Demecarium Bromide

Fungi cause diverse, serious socio-economic problems, including biodeterioration of valuable products and materials that spawns a biocides industry worth ~$11 billion globally. To help combat environmental fungi that commonly colonise material products, this study tested the hypothesis that combination of an approved fungicide with diverse agents approved by the FDA (Food and Drug Administration) could reveal potent combinatorial activities with promise for fungicidal applications. The strategy to use approved compounds lowers potential development risks for any effective combinations. A high-throughput assay of 1280 FDA-approved compounds was conducted to find those that potentiate the effect of iodopropynyl-butyl-carbamate (IPBC) on the growth of Trichoderma virens; IPBC is one of the two most widely used Biocidal Products Regulations–approved fungicides. From this library, 34 compounds in combination with IPBC strongly inhibited fungal growth. Low-cost compounds that gave the most effective growth inhibition were tested against other environmental fungi that are standard biomarkers for resistance of synthetic materials to fungal colonisation. Trifluoperazine (TFZ) in combination with IPBC enhanced growth inhibition of three of the five test fungi. The antifungal hexetidine (HEX) potentiated IPBC action against two of the test organisms. Testable hypotheses on the mechanisms of these combinatorial actions are discussed. Neither IPBC + TFZ nor IPBC + HEX exhibited a combinatorial effect against mammalian cells. These combinations retained strong fungal growth inhibition properties after incorporation to a polymer matrix (alginate) with potential for fungicide delivery. The study reveals the potential of such approved compounds for novel combinatorial applications in the control of fungal environmental opportunists.

• Search with an approved fungicide to find new fungicidal synergies in drug libraries.• New combinations inhibit growth of key environmental fungi on different matrices.• The approach enables a more rapid response to demand for new biocides.

To describe a novel, minimally invasive method for re‐establishing aqueous humor outflow in dogs with refractory glaucoma after fibrous encapsulation of their Ahmed drainage implants.

Three dogs (4 eyes) underwent trans‐capsular implantation of an Alcon EX‐PRESS® glaucoma filtration device under sedation (2 dogs) or general anesthesia (1 dog). After rotating the eye downwards, a 2 mm incision was made in the conjunctiva/Tenon's capsule overlying the encapsulated Ahmed plate, and later closed with absorbable suture. All eyes received subconjunctival mitomycin‐C 0.02 mg.

Mean post‐operative follow‐up was 341 days (range: 77‐530). All eyes were hypertensive pre‐operatively (mean IOP: 31.25 ± 7.14 mmHg) despite receiving topical latanoprost (4/4), timolol (4/4), carbonic anhydrase inhibitors (4/4), and demecarium bromide (2/4). Two eyes (dogs 1 and 2) were visual pre‐operatively, while 2 eyes (dog 3) displayed equivocal or no vision. Post‐operatively, all eyes received timolol and a carbonic anhydrase inhibitor. Other anti‐hypertensive medications were discontinued. Immediately following surgery, all eyes were mildly hypotensive (mean IOP: 5.75 ± 1.71 mm Hg). Two of 4 eyes were normotensive and visual until days 90 (dog 2) and 530 (dog 1) (IOP range: 10‐16 mm Hg). One eye (dog 3) was normotensive for approximately 150 days, and then hypertension returned. One eye (dog 3) from the start displayed severe uveitis, hypertensive episodes, and was phthisical by the end of follow‐up.

Trans‐capsular EX‐PRESS® implantation is a minimally invasive procedure for treatment of refractory glaucoma in dogs with encapsulated Ahmed drainage implants, and further investigation is warranted.