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1.
Osteoporos Int ; 31(10): 1965-1973, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32394062

ABSTRACT

Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures. INTRODUCTION: CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients. METHODS: Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted. RESULTS: A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34, P = 0.024), but not in the pre-dialysis CKD group (OR 1.04, P = 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47, P = 0.034) but not in patients with pre-dialysis CKD (OR 1.04, P = 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11, P = 0.024), but femoral or other site fractures were not. CONCLUSION: In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.


Subject(s)
Kidney Failure, Chronic , Myocardial Infarction , Spinal Fractures , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Renal Dialysis , Republic of Korea/epidemiology , Risk Factors , Spinal Fractures/epidemiology , Spinal Fractures/etiology
2.
Nutr Metab Cardiovasc Dis ; 28(10): 1021-1028, 2018 10.
Article in English | MEDLINE | ID: mdl-29983222

ABSTRACT

BACKGROUND AND AIMS: Bilirubin has antioxidant and anti-inflammatory properties; serum bilirubin levels have been known to be inversely associated with cardiovascular disease. However, the effects of different bilirubin subtypes on cardiometabolic traits are unknown. In this study, we aimed to determine whether direct bilirubin is more strongly correlated with small, dense low-density lipoprotein (sdLDL) compared to other bilirubin subtypes. We also investigated which LDL subfractions exhibited the highest correlation with direct bilirubin. METHODS AND RESULTS: A total of 288 overweight and centrally obese women were included in this study. The Pearson correlation and Steiger's Z test were used to compare the correlation coefficients between bilirubin subtypes and lipoproteins. Multiple linear regression analyses were used to evaluate the independent association between direct bilirubin and mean LDL particle size. Only direct bilirubin levels were significantly associated with the sdLDL subfraction and mean LDL particle size. Mean LDL particle size exhibited a significantly stronger correlation with direct bilirubin than sdLDL, percent sdLDL, and the sdLDL:large LDL ratio. Regression analysis showed that direct bilirubin was significantly associated with mean LDL particle size, according to both the stepwise method (ß = 11.445, P value = 0.002) and the enter method (ß = 11.655, P value = 0.002). CONCLUSIONS: Direct bilirubin is more strongly correlated with the sdLDL subfraction compared with total and indirect bilirubin, and is independently associated with mean LDL particle size in overweight and centrally obese women.


Subject(s)
Bilirubin/blood , Lipoproteins, LDL/blood , Obesity, Abdominal/blood , Overweight/blood , Adiposity , Adolescent , Adult , Aged , Biomarkers/blood , Cross-Sectional Studies , Female , Humans , Middle Aged , Obesity, Abdominal/diagnosis , Obesity, Abdominal/physiopathology , Overweight/diagnosis , Overweight/physiopathology , Particle Size , Predictive Value of Tests , Young Adult
3.
Oral Dis ; 23(2): 241-246, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27783850

ABSTRACT

OBJECTIVE: Both an elevated leukocyte count and periodontitis share well-recognized associations with cardiometabolic diseases. This cross-sectional study aimed to identify whether the leukocyte count is associated with periodontitis in a nationally representative Korean adult population. MATERIALS AND METHODS: Data from 9391 participants (3659 males and 5732 females) enrolled in 2012-2014 Korean National Health and Nutrition Examination Survey were analyzed. Leukocyte quartiles were categorized as follows: 3000 ≤ Q1 ≤ 4870, 4880 ≤ Q2 ≤5790, 5800 ≤ Q3 ≤ 6840, and 6850 ≤ Q4 ≤ 10000 cells/µl. Periodontitis was defined as scoring greater than or equal to 'code 3' in at least one site according to the WHO's Community Periodontal Index. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for periodontitis in each leukocyte count quartile were calculated using multiple logistic regression analyses. RESULTS: The prevalence of periodontitis was directly correlated with increasing leukocyte quartiles: 19%, 20.4%, 24.3%, and 30.3%. Compared with the lowest leukocyte quartile group, the OR (95% CI) for periodontitis of the highest leukocyte quartile was 1.558 (1.285-1.891) after controlling for confounding factors. CONCLUSION: An elevated leukocyte count was positively associated with the presence of periodontitis.


Subject(s)
Periodontitis/blood , Periodontitis/epidemiology , Adult , Aged , Cross-Sectional Studies , Female , Humans , Leukocyte Count , Male , Middle Aged , Nutrition Surveys , Prevalence , Republic of Korea/epidemiology , Young Adult
4.
Niger J Clin Pract ; 18(6): 796-801, 2015.
Article in English | MEDLINE | ID: mdl-26289520

ABSTRACT

BACKGROUND: An important goal in the treatment of chronic hepatitis B virus (HBV) infection is to prevent hepatocellular carcinoma and liver cirrhosis by suppressing HBV replication. Tenofovir and entecavir are effective viral suppression compounds. However, comparative data is scant, especially in Korea. This study compared tenofovir and entecavir concerning efficiencies and side effects. MATERIALS AND METHODS: We retrospectively reviewed data of nucleos (t) ide-naïve patients with chronic HBV infection. Independent variables reflecting virological response were evaluated, and the decline in serum HBV DNA levels, and side effects between tenofovir-and entecavir-treated patients were compared at treatment week 12, 24, and 48. RESULTS: At the end of 48 weeks, there was no statistical difference in the induction of undetectable levels of HBV DNA between the entecavir (82.5%) and tenofovir (69.2%) groups. Entecavir was more effective in reducing serum HBV DNA levels at 24 weeks of treatment (serum HBV DNA decline of 5.53 and 4.95 log10 units for entecavir and tenofovir, respectively; P=0.044), but the rate of decline was similar at other weeks. There was no difference between the two groups in terms of side effects and discontinuance of treatment due to side effects. CONCLUSIONS: Tenofovir is not significantly different from entecavir in virologic response and tolerability in the treatment of chronic HBV.


Subject(s)
Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Tenofovir/therapeutic use , Adult , Antiviral Agents/therapeutic use , Female , Guanine/therapeutic use , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
5.
Phys Rev Lett ; 107(13): 131801, 2011 Sep 23.
Article in English | MEDLINE | ID: mdl-22026842

ABSTRACT

We report on a search for CP violation in τ(±)→K(S)(0)π(±)ν(τ) decays using a data sample of 699 fb(-1) collected by the Belle experiment at the KEKB electron-positron asymmetric-energy collider. The CP asymmetry is measured in four bins of the invariant mass of the K(S)(0)π(±) system and found to be compatible with zero with a precision of O(10(-3)) in each mass bin. Limits for the CP violation parameter Im(η(S)) are given at the 90% confidence level. These limits are |Im(η(S))| < 0.026 or better, depending on the parametrization used to describe the hadronic form factors, and improve upon previous limits by 1 order of magnitude.

6.
Phys Rev Lett ; 103(24): 241801, 2009 Dec 11.
Article in English | MEDLINE | ID: mdl-20366195

ABSTRACT

Using 605 fb(-1) of data collected at the Upsilon(4S) resonance we present a measurement of the inclusive radiative B-meson decay channel, B-->X(s)gamma. For the lower photon energy thresholds of 1.7, 1.8, 1.9, and 2.0 GeV, as defined in the rest frame of the B meson, we measure the partial branching fraction and the mean and variance of the photon energy spectrum. At the 1.7 GeV threshold we obtain the partial branching fraction BF(B-->X(s)}gamma)=(3.45+/-0.15+/-0.40)x10(-4), where the errors are statistical and systematic.


Subject(s)
Light , Mesons , Photons , Spectrum Analysis , Thermodynamics
7.
Transplant Proc ; 51(3): 749-760, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30979460

ABSTRACT

BACKGROUND: This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. METHODS: At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. RESULTS: Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. CONCLUSION: Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , Adult , Cyclosporine/therapeutic use , Delayed-Action Preparations/therapeutic use , Female , Glomerular Filtration Rate , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Patient Satisfaction , Republic of Korea , Research Design , Tacrolimus/adverse effects , Transplant Recipients
8.
Ann Rheum Dis ; 67(10): 1480-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-17998215

ABSTRACT

OBJECTIVES: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. PATIENTS AND METHODS: In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis(a) antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. RESULTS: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis(a) antigen levels were lower in patients. The number of sulfo-Lewis(a) positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. CONCLUSION: Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.


Subject(s)
Mucins/metabolism , Sjogren's Syndrome/metabolism , Xerostomia/metabolism , Adult , Densitometry , Female , Gene Expression , Humans , Lewis Blood Group Antigens , Middle Aged , Mucin-5B , Mucins/genetics , Oligosaccharides/metabolism , RNA, Messenger/genetics , Salivary Glands/metabolism , Salivation , Sulfates/metabolism
9.
Diabetes Metab ; 44(4): 346-353, 2018 Sep.
Article in English | MEDLINE | ID: mdl-28838743

ABSTRACT

AIM: In this study, the impact of serum bilirubin on new-onset type 2 diabetes mellitus (T2DM) in Korean adults was investigated. METHODS: Data were obtained from the Korean Genome and Epidemiology Study (KoGES), a population-based prospective cohort study. The study enrolled 8650 adults (4015 men and 4635 women), aged 40 to 69 years, who underwent a mean follow-up of 8.4 years. The study population was divided into quartiles (Q) of serum bilirubin levels, with cut-off points at 0.46, 0.61 and 0.82mg/dL for men, and 0.35, 0.47 and 0.61mg/dL for women. T2DM was defined based on the following data: fasting blood glucose≥7.0mmol/L, HbA1c level≥6.5% or 2-h plasma glucose≥11.1mmol/L during a 75-g oral glucose tolerance test. RESULTS: Over the mean 8.4-year follow-up, 786 participants (9.1%) developed T2DM. Compared with Q1, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM incidence were 0.52 (0.36-0.74) in men and 0.56 (0.38-0.83) in women aged ≥50 years, respectively, in the highest Q group after adjusting for possible confounding factors. These significant results persisted in those with impaired glucose tolerance and impaired fasting glucose. CONCLUSION: The results of this study reveal a protective role for serum total bilirubin on new-onset T2DM in Korean men and women. In addition, serum total bilirubin had favourable effects on new-onset T2DM in those with impaired glucose tolerance and impaired fasting glucose.


Subject(s)
Bilirubin/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Adult , Aged , Blood Glucose , Female , Humans , Male , Middle Aged , Prospective Studies , Republic of Korea/epidemiology
10.
Transplant Proc ; 50(4): 1183-1186, 2018 May.
Article in English | MEDLINE | ID: mdl-29731090

ABSTRACT

BACKGROUND: Administrative processing by the police may affect the process involved in organ donation in the event of an accidental brain injury. The purpose of this study was to evaluate the knowledge and attitude of police toward brain-dead donors and organ donation. METHODS: This was a descriptive research study using a 41-item questionnaire. As of July 19, 2017, 11 police stations in Seoul had collected questionnaires completed by 115 police officers. Data were analyzed using SAS (version 9.4) software. RESULTS: There were statistically significant differences in the scores on knowledge about brain death/donation according to religion (P = .022). Attitude was significantly positively correlated with the knowledge about brain-death organ donation (P = .029). CONCLUSION: It is necessary to understand and cooperate with the police when processing brain death organs from accidents. Education about organ donation can enhance the information and knowledge of the police and can also help to establish a positive attitude about organ donation.


Subject(s)
Brain Death , Health Knowledge, Attitudes, Practice , Police , Tissue and Organ Procurement , Adult , Comprehension , Female , Humans , Male , Religion , Republic of Korea , Surveys and Questionnaires , Tissue Donors
11.
Curr Med Chem ; 23(2): 142-60, 2016.
Article in English | MEDLINE | ID: mdl-26438251

ABSTRACT

ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates several cellular processes like apoptosis, survival, differentiation, proliferation, cell migration, and transformation. There is increasing evidence supporting that ROS1 plays an important role in different malignancies including glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares about 49% sequence homology with ALK primary structure; therefore, wide range of ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1 kinase. After Crizotinib approval by FDA for the management of ALK-rearranged lung cancer, ROS1-positive tumors have been focused. Although significant advancements have been achieved in understanding ROS1 function and its signaling pathways plus recent discovery of small molecules modulating ROS1 protein, a vital need of medicinal chemistry efforts is still required to produce selective and potent ROS1 inhibitors as an important therapeutic strategy for different human malignancies. This review focuses on the current knowledge about different scaffolds targeting ROS1 rearrangements, methods to synthesis, and some biological data about the most potent compounds that have delivered various scaffold structures.


Subject(s)
Molecular Targeted Therapy , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Chemistry, Pharmaceutical , Humans , Models, Molecular , Molecular Structure , Neoplasms/enzymology , Neoplasms/metabolism , Protein Kinase Inhibitors/chemistry , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism
12.
Biomater Sci ; 3(7): 1124-33, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26221945

ABSTRACT

Polyplexes, complexed nucleic acids by cationic polymers, are the most common forms of nonviral gene delivery vectors. In contrast to a great deal of efforts in synthesizing novel cationic polymers and exploring their extracellular and intracellular delivery pathways, polyplex preparation methods of mixing nucleic acids and cationic polymers are often overlooked. In this study, the mixing sequence, that is adding nucleic acids to polymers or vice versa, was found to greatly affect complexation of both plasmid DNA and siRNA, polyplexes' size, and polyplexes' surface charge, which all collaboratively affected the transfection efficiency and cytotoxicity. Adding polyethylenimine (PEI), the most conventionally used standard in nonviral gene delivery, to plasmid DNA and siRNA resulted in larger polyplexes, higher gene expression and silencing, but higher cytotoxicity than polyplexes prepared in the reverse order. Based on the experimental results, the authors developed a model that gradual addition of cationic polymers (e.g., PEI) to nucleic acids (e.g., plasmid DNA and siRNA) incorporates more copies of nucleic acids in larger polyplexes in a smaller number, results in higher gene expression and silencing levels in transfected cells, and generates higher cytotoxicity by leaving more free polymers upon complete mixing than the other mixing sequence. The proposed model can be explored using a broad range of cationic polymers and nucleic acids, and provide insightful information about how to prepare polyplexed nonviral vectors for efficient and safe gene delivery.


Subject(s)
Cytoplasm/chemistry , DNA/chemistry , Nucleic Acids/chemistry , Plasmids/chemistry , Polyethyleneimine/chemistry , Polymers/chemistry , RNA, Small Interfering/chemistry , Transfection/methods , Cytoplasm/metabolism , DNA/genetics , Gene Transfer Techniques , Genetic Therapy , Genetic Vectors , Particle Size , Plasmids/metabolism , RNA, Small Interfering/genetics , Transfection/instrumentation
13.
SAR QSAR Environ Res ; 26(5): 397-420, 2015.
Article in English | MEDLINE | ID: mdl-25986171

ABSTRACT

Histone deacetylases 8 (HDAC8) is an enzyme repressing the transcription of various genes including tumour suppressor gene and has already become a target of human cancer treatment. In an effort to facilitate the discovery of HDAC8 inhibitors, two quantitative structure-activity relationship (QSAR) classification models were developed using K nearest neighbours (KNN) and neighbourhood classifier (NEC). Molecular descriptors were calculated for the data set and database compounds using ADRIANA.Code of Molecular Networks. Principal components analysis (PCA) was used to select the descriptors. The developed models were validated by leave-one-out cross validation (LOO CV). The performances of the developed models were evaluated with an external test set. Highly predictive models were used for database virtual screening. Furthermore, hit compounds were subsequently subject to molecular docking. Five hits were obtained based on consensus scoring function and binding affinity as potential HDAC8 inhibitors. Finally, HDAC8 structures in complex with five hits were also subjected to 5 ns molecular dynamics (MD) simulations to evaluate the complex structure stability. To the best of our knowledge, the NEC classification model used in this study is the first application of NEC to virtual screening for drug discovery.


Subject(s)
Histone Deacetylase Inhibitors/chemistry , Histone Deacetylases/chemistry , Machine Learning , Quantitative Structure-Activity Relationship , Databases, Chemical , Drug Discovery , Models, Chemical , Molecular Dynamics Simulation , Principal Component Analysis
14.
Ann N Y Acad Sci ; 802: 149-76, 1996 Dec 16.
Article in English | MEDLINE | ID: mdl-8993494

ABSTRACT

In a conference held in Chicago during October 1995, a working group of the National Institute of Aging (NIA) and the Alzheimer's Association (AlzA) drafted consensus recommendations on research and clinical applications of APOE genetic susceptibility testing for Alzheimer's disease (AD). The NIA/AlzA Working Group concluded that in considering future applications of APOE genotyping and other knowledge that has been gained about the genetic basis of AD, the interests of AD patients and their family members must be held paramount. The group acknowledged that a robust association exists between possession of the APOE epsilon 4 allele and the risk of late-onset AD and cited evidence that this allele is more strongly associated with AD than any other form of dementia. They recommended against the use of APOE genotyping to predict the-future development of AD in asymptomatic individuals at this time, and warned against the use of the test in isolation as the sole means for diagnosing AD. The group endorsed the concept of discretionary use of APOE genotyping as an adjunct to other AD diagnostic procedures. However, routine clinical use of the test for this purpose was not recommended at this time. Physicians were advised to weigh any potential benefits of testing against the possibility that genotype disclosure could adversely affect the insurability, employability, and social standing of AD patients and their family members. Adequate provisions for pre-test and post-test counseling and psychosocial support were advised for all future clinical and research applications of APOE genotyping. The group called for the development of improved protocols for AD genetic counseling as well as supplemental measures to assure genetic privacy for AD patients and their family members.


Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Genetic Testing , National Institutes of Health (U.S.) , Alleles , Alzheimer Disease/diagnosis , Apolipoprotein E4 , Gene Frequency , Genotype , Heterozygote , Humans , Odds Ratio , United States
15.
Life Sci ; 52(19): 1527-34, 1993.
Article in English | MEDLINE | ID: mdl-8483381

ABSTRACT

It was aimed to test the role of ATP-sensitive K+ channels in the autoregulatory response of cerebral arterioles in vivo. Changes in pial arterial caliber (mean, 43.2 +/- 2.3 microns in diameter) in response to changes in systemic arterial blood pressure (mean, 104.3 +/- 1.4 mmHg) were observed directly through closed cranial windows in anesthetized normotensive rats. During superfusion with vehicle, pial arterial caliber automatically increased in response to hypotension induced by arterial bleeding into a reservoir and decreased on reverse of arterial blood pressure by infusion of blood. After pretreatment with sulfonylureas, glibenclamide (1 and 3 microM) and glipizide (30 and 100 microM), arteriolar dilatation and constriction observed during hypotension and its reverse were disturbed. A similarity was evidenced when hypotension was induced by sodium nitroprusside (750 nmol kg-1min-1, i.v.). Cromakalim, a K+ channel opener, exerted a concentration-dependent vasodilatation of the pial artery and its effect was antagonized by glibenclamide. These data suggest that the endogenous glibenclamide-sensitive K+ channel opener is involved in the modulation of cerebral microvascular autoregulation.


Subject(s)
Glipizide/pharmacology , Glyburide/pharmacology , Pia Mater/blood supply , Animals , Arterioles/drug effects , Arterioles/physiology , Blood Pressure/drug effects , Blood Pressure/physiology , Cerebral Arteries/drug effects , Cerebral Arteries/physiology , Rats , Rats, Sprague-Dawley , Vasodilation/drug effects , Vasodilation/physiology
16.
Biotechnol Prog ; 17(2): 240-6, 2001.
Article in English | MEDLINE | ID: mdl-11312699

ABSTRACT

Retrovirus-mediated gene transfer is one of the most commonly used methods to deliver, integrate, and express the gene of interest because the retrovirus can insert the desired gene into the chromosome of the target cells with high stability. However, to deliver the gene successfully, the retrovirus requires active division to integrate reversely transcribed DNA into the chromosome of target cells. In this study, we focused on the effect of cell-cell contact inhibition on the efficiency of retroviral transduction with two anchorage-dependent cell lines: NIH 3T3 and 293 cells. These two cell lines have very different cell morphologies and growth patterns on surfaces. Human embryonic kidney epithelial 293 cells tend to stick together after dividing, while NIH 3T3 cells migrate to occupy available surface and spread. Experimental data indicate that the abatement of the transduction rate of 293 cells was initiated in the early stage of the culture, whereas effect of contact inhibition of NIH 3T3 cells on the transduction rate became dominating at the end of the culture period. Experimental results were also quantitatively illustrated by plotting normalized multiplicity of infection (MOI) versus normalized cell density. According to the outcomes, cell inoculation density plays an important role in optimizing the retroviral transduction rate. The optimal time of retroviral transduction should be confined to the accelerating growth phase for 293 cells and at the exponential growth phase for NIH 3T3 cells. The implication drawn from this study is that contact inhibition effect on retroviral transduction should be taken into account for large-scale gene transfer systems such as the microcarrier bioreactor.


Subject(s)
Cell Division , Retroviridae/genetics , Transduction, Genetic , Animals , Cell Line , Gene Transfer Techniques , Humans , Mice
17.
Clin Nephrol ; 56(1): 19-26, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11499655

ABSTRACT

AIM: In the elderly with renal disease, the clinical presentations are frequently inconsistent with the pathologic findings. We tried to clarify the differences in pathological findings between the young and the elderly, in Korea and in Western countries, and the usefulness of a percutaneous renal biopsy in the elderly with renal disease. PATIENTS AND METHODS: We analyzed the clinical presentations and spectrums of renal histopathology by reviewing medical records and renal biopsy reports retrospectively in 117 Korean patients aged 60 years or more with renal disease. RESULTS: 85 patients had primary renal disease. The remaining 32 patients had renal diseases associated with systemic conditions. Out of the 85 patients with primary renal disease, 61 cases presented as idiopathic nephrotic syndrome. Compared with renal biopsy results of younger adult patients (age 15-59, n = 1,908), membranous nephropathy, crescentic glomerulonephritis, membranoproliferative glomerulonephritis, amyloidosis, light chain disease, and thrombotic thrombocytopenic purpura were more prevalent, but IgA nephropathy and lupus nephritis were less common in the elderly patients. In clinical presentation, nephrotic syndrome and rapidly progressive renal failure were more prevalent, but asymptomatic urinary abnormality was less common in elderly patients. The responsiveness to treatment was good in elderly patients with minimal-change lesion (complete remission in all patients) but poor in crescentic glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis. From the above findings, the clinical presentation, patterns of histopathology and responsiveness to treatment of elderly Korean patients were similar to those of the younger Korean control group and the Western elderly group. CONCLUSION: Percutaneous renal biopsy is a useful diagnostic aid and can be used as a therapeutic guideline even in elderly patients with renal disease.


Subject(s)
Kidney Diseases/pathology , Aged , Aged, 80 and over , Aging/physiology , Biopsy/methods , Chi-Square Distribution , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Diseases/drug therapy , Kidney Diseases/epidemiology , Korea/epidemiology , Male , Middle Aged
18.
Eur J Surg Oncol ; 40(3): 330-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24373299

ABSTRACT

BACKGROUND: To assess the safety of transorally-inserted anvil (TOA) for use during esophagojejunostomy (EJ) reconstruction during laparoscopic total gastrectomy (LTG). METHODS: Between March 2009 and December 2011, 39 consecutive open total gastrectomies (OTGs) and 36 LTGs using TOA for gastric cancer were comparatively evaluated. We investigated postoperative complications, using the Clavien-Dindo classification. To evaluate the effect of a learning period in using TOA for LTG, we also investigated shifts in the patterns of complications and changes in total operation time over the course of the study. RESULTS: The patient characteristics at baseline were not different between both groups, except for the extent of lymphadenectomy (P < 0.001) and depth of tumor invasion (P = 0.003). Multivariate analysis revealed that TOA usage elevated the occurrence of infectious complications significantly (OR = 3.32, P = 0.042), but was not associated with EJ-related complications. TOA usage did not need a learning period for the length of time required to complete the operation, or the likelihood of developing an EJ-related or infectious complication. CONCLUSIONS: TOA use for EJ during LTG is relatively simple and easy enough not to require a learning period for surgeons. This procedure did not elevated the occurrence of EJ-related complications compared to circular stapling in open surgery, but it does require special prevention efforts to avoid infectious complications.


Subject(s)
Esophagus/surgery , Gastrectomy/methods , Natural Orifice Endoscopic Surgery/instrumentation , Patient Safety , Stomach Neoplasms/surgery , Aged , Anastomosis, Surgical/methods , Cohort Studies , Female , Gastroscopy/methods , Humans , Jejunostomy/methods , Laparotomy/methods , Male , Middle Aged , Minimally Invasive Surgical Procedures/methods , Natural Orifice Endoscopic Surgery/methods , Neoplasm Invasiveness/pathology , Neoplasm Staging , Operative Time , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Surgical Stapling/methods , Treatment Outcome
19.
Eur J Clin Nutr ; 67(2): 196-201, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23385969

ABSTRACT

BACKGROUND/OBJECTIVES: Gestational diabetes mellitus (GDM) risk factors are well established for Caucasians, but not for Asians. We hypothesized that nutrient intakes, plasma adipokines and/or gestational hormones might be linked to GDM development among pregnant Korean women. This study sought to identify new risk factors for GDM and adverse pregnancy outcomes according to body weight at prepregnancy. SUBJECTS/METHODS: All subjects were pregnant women visiting the Cheil General Hospital and Women's Healthcare Center between June 2006 and March 2009. Non-GDM (n=531) and GDM (n=215) participants were divided into normal-weight and overweight groups according to prepregnancy body mass index (BMI) above or below 23 kg/m(2) at 24-28th week of gestation. At that time, glucose tolerance, insulin resistance as homeostatic model assessment for insulin resistance, insulin secretory capacity as homeostatic model assessment for ß-cell function, anthropometric measurement, nutrient intakes, and plasma levels of adipokines and gestational hormones were determined. RESULTS: GDM women gained more weight in early pregnancy than non-GDM among normal-weight women. GDM was mainly associated with increased insulin resistance in overweight women and decreased insulin secretory capacity in normal-weight women. Plasma visfatin and adiponectin were lower and progesterone levels higher in GDM than non-GDM independent of BMI while plasma resistin levels were higher in non-GDM, but not GDM, overweight women. Energy and saturated fat intakes were higher in GDM independent of body weight, whereas taurine intakes were lower in GDM than non-GDM only in normal-weight women. CONCLUSIONS: Low visfatin and adiponectin and high progesterone levels in the circulation and high energy and saturated fat intakes were common risk factors for GDM and pregnancy outcome such as large for gestational age. Daily reference intakes for energy and fat during pregnancy need to be re-evaluated according to prepregnancy BMI.


Subject(s)
Adiponectin/blood , Body Mass Index , Diabetes, Gestational/etiology , Dietary Fats/adverse effects , Energy Intake , Fatty Acids/adverse effects , Nicotinamide Phosphoribosyltransferase/blood , Diabetes, Gestational/blood , Diet/adverse effects , Female , Humans , Insulin/metabolism , Insulin Resistance , Insulin Secretion , Overweight , Pregnancy , Progesterone/blood , Reference Values , Risk Factors , Taurine/pharmacology , Weight Gain
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