Alterations in the polysialylated neural cell adhesion molecule and retinal ganglion cell density in mice with diabetic retinopathy

AIM: To investigate the impact of polysialylated neural cell adhesion molecule (PSA-NCAM) on the survival of retinal ganglion cells (RGCs) in the experimentally induced diabetes in mice. METHODS: Diabetes was induced in 2.5 months old Swiss Webster mice by intraperitoneal injection of streptozotocin (STZ, 90 mg/kg) once daily for two consecutive days. Examination of the proteins of interest in the retinas from diabetic mice at 2mo after diabetes induction was performed using immunohistochemistry and Western blot analysis. RGCs were counted in the wholemounted retinas, and Brn3a marker was used. RESULTS: Examination of retinas from diabetic mice at 2mo after diabetes induction revealed a considerable reduction in RGC density. Our experiments also demonstrated a redistribution of PSA-NCAM in the retina of diabetic animals. PSA-NCAM immunoreactivity was diminished in the inner part of the retina where RGCs were located. In contrast, an enhanced PSA-NCAM immunoreactivity was detected in the outer layers of the retina. PSA-NCAM signal was co-localized with glial fibrillary acidic protein immunoreactivity in the Müller cell branches. Previous studies have shown that matrix metalloproteinase-9 (MMP-9) is responsible for the reduction in PSA-NCAM levels in neuronal cells. The reduced levels of PSA-NCAM in inner layers (nerve fiber layer, ganglion cell layer) were accompanied by the increased expression of MMP-9. In contrast, in the outer retinal layers, the expression of MMP-9 was much less pronounced. CONCLUSION: MMP-9 induces PSA-NCAM shedding in the inner part of the retina and the decreased level of PSA-NCAM in the inner part of the retina might be, at least in part, responsible for the loss of RGCs in diabetic mice

Analysis of potential interactions between warfarin and prescriptions in Estonian outpatients aged 50 years or more

In Estonia, warfarin is widely prescribed by general practitioners to prevent and treat thromboembolic diseases. To date, there has been no systematic analysis of the potential risk of warfarin interactions with other drugs in the outpatient population. Objective: The aim of the study was to analyze the incidence of potential interactions in prescription schemes in Estonia in a cohort of outpatients receiving warfarin treatment. Methods: The retrospective study population included 203,646 outpatients aged 50 years or older of whom 7,175 received warfarin therapy. Patients who had used at least one prescription drug for a minimum period of 7 days concomitantly with warfarin were analyzed. Potential drug interactions were analyzed using Epocrates online, Stockley�s Drug Interactions and domestic drug interaction databases. Results: The average number of drugs used concomitantly with warfarin was 4.8 (SD=1.9) (males: 4.7 SD=2.0, females: 4.9 SD=2.0). No potential interactions in treatment regimens were found in 38% of patients, one potential interaction was observed in 29% and two or more potential interactions were observed in 33% of patients. The mean number of all potential interactions was 1.2 per patient and about the same in men and women. Potential interactions were associated with the number of drugs. Warfarin-related interactions were detected in 57% of patients, and the number of interactions related to warfarin per patient varied from 1 to 5. Most frequent were use of warfarin with NSAIDs (14%), followed by simvastatin (9%) and amiodarone (7%). Conclusion: This study shows that 57% of outpatients in Estonia receiving warfarin have drugs potentially interacting with warfarin in their treatment schemes. Most interactions (14%) with warfarin are associated with the prescription of NSAIDs.En Estonia, la warfarina es prescrita por médicos generales para tratar enfermedades tromboembólicas. Hasta la fecha, no se ha realizado un análisis sistemático del riesgo de interacciones potenciales de la warfarina con otros medicamentos en la población ambulatoria. Objetivo: El objetivo de este estudio fue analizar la incidencia de interacciones potenciales en los esquemas prescritos en Estonia en una cohorte de pacientes ambulatorios recibiendo warfarina. Métodos: El estudio retrospectivo incluyó 203.646 pacientes ambulatorios de 50 o más años de los que 7.175 recibían tratamiento con warfarina. Se analizó a los pacientes que usaron como mínimo un medicamento de prescripción por un periodo mínimo de 7 días concomitante con warfarina. Las interacciones potenciales fueron analizadas usando Epocrates online, Stockley�s Drug Interactions, y bases de datos locales de interacciones. Resultados: El numero medio de medicamentos usados concomitantemente con warfarina fue de 4,8 (DE=1,9) (hombres 4,7 DE=2,0; mujeres 4,9 DE=2,0). No se encontraron interacciones potenciales en el 38% de los pacientes, se observó una interacción potencial en el 29%, y se encontraron dos o más interacciones potenciales en el 33% de pacientes. El número medio de interacciones potenciales fue de 1,2 por paciente, prácticamente igual en hombres y en mujeres. Las interacciones potenciales estaban asociadas con el número de medicamentos. Se detectaron interacciones relacionadas con la warfarina en el 57% de los pacientes, y el número de interacciones relacionadas con warfarina varió de 1 a 5. Las más frecuentes fueron el uso de warfarina con AINE (14%), seguidas de sinvastatina (9%) y amiodarona (7%). Conclusión: Este estudio muestra que el 57% de los pacientes ambulatorios que reciben warfarina en estonia tienen medicamentos potencialmente interaccionando con la warfarina en sus esquemas terapéuticos. La mayoría de las interacciones (14%) con warfarina estaban asociadas a los AINE

Potential drug interactions with statins: Estonian register-based study

In Estonia, HMG-CoA reductase inhibitors are widely used to modify lipid levels but there are no current data on additional medicines prescribed alongside the statins. The aim of this study was to identify the frequency of potential clinically relevant interactions at a national level among an outpatient population treated with statins between January and June 2008, based on the prescription database of the Estonian Health Insurance Fund. This retrospective prevalence study included 203,646 outpatients aged 50 years or older, of whom 29,367 received statin therapy. The study analysed individuals who had used at least one prescription medicine for a minimum of 7 days concomitantly with statins. Potential drug interactions were analysed using Epocrates online, Stockley’s Drug Interactions, and the drug interaction database developed in Estonia. Statins metabolised by the CYP3A4 isoenzyme were prescribed to 64% of all statin users. Medicines known to have potentially clinically significant interactions with statins were prescribed to 4.6% of patients