Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.

OBJECTIVE: To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion. METHODS: C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH. RESULTS: GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro. CONCLUSION: Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.

Association Between Coffee Consumption and Circulating Levels of Adiponectin and Leptin.

Coffee has been proposed to have benefits for chronic diseases; however, the relevant mechanism remains to be elucidated. We conducted a cross-sectional study and evaluated the levels of adiponectin and leptin in relation to coffee consumption. We included a total of 4406 individuals (men = 2587 and women = 1819) for adiponectin analysis and 2922 individuals (men = 1731 and women = 1191) for leptin analysis. Participants answered number of cups of coffee per week and types of coffee they consumed and their serum levels of adiponectin and leptin were measured using an enzyme-linked immunosorbent assay. We found that increasing coffee consumption was associated with increased levels of adiponectin among women; geometric means of adiponectin were 8.0 (95% CI: 7.2-8.9 µg/mL) among women who regularly consumed 15 or greater cups/week, but 7.5 (95% CI: 6.8-8.4 µg/mL) among women who did not consume coffee (P for trend = .009). Leptin levels were inversely associated with coffee consumption among both men and women (P for trend = .04 for men and 0.04 for women); geometric means of 15 or greater cups of coffee per week were 2.6 (95% CI: 2.4-2.8 ng/mL) among men and 5.1 (95% CI: 4.5-5.8 ng/mL) among women, but for noncoffee drinkers, geometric means were 3.0 (95% CI: 2.7-3.3 ng/mL) for men and 5.8 (95% CI: 5.1-6.6 ng/mL) for women. Coffee consumption was associated with higher circulating levels of adiponectin and lower circulating levels of leptin. Our study may suggest that improvement in adipocyte function contributes to the beneficial metabolic effects of coffee consumption.

Pseudoceramide stimulates peroxisome proliferator-activated receptor-α expression in a murine model of atopic dermatitis: molecular basis underlying the anti-inflammatory effect and the preventive effect against steroid-induced barrier impairment.

Topical pseudoceramides are successfully used in skin barrier repair therapy for atopic dermatitis (AD) and demonstrated to reduce the adverse effects of topical glucocorticoids (GC). However, the molecular mechanisms involved are not fully understood. We investigated whether PC-9S (myristoyl/palmitoyloxostearamide/arachamide MEA, Neopharm, Daejeon, Korea), one of the synthetic pseudoceramides, could stimulate peroxisome proliferator-activated receptor (PPAR)α expression in a hapten [oxazolone (oxa)]-induced AD murine model (oxa-AD mice) and subsequently improved permeability barrier, reduced inflammation, and increased antimicrobial peptides (AMPs) expression. Normal hairless mice and oxa-AD mice were topically treated twice daily with either PC-9S-containing physiologic lipid mixture (PLM), vehicle (PLM), or PPARα agonist for 4 days. Topical PC-9S significantly increased PPARα expression in mouse epidermis in vivo and in oxa-AD mice skin comparable with PPARα agonist. Topical PC-9S-containing PLM significantly reduced basal trans-epidermal water loss (TEWL), surface pH, and mast cell infiltrates and prevented the decline of AMPs expression in oxa-AD mice, which were abrogated by PPARα antagonist. Then, oxa-AD mice were treated with super-potent topical GC twice daily for 4 days with or without PC-9S co-applications. Co-treatment with PC-9S-containing PLM suppressed GC-induced increase in basal TEWL, epidermal thinning, reduced loricrin expression, and impaired barrier recovery and these effects were attenuated by PPARα antagonist. Collectively, our findings suggest that pseudoceramide PC-9S-induced stimulation of PPARα expression provides a new mechanism by which pseudoceramides show anti-inflammatory property, improve the permeability and antimicrobial barrier function, and prevent the negative effects of topical GC.

Prevalence of human papillomavirus infection and RAS mutation in sporadic keratoacanthoma.

BACKGROUND: RAS gene activation and its association with human papillomavirus (HPV) infection have been extensively studied in various cancers. However, the correlation between RAS mutations and HPV in keratoacanthoma (KA) has not yet been investigated. METHODS: Detection of HPV DNA was performed by nested polymerase chain reaction in 28 KA specimens. Molecular analysis was also performed to identify oncogenic mutations (HRAS, KRAS, NRAS). Statistical analyses were performed using the Fisher's exact tests. RESULTS: HPV DNA was detected in eight (28.6%) of the 28 samples, and RAS mutations were detected in eight (28.6%). Six samples had an HRAS mutation, and two showed the NRAS mutation. The presence of an RAS mutation was significantly correlated with a history of chronic sun damage (P = 0.005). However, no significant correlation was observed between HPV infection and RAS mutation. CONCLUSIONS: Our findings suggest that mutational activation of the RAS gene is a common event in KA. However, RAS oncogene activation and HPV infection seem to represent two independent factors in the development of KA.

Predictive factors for occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma by preoperative ultrasonographic and pathological features.

BACKGROUND: The surgical extent and indication for treatment in patients with papillary thyroid microcarcinoma (PTMC) remain a controversial issue. The aim of this study was to investigate the predictive factor for contralateral occult carcinoma in patients with unilateral PTMC by preoperative ultrasonographic and pathological features. METHODS: Of the total patients who underwent thyroidectomy, 455 patients with PTMC confined to one unilateral lobe as diagnosed using preoperative ultrasonography (US) were enrolled in the study. Occult contralateral carcinoma was defined as tumor foci in the contralateral lobe that was not detected preoperatively, but was detected pathologically. All patients underwent preoperative US review to investigate the US features of PTMC such as laterality, location, size, internal component, echogenicity, margin, calcification shape, multifocality, bilaterality, extrathyroidal extension, and location with respect to the trachea. Clinicopathological data were also analyzed. RESULTS: Of the total of 455 patients who underwent total thyroidectomy for preoperatively detected unilateral PTMC, 71 patients (15.6 %) had contralateral occult carcinoma. Clinicopathological characteristics did not significantly differ between patients with and without contralateral occult carcinoma. Multivariate analysis showed that the absence of a well-defined margin and the presence of a probably benign nodule in the contralateral lobe were independent predictive factors for contralateral occult carcinoma in patients with unilateral PTMC in preoperative US images. CONCLUSION: We demonstrated that an absence of a well-defined margin and the presence of a probably benign nodule in the contralateral lobe were independent predictive factors for contralateral occult carcinoma in patients with unilateral PTMC in preoperative US. The prediction of contralateral occult carcinoma in unilateral PTMC using preoperative US features could be useful for determining the optical extent of surgery.

Association between interleukin 17/interleukin 17 receptor gene polymorphisms and papillary thyroid cancer in Korean population.

BACKGROUND: Although numerous recent studies have implicated a role for interleukin 17(IL17) in tumor development, the mechanisms of IL17 involvement are still uncharacterized. The aims of this study were to determine whether single nucleotide polymorphisms (SNPs) in IL17 and IL17R contribute to the development of papillary thyroid cancer (PTC) and to assess the relationship between IL17 and IL17R SNPs and the clinicopathologic characteristics of PTC. MATERIALS AND METHODS: Eight SNPs located within the IL17A, IL17RA, and IL17RB genes were genotyped using direct sequencing in 94 patients with PTC and 260 patients without PTC (controls). Genetic data were analyzed using commercially available software. Statistical analyses were then performed to examine the relationships between these SNPs and the clinicopathologic characteristics of PTC. RESULTS: Genotyping analysis demonstrated that the IL17RA SNP rs4819554 (codominant model 1, odds ratio (OR)=0.39, P=0.001) and the IL17RB SNP rs1025689 (dominant model, OR=0.59, P=0.043) were significantly associated with lack of PTC. Interestingly, the IL17A SNP rs2275913 (codominant model 2, OR=0.19, P=0.034) was significantly associated with lack of multifocality. Furthermore, the IL17RA SNP rs4819554 (dominant model, OR=0.25, P=0.010) was significantly associated with lack of cancer bilaterality. CONCLUSION: In this study of SNPs in the IL17 and IL17R genes in patients with PTC, we demonstrated that IL17RA polymorphisms can influence both the development and the bilaterality of PTC.

Comparison between the therapeutic effect of metformin, glimepiride and their combination as an add-on treatment to insulin glargine in uncontrolled patients with type 2 diabetes.

AIMS: To compare the commonly prescribed oral anti-diabetic drug (OAD) combinations to use as an add-on therapy with insulin glargine in patients with uncontrolled type 2 diabetes despite submaximal doses of OADs. METHODS: People with inadequately controlled type 2 diabetes (n = 99) were randomly assigned on a 1∶1∶1 basis to receive insulin glargin, with fixed doses of glimepiride, metformin, and glimepiride plus metformin. Outcomes assessed included HbA1c, the changes in fasting glucose levels, body weight, serum lipids values, insulin dose and symptomatic hypoglycemia. RESULTS: After 24 weeks, HbA1C levels improved from (mean ± SD) 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol) with insulin glargine plus metformin, from 8.4±1.0% to 7.7±1.3% (68.8±10.6 mmol/mol to 61.1±14.4 mmol/mol) with insulin glargine plus glimepiride and from 8.7±0.9% to 7.3±0.6% (71.7±9.8 mmol/mol to 56.2±6.7 mmol/mol) with insulin glargine plus glimepirde plus metformin. The decrease in HbA1c was more pronounced with insulin glargine plus glimepiride plus metformin than with insulin glargine plus metformin (0.49% [CI, 0.16% to 0.82%]; P = 0.005) (5.10 mmol/mol [CI, 1.64 to 8.61]; P = 0.005) and insulin glargine plus glimepiride (0.59% [CI, 0.13% to 1.05%]; P = 0.012) (5.87 mmol/mol [CI, 1.10 to 10.64]; P = 0.012) (overall P = 0.02). Weight gain and the risk of hypoglycemia of any type did not significantly differ among the treatment groups. CONCLUSION: The combination therapy of metformin and glimepiride plus glargine insulin resulted in a significant improvement in overall glycemic control as compared with the other combinations. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT00708578. The approval number of Kangbuk Samsung hospital's institutional review board (IRB): C0825.

2011 clinical practice guidelines for type 2 diabetes in Korea.

As in other countries, type 2 diabetes is major health concern in Korea. A dramatic increase in the prevalence of type 2 diabetes and its chronic complications has led to an increase in health costs and economic burdens. Early detection of high risk individuals, hidden diabetic patients, and improvement in the quality of care for the disease are the first steps to mitigate the increase in prevalence. The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the '3rd Clinical Practice Guidelines' at the end of 2010. In the guidelines, the committee recommended active screening of high risk individuals for early detection and added the hemoglobin A1c level to the diagnostic criteria for type 2 diabetes based on clinical studies performed in Korea. Furthermore, the committee members emphasized that integrating patient education and self-management is an essential part of care. The drug treatment algorithm based on the degree of hyperglycemia and patient characteristics were also updated.

Planning study for available dose of hypoxic tumor volume using fluorine-18-labeled fluoromisonidazole positron emission tomography for treatment of the head and neck cancer.

PURPOSE: To investigate the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided intensity-modulated radiotherapy (IMRT) in dose escalation to attack the hypoxic volume of a tumor mass without increasing the normal tissue dose in head and neck cancer patients. MATERIALS AND METHODS: Eight consecutive head and neck cancer patients underwent (18)F-FMISO PET/CT simulation. Hypoxic tumor volume (HTV) was defined using a tumor-to-cerebellum ratio (T/C) of 1.3 as the threshold for (18)F-FMISO PET/CT. Dose-escalation plans for treating HTVs using (18)F-FMISO PET/CT-guided IMRT were performed for these patients. The standard plan was 72Gy to the gross tumor volume (GTV) administered as 30 daily fractions of 2.4Gy. In biologically optimized IMRT plans, the daily dose to the HTV ranged from 2.6 to 3.6Gy. Dose-volume histograms (DVHs) were generated as part of each plan, and the results of planning were analyzed. RESULTS: Dose-escalation IMRT plans, delivering 30 daily doses of 2.6Gy (total of 78Gy) to the HTVs without increases in normal tissue doses, were feasible for six patients. Further acceptable dose escalation on HTV depended primarily on the primary tumor site and the extent of disease. CONCLUSIONS: It was possible to dose escalate the HTV radiation to 78Gy in six of eight head and neck cancer patients using (18)F-FMISO PET/CT-guided IMRT.

Generalized acanthosis nigricans related to type B insulin resistance syndrome: a case report.

Acanthosis nigricans (AN) is a cutaneous marker for many underlying states such as endocrine abnormality, obesity, certain drugs, and malignancy. Generalized AN is a rare condition and is commonly seen in adults with an underlying malignancy. The type B insulin resistance syndrome, a rare autoimmune disorder, is caused by the autoantibodies to the insulin receptor. Patients typically present with hyperglycemia but also may present with hypoglycemia. We report a rare case of a 36-year-old man with generalized AN and type B insulin resistance syndrome with hypoglycemia.

The Feasibility of 18F-FDG PET scans 1 month after completing radiotherapy of squamous cell carcinoma of the head and neck.

UNLABELLED: Our purpose was to prospectively evaluate the efficacy of PET with (18)F-FDG 1 mo after the completion of radiotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Ninety-seven patients underwent (18)F-FDG PET scans before and after radiotherapy for nondisseminated SCCHN. The first scans were obtained no more than 4 wk before the start of radiotherapy, and follow-up scans were obtained 1 mo after the completion of radiotherapy. (18)F-FDG PET images were analyzed using standardized uptake values (SUVs). All patients were followed for at least 6 mo or until death. RESULTS: The median SUVs of preradiotherapy primary sites and nodes were 6.5 (range, 2.3-23.0) and 5.6 (range, 1.2-16.8), respectively. The median SUVs of postradiotherapy primary sites and nodes were 1.8 (range, basal status value to 9.7) and 1.8 (range, basal status value to 8.6), respectively. Evaluation of the postradiotherapy status of tumors in these SCCHN patients showed the sensitivity of (18)F-FDG PET to be 88%, the specificity to be 95%, and the overall diagnostic accuracy to be 94.9%. CONCLUSION: Our results indicate that (18)F-FDG PET might be a valuable imaging method for evaluating the response to radiotherapy in patients with SCCHN. One month after the completion of radiotherapy is not too early for follow-up (18)F-FDG PET to be performed to evaluate the response to radiotherapy.

Appropriate waist circumference cutoff points for central obesity in Korean adults.

BACKGROUND: The International Diabetes Federation consensus recently proposed a new definition for the diagnosis of metabolic syndrome, incorporating ethnically specific waist circumference (WC) cutoff points. OBJECTIVE: We investigated the ethnically appropriate WC cutoff values for central obesity in Korean adults to predict increased risk of elevated triacylglycerol, reduced HDL cholesterol, elevated blood pressure, elevated fasting plasma glucose, or two or more of these factors. DESIGN: We used data from 6561 adults, aged 20-80 years, who participated in the Korean Health and Nutritional Examination Survey of 1998, a cross-sectional health survey of a nationally representative sample of Koreans. RESULTS: Based on the receiver operating characteristic curve analysis, the WC value for predicting metabolic risk factors in Koreans was about 85 cm for men and 80 cm for women. The odds ratio for the risk of two or more metabolic risk factors increased abruptly in men with WC >or= 90 cm and women with WC >or= 85 cm. The 80th percentile for WC in the Korean population was 90 cm for men and 86.5 cm for women. Thus, the appropriate WC cutoff point for central obesity in Koreans was determined to be 90 cm for men and 85 cm for women. CONCLUSIONS: Based on our criteria, the prevalence of central obesity was 19.8% in Korean men and 24.5% in Korean women. These findings suggest the applicability of ethnically specific cutoff points for WC in assessing central obesity.

Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using 18FDG-PET.

The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.

Polymorphisms in interleukin-1 beta and Interleukin-1 receptor antagonist genes are associated with kidney failure in Korean patients with type 2 diabetes mellitus.

BACKGROUND/AIM: Cytokines play an important role in the pathogenesis of kidney diseases. The aim of the study was to investigate the impact of interleukin (IL)-1 cluster genes on diabetic nephropathy in Korean patients with type 2 diabetes mellitus (DM). METHODS: We investigated -511 C/T polymorphism of IL-1 beta and tandem repeat polymorphism in intron 2 of IL-1 receptor antagonist in type 2 DM patients with end-stage kidney failure as compared with patients without nephropathy. RESULTS: The IL1B2 allele was found more frequently in patients with kidney failure than in controls (57.4 vs. 46.1%, p < 0.05). An excessive homozygous carriage of IL1B2 was found in patients with kidney failure when compared with controls (30.5 vs. 18.3%, p < 0.05). The allelic frequency of IL1RN*2 was also higher in cases than in controls without nephropathy (8.4 vs. 2.8 %, p < 0.05). The carriage rate of IL1RN*2 was significantly associated with an increased risk of kidney failure (15.8 vs. 5.6%; OR 3.19, 95% CI 1.24-8.17). The risk of kidney failure was highest in those carrying both IL1RN*2 and IL1B2 (OR 3.90, 95% CI 1.34-11.40). CONCLUSION: IL1B2 and IL1RN*2 genotypes of the IL-1 cluster genes are associated with diabetic nephropathy in Korean patients with type 2 DM.

K+ channel currents in rat ventral prostate epithelial cells.

BACKGROUND: Electrophysiological function of the normal prostate has not been extensively studied. In particular, ion channel currents and their regulation have not been studied in freshly-isolated prostate cells. METHODS: Rat prostate secretory epithelial (RPSE) cells were isolated by collagenase treatment. Columnar epithelial cells were used for nystatin-perforated, whole-cell voltage clamp, and the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. RESULTS: Step-like depolarizing pulses (900 msec) starting from - 90 mV induced outwardly rectifying K(+) currents without inactivation. ACh (10 microM) or ATP (100 microM) increased the outward current and hyperpolarized the cell membrane potential. Ionomycin (0.1 microM), a Ca(2+) ionophore, induced a similar increase in the outward current. TEA (5 mM), charybdotoxin (50 nM), and iberiotoxin (30 nM) inhibited the effect of ACh (or ATP) on the outward current, whereas apamin (100 nM) had no effect. The [Ca(2+)](i) of RPSE cells was increased by ACh, ATP, and UTP. CONCLUSIONS: RPSE cells have iberiotoxin-sensitive Ca(2+)-activated K(+) channels that may play an important role in the exocrine secretions of the prostate.