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1.
Article in Chinese | WPRIM | ID: wpr-921927

ABSTRACT

OBJECTIVE@#To evaluate the effect of one-stage treatment of bone morphogenetic protein 2 combined with Jifusheng in the experimental model of osteomyelitis in rabbits.@*METHODS@#The model of chronic osteomyelitis of tibia was established in 30 3-month-old male New Zealand white rabbits with a body weight of (2.0±0.5) kg, and the model was verified 4 weeks after operation. Thirty rabbits with osteomyelitis were randomly divided into 3 groups with 10 rabbits in each group (@*RESULTS@#At 4 weeks after operation, 30 rabbits with osteomyelitis were successfully validated. The results of serological examination showed that the hypersensitive C-reactive protein (CRP) and white blood cell count(WBC)in the model group were significantly higher than those in the blank group at 2 and 4 weeks after operation. Eight weeks after treatment, the detection of blood indexes showed that the white blood cell count (WBC)and hypersensitive C reactive protein (CRP)in treatment group A and treatment group B were significantly lower than those in the model group (@*CONCLUSION@#The combined application of apolipoprotein 2-Jifusheng can promote bone repair and reduce the inflammation of the focus. it can treat rabbits with osteomyelitis in one stage, provide objective basis for the formulation of clinical treatment strategy of osteomyelitis and further promote clinical research.


Subject(s)
Animals , Apolipoproteins , Bone Density , Bone and Bones , Male , Osteomyelitis/drug therapy , Rabbits , Tibia
3.
Arq. bras. cardiol ; 115(1): 102-108, jul. 2020. tab, graf
Article in English, Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1131269

ABSTRACT

Resumo Fundamento Os glicocorticóides (GCs) são amplamente prescritos para o tratamento de numerosos distúrbios clínicos devido às suas propriedades anti-inflamatórias e imunomoduladoras, e um dos efeitos indesejáveis mais comuns desses medicamentos é a dislipidemia. Objetivo Avaliar o efeito da quercetina, um flavonoide derivado de plantas, no perfil lipídico de ratos tratados com glicocorticóides em altas doses. Métodos Um total de 32 ratos Sprague-Dawley foram distribuídos aleatoriamente entre quatro grupos (8 ratos por grupo) e tratados por 6 semanas com uma das seguintes opções : (i) solução salina normal; (ii) 40 mg/kg de succinato sódico de metilprednisolona (MP); (iii) MP + 50 mg/kg de quercetina; (iv) MP + 150 mg/kg de quercetina. O MP foi injetado por via subcutânea e a quercetina foi administrada por gavagem oral 3 dias por semana. No final do estudo, o perfil lipídico dos animais foi medido através de kits enzimáticos. Os dados foram analisados e a significância estatística foi estabelecida em p <0,05. Resultados Os níveis séricos médios de colesterol total (CT), triglicerídeos (TG) e LDL aumentaram drasticamente em animais tratados com GC em comparação com o grupo controle. Ambas as doses de quercetina (50 e 150 mg/kg) melhoraram o CT (43% e 45%), LDL (56% e 56%) e TG (46% e 55%, respectivamente). A razão Apo B/A1 diminuiu mais de 20% após a ingestão de Anti-Inflamatory Agents. Conclusões Esses dados sugerem que a ingestão de quercetina Quercetin; induzida por glicocorticóides. (Arq Bras Cardiol. 2020; 115(1):102-108)


Abstract Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.)


Subject(s)
Animals , Rats , Quercetin/pharmacology , Glucocorticoids , Apolipoproteins , Triglycerides , Rats, Sprague-Dawley , Lipids
5.
Acta bioquím. clín. latinoam ; 54(1): 3-11, mar. 2020. graf, tab
Article in Spanish | LILACS | ID: biblio-1130573

ABSTRACT

En la Republica Argentina, la prevalencia de obesidad se ha incrementado considerablemente y la de diabetes mellitus tipo 2 (DMT2) alcanza 12,7%. La obesidad presenta heterogeneidad y el aumento de la grasa abdominal puede incluir hipertrigliceridemia, hiperglucemia, disminucion de C-HDL, aumentos de apolipoproteina B (Apo B), aumento de lipoproteinas LDL pequenas y densas, hiperinsulinemia, insulino-resistencia (IR), estado inflamatorio cronico, estado protrombotico y otras alteraciones metabolicas, que se han reunido en el llamado sindrome metabolico con prevalencia del 20 al 40%. La resistencia a la insulina (IR) esta presente en 10 al 25% de la poblacion y se asocia con esas alteraciones. La determinacion de IR es compleja, necesita de internacion en clinicas y debe ser realizada por especialistas. En el laboratorio se puede estimar a traves del dosaje de insulina, pero no esta estandarizado, por lo que es necesario disponer de tecnicas sencillas y accesibles. La relacion trigliceridos (TG)/colesterol HDL (C-HDL) puede ser una opcion utilizando como valores de corte TG/C-HDL ≥2,5 en mujeres y ≥3,5 en varones. Se asocia significativamente con IR y enfermedad cardiovascular (ECV), tiene buena especificidad aunque bajo poder discriminador por lo cual cuando esta presente y existe riesgo de DMT2 o ECV deberia complementarse con el calculo del colesterol-no-HDL o Apo B y el colesterol remanente. Teniendo en cuenta la pandemia de obesidad y DMT2 y la elevada frecuencia de ECV, la relacion TG/C-HDL podria ser un marcador que deberia ser informado por el laboratorio bioquimico-clinico.


In Argentina, the prevalence of obesity has increased considerably and type 2 diabetes mellitus (DMT2) reaches 12.7%. Obesity presents heterogeneity and the increase in abdominal fat may include hypertriglyceridemia, hyperglycemia, decrease in HDL-C, increases in apolipoprotein B (Apo B), increase in small and dense LDL lipoproteins, hyperinsulinemia, insulin resistance (IR), chronic inflammatory state, prothrombotic state and other metabolic alterations, which have been included in the so-called metabolic syndrome with 20 to 40% prevalence. Insulin resistance is present in 10 to 25% of the population and is associated with these alterations. The determination of IR is complex; it needs hospitalization and must be performed by specialists. In the laboratory, it can be estimated through insulin dosing, but it is not standardized, so it is necessary to have simple and accessible techniques. The triglycerides (TG)/HDL cholesterol (HDL-C) ratio can be an option using TG/C-HDL cutoff values ≥2.5 in women and ≥3.5 in men. It is significantly associated with IR and CVD and has good specificity but low discriminating power. So when it is present and there is a risk of T2DM or cardiovascular disease, CVD should be complemented with the calculation of non-HDL cholesterol or Apo B and the remaining cholesterol. Considering the pandemic of obesity and DMT2 and the high frequency of CVD, the TG/C-HDL ratio marker should be reported by the biochemical-clinical laboratory.


Na Republica Argentina, a prevalencia de obesidade aumentou em forma consideravel e a de diabetes mellitus tipo 2 (DMT2) atinge 12,7%. A obesidade apresenta heterogeneidade e o aumento da gordura abdominal pode incluir hipertrigliceridemia, hiperglicemia, diminuicao do HDL-C, aumentos da apolipoproteina B (Apo B), aumento das lipoproteinas LDL pequenas e densas, hiperinsulinemia, resistencia a insulina, estado inflamatorio cronico, estado pro-trombotico e outras alteracoes metabolicas, que se encontraram na chamada sindrome metabolica, com prevalencia de 20 a 40%. A resistencia a insulina (RI) esta presente em 10 a 25% da populacao e esta associada a essas alteracoes. A determinacao da RI e complexa, precisa da hospitalizacao em clinicas e deve ser realizada por especialistas. No laboratorio, isso pode ser estimado atraves da dosagem de insulina, mas nao e padronizado, portanto e necessario ter tecnicas simples e acessiveis. A relacao triglicerideos (TG)/colesterol HDL (C-HDL) pode ser uma opcao usando como valores de corte TG/C-HDL ≥2,5 em mulheres e ≥3,5 em homens. Esta significativamente associado a RI e a doenca cardiovascular (DCV), possui boa especificidade, embora apresente baixo poder discriminador; portanto, quando esta presente e ha risco de DMT2 ou DCV, deveria ser complementado com o calculo do colesterol nao-HDL ou Apo B e o restante colesterol. Considerando a pandemia de obesidade e DMT2 e a alta frequencia de DCV, a relacao TG/C-HDL poderia ser um marcador que deveria ser relatado pelo laboratorio bioquimico-clinico.


Subject(s)
Diabetes Mellitus , Diabetes Mellitus, Type 2 , Atherosclerosis , Heart Disease Risk Factors , Obesity , Apolipoproteins , Triglycerides , Insulin Resistance , Cholesterol , Prevalence , Morbidity , Metabolic Syndrome , Abdominal Fat , Cardiometabolic Risk Factors , Hospitalization , Hyperglycemia , Hyperinsulinism , Insulin
6.
Article in English | WPRIM | ID: wpr-811144

ABSTRACT

BACKGROUND: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.METHODS: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.RESULTS: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.CONCLUSION: Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.


Subject(s)
Adipose Tissue , Apolipoproteins , Body Composition , Body Weight , Clusterin , Diabetes Mellitus, Type 2 , Exercise , Female , Humans , Insulin Resistance , Insulin , Muscle, Skeletal , Sarcopenia
7.
Article in English | WPRIM | ID: wpr-786074

ABSTRACT

OBJECTIVE: Postmenopausal women show a more atherogenic lipid profile and elevated cardiovascular risk compared to premenopausal women. The aim of this study was to investigate the efficacy and safety of high-dose atorvastatin on the improvement of the blood lipid profile of postmenopausal women in Korea.METHODS: This study is a prospective, open-label, single-arm clinical trial that was conducted in 3 teaching hospitals. Postmenopausal women with a moderate-to-high cardiovascular risk, according to guidelines from the Korean Society of Lipid & Atherosclerosis, were enrolled. Participants were administered 20 mg of atorvastatin daily for the first 8 weeks, and if the targeted low-density lipoprotein cholesterol (LDL-C) level was not achieved, the dose was increased to 40 mg for the second 8 weeks. The primary endpoint was percentage change of LDL-C from baseline after 16 weeks of drug administration.RESULTS: Forty-four women were enrolled, 28 of whom (75.6%) had diabetes mellitus. By the end of treatment period (16 weeks) all patients had achieved LDL-C target levels, with 33 (94.2%) of the participants achieving it after only 8 weeks of administration. After 16 weeks, LDL-C decreased by 45.8±16.7% (p<0.001) from the baseline, and total cholesterol (33.2±10.9%; p<0.001), triglyceride (24.2±37.5%; p=0.001), and apolipoprotein B (34.9±15.6%; p<0.001) also significantly decreased. Blood glucose and liver enzyme levels slightly increased, but none of the participants developed serious adverse events that would cause them to prematurely withdraw from the clinical trial.CONCLUSION: 20 and 40 mg atorvastatin was effective and safe for treating dyslipidemia in postmenopausal Korean women with moderate-to-high cardiovascular risk.


Subject(s)
Apolipoproteins , Asian Continental Ancestry Group , Atherosclerosis , Atorvastatin , Blood Glucose , Cholesterol , Diabetes Mellitus , Dyslipidemias , Female , Hospitals, Teaching , Humans , Korea , Lipoproteins , Liver , Postmenopause , Prospective Studies , Triglycerides
8.
Immune Network ; : 41-2019.
Article in English | WPRIM | ID: wpr-785820

ABSTRACT

We previously demonstrated that atherogenic Ldlr(−/−)Apobec1(−/−) (LDb) double knockout mice lacking both low-density lipoprotein receptor (LDLR) and apolipoprotein B mRNA-editing catalytic polypeptide-1 (Apobec1) had increased serum IL-17 levels, with T cell programming shifted towards Th17 cells. In this study, we assessed the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in T cell programming and atherogenesis. We deleted the Pcsk9 gene from LDb mice to generate Ldlr(−/−)Apobec1(−/−)Pcsk9(−/−) (LTp) triple knockout mice. Atherosclerosis in the aortic sinus and aorta were quantitated. Lymphoid cells were analyzed by flow cytometry, ELISA and real-time PCR. Despite of dyslipidemia, LTp mice developed barely detectable atherosclerotic lesions. The IL-17, was very low in plasma and barely detectable in the aortic sinus in the LTp mice. In the spleen, the number of CD4⁺CD8⁻ cells and splenocytes were much lower in the LDb mice than LTp mice, whereas, the IL-17-producing cells of γδTCR⁺ T cells and effector memory CD4⁺ T cells (CD44(hi)CD4⁺) in the spleen were significantly higher in the LDb mice than in the LTp mice. The Rorc mRNA expression levels were elevated in LDb mice compared to LTp mice. When re-stimulated with an anti-CD3 Ab, CD44(hi)CD4⁺ T cells from LDb mice secreted more IL-17 than those from LTp mice. T cells from LDb mice (with PCSK9) produce more IL-17 at basal and stimulated conditions when compared with LTp mice (without PCSK9). Despite the dyslipidemic profile and the lack of LDLR, atherogenesis is markedly reduced in LTp mice. These results suggest that PCSK9 is associated with changes in T cell programming that contributes to the development of atherosclerosis.


Subject(s)
Animals , Aorta , Apolipoproteins , Atherosclerosis , Dyslipidemias , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Hyperlipidemias , Interleukin-17 , Lymphocytes , Memory , Mice , Mice, Knockout , Negotiating , Plasma , Proprotein Convertases , Real-Time Polymerase Chain Reaction , Receptors, Lipoprotein , RNA, Messenger , Sinus of Valsalva , Spleen , T-Lymphocytes , Th17 Cells
9.
Article in English | WPRIM | ID: wpr-761785

ABSTRACT

Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with 50 µM curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%–8.05% to 27.63%–35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by 50 µM curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the editosome in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.


Subject(s)
Animals , Apolipoproteins B , Apolipoproteins , Atherosclerosis , Complement System Proteins , Curcuma , Curcumin , Cytidine , Deamination , Hepatocytes , Lipoproteins, LDL , Mice , Plasma , Rats , RNA Editing , RNA, Messenger , RNA-Binding Proteins , Uridine
10.
Article in English | WPRIM | ID: wpr-741709

ABSTRACT

BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at ClinicalTrials.gov as NCT03267901.


Subject(s)
Adiponectin , Adult , Ambulatory Care , Apolipoproteins , Body Mass Index , Cholesterol , Cross-Over Studies , Dietary Supplements , Fasting , Glucose , Humans , Juglans , Leptin , Lipoproteins
11.
Article in English | WPRIM | ID: wpr-740300

ABSTRACT

The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.


Subject(s)
Alleles , Apolipoproteins B , Apolipoproteins E , Apolipoproteins , Genotype , Hepacivirus , Hepatitis C , Hepatitis , Humans , Liver
12.
Article in English | WPRIM | ID: wpr-765668

ABSTRACT

Serum cholesterol is major risk factor and contributor to atherosclerotic cardiovascular disease (ASCVD). Therapeutic cholesterol-lowering drugs, especially statin, revealed that reduction in low-density lipoprotein cholesterol (LDL-C) produces marked reduction of ASCVD events. In the preventive scope, lower LDL-C is generally accepted as better in proven ASCVD patients and high-risk patient groups. However, in patients with low to intermediate risk without ASCVD, risk assessment is clinically guided by traditional major risk factors. In this group, the complement approach to detailed risk assessment about traditional major risk factors is needed. These non-traditional risk factors include ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, lipoprotein(a) (Lp[a]), apolipoprotein B (apoB), or coronary artery calcium (CAC) score. CAC measurements have an additive role in the decision to use statin therapy in non-diabetic patients 40–75 years old with intermediate risk in primary prevention. This review comprises ASCVD lipid/biomarkers other than CAC. The 2013 and 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines suggest these factors as risk-enhancing factors to help health care providers better determine individualized risk and treatment options especially regarding abnormal biomarkers. The recent 2018 Korean guidelines for management of dyslipidemia did not include these biomarkers in clinical decision making. The current review describes the current roles of hsCRP, ABI, LP(a), and apoB in personal modulation and management of health based on the 2018 ACC/AHA guideline on the management of blood cholesterol.


Subject(s)
Ankle Brachial Index , Apolipoproteins , Apolipoproteins B , Biomarkers , C-Reactive Protein , Calcium , Cardiovascular Diseases , Cholesterol , Clinical Decision-Making , Complement System Proteins , Coronary Vessels , Dyslipidemias , Health Personnel , Heart , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Lipoprotein(a) , Lipoproteins , Primary Prevention , Risk Assessment , Risk Factors
13.
Article in English | WPRIM | ID: wpr-765095

ABSTRACT

BACKGROUND: Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. METHODS: This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. RESULTS: In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97–1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74–0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97–1.20) and 0.80 (95% CI, 0.70–0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52–0.92) for the E2 allele and 1.25 (95% CI, 1.03–1.53) for the E4 allele. CONCLUSION: In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans.


Subject(s)
Alleles , Apolipoproteins E , Apolipoproteins , Asian Continental Ancestry Group , Cardiovascular Diseases , Cohort Studies , Ethnic Groups , Genotype , Humans , Life Style , Mortality , Negotiating , Proportional Hazards Models
14.
Article in English | WPRIM | ID: wpr-763687

ABSTRACT

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.


Subject(s)
Apolipoprotein A-I , Apolipoproteins , Apolipoproteins B , Cardiovascular Diseases , Cholesterol, LDL , Diabetes Mellitus, Type 2 , Ezetimibe , Fatty Acids, Nonesterified , Hand , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Korea , Liver , Rosuvastatin Calcium , Triglycerides
15.
Psychiatry Investigation ; : 575-580, 2019.
Article in English | WPRIM | ID: wpr-760974

ABSTRACT

OBJECTIVE: We investigated the impact of depressed mood (dysphoria) and loss of interest or pleasure (anhedonia)on the risk of dementia in cognitively-normal elderly individuals. METHODS: This study included 2,685 cognitively-normal elderly individuals who completed the baseline and 4-year follow-up assessments of the Korean Longitudinal Study on Cognitive Aging and Dementia. We ascertained the presence of dysphoria and anhedonia using the Mini International Neuropsychiatric Inventory. We defined subjective cognitive decline as the presence of subjective cognitive complaints without objective cognitive impairments. We analyzed the association of dysphoria and anhedonia with the risk of cognitive disorders using multinomial logistic regression analysis adjusted for age, sex, education, Cumulative Illness Rating Scale score, Apolipoprotein E genotype, and neuropsychological test performance. RESULTS: During the 4-year follow-up period, anhedonia was associated with an approximately twofold higher risk of mild cognitive impairment (OR=2.09, 95% CI=1.20–3.64, p=0.008) and fivefold higher risk of dementia (OR=5.07, 95% CI=1.44–17.92, p=0.012) but was not associated with the risk of subjective cognitive decline. In contrast, dysphoria was associated with an approximately twofold higher risk of subjective cognitive decline (OR=2.06, 95% CI=1.33–3.19, p=0.001) and 1.7-fold higher risk of mild cognitive impairment (OR=1.75, 95% CI=1.00–3.05, p=0.048) but was not associated with the risk of dementia. CONCLUSION: Anhedonia, but not dysphoria, is a risk factor of dementia in cognitively-normal elderly individuals.


Subject(s)
Aged , Anhedonia , Apolipoproteins , Cognition Disorders , Cognitive Aging , Cohort Studies , Dementia , Depression , Education , Follow-Up Studies , Genotype , Humans , Logistic Models , Longitudinal Studies , Cognitive Dysfunction , Neuropsychological Tests , Pleasure , Prospective Studies , Risk Factors
16.
Chonnam Medical Journal ; : 31-35, 2018.
Article in English | WPRIM | ID: wpr-787260

ABSTRACT

We aimed to evaluate the prevalence of familial hypercholesterolaemia (FH) in a subject with hypercholesterolaemia from two population-based cohorts in South Korea. A total of 283 subjects with total cholesterol levels of 290 mg/dL (7.5 mmol/L) or higher were selected from the Namwon and Dong-gu Studies. We used next generation sequencing (NGS) to detect mutations in low-density lipoprotein receptors (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. We have confirmed 17 different mutations of the LDLR, APOB and PCSK9 in 23 subjects (8.1%). Eleven LDLR variants and one APOB variant have been previously reported. One LDLR and two PCSK9 rare variants were identified in the variants database, but not in the FH mutation database. Two novel LDLR variants were found, p.Leu680Val, and p.Thr734Phe. No LDLR, APOB or PCSK9 deletions nor insertions were found. When the subjects were restricted to 110 subjects with a total cholesterol ≥310 mg/dL, only 10 variants were found in the 10 subjects (9.1%). These results suggest that given the low prevalence of FH mutations in subjects with high total cholesterol levels, NGS-based testing for a population-based approach to FH detection may not be cost-effective.


Subject(s)
Apolipoproteins , Apolipoproteins B , Cholesterol , Cohort Studies , High-Throughput Nucleotide Sequencing , Hyperlipoproteinemia Type II , Korea , Prevalence , Proprotein Convertases , Receptors, Lipoprotein
17.
Article in English | WPRIM | ID: wpr-741682

ABSTRACT

BACKGROUND/OBJECTIVES: This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans. SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured. RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [β = −2.048, P < 0.001; β = −2.199, P < 0.001] as well as elevation of circulating triglyceride levels [β = 0.053, P < 0.001; β = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = −0.277, P = 0.027) and circulating triglyceride level (r = −0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms. CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.


Subject(s)
Alleles , Apolipoproteins , Asian Continental Ancestry Group , Body Mass Index , Cell Line , Cholesterol , Cholesterol, HDL , Cohort Studies , DNA , Epidemiologic Studies , Epidemiology , Genome , Genotype , Hand , Homozygote , Humans , Korea , Linear Models , Lipoproteins , Nutrition Surveys , RNA, Messenger , Triglycerides
18.
Article in English | WPRIM | ID: wpr-714336

ABSTRACT

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00–1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06–1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20–2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.


Subject(s)
Alleles , Alzheimer Disease , Antipsychotic Agents , Apolipoproteins , Behavioral Symptoms , Caregivers , Dementia , Diagnosis , Follow-Up Studies , Humans , Institutionalization , Insurance , Korea
19.
Gut and Liver ; : 201-207, 2018.
Article in English | WPRIM | ID: wpr-713230

ABSTRACT

BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.


Subject(s)
Apolipoprotein A-I , Apolipoprotein A-II , Apolipoprotein C-II , Apolipoprotein C-III , Apolipoproteins , Apolipoproteins B , Apolipoproteins E , Cholesterol , Genotype , Hepacivirus , Hepatitis C , Hepatitis , Humans , Lipid Metabolism , Lipoproteins , Recurrence
20.
Article in Korean | WPRIM | ID: wpr-718773

ABSTRACT

Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.


Subject(s)
Achondroplasia , Acidosis, Lactic , Angelman Syndrome , Apolipoproteins , Brain Diseases , Breast , Deafness , Education , Epilepsies, Myoclonic , Fragile X Syndrome , Gene Rearrangement , Hearing Loss , Hepatolenticular Degeneration , Huntington Disease , Janus Kinase 2 , Korea , Laboratory Proficiency Testing , Leukemia , Li-Fraumeni Syndrome , Methylenetetrahydrofolate Reductase (NADPH2) , Molecular Biology , Multiple Endocrine Neoplasia , Muscular Atrophy, Spinal , Muscular Disorders, Atrophic , Muscular Dystrophy, Duchenne , Optic Atrophy, Hereditary, Leber , Ovarian Neoplasms , Pathology, Molecular , Phosphotransferases , Quality Control , Quality Improvement , Spinocerebellar Ataxias , Vascular Endothelial Growth Factor Receptor-1
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