1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.Temporary replacement of congenital missing incisors on mandible using temporary anchorage devices in growing patient: 2-year follow-up
Youn-kyung CHOI ; Eun-Young KWON ; Kyung-Hwa JUNG ; Na-Rae CHOI ; Soo-Byung PARK ; Seong-sik KIM ; Yong-il KIM
Journal of Dental Rehabilitation and Applied Science 2020;36(4):272-281
Agenesis of permanent tooth in adolescent patients can be treated either by orthodontic treatment for space closure or by main-taining the space until implant restoration can be carried out in adult. However, gradual atrophy of alveolar bone width makes it dif-ficult to restore the prosthesis in the future or may cause unaesthetic results. Therefore, maintaining of not only the missing space but also the alveolar bone width should be considered. This case is a treatment whereby a temporary replacement of missing 2mandibular incisors in adolescent patient was carried out using 2 temporary anchorage devices (TADs). Two TADs were placed hori-zontally 2 - 3 mm below the top of alveolar ridge, and fixed with artificial teeth by stainless steel wires extended. During the 2 year follow-up, neither gingival inflammation nor loss of the TADs have occurred. In the radiographic evaluation, the growth of the adja-cent alveolar bone was not inhibited, and the width of the alveolar bone was maintained.
3.Versatility of the pedicled buccal fat pad flap for the management of oroantral fistula: a retrospective study of 25 cases
Jinyoung PARK ; Byung do CHUN ; Uk Kyu KIM ; Na Rae CHOI ; Hong Seok CHOI ; Dae Seok HWANG
Maxillofacial Plastic and Reconstructive Surgery 2019;41(1):50-
PURPOSE:
Maxillary bone grafts and implantations have increased over recent years despite a lack of maxillary bone quality and quantity. The number of patients referred for oroantral fistula (OAF) due to implant or bone graft failure has increased, and in patients with an oroantral fistula, the pedicled buccal fat pad is viewed as a robust, reliable option. This study was conducted to document the usefulness of buccal fat pad grafts for oroantral fistula closure.
MATERIALS AND METHODS:
We retrospectively studied 25 patients with OAF treated with a buccal fat pad graft from 2015 to 2018. Sex, age, OAF location, cause, duration, presence of systemic disease, smoking, previous dental surgery, and side effects were investigated.
RESULTS:
A total of 25 patients were studied. Mean patient age was 54.8 years, and the male to female ratio was 19:6. Causes of oroantral fistula were cyst enucleation, tumor resection, implant removal, bone graft failure, and extraction. Excellent results were obtained in 23 (92%) of the 25 patients. In the other two patients that both smoked, a small fistula was observed during follow-up. No recurrence of oroantral fistula was observed after 2 months to 1 year of follow-up.
CONCLUSIONS
The incidence of oroantral fistula is increasing due to implant and bone graft failures. Oroantral fistula closure using a pedicled buccal fat pad was found to have a high success rate.
4.Analyses of the TCR repertoire of MHC class II-restricted innate CD4+ T cells.
Byung Hyun KANG ; Hye Sook MIN ; You Jeong LEE ; Bomi CHOI ; Eun Ji KIM ; Jonghoon LEE ; Jeong Rae KIM ; Kwang Hyun CHO ; Tae Jin KIM ; Kyeong Cheon JUNG ; Seong Hoe PARK
Experimental & Molecular Medicine 2015;47(3):e154-
Analysis of the T-cell receptor (TCR) repertoire of innate CD4+ T cells selected by major histocompatibility complex (MHC) class II-dependent thymocyte-thymocyte (T-T) interaction (T-T CD4+ T cells) is essential for predicting the characteristics of the antigens that bind to these T cells and for distinguishing T-T CD4+ T cells from other types of innate T cells. Using the TCRmini Tg mouse model, we show that the repertoire of TCRalpha chains in T-T CD4+ T cells was extremely diverse, in contrast to the repertoires previously described for other types of innate T cells. The TCRalpha chain sequences significantly overlapped between T-T CD4+ T cells and conventional CD4+ T cells in the thymus and spleen. However, the diversity of the TCRalpha repertoire of T-T CD4+ T cells seemed to be restricted compared with that of conventional CD4+ T cells. Interestingly, the frequency of the parental OT-II TCRalpha chains was significantly reduced in the process of T-T interaction. This diverse and shifted repertoire in T-T CD4+ T cells has biological relevance in terms of defense against diverse pathogens and a possible regulatory role during peripheral T-T interaction.
Amino Acid Sequence
;
Animals
;
Antigens, Surface/metabolism
;
CD4-Positive T-Lymphocytes/cytology/*immunology/*metabolism
;
Cell Communication
;
Cell Differentiation/genetics/immunology
;
Clonal Evolution
;
Histocompatibility Antigens Class II/*immunology
;
*Immunity, Innate
;
Immunophenotyping
;
Lymphocyte Count
;
Mice
;
Mice, Knockout
;
Mice, Transgenic
;
Peptide Fragments/chemistry
;
Phenotype
;
Receptors, Antigen, T-Cell/chemistry/*genetics/metabolism
;
Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics
;
Spleen/cytology
;
Thymocytes/cytology/immunology/metabolism
5.Clinicopathological Characteristics of Colon Cancer Diagnosed at Primary Health Care Institutions.
Sang Hyun PARK ; Chi Wook SONG ; Yun Bae KIM ; Young Sun KIM ; Hwang Rae CHUN ; Jung Hyun LEE ; Won Jong SEOL ; Hyung Sun YOON ; Myung Kwon LEE ; Jong Hyup LEE ; Choon Sang BHANG ; Jae Hyung PARK ; Ji Young PARK ; Byung Hun DO ; Young Dae PARK ; Sang Jeong YOON ; Chan Wook PARK ; Su Mi YOON ; Jong Hwan CHOI ; Ki Chul SHIN ; Dong Hoon KO ; Young Jin KIM ; Dong Choon SEOL
Intestinal Research 2014;12(2):131-138
BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic characteristics of colon cancers detected at the SOK Sokpeynhan Internal Medical Network, a nationwide system of primary health care institutions. METHODS: We analyzed 579 colon cancer patients diagnosed using colonoscopy at the SOK network from January 2011 through December 2012. Cancers from the rectum to the splenic flexure were classified as left colon cancer. Patients over 65 were classified as senior. RESULTS: The mean age (+/-SD) of subjects was 60.9+/-10.5 years and 61.1% were men. More than one quarter (28.2%) of patients were asymptomatic. The prevalence of left colon cancer was higher (77.9%) than that for right colon cancer. The most frequent macroscopic and histologic types were depressed (58.9%) and moderately differentiated adenocarcinoma (52.2%), respectively. Asymptomatic subjects displayed protruding or well differentiated adenocarcinoma, while symptomatic patients were more likely to display depressed or moderately differentiated adenocarcinoma (P<0.05). The mean age of the right colon cancer group was higher than that for the left colon cancer group (P<0.05). Among symptomatic patients, the most frequent symptoms were bloody stool for patients with left colon cancer and abdominal discomfort for patients with right colon cancer (P<0.05). The prevalence of depressed cancer was higher in older subjects as compared to younger subjects (P<0.05). The prevalence of right colon cancer tended to increase with age, although this difference did not achieve statistical significance (P>0.05). CONCLUSIONS: Study results indicated an increase of colon cancer amongst younger demographics in recent years. The effectiveness of colonoscopy screening was also evident, as asymptomatic patients demonstrated frequent findings of well differentiated adenocarcinomas. Study results also suggested a need for closer examination of older patients, as right colon cancer tended to increase with age.
Adenocarcinoma
;
Colon, Transverse
;
Colonic Neoplasms*
;
Colonoscopy
;
Demography
;
Humans
;
Male
;
Mass Screening
;
Population Characteristics
;
Prevalence
;
Primary Health Care*
;
Rectum
6.Hyperventilation Induced Syncope: Differential Feature of Head-up Tilt Table Test with Transcranial Doppler in Patient with Hyperventilation Syndrome from True Syncope.
Byung Sung LEE ; Soek Kyung KWON ; Sang Rae LEE ; Jong Wan PARK ; Jang Joon LEE
Journal of the Korean Neurological Association 2014;32(4):310-313
The causes of a transient loss of consciousness (TLOC) are divided into syncope, epileptic seizures, cerebrovascular diseases and functional disorders such as hyperventilation (HV) syndrome, psychogenic pseudosyncope. The differential diagnosis of TLOC is may be difficult due to lack of history, misleading features, or confusion over the definition of syncope. We have experienced a rare case of HV syncope that TLOC developed after HV from mental stress, and differentiated by head-up tilt table test with transcranial doppler.
Diagnosis, Differential
;
Epilepsy
;
Humans
;
Hyperventilation*
;
Syncope*
;
Tilt-Table Test*
;
Unconsciousness
7.SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice.
Ui Jin BAE ; Jae Do YANG ; Sun O KA ; Jeung Hyun KOO ; Seong Ji WOO ; Young Rae LEE ; Hee Chul YU ; Baik Hwan CHO ; Hui Yuan ZHAO ; Jae Ha RYU ; Sang Myeong LEE ; Raok JEON ; Byung Hyun PARK
Experimental & Molecular Medicine 2014;46(8):e109-
Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-kappaB (NF-kappaB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-kappaB subunits. Concomitantly, the expression of NF-kappaB target genes such as IL-1beta, IL-6, TNF-alpha and iNOS was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.
Animals
;
Anti-Inflammatory Agents/*therapeutic use
;
Benzoxazines/*therapeutic use
;
Liver/*drug effects/immunology/*injuries/pathology
;
Male
;
Mice, Inbred C57BL
;
NF-kappa B/immunology
;
Reperfusion Injury/*drug therapy/immunology/pathology
;
Signal Transduction/drug effects
;
Thiourea/*analogs & derivatives/therapeutic use
8.Clinicopathologic Characteristics of Superficial Gastric Cancer Diagnosed at Primary Health Care Institutions in 2011.
Sang Hyun PARK ; Chi Wook SONG ; Yun Bae KIM ; Young Sun KIM ; Hwang Rae CHUN ; Jung Hyun LEE ; Won Jong SEOL ; Hyung Sun YOON ; Myung Kwon LEE ; Jong Hyup LEE ; Choon Sang BHANG ; Jae Hyung PARK ; Young Hwan PARK ; Byung Hun DO ; Young Dae PARK ; Sang Jeong YOON ; Chan Wook PARK ; Jong Pyo KIM ; Jong Hwan CHOI ; Ki Chul SHIN ; Soon Min PARK
The Korean Journal of Gastroenterology 2012;60(5):285-291
BACKGROUND/AIMS: Stomach cancer is prevalent in Korea. The purpose of this study was to evaluate the characteristics of superficial gastric cancers detected at SOK Sokpeynhan Internal Medical Network, the nationwide primary health care institutions. METHODS: We prospectively analysed the clinicopathologic and endoscopic characteristics of 218 superficial gastric cancer patients diagnosed using gastric endoscopy at SOK network from January 2011 through December 2011. RESULTS: The mean age was 58.5 years old and male to female ratio was 1.7 : 1. Asymptomatic patients were most common (45.0%). The macroscopic classification revealed that simple types (63.8%) were more common than complex types (36.2%). The most common type was IIc (28.4%) and other types were as follows; IIb (16.1%), IIb+IIc (13.3%), IIa (10.6%), III (9.2%), IIa+IIc (7.3%), IIc+IIa (6.0%), IIc+IIb (5.0%). The most commonly involved sites were the body (53.1%) and greater curvature (32.6%) of the stomach. The size of lesion was less than 1 cm (69.3%) and less than 5 mm (33.5%) in diameter. The most common pathologic type was tubular adenocarcinoma (75.7%). Helicobacter pylori infection rate was 50.2%. Fifty five percent of the cases were diagnosed via endoscopy of National Health Insurance Corporation screenings. CONCLUSIONS: Superficial gastric cancers in 2011 at primary health care SOK network were different from those of previous reports. Type IIc was most common but type IIb was more prevalent and the body and greater curvature of the stomach were the most commonly involved sites. Therefore, careful observation of the proximal gastric mucosa and mucosal color change is needed.
Adenocarcinoma/pathology
;
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Gastroscopy
;
Helicobacter Infections/diagnosis
;
Humans
;
Male
;
Middle Aged
;
National Health Programs
;
Primary Health Care
;
Prospective Studies
;
Stomach Neoplasms/*pathology
9.Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the expression of beta-catenin, leading to a rapid proliferation of pancreatic cells.
Il Rae CHO ; Sang Seok KOH ; Hye Jin MIN ; Su Jin KIM ; Yangsoon LEE ; Eun Hee PARK ; Srisuttee RATAKORN ; Byung Hak JHUN ; Sangtaek OH ; Randal N JOHNSTON ; Young Hwa CHUNG
Experimental & Molecular Medicine 2011;43(2):82-90
It is not yet understood how the enhanced expression of pancreatic adenocarcinoma up-regulated factor (PAUF; a novel oncogene identified in our recent studies), contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up-regulates the expression and transcriptional activity of beta-catenin while the suppression of PAUF by shRNA down-regulates beta-catenin. The induction of beta-catenin by PAUF is mediated by the activities of Akt and GSK-3beta, but inhibition of downstream ERK does not reduce beta-catenin expression. To test whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated signaling pathway for the stabilization of beta-catenin, we examined the phosphorylation status of beta-catenin in the presence of PAUF compared with that of beta-catenin during treatment with Wnt3a or dibutyryl cAMP, a cell permeable cyclic AMP analogue. PAUF expression induces phosphorylation at Ser-33/37/Thr-41 and Ser-675 of beta-catenin but no phosphorylation at Ser-45, indicating that a unique phosphorylation pattern of beta-catenin is caused by PAUF. Finally, the expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of beta-catenin, leading to a rapid proliferation of pancreatic cells; conversely decreased PAUF expression (by shRNA) results in the reduced proliferation of pancreatic cells. Treatment with hexachlorophene (an inhibitor of beta-catenin) reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken together, we propose that PAUF can up-regulate and stabilize beta-catenin via a novel pattern of phosphorylation, thereby contributing to the rapid proliferation of pancreatic cancer cells.
*Adenocarcinoma/metabolism/pathology
;
Cell Line, Tumor
;
Cell Proliferation
;
Cyclin D1/metabolism
;
Gene Expression Regulation, Neoplastic
;
Glycogen Synthase Kinase 3/metabolism
;
HEK293 Cells
;
Humans
;
Lectins/genetics/*metabolism
;
*Pancreatic Neoplasms/metabolism/pathology
;
Phosphorylation
;
Proto-Oncogene Proteins c-akt/metabolism
;
Proto-Oncogene Proteins c-jun/metabolism
;
Signal Transduction
;
*Up-Regulation
;
beta Catenin/genetics/*metabolism
10.XPD Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck in a Korean Sample.
Yong Bae JI ; Kyung TAE ; Yoon Seo LEE ; Seung Hwan LEE ; Kyung Rae KIM ; Chul Won PARK ; Byung Lae PARK ; Hyoung Doo SHIN
Clinical and Experimental Otorhinolaryngology 2010;3(1):42-47
OBJECTIVES: XPD is a major player in nucleotide excision repair, which is one of the basic pathways of DNA repair. The objective of this study was to investigate the association of XPD single nucleotide polymorphisms (SNPs) and the risk of squamous cell carcinoma of the head and neck (SCCHN) in Koreans. METHODS: We performed XPD +23591G>A and +35931A>C genotyping in 290 SCCHN patients and 358 controls. RESULTS: The frequencies of the XPD +23591G>A (GG/GA/AA) genotypes were 89.0%/11.0%/0% in the patients and 90.3%/8.8%/0.9% in the controls, respectively. The odds ratio (OR) of the XPD +23591 GA genotype was 1.94 (0.92 to 4.08) in reference to the GG genotype. The frequencies of the XPD +35931A>C (AA/AC/CC) genotypes were 86.9%/12.0%/1.1% in the patients and 85.6%/13.8%/0.6% in the controls, respectively. The OR of the XPD +35931 AC and CC genotypes were 0.98 (0.51 to 1.88) and 2.68 (0.71 to 10.1), respectively, in reference to the AA genotype. On the subgroup analyses according to the smoking and drinking statuses, the SNPs and haplotypes of XPD showed no statistically significant association with the risk of SCCHN. CONCLUSION: The results of this study suggest that the XPD +23591G>A and +35931A>C SNPs are not associated with the risk of SCCHN in Koreans; however, a further study with a larger number of subjects is necessary to verify this conclusion.
Carcinoma, Squamous Cell
;
DNA Repair
;
Drinking
;
Genotype
;
Haplotypes
;
Head
;
Head and Neck Neoplasms
;
Humans
;
Neck
;
Odds Ratio
;
Polymorphism, Single Nucleotide
;
Smoke
;
Smoking

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