Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 140
Filter
1.
J Appl Microbiol ; 130(2): 439-449, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32500649

ABSTRACT

AIM OF THE STUDY: Effect of internalized phthalyl starch nanoparticles (PSNs) on the antimicrobial ability of Lactococcus lactis (LL) KCTC 2013. METHODS AND RESULTS: Phthalyl starch nanoparticles were prepared by self-assembly of phthalyl starch and the amount of the hydrophobic phthalic moieties were characterized by nuclear magnetic resonance: PSN1 (DS: 14·3 mol.%), PSN2 (DS: 17·8 mol.%) and PSN3 (DS: 30·4 mol.%). The sizes of PSN1, PSN2 and PSN3 measured by dynamic light scattering were 364·7, 248·4 and 213·4 nm, respectively, and the surface charges of PSNs measured by electrophoretic light scattering were negative charges and PSNs were spherical in shape according to scanning electron microscope. It was found that when PSNs were treated with LL, the PSNs were internalized into LL through nanoparticle size-, energy- and glucose transporter-dependent mechanisms. The internalization was confirmed by confocal laser scanning microscopy and fluorescence-activated cell sorting. Nisin was isolated and identified by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Also, more nisin was produced from PSNs-treated LL than untreated- or starch-treated LL. Co-culture assay and agar diffusion test were performed to test the antimicrobial ability. Antimicrobial ability against Gram-negative Escherichia coli k88, Salmonella gallinarum and Gram-positive Listeria monocytogenes of LL treated with PSNs was higher than that of untreated or starch-treated group. Finally, it was found that the expression level of stress response genes dnaK, dnaJ and groES was significantly higher in PSNs-treated groups compared with starch-treated group or LL alone. CONCLUSION: The internalization of PSNs into LL enhanced the production of nisin through mild intracellular stimulation, resulting in enhanced antimicrobial ability. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows the promising potential of PSNs as new prebiotics for increasing the production of nisin, thus demonstrating a new method for the biological production of such antimicrobial peptides.


Subject(s)
Lactococcus lactis/metabolism , Nanoparticles/metabolism , Nisin/biosynthesis , Probiotics/metabolism , Starch/metabolism , Anti-Bacterial Agents/pharmacology , Listeria monocytogenes/drug effects , Nanoparticles/chemistry , Prebiotics , Probiotics/pharmacology , Salmonella/growth & development , Starch/chemistry , Stress, Physiological/genetics
2.
Lupus ; 26(1): 88-94, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27510601

ABSTRACT

OBJECTIVES: Antiphospholipid antibodies (aPL) are present in a proportion of patients with rheumatoid arthritis but their clinical significance remains unclear. We investigated the association between aPL and thrombotic events in rheumatoid arthritis patients. METHODS: In this cross-sectional study, aPL profiles were evaluated in 376 rheumatoid arthritis patients in accordance with the standard guidelines. Clinical and radiographic data were retrospectively collected. RESULTS: aPL were identified in 39 patients (10.4%). Lupus anticoagulant was the most common subtype (n = 25, 6.6%); anti-cardiolipin antibodies and anti-ß2 glycoprotein I antibodies were detected in six and 12 patients (1.6% and 3.2%), respectively. Compared to the aPL-negative group, aPL-positive patients included more male patients (41.0% vs. 15.4%, P < 0.001) and more smokers (41.0% vs. 16.0%, P = 0.001). There was no difference between the two groups in age, disease duration and body mass index, or the frequency of diabetes, hypertension or dyslipidaemia. Of note, arterial thromboses were more common in the aPL-positive than the aPL-negative group (12.8% vs. 2.1%, P = 0.004), whereas the frequency of venous thrombosis did not differ between the two groups (0.0% vs. 0.9%, P = 1.000). On multivariate regression analysis, aPL, age, hypertension, dyslipidaemia and baseline C-reactive protein level were independently associated with arterial thrombotic events (all P values < 0.05). CONCLUSION: aPL was found in a subset of rheumatoid arthritis patients, who were more often smokers, and aPL was independently associated with development of arterial thrombosis. This result suggests that aPL may contribute to an increased risk of arterial thrombosis in rheumatoid arthritis patients.


Subject(s)
Antibodies, Antiphospholipid/immunology , Arthritis, Rheumatoid/complications , Thrombosis/epidemiology , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/immunology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Regression Analysis , Retrospective Studies , Risk Factors , Thrombosis/immunology , Young Adult
3.
J Nutr Health Aging ; 20(8): 816-824, 2016.
Article in English | MEDLINE | ID: mdl-27709230

ABSTRACT

OBJECTIVE: We aimed to investigate the association between metabolic syndrome (MS) and hearing impairment (HI) using nationally representative data from Korean adults. DESIGN, SETTING AND PARTICIPANTS: A total of 16,799 subjects (≥19 years old; 7,170 men and 9,629 women) who underwent pure tone audiometry testing were included in the analysis. Data were obtained from the fifth Korea National Health and Nutrition Examination Survey (2010-2012). Subjects were divided into two groups according to the presence of MS. RESULTS: Among the subjects with MS, 47% had HI. Logistic regression analysis revealed that MS was not an independent risk factor for HI, although increased fasting plasma glucose (OR 1·4, 95% CI: 1·1-1·8) was independently associated with HI. In addition, older age, male sex, very low body mass index (≤17·5 kg/m2), lower education level, smoking history, and occupational noise exposure were independently associated with HI. For low-frequency HI, independent risk factors included older age, lower educational level, lower economic status, and very low BMI (≤17·5 kg/m2). For high-frequency HI, independent risk factors included older age, male sex, lower educational level, lower economic status, increased blood pressure, lower high-density lipoprotein cholesterol, and smoking history. CONCLUSIONS: MS itself was not an independent risk factor for HI, and, among the individual metabolic components, only increased fasting plasma glucose was independently associated with HI.


Subject(s)
Glucose/metabolism , Hearing Loss/etiology , Metabolic Syndrome/complications , Adult , Aged , Aged, 80 and over , Fasting , Female , Glucose/analysis , Humans , Male , Middle Aged , Risk Factors , Young Adult
4.
J Biomed Mater Res B Appl Biomater ; 104(4): 698-711, 2016 May.
Article in English | MEDLINE | ID: mdl-26471335

ABSTRACT

The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders.


Subject(s)
Drug Carriers , Gene Transfer Techniques , Polymers , Animals , Drug Carriers/chemistry , Drug Carriers/pharmacology , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/therapy , Humans , Polymers/chemistry , Polymers/pharmacology
5.
Clin Neuroradiol ; 25(4): 415-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25373351

ABSTRACT

Central nervous system (CNS) involvement of scrub typhus infection is well known. Most CNS involvement of scrub typhus infection present as meningitis or encephalitis. We report on a patient suffering from hemorrhagic transformation of intracranial lesions caused by Orientia tsutsugamushi. A 53-year-old female farmer who was infected by scrub typhus was treated with doxycycline and recovered from the systemic illness. However, headache persisted. Brain radiologic studies revealed acute intracranial hemorrhage and enhancing lesion, which implied a CNS involvement. Hemorrhagic transformation of encephalitis by scrub typhus is very rare complication and to our best knowledge, this is the first report of hemorrhagic transformation of scrub typhus encephalitis. Clinician should consider the possibility of hemorrhagic transformation of encephalitis in cases of scrub typhus infection.


Subject(s)
Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/etiology , Infectious Encephalitis/complications , Infectious Encephalitis/diagnosis , Scrub Typhus/complications , Scrub Typhus/diagnosis , Cerebral Hemorrhage/therapy , Diagnosis, Differential , Fatal Outcome , Female , Humans , Infectious Encephalitis/therapy , Magnetic Resonance Imaging/methods , Middle Aged , Rare Diseases/diagnosis , Rare Diseases/etiology , Rare Diseases/therapy , Scrub Typhus/therapy , Tomography, X-Ray Computed/methods
6.
Lupus ; 23(3): 236-44, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24531425

ABSTRACT

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased risk for cardiovascular disease. Previous studies disclosed the association of serum osteoprotegerin (OPG) with the presence of symptomatic atherosclerosis in the general population and several disease conditions. We thus investigated the association between serum OPG levels and subclinical atherosclerosis in premenopausal SLE patients. METHODS: Serum OPG levels and carotid artery intima-media thickness (IMT) were measured in 181 premenopausal SLE patients and age-matched 85 control subjects. Traditional cardiovascular risk factors and SLE-related factors were analyzed. RESULTS: Patients with SLE had significantly increased serum OPG levels (1086 versus 517 pg/ml, p < 0.001) and carotid IMT (0.63 versus 0.45 mm, p < 0.001) compared with control subjects. Carotid IMT significantly increased across the quartiles of OPG. Logistic regression analysis revealed that compared to the lowest OPG quartile, the odds ratio (OR, 95% confidence interval) for increased carotid IMT in quartile 2, 3, and 4 was 1.126 (1.013-1.801), 1.562 (1.268-2.799), and 4.460 (1.126-7.128), respectively, after multiple adjustments (p for trend across quartiles < 0.001). These associations remained significant after further adjustment for inflammatory parameters. Interestingly, serum monocyte chemotactic protein-1 (MCP-1) levels were positively correlated with serum OPG levels (γ = 0.332, p < 0.001). Parallel analysis showed that serum MCP-1 was also an independent predictor of carotid IMT incrassation, but this association was lost when serum OPG was included in the model. CONCLUSION: Serum OPG levels were increased and correlated with serum MCP-1 levels in premenopausal SLE patients. Increased serum OPG was independently associated with subclinical atherosclerosis in these patients.


Subject(s)
Carotid Artery Diseases/blood , Chemokine CCL2/blood , Lupus Erythematosus, Systemic/blood , Osteoprotegerin/blood , Premenopause/blood , Adult , Asymptomatic Diseases , Biomarkers/blood , Carotid Artery Diseases/diagnosis , Carotid Artery Diseases/epidemiology , Carotid Intima-Media Thickness , Case-Control Studies , Chi-Square Distribution , Female , Humans , Logistic Models , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Odds Ratio , Predictive Value of Tests , Republic of Korea/epidemiology , Risk Factors , Up-Regulation
7.
Acta Anaesthesiol Scand ; 58(1): 123-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24112235

ABSTRACT

We report a case of significant reduction in bispectral index (BIS) associated with suspected amniotic fluid embolism (AFE) that occurred prior to change in haemodynamic variables. The patient was a 29-year-old nulliparous, who was admitted for Caesarean section under general anaesthesia in the 33rd week of pregnancy. After the baby was born, the BIS value suddenly decreased to 0, with suppression ratio of 100. One minute later, saturation decreased abruptly to 85%, end-tidal carbon dioxide (EtCO2) decreased to 5 mmHg, peak inspiratory pressure increased to 35 cm H2O, and non-invasive blood pressure (BP) failed to obtain a reading. After administration of vasoactive drugs, the systolic BP was maintained at 100 mmHg or higher, the BIS value rose to 10-20, and the EtCO2 increased to 24-33 mmHg. In this case, the BIS monitoring may provide an earlier warning of impending cardiovascular collapse in the case of AFE.


Subject(s)
Cesarean Section , Consciousness Monitors , Shock/etiology , Adult , Amniotic Fluid , Anesthesia, Obstetrical , Blood Pressure/physiology , Carbon Dioxide/blood , Embolism/complications , Female , Hemodynamics/physiology , Humans , Intubation, Intratracheal , Pregnancy , Twins
9.
Colloids Surf B Biointerfaces ; 94: 192-8, 2012 Jun 01.
Article in English | MEDLINE | ID: mdl-22386794

ABSTRACT

Adsorption behaviors of recombinant E-cadherin-IgG Fc (E-cad-Fc) fusion protein and mutated E-cad-Fcs on the polystyrene (PS) surface were investigated using a 27 MHz quartz-crystal microbalance (QCM) and ELISA. The amount of adsorbed E-cad-Fc on PS surface was increased with an increase of E-cad-Fc concentration as a Langmuir-type in a monolayer. Adsorbed E-cad-Fc on PS surface was stable even after washing if calcium ions are absent in the washing solution due to the calcium ion dependence in the adsorption. E-cadherin homophilic adhesion among E-cadherins during adsorption of E-cad-Fc was involved. Deglycosylation of the E-cad in the E-cad-Fc did not affect adsorption of E-cad-Fc on the PS surface although deglycosylation of the E-cad in the E-cad-Fc enhanced cell adhesion compared with E-cad-Fc.


Subject(s)
Cadherins/chemistry , Immunoglobulin G/chemistry , Recombinant Fusion Proteins/chemistry , Adsorption , Animals , CHO Cells , Cadherins/metabolism , Calcium/chemistry , Cell Adhesion , Cricetinae , Embryonal Carcinoma Stem Cells , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/metabolism , Kinetics , Mice , Mutation , Polystyrenes/chemistry , Quartz Crystal Microbalance Techniques , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Tissue Engineering
10.
Lupus ; 20(9): 989-97, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21700655

ABSTRACT

We investigated the causes of death and analyzed the prognostic factors in Korean systemic lupus erythematosus (SLE) patients. We evaluated 1010 patients with SLE who visited Seoul Saint Mary's Hospital from 1997-2007. Changing patterns in the causes of death were analyzed. Survival rate was calculated by the Kaplan-Meier method and the log-rank test. The risk factors for death were analyzed by multivariate logistic regression analysis. The 5-year survival rate was 97.8%. Over the period of the study, 59 deaths were observed. Among 44 patients who died in our hospital, the most common cause of death was infection (37.3%), with SLE-related death as the next most frequent cause (22.0%). In comparison with earlier data, the proportion of SLE-related deaths has fallen and the proportion of infections has risen. SLE-related death was the most frequent cause of early death, while infection was the most common cause of death in the overall population. In univariate analysis, damage related to SLE, cumulative glucocorticoid dose, mean glucocorticoid dose for 1 month before death, intravenous methylprednisolone therapy and cyclophosphamide treatment were associated with death (p < 0.001 each). The late onset of SLE and renal involvement were predictive factors of poor outcome (p = 0.03 and p < 0.001). In multivariate analysis, the risk factors for death were irreversible damage related to SLE, cyclophosphamide therapy and mean glucocorticoid dose for 1 month before death. The most common cause of death in Korean SLE patients was infection. The judicious use of immunosuppressive agents may be important to decrease infection and to improve survival in SLE patients.


Subject(s)
Asian People , Cause of Death , Lupus Erythematosus, Systemic/mortality , Adolescent , Adult , Female , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Male , Risk Factors , Survival Rate , Young Adult
11.
Lupus ; 20(5): 531-6, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21282295

ABSTRACT

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified ('septic meningitis'), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.


Subject(s)
Lupus Erythematosus, Systemic/complications , Meningitis/etiology , Adolescent , Adult , Cryptococcus neoformans/isolation & purification , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Male , Meningitis/epidemiology , Middle Aged , Republic of Korea/epidemiology , Retrospective Studies , Young Adult
12.
Lupus ; 20(1): 102-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20956464

ABSTRACT

This study was undertaken to investigate clinical characteristics of diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) and to determine risk factors and clinical outcomes of DAH in SLE patients. Among the 1521 patients with SLE admitted between January 1993 and June 2009 to affiliated hospitals of Catholic University of Korea, 21 SLE were admitted for DAH. The inclusion criteria for DAH was defined as new infiltrates on chest radiographs, an acute hemoglobin drop of at least 1.5 g/dl in the absence of an obvious source of bleeding, and one or more of the following signs: hemoptysis, hypoxemia, bronchoscopic or biopsy evidence of DAH. Included as disease controls were 83 SLE patients, matched for age and sex, who were admitted for other manifestations. Data based on medical records were analyzed retrospectively. There were no significantly differing demographic characteristics between SLE patients with DAH and those with other manifestations. Multivariate analysis demonstrated coexisting neuropsychiatric lupus (p = 0.002) and high SLE disease activity index scores (SLEDAI > 10) as independent risk factors in the development of DAH (p = 0.029). Among the 21 SLE patients with DAH, 13 died during the admission period (in-hospital mortality rate: 61.9%). Mortality was associated with infection and requirements of mechanical ventilation. Collectively, SLE patients who have neuropsychiatric manifestations or are in the active stage of the disease have an increased risk for developing DAH. Due to the high mortality of SLE patients with DAH, early recognition of risk factors and appropriate intervention is essential.


Subject(s)
Hemorrhage/etiology , Lung Diseases/etiology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/physiopathology , Pulmonary Alveoli/pathology , Adult , Female , Hemorrhage/mortality , Hemorrhage/pathology , Hospital Mortality , Humans , Korea , Lung Diseases/pathology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/psychology , Male , Pulmonary Alveoli/blood supply , Retrospective Studies , Risk Factors , Treatment Outcome
13.
Clin Exp Immunol ; 161(3): 453-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20529085

ABSTRACT

Defective control of T cell apoptosis is considered to be one of the pathogenetic mechanisms in systemic lupus erythematosus (SLE). Oestrogen has been known to predispose women to SLE and also to exacerbate activity of SLE; however, the role of oestrogen in the apoptosis of SLE T cells has not yet been documented. In this study, we investigated the direct effect of oestrogen on the activation-induced cell death of T cells in SLE patients. The results demonstrated that oestradiol decreased the apoptosis of SLE T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in a dose-dependent manner. In addition, oestradiol down-regulated the expression of Fas ligand (FasL) in activated SLE T cells at the both protein and mRNA levels. In contrast, testosterone increased FasL expression dose-dependently in SLE T cells stimulated with PMA plus ionomycin. The inhibitory effect of oestradiol on FasL expression was mediated through binding to its receptor, as co-treatment of tamoxifen, an oestrogen receptor inhibitor, completely nullified the oestradiol-induced decrease in FasL mRNA expression. Moreover, pre-treatment of FasL-transfected L5178Y cells with either oestradiol or anti-FasL antibody inhibited significantly the apoptosis of Fas-sensitive Hela cells when two types of cells were co-cultured. These data suggest that oestrogen inhibits activation-induced apoptosis of SLE T cells by down-regulating the expression of FasL. Oestrogen inhibition of T cell apoptosis may allow for the persistence of autoreactive T cells, thereby exhibiting the detrimental action of oestrogen on SLE activity.


Subject(s)
Apoptosis/drug effects , Estradiol/pharmacology , Lupus Erythematosus, Systemic/blood , T-Lymphocytes/drug effects , Antibodies/pharmacology , Cells, Cultured , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Estrogens/pharmacology , Fas Ligand Protein/genetics , Fas Ligand Protein/immunology , Fas Ligand Protein/metabolism , Flow Cytometry , Gene Expression/drug effects , Humans , Lupus Erythematosus, Systemic/immunology , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/metabolism
14.
Cancer Gene Ther ; 17(11): 751-60, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20539318

ABSTRACT

Cancer gene therapy using tumor suppressor genes is considered to be an attractive approach for arresting cell growth and inducing apoptosis. Programmed cell death 4 (Pdcd4) is a tumor suppressor gene, which prevents tumorigenesis and tumor progression. To address the issue of whether expression of PDCD4 protein induces apoptosis in cancerous cells, the Pdcd4 gene was delivered using folate-PEG-baculovirus. Folate-PEG-baculovirus containing Pdcd4 gene (F-P-Bac-Pdcd4) was constructed by attachment of F-PEG to the baculovirus surface using chemical modification. The F-P-Bac-Pdcd4 showed enhanced transduction efficiency, efficiently expressed PDCD4 protein, and induced apoptosis in human epidermal carcinoma (KB) cells as compared with an unmodified baculovirus. In a tumor xenograft study, injection of F-P-Bac-Pdcd4 into tumors established from the KB cell line by subcutaneous implantation significantly suppressed tumor growth and induced apoptosis. Thus, this study shows a new baculovirus-mediated tumor suppressor gene delivery system for cancer therapy.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Baculoviridae/genetics , Carcinoma/therapy , Genes, Tumor Suppressor , RNA-Binding Proteins/metabolism , Transduction, Genetic , Animals , Baculoviridae/metabolism , Carcinoma/genetics , Carcinoma/pathology , Cell Line, Tumor , Folic Acid/analogs & derivatives , Folic Acid/metabolism , Gene Expression Regulation, Neoplastic , Genetic Therapy , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Polyethylene Glycols , Xenograft Model Antitumor Assays
15.
Expert Opin Drug Deliv ; 6(8): 827-34, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19558333

ABSTRACT

Gene therapy is a powerful approach in the treatment of a wide range of both inherited and acquired diseases. Nonviral delivery systems have been proposed as safer alternatives to viral vectors because they avoid the inherent immunogenicity and production problems that are seen when viral systems are used. Many cationic polymers, including high-molecular-weight polyethylenimine (PEI) have been widely studied as gene-delivery carriers, both, in vitro and in vivo. However, interest has recently developed in degradable polymeric systems. The advantage of degradable polymer is its low in-vivo cytotoxicity, which is a result of its easy elimination from the cells and body. Degradable polymer also enhances transfection of DNA or small interfering RNA (siRNA) for efficient gene expression or silencing, respectively. This review paper summarizes and discusses the recent advances with degradable PEIs, such as cross-linked and grafted PEIs for DNA and siRNA delivery.


Subject(s)
DNA/administration & dosage , Drug Carriers , Polyethyleneimine , RNA, Small Interfering/administration & dosage , Animals , Cross-Linking Reagents/chemistry , Genetic Therapy/methods , Humans , Polyethyleneimine/chemistry , Transfection
16.
Lupus ; 18(2): 133-8, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19151114

ABSTRACT

Patients with antiphospholipid syndrome (APS) have an increased risk for the development of thrombotic complications. Recent studies indicate that osteoprotegerin (OPG) acts as an important molecule in the development of vascular diseases. The aim of the present study was to examine the association between serum OPG levels and APS manifestations in patients with SLE. Seventy-nine patients with SLE and ninety-two healthy controls, matched for age and sex, were included in this study. Serum levels of OPG, monocyte chemoattractant protein(MCP)-1 and soluble E-selectin were determined by ELISA. At the time of serum sampling, various clinical and laboratory parameters were assessed. We found that serum levels of OPG were significantly higher in patients with SLE than in healthy controls (1236 +/- 82 vs 967 +/- 37 pg/mL, P = 0.003). Particularly, serum OPG levels were significantly higher in SLE patients with APS than those without (1615 +/- 191 vs 1171 +/- 91 pg/mL, P = 0.006). Serum OPG levels correlated with titres of IgG anti-cardiolipin antibody (P = 0.026) and anti-beta(2)-glycoprotein I antibody (P < 0.001). Moreover, serum OPG also correlated with serum levels of sE-selectin (P = 0.002), which is an endothelial cell activation marker, and MCP-1 (P = 0.003), a well known chemokine implicated in thrombogenesis. Collectively, serum OPG levels were increased in SLE patients with APS and correlated with titres of antiphospholipid antibodies, suggesting that OPG might be linked to the development of APS.


Subject(s)
Antibodies, Antiphospholipid/blood , Osteoprotegerin/blood , Adult , Case-Control Studies , Chemokine CCL2/blood , E-Selectin/blood , Female , Humans , Lupus Erythematosus, Systemic/blood , Male
17.
Lupus ; 18(1): 16-21, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19074164

ABSTRACT

The study was undertaken to investigate clinical characteristics of thrombotic thrombocytopenic purpura (TTP) in patients with SLE and to determine risk factors and clinical outcome of TTP in patients with SLE. Among the 1203 patients with SLE admitted to catholic medical centre of the catholic university of Korea from January 1990 to December 2006, 26 patients with SLE were found to admit with TTP. TTP was defined if microangiopathic haemolytic anaemia, thrombocytopenia and negative Coombs' test were present and when at least one of the following signs was noted: renal impairment, neurologic deficit or fever. Eighty-seven patients with SLE who admitted with other manifestations, matched for age and sex, were included as disease controls. Data were retrospectively analysed based on medical records. There were no significant demographic characteristics between SLE patients with TTP and those with other manifestations. Multivariate analysis showed that independent risk factors for the development of TTP included high SLE disease activity index score (SLEDAI > 10, P = 0.006) and coexisting nephritis (P = 0.004). Among the 26 SLE patients with TTP, 12 died during admission period (in-hospital mortality rate: 46.1%). SLE patients with infection or neurologic manifestations had higher mortality rates. Multivariate analysis showed that infection is the only independent risk factor for mortality in SLE patients with TTP (P = 0.035). Patients with SLE who are in the active stage or who have renal involvement have the increased risk for TTP. Development of TTP in patients with SLE can be fatal. Therefore, intensive therapy will be needed especially in the presence of infection.


Subject(s)
Lupus Erythematosus, Systemic/complications , Lupus Nephritis/complications , Purpura, Thrombotic Thrombocytopenic/etiology , Adult , Case-Control Studies , Female , Humans , Korea/epidemiology , Lupus Erythematosus, Systemic/mortality , Male , Multivariate Analysis , Purpura, Thrombotic Thrombocytopenic/physiopathology , Retrospective Studies , Risk Factors , Severity of Illness Index
18.
Clin Exp Immunol ; 153(2): 269-76, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18713142

ABSTRACT

Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.


Subject(s)
Arthritis, Experimental/surgery , Interleukin-10/immunology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/immunology , Animals , Arthritis, Experimental/immunology , Cell Proliferation , Collagen Type II/immunology , Flow Cytometry , Gene Expression , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Immunoglobulin G/analysis , Interleukin-10/analysis , Interleukin-4/analysis , Interleukin-4/immunology , Male , Mice , Mice, Inbred DBA , Retroviridae/genetics , Transduction, Genetic/methods
19.
Clin Exp Immunol ; 152(2): 328-35, 2008 May.
Article in English | MEDLINE | ID: mdl-18355352

ABSTRACT

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been demonstrated to regulate the apoptosis of several cell types. Dysregulated apoptosis of fibroblasts has been implicated in a variety of fibrotic diseases, including systemic sclerosis (SSc). In this study, we investigated the role of MIF in the apoptosis of dermal fibroblasts. The concentrations of MIF were measured in sera and in culture supernatants of peripheral blood mononuclear cells (PBMCs) and dermal fibroblasts by enzyme-linked immunosorbent assay. The degree of apoptosis was determined by colorimetric assay, and signalling pathways were examined by Western blot. The results showed that serum levels of MIF were significantly higher in patients with SSc (n = 47) than in healthy controls (n = 56). Stimulation of PBMCs by anti-CD3 and anti-CD28 increased the production of MIF by fourfold over the constitutive levels. SSc dermal fibroblasts produced higher amounts of MIF than normal dermal fibroblasts. When treated with sodium nitroprusside (SNP), SSc dermal fibroblasts showed a lower degree of apoptosis compared with normal dermal fibroblasts. Exogenous MIF (1-100 ng/ml) inhibited SNP-induced apoptosis of dermal fibroblasts dose-dependently. Both extracellular regulated kinase (ERK) inhibitor (PD98059) and protein kinase B (Akt) inhibitor (LY294002) almost completely blocked the inhibitory effect of MIF on apoptosis. Furthermore, MIF increased the expression of Bcl-2, phospho-ERK and phospho-Akt activity in dermal fibroblasts. Taken together, our data suggest that MIF released by activated T cells and dermal fibroblasts decreases the apoptosis of dermal fibroblasts through activation of ERK, Akt and Bcl-2 signalling pathways, which might be associated with excessive fibrosis in SSc.


Subject(s)
Apoptosis/immunology , Fibroblasts/immunology , Macrophage Migration-Inhibitory Factors/physiology , Scleroderma, Systemic/immunology , Up-Regulation/immunology , Adult , Apoptosis/drug effects , Dose-Response Relationship, Immunologic , Female , Humans , Lymphocyte Activation/immunology , Macrophage Migration-Inhibitory Factors/blood , Male , Middle Aged , Nitroprusside/pharmacology , Proto-Oncogene Proteins c-akt/biosynthesis , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Recombinant Proteins/immunology , Skin/immunology , T-Lymphocyte Subsets/immunology , eIF-2 Kinase/biosynthesis
20.
Cancer Gene Ther ; 15(5): 275-83, 2008 May.
Article in English | MEDLINE | ID: mdl-18292798

ABSTRACT

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC-PTEN were delivered into K-ras(LA1) lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC-PTEN may be compatible with noninvasive in vivo gene therapy.


Subject(s)
Chitosan/pharmacology , Genes, ras , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , PTEN Phosphohydrolase/therapeutic use , Urocanic Acid/pharmacology , Administration, Inhalation , Aerosols , Animals , Disease Models, Animal , Gene Deletion , Genetic Vectors , Male , Mice , PTEN Phosphohydrolase/administration & dosage , PTEN Phosphohydrolase/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...