GLS-1027 to Treat Anterior Uveitis in a Cavalier King Charles Spaniel Dog

 

Abstract

Non-infectious, autoimmune anterior uveitis is a significant cause of ocular disease in both dogs, horses, and humans with the potential for significant vision loss. The mainstay of treatment is topical and/or systemic corticosteroids, however, animals, similar to humans, are not uncommonly resistant to therapy. Additionally, prolonged corticosteroid treatment may cause systemic and ocular toxicity. We describe here a case of steroid-resistant uveitis successfully treated with GLS-1027, an immunomodulatory compound that inhibits Th17 maturation and release of multiple inflammatory cytokines involved in the pathogenesis of uveitis. GLS-1027 may provide an alternative as a steroid-sparing therapeutic option.

Introduction

Non-infectious, anterior uveitis is a significant cause of ocular disease in dogs, horses, humans, and other species that has the potential to lead to vision loss and blindness. While the disease is most commonly considered as autoimmune for humans and the most common etiology in dogs [1,2] infectious disease neoplastic etiologies must also be considered [2,3]. In all species, the primary goal of treatment is sight preservation with secondary goals to limit pain, discomfort, photophobia, and in dogs minimizing secondary sequelae such as posterior synechia [3]. In animals, topical corticosteroid treatment combined with topical mydriatics with or without the use of systemic anti-inflammatory medications represents the standard of care for anterior uveitis [2,4]. While immunosuppressives are considered the standard for steroidresistant disease in humans [5], these are seldom used in animals due to toxicity and cost. Studies in animals have reported that approximately 1-35% of the total topical corticosteroid dose is systemically absorbed, [4] and may result in systemic side effects, including endocrinopathies [3]. Steroid-induced ocular pathology, including the development of glaucoma, cataract formation, and keratopathy are not uncommon in dogs with prolonged corticosteroid use [4] with a similar side effect profile for humans. Therefore, a safe and effective alternative to corticosteroid treatment for chronic recurrent idiopathic uveitis is warranted. Autoimmune uveitis in humans [6] and horses [7,8] has been attributed to Th17 mediated pathology with a complex interplay between a number of inflammatory cytokines including TNFα and IL-6. GLS-1027, [S,R]-3-phenyl-4,5-dihydro-isoxazoleacetic acid, is a small molecule compound with anti-inflammatory activity currently in clinical development. GLS-1027 is a potent inhibitor of lipopolysaccharide (LPS)-induced inflammation characterized by normalization of levels of the cytokines tumor necrosis factor (TNFα), interleukin (IL) 1β, and IL-6 both in vitro and in murine animal models [9-12]. Additional unpublished data has shown that GLS-1027 inhibits IL-17 and IL-23 mediated activation and downregulates Th17 T cells.

In this paper, we describe a case report of the use of GLS-1027 to treat canine uveitis.

 

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Cauchy Modeling as a New Trend in Research of Fullerene- Type Nanomaterials

 

Abstract

In the work, based on the analysis of heat and gas with acoustic phonons by fullerene, the physical criterion Cauchy is the kind of thermal strength before spring strain, which is caused by the nanotube fullerene

Keywords: Thermal Conductivity; Fullerene; Optimization; Numbers Similarity Numbers

Introduction

Studies of the thermal conductivity of structured nano systems draw attention to the fact that in micro- and nanoelectronics the urgent task of heat dissipation released during the operation of electrical elements [1-6]. So, in the process of electrical switching of the element energy is consumed which is on the verge of thermal fluctuations This means that a billion (109) transistor chip uses order energy in a single act 10^-3J. Then, in order of speed 1GHz , the energy consumed can reach values far exceeding the power of a jogging electric kettle

In order to remove Joule-Lenz heat in electric nanoelements, both microchannels with liquid carriers of heat and conductive elements, such as nanocomposite ceramics filled with carbon nanotubes, can be used, which, depending on their chiral characteristics, can alter the physical properties of nano cells. Thus, it was established [9-12] and confirmed by theoretical estimates [13,14] that the thermal conductivity at room temperature of a carbon nanotube can reach values of which significantly exceeds the thermal conductivity of diamon which was considered one of the best heat conductors. Carbon nanotubes are thermally stable, characterized by high electrical conductivity [10], high electron mobility [11], and a large specific surface value [15]. It is believed [16] that the abnormally high thermal conductivity of carbon nanotubes is due to their regular structure and the small number of defects and impurity centers in them. In the elementary cell of graphene there are two carbon atoms, so the dispersion spectrum consists of three optical and three acoustic branches, among which the longitudinal and transverse acoustic modes correspond to the speed of sound 2130 and 1360 M/s

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