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  • To our knowledge this is the first report

    2020-03-26

    To our knowledge, this is the first report of an oncocytoma expressing alpha-enolase or causing autoimmune retinopathy and optic neuropathy. Although generally considered benign, oncocytomas have rarely been associated with paraneoplastic syndromes, including tumor-induced hypertension, erythrocytosis, and ataxia.6, 7, 8 Prior histologic studies have demonstrated that oncocytomas can produce known retinal antigens, including recoverin and neuron-specific (gamma) enolase., This patient did not have anti-recoverin or anti-gamma enolase GDC-0084 receptor in his serum, and staining of the oncocytoma was negative for gamma enolase. Treatment of autoimmune retinopathy is challenging, in part due to delay and ambiguity in diagnosis. Currently, immunosuppression is standard care, but the efficacy of such treatments is unclear, with studies showing variable degrees of improvement in cancer-associated retinopathy, and inconsistent responses in other sub-types of autoimmune retinopathy., In general, improvement even with immunosuppression or tumor resection is unusual. This patient did not respond to initial treatment with intravenous methylprednisolone and plasmapheresis, and tumor resection was therefore pursued. Remarkably, the patient noted subjective improvement within weeks of tumor resection, and by 9 months post-operatively, he demonstrated improved visual acuity, visual fields, and ERG waveforms confirming his response to treatment.
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    Introduction Tropical theileriosis is one of the most widespread diseases among thick-borne cases, causing serious losses in livestock production in especially North Africa, the Mediterranean coastal area, South Europe and Asia [1,2]. Theileria annulata is an obligate intracellular protozoan parasite transmitted by Hyalomma genus tick vectors and causes the disease in ruminant animals especially Bos taurus and Bos indicus [2,3]. Buparvaquone has been the most effective antitheilerial drug used for the treatment of tropical theileriosis but resistance of T. annulata against buparvaquone have been reported since 2010 [[4], [5], [6]]. Because of this reported resistance and long time required to drug development process, need for discovering alternative drugs has greatly increased. Advances in genomics, computational chemistry and biology give a chance to design new structure based drugs. In structure based drug design, metabolic enzymes are mostly favorable targets [7]. Glucose catabolism in Theileria macroschizonts predominantly consist of lactic acid production pathway and therefore glycolytic enzyme enolase has an important role in glucose catabolism [[8], [9], [10]]. Enolase is a key enzyme that catalyzes the interconversion of 2‑phosphoglycerate to phosphoenolpyruvate in glycolytic pathway and gluconeogenesis [10,11]. The enzyme is also responsible for non-glycolytic functions such as contributing regulation of the cytoskeletal filaments [10,12]. In addition, enolase is plasminogen binding receptor, located at cell surface and this plasminogen activation mediates pathogen invasion [10,13,14]. Taken together, enolase would be a crucial target protein that these functions of the parasite could be inhibited. The isofunctional host enzyme should be analyzed in parallel with the parasite enzyme according to structure based drug design approach in order to evaluate the selectivity and possible toxicity [15]. Therefore the gene encoding Bos taurus muscle enolase (BtEno3) which is counterpart of T. annulata enolase, was cloned, expressed, purified and biochemically characterized for the first time in the literature. As no empirically defined structure was solved, BtEno3 was modelled to predict 3-dimensional (3D) protein structure of the enzyme. The substrate 2‑phosphoglycerate (2PG) was docked into enzyme and molecular dynamics simulation of the enzyme-ligand complex was carried out to predict binding behavior of the substrate on the enzyme. These in vitro and in silico analyses on BtEno3 were performed to enlighten the further drug design studies to develop alternative drugs to be used in the treatment of tropical theileriosis.