44 research outputs found
An anti-interleukin-2 receptor drug attenuates thelper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis
The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor
drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable
model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after
endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The
histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers)
was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the
levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers
was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with
endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with
a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as
Interleukin-2 and Interferon-c, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment
in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by
about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of
Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory
properties and a substantial concomitant drop in INFc. Concurrently, Daclizumab treatment triggered a significant
reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular
infiltration
Influence of Dll4 via HIF-1α-VEGF Signaling on the Angiogenesis of Choroidal Neovascularization under Hypoxic Conditions
Choroidal neovascularization (CNV) is the common pathological basis of
irreversible visual impairment encountered in a variety of chorioretinal
diseases; the pathogenesis of its development is complicated and still
imperfectly understood. Recent studies indicated that delta-like ligand 4
(Dll4), one of the Notch family ligands might participate in the HIF-1α-VEGF
pathway to regulate CNV angiogenesis. But little is known about the influence
and potential mechanism of Dll4/Notch signals on CNV angiogenesis. Real-time
RT-PCR, Western blotting were used to analyze the expression alteration of Dll4,
VEGF and HIF-1α in hypoxic RF/6A cells. Immunofluorescence staining, a
laser-induced rat CNV model and intravitreal injection techniques were used to
confirm the relationships among these molecules in vitro and
in vivo. RPE-RF/6A cell co-culture systems were used to
investigate the effects of Dll4/Notch signals on CNV angiogenesis. We found that
the Dll4 was involved in hypoxia signaling in CNV angiogenesis. Results from the
co-culture system showed that the enhancement of Dll4 expression in RF/6A cells
led to the significantly faster proliferation and stronger tube forming ability,
but inhibited cells migration and invasion across a monolayer of RPE cells in
hypoxic environment, while siRNA-mediated Dll4 silencing caused the opposite
effects. Pharmacological disruption of Notch signaling using gamma-secretase
inhibitor (GSI) produced similar, but not identical effects, to that caused by
the Dll4 siRNA. In addition, the expression of several key molecules involved in
the angiogenesis of CNV was altered in RF/6A cells showing constitutively active
Dll4 expression. These results suggest that Dll4 play an important role in CNV
angiogenesis, which appears to be regulated by HIF-1α and VEGF during the
progression of CNV under hypoxic conditions. Targeting Dll4/Notch signaling may
facilitate further understanding of the mechanisms that underlie CNV
angiogenesis
Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure
Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted
Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release
Infl ammation results in the production of free radicals. We evaluated the anti-infl ammatory and antioxidant capacity of lipoic acid in an
experimental uveitis model upon a subcutaneous injection of endotoxin into Lewis rats. The role of oxidative stress in the endotoxin-induced
uveitis model is well-known. Besides, the Th1 response classically performs a central part in the immunopathological process of experimental
autoimmune uveitis. Exogenous sources of lipoic acid have been shown to exhibit antioxidant and anti-infl ammatory properties. Our
results show that lipoic acid treatment plays a preventive role in endotoxin-induced oxidative stress at 24 h post-administration and reduced
Th1 lymphocytes-related cytokines by approximately 50 – 60%. Simultaneously, lipoic acid treatment caused a signifi cant reduction in uveal
histopathological grading and in the protein concentration in aqueous humors, but not in cellular infi ltration
Imbalance Between Oxidative Stress and Growth Factors in Human High Myopia
La miopĂa es una de las patologĂas oculares más comunes que podrĂa afectar a 2.560 millones de personas en
2020. Hoy en dĂa, la alta miopĂa es una de las principales causas de ceguera en todo el mundo debido a las enfermedades asociadas enfermedad ocular. Sin embargo, las bases celulares para que se desarrollen estas enfermedades no están claras en muchas áreas. Realizamos un estudio prospectivo sobre estrĂ©s oxidativo y factores de crecimiento en ojos humanos miopes y no miopes en un intento de aumentar nuestra comprensiĂłn
de las condiciones fisiopatolĂłgicas subyacentes para diagnosticar adecuadamente, prevenir y tratar el problema de retina que deriva de la miopĂa. Se tomaron muestras de humor acuoso obtenido de 41 pacientes operados de cataratas en nuestro hospital. Se registrĂł, la longitud axial, el estado refractivo y el examen oftalmolĂłgico completo. El VEGF y los niveles de HGF se determinaron mediante un kit ELISA. Capacidad antioxidante total y total
Los niveles de nitritos/nitratos se establecieron con un kit de laboratorio. Mostramos por primera vez un aumento de los niveles totales de nitrito en personas con alta miopĂa. TambiĂ©n proponemos por primera vez
la concurrencia de tres factores: miopĂa, estrĂ©s oxidativo y estrĂ©s oxidativo juntos con factores de crecimiento en el mismo grupo de pacientes. De esta manera, no serĂa exacto incluir la miopĂa alta como un tipo de miopĂa normal, pero con más dioptrĂas o más longitud axial
Performance of the LightCycler SeptiFast Test Mgrade in Detecting Microbial Pathogens in Purulent Fluidsâ–ż
The performance of the LightCycler SeptiFast (SF) assay was compared to that of culture methods in the detection of microorganisms in 43 purulent fluids from patients with pyogenic infections. The SF assay was more sensitive than the culture methods (86% versus 61%, respectively), irrespective of whether the infections were mono- or polymicrobial