The Role of IL-13, IL-15 and Granulysin in the Pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are Severe Cutaneous Adverse Reactions (SCARS) characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. Conjunctival lesions are reported in 85% of patients. The pathogenesis of SJS/TEN/SCARS is not completely understood. It is hypothesized that IL-13, IL-15 and Granulysin expressed in plasma and skin may play a role. We measured the circulating levels of these cytokines in the plasma using ELISA and their expression in the skin using immunofluorescence microscopy. A total of 12 SJS/TEN skin biopsy samples (8 SJS, 2 SJS/TEN overlap and 2 TEN) were analyzed. Biopsy samples from patients with Lichen Planus (an inflammatory condition of the skin and mucous membranes) served as controls. Studies were also performed in human corneal epithelial cells where expression of these cytokines were measured following a challenge with TNF-α (0, 1, 10 and 100 ng/ml). The intensity of immunofluorescence was measured Using Imaris® software. The results showed significantly increased expression of these cytokines in the skin biopsy samples as measured by the average intensities of IL-13 (6.1 x 133.0 ± 4.231 x 10^8), and Granulysin (4.2 x 123.0 ± 4.231 x 10^8) compared to Lichen planus control (3.0 x 123.0 ±1.62 x 10^5). Increased expression of IL-13 and IL-15 were noted in cell culture studies and in the plasma samples when compared to Normal Human Plasma as controls. It is concluded that IL-13, IL-15 and Granulysin play a role in the pathogenesis of SJS/TEN.

Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version.

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.