Simultaneous Therapy with Intravitreal Dexamethasone Implant and Bevacizumab for the Treatment of Macular Edema

To investigate the safety profile and benefits of a short-term simultaneous treatment regimen combining two drugs—an intravitreal implant of dexamethasone with an intravitreal injection of bevacizumab—in patients with macular edema. This was a retrospective, non-randomized, open-label case series study.  Patients were treated between April 2014 and July 2015 and were diagnosed with recurrent macular edema secondary to diabetic retinopathy and retinal vein occlusion. They underwent simultaneous treatment with an intravitreal injection of bevacizumab (1.25 mg) and an intravitreal implant of dexamethasone (0.7 mg). Patients were evaluated at baseline and at each subsequent visit with a complete ophthalmological examination and spectral-domain optical coherence tomography (OCT) scans. They were examined 24 hours after the treatment, and then followed up after 30 days and 60 days. Twenty patients (representing 20 eyes) were included in the study. At the time of injection (i.e., baseline), the best-corrected visual acuity (BCVA) was 0.758 ± 0.42 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.51 ± 0.33 logMAR at 1 month and to 0.5 ± 0.34 logMAR at 2 months (P ≤ 0.03). The median baseline central macular thickness (CMT) was 542 µm (interquartile range, 466 – 751 µm). The median CMT decreased significantly to 321 µm (interquartile range, 288–381 µm) at 1 month and 310 µm (interquartile range, 286 – 354 µm) at 2 months (P ≤ 0.0002). The mean intraocular pressure (IOP) increased from 14.9 ± 2.29 mmHg (at baseline) to 16.5 ± 2.99 mmHg (P = 0.04) after 2 months. Two (10%) eyes showed cataract progression. There were no other ocular or systemic complications for the duration of this study. Simultaneous therapy combining a dexamethasone implant plus bevacizumab for macular edema may be an attractive treatment regimen with an acceptable safety profile

Analysis of neuroretinal rim distribution and vascular pattern in eyes with presumed large physiological cupping: a comparative study

Background: To investigate possible differences in neuroretinal rim distribution, vascular pattern, and peripapillary region appearance between eyes with presumed large physiological optic disc cupping (pLPC) and eyes with minimal optic disc excavation.Methods: We prospectively enrolled consecutive subjects with pLPC and individuals with minimal excavation (optic disc excavation within normal limits; control group). All eyes had normal visual fields and untreated intraocular pressure (IOP) = 0.6 and >= 30 months of follow-up with no evidence of glaucomatous neuropathy. for controls, VCDR was limited to <= 0.5. We compared ocular signs and characteristics related to the neuroretinal rim distribution, vascular pattern, peripapillary region appearance and disc size between groups. Whenever both eyes were eligible, one was randomly selected for analysis.Results: A total of 74 patients (mean age, 45.6 +/- 14.9 years) with pLPC and 45 controls (mean age, 44.8 +/- 11.6 years) were enrolled (p = 0.76). Median disc size and VCDR was significantly larger in eyes with pLPC compared to controls (p < 0.01). the proportion of eyes with violation of the ISNT rule, laminar dot sign, nasal shifting of the central vessels, nasal excavation and baring of circumlinear vessel was significantly greater in the eyes with pLPC compared to controls (p < 0.01). There were no significant differences regarding the proportions of eyes with peripapillary atrophy between groups (p < 0.09). Finally, disc size was significantly associated with VCDR (r(2) = 0.47, p < 0.01), with an increase of 0.21 in VCDR for each 1 mm(2) in disc area.Conclusion: Compared to normal controls, eyes with pLPC may present a higher proportion of optic nerve head findings frequently observed in glaucomatous eyes. This seems to be explained in part by the larger discs found in these eyes. We believe care should be taken while classifying them as glaucomatous or not based solely on these characteristics.Universidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilHosp Med Olhos, Glaucoma Unit, BR-06018180 Osasco, SP, BrazilMayo Clin, Dept Ophthalmol, Jacksonville, FL 32224 USAUniversidade Federal de São Paulo, Dept Ophthalmol, BR-04021001 São Paulo, BrazilWeb of Scienc

Eyes with Large Disc Cupping and Normal Intraocular Pressure: Using Optical Coherence Tomography to Discriminate Those With and Without Glaucoma

We evaluated the ability of spectral-domain optic coherence tomography (SD-OCT) to differentiate large physiological optic disc cupping (LPC) from glaucomatous cupping in eyes with intraocular pressure (IOP) within the normal range.  We prospectively enrolled patients with glaucoma or presumed LPC. Participants  had optic discs with confirmed or suspected glaucomatous damage (defined as a vertical cup-to-disc ratio≥0.6), and all eyes had known untreated IOP&lt;21 mmHg. For glaucomatous eyes, a reproducible glaucomatous visual field (VF) defect was required. LPC eyes required normal VF and no evidence of progressive glaucomatous neuropathy (follow-up≥30 months). Peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (GCC) thicknesses were obtained using SD-OCT. For all studied parameters of pRNFL and GCC thicknesses, eyes with glaucoma (n=36) had significantly thinner values compared to eyes with LPC (n=71; P&lt;0.05 for all comparisons). In addition, pRNFL parameters had sensitivity of 66.7% and specificity of 83.1%, and GCC parameters had sensitivity of 61.2% and specificity of 81.7%. The combination of the two analyses increased the sensitivity to 80.6%. In conclusion, while evaluating patients with large optic disc cupping and IOP in the statistically normal range, SD-OCT had only limited diagnostic ability to differentiate those with and without glaucoma. Although the diagnostic ability of the pRNFL and the GCC scans were similar, these parameters yielded an increase in sensitivity when combined, suggesting that both parameters could be considered simultaneously in these cases

Mecanismos de fechamento angular sem bloqueio pupilar: análise de prevalência e resultados terapêuticos

Purpose: To assess the prevalence and treatment outcomes of angle-closure mechanisms other than pupillary block in a population of Brazilian patients.Methods: A retrospective chart review was conducted to evaluate patients who had undergone laser peripheral iridotomy (LPI) due to occludable angles at a single institution between July 2009 and April 2012. An occludable angle was defined as an eye in which the posterior trabecular meshwork was not visible for >= 180 degrees on dark-room gonioscopy. Key exclusion criteria were any form of secondary glaucoma and the presence of >90 degrees of peripheral anterior synechiae. Collected data were age, race, gender, angle-closure mechanism (based on indentation goniocopy and ultrasound biomicroscopy), intraocular pressure (IOP), number of antiglaucoma medications and subsequent management during follow-up. If both eyes were eligible, the right eye was arbitrarily selected for analysis.Results: A total of 196 eyes of 196 consecutive patients (mean age 58.3 +/- 11.6 years) who underwent LPI were included. in most of the patients [86% (169 patients; 133 women and 36 men]), LPI sucessfully opened the angle. Mean IOP was reduced from 18.3 +/- 6.4 mmHg to 15.4 +/- 4.5 mmHg after LPI (p<0.01). Among the 27 patients with persistent occludable angles, the most common underlying mechanisms were plateau iris (56%) and lens-induced component (34%). Most of these patients (85%) were treated with argon laser peripheral iridoplasty (ALPI); approximately 90% showed non-occludable angles following the laser procedure (mean IOP reduction of 18.9%), with no significant differences between patients with plateau iris and lens-induced components (p=0.34; mean follow-up of 11.4 +/- 3.6 months).Conclusions: Our findings suggest that, in this population of Brazilian patients, several eyes with angle closure were not completely treated with LPI. in the present large case series involving middle-age patients, plateau iris was the leading cause of persistent angle closure and was effectively treated with ALPI. A detailed eye examination with indentation gonioscopy should always be performed after LPI to rule out persistent angle closure due to non-pupillary block mechanisms.Hosp Med Olhos, Glaucoma Unit, Osasco, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilMayo Clin, Jacksonville, FL 32224 USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

β-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders

It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested in three breast cell lines: MCF-10, a healthy cell; MCF-7, a hormone responsive cancer cell; and MDA-MB-231, a triple negative breast cancer cell. Both aziridines and their precursors, β-amino alcohols, showed activity towards these cells, and some of the compounds showed higher selectivity index than cisplatin, the drug used as control. When the type of cell death was investigated, the synthesized compounds demonstrated higher apoptosis and lower necrosis rates than cisplatin, and when the mechanism of action was studied, the compounds were shown to interact with DNA via its minor groove instead of alkylation or intercalation

Inhibitory action of Lippia gracilis Schauer essential oil on pathogenic bacteria and its effects as a growth promoter on quail

Aim of the study: To examine the in vitro sensitivity of Salmonella sp. and Escherichia coli strains to the microbial activity of Lippia gracilis Schauer essential oil (LGSEO) and to determine the optimal level of LGSEO as a growth promoter in diets for Japanese quail up to 35 days of age.Area of study: São Cristovão, Sergipe, Brazil.Material and methods: A total of 504 female Japanese quails (Coturnix coturnix japonica) at an initial average body weights of 6.80±0.10 g was allotted to one of six treatments (0, 100, 200, 300, 400 mg/kg of LGSEO and a diet containing 500 mg/kg of bacitracin methylene disalicylate) in 7 replicates, using 12 birds per experimental unit.Main results: In the age period of 21 to 35 days, feed intake declined linearly (p=0.04) and feed efficiency improved (p&lt;0.01), whereas no changes were observed in production performance (p&gt;0.05). The estimated (p=0.01) maximum relative weights of proventriculus and pancreas were obtained at the LGSEO inclusion levels of 196.5 and 251 mg/kg, respectively. Inclusion of 100 to 300 mg/kg of LGSEO in the diet reduced the total Salmonella sp. bacterial count.Research highlights: The use of 196.5 mg/kg of LGSEO in the diet of Japanese quail improved production performance and organ development and demonstrated potential antimicrobial capacity against Salmonella sp. bacteria. Due its pharmacological composition, LGSEO can potentially substitute to antimicrobials, because contains thymol and carvacrol as main active constituents

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Blood Levels of Glutamate and Glutamine in Recent Onset and Chronic Schizophrenia

Converging evidence indicates that dysfunctions in glutamatergic neurotransmission and in the glutamate-glutamine cycle play a role in the pathophysiology of schizophrenia. Here, we investigated glutamate and glutamine levels in the blood of patients with recent onset schizophrenia or chronic schizophrenia compared to healthy controls. Compared with healthy controls, patients with recent onset schizophrenia showed increased glutamine/glutamate ratio, while patients with chronic schizophrenia showed decreased glutamine/glutamate ratio. Results indicate that circulating glutamate and glutamine levels exhibit a dual behavior in schizophrenia, with an increase of glutamine/glutamate ratio at the onset of schizophrenia followed by a decrease with progression of the disorder. Further studies are warranted to elucidate the mechanisms and consequences of changes in circulating glutamate and glutamine in schizophrenia

Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

Abstract\ud \ud Background\ud The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP), a natural naphthoquinone, as a potential DHODH inhibitor and addressed its immunosuppressive properties.\ud \ud \ud Methods\ud Molecular flexible docking studies and bioactivity assays were performed to determine the ability of LAP to interact and inhibit DHODH. In vitro studies were conducted to assess the antiproliferative effect of LAP using isolated lymphocytes. Finally, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models were employed to address the anti-arthritic effects of LAP.\ud \ud \ud Results\ud We found that LAP is a potent DHODH inhibitor which had a remarkable ability to inhibit both human and murine lymphocyte proliferation in vitro. Importantly, uridine supplementation abrogated the antiproliferative effect of LAP, supporting that the pyrimidine metabolic pathway is the target of LAP. In vivo, LAP treatment markedly reduced CIA and AIA progression as evidenced by the reduction in clinical score, articular tissue damage, and inflammation.\ud \ud \ud Conclusions\ud Our findings propose a binding model of interaction and support the ability of LAP to inhibit DHODH, decreasing lymphocyte proliferation and attenuating the severity of experimental autoimmune arthritis. Therefore, LAP could be considered as a potential immunosuppressive lead candidate with potential therapeutic implications for RA.The research leading to these results received funding from the European\ud Union Seventh Framework Programme (FP7-2007-2013) under grant\ud agreement n° HEALTH-F4-2011-281608 (TIMER), from the São Paulo Research\ud Foundation (FAPESP) under grant agreements n° 2009/54014-7, 2011/1967-0,\ud 2012/25075-0, 2014/50265-3, 2012/20990-2 and 2013/08216-2 (Center for\ud Research in Inflammatory Diseases), and from the University of São Paulo\ud NAP-DIN and NPPNS under grant agreement n° 11.1.21625.01.0 and\ud 2012.1.17587.1.1, respectivel