Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown. METHODS: From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated. RESULTS: Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores. CONCLUSION: Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease

OBJECTIVE: Fibroblast growth factor (FGF) 21 is a recently established therapeutic target for treating metabolic syndromes, which include potential precursors to cardiovascular disease, suggesting a link between FGF21 and atherosclerosis. However, the association between serum FGF21 concentrations and coronary artery disease remain controversial. The aim of this study is to evaluate the association between circulating FGF21 concentrations and coronary artery lesions and clinical severity. METHODS: We enrolled 137 subjects who underwent coronary angiography, due to suspected acute coronary syndrome (ACS), from December 2009 to July 2012. Serum FGF21 levels were measured. Coronary artery lesions and clinical severities of the subjects were evaluated using the SYNergy between percutaneous coronary intervention with (paclitaxel-eluting) TAXus stent and cardiac surgery (SYNTAX) and Global Registry of Acute Coronary Events (GRACE) scoring system, respectively. RESULTS: After adjusting for established cardiovascular disease risk factors, including age, body mass index, total cholesterol, and low-density lipoprotein cholesterol, patients with coronary artery lesions (n=112 men) had significantly higher levels of FGF21 than individuals without such lesions (n=25; men) (377.1±20.1 pg/mL vs. 267.1±43.5 pg/mL; p=0.026). However, no correlations were found between serum levels of FGF21 and either the calculated STNTAX score (r=0.117; p=0.176) or GRACE risk score, which is a risk prediction tool applicable for ACS subjects (r=0.113; p=0.193). CONCLUSION: Although serum levels of FGF21 were higher in individuals with coronary lesions than in those without such lesions, FGF21 levels were not associated with angiographic severity.

Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

BACKGROUND: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. METHODS: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. RESULTS: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. CONCLUSION: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.

Association between household size, residential area, and osteoporosis: analysis of 2008 to 2011 Korea National Health and Nutrition Examination Survey

BACKGROUND/AIMS: The prevalence of single-person households has rapidly increased in Korea. Individuals living alone and in rural areas may have a higher risk of various metabolic diseases due to differences in lifestyle. However, few studies have investigated the association of household size and residential area with health-related problems. This study aimed to evaluate the association of household size and residential area with risk of osteoporosis in postmenopausal women. METHODS: This cross-sectional study enrolled 3,058 postmenopausal women from the 2008 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES). We examined the association between bone mineral density (BMD) and household size and residential area. RESULTS: Individuals living in rural areas had significantly lower BMD of the lumbar spine than those living in an urban area. Subsequently, we divided the participants into four groups according to household size and residential areas. Lumbar spine BMD was significantly lower in individuals living in rural single-person households than those in urban households with two or more individuals, even after adjustment for multiple confounding factors. In addition, individuals in rural single-person households had significantly greater odds of osteoporosis in the lumbar spine than those in urban households with two or more residents. CONCLUSIONS: Individuals in rural single-person households had significantly lower BMD and greater odds of osteoporosis in lumbar spine than urban households with two or more individuals. The results of this study suggest that individuals living in rural single-person households may benefit from more careful screening for osteoporosis.

Transcriptional Regulation of Fibroblast Growth Factor 21 Expression

Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.

Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding protein-1c via inhibition of LXR and Sp1

Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1). Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes. Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay. EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.

Clinical Characteristics for 348 Patients with Adrenal Incidentaloma

BACKGROUND: Adrenal incidentaloma is an adrenal neoplasm frequently encountered in clinical practice for which detection rates have recently increased. We describe here the clinical characteristics of adrenal incidentalomas. METHODS: A retrospective study was performed examining the age, sex, location, size, function, and the histological findings for 348 patients with an adrenal mass discovered incidentally on computed tomography (CT) undertaken for health examination or nonadrenal disease from August 2005 to May 2012. RESULTS: Patients consisted of 156 males (44.8%) and 192 females (55.2%), aged between 20 and 86. Adrenal masses were most commonly found in patients in their sixth decade (32.5%). Regarding the location of the masses, 62.0% were found in the left adrenal gland, 30.2% were found in the right, and 7.8% were found bilaterally. Of all of the masses analyzed, 87.1% were 1 to 4 cm in size, and an adenoma-like appearance was the most common finding (75.3%) seen on CT scans. Hormonal analysis showed that 82.2% of the masses were nonfunctioning, 6.0% were diagnosed as subclinical Cushing's syndrome, 4.6% were aldosterone-producing adenomas, and 7.2% were pheochromocytomas. Adrenalectomy was performed in a total of 69 patients having adenoma (50.7%), pheochromocytoma (24.6%), and carcinoma (4.3%). CONCLUSION: The characteristics of benign, malignant, nonfunctional, and functional adrenal masses that were incidentally found at our hospital were similar to those presented in other studies.

Case of Subacute Thyroiditis Presenting as the Cause of Fever of Unknown Origin / 대한내과학회지

Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases. Endocrine causes of FUO are rare. The only endocrine disorder likely to present as FUO is subacute thyroiditis. Subacute thyroiditis usually occurs in middle-aged women as viral prodrome, neck tenderness, classic symptoms of thyrotoxicosis, and an elevated erythrocyte sedimentation rate. The patient may have abrupt onset of fever and chills with complaints of thyroid pain, or only low-grade fever with poorly characterized anterior neck pain. We present a case of FUO in a 48-year-old female who had had fever and neck pain for more than one month. Despite an extensive evaluation, the patient had persistent fever and no cause was found, with the exception of subacute thyroiditis. The fever resolved from the second day of treatment with low-dose steroid (prednisolone, 10 mg per day). This case illustrates that subacute thyroiditis should be considered in cases of FUO.

Yellow Fever Vaccine-associated Viscerotropic Disease / 대한내과학회지

This report describes a case of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) that occurred after vaccination in a 23-year-old male. Seven days after vaccination, our patient presented with fever, myalgia, and nausea. The IgM enzyme-linked immunosorbent assay (ELISA) for yellow fever virus was positive. After a 24 day hospitalization, he recovered and was discharged. Yellow fever is a viral hemorrhagic febrile illness caused by a flavivirus and transmitted by mosquitoes. The clinical presentation ranges from a mild febrile illness to a serious infection, leading to hepatic and renal failure, myocardial injury, hemorrhage, and shock, with a case fatality rate of 20-30%. Because yellow fever is a potentially fatal disease, vaccination is encouraged for people traveling to high-risk areas. Although considered a safe vaccine, severe adverse reactions have been reported. In 2001, rare, but severe, acute viscerotropic disease following vaccination was first described. We report the case of a 23-year-old male with fever and hepatitis following vaccination with 17D yellow fever vaccine.

A Case of Cytomegalovirus and Pseudomembranous Colitis in an Immunocompetent Adult / 대한소화기내시경학회지

Cytomegalovirus (CMV) colitis is a rare event that has been described mainly in immunocompromised patients who are on immunosuppressive medication or they have HIV infection. CMV colitis manifesting in an immunocompetent host is exceedingly rare, but this has occasionally been described in pregnant patients and patients with chronic renal failure. Pseudomembranous colitis (PMC) is known to develop with long-term antibiotic administration and it is caused by the abnormal overgrowth of toxin-producing Clostridium difficile that colonize the large bowel. Appropriate diagnostic testing and early treatment may avert morbidity and mortality. A case of the simultaneous occurrence of cytomegalovirus and Clostridium difficile colitis in an immunocompetent adult has not yet been reported in the Koran medical literature. We report here on a case of the simultaneous occurrence of cytomegalovirus and Clostridium diffiicle colitis in an immunocompetent Korean adult.

A case of combined herpes simplex virus, cytomegalovirus, and candidal esophagitis in an AIDS patient / 대한내과학회지

Since the first case of human immunodeficiency virus (HIV) infection was reported in Korea in 1985, the number of HIV patients has risen steadily and reached 5,323 in December 2007. Consequently, multiple opportunistic infections have become a significant clinical problem. Diseases of the gastrointestinal tract are among the most frequent complications of acquired immunodeficiency syndrome (AIDS) and cause morbidity in patients with HIV infection. Opportunistic infections are the leading cause of esophageal complaints. Candida albicans is the most frequently identified cause of esophageal symptoms, followed by herpes simplex virus (HSV) and cytomegalovirus (CMV) infections. Esophageal candidiasis often occurs concurrently with other infectious esophageal disorders. Simultaneous esophageal infection with HSV, CMV, and Candida spp. is rare. We report a case of combined HSV, CMV, and candidal esophagitis in an AIDS patient. He was treated with highly active antiretroviral therapy (HAART) and the appropriate antiviral and antifungal agents.