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1.
J Appl Gerontol ; 42(11): 2233-2241, 2023 11.
Article in English | MEDLINE | ID: mdl-37522401

ABSTRACT

A high level of resilience is positively related to successful aging. However, interventions to increase resilience in older adults are not yet available. This study aimed to examine the mediating role of community participation in the relationship between resilience and successful aging. Data from 284 individuals aged 60 years and above were analyzed in this cross-sectional study. The pathways among resilience, community participation, and successful aging were statistically significant after controlling for sociodemographic characteristics, depression, disability, and chronic disease. The analysis revealed a partial mediating effect of community participation (unstandardized estimate = .01, p < .01), explaining 16.4% of the total effect of resilience on successful aging. Promoting community participation may be beneficial for enhancing successful aging in community-dwelling older adults. Further studies to examine the causal relationship between community participation and successful aging and to develop community services are recommended to use community resources as means to support successful aging.


Subject(s)
Aging , Disabled Persons , Humans , Aged , Cross-Sectional Studies , Independent Living , Republic of Korea , Social Participation
2.
OTJR (Thorofare N J) ; 43(4): 691-701, 2023 10.
Article in English | MEDLINE | ID: mdl-37403816

ABSTRACT

There is no comprehensive predischarge occupational therapy assessment tool in South Korea. The objective of this study was to determine Stroke-Predischarge Occupational Therapy Assessment (S-POTA) validity and reliability. Twenty-seven occupational therapists (OTs) assessed 97 patients with stroke. Concurrent validity was evaluated by comparing S-POTA scores with stroke-specific quality of life (SS-QOL). Discriminant validity was evaluated by comparing S-POTA scores between outpatient and readmitted groups, and a receiver operating characteristic analysis was conducted. The test-retest was conducted twice in 20 patients, and the inter-rater test was conducted with two OTs per patient. S-POTA positively correlated with SS-QOL. S-POTA rating differs significantly across outpatients and readmitted groups. All S-POTA areas under curve values ranged from .70 to .85, and cut-off points were derived. Cronbach's α for internal consistency was .953, the intraclass correlation coefficient for test-retest was .990, and .987 for inter-rater reliability. The results suggest S-POTA is a reliable tool for efficient implementation of discharge planning.


Subject(s)
Occupational Therapy , Stroke Rehabilitation , Stroke , Humans , Quality of Life , Reproducibility of Results , Stroke Rehabilitation/methods , Surveys and Questionnaires , Psychometrics
3.
Occup Ther Int ; 2020: 1250801, 2020.
Article in English | MEDLINE | ID: mdl-32728351

ABSTRACT

BACKGROUND: School-aged children with attention deficit hyperactivity disorder (ADHD) face many difficulties with self-directed learning because of their poor executive function. This leads to secondary problems such as learning disabilities and depression, so the role of intervention to improve executive function in school-aged children with ADHD is important. OBJECTIVE: The present study is aimed to investigate how cognitive-functional (Cog-Fun) intervention affected executive function of school-aged children with ADHD and the sustainability of these effects. To investigate the effects of changes in the executive function of school-aged children with ADHD through Cog-Fun intervention in self-directed learning. METHOD: A single-subject A-B-A research design was employed in this study. Three children aged 9-10 years who were diagnosed with ADHD were selected. A total of 17 experimental sessions were conducted. The Cog-Fun intervention program was implemented during the intervention phase. To measure dependent variables, Behavior Rating Inventory of Executive Function (BRIEF) and Homework Problems Checklist (HPC) were used. Significant changes in executive function assessed by the Children's Color Trails Test (CCTT) and Stroop test were analyzed through two-standard deviation band analysis. Additionally, video clips of task performance were analyzed to examine qualitative performance changes in self-directed learning. RESULT: All three participants presented statistically significant changes with a number of near-misses of CCTT and color words score of Stroop test during the intervention. T-scores of the Global Executive Composite (GEC) decreased after the intervention, indicating improvement in executive function. The follow-up period revealed retention of the improved executive function. Additionally, self-directed learning improved in all participants after the implementation Cog-Fun intervention. CONCLUSION: The study supports the effectiveness of Cog-Fun intervention in improving executive function in school-aged children with ADHD and confirmed that the improvement of executive function ultimately leads to the improvement of self-directed learning performance.


Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit Disorder with Hyperactivity/therapy , Cognition , Cognitive Behavioral Therapy/methods , Executive Function , Self-Directed Learning as Topic , Child , Humans , Learning Disabilities/psychology , Male , Schools
4.
Occup Ther Int ; 2020: 9395629, 2020.
Article in English | MEDLINE | ID: mdl-33500686

ABSTRACT

OBJECTIVES: This study is aimed at developing multidimensional leisure participation assessment tool for the elderly to achieve quantitative and qualitative assessment of leisure participation and leisure exploration. METHODS: This study collected preliminary items through literature review, statistical office data, and survey of the elderly's leisure activities and considered the list of leisure activities as assessment items by conducting a Delphi survey. Reliability was verified through internal consistency and test-retest reliability. The assessment tool was finally confirmed using content validity and discriminant validity. RESULTS: A total of 81 leisure items classified into 8 categories and 22 subcategories were obtained through data collection and Delphi survey. Cronbach's α value was 0.939, and Intraclass Correlation Coefficient was 0.941. A content validity test was confirmed by validating that I-CVI was 0.78 or more and the S-CVI was 0.95. According to the result of discriminant validity, there was a difference in the number of participating leisure activities and leisure activities with participation intention by age. CONCLUSION: The leisure participation assessment tool for the elderly developed in this study can obtain information on the overall view of the leisure of the elderly by measuring leisure exploration, leisure participation, and interference factor affecting leisure participation.


Subject(s)
Leisure Activities , Occupational Therapy , Surveys and Questionnaires , Aged , Aged, 80 and over , Humans , Reproducibility of Results
5.
Int Psychogeriatr ; 30(10): 1455-1463, 2018 10.
Article in English | MEDLINE | ID: mdl-29923471

ABSTRACT

ABSTRACTBackground:The mobile screening test system for screening mild cognitive impairment (mSTS-MCI) was developed for clinical use. However, the clinical usefulness of mSTS-MCI to detect elderly with MCI from those who are cognitively healthy has yet to be validated. Moreover, the comparability between this system and traditional screening tests for MCI has not been evaluated. OBJECTIVE: The purpose of this study was to examine the validity and reliability of the mSTS-MCI and confirm the cut-off scores to detect MCI. METHOD: The data were collected from 107 healthy elderly people and 74 elderly people with MCI. Concurrent validity was examined using the Korean version of Montreal Cognitive Assessment (MoCA-K) as a gold standard test, and test-retest reliability was investigated using 30 of the study participants at four-week intervals. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were confirmed through Receiver Operating Characteristic (ROC) analysis, and the cut-off scores for elderly people with MCI were identified. RESULTS: Concurrent validity showed statistically significant correlations between the mSTS-MCI and MoCA-K and test-rests reliability indicated high correlation. As a result of screening predictability, the mSTS-MCI had a higher NPV than the MoCA-K. CONCLUSIONS: The mSTS-MCI was identified as a system with a high degree of validity and reliability. In addition, the mSTS-MCI showed high screening predictability, indicating it can be used in the clinical field as a screening test system for mild cognitive impairment.


Subject(s)
Cognitive Dysfunction/diagnosis , Mass Screening/methods , Neuropsychological Tests/standards , Aged , Aged, 80 and over , Female , Humans , Male , ROC Curve , Reproducibility of Results , Sensitivity and Specificity
7.
PLoS One ; 8(7): e68845, 2013.
Article in English | MEDLINE | ID: mdl-23894352

ABSTRACT

Bile acids concentration in liver is tightly regulated to prevent cell damage. Previous studies have demonstrated that deregulation of bile acid homeostasis can lead to cholestatic liver disease. Recently, we have shown that ER-bound transcription factor Crebh is a downstream effector of hepatic Cb1r signaling pathway. In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process. We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo alongwith significant increase in Crebh gene expression and activation. Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis. Overexpression of Crebh increased the expression of key bile acid synthesis enzyme genes via direct binding of Crebh to their promoters, whereas Cb1r knockout and Crebh-knockdown mice were protected against alcohol-induced perturbation of bile acid homeostasis. Interestingly, insulin treatment protected against Cb1r-mediated Crebh-induced disruption of bile acid homeostasis. Furthermore, Crebh expression and activation was found to be markedly increased in insulin resistance conditions and Crebh knockdown in diabetic mice model (db/db) significantly reversed alcohol-induced disruption of bile acid homeostasis. Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.


Subject(s)
Bile Acids and Salts/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Ethanol/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Liver/enzymology , Receptor, Cannabinoid, CB1/metabolism , Animals , Bile Acids and Salts/biosynthesis , Cyclic AMP Response Element-Binding Protein/deficiency , Endocannabinoids/pharmacology , Gene Deletion , Hep G2 Cells , Homeostasis/drug effects , Humans , Insulin/deficiency , Insulin/pharmacology , Insulin Resistance , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Organ Specificity , Receptor, Cannabinoid, CB1/deficiency , Receptor, Cannabinoid, CB1/genetics , Transcriptional Activation/drug effects
8.
J Med Microbiol ; 62(Pt 5): 797-800, 2013 May.
Article in English | MEDLINE | ID: mdl-23449873

ABSTRACT

A case of subcutaneous phaeohyphomycosis caused by Exophiala equina is reported in a 75-year-old female, who showed subcutaneous abscesses on both forearms for 8 months. A lesion was initiated by inoculation with a spine from a tree. Histopathologically, suppurative granulomatous inflammation was present and short hyphal elements were observed. Upon culture greyish-black, velvety colonies of a black yeast were obtained after 3 weeks. The strain grew well at 25 °C, but poorly at 37 °C. After sequencing the internal transcribed spacer domain and the partial ß-tubulin gene, the fungus was identified as E. equina. The patient was successfully treated with fluconazole for 3 months.


Subject(s)
Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Exophiala/drug effects , Exophiala/isolation & purification , Phaeohyphomycosis/microbiology , Aged , DNA, Fungal/genetics , DNA, Ribosomal Spacer/genetics , Drug Resistance, Multiple, Fungal , Female , Humans , Hyphae , Microbial Sensitivity Tests , Phaeohyphomycosis/drug therapy , Treatment Outcome
9.
Lipids ; 48(3): 287-96, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23392774

ABSTRACT

Diacylglycerol (DAG) is an intermediate lipid involved in the synthesis of phospholipids and triglycerides. As signaling regulators, DAG activate novel protein kinase C leading to decreased response to insulin in skeletal muscle. Alteration of DAG contents correlates with development of metabolic dysregulation in obese and diabetic conditions. Recent advances in lipidomics using mass spectrometry allow expanded measurements of various lipid species. This study describes a rapid measurement of DAG species using the triple quadrupole mass spectrometry using atmospheric pressure chemical ionization in a positive ion mode. DAG in the cells and muscle tissues were separated depending on differences in chain lengths and degree of unsaturation. The limit of detection and quantification for DAG was 0.2 to 17 pmol for this method. When C2C12 cells were treated with palmitate or oleate, we found a 12-fold and 2-fold DAG increase respectively compared to the no-treatment control. In the muscles of obese db/db mice, DAG levels were elevated by 6-fold compared to those of wild-type skeletal muscles. The present analytical method provides a rapid and sensitive quantification of DAG molecular species from various biological samples and can be used to correlate the degree of metabolic dysregulation with lipotoxic metabolites.


Subject(s)
Diglycerides/analysis , Muscle, Skeletal/chemistry , Tandem Mass Spectrometry/methods , Animals , Cell Line , Chromatography, High Pressure Liquid/methods , Diglycerides/metabolism , Limit of Detection , Mice , Mice, Inbred C57BL , Mice, Obese , Muscle, Skeletal/metabolism , Obesity/metabolism
10.
Gut ; 62(7): 1044-54, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23023167

ABSTRACT

BACKGROUND: The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor γ (ERRγ) is a constitutively active transcriptional activator regulating gene expression. OBJECTIVE: To investigate the role of ERRγ in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRγ inverse agonist. DESIGN: For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1(-/-) mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice. RESULTS: Hepatic ERRγ gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRγ gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRγ inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRγ and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice. CONCLUSIONS: ERRγ, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure.


Subject(s)
Cytochrome P-450 CYP2E1/metabolism , Liver Diseases, Alcoholic/metabolism , Receptor, Cannabinoid, CB1/physiology , Receptors, Estrogen/physiology , Animals , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1 Inhibitors , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Ethanol/pharmacology , Gene Expression Profiling/methods , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/physiology , Liver/metabolism , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/prevention & control , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidation-Reduction , Oxidative Stress/physiology , Receptors, Estrogen/deficiency , Receptors, Estrogen/genetics , Signal Transduction/drug effects , Signal Transduction/physiology , Tamoxifen/analogs & derivatives , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Transcription, Genetic/physiology
11.
J Biol Chem ; 287(22): 18429-39, 2012 May 25.
Article in English | MEDLINE | ID: mdl-22493506

ABSTRACT

The role of serine palmitoyltransferase (SPT) and de novo ceramide biosynthesis in cardiac ceramide and sphingomyelin metabolism is unclear. To determine whether the de novo synthetic pathways, rather than ceramide uptake from circulating lipoproteins, is important for heart ceramide levels, we created cardiomyocyte-specific deficiency of Sptlc2, a subunit of SPT. Heart-specific Sptlc2-deficient (hSptlc2 KO) mice had a >35% reduction in ceramide, which was limited to C18:0 and very long chain ceramides. Sphingomyelinase expression, and levels of sphingomyelin and diacylglycerol were unchanged. But surprisingly phospholipids and acyl CoAs contained increased saturated long chain fatty acids. hSptlc2 KO mice had decreased fractional shortening and thinning of the cardiac wall. While the genes regulating glucose and fatty acid metabolism were not changed, expression of cardiac failure markers and the genes involved in the formation of extracellular matrices were up-regulated in hSptlc2 KO hearts. In addition, ER-stress markers were up-regulated leading to increased apoptosis. These results suggest that Sptlc2-mediated de novo ceramide synthesis is an essential source of C18:0 and very long chain, but not of shorter chain, ceramides in the heart. Changes in heart lipids other than ceramide levels lead to cardiac toxicity.


Subject(s)
Ceramides/metabolism , Heart/physiopathology , Myocardium/enzymology , Serine C-Palmitoyltransferase/metabolism , Animals , Blood Glucose/metabolism , Blotting, Western , Cells, Cultured , In Situ Nick-End Labeling , Lipids/blood , Mice , Mice, Inbred C57BL , Mice, Knockout , Serine C-Palmitoyltransferase/genetics
12.
J Biol Chem ; 286(44): 38035-38042, 2011 Nov 04.
Article in English | MEDLINE | ID: mdl-21911493

ABSTRACT

LIPINs have been reported to perform important roles in the regulation of intracellular lipid levels. Their mutations induce lipodystrophy, myoglobinuria, and inflammatory disorders. Recently, the phosphatidic acid phosphatase function of LIPINs has been associated with the perturbation of hepatic insulin receptor signaling via the diacylglycerol-mediated stimulation of PKCε activity. Here, we report that nuclear estrogen-related receptor (ERR) γ is a novel transcriptional regulator of LIPIN1. Overexpression of ERRγ significantly increased LIPIN1 expression in primary hepatocytes, whereas the abolition of ERRγ gene expression attenuated the expression of LIPIN1. Deletion and mutation analyses of the LIPIN1 promoter showed that ERRγ exerts its effect on the transcriptional regulation of LIPIN1 via ERRE1 of the LIPIN1 promoter, as confirmed by ChIP assay. We also determined that the gene transcription of LIPIN1 by ERRγ is controlled by the competition between PGC-1α and small heterodimer partner. Additionally, ERRγ leads to the induction of hepatic LIPIN1 expression and diacylglycerol production in vivo. Finally, an inverse agonist of ERRγ, GSK5182, restores the impaired insulin signaling induced by LIPIN1-mediated PKCε activation. Our findings indicate that the selective control of ERRγ transcriptional activity by its specific inverse agonist could provide a novel therapeutic approach to the amelioration of impaired hepatic insulin signaling induced by LIPIN1-mediated PKCε activation.


Subject(s)
Gene Expression Regulation, Enzymologic , Insulin/metabolism , Liver/metabolism , Nuclear Proteins/biosynthesis , Phosphatidate Phosphatase/genetics , Receptors, Estrogen/metabolism , Transcription, Genetic , Animals , Cell Line , Cell Nucleus/metabolism , Hepatocytes/cytology , Humans , Male , Mice , Mice, Inbred C57BL , Phosphatidate Phosphatase/biosynthesis , Protein Kinase C/metabolism , Rats , Signal Transduction , Transfection
13.
Biomacromolecules ; 12(7): 2822-33, 2011 Jul 11.
Article in English | MEDLINE | ID: mdl-21595437

ABSTRACT

Two new DNA-mimicking brush polymers were synthesized: poly[oxy(11-(3-(9-adeninyl)propionato)-undecanyl-1-thiomethyl)ethylene] (PECH-AP) and poly[oxy(11-(5-(9-adenylethyloxy)-4-oxopentanoato)undecanyl-1-thiomethyl)ethylene] (PECH-AS). These polymers were found to be thermally stable up to 220 °C and could be applied easily by conventional coating processes to produce good quality films. Interestingly, both brush polymers formed molecular multibilayer structures to provide an adenine-rich surface. Despite the structural similarities, PECH-AS surprisingly exhibited higher hydrophilicity and better water sorption properties than PECH-AP. These differences were attributed to the chemical structures in the bristles of the polymers. The adenine-rich surfaces of the polymer films demonstrated selective protein adsorption, suppressed bacterial adherence, facilitated HEp-2 cell adhesion, and exhibited good biocompatibility in mice. However, the high hydrophilicity and good water sorption characteristics of the PECH-AS film suggest that this brush polymer is better suited to applications requiring good biocompatibility and reduced chance of bacterial infection compared with the PECH-AP film.


Subject(s)
Adenine/chemistry , Biocompatible Materials/chemistry , DNA/chemistry , Polymers/chemistry , Adsorption , Animals , Bacteria/chemistry , Bacterial Adhesion , Biocompatible Materials/chemical synthesis , Cell Adhesion , Cell Line, Tumor , Humans , Materials Testing , Mice , Mice, Inbred ICR , Molecular Structure , Particle Size , Polymers/chemical synthesis , Proteins/chemistry , Stereoisomerism , Surface Properties
14.
J Lipid Res ; 52(6): 1234-1246, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21447485

ABSTRACT

The mechanism of FFA-induced insulin resistance is not fully understood. We have searched for effector molecules(s) in FFA-induced insulin resistance. Palmitic acid (PA) but not oleic acid (OA) induced insulin resistance in L6 myotubes through C-Jun N-terminal kinase (JNK) and insulin receptor substrate 1 (IRS-1) Ser307 phosphorylation. Inhibitors of ceramide synthesis did not block insulin resistance by PA. However, inhibition of the conversion of PA to lysophosphatidylcholine (LPC) by calcium-independent phospholipase A2 (iPLA2) inhibitors, such as bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACOCF3), prevented insulin resistance by PA. iPLA2 inhibitors or iPLA2 small interfering RNA (siRNA) attenuated JNK or IRS-1 Ser307 phosphorylation by PA. PA treatment increased LPC content, which was reversed by iPLA2 inhibitors or iPLA2 siRNA. The intracellular DAG level was increased by iPLA2 inhibitors, despite ameliorated insulin resistance. Pertussis toxin (PTX), which inhibits LPC action through the G-protein coupled receptor (GPCR)/Gα(i), reversed insulin resistance by PA. BEL administration ameliorated insulin resistance and diabetes in db/db mice. JNK and IRS-1Ser307 phosphorylation in the liver and muscle of db/db mice was attenuated by BEL. LPC content was increased in the liver and muscle of db/db mice, which was suppressed by BEL. These findings implicate LPC as an important lipid intermediate that links saturated fatty acids to insulin resistance.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Insulin Receptor Substrate Proteins/metabolism , Insulin Resistance , JNK Mitogen-Activated Protein Kinases/metabolism , Liver/metabolism , Lysophosphatidylcholines , Palmitic Acid , Phospholipases A2, Calcium-Independent/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Blood Proteins/pharmacology , Cells, Cultured , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Disease Models, Animal , Gene Silencing , Glucose/metabolism , Insulin/metabolism , Insulin Receptor Substrate Proteins/antagonists & inhibitors , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Liver/pathology , Lysophosphatidylcholines/analysis , Lysophosphatidylcholines/metabolism , Mice , Mice, Knockout , Muscle Fibers, Skeletal , Naphthalenes/pharmacology , Palmitic Acid/metabolism , Palmitic Acid/pharmacology , Pertussis Toxin/pharmacology , Phospholipases A2, Calcium-Independent/antagonists & inhibitors , Phosphorylation/drug effects , Pyrones/pharmacology , RNA, Small Interfering/metabolism , RNA, Small Interfering/pharmacology , Receptors, G-Protein-Coupled/antagonists & inhibitors , Signal Transduction/drug effects
15.
Prostaglandins Other Lipid Mediat ; 94(1-2): 44-52, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21167294

ABSTRACT

Sphingolipids are membrane components and are involved in cell proliferation, apoptosis and metabolic regulation. In this study we investigated whether de novo sphingolipid biosynthesis in macrophages is regulated by inflammatory stimuli. Lipopolysaccharide (LPS) treatment upregulated Sptlc2, a subunit of serine palmitoyltransferase (SPT), mRNA and protein in Raw264.7 and mouse peritoneal macrophages, but Sptlc1, another subunit of SPT, was not altered. SPT activation by LPS elevated cellular levels of ceramides and sphingomyelin (SM). Pharmacological inhibition of nuclear factor kappa B (NFκB) prevented LPS-induced upregulation of Sptlc2 while transfection of p65 subunit of NFκB upregulated Sptlc2 and increased cellular ceramide levels. In contrast, MAP kinases were not involved in regulation of sphingolipid biosynthesis. Analysis of Sptlc2 promoter and chromatin immunoprecipitation (ChIP) assay showed that NFκB binding sites are located in Sptlc2 promoter region. Our results demonstrate that inflammatory stimuli activate de novo sphingolipid biosynthesis via NFκB and may play a critical role in lipid metabolism in macrophages.


Subject(s)
Lipopolysaccharides/pharmacology , NF-kappa B/metabolism , Serine C-Palmitoyltransferase/genetics , Sphingolipids/biosynthesis , Up-Regulation , Animals , Macrophages/metabolism , Mice , Promoter Regions, Genetic , RNA, Messenger/metabolism , Serine C-Palmitoyltransferase/metabolism , Sphingomyelins/genetics , Sphingomyelins/metabolism , Transfection
16.
Epidemiol Health ; 32: e2010002, 2010 Apr 26.
Article in English | MEDLINE | ID: mdl-21191455

ABSTRACT

The authors report a fatal case of disseminated tuberculosis in a 14-yr-old girl, which developed immediately after a measles-rubella (MR) vaccination. Despite a markedly accelerated clinical course which led to death within two weeks, the authors could not identify any possible cause of the tuberculosis aggravation in this case, with the exception of the MR vaccination. The possible role that MR vaccination had on the clinical course of tuberculosis in this case is discussed.

17.
Biomaterials ; 31(14): 3816-26, 2010 May.
Article in English | MEDLINE | ID: mdl-20167363

ABSTRACT

We have synthesized brush polymers with various glycine derivatives as the end groups of their long alkyl bristles. The polymers are thermally stable up to 170-210 degrees C and form good quality films through conventional spin- or dip-coating and subsequent drying. Interestingly, the thin films of these brush polymers exhibit different molecular multi-layer structures that arise through the efficient self-assembly of the bristles with glycine derivative end groups. These brush polymer films have hydrophilic surfaces and exhibit some water sorption. The extent of the water sorption by these films depends upon the nature of the glycine derivatives in the bristle end. These films not only repel fibrinogen molecules and platelets from their surfaces, but also have high resistance to bacterial adherence. Moreover, the films were found to provide conducive surface environments for the successful anchoring and growth of HEp-2 cells, and to exhibit excellent biocompatibility in mice. These brush polymers have potential uses in biomedical applications including medical devices, especially blood contacting devices such as catheters, stents, blood vessels, and biosensors, due to their enhanced biocompatibility and the reduced possibility of post-operative infection.


Subject(s)
Glycine/analogs & derivatives , Materials Testing , Polymers/chemistry , Absorption , Adsorption , Animals , Bacteria/cytology , Bacterial Adhesion , Calorimetry, Differential Scanning , Cell Adhesion , Cell Line , Cell Survival , Humans , Implants, Experimental , Mice , Platelet Adhesiveness , Polymers/chemical synthesis , Solutions , Thermogravimetry , Water/chemistry
18.
Biomaterials ; 31(9): 2517-25, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20045180

ABSTRACT

New mesoporous silicate-titania resin systems hybridized with 4,5-dihydroxy-m-benzenedisulfonic acid and poly(ethylene glycol)-dimethacrylate component were developed. These inorganic-organic hybrid resins were found to reveal highly controlled ionic and hydrophilic surface with excellent durability and adhesion onto various substrates. The resin films revealed high resistance to nonspecific adsorption of fibrinogen and to adherence by several bacterial pathogens such as Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. Furthermore, excellent biocompatibility of the developed resins was proved by both HEp-2 cell adhesion in vitro and subcutaneous implantation in mice. The inorganic-organic hybrid resins are strongly promising for biomedical applications including biomedical devices and biosensors.


Subject(s)
Benzenesulfonates/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Materials Testing/methods , Methacrylates/pharmacology , Polyethylene Glycols/pharmacology , Resins, Synthetic/pharmacology , Animals , Bacteria/cytology , Bacteria/drug effects , Bacterial Adhesion/drug effects , Cell Adhesion/drug effects , Cell Line , Humans , Ions , Mice , Microscopy, Electron, Transmission , Porosity/drug effects , Scattering, Small Angle , X-Ray Diffraction
19.
Arterioscler Thromb Vasc Biol ; 30(2): 290-7, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19965780

ABSTRACT

OBJECTIVE: Fatty acids increase reactive oxygen species generation and cell apoptosis in endothelial cells. The peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) is a transcriptional coactivator that increases mitochondrial biogenesis and fatty acid oxidation in various cells. This study was undertaken to investigate the possible preventive effect of PGC-1alpha on endothelial apoptosis and its molecular mechanism. METHODS AND RESULTS: Treatment with linoleic acid in cultured human aortic endothelial cells increased reactive oxygen species generation and cell apoptosis. These effects appeared to be mediated by increases in cytosolic fat metabolites, ie, fatty acyl CoA, diacylglycerol, and ceramide, and consequent decreases in ATP/ADP translocase activity of adenine nucleotide translocator. Adenoviral overexpression of PGC-1alpha prevented linoleic acid-induced increases in reactive oxygen species generation and cell apoptosis in human aortic endothelial cells by increasing fatty acid oxidation, decreasing diacylglycerol and ceramide, and increasing ATP/ADP translocase activity. In isolated aorta, PGC-1alpha overexpression prevented linoleic acid-induced decrease in endothelium-dependent vasorelaxation, and this effect was abolished by adenine nucleotide translocator1 shRNA. CONCLUSIONS: PGC-1alpha regulates reactive oxygen species generation and apoptosis in endothelial cells by increasing fatty acid oxidation and enhancing ATP/ADP translocase activity. Measures to increase PGC-1alpha expression or ATP/ADP translocase activity in vascular cells may aid in the prevention or treatment of atherosclerosis.


Subject(s)
Apoptosis , Endothelial Cells/enzymology , Heat-Shock Proteins/metabolism , Mitochondria/enzymology , Transcription Factors/metabolism , Acyl Coenzyme A/metabolism , Adenine Nucleotide Translocator 1/genetics , Adenine Nucleotide Translocator 1/metabolism , Animals , Cells, Cultured , Ceramides/metabolism , Diglycerides/metabolism , Endothelial Cells/pathology , Fatty Acids/metabolism , Heat-Shock Proteins/genetics , Humans , Linoleic Acid/metabolism , Male , Membrane Potential, Mitochondrial , Mitochondria/pathology , Oxidation-Reduction , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , RNA Interference , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Time Factors , Transcription Factors/genetics , Transfection , Up-Regulation , Vasodilation
20.
Ann Dermatol ; 20(2): 77-81, 2008 Jun.
Article in English | MEDLINE | ID: mdl-27303165

ABSTRACT

NK/T-cell lymphoma (NKTCL) is characterized by the expression of the NK-cell antigen CD56. Non-nasal NK/T-cell lymphomas are subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas; nasal type, aggressive, blastic (blastoid), and other specific NK-like cell lymphoma. Aggressive NK/T-cell lymphoma/leukemia is a rare leukemic variant of nasal type NKTCL. We herein report a rare case of aggressive NK/T-cell lymphoma/leukemia with cutaneous involvement in adolescence.

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