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1.
Future Sci OA ; 9(2): FSO839, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37009052

RESUMO

Aim: This study aims to determine the prevalence of refractive errors among medical students in Jordan. Materials & methods: Cross-sectional model through an online questionnaire was conducted. The questionnaire was distributed randomly to 700 medical students. Results: Females participated more than males. It was revealed that 525 (75%) of the total students were found to have a refractive error. Myopia was the most common type. About 79.0% of students have a positive family history of refractive errors which was more significant in students with refractive errors. Spectacles were the most common used method of treatment. Conclusion: The prevalence of refractive errors was high among medical students in Jordan. A positive family history was associated with students having refractive errors.


Many reports have studied refractive errors and their risk factors in different groups and ethnicities. Also, types of refractive errors were found to have a different prevalence in different age groups. Whilst refractive errors in medical students have been studied in many countries, the prevalence of refractive errors has never been studied in Jordanian medical students before. In this study, we found that myopia (with or without astigmatism) was the most common type of refractive error in medical students.

2.
Cornea ; 42(8): 934-939, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36731078

RESUMO

PURPOSE: We aimed to compare the rate of 6-month endothelial cell loss (ECL) and 6-month graft survival in eyes that did not require a postoperative rebubble with eyes that did require a postoperative rebubble after Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A consecutive series of DMEK surgeries performed from September 2013 to March 2020 was retrospectively analyzed. Eyes that did not require a rebubble for graft detachment were compared with eyes with 1 rebubble and eyes with 2 or more rebubbles for 6-month ECL and graft survival. A subanalysis of the rebubble rate for different indications for transplantation was also performed. RESULTS: One thousand two hundred ninety-eight eyes were included in this study. The 6-month ECL for eyes with no rebubbles, 1 rebubble, and ≥2 rebubbles was 29.3% ± 16.2% (n = 793), 36.4% ± 18.6% (n = 97, P = 0.001), and 50.1% ± 19.6% (n = 28, P < 0.001), respectively. The 6-month graft survival rate for eyes with no rebubbles, 1 rebubble, and ≥2 rebubbles was 99.5%, 97.8% ( P = 0.035), and 81.8% ( P < 0.001), respectively. When compared to the rebubble rate for DMEK for Fuchs dystrophy (156/1165 eyes = 13.4%), the rebubble rates were statistically higher for DMEK for failed penetrating keratoplasty (28.5%, P = 0.021) and pseudophakic bullous keratopathy (28.0%, P = 0.036). CONCLUSIONS: Eyes undergoing any rebubble procedure in the postoperative period after DMEK have an increased risk of endothelial cell loss and graft failure at 6 months postoperative. DMEK in eyes for failed penetrating keratoplasty and failed DMEK had the highest rebubble rate, with the former reaching statistical significance.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Lâmina Limitante Posterior/cirurgia , Estudos Retrospectivos , Sobrevivência de Enxerto , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Células Endoteliais , Contagem de Células , Endotélio Corneano
3.
Cornea ; 40(8): 1024-1030, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33264145

RESUMO

PURPOSE: To determine whether using younger donor tissue for Descemet membrane endothelial keratoplasty (DMEK) surgery influences clinical outcomes. METHODS: Scroll tightness, unscrolling time, rebubble rate, and preoperative and 3- and 6-month postoperative endothelial cell density (ECD) and endothelial cell loss (ECL) were compared for 661 DMEK grafts prepared from younger (aged younger than 50 yrs, n = 81) and older donors (aged 50 yrs or older, n = 580) with Student t test, χ2 test, or Mann-Whitney U test. RESULTS: There was no difference in overall unscrolling time (younger donors: 3.1 ± 3.1 min, older donor: 2.9 ± 2.7 min, P = 0.503). Experienced faculty surgeons, compared with fellows, had a significantly lower unscrolling times for both younger donors (2.4 ± 2.3 vs. 4.6 ± 3.9 min, P = 0.002) and older donors (2.5 ± 2.1 vs. 3.7 ± 3.3 min, P <0.001). Rebubble rates were not statistically different between younger (12.3%) and older donors (15.0%, P = 0.527). Three-month ECD was higher in grafts from younger compared with that in those from older donors (2138 ± 442 vs. 1974 ± 470 cells/mm2, P = 0.024). Six-month ECD was similar for younger (1972 ± 509 cells/mm2) and older donors (1947 ± 460 cells/mm2, P = 0.585). There was no difference in 3- or 6-month ECL comparing younger (3-mo: 24.3% ± 13.4%; 6-mo: 31.1% ± 15.2%) with older donors (3-mo: 25.9% ± 15.5%, P = 0.489; 6-mo: 27.8% ± 15.1%, P = 0.231). CONCLUSIONS: DMEK grafts prepared from younger donors exhibited similar unscrolling times, rebubble rates, and 3- and 6-month ECL compared with older donors. Experienced surgeons might begin to accept DMEK grafts from younger donors with confidence.


Assuntos
Perda de Células Endoteliais da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Endotélio Corneano/transplante , Doadores de Tecidos , Acuidade Visual , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Perda de Células Endoteliais da Córnea/diagnóstico , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 99(45): e23139, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157995

RESUMO

The purpose is to determine if the preoperative central endothelial cell density (ECD) in triple (phacoemulsification plus intraocular lens implantation plus DSAEK) and non-triple Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) procedures have a relationship with the 5-year postoperative ECD or percent Endothelial Cell Loss (ECL).Out of 986 consecutive DSAEK surgeries for Fuchs dystrophy, 241 eyes had 5-year ECD measurements available. Endothelial cell densities were then evaluated against preoperative ECDs to obtain measures of ECL. Triple and non-triple procedures were isolated and compared independently.One hundred eighty two eyes had undergone a triple procedure and 59 had not. The mean ECD at 5 years was 1560 ±â€Š648 cells/mm for triples and 1483 ±â€Š621 cells/mm for non-triples (P = .42). Endothelial Cell loss was 44.4% ±â€Š21.7% and 44.4% ±â€Š22.0%, respectively for eyes that underwent a triple or non-triple (P = .99). There was a moderate, but significant correlation between preoperative ECD and the ECD at 5 years after DSAEK for both triples (r = 0.39, P < .001), and non-triples (r = 0.32, P = .01), respectively.In Descemets stripping automated endothelial keratoplasty grafts, higher preoperative donor ECD was correlated with higher ECD at 5 years postoperatively but was unaffected by a concurrent cataract surgery in the triple procedure.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Células Endoteliais/citologia , Distrofia Endotelial de Fuchs/patologia , Distrofia Endotelial de Fuchs/cirurgia , Implante de Lente Intraocular , Facoemulsificação , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Tempo
5.
Cornea ; 39(10): 1267-1273, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32558729

RESUMO

PURPOSE: To determine whether specific donor characteristics influence postoperative rebubble rate and 6-month endothelial cell loss (ECL) in Descemet membrane endothelial keratoplasty (DMEK). METHODS: A retrospective analysis of a consecutive series of 857 DMEK surgeries using eye bank-prepared donor tissue was performed between September 2013 and April 2018. DMEK graft characteristics including donor age, preoperative endothelial cell density (ECD), preservation time, death-to-preservation time, and donor diabetes status were analyzed for correlation with rebubble rate and 6-month postoperative ECL. Subgroup analyses of donor age, preoperative ECD, preservation time, death-to-preservation time, preparation-to-surgery time, and diabetes severity were also performed. Statistically significant relationships between donor characteristics and rebubble rate or 6-month postoperative ECL were determined using Pearson correlation, one-way analysis of variance, t test, and χ analysis. RESULTS: The overall rate of rebubble after 857 surgeries performed by 7 surgeons during the study period was 12.6%. There was no significant relationship between postoperative rebubble rate and donor age, preoperative ECD, preservation time, death-to-preservation time, preparation-to-surgery time, or donor diabetes status. The subgroup analysis of these characteristics also yielded no significant relationship with rebubble rate. There was also no significant relationship between 6-month postoperative ECL and analyzed donor factors. CONCLUSIONS: Donor characteristics such as higher donor age, lower preoperative ECD (<2500), longer preservation time, and donor diabetes did not increase the rebubble rate or the 6-month ECL after DMEK. These results indicate that common surgeon preferences for donor tissues that are younger, fresher, with higher cell count, and without diabetes do not translate into superior postsurgical outcomes.


Assuntos
Perda de Células Endoteliais da Córnea/fisiopatologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Complicações Pós-Operatórias , Doadores de Tecidos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Endotélio Corneano/patologia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto Jovem
6.
Cornea ; 39(10): 1261-1266, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32541187

RESUMO

PURPOSE: The purpose of this study was to compare the clinical outcomes from using eye bank-prepared, endothelium-out preloaded Descemet membrane endothelial keratoplasty (DMEK) tissue with those obtained with endothelium-out surgeon-loaded DMEK tissue using the same surgical technique at 1 site. METHODS: This study retrospectively reviewed 400 consecutive cases of DMEK from March 2016 to April 2018. The last 200 cases using surgeon-loaded tissue were compared with the first 200 cases using preloaded tissue. Statistical analysis was performed using the Wilcoxon signed-rank test, binomial logistic regression, Kruskal-Wallis 1-way analysis of variance, Student t test, or Pearson χ tests. RESULTS: Comparing surgeon-loaded versus preloaded DMEK tissue, respectively, no statistical difference was found in the mean 6-month postoperative values for endothelial cell loss (32.9% ± 18.5% vs. 29.9% ± 16.4%, P = 0.31), best corrected visual acuity (20/26 vs. 20/25, P = 0.54), or change in central corneal thickness (-14.4% ± 8.9% vs. -15.6% ± 11.7%, P = 0.43). The mean 1-year endothelial cell loss was also not significantly different (37.6% ± 17.2% vs. 33.2% ± 14.8%, P = 0.07). Overall, the rebubble rate for surgeon-loaded tissue was 17.5% and 12.5% for preloaded tissue, a statistically nonsignificant difference. Operative outcomes for mean tissue scroll tightness (1-4) and tissue unscroll time (minutes) for surgeon-loaded and preloaded tissue were similar between groups (2.4 vs. 2.2, P = 0.12 and 3.5 vs. 3.3 minutes, P = 0.50). CONCLUSIONS: Tissue that is trephinated, stained, and loaded into an injector by the eye bank and then shipped to the surgeon had no difference in clinical outcomes compared with tissue where the surgeon performs these steps. The safety and speed of using preloaded tissue should be considered by DMEK surgeons.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Bancos de Olhos/métodos , Oftalmologia/métodos , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Contagem de Células , Córnea/patologia , Distrofias Hereditárias da Córnea/cirurgia , Perda de Células Endoteliais da Córnea/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , Acuidade Visual/fisiologia
7.
Am J Ophthalmol Case Rep ; 18: 100686, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32292835

RESUMO

PURPOSE: To describe Descemet membrane endothelial keratoplasty (DMEK) cases complicated by spontaneous intraoperative fibrin formation. METHODS: DMEK surgeries performed at two centers using a standardized technique were reviewed retrospectively for the occurrence of intraoperative fibrin formation. Cases were assessed for recipient medical history, donor age, best spectacle-corrected visual acuity (BSCVA), intraoperative unscrolling time, 6-month endothelial cell loss (ECL), and the course of the mate donor cornea. RESULTS: In this review of 868 cases of standardized DMEK surgery with surgical peripheral iridotomy, 32 eyes of 29 patients (3.7%) were complicated by the formation of intraoperative fibrin formation, including 3 patients that developed fibrin in both eyes. Three of the 32 grafts failed (9.4%). None of the mate corneas transplanted (n = 27) developed complications related to fibrin. The donor age ranged from 51 to 75 years and recipient age ranged from 49 to 82 years (median, 66 years). Unscrolling time ranged from 1 to 105 min (median, 15 min). Nine eyes required one rebubble procedure. No eyes had vision-limiting comorbidities, and the 6-month BSCVA was ≥20/40 in all eyes. Six-month ECL ranged from 19% to 73% (median, 44%). CONCLUSIONS: We conclude that fibrin formation during DMEK surgery is an uncommon but important complication that can make graft manipulation more difficult, and may have deleterious effects on endothelial cell density and graft survival.

8.
Gerontol Geriatr Med ; 5: 2333721419855668, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276020

RESUMO

There is an emerging population of older adults living with HIV, and among them, Black older adults experience the greatest burden of the disease. This is a growing public health concern, as older adults are disproportionately diagnosed at a later stage of the disease, while reporting similar risk factors as younger adults. It has also been shown that the Black Church is well positioned to offer health screenings. Thus, this study aimed to assess HIV knowledge, beliefs, and risk behaviors of older church-affiliated Black adults. Data were collected from a sample of Black adults (N = 543) from four predominately Black churches in Kansas City, MO. Participants were surveyed on measures assessing demographic characteristics, HIV knowledge and attitudes, and HIV testing and risk behaviors. Results indicated that compared to younger Black adults, Black older adults were less knowledgeable about the transmission of HIV and were less willing to be tested for HIV in church settings. However, there was no significant difference on the perceived seriousness of HIV in the community. Results further showed that Black older adults were less likely to use condoms/barriers during the past 6 months and over their lifetime. We discuss the implications of results for HIV intervention programs.

9.
Medicine (Baltimore) ; 98(25): e16171, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232975

RESUMO

PURPOSE: To determine the relationship between anterior chamber depth (ACD) and percent endothelial cell loss (ECL) after Descemet Stripping Automated Endothelial Keratoplasty (DSAEK). METHOD: In 78 eyes receiving triple procedure (DSAEK combined with cataract extraction and posterior chamber intraocular lens (PCIOL) implantation), ACD was measured preoperatively with an intraocular lens (IOL) Master and ECL was calculated with specular microscopy at 6 months, 1, 2, 3, and 4 years postoperatively. ACD and ECL from all 78 eyes were compared using correlation analysis and students t test. Eyes were then separated into 2 groups based on ACD, group 1 with ACD < 3mm and group 2 with ACD ≥ 3mm. Students t test was then performed to compare group 1 and group 2 ECL at 6 months, 1, 2, 3, and 4 years postoperative. RESULTS: Mean ACD for all 78 eyes was 2.93 ±â€Š0.43 mm. Mean ECL was 32.7%, 27.6%, 29.6%, 32.5%, and 37.2% at 6 months, 1, 2, 3, and 4 years. No significant correlation between ACD and ECL was observed at any time point for the combined analysis of 78 eyes (P > .05). At 2 and 4 years postoperative, mean ECL was 32.6% ±â€Š16.1% and 43.0% ±â€Š23.2% in eyes with ACD < 3mm and 25.3% ±â€Š13.0% and 29.6% ±â€Š18.2% in eyes with ACD ≥ 3 mm (P = .041 at 2 years and .008 at 4 years). CONCLUSION: ACD and ECL were not directly correlated; however, there may be a threshold ACD in which shallower anterior chambers preoperatively result in greater donor ECL over time.


Assuntos
Perda de Células Endoteliais da Córnea/classificação , Transplante de Córnea/efeitos adversos , Endotélio Corneano/lesões , Pesos e Medidas , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Perda de Células Endoteliais da Córnea/fisiopatologia , Transplante de Córnea/métodos , Endotélio Corneano/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Facoemulsificação/efeitos adversos , Estudos Retrospectivos
10.
Cornea ; 38(10): 1322-1327, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31205156

RESUMO

PURPOSE: To determine whether Patent Blue V (PB) can be used as an alternative dye for staining Descemet membrane endothelial keratoplasty (DMEK) grafts. METHODS: DMEK grafts from donor corneas were stained with 2.5% PB for 4 minutes (n = 2), 2.5% PB for 10 minutes (n = 2), or 0.06% trypan blue (TB) for 4 minutes (n = 1). The stain intensity of the grafts was compared initially and at different time points over a 15-minute period of balanced salt solution wash using a grading scale based on a serial dilution series of PB. Three additional grafts were stained with 2.5% PB for 10 minutes and used in mock surgeries to assess stain retention after injection and manipulation in a donor eye model for 25 minutes. To assess the safety of PB, DMEK grafts were prepared from 10 pairs of corneas where one cornea was stained with 0.06% TB for 4 minutes and the mate cornea was stained with 2.5% PB for 10 minutes. The grafts were preloaded and stored for 5 days in Optisol-GS at 2°C to 8°C, and endothelial cell loss was quantified using Calcein-AM staining and FIJI segmentation by 2 masked readers. RESULTS: PB stain intensities were lighter than TB-stained grafts. Grafts stained with 2.5% PB for 10 minutes retained sufficient color for the 25-minute duration of mock surgery. The average endothelial cell loss for PB versus TB grafts was 21.6% ± 5.3% versus 20.2% ± 5.4% (P = 0.202) as determined by reader 1 and 23.6% ± 4.8% versus 21.2% ± 5.8% (P = 0.092) as determined by reader 2. CONCLUSIONS: PB is a viable alternative dye in DMEK grafts for applications where TB may not be available or approved for use.


Assuntos
Doenças da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Endotélio Corneano/transplante , Corantes de Rosanilina/farmacologia , Coloração e Rotulagem/métodos , Doadores de Tecidos , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Sobrevivência Celular , Corantes/farmacologia , Doenças da Córnea/diagnóstico , Endotélio Corneano/citologia , Bancos de Olhos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Coleta de Tecidos e Órgãos
12.
J Ocul Pharmacol Ther ; 35(2): 98-105, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30547709

RESUMO

PURPOSE: The purpose of these studies was (1) to investigate the ability of human M1 phenotype macrophages to secrete vascular endothelial growth factor (VEGF) and the influence of prostacyclin receptor (IP) stimulation (2) to evaluate the contribution of the proangiogenic prostanoid prostacyclin to experimental choroidal neovascularization Methods: Human macrophages derived from primary blood mononuclear cells were functionally biased toward the M1 phenotype by using tumor necrosis factor α (TNFα). Experimental choroidal neovascularization was produced by laser photocoagulation. Antagonist drugs RO-3244794 (IP antagonist) and GW 627368 (EP4 antagonist) were administered according to an optimal dosing regimen that was predetermined by bioavailability studies. RESULTS: IP receptor stimulation had diametrically opposed effects on VEGF release compared with reported data on cytokine/chemokine secretion from human macrophages. For example, the IP agonist cicaprost stimulated VEGF secretion although it inhibits monocyte chemoattractant protein-1 (MCP-1) secretion: both would favor a proangiogenic effect. The IP receptor antagonist RO-3244794 produced an ∼20% statistically significant reduction in the neovascularized lesion area in the choroidal neovascularization model, which was a similar level to that produced by the EP4 antagonist GW 627368. Combining the 2 drugs produced a statistically significant reduction in neovascularization but only of slightly greater magnitude than that obtained with each antagonist administered alone. CONCLUSIONS: IP receptor stimulation potently and highly efficaciously promoted VEGF release from human M1 macrophages, indicating a possible contribution of the M1 macrophage subtype to VEGF-induced choroidal neovascularization. Studies in living animals suggest that prostacyclin and its target IP receptor contribute to choroidal neovascularization, although to a more modest extent than might have been expected.


Assuntos
Anti-Hipertensivos/farmacologia , Neovascularização de Coroide/tratamento farmacológico , Epoprostenol/farmacologia , Macrófagos/efeitos dos fármacos , Soluções Oftálmicas/farmacologia , Animais , Células Cultivadas , Quimiocina CCL2/análise , Quimiocina CCL2/deficiência , Quimiocina CCL2/metabolismo , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , Ratos , Ratos Sprague-Dawley , Fatores de Crescimento do Endotélio Vascular/análise , Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Cornea ; 37(8): 981-986, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29863542

RESUMO

PURPOSE: To describe the technique, advantages, and early complication rates of using Descemet membrane endothelial keratoplasty (DMEK) donor tissue that is prestained and preloaded into an injector at the eye bank and delivered in a storage medium to the surgeon for transplantation 1 to 2 days later. METHODS: A total of 111 eyes with endothelial failure underwent DMEK using donors that were prestripped, prestained, S-stamped, and preloaded into a Straiko modified Jones tube and delivered in an Optisol-filled viewing chamber 1 to 2 days later. Scroll tightness, time to unscroll and center the tissue, postoperative rebubble rate, and graft failure rate were recorded. Endothelial cell density was measured at 3 and 6 months. RESULTS: All tissues remained well stained with easy visualization at the time of surgery (n = 111). The mean scroll tightness was 2.2 (range: 1-4). The mean time to center and unscroll the tissue was 3.5 minutes (range: 0.5-11.25 min). There was no primary graft failure. There were 16 cases with the placement of another bubble postoperatively (with a 14.4% rebubble rate). Of those 16 cases, 2 required a second rebubble. Endothelial cell loss at 3 and 6 months postoperatively was 26.7% (n = 63 eyes) and 30.9% (n = 67 eyes), respectively. CONCLUSIONS: This is the first report of the clinical use of prestained, preloaded tissue for DMEK. The characteristics and handling of the tissue were not different from those of surgeon-loaded tissue. Because punching, staining, and loading the graft intraoperatively is not necessary, the surgery time and risk of damaging donor tissue are reduced when using preloaded tissue.


Assuntos
Doenças da Córnea/cirurgia , Endotélio Corneano/transplante , Bancos de Olhos , Rejeição de Enxerto/prevenção & controle , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/métodos , Idoso , Contagem de Células , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia
14.
FASEB J ; 31(1): 368-375, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27770021

RESUMO

The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors. Established rodent models of ocular inflammatory diseases were used to determine therapeutic effects in living animals. The drugs were administered systemically after predetermination of their blood levels to ensure bioavailability at an appropriate dose level. Whereas compounds selective for a single prostanoid receptor typically exhibited modest but statistically significant inhibition, AGN 211377 profoundly inhibited S-antigen-induced uveitis and laser-induced retinal neovascularization. Consistent with previous polypharmacological studies on chemokine/cytokine release from human macrophages, the prostanoid EP1 receptor played a permissive role in suppressing neovascularization and inflammation in vivo Comparing AGN 211377 with a close structural congener lacking EP1 antagonism (AGN 197727), AGN 197727 was much less active than AGN 211377, but pronounced anti-inflammatory and angiostatic effects were achieved by adding the EP1 antagonist compound (SC-51322) to AGN 197727 in the systemic dosing regimen. Further, AGN 211377 produced superior anti-inflammatory activity compared with the nonsteroidal anti-inflammatory agent ketorolac. These results indicate the value of using a polypharmacological approach in the design of novel therapeutic agents in preference to compounds targeting a single receptor or enzyme. A compound such as AGN 211377 may represent more effective therapy than COX inhibitors in treating uveitis and ocular diseases where neovascularization is a significant part of the pathology.-Woodward, D. F., Wang, J. W., Ni, M., Bauer, A., Martos, J. L., Carling, R. W., Poloso, N. J. In vivo studies validating multitargeting of prostanoid receptors for achieving superior anti-inflammatory effects.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Cinamatos/farmacologia , Neovascularização Patológica/prevenção & controle , Receptores de Prostaglandina/antagonistas & inibidores , Animais , Doenças Autoimunes , Sinalização do Cálcio , Lasers/efeitos adversos , Ratos , Ratos Endogâmicos Lew , Retina/patologia , Retina/efeitos da radiação , Vasos Retinianos/patologia , Vasos Retinianos/efeitos da radiação , Uveíte/tratamento farmacológico , Uveíte/etiologia
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