Bioactivity of Acanthus mollis - Contribution of benzoxazinoids and phenylpropanoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus mollis is a plant native to the Mediterranean region, traditionally used as diuretic, anti-inflammatory and soothing of the mucous membranes of the digestive and urinary tract and externally as healing of wounds and burns, also demonstrating analgesic and anti-inflammatory activities. However, studies focused on its phytochemical composition as well as scientific proof of Acanthus mollis efficacy are scarce. AIM OF THE STUDY: The proposed work aims to perform a phytochemical characterization and evaluation of the therapeutic potential of Acanthus mollis, based on biological properties that support its traditional uses. MATERIAL AND METHODS: In this study, an 96% ethanol extract from Acanthus mollis leaves was obtained and its phytochemical composition evaluated using High Performance Liquid Chromatography with Photodiode Array Detector coupled to Electrospray Ionization Mass Spectrometry (HPLC-PDA-ESI/MSn). The chemical structure of the compound isolated was elucidated using 1H and 13C Nuclear Magnetic Resonance (NMR), 1H-correlation spectroscopy (1H-COSY), heteronuclear single quantum correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC). The quantification of the constituents was performed using two external standards (2,4-dihydroxy-1,4-benzoxazin-3-one and verbascoside). The antioxidant activity was determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) assay. Anti-inflammatory activity was determined measuring the inhibition of nitric oxide production by RAW 264.7 macrophages stimulated with the TLR4 agonist lipopolysaccharide (LPS) and through lipoxygenase (LOX) inhibition assay. The cytotoxicity was screened on two lines (RAW 264.7 and HaCaT) using the resazurin assay. RESULTS: Compounds such as verbascoside and its derivatives, as well as benzoxazinoids were found as the main constituents. A percentage of 5.58% was verified for the 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) derivatives. DIBOA was the main compound of the extract. Significant concentrations were also found for phenylpropanoids, which constitute about 4.39% of the total compounds identified. This extract showed antioxidant capacity against DPPH (IC50 = 40.00 ±â€¯1.59 µg/mL) and superoxide anion (IC50 = 29.42 ±â€¯1.99 µg/mL). It also evidenced anti-inflammatory potential in RAW 264.7 macrophages, presenting capacity for nitric oxide reduction (IC50 = 28.01 µg/mL). Moreover, in vitro studies have shown that this extract was able to inhibit the lipoxygenase, with an IC50 of 104.39 ±â€¯4.95 µg/mL. Importantly, all effective concentrations were devoid of cytotoxicity in keratinocytes, thus highlighting the safety of the extract for the treatment of skin inflammatory related diseases. Concerning macrophages it was also possible to disclose concentrations showing anti-inflammatory activity and without cytotoxicity (up to 30 µg/mL). The benzoxazinoid DIBOA demonstrated a considerable anti-inflammatory activity suggesting its important contribution to this activity. CONCLUSIONS: These results corroborate the anti-inflammatory properties traditionally attributed to this plant. Among the compounds identified in this study, benzoxazinoids exhibited a significant anti-inflammatory activity that was never previously described. Ethanol seems to be a good option for the extraction of these bioactive compounds, since relevant antioxidant/anti-radical and anti-inflammatory activities were found for this extract.

DHM in human-centered product design: a case-study on public transport vehicle.

The goal of this paper is to present the advantages on the use of 3D Digital Human Models (DHM) on the design of public transport vehicles. In this case, the subjects were scanned using the WBX Cyberware 3D Whole Body Scanner, with functional and daily postures according to the use of public transportation and some especial cases, such as a mother with her offspring or a business man with his valise, so the volume of the person would be taken in consideration. A data collection was created to simulate several situations of the daily use of the vehicle.

1D and 3D anthropometric data application on public transport vehicle layout and on oil and gas laboratories work environment design.

The goal of this paper is to present 1D and 3D anthropometric data applied to two distinct design situations: one related to the interior layout of a public transport vehicle and another one related to oil and gas laboratories work environment design. On this study, the 1D anthropometric data were extracted from the Brazilian anthropometric database developed by INT and the 3D anthropometric data were obtained using a Cyberware 3D whole body scanner. A second purpose of this paper is to present the 3D human scanning data as a tool that can help designers on decision making.

Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients.

PURPOSE: To investigate factors associated with changes in optic nerve head (ONH) topography after acute intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG). METHODS: Untreated POAG patients (IOP >21 mm Hg) were prospectively enrolled. Systemic and ocular information were collected, including central corneal thickness (CCT) and corneal hysteresis (CH). All patients underwent confocal scanning laser ophthalmoscopy and tonometry (Goldmann) before and 1 h after pharmacological IOP reduction. The mean of three measurements was considered for analysis. Changes in each ONH topographic parameter were assessed (one eye was randomly selected), and those that changed significantly were correlated with patient's systemic and ocular characteristics. RESULTS: A total of 42 patients were included (mean age, 66.7 ± 11.8 years). After a mean IOP reduction of 47.3 ± 11.9%, significant changes were observed in cup area and volume, and in rim area and volume (P < 0.01), but not in mean cup depth (P = 0.80). Multiple regression analysis (controlling for baseline IOP and magnitude of IOP reduction) showed that CH (r(2) = 0.17, P < 0.01) and diabetes diagnosis (r(2) ≥ 0.21, P < 0.01) were negatively correlated with the magnitude of changes in ONH parameters, whereas the cup-to-disc ratio was positively correlated (r(2) = 0.30, P < 0.01). Age, race, disc area, and CCT were not significant (P ≥ 0.12). Including all significant factors in a multivariable model, only the presence of diabetes remained significantly associated with all ONH parameters evaluated (P < 0.01). CONCLUSIONS: Different systemic and ocular factors, such as diabetes, CH, and the relative size of the cup, seem to be associated with the magnitude of changes in ONH topography after acute IOP reduction in POAG patients. These associations partially explain the ONH changes observed in these patients and suggest that other factors are possibly implicated in an individual susceptibility to IOP.

Evaluation of the impact of intracorneal ring segments implantation on the quality of life of patients with keratoconus using the NEI-RQL (National Eye Institute Refractive Error Quality of life) instrument.

BACKGROUND/AIMS: A prospective study evaluating the impact of intracorneal ring segment (ICRS) implantation on the quality of life of patients with keratoconus using the NEI-RQL (National Eye Institute Refractive Error Quality of Life) instrument. METHODS: Sixty-nine eyes of 42 keratoconus patients were implanted with the Keraring. All patients self-administered the NEI-RQL before and 4(1/2) to 8 months after surgery. The results were evaluated and analysed, along with best-corrected visual acuity (BCVA), refraction, contrast sensitivity, corneal topography and aberrometry preoperatively and 3 months postoperatively. RESULTS: There was a significant improvement in all NEI-RQL scales and the overall scale. "Clarity of vision," "far vision," "near vision," "activity limitations," "appearance" and "satisfaction with correction" had the greatest improvement, ranging from 25 to 50 preoperatively to 80 to 90 after surgery. Best spectacle-corrected visual acuity and binocular BCVA improved significantly, and there was a significant decrease in keratometric values, from 50.22 dioptres preoperatively to 46.27 dioptres postoperatively. Contrast sensitivity function improved postoperatively, especially at the frequency of 6 cpd. Low-order root mean square (RMS) improved after surgery, but high-order RMS did not. CONCLUSION: ICRS implantation not only improves the quantitative metrics such as visual acuity and refraction, but also has a positive impact on patients' quality of life.

Laser trabeculoplasty for open angle glaucoma.

BACKGROUND: Open angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence. OBJECTIVES: The objective of this review was to study the effects of laser trabeculoplasty for OAG. SEARCH STRATEGY: We identified trials from CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and manual searching. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised controlled trials comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery. We also included trials comparing different technical modalities of laser trabeculoplasty. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted the data. We contacted trial investigators for missing information. MAIN RESULTS: This review included 19 trials involving 2137 participants. Only five trials fulfilled the criteria of good methodological quality. One trial compared laser trabeculoplasty with topical beta-blocker to no intervention in early glaucoma. The risk of glaucoma progression was higher in the control group at six years of follow up (risk ratio (RR) 0.71 95% confidence interval (CI) 0.53 to 0.95). No difference in health-related quality of life was observed between the two groups. Three trials compared laser trabeculoplasty to medication (regimens used before the 1990s) in people with newly diagnosed OAG. The risk of uncontrolled intraocular pressure (IOP) was higher in the medication group compared to the trabeculoplasty group at six months and two years of follow up. Three trials compared laser trabeculoplasty with trabeculectomy. The risk of uncontrolled IOP was significantly higher in the trabeculoplasty group at six months but significant heterogeneity was observed at two years. Diode and selective laser are compared to argon laser trabeculoplasty in three trials and there is some evidence showing a comparable effect in controlling IOP at six months and one year of follow up. AUTHORS' CONCLUSIONS: Evidence suggests that, in people with newly diagnosed OAG, the risk of uncontrolled IOP is higher in people treated with medication used before the 1990s when compared to laser trabeculoplasty at two years follow up. Trabeculoplasty is less effective than trabeculectomy in controlling IOP at six months and two years follow up. Different laser technology and protocol modalities were compared to the traditional laser trabeculoplasty and more evidence is necessary to determine if they are equivalent or not. There is no evidence to determine the effectiveness of laser trabeculoplasty compared to contemporary medication (prostaglandin analogues, topical anhydrase inhibitors and alpha2-agonists) and also with contemporary surgical techniques. Also there should be further investigation in to the effectiveness of laser trabeculoplasty in specific racial groups, specific diagnostic groups, such as pseudoexfoliation and pigmentary glaucoma and different stages of OAG. More research is also required determining cost-effectiveness of laser trabeculoplasty in the management of glaucoma.

Trabeculectomy and optic nerve head topography.

The objective of the present study was to evaluate changes in optic nerve head parameters, measured by confocal laser tomography, before and after trabeculectomy in order to identify outcome measures for the management of glaucoma. The optic nerve head of 22 eyes (22 patients) was analyzed by confocal laser tomography with the Heidelberg retinal tomogram (HRT) before and after trabeculectomy. The median time between the first HRT and surgery was 4.6 months (mean: 7.7 +/- 8.3) and the median time between surgery and the second HRT was 10.8 months (mean: 12.0 +/- 6.8). The patients were divided into two groups, i.e., those with the highest (group A) and lowest (group B) intraocular pressure (IOP) change after surgery. Differences in the 12 standard topographic parameters before and after surgery for each group were evaluated by the Wilcoxon signed rank test and the differences in these parameters between the two groups were compared by the Mann-Whitney rank sum test. Multiple regression analysis was used to evaluate the influence of the change in IOP (DeltaIOP and DeltaIOP%) and the changes in the other parameters. There were significant differences in the HRT measures before and after surgery in group A only for cup volume. In group B, no parameter was statistically different. The changes in group A were not significantly different than those in group B for any parameter (P > 0.004, Bonferroni correction for multiple comparisons). DeltaIOP and DeltaIOP% had a statistically significant effect on Delta cup disk area, Delta cup volume and Delta mean cup depth. Changes in cup shape size were influenced significantly only by DeltaIOP. Some optic disc parameters measured by HRT presented a significant improvement after filtering surgery, depending on the amount of IOP reduction. Long-term studies are needed to determine the usefulness of these findings as outcome measures in the management of glaucoma.

Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma.

AIM: To evaluate tumour angiogenesis as a predictor of prognosis in retinoblastoma. METHODS: This was a retrospective, non-randomised comparative clinicopathological study. The histopathology from 24 cases of Reese-Ellsworth (RE) group V unilateral retinoblastoma treated by enucleation alone was reviewed. Group I consisted of five patients (four RE group Vb and one group Va) who developed disseminated disease at a mean of 10.4 months after enucleation. The remaining 19 patients constitute group II (18 RE group Vb and 1 group Va), none of whom had developed metastatic disease with a mean follow up of 54 months. None of the 24 patients had evidence of extraocular disease at enucleation. The surgical specimens from patients with unilateral retinoblastoma treated by enucleation at Hospital do Cancer AC Camargo between January 1992 and December 1995 were identified, reviewed and the clinical data recorded. Two subsequent histological sections were prepared. One stained with haematoxylin and eosin for assessment of choroidal and optic nerve invasion, and the other for immunoreaction with an endothelium specific marker (antibody anti-CD 34). The main outcome measures were choroidal and/or optic nerve invasion and quantification of the tumour's relative vascular area (TRVA) obtained by Chalkley counting. RESULTS: Choroidal invasion was present in three eyes of group I (all massive) and six eyes of group II (two focal and four massive). Optic nerve invasion was found in two eyes of group I (all post-laminar) and four eyes of group II (three prelaminar and one post-laminar). There was no statistical difference regarding choroidal or optic nerve between the two groups. The TRVA was the only independent variable found to predict disease dissemination (p = 0.008 by Cox analysis). A TRVA equal to or greater than 3.9% had 100% sensitivity and 79% specificity in predicting disease dissemination. CONCLUSIONS: Quantification of angiogenesis, through measurement of the TRVA, can help to identify patients with retinoblastoma at high risk for disease dissemination after enucleation.

Influence of surgical reduction of intraocular pressure on regions of the visual field with different levels of sensitivity.

PURPOSE: To determine whether the ability to document improvement in visual fields after intraocular pressure (IOP) reduction can be enhanced by focusing on regions of the field with different levels of sensitivity. DESIGN: Cohort study. METHODS: This is a retrospective study. SETTING: Yale Eye Center. STUDY POPULATION: The visual fields (Octopus G2) of 30 eyes of 30 patients undergoing trabeculectomy. OBSERVATION PROCEDURE: Visual fields were evaluated a mean of three months before and 7.8 months after surgery. MAIN OUTCOME MEASURES: Change in sensitivity between the preoperative and postoperative visual fields (Delta S) was evaluated globally by comparing all 59 points of sensitivity and regionally in three groups according to preoperative sensitivity (pre-S): 25% of highest, 50% intermediate, and 25% of lowest points of sensitivity. Improvement in Delta S was also correlated with preoperative mean defect (pre-MD), percent intraocular pressure (IOP) reduction (Delta IOP%), and patient's age. RESULTS: Six visual fields showed improvement in Delta S when evaluated globally and nine showed improvement in pre-S subgroups. Of the latter, all nine showed improvement in the subgroup with the lowest pre-S, and two in the intermediate subgroup, but none in the subgroup with the highest pre-S. Combining the subgroups with the lowest pre-S and the highest Delta IOP% was associated with the highest mean Delta S. CONCLUSION: The ability to document improvement in visual fields following surgical reduction of IOP may be enhanced by focusing on subgroups of test points with lower baseline sensitivity.

Long-term effect of Nd:YAG laser posterior capsulotomy on intraocular pressure.

OBJECTIVE: To study the long-term effect of Nd:YAG capsulotomy on intraocular pressure (IOP). METHODS: We reviewed the records of patients with bilateral pseudophakia who received Nd:YAG capsulotomy in only 1 eye. Using the Wilcoxon rank sum test, we compared the mean change in IOP in eyes before and after capsulotomy with that of the noncapsulotomy eyes at corresponding time intervals. Using multiple regression tests, we analyzed the factors significantly associated with postcapsulotomy long-term IOP increases. RESULTS: The study included 100 patients who were followed up for a median of 1.5 years after capsulotomy. The mean +/- SD age of the study group was 76+/-7 years, and 37 patients had glaucoma. The changes in IOP in the eyes treated with capsulotomy were significantly higher than those in noncapsulotomy eyes at each time interval following capsulotomy. The long-term IOP increase was significantly associated with the IOP increase measured 1 hour after the capsulotomy (P =. 001). Patients with glaucoma were more likely to require long-term additional glaucoma medication than were nonglaucoma patients to require initial glaucoma therapy after the capsulotomy (P =.002). CONCLUSION: After Nd:YAG capsulotomy, long-term IOP is often elevated above precapsulotomy baselines, especially in glaucoma patients or patients who experience a significant IOP increase within hours after the capsulotomy.

Visually significant cystoid macular edema in pseudophakic and aphakic patients with glaucoma receiving latanoprost.

PURPOSE: To investigate the incidence of visually significant cystoid macular edema associated with the use of latanoprost in patients with glaucoma after cataract surgery. PATIENTS AND METHODS: This is a multicenter, retrospective study of 185 patients, of whom 173 were pseudophakic (212 eyes) and 12 were aphakic (13 eyes), who were treated for glaucoma with latanoprost 0.005%. The posterior lens capsule was intact in 125 eyes, open or absent as a result of surgery in 25 eyes, and status-post-yttrium-aluminum-garnet capsulotomy in 75 eyes. Visual acuity was documented before and after initiating latanoprost therapy, and patients with a reduction of two or more lines on the Snellen chart were examined by fluorescein angiography for cystoid macular edema. RESULTS: Visual reduction was documented in four (2.16%) patients. Three of the four patients had cystoid macular edema, and the fourth was thought to have lost a central island of vision from glaucoma. The three patients with cystoid macular edema all had ruptured posterior capsules, requiring anterior vitrectomy, and one had a previous episode of cystoid macular edema 3 years before starting latanoprost therapy. CONCLUSION: These findings suggest that visually significant cystoid macular edema associated with latanoprost therapy in pseudophakic or aphakic patients is uncommon. If there is a cause-and-effect relationship between latanoprost therapy and clinically significant cystoid macular edema, the incidence appears to be low.

Influence of keratometric readings on comparative intraocular pressure measurements with Goldmann, Tono-Pen, and noncontact tonometers.

PURPOSE: To evaluate the influence of keratometric measurements on the concordance of intraocular pressure (IOP) readings with three applanation tonometers. PATIENTS AND METHODS: The IOPs of 404 eyes of 202 patients from a general eye clinic were measured by Goldmann, Tono-Pen XL, and noncontact Nidek NT 2000 tonometers. Differences in the IOP measurements between Goldmann and the other two tonometers (deltaIOPG-TP and deltaIOPG-NCT) were analyzed in the overall group and within three subgroups based on keratometry measures: flatter, intermediate, and steeper corneas (quartiles as cut-off points). Regression analysis of deltaIOP and keratometry measures was also performed. Right and left eyes were analyzed separately. RESULTS: The IOP readings taken with the Goldmann tonometer were significantly higher than those taken with either of the other two tonometers within the overall study population. The deltaIOP within the three keratometric subgroups was not statistically significant except for deltaIOPG-TP in the right eyes. Regression analysis showed that keratometry and deltaIOPG-TP and deltaIOPG-NCT had a significant but very weak coefficient of correlation in the right eye, but not in the left. CONCLUSION: Corneal curvature within the normal range does not have a clinically significant influence on the concordance of IOP readings obtained with Goldmann and Tono-Pen or noncontact tonometers.