Knowledge, Attitudes, and Practices in Antibiotic Dispensing amongst Pharmacists in Trinidad and Tobago: Exploring a Novel Dichotomy of Antibiotic Laws.

The inappropriate consumption, use, and dispensing of antibiotics are problems faced globally, with a pattern of inappropriate consumption differing in higher-income countries due to the ease of accessibility of antibiotics. The main drivers of consumption and inappropriate use are the over-the-counter sales of antibiotics by pharmacies. Trinidad and Tobago (T&T), a twin island state in the Caribbean, has two Acts of Parliament that regulate antibiotics: the Antibiotics Act and the Food and Drug Act, yet the Over-the-Counter (OTC) sale of antibiotics still exists. This study sought to determine the knowledge, attitudes, and practices regarding the OTC dispensing of antibiotics in T&T. A cross-sectional study gathered data from pharmacists in both the private and public sectors of Trinidad over 7 months. The results showed that antibiotic resistance and antibiotic abuse were seen as significant problems. The level of experience, gender (female), and age (younger) were significantly associated with having good overall knowledge of good dispensing habits and antibiotic laws (p = 0.036, p = 0.047, and p = 0.001, respectively). Pharmacists generally agreed that antibiotics under the Food and Drug Act may have contributed to OTC dispensing in the private sector (p = 0.013) and that all antibiotics should be under the Antibiotic Act (p = 0.002). Additionally, it was found that the dispensing of antibiotics OTC in the private sector (p = 0.006) occurred: without doctors' advice and without requesting prescriptions; because it was perceived as lawful (especially by older pharmacists); and because of the perceived motivation of profit. Regulation enforcement was perceived as deficient. OTC dispensing for reasons, such as misunderstanding of laws, occurs in T&T.

miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

Liver Transplantation for Acute Liver Failure due to Yellow Fever: A Case Report.

Yellow fever is a noncontagious disease caused by an arbovirus in the Flaviviridae family. It is an endemic disease in the tropical forests of Africa and South America, with the mosquito as a vector. Approximately half of those infected will be asymptomatic, while 15% will develop the severe/malignant form of the disease that includes renal and hepatic failure, bleeding, and neurological impairment as the principal symptoms. The lethality of the severe form reaches up to 70%. The objective of this study was to report on the case of a patient who was transferred to the hepatobiliary unit of our service due to acute liver failure due to yellow fever. He was treated with liver transplantation. The patient progressed satisfactorily, being discharged from the intensive care unit in 10 days and discharged from the hospital within 19 days after transplantation. Despite the encouraging result of our team, this has not been applied to other centers that have also performed this modality of treatment; therefore, the question remains as to whether and when to recommend liver transplantation for treatment of severe yellow fever.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks (AU)

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Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments.

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks.

Quantitative identification of dynamical transitions in a semiconductor laser with optical feedback.

Identifying transitions to complex dynamical regimes is a fundamental open problem with many practical applications. Semi- conductor lasers with optical feedback are excellent testbeds for studying such transitions, as they can generate a rich variety of output signals. Here we apply three analysis tools to quantify various aspects of the dynamical transitions that occur as the laser pump current increases. These tools allow to quantitatively detect the onset of two different regimes, low-frequency fluctuations and coherence collapse, and can be used for identifying the operating conditions that result in specific dynamical properties of the laser output. These tools can also be valuable for analyzing regime transitions in other complex systems.

BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB.

Impact of model for end-stage liver disease score on long-term survival following liver transplantation for hepatocellular carcinoma.

BACKGROUND AND AIMS: Survival rates after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have significantly increased after Milan criteria and Model for End-Stage Liver Disease (MELD) score implementation. However, few studies have reported this survival in countries with organ donor shortages over a period of 10 years and long waiting lists. METHODS: This retrospective analysis of clinical data from 93 consecutive HCC patients who underwent OLT from June 2001 to September 2011 excluded 22 who underwent living donor liver transplantation (LDLT). Seventy-one deceased donor liver transplantations (DDLT) were evaluated before and after the MELD era. Kaplan-Meier analysis was used to plot survival rates. The follow-up was 2 months to 10 years. RESULTS: The overall survival and recurrence rates at 10 years were 67% and 12.2%, respectively. After MELD, patient survival at 5 years decreased from 70% to 64% and the recurrence rate decreased from 15.3% to 12.5%. The most frequent recurrence sites were lung and liver. CONCLUSION: In our center MELD score implementation had a small impact on long-term survival post OLT for HCC.

Notch-mediated induction of N-cadherin and α9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells.

BACKGROUND: Rhabdomyosarcoma (RMS) is the commonest type of soft-tissue sarcoma in children. Patients with metastatic RMS continue to have very poor prognosis. Recently, several works have demonstrated a connection between Notch pathway activation and the regulation of cell motility and invasiveness. However, the molecular mechanisms of this possible relationship remain unclear. METHODS: The Notch pathway was manipulated pharmacologically and genetically. The mRNA changes were analysed by quantitative PCR and protein variations by western blot and immunofluorescence. Finally, the capabilities of RMS cells to adhere, heal a wound and invade were assessed in the presence of neuronal cadherin (N-cadherin)- and α9-integrin-blocking antibodies. RESULTS: Cells treated with γ-secretase inhibitor showed lower adhesion capability and downregulation of N-cadherin and α9-integrin. Genetic manipulation of the Notch pathway led to concomitant variations in N-cadherin and α9-integrin. Treatment with anti-N-cadherin-blocking antibody rendered marked inhibition of cell adhesion and motility, while anti-α9-integrin-blocking antibody exerted a remarkable effect on cell adhesion and invasiveness. CONCLUSION: Neuronal cadherin and α9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion, pointing to these proteins and the Notch pathway itself as interesting putative targets for new molecular therapies against metastases in RMS.

Translocaciones cromosómicas en los sarcomas de partes blandas: de la biología molecular a la aplicación clínica / Chromosomal translocations in soft tissue sarcomas: from molecular biology to clinical application

Los avances recientes en el campo de la biología molecular de los sarcomas pediátricos, en especial el descubrimiento y caracterización de translocaciones cromosómicas específicas, han sentado las bases para la implantación de nuevas herramientas diagnósticas. En esta revisión se repasan las principales translocaciones asociadas a tumores pediátricos y se resumen sus características moleculares en relación a su capacidad oncogénica, su posible utilidad como herramientas de diagnóstico diferencial así como su posible relación con parámetros clínicos(AU)

Recent advances in the knowledge of the molecular biology of paediatric sarcomas, especially the characterisation of chromosomal translocations associated specifically with particular types of cancer, have established bases for the introduction of new diagnostic tools. This article reviews the main chromosomal translocations associated with paediatric tumours, and summarises their molecular characteristics regarding their oncogenic capabilities, possible usefulness as a differential diagnostic tools and possible correlation with clinical parameters(AU)

[Chromosomal translocations in soft tissue sarcomas: from molecular biology to clinical application]. / Translocaciones cromosómicas en los sarcomas de partes blandas: de la biología molecular a la aplicación clínica.

Recent advances in the knowledge of the molecular biology of paediatric sarcomas, especially the characterisation of chromosomal translocations associated specifically with particular types of cancer, have established bases for the introduction of new diagnostic tools. This article reviews the main chromosomal translocations associated with paediatric tumours, and summarises their molecular characteristics regarding their oncogenic capabilities, possible usefulness as a differential diagnostic tools and possible correlation with clinical parameters.

Tuberculosis in liver transplant recipients: prophylaxis in an endemic area.

BACKGROUND: Tuberculosis (TB) has a high prevalence in Brazil. The scenario of liver transplantation (LT) creates challenges: atypical presentation, treatment hepatotoxicity, and increased mortality. The majority of TB cases after transplantation represent reactivation of latent infections; therefore, prophylaxis (PX) plays a major role. The aim of this study was to evaluate the benefits of PX after LT based on a pretransplantation tuberculin test (TT) in an endemic area. METHODS: Retrospective analysis of medical data from 376 adult cirrhotic patients undergoing OLT from 2001 to 2009. RESULTS: Among 191 selected patients, 137 (71%) showed a pretransplant TT including 41 (30%) with a TT ≥5 mm. The 17 (40%) of these patients who were prescribed PX did not experience TB. Prophylaxis was discontinued in 5 patients (20%) owing to suspicion of hepatotoxicity (medium serum alanine transaminase 175 U/L). In the group without PX, we diagnosed 1 case of pulmonary TB. The overall prevalence of anergic patients in the cirrhotic phase was 65% and prevalence of TB 1%. CONCLUSIONS: The prevalence of TB was similar to that reported in the literature, but positivity to TT was higher (34% vs 25%), possibly because of the endemicity of the area. There was a lower prevalence of extrapulmonary disease and no mortality. No patient undergoing PX with isoniazid, although incomplete due to suspicion of hepatotoxicity displayed TB. One patient without PX was affected by TB. The drug was effective but not always safe.

Vascular complications after living donor liver transplantation: a Brazilian, single-center experience.

BACKGROUND: In living donor liver transplantation (LDLT), vascular complications are more frequently seen than in deceased donor transplantation. Early arterial, portal vein, or hepatic vein thromboses are complications that can lead to graft loss and patient death. The aim of this study was to assess the incidence, treatment, and outcome of vascular complications after LDLT in a single Brazilian center. METHODS: Between December 2001 and December 2010, we performed 130 LDLT. Sixty-four recipients were children (27 weighing <10 kg). RESULTS: Nine recipients had vascular complications. Hepatic artery thrombosis (HAT) occurred in 4 (3.1%), portal vein thrombosis (PVT) in 3 (2.3%), and hepatic vein thrombosis (HVT) and hepatic arterial stenosis (HAS) in 1 (0.8%) patient each. Complications were identified by Doppler and confirmed by angiography or angiotomography. Patients with HAT were listed for retransplantation. One died before retransplant. Two children were submitted to retransplantation; one is still alive, with neurologic sequelae. One adult with HAT was retransplanted with a deceased donor graft and is doing well 58 months after surgery. Two patients with PVT died as a consequence of graft malfunction. In the other case, portal vein arterialization was performed, but patient died 11 months posttransplant. HVT was detected after cardiac reanimation and was treated with an endovascular stent. This patient died 3 months after LDLT. HAS was diagnosed after liver abscess development and was successfully treated by endovascular angioplasty. No recurrence was observed after 22 months. Follow-up ranged from 9 to 117 months. CONCLUSION: Pediatric patients are more prone to develop vascular complications after LDLT. Long-term survival was statistically lower for recipients with vascular complications (33.3% vs 77.7%; P = .008).

Cellulitis and nodular skin lesions due to Fusarium spp in liver transplant: case report.

Fusariosis is one of the emerging invasive fungal infections over the last decade. However, its recent rise has been in its ability to produce disseminated infection in severely immunosuppressed patients with neutropenia. In solid organ transplantation, fusariosis remains an uncommon picture mainly with nodules, subcutaneous abscesses, ulcers, or necrotic skin lesions resembling erthyma gangrenosum. Herein, we have reported a case of cellulitis, subcutaneous nodules, and abscesses due to Fusarium spp in a liver transplantation patient who was successfully treated with polyenes and surgical resection.

Methylene blue used as a bridge to liver transplantation postoperative recovery: a case report.

Hepatopulmonary syndrome is defined as a triad of liver disease, arterial hypoxemia, and intrapulmonary vascular dilatation. The clinical hallmark of this disorder is the impairment of pulmonary gas exchange, not necessarily correlated with the severity of the underlying liver disease. Liver transplantation (OLT) is the only definitive treatment for this syndrome. However, patients with preoperative partial pressure of arterial oxygen (PaO(2)) under 50 mm Hg are exposed to an unacceptably high postoperative mortality and morbidity. Herein we have described a case of a 15-year-old female patient who underwent OLT and was treated with methylene blue in the early postoperative period to improve hypoxemia. We suggest that the use of methylene blue after liver transplantation can decrease postoperative complications and mortality rates in these patients.

Treatment for recurrent hepatitis C virus infection after liver transplantation.

Cirrhosis due to hepatitis C virus (HCV) infection is the current leading indication for orthotopic liver transplantation (OLT) in the world. This series reports our program's experience with the treatment of HCV infection after the development of histological hepatitis. Between March 2002 and June 2008, patients with recurrent HCV were selected for treatment if the liver biopsy showed at least the F2 degree of Metavir score. HCV viral load was measured at 4, 12 and 24 weeks as well as at the end of treatment and at 6 months thereafter for patients who became HCV RNA negative (sustained virological response [SVR]). In this period, we performed 287 liver transplantations in 279 patients, including 117 (42%) who had HCV cirrhosis as the indication for OLT of whom 25 were eligible for antiviral treatment. Twelve patients completed treatment, 7 remain on treatment, and 6 were discontinued. The principal collateral effect was anemia. Only 1 patient had an episode of acute cellular rejection, which responded to adjustment of immunosuppression. Antiviral treatment in transplanted patients was feasible and did not seem to induce severe immunological effects. Adjuvant therapies to reduce cytopenias are frequently required, principally erythropoietin. The best results were observed with the pegylated interferon alfa (PEG) plus ribavirin (RBV) group: 38.9% of SVR. We recommend antiviral treatment of eligible patients with confirmed HCV recurrence using PEG plus RBV.

Liver transplantation for acute liver failure: trying to define when transplantation is futile.

BACKGROUND: Recently, the model of end-stage liver disease (MELD) index has been used to select patients with acute liver failure (ALF) or transplantation. By the time the indication for orthotopic liver transplantation (OLT) is defined, the patient's clinical status may worsen. OBJECTIVE: In this study, MELD was used to define patients beyond OLT. METHODS: Among adult patients ALF was responsible for 17 OLT. Their medical records were reviewed to calculate the MELD score just before the OLT. MELD of the deceased patients after OLT (group 1, n=8), was compared with the MELD score of living recipients (group 2, n=9). Creatinine level, need for dialysis, use of vasoactive amines, and mechanical ventilation before OLT were also analyzed in these groups. A significant difference was defined when P<.05. RESULTS: The mean MELD score+/-SD was 51.86+/-12.3 for group 1, and 38.47+/-7.1 for group 2 (P=.02). There was no difference between the creatinine values for patients in the 2 groups (P=.20). Also, the use of vasoactive amines or the need of dialysis before OLT were not different (P=.12 and P=.25, respectively). Group 1 was more frequently under mechanical ventilation, and showed a 4.29 relative risk for death after OLT. CONCLUSION: MELD score could be useful to define the prognosis of OLT among patients with ALF.

Prevalencia de disfunción diastólica en los pacientes hipertensos de nuevo diagnóstico y sin tratamiento / Prevalence of diastolic dysfunction in non-treated, newly diagnosed hypertensive patients

Objetivo. El propósito de este estudio observacional es conocer la prevalencia de disfunción diastólica (DD) en los pacientes hipertensos de nuevo diagnóstico y sin tratamiento. Pacientes y métodos. Se han incluido 105 pacientes (69 varones y 36 mujeres), con una edad media de 51,11 años los hombres y 54,25 años las mujeres, con hipertensión arterial de nuevo diagnóstico y sin tratamiento antihipertensivo. El estudio tuvo lugar entre junio de 2002 y junio de 2003. Fueron excluidos los pacientes con cardiopatía isquémica, hipertrófica, valvular, dilatada, fibrilación auricular y enfermedad pulmonar obstructiva crónica (EPOC) evolucionada. A todos los pacientes se les practicó un ecocardiograma doppler. Se consideró que existía DD del ventrículo izquierdo al registrarse al menos dos de los siguientes parámetros ecocardiográficos: tiempo de relajación isovolumétrica (TRIV) > 100 mseg, tiempo de desaceleración de la onda E (TDE) > 250 mseg y cociente E/A 130 g/m2 y en mujeres > 110 g/m2. Resultados. El 60 % de los pacientes estudiados tenían parámetros de DD en el ecocardiograma. El 37,1 % presentaban patrón de DD sin hipertrofia ventricular izquierda (HVI), el 16,2 % presentaban patrón de DD con HVI y un 6,7 % presentaban HVI y patrón de DD por mala relajación del VI. Se observaba una clara correlación entre la presencia de DD y la edad, presión arterial sistólica (PAS), presión del pulso (PP) y el índice de masa corporal (IMC), no encontrándose relación con el sexo y otras variables estudiadas (diabetes, insuficiencia renal, dislipemia, presión arterial diastólica [PAD] y frecuencia cardíaca [FC]). Conclusiones. La prevalencia de la DD valorada por ecocardiograma doppler en pacientes hipertensos de nuevo diagnóstico es muy elevada (60%), observando una correlación directa con la edad de los pacientes, PAS, PP y el IMVI

Objective. This study aims to evaluate the prevalence of diastolic dysfunction (DD) in newly diagnosed hypertensive patients without treatment. Patients and method. 105 patients (69 men and 36 women), with a mean age of 51.11 years in men and 54.25 years in women, with newly diagnosed hypertension and without treatment have been included. The study took place between June 2002 and June 2003. Exclusion criteria were ischemic heart disease, hypertrophy, valvular disease, dilated heart disease, atrial fibrillation and fully-developed COPD. A doppler echocardiogram was practiced on all patients. Diastolic dysfunction was considered to exist if two of the following echocardiographic parameters were found: isovolumetric relaxing time (TRI-V) > 100 ms, deceleration time of the E wave (TDE) > 250 ms, early filling rate peak/late filling rate peak ratio (E/A) 130 g/m2 in men and > 110 g/m2 in women. Results. A total of 60 % of patients had DD parameters and 37.1 % had DD without Left Ventricular Hypertrophy (LVH); 6.7 % had LVH and DD due to impaired relaxation of the left ventricle. There is a clear correlation between DD and age, Systolic Blood Pressure (SBP), Pulse Pressure (PP) and Body Mass index (BMI). We found no relationship with gender and other variables (heart rate, diabetes, renal insufficiency, dyslipidemia, diastolic blood pressure). Conclusion. The prevalence of DD evaluated by doppler echocardiogram is very high in newly diagnosed hypertensive patients (60 %), a direct correlation being observed with the patient's age, SBP, PP and LVMI

[Oxidative stress in a model of experimental diabetic retinopathy: the utility of peroxinytrite scavengers]. / Estrés oxidativo en un modelo de retinopatía diabética experimental II: utilidad de agentes secuestrantes de peroxinitritos.

PURPOSE: The retina is the neurosensorial tissue of the eye and is extremely rich in polyunsaturated lipid membranes. This feature makes it especially sensitive to oxygen and/or nitrogen activated species and lipid peroxidation. Several authors have postulated the importance of superoxide (O2-) and peroxynitrite production in the development of diabetic complications. In the present study, we have used two different antioxidants, ebselen and lutein, that present as a common feature their peroxynitrite scavenging capacity, to ameliorate the oxidative stress that exists in the retina in diabetic patients. METHODS: Hyperglycemia was accomplished by the intraperitoneal injection of Alloxan in a mouse model of diabetic retinopathy. Malondialdehyde (MDA) and glutathione (GSH) concentrations in eye homogenates (without the lens) were determined. We also recorded serial electroretinograms (ERG) and measured latency and implicit times. RESULTS: The MDA concentration increased and the GSH concentration decreased in the eyes of the diabetic animals. Treatment with ebselen and lutein restored the MDA and GSH concentrations to control values. Latency and implicit times were not affected by the diabetes. CONCLUSION: New studies are required to better understand the protective mechanism of ebselen and lutein in this model of experimental diabetic retinopathy.