PURPOSE.To evaluate the effects of the activation of endogenous angiotensin-converting enzyme 2 (ACE2) using the compound diminazene aceturate (DIZE) in an experimental model of glaucoma in Wistar rats.METHODS. DIZE (1 mg/kg) was administered daily, either systemically or topically, and the IOP was measured weekly. To examine the role of the Mas receptor in the effects of DIZE, the Ang-(1-7) antagonist A-779 was co-administered. Drainage of the aqueous humor was evaluated by using scintigraphy. The analysis of ACE2 expression by immunohistochemistry and the counting of retinal ganglion cells (RGCs) were performed in histologic sections. Additionally, the nerve fiber structure was evaluated by transmission electron microscopy. RESULTS.The systemic administration and topical administration (in the form of eye drops) of DIZE increased the ACE2 expression in the eyes and significantly decreased the IOP of glaucomatous rats without changing the blood pressure. Importantly, this IOP-lowering action of DIZE was similar to the effects of dorzolamide. The antiglaucomatous effects of DIZE were blocked by A-779. Histologic analysis revealed that the reduction in the number of RGCs and the increase in the expression of caspase-3 in the RGC layer in glaucomatous animals were prevented by DIZE. This compound also prevented alterations in the cytoplasm of axons in glaucomatous rats. In addition to these neuroprotective effects, DIZE facilitated the drainage of the aqueous humor. CONCLUSIONS.Our results evidence the pathophysiologic relevance of the ocular ACE2/Ang-(1-7)/Mas axis of the renin-angiotensin system and, importantly, indicate that the activation of intrinsic ACE2 is a potential therapeutic strategy to treat glaucoma.
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia.] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81 ± 2.71 area%; HG: 14.29 ± 4.30 area%; HG+XNT: 26.87 ± 1.86 area%; Po0.05). Importantly, ACE2 activation significantly increased the RCG number in comparison with HG animals (control: 553.5 ± 14.29; HG: 530.8 ± 10.3 cells; HG+XNT: 575.3 ± 16.5 cells; Po0.05). This effect was accompanied by a reduction in the expression of caspase-3 in RGC of the HG+XNT group when compared with untreated HG rats (control: 18.74 ± 1.59; HG: 38.39 ± 3.39 area%; HG+XNT: 27.83 ± 2.80 area%; Po0.05). Treatment with XNT did not alter the VEGF expression in HG animals (P40.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats.
Fetuses with digestive anomalies such as gastroschisis may present intrauterine growth restriction (IUGR) and shortened intestines. Objective: The aim of this study was to assess the influence caused by amniotic fluid (AF) in intestinal length and somatic growth in an experimental gastroschisis fetal model at two distinct gestational ages. Material and Method: Fetal rats were operated according to Correia-Pinto on 2 different days of gestation: day 18.5 (group I) and day 19.5 (group II). Each group was divided into three sub-groups: fetuses with gastroschisis (G), control (C) and sham(S). Body measurements and histological analysis were done. Result: Body measurement analysis showed: average body weight (g) in group I was G = 5.32, C = 5.68, S = 5.86; group II was G = 5.32, C = 5.80, S = 5.66. Average intestine weight (g) in group I was G = 0.283, C = 0.238, S = 0.231; group II was G = 0.272, C = 0.231, S = 0.233. Average intestine length (mm) in group I was G = 125, C = 216, S = 209; group II was G = 148, C = 226, S = 226. Histological analysis showed a decrease in the number and size of the intestinal microvillae and a light edema of serosa. Conclusion: Gastroschisis had a direct correlation with IUGR and the time of exposure of the fetuses to AF had no influence on body weight in gastroschisis fetuses but did interfere with intestinal length.
Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5–60; p-value < 0.001) and GFAP (OR 0.002, 95% CI 0–0.68; p-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (p-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87–99%), with sensitivity of 91% (95% CI: 72–99%), and specificity of 96% (95% CI: 90–99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87–99%), with a sensitivity of 82% (95% CI: 57–96%), and specificity of 98% (95% CI: 92–100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.
Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.
Background and PurposeAcute ischemic stroke caused by large vessel occlusions (LVO) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging.AimsTo evaluate the diagnostic accuracy of a panel of biomarkers for LVO prediction.Methods170 patients with suspected stroke were recruited retrospectively at one hospital. We analysed the plasma levels of D-dimer, OPN, OPG, GFAP, vWF, and ADAMTS13 in LVO vs non-LVO. Diagnostic performance was estimated by using blood biomarkers alone or in combination with NIHSS-derived stroke severity scales.ResultsOur patient cohort comprised 20% stroke mimics, 11% transient ischemic attack, 11% hemorrhagic stroke, 15% LVO ischemic stroke, 28% non-LVO ischemic stroke, and 15% ischemic stroke with unknown LVO status. Multivariable analysis found that the optimal set of blood biomarkers for LVO prediction was D-dimer (OR 15.4, 95% CI 4.9 to 57.6; p-value<0.001) and GFAP (OR 0.83, 95% CI 0.90 to 0.99; p-value=0.03). The combination of D-dimer and GFAP with stroke scales significantly improved LVO prediction, compared to the stroke scales alone (p-value<0.001). The combination of biomarkers with constructed FAST-ED or EMSA scales achieved an AUC of 95% (95% CI 91-100%) or 93% (CI 95% 89-97%), a sensitivity of 91% (95% CI 71-98%) or 86 (95% CI 66-97%), and a specificity of 95% (95% CI 89-98%) or 94% (95% CI 88-98%), for LVO prediction, respectively.ConclusionsThe combination of D-dimer, GFAP, and stroke scales could provide a simple and highly accurate tool for identifying LVO patients.
Introduction:A phase II/III study of a Brazilian tailor-made meningococcal B vaccine in children from 4 to less than 12 years was designed after promising results from phase I study. A randomized study using three concentrations of vaccine antigens were compared with VAMENGOC-BC® vaccine. Objectives:In experimental vaccines were used the following protein antigens concentrations: 50μg, the same used in VAMENGOC-BC®; half (25μg) and 1⁄4 (12.5μg). All test vaccines received 1⁄2 the protein concentration in dLOS and aluminum hydroxide as adjuvant. Vaccination-adopted scheme was a primary immunization with three doses with two-months apart and a booster 6-12 months after the third dose.Methodology: Sixteen volunteers from each vaccine group constituted a subsample of phase II/III study to evaluate the role of vaccine-induced antibodies in inhibiting the adhesion of vaccine strains to epithelial cells. Epithelial cell line Detroit-562 were used in adherence, invasion and persistence assays. Mid-logphase bacteria were cultured and added to each well with MOI 100 bacteria/epithelial cell. To determine the level of bacterial adhesion, 96-well plates were prewashed and lysed. For invasion and persistence assays, all strains were shown to be susceptible to ≤ 150 mg/mL of gentamicin and incubated for 1h. and 24h. respectively. Invasion and persistence ability was expressed as the percentage of inoculum that survived after the incubation period. Results:The results were recorded as percentage of the original inoculum. Antibodies induced by the experimental vaccines inhibited adherence from 44 to 53% of the first prevalent, N44/89, and from 40 to 100% of the second strain, N603/95. When compared to the reference vaccine, the inhibition observed in Vamengoc-BC was 36 and 60%, respectively, for the vaccine strains. Conclusion:The results suggest greater pathogenicity of N44/89 strain compared to N603/95, which justifies its role as the main cause of meningococcal meningitis by serogroup B in the country. They also suggest that antibodies induced by test and reference vaccines, both consisting of outer membrane vesicles vaccines, are important in reducing N.meningitidis adhesion to the epithelium, an important phenomenon in meningococcal disease.
O artigo propõe-se a analisar três obras do artista visual Leonilson, explorando procedimentos da semiótica discursiva, a fim de compreender como se articulam os elementos do plano da expressão e do plano do conteúdo no desenho We look to the left (1989), na pintura Leo não consegue mudar o mundo (1989) e no desenho Converso no seio do Cristo (1993). Buscou-se ainda observar e identificar os aspectos marcantes da produção artística de Leonilson e apresentar breve contextualização sobre a semiótica discursiva. Ao final, concluiu-se que a semiótica discursiva pode contribuir para interpretações mais abrangentes de obras de artes visuais.
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