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Dodt J.,Paul Ehrlich Institute | Pasternack R.,Zedira GmbH | Seitz R.,Paul Ehrlich Institute | Volkers P.,Paul Ehrlich Institute
British Journal of Haematology | Year: 2016

In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2B2). FXIII-A2B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2B2, indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2′) also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2′B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2′B2. In addition to its well-known role, FXIII-B also contributes to FXIII-A2B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2016 John Wiley & Sons Ltd. Source


The invention relates to pyridinone derivatives of general formula (I) as inhibitors of tissue transglutaminase, to methods for producing the pyridinone derivatives, to pharmaceutical compositions containing said pyridinone derivatives and to their use for the prophylaxis and treatment of diseases associated with tissue transglutaminase.


Trademark
Zedira GmbH | Date: 2010-02-23

Chemical and biochemical products, namely, chemicals, chemical preparations, and biochemical preparations for industrial or scientific purposes; chemical or biochemical products for medical science for application in or to the human and animal body, namely, chemical reagents. Pharmaceuticals, pharmaceutical and veterinary products as well as preparations for health care, namely, for the treatment and prophylaxis of celiac disease, autoimmune diseases, food intolerances, bowel diseases, irritable bowel, fibroses, scar formation, hypertrophic scars, scleroderma, diabetic nephropathies, liver fibrosis, cirrhosis, lung fibrosis, arteriosclerosis, cancer, thrombolysis, acne, skin aging, psoriasis, neurodegenerative diseases, Alzheimers disease, Huntingtons disease, Parkinsons disease, cataract, infestation with microorganisms, infections or candidoses; chemical and biochemical products for healing purposes and health care, namely, chemical and biochemical preparations for sanitary use; chemical and biochemical products, namely, chemical and biochemical reagents for human and veterinary medical purposes; dietetic products for medical purposes and health care, namely, dietetic foods and sugar for medical use; dietetic products for human and veterinary medical purposes, namely, dietary supplements; dietary supplements for medical purposes; disinfectants for sanitary purposes; preparations for exterminating noxious animals; diagnostic preparations for medical purposes; X-ray contrast agents for medical purposes; detergents for medical purposes. Contract medical research; conducting research and development projects in the fields of medicine, pharmacy, pharmacology, biochemistry or medical technology on behalf of third parties; commissioned performance of clinical trials and clinical studies for medical research purposes; commissioned assessment of the performance of clinical trials and studies for medical research purposes; biochemical laboratories; chemical analysis laboratories; medical laboratories and bacteriological research laboratories.


Trademark
Zedira GmbH | Date: 2011-03-08

Chemical and biochemical products, namely, chemicals, chemical preparations, biochemical preparations for industrial or scientific purposes. Medicines for the treatment of celiac diseases, autoimmune diseases, food intolerances, intestinal diseases, irritable bowel syndrome, fibrosis, scarring, hypertrophic scars, scleroderma, diabetic nephropathy, hepatic fibrosis, cirrhosis, pulmonary fibrosis, atherosclerosis, cancer, thrombolytic therapy, acne, skin aging, psoriasis, neurodegenerative diseases, Alzheimers disease, Huntingtons diseases, Parkinsons disease, cataracts, affection by microorganisms, infections or candidiasis; pharmaceutical and veterinary medical products, namely, preparations for healthcare for the treatment of celiac diseases, autoimmune diseases, food intolerances, intestinal diseases, irritable bowel syndrome, fibrosis, scarring, hypertrophic scars, scleroderma, diabetic nephropathy, hepatic fibrosis, cirrhosis, pulmonary fibrosis, atherosclerosis, cancer, thrombolytic therapy, acne, skin aging, psoriasis, neurodegenerative diseases, Alzheimers disease, Huntingtons diseases, Parkinsons disease, cataracts, affection by microorganisms, infections or candidiasis; preparations or pharmaceuticals, namely, for the treatment and prophylaxis of celiac diseases, autoimmune diseases, food intolerances, intestinal diseases, irritable bowel syndrome, fibrosis, scarring, hypertrophic scars, scleroderma, diabetic nephropathy, hepatic fibrosis, cirrhosis, pulmonary fibrosis, atherosclerosis, cancer, thrombolytic therapy, acne, skin aging, psoriasis, neurodegenerative diseases, Alzheimers disease, Huntingtons disease, Parkinsons disease, cataracts, bacterial or yeast infection, infections, or candidiasis; chemical and biochemical products, namely, chemical preparations in the nature of chemical reagents and biochemical preparations for medical purposes; chemical and biochemical products, namely, chemical preparations in the nature of chemical reagents and biochemical preparations for healthcare; chemical and biochemical products, namely, chemical preparations in the nature of chemical reagents and biochemical preparations for human and veterinary medical use; dietetic products, namely, dietary supplements, dietetic foods adapted for medical use; dietetic products, namely, dietary supplements, dietetic foods adapted for healthcare; dietetic products, namely, dietary supplements, dietetic foods adapted for human and veterinary medical use; dietary supplements for medical purposes; disinfectants for medical instruments, for hygienic purposes, for sanitary purposes; preparations for destroying vermin; chemical and biochemical products for medical science for use in or on the human or animal body, namely, biochemical preparations and chemical reagents; diagnostic agent for medical purposes; X-ray contrast agent for medical purposes; germicidal detergents for medical purposes. Commissioned research in the field of medical research, medical devices and biological research; conducting research and development work in the medical, pharmaceutical, pharmacological, biochemical and/or medicine technological area on behalf of third parties; commissioned execution of clinical trials and clinical studies in the field of medical and scientific research; commissioned assessment of scientific projects in the field of quality assessment and evaluation, commissioned evaluation of clinical trials and studies in the field of quality assessment and evaluation; services of a biochemical laboratory; services of an analytical laboratory in the field of medical, biological and chemical.


Elli L.,Center for Prevention and Diagnosis of Coeliac Disease | Roncoroni L.,Center for Prevention and Diagnosis of Coeliac Disease | Hils M.,Zedira GmbH | Pasternack R.,Zedira GmbH | And 6 more authors.
Human Immunology | Year: 2012

Coeliac disease pathogenesis is characterized by an immune response triggered, in genetically predisposed subjects, by ingested gluten and its withdrawal from the diet is the only available therapy. However, enzymatic modification of gluten through the insertion of lysine to avoid antigen presentation could represent a new therapeutical approach for patients. Sixty-six duodenal biopsies from 17 coeliac patients were cultured for 48. h with gluten or enzymatically-modified gluten (treated with human recombinant transglutaminase type 2 or bacterial transglutaminase, with or without lysine). Interferonγ, anti endomisium and anti transglutaminase IgA antibodies, lactate dehydrogenase and transglutaminase activity were measured in the culture medium. Transglutaminase type 2 expression was evaluated on biopsies by immunohistochemistry. Gluten and transglutaminase-treated gluten increased by 13-15 fold interferon γ release, as well as antibodies, transglutaminase activity, and the immunohistochemical expression of transglutaminase type 2. Addition of lysine to the enzymatic modification of gluten normalized interferon γ, antibodies, transglutaminase activity and immunohistochemical expression of transglutaminase type 2. Lactate dehydrogenase did not differ among the studied groups. Enzymatic modification of gluten by transglutaminase plus lysine prevents the immunologic effects on cultured duodenal biopsies from coeliac patients and could be tested as an alternative therapy in coeliac disease. © 2012 American Society for Histocompatibility and Immunogenetics. Source

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