We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson’s disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.

BACKGROUND AND OBJECTIVES: Blood pressure variability (BPV) was recently shown to be a risk factor of stroke. White coat hypertension (WCH) used to be regarded as innocuous, but one long-term follow-up study reported that WCH increased stroke rate compared to normotension (NT). In this study, we aimed to evaluate the relationship between WCH and BPV. SUBJECTS AND METHODS: We analyzed 1398 subjects from the Korean Ambulatory Blood Pressure Registry, who were divided into NT (n=364), masked hypertension (n=122), white coat hypertension (n=254), and sustained hypertension (n=658) groups. RESULTS: Baseline characteristics were similar among groups. The average real variability (ARV), a highly sensitive BPV parameter, was highest in the WCH group, followed by the sustained hypertension, masked hypertension, and NT groups. The results persisted after being adjusted for covariates. The WCH vs. sustained hypertension results (adjusted mean±standard error) were as follows: 24-h systolic ARV, 22.9±0.8 vs. 19.4±0.6; 24-h diastolic ARV, 16.8±0.6 vs. 14.3±0.5; daytime systolic ARV, 21.8±0.8 vs. 16.8±0.6; and daytime diastolic ARV, 16.2±0.6 vs. 13.4±0.5 (p<0.001 for all comparisons). CONCLUSION: From the registry data, we found that subjects with WCH or masked hypertension had higher BPV than NT. However, long-term follow-up data assessing the clinical influences of WCH on stroke are needed.
Blood Pressure Monitoring, Ambulatory* ; Blood Pressure* ; Follow-Up Studies ; Hypertension ; Masked Hypertension ; Risk Factors ; Stroke ; White Coat Hypertension*

BACKGROUND/AIMS: The detection of white coat hypertension (WCH), treated normalized hypertension, and masked hypertension (MH) is important to improve the effectiveness of hypertension management. However, whether global cardiovascular risk (GCR) profile has any effect on the discordance between ambulatory blood pressure (ABP) and clinic blood pressure (CBP) is unknown. METHODS: Data from 1,916 subjects, taken from the Korean Multicenter Registry for ABP monitoring, were grouped according to diagnostic and therapeutic thresholds for CBP and ABP (140/90 and 135/85 mmHg, respectively). GCR was assessed using European Society of Hypertension 2007 guidelines. RESULTS: The mean subject age was 54.1 ± 14.9 years, and 48.9% of patients were female. The discordancy rate between ABP and CBP in the untreated and treated patients was 32.5% and 26.5%, respectively (p = 0.02). The prevalence of WCH or treated normalized hypertension and MH was 14.4% and 16.0%, respectively. Discordance between ABP and CBP was lower in the very high added-risk group compared to the moderate added-risk group (odds ratio [OR], 0.649; 95% confidence interval [CI], 0.487 to 0.863; p = 0.003). The prevalence of WCH or treated normalized hypertension was also lower in the very high added-risk group (OR, 0.451; 95% CI, 0.311 to 0.655). CONCLUSIONS: Discordance between ABP and CBP was observed more frequently in untreated subjects than in treated subjects, and less frequently in the very high added-risk group, which was due mainly to the lower prevalence of WCH or treated normalized hypertension.
Adult ; Aged ; *Blood Pressure ; *Blood Pressure Monitoring, Ambulatory ; Chi-Square Distribution ; Cross-Sectional Studies ; Female ; Humans ; Logistic Models ; Male ; Masked Hypertension/*diagnosis/epidemiology/physiopathology ; Middle Aged ; Multivariate Analysis ; Observer Variation ; Odds Ratio ; *Office Visits ; Predictive Value of Tests ; Prevalence ; Registries ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; White Coat Hypertension/*diagnosis/epidemiology/physiopathology

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Adult ; Aged ; Biopterin/*analogs & derivatives/analysis ; *Chromatography, High Pressure Liquid ; Chronic Disease ; Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications/*diagnosis/metabolism ; Liver/pathology ; Liver Cirrhosis/ultrasonography ; Liver Diseases/complications/*diagnosis/metabolism ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Portal Pressure ; Regression Analysis ; Severity of Illness Index

BACKGROUND: The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma. METHODS: We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves. RESULTS: Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve. CONCLUSION: The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.
Acromegaly* ; Body Mass Index ; Diagnosis ; Discrimination (Psychology) ; Glucose Tolerance Test ; Growth Hormone* ; Growth Hormone-Secreting Pituitary Adenoma ; Humans ; Hyperprolactinemia ; Hypogonadism ; Octreotide ; Prevalence ; Retrospective Studies ; ROC Curve

OBJECTIVES: The purpose of this in vivo study was to investigate the microbial diversity in symptomatic and asymptomatic canals with primary endodontic infections by using GS FLX Titanium pyrosequencing. MATERIALS AND METHODS: Sequencing was performed on 6 teeth (symptomatic, n = 3; asymptomatic, n = 3) with primary endodontic infections. Amplicons from hypervariable region of the small-subunit ribosomal RNA gene were generated by polymerized chain reaction (PCR), and sequenced by means of the GS FLX Titanium pyrosequencing. RESULTS: On average, 10,639 and 45,455 16S rRNA sequences for asymptomatic and symptomatic teeth were obtained, respectively. Based on Ribosomal Database Project Classifier analysis, pyrosequencing identified the 141 bacterial genera in 13 phyla. The vast majority of sequences belonged to one of the seven phyla: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, Spirochetes, and Synergistetes. In genus level, Pyramidobacter, Streptococcus, and Leptotrichia constituted about 50% of microbial profile in asymptomatic teeth, whereas Neisseria, Propionibacterium, and Tessaracoccus were frequently found in symptomatic teeth (69%). Grouping the sequences in operational taxonomic units (3%) yielded 450 and 1,997 species level phylotypes in asymptomatic and symptomatic teeth, respectively. The total bacteria counts were significantly higher in symptomatic teeth than that of asymptomatic teeth (p < 0.05). CONCLUSIONS: GS FLX Titanium pyrosequencing could reveal a previously unidentified high bacterial diversity in primary endodontic infections.
Actinobacteria ; Bacteria ; Bacteroidetes ; Fusobacteria ; Genes, rRNA ; Leptotrichia ; Neisseria ; Polymers ; Propionibacterium ; Proteobacteria ; Spirochaetales ; Streptococcus ; Titanium ; Tooth

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.
Blood Glucose ; Cardiovascular Diseases ; Consensus ; Diabetes Complications ; Diabetes Mellitus ; Drug Combinations ; Gliclazide ; Glucose ; Humans ; Indapamide ; Perindopril ; Solar System ; Veterans

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.
Blood Glucose ; Cardiovascular Diseases ; Consensus ; Diabetes Complications ; Diabetes Mellitus ; Drug Combinations ; Gliclazide ; Glucose ; Humans ; Indapamide ; Perindopril ; Solar System ; Veterans

BACKGROUND: The prevalence of the metabolic syndrome in Korea is about 20%. The metabolic syndrome is known to increase the risk of cardiovascular disease. However, the relationship of this syndrome with electrocardiographic subclinical risk factors such as corrected QT (QTc) interval prolongation has not been evaluated extensively in Korea. In this perspective, we studied the relationship between metabolic syndrome and QTc interval prolongation among Korean adults. METHODS: We analysed 1,560 Korean subjects (men, 873; women, 687; age, 30 to 75 years) at a health promotion center of a university hospital from November, 2006 to Jun, 2007. Subjects were evaluated for metabolic syndrome using a questionnaire, physical examination, blood pressure and blood test. QTc interval was measured from the standard 12-lead electrocardiogram. RESULTS: In women, the odds ratios of QTc interval prolongation according the number 1, 2, 3 > or = of diagnostic criteria of metabolic syndrome were 1.62 (1.07 to 2.45), 2.70 (1.59 to 4.59), 3.24 (1.65 to 6.32) compared to the number 0 (P for trend < 0.001). In men, the odds ratios according the number 2, 3 > or = of them were 2.53 (1.56 to 4.11), 3.49 (2.05 to 5.93) (P for trend < 0.001). CONCLUSION: In Korean Adult, metabolic syndrome is significantly associated with QTc prolongation. As the number of diagnostic criteria of this syndrome increased, the ratio of QTc prolongation tends to be increased. This study suggest that the measurement of QTc interval of subjects with the diagnostic components of this syndrome can help predict cardiovascular risk of prolonged QTc.
Adult ; Blood Pressure ; Cardiovascular Diseases ; Electrocardiography ; Female ; Health Promotion ; Hematologic Tests ; Humans ; Korea ; Male ; Odds Ratio ; Physical Examination ; Prevalence ; Risk Factors

BACKGROUND/AIMS: Treatment using multiple daily insulin (MDI) should give diabetic patients many benefits. Nevertheless, few studies have examined the impact of an increased frequency of daily insulin injection on quality of life, anxiety levels, and depression in diabetic patients, and individual's continued compliance with MDI is unclear. This study examined these issues using standardized questionnaires. METHODS: This was a cross-sectional, randomized study. Ninety-nine insulin-treated type 2 diabetic patients (mean age 53.1+/-12 years, mean duration of diabetes 10.3+/-6.5 years) were divided a group (n=50) who injected insulin four times daily (mean age 49.6+/-12.3 years, mean duration of diabetes 6.5+/-6.4 years) and a group (n=49) who injected insulin once or twice daily (mean age 56.4+/-11.6 years, mean duration of diabetes 11.5+/-5.8 years). All patients independently completed the Korean Version of the World Health Organization Quality of Life Scale Abbreviated Version and standardized Hospital Anxiety and Depression Scale for Koreans. RESULTS: No significant differences were evident with respect to age, gender, and duration of diabetes between the two groups (p<0.05). No significant differences were evident in the results of the questionnaires between the two groups, except for the physical health domain (p<0.05). CONCLUSIONS:Multiple daily insulin injections had nearly no influence on quality of life, anxiety levels, or depression in type 2 diabetic patients. Therefore, treatment with MDI should be considered for patients who would benefit from this.
Anxiety ; Compliance ; Depression ; Diabetes Mellitus ; Humans ; Insulin ; Quality of Life ; World Health Organization ; Surveys and Questionnaires