We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and downregulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.

BACKGROUND: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various platelet-function tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy. METHODS: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis. RESULTS: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the kappa statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively. CONCLUSIONS: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events.
Aged ; Aspirin/*administration & dosage ; Coronary Artery Disease/*drug therapy ; Drug Resistance ; Drug Therapy, Combination ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/*administration & dosage ; Platelet Function Tests ; Purinergic P2Y Receptor Antagonists/administration & dosage ; Receptors, Purinergic P2Y12/metabolism ; Tetrazoles/administration & dosage ; Ticlopidine/administration & dosage/*analogs & derivatives

A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.
Aged ; Airway Resistance/physiology ; Carbon Dioxide/blood/physiology ; Diaphragm/physiopathology/*ultrasonography ; Female ; Humans ; Hypercapnia/complications/*physiopathology ; Male ; Middle Aged ; Portal Vein ; Pulmonary Disease, Chronic Obstructive/complications/*physiopathology/ultrasonography ; Pulmonary Gas Exchange ; Respiratory Muscles/physiopathology

Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (> or =70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.
Adult ; Aged ; Chronic Disease ; Demography ; Female ; Humans ; Logistic Models ; Lung/physiopathology ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Pulmonary Disease, Chronic Obstructive/*epidemiology/physiopathology ; Questionnaires ; Republic of Korea ; Risk Factors ; Smoking ; *Sputum/microbiology ; Tuberculosis/*epidemiology/physiopathology

BACKGROUND: This study attempted to investigate the main causes of hemoptysis, the type of examinations used for diagnosis, the treatment modalities and outcomes. METHODS: A retrospective study was conducted on the medical records of 221 patients admitted to the Chonnam National University Hospital, between January 2005 and February 2010, with hemoptysis. RESULTS: Bronchiectasis (32.6%), active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the most sensitive diagnostic test when employed alone, with positive yield of 93.2%. There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients were treated conservatively, but if there was more bleeding present, BAE or surgery was more commonly performed than the conservative treatment (p< or =0.0001). In the multivariate model, severe hemoptysis and lung cancer were independently associated with short-term recurrence. BAE was independently associated with long-term recurrence, and lung cancer was associated with in-hospital mortality. The overall in-hospital mortality rate was 11.3%. CONCLUSION: Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with malignancy had a poorer prognosis. In-hospital mortality was strongly related to the cause, especially in lung cancer.
Bronchial Arteries ; Bronchiectasis ; Diagnostic Tests, Routine ; Fungi ; Hemoptysis ; Hemorrhage ; Hospital Mortality ; Humans ; Lung Neoplasms ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome ; Tuberculosis, Pulmonary

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the PKD1 and PKD2 genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of PKD1 and PKD2 demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that PKD1 and PKD2 probably play important roles during normal renal tubular development. However, their precise role in development and the cellular mechanisms of cyst formation induced by PKD1 and PKD2 mutations are not fully understood. To address this question, we presently created Pkd2 knockout and PKD2 transgenic mouse embryo fibroblasts. We used a mouse oligonucleotide microarray to identify messenger RNAs whose expression was altered by the overexpression of the PKD2 or knockout of the Pkd2. The majority of identified mutations was involved in critical biological processes, such as metabolism, transcription, cell adhesion, cell cycle, and signal transduction. Herein, we confirmed differential expressions of several genes including aquaporin-1, according to different PKD2 expression levels in ADPKD mouse models, through microarray analysis. These data may be helpful in PKD2-related mechanisms of ADPKD pathogenesis.
Animals ; Biological Processes ; Cell Adhesion ; Cell Cycle ; Embryonic Structures ; Fibroblasts ; Kidney ; Mice ; Mice, Transgenic ; Microarray Analysis ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Polycystic Kidney Diseases ; Polycystic Kidney, Autosomal Dominant ; Proteins ; RNA, Messenger ; Signal Transduction

OBJECTIVE: Prevalence of coronary artery disease (CAD) has been reported to be high in patients with atherosclerotic peripheral artery disease (PAD) in lower extremities. Various inflammatory markers have been known to be associated with CAD. The aim of study was to explore the role of inflammatory makers for CAD in patients with PAD. METHODS: A total of 346 PAD patients (71.51+/-9.41 years, 337 males) who underwent percutaneous transluminal angioplasty from June 2006 to April 2012 were included in this study. Patients were divided into the Group I (PAD with CAD: n=151, 149 males) and the Group II (PAD without CAD: n=195, 188 males). RESULTS: Among 346 patients, 149 patients had CAD (43.6%). The prevalence of diabetes mellitus (DM) (p=0.023) and smoking (p=0.010) were significantly higher in the group I when compared withthe group II. The level of high sensitivity C-reactive protein (hs-CRP) increased (p<0.001) significantly in the group I compared with the group II. By multiple logistic regression analysis, smoking (odds ratio [OR]=1.991, 95% confidence interval [CI]: 1.162-3.411; p=0.012), DM (OR=1.922, 95% CI: 1.145-3.228; p=0.015), hs-CRP (> or =3.0 mg/dL) (OR=2.595, 95% CI: 1.548-4.350, p<0.001), and age (OR=0.645; 95% CI, 0.454-0.915; p=0.014) were independent predictors for the development of CAD in PAD patients. CONCLUSION: 43.6% of patients with PAD also had CAD, and the predictors of CAD were smoking, DM, and high level of hs-CRP.
Angioplasty ; C-Reactive Protein ; Coronary Artery Disease* ; Coronary Vessels* ; Diabetes Mellitus ; Humans ; Inflammation* ; Logistic Models ; Lower Extremity ; Peripheral Arterial Disease* ; Prevalence ; Smoke ; Smoking

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.
B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Gene Expression ; Humans ; Immunosuppression ; Kidney Transplantation ; Kidney* ; Lymphocyte Subsets ; Lymphocytes ; Memory ; Precursor Cells, B-Lymphoid ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; T-Lymphocytes ; Transplant Recipients* ; Transplants

Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib;2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400–600 mg (9.6 months). Conclusions Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.