Comparison of Travoprost and Bimatoprost plus timolol fixed combinations in open-angle glaucoma patients previously treated with latanoprost plus timolol fixed combination

To compare the ocular hypotensive effect of bimatoprost plus timolol and travoprost plus timolol fixed combinations in glaucoma patients whose disease was controlled but had not reached their target intraocular pressure (IOP) with the fixed combination of latanoprost plus timolol

A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

A Scoping Review of Quality of Life Questionnaires in Glaucoma Patients

PRECIS: Multiple questionnaires exist to measure glaucoma's impact on quality of life (QoL). Selecting the right questionnaire for the research question is essential, as is patients' acceptability of the questionnaire to enable collection of relevant patient-reported outcomes. PURPOSE: QoL relating to a disease and its treatment is an important dimension to capture. This scoping review sought to identify the questionnaires most appropriate for capturing the impact of glaucoma on QoL. METHODS: A literature search of QoL questionnaires used in glaucoma, including patient-reported outcomes measures, was conducted and the identified questionnaires were analyzed using a developed quality criteria assessment. RESULTS: Forty-one QoL questionnaires were found which were analyzed with the detailed quality criteria assessment leading to a summary score. This identified the top 10 scoring QoL questionnaires rated by a synthesis of the quality criteria grid, considering aspects such as reliability and reproducibility, and the authors' expert clinical opinion. The results were ratified in consultation with an international panel of ophthalmologists (N=49) from the Educational Club of Ocular Surface and Glaucoma representing 23 countries. CONCLUSIONS: Wide variability among questionnaires used to determine vision related QoL in glaucoma and in the responses elicited was identified. In conclusion, no single existing QoL questionnaire design is suitable for all purposes in glaucoma research, rather we have identified the top 10 from which the questionnaire most appropriate to the study objective may be selected. Development of a new questionnaire that could better distinguish between treatments in terms of vision and treatment-related QoL would be useful that includes the patient perspective of treatment effects as well as meeting requirements of regulatory and health authorities. Future work could involve development of a formal weighting system with which to comprehensively assess the quality of QoL questionnaires used in glaucoma

Comparing Prostaglandin Analogues Plus Timolol Fixed Combinations for the Treatment of Open Angle Glaucoma. The Glaucoma Randomized European Assessment Trial

Purpose:To investigate and compare the efficacy and safety of the fixed combinations of bimatoprost and travoprost plus timolol (BTFC and LTFC) in open angle glaucoma patients (OAG) under treatment with latanoprost and timolol fixed combination. Methods:Eighty-nine OAG patients were included in this multicentre, prospective, randomized, double masked, cross-over clinical trial. After 6 weeks run-in period with LTFC, patients were allocated to be treated with either TTFC or BTFC for 3 months. After 3 months patients switched to the opposite therapy for 3 more months. The primary endpoint was the comparison of mean daily intraocular pressure (IOP) after 3 months of each treatment. Results:baseline IOP was 16.5 mmHg (95%CI 16.0-17.0) under treatment with LTFC. Both BTFC and TTFC reduced the mean IOP from baseline (p<0.0001). After 3 months of each treatment mean IOP was significantly lower in BTFC group compared to TTFC group (14.7 [14.3-15.3] vs 15.4 mmHg [15.0-15.9], p=0.0041). IOP was lower during BTFC treatment at all time points and statistical significance was reached at 8am, 11am, 5pm but not at 2pm and 8pm. The safety profile was similar between groups. Conclusions:both BTFC and TTFC are effective in reducing the IOP in patients not fully controlled with LTFC. The observed additional IOP reduction was greater with BTFC with similar safety profile