RESUMO
BACKGROUND: This study aimed to determine the socioeconomic and clinical characteristics affecting health-related quality of life (HRQoL) in patients with psoriasis. METHODS: A cross-sectional study was conducted between March and June 2015 using data obtained via an Internet-based survey completed by a psoriasis patient group in Korea. The survey included items regarding demographic, socioeconomic, and clinical characteristics and HRQoL. Patients' HRQoL impairment was classified as severe if their Dermatology Life Quality Index Scores were ≥ 11. Factors influencing HRQoL impairment were identified using multivariate logistic regression analysis. RESULTS: Of the 299 respondents, 161 (53.8%) exhibited severe HRQoL impairment. The Dermatology Life Quality Index scores were significantly associated with gender, annual income, neck psoriasis, psoriasis-related resignation from work, and use of oral and herbal medications. The severity of HRQoL impairment in women was twice that observed in men (odds ratio [OR] = 2.00, 95% confidence interval (CI): 1.05-3.80). Patients with psoriasis on the neck exhibited significantly greater HRQoL impairment than those with psoriasis on other areas of their bodies (OR = 2.30, 95% CI: 1.20-4.43). With respect to the socioeconomic status, patients who earned > 40 million KRW (approximately 34,000 USD; high-income group) showed less HRQoL impairment compared with those who had lower incomes (OR = 0.47, 95% CI: 0.28-0.80). Patients with severe HRQoL impairment used oral (OR = 2.04, 95% CI: 1.20-3.44) and herbal (OR = 1.86, 95% CI: 1.04-3.34) medications more often relative to patients with less severe HRQoL impairment. CONCLUSIONS: HRQoL in patients with psoriasis was significantly associated with their demographic and socioeconomic characteristics and employment status. The presence of psoriasis on exposed areas of the body was significantly associated with patients' HRQoL and employment status. Further research is required to evaluate the impact of psoriasis on patients' productivity.
Assuntos
Disparidades nos Níveis de Saúde , Psoríase/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Pobreza/estatística & dados numéricos , Psoríase/terapia , República da Coreia , Classe SocialRESUMO
A change in intracellular free calcium (Ca(2+)) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca(2+) signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca(2+)-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H2O2-mediated Ca(2+) overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca(2+) overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca(2+)-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca(2+) overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Peróxido de Hidrogênio/metabolismo , MicroRNAs/farmacologia , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Increased cell mass is one of the characteristics of senescent cells, but this event has not been clearly defined. When subcellular organellar mass was estimated with organelle-specific fluorescence dyes, we observed that most membranous organelles progressively increase in mass during cell senescence. This increase was accompanied by an increase in membrane lipids and augmented expression of lipogenic enzymes, such as fatty acid synthase (FAS), ATP citrate lyase, and acetyl-CoA carboxylase. The mature form of sterol regulatory element-binding protein (SREBP)-1 was also elevated. Increased expression of these lipogenic effectors was further observed in the liver tissues of aging Fischer 344 rats. Ectopic expression of mature form of SREBP-1 in both Chang cells and primary young human diploid fibroblasts was enough to induce senescence. Blocking lipogenesis with FAS inhibitors (cerulenin and C75) and via siRNA-mediated silencing of SREBP-1 and ATP citrate lyase significantly attenuated H(2)O(2)-induced senescence. Finally, old human diploid fibroblasts were effectively reversed to young-like cells by challenging with FAS inhibitors. Our results suggest that enhanced lipogenesis is not only a common event, but also critically involved in senescence via SREBP-1 induction, thereby contributing to the increase in organelle mass (as a part of cell mass), a novel indicator of senescence.
Assuntos
Senescência Celular/fisiologia , Lipogênese/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Animais , Western Blotting , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Cromatografia em Camada Fina , Desferroxamina/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Lipídeos de Membrana/metabolismo , Organelas/efeitos dos fármacos , Organelas/metabolismo , RNA Interferente Pequeno , Ratos , Ratos Endogâmicos F344 , Espécies Reativas de Oxigênio/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Glycogen biogenesis and its response to physiological stimuli have often been implicated in age-related diseases. However, their direct relationships to cell senescence and aging have not been clearly elucidated. Here, we report the central involvement of enhanced glycogenesis in cellular senescence. Glycogen accumulation, glycogen synthase (GS) activation, and glycogen synthase kinase 3 (GSK3) inactivation commonly occurred in diverse cellular senescence models, including the liver tissues of aging F344 rats. Subcytotoxic concentrations of GSK3 inhibitors (SB415286 and LiCl) were sufficient to induce cellular senescence with increased glycogenesis. Interestingly, the SB415286-induced glycogenesis was irreversible, as were increased levels of reactive oxygen species and gain of senescence phenotypes. Blocking GSK3 activity using siRNA or dominant negative mutant (GSK3beta-K85A) also effectively induced senescence phenotypes, and GS knock-down significantly attenuated the stress-induced senescence phenotypes. Taken together, these results clearly demonstrate that augmented glycogenesis is not only common, but is also directly linked to cellular senescence and aging, suggesting GSK3 and GS as novel modulators of senescence, and providing new insight into the metabolic backgrounds of aging and aging-related pathogenesis.
Assuntos
Senescência Celular/fisiologia , Quinase 3 da Glicogênio Sintase/fisiologia , Glicogênio Sintase/fisiologia , Glicogênio/biossíntese , Fatores Etários , Aminofenóis/farmacologia , Animais , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glicogênio/metabolismo , Glicogênio Sintase/deficiência , Glicogênio Sintase/genética , Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Maleimidas/farmacologia , Ratos , Ratos Endogâmicos F344RESUMO
BACKGROUND: In Korea, the drug use process has changed significantly since the new pharmacy law was implemented in 2000, separating the prescribing and dispensing functions between physicians and pharmacists and mandating prospective drug use review (DUR) practice by pharmacists immediately before dispensing medications. However, a high prevalence of inappropriate prescribing has been suspected by the public, pharmacists, and health insurance managers, possibly due to suboptimal DUR practice by pharmacists. OBJECTIVE: To assess overall patterns of drug usage and potential problems of inappropriate use in outpatient settings by analyzing prescription data that were electronically submitted to the national health insurance manager with a computerized DUR system and develop a computerized adjudication system model for drug claims. METHODS: The national prescription drug claims data that were submitted electronically by pharmacies located in the northern part of Korea during 15 days in 2002 were retrospectively screened against the predetermined DUR standards of the selected criteria on drug dosage, duration of therapy, and drug interaction using the DUR screening system. The results of all the DUR conflicts were further validated manually by an expert panel and statistically analyzed to determine drug use patterns. RESULTS: Of 31,994,260 drugs prescribed, 3,325,760 (10.4%) items showed a conflict with at least one of the DUR standards. The average number of drugs prescribed on each prescription was 4.07, and even more troubling was the high incidence of under-dosing, over-dosing, and contraindicated drug prescribing. CONCLUSIONS: It is evident that inappropriate drug prescribing is very common in Korea; thus, a great deal of attention is urgently needed in the country with respect to proper prescribing and supportive interventions.