61, 95% CI = 1.14-2.26, p = 0.006). A nonsense SNP (rs2039381, Gln71Stop) of IFNE was associated with ICH in Korean population. Our findings raise the possibility that the T allele of rs2039381 is a risk factor which is susceptible to ICH.