Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

BACKGROUND: In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. METHODS: To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. RESULTS: BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. CONCLUSION: These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity.

Predictive Factors of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma / 대한내분비외과학회지

PURPOSE: Despite the excellent overall prognosis for patients with papillary thyroid microcarcinoma (PTMC), the rate of central lymph node (CLN) metastasis has been reported to be as great as 60% and the optimal surgical extent of PTMC has been controversial. The aim of this study is to identify factors for predict CLN metastasis in patients with PTMC. METHODS: We conducted a retrospective study of 535 patients with PTMC who underwent total thyroidectomy with prophylactic CLN dissection between Jan. 2008 and Aug. 2011. We analyzed the association of CLN metastasis and clinicopathologic characteristics. RESULTS: CLN metastasis was found in 181 patients (33.8%). Results of univariate analysis showed an association of younger than 45 years of age, male gender, a tumor size greater than 5 mm, bilaterality, multiplicity, extrathyroidal extension, and positivity of resection margin with CLN metastasis. Of these, results of multivariate analysis showed that age (P=0.003), gender (P=0.004), tumor size (P5 mm), male gender, young age (<45 yr), extrathyroidal extension, and positive resection margin were determined as the predictive factors for CLN metastasis, which occurred in approximately one third of patients with PTMC. Therefore, prophylactic CLN dissectionshould be considered in patients with PTMC who have these factors through investigation before surgery.

The Change of Bone Mineral Density in Relation to Stroke Duration and Affected Sides

OBJECTIVE: To investigate the mode of the development of osteoporosis in hemiplegic stroke patients and to study the change in bone mineral density (BMD) in relation to stroke duration and affected sides. METHOD: The subjects were 79 hemiplegic stroke patients (39 males, 40 felames, mean age 61.9 years). We measured the BMD of the subjects, compared the BMD of affected sides with that of unaffected sides, and evaluate the BMD in connection with stroke duration and affected sides. RESULTS: The reduction of the BMD in affected sides was highly correlated with the duration of hemiplegia, but the correlation was not shown in the case of those in unaffected sides. In addition, the difference of BMD in affected sides between those in unaffected sides had an obvious negative correlation with the stroke duration of left hemiplegia, but not with that of right hemiplegia. CONCLUSION: Stroke patients have a high prevalence of osteoporosis and this findings were particularly prominent in people who suffer from left hemiplegia. Early rehabilitative care, including weight-bearing exercise and outdoor ambulation, is essential for left side hemiplegic patients in order to prevent possible complications.

The Relationship between Korean Version of Falls Efficacy Scale - International and Frequency of Falls in the Healthy Elderly Visiting the Public Health Centers

OBJECTIVE: To see whether there is a relationship between Korean Falls Efficacy Scale-International (KFES-I) developed for measuring fear of falling and frequency of fall. METHOD: KFES-I was composed with 16 items of activities of daily living including social activities and graded from 1 to 4 in each item. Surveys of 250 patients over 65 years of age from the public health center of Kang-dong and Seong-buk based on KFES-I and fall questionnaire such as presence, frequency and severity of fracture within last 6 months, and combined medical illness were taken. The data of KFES-I, fall questionnaire, and the inter-relationship of KFES-I items had been analyzed by Spearman and Kendall test. RESULTS: There was strong positive correlation between KFES-I total score and the frequency of falls. Four items (item 4, 7, 11, 15) of KFES-I showed strong correlation with the frequency of falls. There was significant difference in KFES-I total score between control and fracture groups (p<0.05). CONCLUSION: Our results showed that there was strong positive correlation between frequency of falls and KFES-I. It is suggested that frequency of falls can be predicted by KFES-I.

Conventional Angiogram versus Multi-detector Row Helical Computed Tomography Angiogram for Preoperative Diagnostic Imaging in Low Extremity Arterial Surgery

PURPOSE: We performed this study to assess the suitability of conventional angiography (CA) vs. multi-detector row helical CT angiogram (MD-CTA) as a method of preoperative diagnostic imaging for low extremity arterial surgery. METHODS: From February 2004 to September 2006, 23 patients (4 claudicants, 19 limb-threatening ischemia) were studied with CA and MD-CTA preoperatively. The site and degree of stenotic or occlusive lesions in arterial segments from the renal artery to the dorsalis pedis artery were compared with both methods. We also compared the surgical inflow and outflow site changes in preoperative planning based on CA and MD-CTA and the final outcome. Additional diagnostic value and test-related complications were also analyzed. RESULTS: The median age of patients was 68 years old (range: 43~89 years), with a male to female ratio of 1.3:1. Twenty-three patients had CA after an MD-CTA scan. One hundred fifty lesions were detected in these patients. The total ratio of consistency for occlusion in CA vs. MD-CTA was 69.6%. Three patients received amputation treatment and eleven patients received a bypass operation. The agreement between the preoperative plan based on MD-CTA and the final operation was 100%, even in critical limb ischemia. There were no serious complications related to the tests. CONCLUSION: These findings suggest that MD-CTA is an adequate preoperative imaging study of infrainguinal arterial surgery and may be substituted for conventional angiography without any serious complications.

Childhood Glomerular Disease and Renal Biopsy

No abstract available.

A Cases of Patent Urachus

No abstract available.