Diabetic retinopathy remains the leading vascular-associated cause of blindness throughout the world. Its treatment requires a multidisciplinary interventional approach at both systemic and local levels. Current management includes laser photocoagulation, intravitreal steroids, and anti-vascular endothelial growth factor (VEGF) treatment along with systemic blood sugar control. Anti-VEGF therapies, which are less destructive and safer than laser treatments, are being explored as primary therapy for the management of vision-threatening complications of diabetic retinopathy such as diabetic macular edema (DME). This review provides comprehensive information related to VEGF and describes its role in the pathogenesis of diabetic retinopathy, and in addition, examines the mechanisms of action for different antiangiogenic agents in relation to the management of this disease. Medline (Pubmed) searches were carried out with keywords “VEGF”, “diabetic retinopathy”, and “diabetes” without any year limitation to review relevant manuscripts used for this article.

The 582 data collected from Central, Zonal and District level Hospitals, which occurred from Magh 2057 to Poush 2058 produced significant results. Various parameters (age, sex, marital status, time of ingestion, month of occurrence, Agent responsible for the incidence, type of poisoning, outcome and duration of treatment) were analyzed. Similarly the pattern of frequency distribution of the above-mentioned parameter in central, zonal and district level of hospitals were compared.Hypothesis were made and tested. Females were found to be more susceptible to the intentional incidence than male (p = 0.000). Intentional poisoning for unmarried male was found to be more (34%) than for female. On the contrary, intentional poisoning in female was high in case of married subjects (57%)(p = 0.000). The most common type of poisoning causing the intentional attempt was organophosphates (40%) followed by Phosphides (14%). On the other hand unintentional poisoning was most common due to the unclassified and other agents (8%), which were followed by hydrocarbons (6.3%). (p = 0.000). The most common organophosphate used for intentional attempt for poisoning is methyl parathion (31%) when compared with other groups of organophosphates (26%). Sedative and hypnotics were the most common type of drugs (43%) used for intentional attempt. Nighttime incidence was more frequent (31%). Homicidal poisoning occurring in both central and district hospital were equal being 3.6% of the total types of attempt of incidence. Most of the cases as obvious were found to be cured (84.8% out of total cases). The zonal hospital shows the highest cure rate (89.2%) followed by district hospital (74.2%)-the comparison however excludes central level hospitals. The mortality however is similar in both hospitals (4.4% and 4.5% respectively in zonal and district hospitals).Accidental intake of hydrocarbon was found to be most frequent in the children (33%) while intentional intakes of other agents were more frequent in adults (97%). The rainy season was the most common season for the attempt of intentional incidence (47.8%) adding to mortality. The most common age group of subjects exposed to intentional attempt that adds to the mortality is 15-24 years (39.1%). The TYPE, primarily adding to mortality was intentional intake (91.3%) (p = 0.008). Most of the intentional incidence adding to mortality is caused by organophosphates (66.7%) followed by Phosphides (19%). Subjects between age group 15-24 are more likely to cause the intentional exposure (44%) while children below five years are more likely to cause accidental KATHMANDU UNIVERSITY JOURNAL OF SCIENCE, ENGINEERING AND TECHNOLOGY VOL. I, No. V, SEPTEMBER 2008, pp 40-48. 41 exposure (6%) (p = 0.000). Seasonal comparison showed a high incidence in rainy season (24%) as compared to that of autumn (23%).

Free radicals are formed as a part of normal metabolic activities but are neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining the redox balance. This redox balance is disrupted in certain neuropathophysiological conditions, causing oxidative stress, which is implicated in several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression is also caused by excessive production of free radicals. Highly reactive free radicals, mainly the reactive oxygen species (ROS) and reactive nitrogen species (RNS), damage the cell membrane, proteins, and DNA, which triggers a self-propagating inflammatory cascade of degenerative events. Dysfunctional mitochondria under oxidative stress conditions are considered a key mediator in progressive neurodegeneration. Exogenous delivery of antioxidants holds promise to alleviate oxidative stress to regain the redox balance. In this regard, natural and synthetic antioxidants have been evaluated. Despite promising results in preclinical studies, clinical translation of antioxidants as a therapy to treat neurodegenerative diseases remains elusive. The issues could be their low bioavailability, instability, limited transport to the target tissue, and/or poor antioxidant capacity, requiring repeated and high dosing, which cannot be administered to humans because of dose-limiting toxicity. Our laboratory is investigating nanoparticle-mediated delivery of antioxidant enzymes to address some of the above issues. Apart from being endogenous, the main advantage of antioxidant enzymes is their catalytic mechanism of action; hence, they are significantly more effective at lower doses in detoxifying the deleterious effects of free radicals than nonenzymatic antioxidants. This review provides a comprehensive analysis of the potential of antioxidant therapy, challenges in their clinical translation, and the role nanoparticles/drug delivery systems could play in addressing these challenges.

Abstract. Recently, the use of triamcinolone acetonide (TA) injection has increased dramatically in treatment for several ocular diseases. Among them, macular diseases such as macular edema due to diabetic retinopathy, venous occlusive diseases, ocular inflammation and age-related macular degeneration (AMD) are very common vision threatening disorders and are great challenges to treat. In these types of chronic retinal diseases, repeated intraocular injections of TA are often required which increases the likelihood of complications. In order to achieve sustained-release, maintain therapeutic levels of TA over longer times and reduce frequency of intravitreal injections, researchers are investigating different implantable devices or injectable systems. However, as of yet, there is no sustained-release product for TA available on the commercial market. This review discusses and compares different sustained-release devices or injectable systems that are currently being developed.

Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL.min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL.min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL.min). Tmax (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.