Browsing by Author "Waller, Sydney"

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    More Is Not Always Better: A Case Report of Excess Calcium Carbonate Ingestion Causing Milk-Alkali Syndrome
    (2021-03-25) Waller, Sydney; Luster, Taylor; Collins, Angela J.; Raymond-Guillen, Luke
    CASE DESCRIPTION: A 54-year-old female with a medical history significant for CKD stage 4 and alcohol use disorder presented to the Emergency Department with altered mental status. Labs were significant for hyponatremia, hypokalemia, hypochloremia, hypercalcemia, metabolic alkalosis, and Cr 9.3. Lorazepam was given due to concern for alcohol withdrawal. Ultimately, her symptoms were discovered to be due to excessive ingestion of calcium carbonate (aka: Tums), and she was diagnosed with milk-alkali syndrome (MAS). Pt was treated with IV KCl and normal saline, and her labs and mental status normalized over the subsequent 48 hours. | CLINICAL SIGNIFICANCE: MAS is constituted by metabolic alkalosis, acute kidney injury, and hypercalcemia. It is a result of a large intake of calcium and absorbable alkali. The syndrome was first recognized in the early twentieth century, and it essentially disappeared when histamine blockers began being used to treat peptic ulcers in the 1980s. Recently, the syndrome is becoming more common with the increased use of calcium-carbonate in antacids and osteoporosis prevention medications. MAS is the third most common cause of hypercalcemia, after malignancy and hyperparathyroidism. Management involves holding calcium and vitamin D supplements and administering aggressive intravenous hydration. Bisphosphonates and dialysis may be useful in severe cases. Prognosis of MAS is typically good as the condition is reversible. | CONCLUSION: The prevalence of MAS is increasing due to the wide availability of calcium-containing supplements and antacids. In order to counteract this, increased awareness amongst at risk patient populations, such as the elderly and those with renal disease, is vital. Furthermore, increased awareness amongst healthcare professionals may help prevent complications that can arise from untreated MAS.
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    Small-molecule inhibitors of ferrochelatase are antiangiogenic agents
    (Elsevier, 2022-01-31) Sishtla, Kamakshi; Lambert-Cheatham, Nathan; Lee, Bit; Han, Duk Hee; Park, Jaehui; Sardar Pasha, Sheik Pran Babu; Lee, Sanha; Kwon, Sangil; Muniyandi, Anbukkarasi; Park, Bomina; Odell, Noa; Waller, Sydney; Park, Il Yeong; Lee, Soo Jae; Seo, Seung-Yong; Corson, Timothy W.; Ophthalmology, School of Medicine
    Activity of the heme synthesis enzyme ferrochelatase (FECH) is implicated in multiple diseases. In particular, it is a mediator of neovascularization in the eye and thus an appealing therapeutic target for preventing blindness. However, no drug-like direct FECH inhibitors are known. Here, we set out to identify small-molecule inhibitors of FECH as potential therapeutic leads using a high-throughput screening approach to identify potent inhibitors of FECH activity. A structure-activity relationship study of a class of triazolopyrimidinone hits yielded drug-like FECH inhibitors. These compounds inhibit FECH in cells, bind the active site in cocrystal structures, and are antiangiogenic in multiple in vitro assays. One of these promising compounds was antiangiogenic in vivo in a mouse model of choroidal neovascularization. This foundational work may be the basis for new therapeutic agents to combat not only ocular neovascularization but also other diseases characterized by FECH activity.