RESUMEN
Chronic obstructive pulmonary disease (COPD) and age-related macular degeneration (AMD) are both common diseases of the elderly people. COPD induced systemic inflammation and hypoxia may have an impact on the development of AMD. This study investigated the possible association between COPD and subsequent risk of AMD. A retrospective cohort study was conducted based on the data from the National Health Insurance Research Database in Taiwan. The COPD cohort comprised 24,625 adult patients newly diagnosed during 2000-2012, whereas age-, gender-, and the year of diagnosis-matched non-COPD cohort comprised 49,250 individuals. Incident AMD was monitored to the end of 2013. A Cox proportional hazards model was applied to evaluate the risk of AMD. The COPD cohort showed 1.25 times higher AMD incidence than the non-COPD cohort (4.80 versus 3.83 per 1000 person-years, adjusted hazard ratio (HR) = 1.20 [95% confident interval (CI) = 1.10-1.32]). Stratified analyses for age, gender, and presence of comorbidity resulted in significant adjusted HRs in most subgroups. Further analysis revealed that the COPD group had an increased risk of both the exudative and non-exudative types of AMD (adjusted HRs = 1.49 [95% CI = 1.13-1.96] and 1.15 [95% CI = 1.05-1.26], respectively). COPD patients have an increased risk for AMD development. Clinicians should provide adequate care for the ocular health to these patients.
Asunto(s)
Degeneración Macular/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Adulto , Anciano , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , TaiwánRESUMEN
PURPOSE: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD). METHODS: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort. RESULTS: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years). CONCLUSION: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.
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Degeneración Macular/epidemiología , Periodontitis/complicaciones , Anciano , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Degeneración Macular/diagnóstico , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
Expression of cell adhesion molecules by the endothelium and the attachment of leukocytes to these cells play major roles in inflammation and cardiovascular disorders. Magnolol, a major active component of Magnolia officinalis, has antioxidative and anti-inflammatory properties. In the present study, the effects of magnolol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells (HAECs) and the related mechanisms were investigated. TNF-α induced VCAM-1 protein expression and mRNA stability were significantly decreased in HAECs pre-treated with magnolol. Magnolol significantly reduced the phosphorylation of ERK, JNK, and p38 in TNF-α-treated HAECs. The decrease in VCAM-1 expression in response to TNF-α treatment was affected by JNK and p38 inhibitors, not by an ERK inhibitor. Magnolol also attenuates NF-κB activation and the translocation of HuR (an RNA binding protein) in TNF-α-stimulated HAECs. The VCAM-1 expression was weaker in the aortas of TNF-α-treated apo-E deficient mice with magnolol treatment. These data demonstrate that magnolol inhibits TNF-α-induced JNK/p38 phosphorylation, HuR translocation, NF-κB activation, and thereby suppresses VCAM-1 expression resulting in reduced leukocyte adhesion. Taken together, these results suggest that magnolol has an anti-inflammatory property and may play an important role in the prevention of atherosclerosis and inflammatory responses.
Asunto(s)
Compuestos de Bifenilo/farmacología , Células Endoteliales/metabolismo , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Lignanos/farmacología , Sistema de Señalización de MAP Quinasas/genética , Sistema de Señalización de MAP Quinasas/fisiología , FN-kappa B/genética , FN-kappa B/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/efectos adversos , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Animales , Antiinflamatorios , Antioxidantes , Aorta/citología , Aorta/efectos de los fármacos , Apolipoproteínas E/deficiencia , Aterosclerosis/prevención & control , Células Cultivadas , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Fosforilación/efectos de los fármacos , Fosforilación/genética , Fitoterapia , Transducción de Señal/efectos de los fármacosRESUMEN
The expression of inflammatory cytokines on vascular walls is a critical event in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi) polysaccharides (EORPs), which is effective against immunological disorders, on interleukin- (IL-) 1 ß expression by human aortic smooth muscle cells (HASMCs) and the underlying mechanism. The lipopolysaccharide- (LPS-) induced IL-1 ß expression was significantly reduced when HASMCs were pretreated with EORP by Western blot and immunofluorescent staining. Pretreatment with 10 µ g/mL EORP decreased LPS-induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1 ß expression with LPS treatment was only inhibited by pretreatment with the ERK1/2 inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP reduced the phosphorylation and nuclear translocation of nuclear factor- (NF-) κ B p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1 ß expression was strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of EORP decreased IL-1 ß expression. The level of IL-1 ß expression in LPS-treated or in LPS/EORP-treated group was very low and was similar to that of the saline-treated group in toll-like receptor 4-deficient (TLR4(-/-)) mice. These findings suggest that EORP has the anti-inflammatory property and could prove useful in the prevention of vascular diseases and inflammatory responses.
RESUMEN
BACKGROUND: Dementia, which leads to disability, is one of the important diseases occurring among older populations. However, the exact mechanism of the disease remains unknown. The potential risk factor of general anesthesia (GA) in the development of dementia is a controversial topic. Therefore, this study aimed to evaluate the association between previous exposure to different GA types and the incidence of dementia. METHODS: Using the claims data of 1 million insured residents covered by Taiwan's universal health insurance from 2005 to 2009, 5345 newly diagnosed dementia patients older than 50 years were eligible for the study group. The control group, which consisted of 21,380 individuals without dementia, was matched for age, gender, and index date. GA was categorized into three subtypes: endotracheal tube intubation general anesthesia (ETGA), intravenous injection general anesthesia (IVGA) or intramuscular injection general anesthesia (IMGA), and heavy sedation. The multiple logistic regression model was used for analyses. RESULTS: Individuals exposed to surgery under ETGA (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.25-1.44) and those exposed to surgery under IVGA or IMGA (OR, 1.28; 95% CI, 1.14-1.43) were at significantly higher risk of dementia in a dose-response relationship (P < .0001), whereas surgery under heavy sedation was not associated with increased risk of dementia (OR, 1.04; 95% CI, 0.68-1.59). The dementia risk for subjects with diabetes mellitus who received surgery under ETGA (OR, 1.59; 95% CI, 1.42-1.78), hypertension (OR, 1.98; 95% CI, 1.78-2.21), atherosclerosis (OR, 1.35; 95% CI, 1.22-1.50), or after having experienced a stroke (OR, 3.52; 95% CI, 3.13-3.97), but no interaction was found between surgery under ETGA and depression for the risk of dementia. CONCLUSIONS: A history of previous exposure to surgery under GA might be associated with an increased risk of dementia, particularly in subjects who have undergone repeated exposure to GA. In addition, subjects who had received surgery under ETGA with comorbidities such as stroke, hypertension, diabetes mellitus, and atherosclerosis could have a potential relationship with dementia risk.
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Anestesia General/efectos adversos , Demencia/inducido químicamente , Demencia/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Planificación en Salud Comunitaria , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Riesgo , TaiwánRESUMEN
Chlorhexidine has been widely used for infection control. Although the use of chlorhexidine-impregnated catheters has reduced catheter-related infections, chlorhexidine-resistant Staphylococcus aureus has emerged. The correlation between the existence of the chlorhexidine-resistant genes qacA and qacB (qacA/B) in methicillin-resistant Staphylococcus aureus (MRSA) isolates and the effectiveness of chlorhexidine-impregnated catheters in the prevention of MRSA infections is unknown. Sixty methicillin-sensitive Staphylococcus aureus (MSSA) and 96 MRSA isolates from the blood cultures of different patients were collected, and a case-control study was conducted to determine whether more clinical S. aureus isolates from chlorhexidine-impregnated catheter-related bloodstream infections (CRBSI) have the biocide-resistant genes (qacA/B or smr) than those from other infections. The chlorhexidine MIC(50)s of MSSA and MRSA isolates were 1 µg/ml and 2 µg/ml, respectively. Results of PCR analyses showed that 3.3% (n = 2) of MSSA and 43.8% (n = 42) of MRSA isolates harbored qacA/B and 5% (n = 3) of MSSA and 25% (n = 24) of MRSA isolates contained smr. With multivariate logistic regression analyses, the significant risk factors for definite CRBSI with chlorhexidine-impregnated catheters were determined to be S. aureus isolates with qacA/B and a chlorhexidine MIC of ≥2 µg/ml (odds ratios [OR], 9.264 and 8.137, respectively, in all 156 S. aureus isolates and 6.097 and 4.373, respectively, in the 96 MRSA isolates). Further prospective studies are needed to investigate the transmission of these biocide-resistant genes.
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Antiinfecciosos Locales/uso terapéutico , Bacteriemia/microbiología , Proteínas Bacterianas/genética , Infecciones Relacionadas con Catéteres/microbiología , Clorhexidina/uso terapéutico , Proteínas de Transporte de Membrana/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/microbiología , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos Locales/farmacología , Bacteriemia/tratamiento farmacológico , Proteínas Bacterianas/análisis , Estudios de Casos y Controles , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Catéteres Venosos Centrales/microbiología , Clorhexidina/farmacología , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Masculino , Proteínas de Transporte de Membrana/análisis , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3ß on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.
RESUMEN
Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21(Cip1) and upregulation of the cyclin-dependent kinase inhibitor p27(Kip1). The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100 mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67 ± 0.03 vs. 1.46 ± 0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Miocitos del Músculo Liso , Neointima , Polisacáridos/farmacología , Reishi , Animales , Aorta/citología , Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Técnicas de Silenciamiento del Gen , Humanos , Lipopolisacáridos/farmacología , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Fosforilación/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacologíaRESUMEN
Monocytes expressing toll-like receptor 4 (TLR4) play a major role in regulating the innate immune response and are involved in systemic inflammation. Previous studies have shown that Ginkgo biloba extract (GBE) may act as a therapeutic agent for some cardiovascular and neurological disorders. The objective of this study was to determine whether GBE could modulate immunity in human cells. The monocytic cell line THP-1 was used. Enzyme-linked immunosorbent assay results showed that lipopolysaccharide (LPS) induces the expression of monocyte chemotactic protein-1 (MIP-1), tumor necrosis factor-α, stromal cell-derived factor-1, and MIP-1α, and this induction may be repressed by GBE treatment due to TLR4 blockade. The Griess reagent assay and western blot analysis showed that GBE-mediated inhibition of TLR4 expression was associated with the activation of mitogen-activated protein kinase and production of nitric oxide (NO). Actinomycin D chase experiments demonstrated that GBE decreased the TLR4 mRNA stability in cells. Confocal microscopy and real-time polymerase chain reaction showed that GBE induced the expression of intracellular tristetraprolin (TTP). Transfection with TTP siRNA reversed the effects of GBE in naïve or TLR4-overexpressing cells. Treatment with SNAP (an NO donor) may increase intracellular TTP expression in cells. Immunoprecipitation analysis showed that GBE mediates TTP activation and increases the interaction of TTP with the 3' untranslated region (UTR) of TLR4 mRNA by regulating NO production. Our findings indicate that GBE could decrease the sensitivity of monocytes to LPS. Utilizing TTP to control TLR4 expression may be a promising approach for controlling systemic inflammation, and GBE may have potential applications in the clinical treatment of immune diseases.
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Ginkgo biloba/química , Monocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Receptor Toll-Like 4/biosíntesis , Línea Celular , Dactinomicina/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Humanos , Lipopolisacáridos , Monocitos/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , Tristetraprolina/antagonistas & inhibidores , Tristetraprolina/farmacologíaRESUMEN
Toll-like receptor 4 (TLR4) initiates the inflammatory response in blood vessels in reaction to immune stimuli such as lipopolysaccharide (LPS) produced by gram-negative bacteria. LPS-induced proliferation and functional perturbation in vascular smooth muscle cells play important roles during atherogenesis. Ginkgo biloba extract is an antiatherothrombotic Chinese herbal medicine with anti-inflammatory properties. The effects of G. biloba extract on LPS-induced proliferation and TLR4 expression and the underlying mechanisms for these actions, in human aortic smooth muscle cells (HASMCs), were examined in vitro. LPS-induced proliferation was mediated by the expression of TLR4 in HASMCs. LPS increased the expression of TLR4 in HASMCs, and this effect was mediated by the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, phosphorylation of intracellular mitogen-activated protein kinases (MAPKs), and increases in the cytoplasmic level of HuR and TLR4 mRNA stability. G. biloba extract inhibited LPS-induced HASMC proliferation and decreased the expression of TLR4 by inhibiting LPS-induced NADPH oxidase activation, mRNA stabilization, and MAPK signaling pathways. These results suggest that LPS-induced TLR4 expression contributes to HASMC proliferation and that G. biloba inhibits LPS-stimulated proliferation of HASMCs by decreasing TLR4 expression.
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División Celular/efectos de los fármacos , Ginkgo biloba/química , Lipopolisacáridos/farmacología , Músculo Liso Vascular/citología , NADPH Oxidasas/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Aorta , Activación Enzimática/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología , Receptor Toll-Like 4/genéticaRESUMEN
Corticosteroids have long been proposed as a therapeutic adjuvant in septic renal dysfunction because of their anti-inflammatory properties and favorable results from animal experiments. However, some reports suggested the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Thus, we examined the effects of low-dose dexamethasone (0.01 and 0.1 mg/kg) on hemodynamics and renal function in conscious rats with endotoxemia. Intravenous injection of rats with endotoxin (E. coli lipopolysaccharide, LPS, 1 mg/kg) caused hypotension, vascular hyporeactivity, and tachycardia as well as renal dysfunction. Circulatory failure and renal dysfunction caused by LPS were significantly attenuated in the dexamethasone 0.1 mg/kg-treated group. The nitric oxide (NO) production in plasma and renal tissue and the iNOS protein expression in the kidney were suppressed by cotreatment of LPS rats with dexamethasone, 0.1 mg/kg. Light microscopy showed that 0.1 mg/kg dexamethasone reduced marked infiltration of neutrophils in renal tissues from LPS rats. Moreover, the survival rate at 18 h was significantly increased in the dexamethasone 0.1 mg/kg-treated group when compared with the LPS group. These results suggest that the beneficial effects of low-dose dexamethasone (0.1 mg/kg) in conscious rats with endotoxic shock are associated with amelioration of circulatory failure and renal dysfunction, and this is attributed to inhibition of NO production.
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Dexametasona/uso terapéutico , Endotoxemia/tratamiento farmacológico , Riñón/lesiones , Riñón/microbiología , Animales , Arterias/metabolismo , Presión Sanguínea , Western Blotting , Calcio/sangre , Escherichia coli/metabolismo , Glucocorticoides/uso terapéutico , Concentración de Iones de Hidrógeno , Riñón/patología , Lipopolisacáridos/metabolismo , Masculino , Neutrófilos/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Oxígeno/metabolismo , Potasio/sangre , Ratas , Ratas Wistar , Sepsis/tratamiento farmacológico , Choque Séptico/terapia , Taquicardia , Factores de TiempoRESUMEN
We have investigated the developdment of potential antioxidants based on magnolol, a naturally occurring biphenolic obtained from the bark of Magnolia officinalis. A series of aminomethylated derivatives of magnolol were synthesized under the aromatic Mannich reaction. In-vitro testing for diphenyl-p-picrylhydrazyl (DPPH) scavenging and chemiluminescence assays in whole cell models revealed that the pyrrolidyl-containing magnolols (2b (5,5'-diallyl-3-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol), 3a (5,5'-diallyl-3,3'-bis-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol) and 4c (5,5'-diallyl-3-(morphorin-4-ylmethyl)-3'-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol)) displayed promising free radical scavenging effects as compared with magnolol. The results from compound 4c indicated that the naturally occurring component was suitable to be a lead compound toward promising antioxidants.